Scientific Information Sharing Resource

Scientific Resource Navigation

2009-10-04T15:13:00.000-07:00

Scientific Resource Navigation:

Note: The list below is not complete and there are more and more resources continously added to the SISR. For complete listing, check out Spicy Science Link List on the left side of this page. For others, read on..

Bacterial Genes in Animals

Now new research suggests that bacteria are also easygoing about passing genes on to more complex organisms.
Read more...

Smoking stays in your genes after you quit

Gene expression changes brought on by heavy smoking may persist long after the smoker has kicked the habit.
Read more...

Securing accuracy and precision when pipetting hot and cold liquids

Biotechnology researchers and laboratory technicians cannot always prevent errors in their results owing to the temperature variation between samples and pipettes. Read more...

Extra Strong Paper!

Researchers have developed a remarkably simple way to convert ordinary graphite particles into very thin but superstrong sheets that are tougher than steel and as flexible as carbon fiber but can be made much more cheaply. Read more...

Physics in a cell: Spring Theory

Physicists interested in the mechanics of single molecules are helping open one of the blackest boxes in biology. Brendan Maher discovers how the disciplines are working together.
Read more...

Cilia - Unexpected

"Almost every cell in the human body carries a cilium, even neurons buried deep in the brain.." Read more...

Invisible Nanofibres

Tiny plastic fibers could be the key to some diverse technologies in the future -- including self-cleaning surfaces, transparent electronics, and biomedical tools that manipulate strands of DNA.. Read more...

RNA May play Larger Role in Cell's gene activity

Large, seemingly useless pieces of RNA - a molecule originally considered only a lowly messenger for DNA - play an important role in letting cells know where they are in the body and what they are supposed to become, researchers at Stanford University School of Medicine have discovered. Read more...

Curing Cancer with Mathematics

"In this cross-disciplinary project, we are developing computational and mathematical tools capable of modeling the complex cascade of biological tumor-immune interactions, and of determining effective combination treatment strategies. Our tools have the potential to provide clinical guidance in the development of new treatment protocols through preliminary evaluations of simulated scenarios." Read more...

Changing One Species to Another - Genome Transplantation

Researchers at the J. Craig Venter Institute (JCVI) have announced the results of work on genome transplantation methods allowing them to transform one type of bacteria into another type dictated by the transplanted chromosome. Read More...

Nanoparticle based Drug Delivery System

University of California-Santa Barbara researchers determined the procedure dramatically increases the in vivo lifetime of the nanoparticles, suggesting new applications for the delivery of drugs and circulating bioreactors. They said attaching polymeric nanoparticles to red blood cells might become a new way to deliver drugs. Read more...

NanoMedicine

Nanomedicine is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials Read more...

Stem Cells

Stem cells are primal cells common to all multi-cellular organisms that retain the ability to renew themselves through cell division and can differentiate into a wide range of specialized cell types. Research in the human stem cell field grew out of findings by Read more...

Drug Designing

In this Exciting wonderful animation, you shall learn the approach used in Drug Designing Research nowadays! Watch Drugs in Action...

RNA Interference

RNA interference (also called "RNA-mediated interference", abbreviated RNAi) is a mechanism for RNA-guided regulation of gene expression in which double-stranded ribonucleic acid inhibits the expression of genes with complementary nucleotide sequences. Read more...

Human Genome Resources

Here you'll find quite useful links to various Human Genetic Resources along with information on Human Genome Project. Read more...

Protein BioSynthesis

Protein biosynthesis (Synthesis) is the process in which cells build proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription which are then Read more...

Immune System

An Immune system is a collection of mechanisms within an organism that protects against infection by identifying and killing pathogens. It detects pathogens ranging from viruses to parasitic worms and distinguishes them from the organism's normal cells and tissues. Detection is complicated as Read more...

Mitosis

Mitosis is the process by which a cell duplicates its chromosomes, in order to generate two, identical cells. It is generally followed immediately by cytokinesis which divides the cytoplasm and cell membrane. This results in two identical cells with Read more...

Meiosis

In biology, meiosis (IPA: /maɪˈəʊsɪs/) is the process by which one diploid eukaryotic cell divides to generate four haploid cells often called gametes. The word "meiosis" comes from the Greek meioun, meaning "to make smaller," since it results in Read more...

Histone Proteins

Histones are the chief protein components of chromatin. They act as spools around which DNA winds and they play a role in gene regulation. Six major histone classes are known Read more...

Bioinformatics Resources

This simple, yet extensive, Bioinformatics Resource is a platform with various Bioinformatics Resources for students/professionals in Bioinformatics and other relevant branches of Biomedical Sciences. Visit Bioinformatics Resources! It has various useful subsections:
Bioinformatics Basics
Bioinformatics Tools
Major Chemical Databases
Universities offering Bioinformatics - Worldwide
Summer Trainings - Bioinformatics/Biotech
Bioinformatics companies in India
Bioinformatics companies in Rest of the world
Bioinformatics companies in USA

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Scientific and Job related Announcements

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Amazon Store

2009-04-09T21:01:00.000-07:00

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PhD or NOT - How to Decide?

2009-02-08T05:21:00.000-08:00

1. Do not do PhD just for fashion sake, just because some XYZ is also doing it, or just because your family/friends/yourself. would love to see the word Dr. before your name. PhD is not fashion. It is a hard committment at the cost of you personal and social life.

2. Be aware that the job market is very bad and that many people have to do more than one postdoc to get first faculty job. Be aware that a majority of grad students are unhappy. Be true to your own needs and career goals--don't hang in there just for the sake of not being a quitter. Be aware that academic ideals do not play a major role in your career. Rather, politics, money, and fashionable research are more important for career success than good solid work.

3. Graduate school is a very arduous process. You should make sure that you know what the hell you're getting into. You'd better have spent some time as a research assistant, a tech, or something like that. It's very difficult and fraught with setbacks and emotionally draining experiences. And when you're done there's no definite future. It's very hard to get a job in academic research. If you don't want to do academic research, don't go to grad school. If you want to work in industry, go work in industry with a B.S., you don't need a Ph.D. Unless you just want to do grad school for the mental experience, be very careful about your experiences. Of course, when you finish it's quite a sense of personal reward after doing all of this. Just make sure you've thought through it and know what you're getting into.

4. Make sure you REALLY want to do it, because it is a lot of hard work without readily available gratification or compensation (monetarily or emotionally). Additionally, it is a huge commitment. You will have to or be forced to give up most outside interests. Particularly in science, only those who sell their souls to science will really make major accomplishments or succeed in advancing. In general, if you have multi and variable interests or if you desire a fulfilling life defined by an active family life, social life, and financial security, and time to enjoy it along the way, do not go into science.

5. Be sure you know what you are getting involved with and that it is what you want to do for a career. Consider that there are too many doctoral degrees awarded in biological fields relative to the number of career positions available in academic research. Realize how bleak the opportunities in science are, especially how low-paying jobs are for Ph.D.s in biology. Getting a faculty position is a crap shoot, but with worse odds you have to spend 3-6 years as a low-paid postdoc, right when you want to get married, have a family, live in a real house, have a nicer car, but instead you're making all of $28,000 a year, a pittance of what a bachelor's would make in computer science. Then, if you survive the post-doc, you've got more crap-shooting to do if you want to get a tenure-track position someplace where you'd actually want to go. Don't assume that a permanent job in science, especially academic science, will be available when you graduate.Consider other career options. I am happy with my choice, but many are not. Faculty positions are both a long way away (5-6 years grad school and 3-6 years post-doc) and very rare. It's a long haul for an uncertain future.

6. Manging social and professional life is a difficult challenge for PhDs. We all are just busy. People say ‘don’t get distracted’ and/or ‘focus!’. These voices sometimes stay in our mind and we end up to feel caught in the middle of nowhere.

Prions and Cancer

2009-01-06T05:11:00.000-08:00

Recently, I came across a very interesting paper by a chinese group that discusses the possible role of cellular prions in invasiveness and metastasis in gastric cancers. Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI) - anchored membrane protein that is highly conserved in mammalian species. They report that cellular prions are highly expressed in metastatic gastric cancers compared to nonmetastatic ones and significantly promote the adhesive, invasive, and *in vivo*metastatic abilities of gastric cancer cell lines SGC7901 and MKN45. These prions are also reported to increase promoter activity and the expression of MMP11 by activating phosphorylated ErK1/2 in gastric cancer cells.

For further reading, you can refer to original paper: FASEB J. 20, E1205–E1215 (2006) or you may also find this paper attached here:

http://groups.google.com/group/exciting-science/attach/98b4fb3b909901f8/Prions+and+Gastric+Cancer.pdf?part=4

Bacteria induced Sex conversion

2008-12-15T10:51:00.001-08:00

Dear All,

I have a query regarding feminizing effects of Wolbachia strain in the isopod Armadillidium vulgare. In 1973, a french group published an exciting paper (Martin, G. et. al. 1973. C. R. Acad. Sci. Paris III 276, 2313-2316.) in which they reported that Males infected with Wolbachia become functionally females in Armadillidium vulgare.

Wolbachia bacteria are known to reside in the isopod cells and are transmitted through one isopod to another strictly through the cytoplasm of an isopod egg; because sperms contain little or no cytoplasm, the bacteria are not trasmitted by males. Thus bacteria that end up inside a male isopod are at a dead end. So, over evolutionary time, these bacteria have developed an ability to convert male isopods into females!

The first thing that comes to mind is 'How'? Since this was reported first in 1973 and has been followed by a lot of reports, I am hopeful to find an answer to the mechanistic aspects. While this also highlights the intelligent moves developed by cells to promote their survival, what is more inquisitive to me about this conversion is that How on earth do these bacteria get to know that they are inside a male cell?

Kindly feel free to share your views in the comments section: http://hotbacteria.wordpress.com/2008/12/01/open-science

Many Thanks and Kind Regards,

Tarun Gupta
--
MSc Human Genomics
C/o Prof.Tapas Mukhopadhyay
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

The important thing is not to stop questioning. Curiosity has its own reason for existing ~Albert Einstein

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~About Me: http://hotbacteria.wordpress.com
~Exciting Science forum: http://groups.google.com/group/exciting-science
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

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SELEX and Aptamers

2008-08-08T16:05:00.001-07:00

Dear All,

I came across a term SELEX while I was going through some PCR tricks. When I searched about it, I found that its a pretty old technique, wrapped up a nice manner with a trendy name. So what is SELEX? Kindly have a look:

SELEX" (systematic evolution of ligands by exponential enrichment) is a technique which allows the simultaneous screening of more than 10exp15 individual nucleic acid molecules for different functionalities.

With this selection-technique large random pools of nucleic acids can be screened for a particular functionality, such as the binding to small organic molecules, large proteins ,or the alterations, or de novo generation of ribozyme-catalysis etc. Functional molecules (aptamers) are selected from the mainly non-functional pool of RNA or DNA by column chromatography or other selection techniques that are suitable for the enrichment of any desired property.

The method is conceptually straightforward: In a standard DNA-oligonucleotide synthesizer a starting pool is generated. The machine synthesizes an oligonucleotide with a completely random base-sequence which is flanked by defined primer binding sites. In this way, up to 10exp15 different DNA molecules can be synthesized at once, which is an incredibly complex pool. The immense complexity of the generated pool justifies the assumption that it contains a few molecules with the correct receptor structure or with tertiary structures which lead to catalytic activity.

The sequences in the library are exposed to the target ligand - which may be a protein or small organic compound - and those that do not bind the target are removed, usually by affinity chromatography. The bound sequences are eluted and amplified by (RT)-PCR to prepare for subsequent rounds of selection in which the stringency of the elution conditions is increased to identify the tightest-binding sequences.

Successive selection and amplification cycles result in an exponential increase in the abundance of functional sequences, until they dominate the population. The method has been applied to a number of different applications; for example, in vitro selection has proven to be extremely efficient for the identification of bases which cannot be changed without loss of function. Recently, in vitro selection has been used for the de novo isolation of catalytic RNAs. Clinical uses of the technique are suggested by aptamers that bind tumor markers and clinical trials are underway for a VEGF-binding aptamer trade-named Macugen in treating macular degeneration.

SELEX is commonly known as "in vitro selection" or "in vitro evolution". And, if you are wondering what aptamers are - They are simply oligonucleic acid or peptide molecules that bind a specific target, which may be small molecule, or a set of proteins or nucleic acids, or even complete cells.

(Source: (a) Angew. Chem. Int. Ed. Engl. 1992, 31, 979-988, (b) Mol. Biol. Reports 1994, 20, 97-107, (c) Tumour Biol 27(6):289-301)

For those who wish to dig deep, these nature articles may be an interesting read:

1) http://www.nature.com/nature/journal/v346/n6287/abs/346818a0.html;jsessionid=FF915EA18E222BF267248878C32C7B4D
2) http://www.nature.com/nrmicro/journal/v4/n8/abs/nrmicro1458.html;jsessionid=F80B39292BD0666B99056F0E6C8CA2F0

Kind Regards,
Tarun Gupta
--
MSc Human Genomics
C/o Prof.Tapas Mukhopadhyay
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.wordpress.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

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Agarose Polymerization!

2008-08-06T11:53:00.001-07:00

Dear All,

Yet again a very nice post by Nick which deals with the one of those common scientific myths that needs some confusion-whacking.

Most of the people, usually grad students, believe that Agarose polymerizes to form gel! It is nothing but just a scientific myth.

So, what is polymerization? Addition polymerization is a chain reaction in which the chain carrier may be an ion or a reactive substance with a free radical that forms a covalent bond with an electron on another molecule. For instance, in polyacrylamide gel formation, TEMED induces free radical formation from ammonium persulphate (APS) and these free radicals transfer electrons to the acrylamide/bisacrylamide monomers, radicalizing them and causing them to react with each other to form the polyacrylamide chain.

And what happens in case of Agarose? Chemically, agarose is a polysaccharide, whose monomeric unit is a disaccharide of D-galactose and 3,6-anhydro-L-galactopyranose. In aqueous solutions below 35Â°C these polymer strands are held together in a porous gel structure by non-covalent interactions like hydrogen bonds and electrostatic interactions. Heating the solution breaks these non-covalent interactions and separates the strands. Then as the solution cools, these non-covalent interactions are re-established and the gel forms but there is no polymerization involved!

So agarose (and agar) gels form by gellation through hydrogen bonding and electrostatic interactions, not through polymerisation!

(Credits: Nick @ Bitesize)

DEPC Treatment of RNases

2008-08-04T11:01:00.001-07:00

Dear All,

I found a very good post by Nick oswald which summerizes the myths and truths about DEPC treatment for RNases. Here's a replica-paging version of his post:

Ambion has a really nice article about the truths and myths behind DEPC treatment for RNase contamination. In it they test and report on 6 commonly held beliefs about DEPC treatment… here's a summary of what they found:

FALSE: RNases re-nature after denaturation by autoclaving, so autoclaving is no good for RNase decontamination.

Tests on RNase A before and after autoclaving showed that most of it's activity was wiped out by autoclaving, so maybe RNases aren't so invincible after all. That said, some RNase activity remained, so while not invincible RNase are certainly hardy.

TRUE: Autoclaving inactivates DEPC
Well thank goodness - DEPC is indeed inactivated by autoclaving. The mechanism is hydrolysis of DEPC to produce ethanol and water. 0.1% DEPC/water solutions should be completely DEPC-free after autoclaving for 15 minutes/ litre.

FALSE: DEPC solutions should be odor-free after autoclaving
The solution will still smell of ethanol, but also sweet-smelling volatile esters formed by the reaction of ethanol with trace carboxylic acids.

TRUE: Tris-containing solutions cannot be treated with DEPC
The amino group on tris interacts with DEPC, making it unable to do it's job of decontaminating the solution.

FALSE: 0.1% DEPC is sufficient to inhibit any amount of RNase in solution.
DEPC is not catalytic so the amount of DEPC required for full RNase removal increases with the concentration of RNase, as shown by a neat experiment in the report.

TRUE: 1% DEPC is better at removing RNase than 0.1%
It is certainly true but higher DEPC concentrations mean that there is likely to be more left-over DEPC/DEPC by-products after autoclaving, and these can inhibit downstream applications. The report documents that the efficiency of an in vitro transcription reaction decreases with as the DEPC concentrations used to treat the water are increased.

Credits: Ambion technical bullitons (http://www.ambion.com/techlib/tb/tb_178.html) & Nick Oswald, Bitesizebio

Kind Regards,

Tarun Gupta
--
MSc Human Genomics
C/o Prof.Tapas Mukhopadhyay
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.wordpress.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

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Regarding cognitive neuroscience & behavior control

2008-05-23T02:13:00.001-07:00

Respected All,

Last night, I have been discussing about memory storage with a PhD student who works on Alzheimer's and has interests in cognitive neuroscience. He has been explaining various processes related to memory storage in brain exclusively in terms of polarization / depolarization, ion channels and various signalling pathways but a very fundamental query that had arisen in our discussion remained unanswered. Kindly have a look:

"When we speak of memory, our brain stores information in various formats. It can be imprints of images, whether static or dynamic, of various persons, objects, locations etc. or it can be audio-impressions that help us recognize a person just by hearing his/her voice. The question is - How such audio-visual memory imprints are stored in our brain? How do our current understanding of Molecular Neuroscience explains such sort of imprinting?"

Further through our discussion, we again came at a very interesting question:

"It is well substantiated that Hormones control our behaviour but sometimes we consciously control our behaviour to further regulate hormonal control of our behaviour. For instance, a person's wife dies. Shocked, his hormonal levels go crazy and he is deeply in grief. But after somedays, he comes to an understanding with himself and tries to consol his mind that - Boy, what has been done, has been done. Lets continue with the life and he delibrately tries to forget his grief i.e. in other words, he delibrately controls his hormonal changes. How such sort of "active control" over behavior is explained by Molecular Neuroscience?"

I am a just a kid in the block with little or no understanding of neuroscience. I shall be grateful for any comments or views regarding this. You can write to me at: tarun.gupta@nchgsr.acads.in

Kind Regards,

Tarun Gupta

--
C/o Prof.S.C.Lakhotia
Cytogenetics Lab
Banaras Hindu University
Varanasi - India

MSc Human Genomics
C/o Prof.Tapas Mukhopadhyay
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

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You can't escape from Mosquitoes!

2008-05-02T06:45:00.001-07:00

Dear All,

For many months, I have been wondering why mosquitoes bite only me and not my successive roommates as a result of which, a significant amount of my pocket money goes on mosquito repellents and odomos. A paper by Dr.Ditzen's group at Rockfellar seems to answer this.

They have shown that DEET i.e. N,N-diethyl-meta-toluamide, which is the world's most widely used topical insect repellent, with broad effectiveness against most insects, blocks electrophysiological responses of olfactory sensory neurons to attractive odors in Anopheles gambiae and Drosophila melanogaster. They have concluded that DEET masks host odor by inhibiting subsets of heteromeric insect odorant receptors that require the OR83b co-receptor.

Check out this recent Science Paper: http://www.sciencemag.org/cgi/content/abstract/319/5871/1838

So finally, I have got an answer - I release some factors which, rather unortunately, mosquitoes find very attractive!! Too bad! But its intriguing; these attractants are then seem to be released on a case to case basis because there are some people who usually do not get bitten by mosqitoes!!

Kind Regards,
Tarun Gupta

Using Animal Models in Research

2008-03-21T09:31:00.001-07:00

Imagine that a species emerge that is stronger and more intelligent than Humans. Now this species, out of curiosity, tries to understand their physiology and decides to use Humans as Model systems and unfortunately, the model organism that a curious researcher of their species grabs is no one else but you. They inject tumors in you to study effect of various drugs, dissect you out to culture your brain cells, irradiate your testis to study effect of random mutagenesis so and so forth.

Out of pain, you cry and ask them - Whats my fault? Why are you torturing me? Please leave me because I can't tolerate this pain anymore and I don't wnanna die. But they justify their actions by saying that its for "greater good" of their community as research on you would provide crucial insights about their physiology and help in reducing suffering of their species. Would you accept this statement and keep on suffering that never ending pain and die for it?

Same goes for all the animal models that we use in our Labs on everyday basis. We do all sorts of cruelty to them and try to sooth ourselves out by saying "its for betterment of humankind". But what about animalkind? Don't they have pain receptors? Don't they feel anything? Don't they have right to live?

Last time we tried to dissect a mice by cervical dislocation, the poor fellow went in trauma and started shaking badly. That also shaked my mind a bit. Perhaps we need to start looking for alternatives. Perhaps solid predictive algorithms or invitro culture based simulation of various physiological process or anything else. I know its easy said than done & multifactorial aspects of our physiology makes things quite complicated but we certainly need to stop, think, rethink and work in this direction.

ChIP-SNP based Imprinting identification

2008-03-20T08:08:00.001-07:00

Dear All,

A group has developed a genome-wide technique to identify genomic imprinting on a genome wide scale, as reported online in Nature Methods.

A mammalian genome contains two copies per gene, one allele from the father, the other from the mother. But often the organism does not need the products from both genes, especially during development and therefore one copy is silenced, a process known as imprinting.

Bing Ren and colleagues devised an assay that allows the genome-wide interrogation of gene expression to determine which of the two alleles is being expressed. The researchers start with chromatin immunoprecipitation (ChIP), which fishes out areas of the genome that bind to proteins responsible for transcription and are therefore likely to be expressed. Then they determine which of the two alleles they isolated by interrogating the presence of single nucleotide polymorphisms (SNP) on microarrays. This combination of ChIP and SNP will allow not only the discovery of new imprinted genes across the genome, but also permit a closer look at the mechanism of allele-specific expression.

(Source: http://dx.doi.org/10.1038/nmeth.1194 - Nature Methods)

Psychosocial Treatment of Cancer - a Lancet report

2008-03-13T11:16:00.001-07:00

Respected All,

A paper published in The Lancet in 1989 reported a very interesting finding. (Spiegel, D. et al. (1989). Effect of Psychosocial Treatment on Survival of Patients with Metastatic Breast Cancer. Lancet,2, 888-891). This study was a 10 year follow-up to a previous study in order to determine the effect of psychosocial intervention on the time of survival of 86 patients with metastatic breast cancer. The 1 year intervention consisted of a weekly supportive group therapy with self hypnosis for pain. Patients imagined their wbc's killing their cancer cells and dead cancer cells being flushed out of the body. Both the treatmnent and control groups had routine oncological care. At 10 year follow-up, survival time for the treatment group was significantly longer compared with controls. In addition, the interval from fist metastasis to death was significantly longer for the group randomized to treatment. Th\1S the intervention group lived on average twice as long as did controls.

Interesting, isn't it. I wonder what is going on at molecular levels in this case? Are there imagination based changes in gene expression?

Kind Regards,

Tarun Gupta
--
MSc Human Genomics
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

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Abortive RNAs - What good are they?

2008-03-05T10:28:00.000-08:00

Dear All,

Since that last Gene regulation lecture of Dr.Sharma, I have been wondering what good are these large number of small RNA products called Abortive RNAs that are formed after successive rounds of Abortive transcriptions. This query became all the more imperative when I found out a paper which reported that in vaccinia virus theshort transcripts i.e. Abortive RNAs are capped (initiated with both ATP and GTP), methylated, and polyadenylylated,indicating that neither completion of an RNA chain nor processingfrom a polycistronic precursor was required for modificationof either end of the RNA (J Virol. 1979 September; 31(3): 849-853). I couldn't find similar studies in higher systems but probably such modifications do occur in these systems.

In such a case, one wonders that why would cells "waste" so much of their energy & resources? Apparently they don't. A 1997 PNAS paper reports a novel mechanism in which these abortive RNAs play a major role in 3' end repair of short, single stranded 3' ends of turnip crinkle carmovirus RNA which is vulnerable to degradation by host cell RNAses (PNAS, 94, Feb 1997, 1113–18).

I wonder if they have regulatory roles? Do they regulate expression of same genes by RNAi which codes for them in a way miRNAs work? Perhaps only time will tell! Kindly feel free to enlighten me on this.

Kind Regards,

Tarun Gupta

--
MSc Human Genomics
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

*************************************************

Inflammation and cancer

2008-03-05T09:28:00.001-08:00

A potential link between inflammation and cancer has been suspected for over a century, but the exact molecular mechanisms connecting the two remained nebulous.

A group at UCSD has proposed that NF-B transcription factors regulated via the IB kinase (IKK) complex play a critical role in coupling inflammation and cancer and tested this hypothesis in mouse models of cancer. Using mice bearing mutations in the genes coding for the IKK and IKK catalytic subunits they have obtained evidence supporting a critical role for IKK in tumor promotion and more recently identified the involvement of IKK in metastatogenesis. Whereas the major pro-tumorigenic function of IKK is mediated via NF-B, the pro-metastatic function of IKK is NF-B-independent.

In addition to illustrating the critical roles of the two IKK molecules in linking inflammation and cancer and providing an explanation for increased cancer risk in response to persistent infections and inflammation, these results also identify new targets for development of novel anti-cancer therapies and preventive strategies. Instead of targeting the cancer cell itself, as done by conventional anti-cancer drugs, the new therapeutics will target processes that occur within inflammatory cells that are essential for cancer development and progression. Unlike cancer cells, inflammatory cells retain a normal and stable genome and therefore are unlikely to become genetically resistant to therapeutic intervention.

(Source: Cell Research (2008) 18:334–342 - http://www.nature.com/cr/journal/v18/n3/full/cr200830a.html)

Webinar on miRNAs and Cancer

2008-03-04T07:35:00.000-08:00

Hi Guys,

I found this cool webinar on miRNA and their role in tumorigenesis at Science: http://www.sciencemag.org/webinar/. microRNAs (miRNAs) play critical roles in developmental and physiological processes by regulating target gene expression at the posttranscriptional level. It is therefore not surprising that deregulation or dysregulation of miRNA expression could result in specific disease phenotypes. Increased interest in the function of miRNAs in tumor initiation and progression has rapidly propelled research forward as new technologies, or the adaptation of old technologies, has allowed researchers to screen both more broadly and more specifically for aberrant miRNA expression in cancers.

This webinar focuses on some key cancer-related miRNAs currently under investigation, as well as methods for detection and characterization of miRNAs, particularly those suspected to be involved in tumorigenesis. Progress toward the development of possible cancer biomarkers will be discussed, as will problems and hurdles that miRNA researchers might encounter and how to overcome them.

Cells make sound and are responsive to it!

2008-02-11T08:37:00.001-08:00

Respected All,

Today, at breakfast, I was discussing the cellular response to near-infrared light wih a PhD fellow & a good friend of mine when he proposed the idea -"Do you think cells make sound or they respond to sound?" It was a wonderful question and a little Pubmed search gave me my Valentine's gift. Check this out:

"Bacterial cells enhance the proliferation of neighboring cells under stress conditions by emitting a physical signal. Continuous single sine sound waves produced by a speaker at frequencies of 6–10, 18–22, and 28–38 kHz promoted colony formation by Bacillus carboniphilus under non-permissive stress conditions of high KCl concentration and high temperature. Furthermore, sound waves emitted from cells of Bacillus subtilis at frequencies between 8 and 43 kHz with broad peaks at approximately 8.5, 19, 29, and 37 kHz were detected using a sensitive microphone system. The similarity between the frequency of the sound produced by B. subtilis and the frequencies that induced a response in B. carboniphilus and the previously observed growth-promoting effect of B. subtilis cells upon B. carboniphilus through iron barriers, suggest that the detected sound waves function as a growth-regulatory signal between cells."

Source: http://www.ncbi.nlm.nih.gov/pubmed/12501293

It further strenthens my view that - Cells are "complete" individuals with all the senses that we possess! I am sure you all are aware of the intelligent visual capabilities of cells. If not, have a look here: The cellular infrared detector appears to be contained in the centrosome. Cell Motiltiy and the Cytoskeleton 27:262-271 (1994)

Kind Regards,
Tarun Gupta

--
MSc Human Genomics
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India
Mob: +91-9888237906

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

****************************** *******************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

*************************************************

Centrosomal Genome! - A PNAS report

2008-02-10T04:02:00.001-08:00

Respected All,

I wonder how I missed it! A 2006 paper in PNAS indicates that centrosomes may have their own genome! Unlike the nuclear, mitochondrial or chloroplast genome, it is RNA-based rather than DNA-based, and apparently includes an RNA sequence capable of duplicating the centrosome genome. The putative centrosome genome RNA sequences were purified from oocytes of the surf clam, Spisula solidissima.

They have shown by biochemical means and subcellular in situ hybridization that the first transcript they analyzed is intimately associated with the centrosomes. Sequence analysis reveals that this centrosome-associated RNA encodes a conserved RNA-directed polymerase domain. In this paper authors hypothesise that centrosomes contain an intrinsic complement of specific RNAs whch may provide new opportunities to address the century-old problem of centrosome function, heredity, and evolution.

Source: Proc Natl Acad Sci U S A. 2006 June 13; 103(24): 9034–9038

Link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16754862

Kind Regards,

Tarun Gupta

--
MSc Human Genomics
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India
Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

****************************** *******************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

*************************************************

Comments to - Questionable Data in reputed journals

2008-02-07T09:45:00.001-08:00

Hello,

I am a Masters Student at National Centre for Human Genome Studies and Research, India. I have been discussing experimentation designing for my senior's dissertation when I came across a strange yet deeply purturbing issue which i really want to share with the Scientific community here.

I came across a paper in very reputed scientific journal that had quite questionable data in terms of appropriate Control selection and experiment analysis, yet what bothered me is that inspite of such irregularities, it managed to get published in one of those so called "journals of very high repute!" Moreover, not even once, the author tried to relate/design his experiment to simulate physiological conditions but at the end he is simply extrapolating his data hypothetically to make a statement at physiological levels!

All my concerns regarding that paper were confirmed by senior PI's. I am not in favor of creating any controversies by naming the paper but with such papers keep on getting published in good journals, I am sure the day is not far away when we'll lose our trust in "good" journals?

Kind Regards,
Tarun Gupta

MSc Human Genomic
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

Questionable Data in reputed journals. Where are we heading to?

username: Elsie Mon, 04 Feb 2008 10:21 AM

Oh...this is something that happens all the time in science. It is frustrating because even if a paper in a highly respected journal (let's say Science Cell or Nature) is debunked by the community in later publications, the first author still gets to put a "Big 3" paper on his or her resume...and hiring committees and grant reviewers see "Big 3" and go "oooooohhhh!" and don't look any further. It is very frustrating. The lesson to be learned here: A lot of really good, groundbreaking science is published in field specific journals. Judge by the content, not by the location. The best thing you can do (and which is what I have done) is do the experiment right, publish it, refer to the bad paper and in your discussion say something like "our results conflict with ______. One possible explanation is that their controls were screwy" of course you have to say it in a much more professional way.

Questionable Data in reputed journals. Where are we heading to?

username: Justin Mon, 04 Feb 2008 12:37 PM

Happens all the time. It is well-known in the field that ~50% of all material published in Cell, Science, and Nature have glaring problems. We are not talking about inherent ambiguities of science, but the accuracy and quality of the actual printed material. Unfortunately, in the field of publishing, there is a lot more than meets the eye about what gets published. Many times, it's about politics, position, power, or connections.

Interesting Article about "Ethics Educator" Grant

username: Eric Mon, 04 Feb 2008 03:52 PM

Tarun,

Your frustrations are common to us all. Elsie, Justin, and Dave have given excellent assesments of this problem, and there is little else to add to their posts other than to say that science is in reality a very political business far removed from purity. Another problem you may have noticed, one that relates to Elsie's observations, is the tendency of authors to reference lower-quality studies from big-name labs pblished in big-name journals rather than a more appropriate and more scientifically-sound study published in field-specific journals. There is a tendency to assume a Cell/Nature paper must be good science, and a not-so-subtle desire to curry favor with powerful people by giving them undue credit and reference. It happens all the time, and I see no end to the problem short of eliminating this absurd construction called the "impact factor."

Interesting Article about "Ethics Educator" Grant

username: Baoloa Mon, 04 Feb 2008 06:47 PM

An interesting perspective on this issue was recently published in Nature, where Pubmed was trawled for duplicate publications:
http://www.nature.com/nature/journal/v451/n7177/full/451397a.html

A good comment was also made here:
http://pipeline.corante.com/archives/2008/01/30/recycle_reuse_republish.php

However, one would have to be pretty inept to be caught by this method.

Ethics and Misconduct in research

username: Garth Tue, 05 Feb 2008 10:57 AM

The Office of Research Integrity (ORI) is a high-level office in the Department of Health and Human Services (which is the home department of may research funding gov't agencies, including NIH). Its mission is to monitor (and sometimes spearhead) investigations of misconduct and promote responsible conduct of research through policy, education, and regulatory activities. There are regular reports of ethics violations, and established researchers loosing HHS and Fed gov't funding, their positions, and fines against university wide ethics violations.

It is worth checking out the ORI website, and keeping abreast of what ORI does. Most scientists (young and old) are not aware that the Federal Government has an appointed office of scientifically trained (i.e., with PhDs and MS degrees, and years of research/lab experience) investigators to deal with ethics and integrity violations. Being an active member of 'the science community' means promoting ethics and integrity, and ORI is a great way for you to become more involved and aware of what is being done in ethics education for scientist. And besides, if you do not become aware an involved in what ORI does, and pass this on to your friends (or eventually the young scientists you will mentor), then who will?

http://ori.dhhs.gov/

Questionable Data in reputed journals. Where are we heading to?

username: Tarun Wed, 06 Feb 2008 10:28 AM
affiliation/organization: National Centre for Human Genome Studies & Research

Being a new kid in the block, these are real eye openers. I still wonder how such articles escape editors eye! Do they simply believe that if a paper is from so-and-so lab, it must be OK!

As an outset, These publishing houses are more of buisnesses than just science journals. They charge a significant amount of money from its readers and its their responsibility to maintain "quality" of information. They simply can't sell junk for so much money! There must be a stringent "quality control mechanism".

Perhaps, at least "Big3", should take a note of this and include someone from ORI or people with special training in ethical aspects of science. I wonder if editors are reading this!

Questionable Data in reputed journals. Where are we heading to?

username: S.H. Wed, 06 Feb 2008 10:37 AM

This thread raised a very valid point. From the past few years, 0nly 10%-20% of the papers presented in my lab's journal club have somehow proved their points by the evidence they provided in the paper. Good quality papers are hard to come across.

Questionable Data in reputed journals. Where are we heading to?

username: Elsie Wed, 06 Feb 2008 11:09 AM

Another good thing to remember is that when you are asked to peer review articles...it is your job to protect the literature! It is easy to fall into the trap of feeling bad for some poor postdoc or graduate student who did a lot of work... but if their data is bad, publishing it validates it and it makes it that much harder for the next poor postdoc or graduate student who might actually be on the right track.

Questionable Data in reputed journals. Where are we heading to?

username: Ale Wed, 06 Feb 2008 01:53 PM

But Elsie, a reviewer can catch up missing controls or retouched pictures, you cannot see pure fake data or the double publications (most of which were found to be submitted at the same time to different journals since teh publication dates were to close).

I also think there is a part of this due to the good reputation of some big senior authors. Revieweers and Editors trust in her internal filter before sending the manuscript out and labs with no reputation (no one knows you) have to prove themselves right on every paper. I agree with Tarun on this.

Questional Data in Reputed journals. Where are we heading to?

2008-02-03T23:35:00.001-08:00

Kind Regards,
Tarun Gupta

--
MSc Human Genomics
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India
Mob: +91-9888237906

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

****************************** *******************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

*************************************************

How Loud Is Safe?

2008-01-27T04:21:00.001-08:00

Following data from Harvard Medical School's HealthBeat online magazine reports the sound levels that are safe for your ears:

Protect your ears from sounds louder than 80 decibels.
Decibels	Sounds
20	Watch ticking
30	Whispering
40	Leaves rustling, refrigerator humming
50	Neighborhood street, average home
60	Dishwasher, normal conversation
70	Car, alarm clock, city traffic
80	Garbage disposal, noisy restaurant, vacuum cleaner, outboard motor, hair dryer
85	Factory, screaming child, portable stereo at high volume
90	Power lawn mower, highway driving in a convertible
100	Diesel Truck, subway train (outside, not as a passenger), chain saw
120	Rock concert, propeller plane, portable stereos on maximum volume
130	Jet plane (100 feet away), air-raid siren
140	Shotgun blast, explosion
Sounds of 80 dB or less are believed to be safe for nearly all healthy adults, no matter how long you hear them. Sounds of 91 dB should be limited to no more than two hours for a healthy adult. Limit 100dB sounds to 15 minutes and 120 dB sounds to about nine seconds. The long-term effects of high noise levels for children are unknown; therefore, the thresholds cited here may be too high for them.

Kindly pass it on further in the best interests of your near and dear ones..

Phyhormone controls animal-like protozoans!

2008-01-14T00:52:00.001-08:00

Respected All,

The single-celled creatures known as protozoans are primitive, exotic, and sometimes just plain weird, resembling animals, plants, or a combination of both. Animal-like parasitic protozoans are extremely difficult to control because their animal-like bioloy which is often very similar to that of their hosts. As a result, drugs that target these parasites all too often damage the cells of the patient.

However, a paper in Nature reports that one animal-like protozoan - Toxoplasma gondii, which is a parasite that causes the disease toxoplasmosisrelies, has a biochemical pathway that is strikingly plantlike i.e . production of abscisic acid, a hormone that in plants controls stress responses and dormancy. In this parasite, phytohormone abscisic acid (ABA) controls calcium signalling which controls a number of critical events, including motility, secretion, cell invasion and egress by apicomplexan parasites.

When the researchers disrupted abscisic acid production using a commonly available herbicide, the parasites inside animal cells in culture remained inactive even after reaching numbers that would normally have led to a violent mass exodus. The discovery could open up a new method of attacking protozoans that cause diseases such as malaria.

(Source: Nature 451, 207-210, 10 Jan 08)

DNA boosted Anticancer Sunscreen!

2008-01-09T00:59:00.001-08:00

Respected All,

A recent report in PNAS suggest that slapping on sun-cream containing DNA fragments might cut the risk of skin cancer, after showing that the treatment works for mice. The DNA fragments are thought to trick skin cells into thinking that sunlight has damaged their DNA. This triggers production of proteins that repair and protect cells' genetic material from further mutations that might spark cancer.

The team slathered mice with the DNA lotion and then mimicked mild sunburn using ultraviolet (UV) light. The treated animals stayed free of pre-cancerous skin lesions for 16 weeks, while unprotected ones succumbed after 9 weeks. Researchers hope that the fragments could be a powerful new ingredient in sunscreens - one whose effect lasts days rather than hours. It might even help cells resist the sun damage that contributes to ageing, speculates team member David Goukassian. Their team has shown before that the DNA fragments, called thymidine dinucleotide (pTT), stop animals from racking up mutations after exposure to UV light. But the new study is the first time they have shown that the fragments might also retard tumour growth.

References: Goukassian, D. A. et al. Proceedings of the National Academy of Sciences, doi:10.1073/pnas.0306389101 (2004).

Source: Nature - doi:10.1038/news040301-3

Alcoholic drosophila gets lusty!

2008-01-05T08:27:00.001-08:00

Dear All,

Heavy boozing has been shown to send male fruitflies, like their human counterparts, into a lusty fog.

In the flies, hypersexuality caused by chronic alcohol exposure has the effect of making the males chase anything with wings — other males included. Although sexual preference in humans is obviously a complex phenomenon not replicated by the fly work, the findings could be used to further establish a fly model system for the study of alcoholism, observers say.

Although it may seem a bit of a stretch to study alcoholism in fruitflies, intoxicated insects bear many similarities to intoxicated humans, says Ulrike Heberlein, who studies alcohol and cocaine responses in fruitflies at the University of California, San Francisco.

As the concentration of ethanol in the body rises, flies begin to become uncoordinated and oblivious to their surroundings: they get tipsy. Add more alcohol and the flies become sedated. Add still more and the soused flies die. Remarkably, even the concentrations of ethanol that induce these behaviours are nearly the same in flies and humans, says Heberlein. Flies also develop a tolerance to alcohol, and can develop withdrawal-like symptoms.

The researchers noted that male flies repeatedly exposed to ethanol vapour became less discriminate in their mate selection. The buzzed flies often courted fellow males, pursuing them around the cage while serenading with a traditional fruitfly courtship song played on vibrating wings. Eventually, the lusty flies devolve into a courting frenzy.

The findings suggest that the flies do not fundamentally change their sexual orientation, but rather get over-sexed. Multiple alcohol exposures makes them essentially hypersexual. The mind-dulling effects of alcohol might also make it more of a challenge for male fruitflies to distinguish the gender of other flies in the crowd.

Although the drunken dipterans were more amorous, their rates of successful copulation declined after getting tipsy, the researchers found — a trend that has long been observed in humans. In human genetic association studies, the only thing you can reliably detect is genes that have relatively large effects. In flies you have far better resolution because you can grow many flies cheaply and quickly.

References: Lee, H. G., Kim, Y. C., Dunning, J. S. & Han, K. A. PLoS ONE 3, e1391 (2008). & Nature | doi: 10.1038/news.2007.402

Behavior associated developmental Biology

2008-01-01T06:46:00.001-08:00

Respected All,

For quite some time, a rather interesting question is popping up in my mind regarding behavior associated-developmental biology. It may sound vague in first go but as I believe, this question may have a very deep meaning in our understanding of ourselves. I am sure someone would have done some work on it, although I couldn't find any specific papers on this. Here it goes:

Like all humans, all animals have a sense of self-consciousness, the state of identifying oneself as a (human/animal) "being", a sense of self individuality. My question is very simple: When does this sense of self-individuality, or recognition of self, originates during the development? At what stage does it happen - blastula? gastrula? what? This question is complicated by the fact that even a cell is a complete organism in itself and responds to chemical/physical changes so as to get food for "itself", protect "itself" to name a few!

I am not sure if I have been able to convey my points clearly but I would really appreciate your valuable comments on this.

Kind Regards,
Tarun Gupta
--
MSc Human Genomics
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

****************************** *******************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

*************************************************

Wake up p53!

2007-11-22T07:12:00.001-08:00

Respected All,

As we all know, in case of DNA damage, irrespective of the source of mutation, some kinases like ATM, ATR, CHK1,2 etc. sense this DNA damage & go on to phosphorylase p53 and prevent it from binding to mdm2 ubiquitin ligase. This active p53 then stimulates transcription of various proteins like p21 which inhibit G1/S transition.

My Question is: "How exactly this DNA Damage is sensed by ATM/ATR/CHK1,2 kinases? In what form damaged DNA tells these kinases that - hey guys, I am damaged. Go and wake up p53 or any other protein for that matter!"

I would certainly appreciate your valuable views/comments on this. Kindly write to me at: Hotbacteria [at] gmail [dot] com or post your views in Exciting Science Forum: here

Hoping to hear from you!

Many Thanks & Kind Regards,
Tarun Gupta
--
MSc Human Genomics
National Centre for Human Genome Studies and Research
Panjab University
Chandigarh-India
Mob: +91-9888237906

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

****************************** *******************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~About Me: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~My Department: http://nchgsr.puchd.ac.in

*************************************************

A chromatin twist to gene silencing

2007-10-24T13:31:00.001-07:00

Althoughcells typically transcribe both copies of a particular gene,they sometimes flip off one copy and rely on the other. A histone-modifyingprotein might help determine which copies are turned on or off by tweaking the structure of chromatin, according to a recent paper in JCB.

This silencing—called monoallelic expression—reachesan extreme in female mammals, in which one X chromosome almostcompletely shuts down. Which copy a cell chooses to switch offappears to be random, and the selection mechanism remains unexplained.

Last year, the researchers showed that, in embryonic stem cells, would-be active and inactive X chromosomes differ even before one gets silenced. When the scientists tagged specific genes on the chromosomes using fluorescence in situ hybridization (FISH), one X chromosome typically carried two glowing spots (usually a sign that it will be shut down), whereas its counterpart had one (a sign of future expression). What structural differences between chromosomes this pattern reveals is unknown. Autosomal genes that don't need to be silenced tend to show up as either two single dots or two double dots.

This single dot–double dot (SD) pattern also marked monoallelic genes on autosomes, which haven't yet picked which allele to close down. Before a stem cell made that choice, however, the alleles often flipped between single and double states, indicating that the cell is sometimes undecided about which allele to quiet. Switching also occurred on X chromosomes.

Suspecting that the SD arrangement might reflect a differencein chromatin structure, the researchers tested the effects ofdeleting the protein Eed, which helps tighten chromatin by methylating histone H3. Loss of Eed reduced the prevalence of SD cells andresulted in more double dot states. A single spot might indicatescrunched together sister chromatids, while a double spot might reveal standoffish sisters. But how Eed chooses which alleleto target is unknown. The researchers now want to determinewhether the single-spot-on–double-spot-off pattern shown by X chromosomes holds true for autosomes.

(Source: Alexander, M.K., et al. 2007. J. Cell Biol. 179:269–276)

Killer RBCs!

2007-10-24T13:22:00.000-07:00

Red bloodcells need their space. A recent report published in JCB suggests that fetal developingred blood cells might just kill some of the brethrenthey are close enough to touch!

During early embryogenesis, red blood cells need to be producedat a high rate to keep the embryo well oxygenated. Their precursorstherefore start out growing ten times faster than the fetusas a whole. This fecundity must be shut down at the right timeto prevent overgrowth. To determine how growth is limited, agroup at UMMS measured cell numbers at each stage of RBC development and constructed a mathematical model to fit the numerical data.The model predicted the existence of negative autoregulationas a result of physical contact between immature red cell progenitors.

The regulatory system not only keeps the number of cells fromgrowing too large of its own accord, it also protects the systemfrom external perturbations. If a trauma, for example, depletesthe body of red blood cells, their new-found personal spacewill allow for replenishment.

(Source: Socolovsky, M., et al. 2007. PLoS Biol. doi:10.1371/journal.pbio.0050252)

RNA Polymerase on the run

2007-10-22T23:41:00.001-07:00

IsRNA polymerase II slacking off while it's supposed to be onthe job? Probably not. But according to a recent report in JCB, the firstmeasurements of RNA kinetics in individual cells show an unaccounted for two and a half minutes in the protein's schedule!

The polymerase spent justover five and a half minutes at the transcription site. Of thistime, making the RNA strand took 114 seconds, and processingthe 3' end and other housekeeping tasks required another 63 seconds. That left 156 seconds unexplained.

What the protein does during this gap is unclear. The extratime might indicate that the protein pauses on the promoterbefore it starts transcribing or that it performs some otherundiscovered function.

(Source: The Journal of Cell Biology, Vol. 179, No. 2, 171)

Language, Invention & Drosophila!

2007-10-12T07:01:00.001-07:00

Respected All,

I was going through an interesting & thought provoking interview of Dr. Campbell of University of California Riverside with Dr. John Maynard Smith of Univ. of Sussex. At the end of this interview, I observed 2 factual, yet contradictory statements & got abruptly held at an unrequited query which, I am sure, would equally fascinate every single person with general interest in Biology & Science. Kindly read on:

Statement 1: In due course of evolution, humans were incredibly conservative in the tools they used. The same of hand ax was made for quarter of a million years. It's an unbelievable fact, but it's true! Then suddenly, about 50,000 years ago, people became very inventive. They refined hooks, spears, needles, figurines, wall paintings etc. All sorts of new things suddenly started happening! What on earth happened 50,000 years ago that made this happen? The answer to this, as most of the scientists believe, is – Development of Language! Don't believe it? Just try thinking without words!

Take-home-message 1: Language leads to thinking & invention. Without thinking, you can't invent & without Language, you can't think!

Statement 2: Dr. Smith did some sex selection experiments on drosophila in 1950's & found that while selecting the males for mating, female drosophila "dances". When the male sees the female, he comes & faces her. When he's facing her, the female quickly darts to one side & the male has to dart sidewise to keep on facing her. There is a very quick dance with female going from side to side & the male following her. If the male succeeds in facing her for few passages, the female stands still & allows mating but if the male is old, ill or can't see properly, he can't keep up and the female just flies away! So, she's apparently involved in a "decision making process" of testing & selecting males which are healthy enough to produce healthy offsprings!

Take-home-message 2: Female drosophila is involved in a "thinking & deciding" process without Language!

Now, just read both the take-home-messages together:

"Without Language, you can't think BUT female drosophila is involved in a "thinking & deciding" process without Language!"

Any takers?

Kindly express your opinions & views either by writing to me at: hotbacteria (AT) gmail (DOT) com

or at Exciting Science Forum: http://groups.google.com/group/exciting-science

Kind Regards,

Tarun
--
MSc Human Genomics
National Centre of Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

Ingenious inventions

2007-10-09T22:17:00.001-07:00

Sometimes the simplest solutions are the best. Scientists have transformed

A blender into a centrifuge (a)

Recycled gloves (b)

Used a soda bottle as a make-do ice bucket (c)

Devised a simpler flow cytometer (d)

Invented a tip washer for rinsing out pipet tips (e).

Source: Nature Medicine 13, 1130 - 1131 (2007)
doi:10.1038/nm1007-1130b

Turning one Lab's Trash into anothers treasure

2007-10-09T22:10:00.001-07:00

Are you short of grants & equipments?

There is a Seeding Lab, a non profit opened by Graduate students in Molecular Biology at Harvard Medical School. They are doing wonders by turning One Lab's Trash into anothers treasure.

Check out this Nature Medicine Article: http://www.nature.com/nm/journal/v13/n10/full/nm1007-1130a.html

Memory shuts down as you doze off

2007-10-09T11:32:00.001-07:00

Respected All,

Next time you whisper sweet nothings to the object of your affections as they peacefully doze off, don't be surprised if they can't remember a word of it the next morning. Neuroscientists have shown that the brain's pathways for deciphering speech, and forming memories of it, switch off as anaesthetized patients begin to nod off. They suspect the same holds true for normal, non-drug-induced sleep.

David Mellon of Univ. of Cambridge found that the volunteers' brains were more active in response to speech than to generic noise, suggesting that they still recognised spoken words. But the part of the brain involved with the more subtle job of untangling words that can have alternative meanings depending on context or spelling (such as 'pear/pair') showed no activity in the drowsiest volunteers. Neither did the part involved with forming memories of speech.

This suggests that the brain simply shuts down higher-level aspects of speech recognition as sleep starts to set in, making it hard to remember or understand what was said in the moments before sleep.

(Source: Proceedings of the National Academy of Sciences, DavisM. H., et al.)

Following this study, I saw an interesting comment on Nature about remembering dreams. "How can we relate this study with dreams? We can remember some dreams but not others!"

Any comments? Write to me at hotbacteria (at) gmail (dot) com or post them in Scientific Information Sharing Resource: http://sisr.blogspot.com

Kind Regards,
Tarun Gupta

---
MSc Human Genomics
National Centre of Human Genome Studies and Research
Panjab University
Chandigarh-India
Mob: +91-9888237906

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~Bioinformatics Resources: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~About Me: http://hotbacteria.tripod.com

*************************************************

Replies - Water Crystals in Frozen Bacteria!

2007-10-04T14:25:00.001-07:00

Dear Friends,

Referring to my query about water crystals in bacterial cells (see here), I recieved some very interesting replies. Here they are:

1. Jim Dickson, Professor, Dept. of Animal Science at Iowa says:

The crystals that you noticed in your home made ice cream may have been lactose crystals. This is a defect known as "sandiness" in ice cream, and has been documented for many years. There is a great short write up on this from UC Davis. http://drinc.ucdavis.edu/dfoods10_new.htm

Beyond that, freezing does produce ice crystals, which do in fact damage cellular structures . It is related to freezing rate. Slower freezing results in larger crystals with more damage, while rapid freezing results in smaller ice crystals with less damage.

2. Marcos Raul Carot Collins wrote:

Of course the cristals form, and that why you never get back all bacteria. You get SOME of them back, Since they are so many, some survive and start replicating again.

Also the way used to frozen them has been found to minimize the damage. I don't remember the rate of degrees/minute, but it was not too fast, nor too slow. The same to heat them back. And finally you don use just water. You can add to the medium different additives to minimize the damage too.

3. Dr.Arif Khan, Professor of Microbiology, Cancer Hospital & Research Institute, Gwalior wrote:

Your question is really good. Actually it is a exceptional property of water that it expand while freezing. So it should damage the cells during low temperature storage.

Your idea is really true. If we will keep normal cell at -80 degree celcius, it will definately get damaged. So when we keep the cells at -80 0r -20 so we always use cryoprotectant (DMSO, Glycerol etc.)with the solvent used to keep the cells. This cryoprotectants protacts cell from damage by water molecule expansion.

So, we come to a nice conclusion that next time you transform your bacteria and store them in -80, however less, you can expect some DNA damage for sure!

Kind Regards,

Tarun Gupta
--
MSc Human Genomics
National Centre of Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~Bioinformatics Resources: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~About Me: http://hotbacteria.tripod.com

*************************************************

About Schizophrenia

2007-09-26T08:46:00.001-07:00

Hello Friends,

For those of you, who have been wondering about hallucinations of Dr.John Nash, a Nobel Laureate mathematician from Princeton, as depicted in movie "A Beautiful Mind", there is a nice introductory lesson on Schizophrenia.

Its an exciting area for geneticists to hopp in as it has long been known that schizophrenia runs in families. People who have a close relative with schizophrenia are more likely to develop the disorder than are people who have no relatives with the illness.

Research indicates that multiple genes are involved in creating a predisposition to develop the disorder. In addition, factors such as prenatal difficulties like intrauterine starvation or viral infections, perinatal complications, and various nonspecific stressors, seem to influence the development of schizophrenia. However, it is not yet understood how the genetic predisposition is transmitted, and it cannot yet be accurately predicted whether a given person will or will not develop the disorder.

You can find introductory details about Schizophrenia in the following file: http://groups.google.com/group/exciting-science/web/Schizophrenia+-+an+Introduction.pdf

(Source: http://www.schizophrenia.com)

Kind Regards,
Tarun Gupta

--
MSc Human Genomics
National Centre of Human Genome Studies and Research
Panjab University
Chandigarh-India
Mob: +91-9888237906

*************************************************
~Exciting Science forum: http://groups.google.com/group/exciting-science
~Bioinformatics Resources: http://hotbacteria.blogspot.com
~Scientific Information Sharing Resource: http://sisr.blogspot.com
~About Me: http://hotbacteria.tripod.com

*************************************************

Research Links

2007-09-26T06:28:00.000-07:00

Research:

Sponsored Listings

IBM Human Genome

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Room Temperature Storage

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Islet Cell Transplantation

Information on Islet Cell transplantations for diabetics

Shotgun Sequencing

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Microbial Corrosion

Information about Microbial Corrosion

Peptide DNA Synthesis

Peptide DNA hybrid-oligo ultra fast synthesis

Competence in RNAi

Automated validation of siRNA, shRNA and genetic targets

siRNA Transfection

Efficient transfer of siRNA into primary cells and cell lines.

DNA Ancestry project

Discover your ancestry with DNA. Find your ethnic and geographical origins.

Macrogen DNA Sequencing

Mixing the oceans to reduce global warming

2007-09-25T00:08:00.000-07:00

Could mighty pumps be installed in the ocean to mix up the waters and cool the planet? At least some scientists and businessmen believe so — but the idea is controversial.

In a letter to the editor published in Nature this week, James Lovelock and Chris Rapley suggest that this deus ex machina could be an "emergency treatment for the pathology of global warming". Large vertical pipes could, they say, be used to mix nutrient-rich waters from hundreds of metres down with the more barren waters at the surface. This could cause algal blooms at the surface, which would consume carbon dioxide (CO ₂) through photosynthesis. When the algae die, some of this carbon could sink into deep waters.

The algae may also produce chemicals that spur cloud formation, further cooling the planet.

The notion of fertilizing the ocean to increase biological productivity and decrease atmospheric CO₂ is not new. And it is just one of several controversial geo-engineering techniques, including putting mirrors in space to reflect sunlight, that have been proposed as means to cool the climate.

There is an amazing paper on "technological approaches to cooling the Earth" that was published in Nature in May 2007. This paper discusses various mazing concepts like:

Burying carbon dioxide underground,
Increasing the proportion of sunlight that bounces off hazes in the atmosphere and back into space,
Creating 'artificial volcanoes' for injecting sulphur high into the atmosphere like what happened in Philippines on 15 June the volcano Mount Pinatubo exploded cataclysmically, blowing a plume of molten rock, ash and gas as high as 40 kilometres into the atmosphere and much of the plume's sulphur dioxideended up in a cloud of tiny particles spread around the stratosphere, more than 20 kilometres up, and there it remained for years. The thin global veil of sulphates made the planet's sunlight more diffuse.
Using a fleet of 'fliers', the size of dustbin lids, that would be launched from Earth in prepacked stacks by means of a vast electromagnetic cannon. Once in orbit, the gossamer-thin fliers would peel off these stacks and arrange themselves in orbits that keep them between the Earth and the Sun at almost all times. The shadow of this cloud of spacecraft 1.85 million kilometres away, Angel calculated, would be a little larger than the Earth, and would cut down sunlight by about 1.8%.

You can access this article here: Nature, Vol 447, 10 May 2007

In case you do not find the article or you do not have access to Nature, you can send a request mail to me at Hotbacteria [at] gmail [dot] com

Education Tools and Jobs

2007-09-22T12:04:00.001-07:00

Education Tools and Jobs

Education:

Sponsored Listings

IGE

Institute of Genetic Engineering, WB Biotech Foundation, Genetics

Summer training 2007

Appin Hi-tech Training New Delhi Project based.

Bioinformatics Programs

Distance Participation Training for students and professionals

Sangar PhD Programme

Fully funded 4 year studentships in genomics

Zenosis

up to minute online regulatory training for global life sciences

Bioinformatics at Oxford

Statistics for BioSciences course

Bioinformatics

New International MSc programs at Technical University of Denmark

Complete list of Colleges

Top Indian Educational Institutes

Tools:

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Fast real-time PCR

LightCycler 480 system, 96/384 multiwell format!

The RNAi Resource

Everything you need to know about RNAi and gene silensing!

Knockout Transgenic mice
Everything you need to know about RNAi and gene silensing!

Free Bioinformatics Tools

DNA and Protein Alignment Software User-friendly, Integrated and Free!

Bioinformatics Software

Bioinformatics using neural network software. Free eval download.

DNA Sequence Analysis

Fast, Easy software, Visualizations, Next-Gen assembly, SNP discovery

PhosphoSite Database

A curated scientific resource of in vivo protein phosphorylation

Protein-Protein Binding

Visualize protein interactions mined from literature. Free download

Pathway Analysis Software

Discover relationships among genes. Free Download

Jobs:

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Hot Jobs in Biotechnology

Immediate Requirement in companies

Clinical Research Jobs

Orphan Disease Drug development On Gilford harbor. Near Yale.

Chandigarh Job Openings

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Synthetic Genes Give Cells Something to Remember

2007-09-22T06:05:00.001-07:00

A genetic feedback loop installed in a yeast cell, the first of these circuits to be built in a eukaryotic cell—one with membrane-bound structures, such as a nucleus—may allow scientists to construct cells that can remember when they've been exposed to certain signals, a development that could one day halt the spread of cancer and better assess environmental damage.

Such a project—involving new gene construction, a predictive behavioral model, and the synthesis of their desired functions—is a major step forward for the fledgling field of synthetic biology, which seeks to better understand and co-opt the machinery of cells.

"Synthetic biology is a new area that's really exciting to young scientists—to have things begin to work in this way is a sort of validation of the field," says Pamela Silver, a professor of systems biology at Harvard University Medical School and co-author of a study demonstrating one of the first synthetic restructurings of a eukaryotic cell that is described in the journal Genes & Development. "Even though these are sort of demonstration experiments" (indicating that the technology is feasible), "they can be carried over into applications."

Among the possible applications, says Silver, would be tinkering with cells so that they can be used to assess the severity of an environmental incident, such as an oil spill, when they activate synthesized genes that respond to the presence of certain chemical. They could also be jerry-rigged to recognize and quantify the amount of DNA damage they have sustained—a development that would be helpful in preventing and combating diseases such as cancer.

Silver and her team constructed two new genes that would code for two artificial proteins designed to behave as transcription factors (proteins that control the amount of other proteins that a particular gene can make.) The genes for each transcription factor were made from different bits of DNA that code for the functional parts of proteins, such as a domain that can bind to DNA and another that provides the protein with access to the cell's nucleus.

In a nutshell, the researchers set up a system in which the yeast cell would activate the first of the implanted genes and its corresponding transcription factor (tasked with switching on the second gene) when exposed to the sugar galactose. The second gene would then manufacture its corresponding transcription factor, which was designed to bind to and ratchet up the activity of the same gene that created it.

This created a closed loop that did little to affect the normal life of the cell. Because of the looping effect that the second transcription factor had on its own gene, the second transcription factor continued to be manufactured even when galactose was eliminated from the cells' environment (thus shutting off the activity of the first gene). Silver says that this effectively sustains the memory of galactose exposure.

"Think of it as you expose the cells to something and then you take it away, but they remember that they saw it," she says. "Imagine going forward [that] you might want to build a cell that not only told you it was exposed to something but it could tell you how much or when." Silver says her lab will try to build such a cell that they can then implant into mammals to detect and report on the extent of harm caused by UV radiation, which damages DNA and is a risk factor in the development of cancer.

(Source:Scientific American)

Scent in your genes

2007-09-22T06:02:00.001-07:00

A single gene that codes for one odor receptor (of more than 400 functional receptors in humans) can determine whether someone perceives a particular steroid derivative of testosterone as odorless, smelling like urine—or sweet vanilla.

A team of scientists at the Duke University Medical Center in Durham, N.C., and The Rockefeller University in New York City had nearly 400 blood-tested volunteers sniff 66 scents to determine whether there is a genetic link to the way an individual perceives the odor of androstenone (a key component in male sweat and urine).

The results of the study, published in Nature, indicate that a person's perception of the pheromone (a chemical that conveys information between individuals within a species) androstenone is largely determined by an odor receptor known as OR7D4; variations in the gene that codes that receptor influence the spectrum of responses people have to the scent of androstenone as well as a related chemical androstadienone (also found in male sweat and urine).

"In my mind, this work represents the first example of a direct link between genetic variability in olfactory receptor genes and differences in the sense of smell," says Yoav Gilad, a professor of human genetics at the University of Chicago, who was not involved in this study.

The Rockefeller team, led by Leslie Vosshall, an associate professor of neurogenetics and behavior, directed 391 volunteers to sample the scents (ranging from spearmint to banana to butanol) in two different concentrations and describe how they smelled. Researchers in the lab of Hiroaki Matsunami, an assistant professor of molecular genetics and microbiology at Duke analyzed the subjects' DNA in an attempt to determine whether a person's perception of androstenone smells can be traced to variations in the gene for OR7D4, previously found to interact with the steroid.

Matsunami's team found two variations (or alleles) of the gene associated with different characterizations of androstenone's smell: Subjects with two "normal" copies of the gene, about 62 percent of the study population, described androstenone's aroma as having an intense, unpleasant odor similar to that of urine. If a person had one of each allele, he or she described the scent as ranging from imperceptible to unpleasant, but not intense.

Only 10 of the study participants had two copies of the mutated gene, according to Hanyi Zhuang, a graduate student in Matsunami's lab. "[These] subjects indeed show even lower intensity ratings to androstenone and androstadienone in our study," she says, and even described the smell of the steroids as sweet, like vanilla. The fact that some [of these] subjects could smell androstenone, she continues, "suggests additional odorant receptors are activated by these chemicals."

Zhuang believes that the odor receptor has likely been shaped by evolution, because of the role the scent of androstenone and androstadienone plays in evaluating mates. "One aspect of it is whether we can find evidence that odorant receptor variants play any roles in physiological changes caused by exposure of these sex steroid–derived odors," she says. "In other words, people who have two copies of functional variants might show more changes in mood or hormonal levels when exposed to androstenone or androstadienone."

(Source: Scientific American)

Testes May Prove Fertile Source of Stem Cells

2007-09-22T05:59:00.001-07:00

Researchers say they have found a way to pluck out a potent type of stem cell from the testes of adult mice and transform it into other kinds of tissue, including heart muscle and blood vessels.

The result—the second such finding in the past year—suggests that similar cells from human testicles might have similar powers, paving the way to creating replacement tissue for men who have suffered damage from heart attacks or other injuries and avoiding some of the controversy surrounding embryonic stem cells (ESC).

Three separate groups reported in June that they had reprogrammed adult mouse skin cells into a form nearly indistinguishable from ESCs. But researchers still have to figure out how to prevent those cells from causing cancer.

Women already have a source of custom stem cells (in principle) in the form of parthenogenetic embryos grown without sperm.

To give men their fair shake, Shahin Rafii, professor of genetic medicine at Weill Cornell Medical College in New York City, along with Memorial Sloan-Kettering Cancer Center medical oncologist Marco Seandel and their colleagues homed in on a specific group of mouse spermatogonial progenitors—stemlike cells that give rise to cellular sperm factories called spermatogonia.

Normally, adult stem cells can only morph into the type of tissue in which they reside, such as blood, brain or muscle. Rafii says, however, that cells giving rise to sperm—and, therefore, embryos—should have the same developmental potential as sperm do. He notes that testicular and ovarian cancers often produce teratomas, noninvasive tumors made up of tissues from all three embryonic layers.

The group first extracted and purified progenitor cells bearing a protein molecule called GPR125. When transplanted back into the mouse testis, they produced spermatogonia as expected.

The team then cultured the cells for several months in a bath of growth-promoting proteins, trying to get the cells to reverse course and become more like stem cells. When they injected the tissue into growing mouse embryos, the cells formed teratomas like ESCs do, and mingled with the blood vessels of the mice, the group reports in this week in Nature.

Other groups reprogrammed mouse skin cells by inserting four embryonic genes, some of which are oncogenes (genes that promote cancer). "To me the therapeutic potential of this is much more tremendous than to reprogram a skin cell with four oncogenes," Rafii says. "We reprogram without genetic tweaking."

The challenge, he says, will be figuring out how to force the transition from progenitors to stem cells, which spontaneously occurred in about one third of testicular cell lines.

Scientists in Germany last year reported that they could transform adult mouse spermatogonial progenitors into cells genetically resembling ESCs by using a different growth medium for just a few weeks. Without a marker, however, "they have no clue where their cells came from," Rafii says.

Better markers would be valuable for purifying and studying cells, says molecular geneticist Takashi Shinohara of Kyoto University in Japan, who led a group that in 2004 discovered cells similar to ESCs from newborn mouse testes. But he is skeptical about the newer studies, which are yet to be confirmed by other labs.

Others are more upbeat, but agree more research is needed. "The studies seem carefully done to me," says stem cell biologist Sean Morrison of the University of Michigan Medical School. "I suspect a lot of people are watching to see if the results will fully hold up or whether it will turn out to be only partially true."

(Source: Scientific American)

Putting the Brakes on Cell Death

2007-09-22T05:54:00.001-07:00

The sudden death of worms in room-temperature water has helped scientists identify a regulator of necrosis, a common form of cell death. Although preliminary, the discovery could help scientists better understand necrosis and perhaps figure out ways to stop it in human diseases.

There are several ways a cell can die. One, apoptosis, is a form of controlled cellular suicide, usually for the benefit of the organism. The gaps between our fingers and toes are one mark of this process. Necrosis is virtually the opposite: The cell isn't trying to die, but factors such as blood loss or oxygen deprivation make it swell and explode. Necrosis has gotten much less attention than apoptosis, and although some scientists have found ways to accelerate it, it's never been clear that it can be halted.

Neonatologist and molecular biologist Gary Silverman of the University of Pittsburgh in Pennsylvania and his colleagues came to necrosis in a roundabout fashion. The team was interested in proteins called serpins, some of which help control blood clotting and inflammation. So they knocked out the gene for a serpin called SRP-6 in worms. To their disappointment, the animals seemed unbothered.

But postdoc Cliff Luke noticed that the worms died rapidly when he washed them in room-temperature water. The death was necrotic, the team found, and appeared to be a stress response gone awry; the animals couldn't adjust the volume of fluid in their cells as normal worms do when exposed to water. Looking more closely, the scientists saw that lysosomes, sacs in cells that help break down cellular garbage, had burst. The worms without SRP-6 were also more likely to die than normal worms when subjected to other stressors, including heat and oxygen deprivation. Finally, the researchers found that, when they injured the worms' lysosomes, worms lacking SRP-6 could not repair their lysosomes, whereas normal worms could. Taken together, this suggests that SRP-6 protects worm cells against lysosome rupture and necrosis, the scientists conclude in the 21 September issue of Cell.

"I'm quite amazed," says Wei-Xing Zong, a molecular biologist who studies cell death at Stony Brook University in New York. "When people look at necrosis, ... they kind of never think that this can be controlled."

The distinction is important, says Guy Salvesen of the Burnham Institute for Medical Research in San Diego, California, because "if there's a pathway" governing the process, interfering with it may help fight the damage from those diseases. Still, it's not clear yet how well necrosis can be controlled, he cautions, and the jury's still out on whether Silverman's work will translate to humans.

(Source: ScienceNow)

Honey Bee Defense Leaves Hornets Breathless

2007-09-22T05:52:00.001-07:00

Faced with a giant marauding hornet, Cyprian honey bees swarm the insect, killing it by literally squeezing its breath away, according to a new study. The behavior takes advantage of the hornet's vulnerable mode of respiration and represents a unique form of defense among insects.

Bees can defend themselves with more than their stingers. Certain subspecies, such as Japanese honey bees, guard against hornets by "thermoballing." Tens to hundreds of bees surround the predator and vibrate their muscles, heating the hornet to a deadly 45°C.

That trick won't work on Oriental hornets (Vespa orientalis), which are native to Cyprus and other warm locales, such as Saudi Arabia, and thus tolerate heat. Yet Cyprian bees (Apis mellifera cypria) still manage to kill the insects by mobbing them. The phenomenon led entomologist Alexandros Papachristoforou of Aristotle University in Thessaloniki, Greece, and his colleagues to wonder if the bee swarm might somehow suffocate the hornet.

Hornets breathe through holes in their abdomens called spiracles. They contract their abdominal muscles to exhale and relax the muscles to inhale. As the insects exhale, the plates of their exoskeleton gradually cover the spiracles, and hornets can only open the plates back up to uncover the holes when their abdomens are free to move. Papachristoforou's team wondered if the sheer weight of the bee ball might keep the plates closed, preventing the hornets from sucking in fresh air. To find out, the researchers fit hornets with plastic blocks designed to wedge open the spiracle covers, allowing some air to move back and forth no matter how much insect weight was on the hornets' backs. It took the bees an hour and a half--nearly 50% longer--to kill hornets whose spiracle covers were wedged open versus control animals without the wedges, the team reports in the 18 September issue of Current Biology.

It's a good example of an evolving arms race between predator and prey, says Papachristoforou. Cyprus is isolated, he notes, meaning that the Cyprian bees have likely not faced many invasions of new predators. That's allowed them to evolve tailored defenses that exploit the weaknesses of the native hornets, Papachristoforou says.

The results may prompt researchers to take a closer look at how other bee subspecies deal with their own native hornet predators, says Randall Hepburn, an entomologist at Rhodes University, in Grahamstown, South Africa.

(Videao of honey bees swarming the hornet: http://sciencenow.sciencemag.org/feature/data/beeswarm.avi)

(Source: ScienceNow)

Fish Quick to Recover From Mercury

2007-09-22T05:50:00.001-07:00

The bad news about mercury pollution is that it's harmful, widespread, and has been going on for decades. The good news is that if emissions of mercury can be limited, its concentration in fish and other creatures will decline in relatively short order. That's what a team of researchers has found during a years-long controlled experiment on a large lake ecosystem in Canada.

Mercury is one of the most toxic materials affecting the environment. As early as the mid-18th century, it was used in everything from hatmaking to dentistry. Now the biggest source of emissions in the United States is the smokestacks of coal-burning power plants. They have been depositing mercury in lakes and other aquatic ecosystems, where bacteria transform it into a dangerous form called methylmercury. This becomes even more concentrated through the food chain, finally reaching humans when they eat fish.

To study the effects of mercury, a team of researchers added an inorganic and much less toxic form of mercury to a lake and its watershed in western Ontario, artificially increasing mercury input sixfold. Since the beginning of the 7-year experiment, the team has regularly measured mercury levels in the food chain and in its top predator, the northern pike. Reporting online this week in the Proceedings of the National Academy of Sciences, the researchers reveal that their experiment, called METAALICUS, found that almost all of the mercury absorbed by the pike population came from the amounts they added to the lake's surface. A small additional amount accumulated from the watershed. Based on the fact that most environmental mercury enters lakes at their surface, the team concludes that restricting or removing mercury from power-plant emissions should result in a decontamination of the pike population within a few years.

"There's a lot of other circumstantial evidence supporting this conclusion," says biogeochemist and co-author John Rudd of R & K Research Inc. in Salt Spring Island, British Columbia. The levels of mercury in the ecosystem "may not go down in exactly the same way" as they accumulated, he says, "but they will go down." Rudd says the next phase of the experiment is to stop adding mercury to the lake and observe how quantities in the lake inhabitants change.

The researchers have done a "superb job" of detailing the changes in mercury in the lake system, says aquatic toxicologist James Wiener of the University of Wisconsin, La Crosse. In particular, he says, the study shows how readily mercury can accumulate within the bodies of fish, which reinforces health concerns about the consumption of contaminated fish by humans. Moreover, he says, the work "demonstrates the probable effectiveness of reducing emissions."

(More Details can be found here: http://www.epa.gov/region5/mercury/meetings/May05/harris.pdf)

(Source: ScienceNow)

Special skin cells get pigments

2007-09-20T05:15:00.000-07:00

Skin coloration comes from melanocytes, which donate pigment to epithelial cells. Now, findings from Lorin Weiner, Rong Han, Janice Brissette (Massachusetts General Hospital, Charlestown, MA), and colleagues reveal that color is given out selectively to the dedicated skin cells that request it.

Since melanocytes are the givers of melanin, they've been the focus of studies on coloration. "But we are now showing that epithelial cells tell the melanocytes what to do," says Brissette. "It's analogous to a child's coloring book. Pigment recipients collectively form the outline of the picture, where the pigments should be placed. And the melanocytes color in the picture."

Brissette's group is interested in a transcription factor called Foxn1 and its role in the skin. For functional studies, they created mice whose skin precursor cells made extra Foxn1. The mice developed dark skin that had extra melanocytes. As the mice matured, the cells making Foxn1 became sparser. Melanocytes persisted mainly near the remaining Foxn1-expressing cells, suggesting that those cells might help melanocytes survive or proliferate.

One survival factor that melanocytes don't make themselves but do need in culture is Fgf2. The authors found that Foxn1 activated Fgf2 expression, resulting in its secretion from epithelial cells. Blocking Fgf2 activity killed off the extra melanocytes in the transgenic mice.

Humans, who have darker skin than do mice, expressed Foxn1 more widely in epithelial cells. But whether Foxn1 defects cause human pigmentation diseases is not yet known.

(Source: Weiner,L., et al. 2007. Cell. 130:932-942).

proteinase K - extra power

2007-09-19T08:24:00.001-07:00

Hello Friends,

Yesterday, we were isolating Genomic DNA from Chicken's blood and I came across a strange step in the protocol - My Supervisor told me to add Proteinase K to chop off the cellular proteins and also add 1 % SDS to assist proteinase K in protein degradation! Noticed something..?? SDS is being used to denature polypeptides while proteinase K is also supposed to work! If I remember right, proteinase K is an enzyme itself and SDS binds to amino acids non specifically and renders an overall negative charge to the protein resulting in protein degradation by swamping its intrinsic chage. But strangely, SDS here does NOT denature proteinase K; rather it increases its activity!! This is really interesting and strange.

I tried some research over the net but couldn't find any paper describing this. Any comments or suggestions on this will be most appreciated. Kindly write to me at hotbacteria [at] gmail [dot] com or kindly share your views at the Exciting Science Forum at - http://groups.google.com/group/exciting-science/topics

Kind Regards,
Tarun

Genes for running races!

2007-09-17T09:16:00.001-07:00

Marathon running might be in some people's genes, according to a new study, which shows that a genetic mutation that boosts muscle endurance has spread widely in some human populations.

There are two types of skeletal muscle fibers. Fast fibers, which use sugars for fuel and do not require oxygen, kick in for tasks that require maximum force and quick action, such as sprinting. Slow fibers, which employ oxygen-using (or aerobic) pathways, power activities that require endurance, such as long-distance running. A protein called alpha-actinin-3 is made mostly by fast fibers and is implicated in their capacity for rapid force generation. About 18% of people of European descent do not produce the protein at all due to mutations in both their copies of the gene ACTN3, which codes for alpha-actinin-3. Previous studies have shown that endurance athletes such as long-distance runners have higher frequencies of this mutation, whereas sprinters and athletes in other sports that require quick muscle strength have lower frequencies.

But, how ACTN3 affects muscle activity so dramatically?? Read on...

(Source: European Journal of Human Genetics (2007) 15, 88–93)

"If you don't have access to Nature Publications, you can send aan artcile request to me at hotbacteria [at] gmail [dor] com. I have a copy on my disk". - Tarun

Loneliness Is in the Genes

2007-09-17T08:57:00.001-07:00

A new study shows that loneliness may change how certain genes in the body work, leaving chronically lonely people with less effective immune systems and lower defenses against disease. The results, if confirmed, could enable doctors to better prevent those ills for which the lonely are at greater risk, such as heart disease, infection, age-related dementia, and certain types of cancer.

Researchers at the University of California, Los Angeles (UCLA), tracked a group of 153 people in their 50s and 60s and ranked the volunteers using the UCLA Loneliness Scale, a test that measures a subject's loneliness by their responses to statements such as "I'm alone in the world" and "There's no one I can count on". The researchers then studied DNA from the white blood cells of eight people who scored in the top 15th percentile of loneliness and six who scored in the bottom 15th percentile.

Of the 22,000 human genes, 209 were abnormally expressed in the very lonely group. Most of these genes help control the body's immune response. In the loneliest, the response was haywire: Those that activate the immune system and inflammation were overexpressed, whereas those that regulate the production of antibodies and antiviral factors were underexpressed. The results explain why lonely people suffer from chronic inflammation in spite of their high levels of cortisol and are vulnerable to microbes, viruses, and other sources of tissue damage, the researchers say.

(Source: Genome Biology 2007, 8:R189) If you can't find the paper, you can send a request to me at hotbacteria [at] gmail [dot] com. I have a copy on my disk.

Salmon parents give birth to trout

2007-09-14T11:58:00.001-07:00

Researchers have succeeded in making salmon couples give birth to trout.

It has previously been shown that male salmon could be injected with cells from closely-related trout to produce viable trout sperm. When the sperm were introduced to trout eggs, healthy trout offspring were produced (see ' Salmon give birth to trout').

Now the researchers have taken the work a step further, showing that salmon can be not only the biological fathers but also the mothers of trout offspring.

Read this Exciting paper here: http://www.nature.com/news/2007/070910/full/070910-11.html

(In case you can not access Nature, you can send a request for a copy to me at - hotbacteria [at] gmail [dot] com. I have it on my disk).

Matter - Antimatter Molecules

2007-09-14T11:48:00.001-07:00

Two years after reporting the first tantalizing hints that matter might be able to bind with antimatter, researchers in California have nailed convincing evidence for the pairing.

These molecules are very hard to see because matter and antimatter annihilate each other, releasing a burst of energy in the form of gamma-rays. When isolated in a vacuum, positronium atoms typically survive for less than a millionth of a second before they self-destruct. "Almost as soon as they are made, they disappear again with a puff and a flash of light," says Surko.

Kindly find more information here: http://www.nature.com/news/2007/070910/full/070910-5.html

(Source: Nature Publications)

Bacteria can control their Temperature!

2007-09-11T08:08:00.001-07:00

Few days back, Nature reported that Bacteria can control their Temperature!

Most organisms, from bacteria to humans, can follow temperature gradients to an optimal temperature. Experience influences eukaryotes' preferred temperature, and, as it turns out, bacteria also adjust their temperature preference depending on growth conditions.

A study from Salman and Libchaber finally provides a physiological reason for this altered behaviour — it may help bacteria to conserve energy until better nutrient supplies become available. When Salman and Libchaber tested the thermotactic responses in E. coli at different growth stages, they observed a surprisingly sharp switch from a thermophilic to a cryophilic response as soon as the cell density crossed a critical threshold.

(Source: Victor Sourjik and Ned S. Wingreen. Turning to the cold. nature cell biology, volume 9, number9, Sept 2007)

In case you don't have access to Nature, you can send me a request for a reprint. I have a copy with me.

Tumour suppressors: The dark side of p27

2007-09-08T23:06:00.000-07:00

Several pieces of evidence indicate that the tumour suppressor p27 (encoded by CDKN1B) has other functions beyond its role as a cell-cycle inhibitor. James Roberts, Arnaud Besson and colleagues now show that, unexpectedly, p27 can behave as a dominant oncoprotein in vivo. So, as well as having a role as a cell-cycle inhibitor, the tumor suppressor p27 can also behave as a dominant oncoprotein in vivo.

Kindly have a look at this article published in Nature's Signalling Gateway: http://www.signaling-gateway.org/update/updates/200709/nrc2216.html

Immortal Strand Hypothesis Ruled out

2007-09-05T04:11:00.001-07:00

To keep organisms running smoothly, stem cells rejuvenate tissues by providing a constant supply of fresh cells. But every time a stem cell copies its chromosomes, it puts itself at risk of generating mutations in the new chromosomes. Scientists have thought for more than 30 years that stem cells avoid mutations by segregating their chromosomes asymmetrically-- placing all the new chromosomes they create when replicating into the new cell and keeping the old ones as an error-free template, an idea called the "immortal strand hypothesis."

But new results show that this isnt true after all; stem cells divide just like any other cell, parsing their chromosomes randomly between the progeny. The experiments, reported in Nature, show that at least for blood stem cells, asymmetric segregation doesn't hold up.

Kindly have a look at the following article: http://sciencenow.sciencemag.org/cgi/content/full/2007/829/3

Diploid Genome needed for Sequencing, not haploid one...

2007-09-05T03:58:00.001-07:00

Craig venter has just published a paper in PLOS Biology which says that haploid genomes underestimate the amount of genetic variation between individuals by a factor of 5.

Venter and co-workers compared his two haploid genomes to assess the differences between the DNA he inherited from his mother and that from his father. They looked for everything from easy-to-find differences in single bases to much more obscure variations in chunks of DNA sequence that had been inserted or deleted from chromosomes. All told, the analysis found more than 4 million variants between Venter's maternal and paternal chromosomes. This suggests that humans differ by 0.5%, not 0.1% as suggested by earlier estimates.

"We need to have diploid genomes to sort out our full inheritance, not just haploid genome."

Kindly have a look at complete article here: http://sciencenow.sciencemag.org/cgi/content/full/2007/904/1

Water Crystal in Frozen Bacteria!

2007-09-03T13:22:00.000-07:00

Dear Friends,

I remember once my mom made milk based ice cream for me and kept it at 4 degrees in refrigerator. The next thing I found was that ice cream was not smooth and there were water crystals formed.

Now, my query has two parts:

1. Biological Cells have a large volume of water as its consituents. I have been wondering that when we store our bacterial plates in frozen condition at -80 degrees, don't this water forms sharp crystals and damage the cells? If crystals do form, they should damage cellular membranes and macromolecules like proteins and DNA (suspended in solvent, ain't they?)! Logically, this should happen, shouldn't it?

2. If this does happen, how do these frozen bacteria revive when we bring them back to normal temperatures in appropriate media? Any comments ?

Kindly send in your comments at hotbacteria [at] gmail [dot] com

Kind Regards,

Tarun Gupta

--
MSc Human Genomics
National Centre of Human Genome Studies and Research
Panjab University
Chandigarh-India

Appeal: Let's not make information inaccessible to masses; Let's publish in Open Access Journals!

Securing accuracy and precision when pipetting hot and cold liquids - Nature

2007-08-31T08:40:00.001-07:00

Biotechnology researchers and laboratory technicians cannot always prevent errors in their results owing to the temperature variation between samples and pipettes.
Observant scientists will have noticed that when they pipette cold samples, they invariably aspirate a larger-than-expected sample volume each time the tip is changed. Oddly, a smaller volume is delivered from the second aspiration onward if the tip is not changed. For example, pipetting hot samples, while they are cooling after their incubation at 37 °C, has the opposite effect.

Gilson conducted a study to determine the influence of sample temperature on the performance of Microman and Pipetman pipettes. Read More...

(Original Article - http://www.nature.com/nmeth/journal/v4/n9/full/nmeth1086.html )

Smoking stays in your genes after you quit

2007-08-31T07:51:00.001-07:00

Gene expression changes brought on by heavy smoking may persist long after the smoker has kicked the habit, researchers have found. The results could provide a molecular explanation for the continued increased risk of lung cancer and other pulmonary ailments among former smokers. Read More...

(Original Article: Nature - http://www.nature.com/news/2007/070827/full/070827-5.html )

Bacterial Genes in Animals

2007-08-31T07:45:00.001-07:00

Microorganisms such as bacteria enjoy swapping genes, and the trades have made a big difference in how they've evolved. Now new research suggests that bacteria are also easygoing about passing genes on to more complex organisms. The findings have researchers rethinking the prevalence of interspecies gene transfer and its role in evolution; they may also change the way geneticists filter out bacterial "contamination" when they sequence a new genome. Read More...

(Original Article: Science - http://sciencenow.sciencemag.org/cgi/content/full/2007/830/1
Nature - http://www.nature.com/news/2007/070827/full/070827-6.html#B1)

Scientific & Job Related Announcements

2007-08-30T08:49:00.001-07:00

== 1 of 4 ==

==============================================================================
Scientist/Jr. Scientist- R & D team - 6 Positions Available:
==============================================================================

Positions Available:

Scientist/Jr. Scientist- R & D team - 6 positions

( Microarray Data Analyst - 3, Microarray Wet Lab - 3 )

Qualification: M.Sc / B.Tech in Biotechnology / Bioinformatics / Life
Sciences.
Experience: At least 2 years of experience in a similar portfolio.

Prior knowledge of Microarray analysis using standard packages is
essential. The use of MS office tools as well bioinformatics databases
will be integral to this position. Prior experience will not be a pre-
requisite for exceptional candidates.

For the above position, we need candidates with good communication
skills, dynamism and capacity to be independent as well as multi-task.

*Email your resumes to: jobs@genotypic. co.in We look forward to
hear from you. *

*About Genotypic: *

Genotypic Technology (www.genotypic. co.in) is a Genomics R & D
company specializing in Microarray technology developing customized
genomics and bioinformatics solutions for a wide-range of
applications. Established in the year 2000, it is the first and major
Indian company catering to Academic institutions, Pharma and Biotech
companies worldwide in the Microarray space. Genotypic also provides
indigenous informatics solutions that enable the Customer to arrive at
meaningful hypotheses in a short period of time. Genotypic is an
Agilent Certified Service Provider in India .

Contact Details:

Rohit N. Shukla
Scientist, Bioinformatics
Genotypic Technology [Pvt] Ltd.,Bangalore
email: rohit@genotypic. co.in

== 2 of 4 ==
==============================================================================
TOPIC: Bioinformatics Work Shop at BIOINTELLIGENCE in Indore
==============================================================================

Biointelligence - in Silico Biology

Biointelligence is an upcoming coaching institute for all subjects
of Bio-Sciences in Indore. We have a felt a great need of a training
centre in the field of Bioinformatics and Chemoinformatics in the
whole central India.

So, we the people at biointelligence are now planning out a hands on
training on AutoDoc software, which is a very powerful tool for
people in Drug Design and Development.

Who should attend the workshop :
1)Professionals involved in Drug Design and Development.
2)Students persuing courses in Pharmecy, BioChemistry,
Pharmachemistry, etc.

Minimum Requirements :
1)B.E. [Final year or above]
2)M.Sc.
3)Professional of any background working in any pharmasuitical
company.

* for details contact
contact no : +919993904994
e-mail : info@biointelligenc e.in
website : www.biointelligence .in
address : 4-Manish Baug, Sapna Sangeeta Rd., Indore ( M.P.)

== 3 of 4 ==
==============================================================================
TOPIC: Journal of Cell and Molecular Biology calls for paper
==============================================================================

Journal of Cell and Molecular Biology is an
international journal which covers original research works
in the field of cell biology, molecular biology, genetics,
microbiology, neurobiology, bioinformatics and related
topics. The Journal aims to encourage publications with an
interdisciplinary approach.

This journal publishes research articles, review
articles, short communications, book/software reviews, case
reports and letters to the editor.
All contributions are published in English.

Independent peer-review system guarantees that all
studies appearing in Journal of Cell and Molecular Biology
will be of high standard.

Publication is free of charge

Journal of Cell and Molecular Biology is published as two
issues annually.

Journal of Cell and Molecular Biology is now indexed in
ULAKBIM, BIOSIS, EBSCO, DOAJ, EMBASE, CAPCAS and EMBiology

Web site: http://jcmb.halic.edu.tr
E-mail: jcmb@halic.edu.tr

== 4 of 4 ==

3RD CALL FOR POSTERS

The 18th International Conference on Genome Informatics (GIW 2007)
Biopolis, Singapore.
December 3-5 2007.
http://www.comp.nus.edu.sg/~giw2007

The 18th International Conference on Genome Informatics (GIW 2007) will be
held at the Biopolis in Singapore on December 3-5, 2007. The GIW is the
longest running international bioinformatics conference, which has provided
unique opportunities that bridge theory and experiments, academia and
industry, and East and West.

SUBMISSIONS:

Poster or software demonstration abstracts are limited to 2 pages, including
title, figures, tables, text, and bibliography. Please see below for
Abstract Templates. All abstract should be submitted at the site
http://www.easychair.org/GIWPoster2007.

Accepted posters and software demonstration abstracts will be compiled into
"The 18th International Conference on Genomic Informatics, Posters and
Software Demonstrations". Additionally, a number of notable abstracts will
be selected for oral presentations.

IMPORTANT DATES:

Poster submission deadline: 16 September 2007
Poster decision: 14 October 2007
Poster templates: http://www.comp.nus.edu.sg/~giw2007/poster.html

Physics in the cell: Spring theory

2007-08-30T08:31:00.001-07:00

Physicists interested in the mechanics of single molecules are helping open one of the blackest boxes in biology. Brendan Maher discovers how the disciplines are working together.

When trying to explain why he has become fascinated by physics lately, Kerry Bloom, a cell and molecular biologist at the University of North Carolina, Chapel Hill, pulls a handful of paper clips from his pocket and links them together. Stretching a small chain across the surface of his palm, he says: "Imagine this is DNA. You can stretch it to its full length, but each link in this chain is vibrating all the time." Bloom jiggles his hand, causing the paper clips to dance. The links twist at random, but once a couple of kinks or bends are introduced some force is needed to stretch the chain out again. After a few seconds of simulated brownian motion, the paper-clip chain collapses back into his hand.

Bloom's paper clips are a demonstration of the properties of an 'entropic spring', a system where thermodynamics favours a resting state in which all the chain's components are bunched and tangled. Rubber bands and silk share these properties, and so does DNA. ( Read more here)

(Original Article at: http://www.nature.com/nature/journal/v448/n7157/full/448984a.html)

Extra Strong Paper!

2007-08-19T06:22:00.000-07:00

Researchers have developed a remarkably simple way to convert ordinary graphite particles into very thin but superstrong sheets that are tougher than steel and as flexible as carbon fiber but can be made much more cheaply. The discovery could spawn entirely new types of materials for applications as diverse as protective coatings, electronic components, batteries, and fuel cells.

For tensile strength and stiffness, carbon is king. So it's no surprise that scientists have been working for years to develop ways to add Element 6 to composite materials for aircraft fuselages, military vehicles, and even racing bicycles and tennis rackets. Even bigger payoffs are possible by constructing carbon materials at microscopic scales, yielding the strongest materials of all. Researchers have made some progress building structures called carbon nanotubes--whose single-layer atomic structure is tightly bound and therefore super rigid--but the tubes are expensive to manufacture and so far can only be used in tiny amounts.

Now, a research team from Northwestern University in Evanston, Illinois, has assembled particles of graphene oxide, a form of graphite and a cousin of diamonds, into very thin sheets that are even stronger than those made of the nanotubes. The process works like this: the team disperses graphene oxide particles in specially treated water and then draws the mixture through a filter membrane. The water somehow causes the particles to bind into a paperlike layer on the filter's surface, the researcher reports in tomorrow's Nature. "We actually don't know all of the details of how the layering takes place," says physical chemist and co-author Rod Ruoff. Laboratory tests showed that the grapheme paper was as strong as that made from carbon nanotubes, yet unlike nanotubes, the material can be fabricated to any size. That makes graphene paper a prime candidate for a new generation of superstrong composite materials, Ruoff says.

The super paper does have its kryptonite, however. The sheets remain stable when exposed to air, says Ruoff, but immersing them in water slowly loosens the bonds. Also, says materials scientist Boris Yakobson of Rice University in Houston, Texas, because water is so common as either liquid as rain or vapor as humidity, it will likely affect graphene sheets exposed to the environment in the long run if the material can't be protected from water's effects. So, the next task is to find other molecules that can replace water in the fabrication process. That research challenge and others probably puts commercialization of the technology at least 5 or 10 years awa

(Original Article: http://sciencenow.sciencemag.org/cgi/content/full/2007/725/2)

Chronic stress can cause or exacerbate MS

2007-08-19T05:57:00.001-07:00

It's long been thought that stress is harmful to your health, but a new study finds chronic stress may increase a person's risk of developing or accelerating a neurodegenerative disease like multiple sclerosis.

Researchers have demonstrated for the first time that inflammation brought on by stress leads to the worsening of the mouse equivalent of MS.

The findings were presented Friday at the annual convention of the American Psychological Association.

In the study, scientists simulated stressful situations on mice infected with Theiler's murine encephalomyelitis (TMEV), an acute infection of the central nervous system which is followed by a chronic autoimmune disease similar to that seen in humans with MS.

Another group of mice was also infected but not exposed to stress.

Researchers found that the stressed mice produced a cytokine — interleukin-6 (IL-6) — which is released during stress and regulates the part of the immune system that fights infection. IL-6 increases the severity of the MS-like illness.

Stressed mice were unable to clear the virus from their systems and had higher levels of inflammation, while the non-stressed mice had lower levels of the virus in their bloodstreams and less inflammation, researchers found.

They also discovered that injecting an antibody into the brain that neutralizes IL-6 prior to the stressful episode prevented the stress-related worsening of the disease, said the authors.

Blocking IL-6 halts disease

By blocking the elevation of IL-6, the TMEV infection was weakened, which decreased symptoms such as motor impairment, inflammation in the brain and spinal cord and the viral level in the central nervous system, researchers found.

Based on these findings, Mary Meagher, the lead researcher, theorizes that the adverse effects of stress-induced IL-6 on TMEV infection create a pro-inflammatory environment that interrupts a person's immune response to infection.

Scientists believe that the effects of stress on people who are vulnerable to certain inflammatory diseases may be prevented or reversed by treatments aimed at blocking increases in this cytokine.

Recent evidence suggests that some potential interventions include certain anti-inflammatory drugs, exercise, antidepressants, omega-3 fatty acids and relaxation training.

However, researchers say human clinical trials are needed to determine what preventive approaches will work.

(Original Article: http://www.cbc.ca/health/story/2007/08/17/stress-ms.html)

Cilia - Unexpected

2007-08-09T10:59:00.001-07:00

"For a long time, cilia were regarded as lowly janitors, lining our airways and beating in coordination to sweep up dirt and mucus, or wafting eggs down fallopian tubes. True, they had shown flashes of brilliance: single cilia, called kinocilia on the hair cells in the inner ear, for example, help us to hear. Cilia play similar roles in sight and smell, but biologists have only recently started to realize that cells carrying cilia are far from exceptions. Almost every cell in the human body carries a cilium, even neurons buried deep in the brain."
- (Kindly see full article here: http://www.nature.com/nature/journal/v448/n7154/full/448638a.html )

This is also a new interesting addition: A highly selective fluorescent probe for in vivo monitoring of mercury (Nature)

And, This must be very interesting and useful for determining where proteins bind to DNA on a genome-wide scale is important for understanding how gene expression is regulated: DamID: a tool for studying genome-wide protein:DNA interactions.

It uses a targeted methylation approach to map protein binding sites. It is an attractive alternative to chromatin immunoprecipitation (ChIP)-based methods, particularly when high quality antibodies are not available.

Invisible Nano-fibers to Conduct Electricity & Repel Dirt

2007-06-30T07:03:00.001-07:00

Tiny plastic fibers could be the key to some diverse technologies in the future -- including self-cleaning surfaces, transparent electronics, and biomedical tools that manipulate strands of DNA.

In the June issue of the journal Nature Nanotechnology, Ohio State University researchers describe how they created surfaces that, seen with the eye, look as flat and transparent as a sheet of glass. But seen up close, the surfaces are actually carpeted with tiny fibers.

The patent-pending technology involves a method for growing a bed of fibers of a specific length, and using chemical treatments to tailor the fibers' properties, explained Arthur J. Epstein, Distinguished University Professor of chemistry and physics and director of the university's Institute for Magnetic and Electronic Polymers.

"One of the good things about working with these polymers is that you're able to structure them in many different ways," Epstein said. "Plus, we found that we can coat almost any surface with these fibers."

For this study, the scientists grew fibers of different heights and diameters, and were able to modify the fibers' molecular structures by exposing them to different chemicals.

They devised one treatment that made the fibers attract water, and another that made the fibers repel water. They found they could also make the surfaces attract or repel oil. Depending on what polymer they start with, the fibers can also be made to conduct electricity.

The ability to tailor the properties of the fibers opens the surface to many different applications, he said.

Since dirt, water, and oil don't stick to the repellant fibers, windows coated with them would stay cleaner longer.

In contrast, the attracting fibers would make a good anti-fog coating, because they pull at water droplets and cause them to spread out flat on the surface.

What's more, researchers found that the attracting surface does the same thing to coiled-up strands of DNA. When they put droplets of water containing DNA on the fibers, the strands uncoiled and hung suspended from the fibers like clotheslines.

Epstein said scientists could use the fibers as a platform to study how DNA interacts with other molecules. They could also use the spread-out DNA to build new nanostructures.

"We're very excited about where this kind of development can take us," he added.

Epstein's research centers on polymers that conduct electricity, and light up or change color. Depending on the choice of polymer, the nano-fiber surface can also conduct electricity. The researchers were able to use the surface to charge an organic light-emitting device -- a find that could pave the way for transparent plastic electronics.

Finally, they also showed that the fibers could be used to control the flow of water in microfluidic devices --- a specialty of study co-author L. James Lee, professor of chemical and biomolecular engineering and head of Ohio State's Center for Affordable Nanoengineering of Polymeric Biomedical Devices.

Lee and Epstein are advisors to former graduate student Nan-Rong Chiou, who developed the technology to earn his doctorate. He is now a visiting scholar at the university. Other co-authors on the paper included former doctoral students Chunmeng Lu and Jingjiao Guan.

The technology is a merger of two different chemical processes for growing polymer molecules: one grows tiny dots of polymer "seeds" on a flat surface, and the other grows vertical fibers out from the top of the seeds. The fibers grow until the scientists cut off the chemical reaction, forming a carpet of uniform height.

The university will license the technology, and Epstein and his colleagues are looking for new applications for it.

Aside from anti-fog windows, self-cleaning windows, and organic LEDs, Chiou said that he foresees the surfaces working in glucose sensors, gene therapy devices, artificial muscles, field emission displays, and electromagnetic interference shielding.

This research was partially funded by the National Science Foundation.

Note: This story has been adapted from a news release issued by Ohio State University. (Source: Science Daily)

Researchers Identify Target Of Angiogenesis And Tumor Inhibitor

2007-06-30T07:01:00.001-07:00

Researchers at the University of Kentucky have advanced research of a natural product found in an Indian medicinal plant that has shown effectiveness in blocking blood-vessel and tumor growth. The discovery may help lead to treatments for certain types of metastatic breast, prostate and colon cancers.

Royce Mohan, assistant professor of ophthalmology and principal scientist leading this study, reports isolating vimentin, an intermediate filament protein, as the binding target of withaferin-A. The findings are in the June 22 issue of Chemistry & Biology.

The lead author in this study, ophthalmology assistant professor Paola Bargagna-Mohan, utilizing a chemical analog of withaferin-A (synthesized in collaborator pharmaceutical sciences assistant professor Kyung Bo Kim's lab), shows that the drug-like activity of withaferin-A results from binding to and destroying this filament protein. This cytoskeleton targeting activity shuts down the ability of blood vessel cells to grow and migrate, a mechanism which also appears to be relevant to how withaferin-A can block tumor cells from spreading.

Furthering this discovery in developing new classes of drugs from withaferin-A, Adel Hamza, a postdoctoral candidate in pharmaceutical sciences associate professor Chang-Guo Zhan's lab, has developed a molecular model that reveals the specific binding interaction of withaferin-A with vimentin.

This discovery also signals possible new methods of identifying a number of cancers early in their development, when tumors produce vimentin to enable them to invade tissues and spread to different organs.

The researchers hope certain aspects of their findings will lead to therapeutic developments for individualized medicine due to the well known disease involvement of vimentin.

Note: This story has been adapted from a news release issued by University of Kentucky. (Source: Science Daily)

RNA May Play Larger Role In Cell's Gene Activity

2007-06-30T06:58:00.001-07:00

Large, seemingly useless pieces of RNA - a molecule originally considered only a lowly messenger for DNA - play an important role in letting cells know where they are in the body and what they are supposed to become, researchers at Stanford University School of Medicine have discovered.

The finding implies that ancient RNA molecules can orchestrate gene activity across vast portions of the human genome - a cell's genetic blueprint. It also suggests they may be important in cancer development and stem cell maintenance. Overall, the work adds another brick to the growing wall of evidence suggesting that RNA is more than a mere genomic servant.

RNA is best known for ferrying protein-coding instructions from DNA, once thought to be the master molecule of the genome, to the cell's assembly factories. But cracks in this theory began to appear when it became evident that many RNA molecules aren't capable of making protein. While more recent research has shown that small bits of RNA can silence individual genes by interfering with their expression - a la Stanford professor Andrew Fire's recent Nobel work - longer pieces, called non-coding RNAs, have been more perplexing.

"These ncRNAs have long been molecules of mystery," said John Rinn, PhD, a postdoctoral scholar in the laboratory of Howard Chang, MD, PhD, assistant professor of dermatology. "They look just like they should code for proteins, but they don't."

Although ncRNAs have been shown to affect the expression of neighboring genes, the relative abundance of the molecules - accounting for about half of the DNA transcribed in the cell - suggests that they may have a wider sphere of influence than previously thought. Now Rinn, Chang, and their collaborators have discovered that ncRNAs can influence gene expression patterns at distant locations in the cell.

"We were surprised to find that at least one of these molecules can suppress genes on a completely different chromosome," said Chang. "This opens up the whole genome to potential regulation by ncRNAs." The research will be published in the June 29 issue of the journal Cell.

The researchers were investigating how human skin cells, or fibroblasts, know where they are in the body. They had previously shown in different types of cells that groups of genes known as HOX act as a sort of global positioning system by maintaining unique patterns of expression over many generations of cell division. But until Rinn used a new type of gene chip called a tiling array in the new study to home in on nearby regions of DNA, they didn't know how the HOX expression patterns themselves were determined.

"I like to think of it as genomic scuba diving," said Rinn of the new experiments. The tiling array allowed him to map the boundaries of the regions around four clustered sets, or loci, of HOX genes, known as HOXA through HOXD, to near-nucleotide resolution. That's somewhat like zooming in on a single home from a satellite map on Google Earth. "It gives us an up-close, unbiased view of what's actually happening at the chromosomal level," said Rinn.

Not only did Rinn locate many previously unknown ncRNA genes nestled among the HOX genes, he also identified areas that serve as shared landing pads for proteins that either activate or suppress the neighboring regions. "It's a striking pattern," said Rinn. "Like a light switch, the same stretch of DNA can be used to turn genes either on or off, depending on their protein partners." But then Rinn looked more deeply.

The fact that the ncRNAs have remained virtually unchanged over millions of years suggests they may be playing non-traditional but vital roles in gene expression. The researchers found that depleting one ncRNA dubbed HOTAIR, in the HOXC region on chromosome 12 of a skin cell, significantly increased the expression of HOXD genes on chromosome 2. The finding marks the first time that ncRNA has been shown to affect gene expression on a chromosome other than its own.

The researchers believe that HOTAIR functions by affecting chromosomal packing in the nucleus. Inactive chromosomal regions are tightly wound around proteins called histones and cannot be copied into RNA. Loss of HOTAIR in skin cells specifically frees the HOXD control region for binding by activating proteins.

"Next we need to find out how these RNAs work structurally," said Rinn, "and what upstream regulatory molecules might be controlling their expression." They have one clue: HOTAIR binds to and activates a group of enzymes called the Polycomb Repressive Complex 2 that modifies histones and helps them wind up the DNA.

The researchers' interest is more than just theoretical. Polycomb proteins are improperly regulated in some types of cancers. HOX gene expression patterns are likely important to keep stem cells from improperly differentiating into skin, muscle, or other tissues. Understanding how ncRNAs affect these processes will have important implications for cancer therapies and stem cell research, they believe.

"We are really interested in how ncRNA finds its putative target in the genome," said Chang. "There remains a whole level of biological complexity to be explored, including how HOTAIR knows where to go, how it talks to other factors and how it controls histones."

The work will also provide insight into the evolution of gene regulation. Because RNA is thought to have preceded DNA in the evolutionary timeline, it makes sense that it still plays a role in controlling DNA's function.

Rinn and Chang's Stanford collaborators on the research include cancer biology graduate students Jordon Wang and Xiao Xu; surgical postdoctoral scholar Samantha Brugmann, PhD; research assistant Henry Goodnough; and Jill Helms, PhD, associate professor of surgery. Non-Stanford collaborators include graduate student Michael Kertesz and Eran Segal, PhD, at the Weizmann Institute of Science, and Sharon Squazzo and Peggy Farnham, PhD, at the University of California at Davis.

This research was supported by the National Institutes of Health, the Beckman Center Interdisciplinary Translational Research Program, the Damon Runyon Cancer Research Foundation and the Emerald Foundation.

Note: This story has been adapted from a news release issued by Stanford University Medical Center. (Source: Science daily)

Curing Cancer With Mathematics

2007-06-30T06:56:00.001-07:00

Members of a Harvey Mudd College (HMC)-led research team recently present their research "Curing Cancer with Mathematics" at the 13th annual meeting of the Coalition for National Science Funding (CNSF) on Tuesday, June 26, in Washington, D.C.

Leading the team was Lisette de Pillis, HMC professor of mathematics, who is lead principal investigator (PI) on the National Science Foundation (NSF)-sponsored research project. The team is working to develop and test models of cancer growth and to implement mathematically optimal approaches to controlling multiple simultaneous cancer treatment strategies, which include chemotherapy, immunotherapy and vaccine therapy.

According to de Pillis, "Harnessing the power of the body's own immune system is a promising approach to combating a growing cancer. However, precisely how cancer immunotherapies work, and how they should be administered optimally, either alone or in conjunction with chemotherapies, remains an open question of great interest and import to the medical community.

"In this cross-disciplinary project, we are developing computational and mathematical tools capable of modeling the complex cascade of biological tumor-immune interactions, and of determining effective combination treatment strategies. Our tools have the potential to provide clinical guidance in the development of new treatment protocols through preliminary evaluations of simulated scenarios."

HMC Professor of Mathematics and co-PI Weiqing Gu brings to the project her expertise in analytic geometry. Renee Fister from Murray State University (Ky.) is the other co-PI, bringing her expertise in optimal control theory. Also representing HMC were students and recent graduates: Benjamin David Preskill '09 of Claremont, Calif., David Gross '08 of Pasadena, Calif., and James Moore '07 of Mercer Island, Wash.

The project and team were selected to represent the Mathematical Association of America (MAA) at the CNSF exhibition, where they will showcase the kind of active research that takes place with undergraduates at Harvey Mudd College. In 2006, the American Mathematical Society recognized HMC with its first Award for an Exemplary Program or Achievement in a Mathematics Department.

Since 1995, the Coalition for National Science Funding has sponsored an exhibition and reception each spring, showcasing research made possible by the National Science Foundation. Exhibit booths display a wide range of scientific research and education projects, and university researchers and educators are on hand to describe their work to interested members of Congress and their staffs.

Note: This story has been adapted from a news release issued by Harvey Mudd College.
(Source: Science Daily)

First Bacterial Genome Transplantation Changes One Species To Another

2007-06-30T06:50:00.001-07:00

Researchers at the J. Craig Venter Institute (JCVI) have announced the results of work on genome transplantation methods allowing them to transform one type of bacteria into another type dictated by the transplanted chromosome. The work, published online in the journal Science, by JCVI's Carole Lartigue, Ph.D. and colleagues, outlines the methods and techniques used to change one bacterial species, Mycoplasma capricolum into another, Mycoplasma mycoides Large Colony (LC), by replacing one organism's genome with the other one's genome.

"The successful completion of this research is important because it is one of the key proof of principles in synthetic genomics that will allow us to realize the ultimate goal of creating a synthetic organism," said J. Craig Venter, Ph.D., president and chairman, JCVI. "We are committed to this research as we believe that synthetic genomics holds great promise in helping to solve issues like climate change and in developing new sources of energy."

Methods and techniques

The JCVI team devised several key steps to enable the genome transplantation. First, an antibiotic selectable marker gene was added to the M. mycoides LC chromosome to allow for selection of living cells containing the transplanted chromosome. Then the team purified the DNA or chromosome from M. mycoides LC so that it was free from proteins (called naked DNA). This M. mycoides LC chromosome was then transplanted into the M. capricolum cells. After several rounds of cell division, the recipient M. capricolum chromosome disappeared having been replaced by the donor M. mycoides LC chromosome, and the M. capricolum cells took on all the phenotypic characteristics of M. mycoides LC cells.

As a test of the success of the genome transplantation, the team used two methods — 2D gel electrophoresis and protein sequencing, to prove that all the expressed proteins were now the ones coded for by the M. mycoides LC chromosome. Two sets of antibodies that bound specifically to cell surface proteins from each cell were reacted with transplant cells, to demonstrate that the membrane proteins switch to those dictated by the transplanted chromosome not the recipient cell chromosome. The new, transformed organisms show up as bright blue colonies in images of blots probed with M. mycoides LC specific antibody.

The group chose to work with these species of mycoplasmas for several reasons — the small genomes of these organisms which make them easier to work with, their lack of cell walls, and the team's experience and expertise with mycoplasmas. The mycoplasmas used in the transplantation experiment are also relatively fast growing, allowing the team to ascertain success of the transplantation sooner than with other species of mycoplasmas.

According to Dr. Lartigue, "While we are excited by the results of our research, we are continuing to perfect and refine our techniques and methods as we move to the next phases and prepare to develop a fully synthetic chromosome."

Genome transplantation is an essential enabling step in the field of synthetic genomics as it is a key mechanism by which chemically synthesized chromosomes can be activated into viable living cells. The ability to transfer the naked DNA isolated from one species into a second microbial species paves the way for next experiments to transplant a fully synthetic bacterial chromosome into a living organism and if successful, "boot up" the new entity. There are many important applications of synthetic genomics research including development of new energy sources and as means to produce pharmaceuticals, chemicals or textiles.

This research was funded by Synthetic Genomics Inc.

Nanoparticle Drug Delivery System Created

2007-06-27T09:43:00.001-07:00

(Source: Sciencedaily.com) -- U.S. scientists said attaching polymeric nanoparticles to red blood cells might become a new way to deliver drugs.

University of California-Santa Barbara researchers determined the procedure dramatically increases the in vivo lifetime of the nanoparticles, suggesting new applications for the delivery of drugs and circulating bioreactors.

One drawback to using polymeric nanoparticles has been their short duration -- they are quickly removed from the blood, sometimes in minutes, rendering them ineffective in delivering drugs.

The University of California-Santa Barbara scientists, led by Professor Samir Mitragotri and researcher Elizabeth Chambers, found nanoparticles can be forced to remain in the circulation when attached to red blood cells.

"Attachment of polymeric nanoparticles to red blood cells combines the advantages of the long circulating lifetime of the red blood cell, and their abundance, with the robustness of polymeric nanoparticles," said Mitragotri. "Using red blood cells to extend the circulation time of the particles avoids the need to modify the surface chemistry of the entire particle, which offers the potential to attach chemicals to the exposed surface for targeting applications."

The research appears in the July issue of the journal Experimental Biology and Medicine.

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RNA Interference - Animated Tutorial

2007-06-26T13:17:00.001-07:00

RNA interference (also called "RNA-mediated interference", abbreviated RNAi) is a mechanism for RNA-guided regulation of gene expression in which double-stranded ribonucleic acid inhibits the expression of genes with complementary nucleotide sequences. Conserved in most eukaryotic organisms, the RNAi pathway is thought to have evolved as a form of innate immunity against viruses and also plays a major role in regulating development and genome maintenance.

The RNAi pathway is initiated by the enzyme dicer, which cleaves double-stranded RNA (dsRNA) to short double-stranded fragments of 20–25 base pairs. One of the two strands of each fragment, known as the guide strand, is then incorporated into the RNA-induced silencing complex (RISC) and base-pairs with complementary sequences. The most well-studied outcome of this recognition event is a form of post-transcriptional gene silencing. This occurs when the guide strand base pairs with a messenger RNA (mRNA) molecule and induces degradation of the mRNA by argonaute, the catalytic component of the RISC complex. The short RNA fragments are known as small interfering RNA (siRNA) when they derive from exogenous sources and microRNA (miRNA) when they are produced from RNA-coding genes in the cell's own genome. The RNAi pathway has been particularly well-studied in certain model organisms such as the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the flowering plant Arabidopsis thaliana.

The selective and robust effect of RNAi on gene expression makes it a valuable research tool, both in cell culture and in living organisms; synthetic dsRNA introduced into cells can induce suppression of specific genes of interest. RNAi may also be used for large-scale screens that systematically shut down each gene in the cell, which can help identify the components necessary for a particular cellular process or an event such as cell division. Exploitation of the pathway is also a promising tool in biotechnology and medicine.

Historically, RNA interference was known by other names, including post transcriptional gene silencing, transgene silencing, and quelling. Only after these apparently-unrelated processes were fully understood did it become clear that they all described the RNAi phenomenon. RNAi has also been confused with antisense suppression of gene expression, which does not act catalytically to degrade mRNA but instead involves single-stranded RNA fragments physically binding to mRNA and blocking translation. In 2006, Andrew Fire and Craig C. Mello shared the Nobel Prize in Physiology or Medicine for their work on RNA interference in the nematode worm C. elegans, which they published in 1998.

(Acknowledgement: Nature)

Meiosis - Animated Tutorial

2007-06-26T12:52:00.000-07:00

In biology, meiosis (IPA: /maɪˈəʊsɪs/) is the process by which one diploid eukaryotic cell divides to generate four haploid cells often called gametes. The word "meiosis" comes from the Greek meioun, meaning "to make smaller," since it results in a reduction in chromosome number in the gamete cell. Among fungi, spores in which the haploid nuclei are at first disseminated are called meiospores, or more specifically, ascospores in asci (Ascomycota) and basidospores on basidia (Basidiomycota).

Meiosis is essential for sexual reproduction and therefore occurs in all eukaryotes, including single-celled organisms that reproduce sexually. A few eukaryotes, notably the Bdelloid rotifers, have lost the ability to carry out meiosis and have acquired the ability to reproduce by parthenogenesis. Meiosis does not occur in archaea or prokaryotes, which reproduce by asexual mitotic cell division.

During meiosis, the genome of a diploid germ cell, which is composed of long segments of DNA packaged into chromosomes, undergoes DNA replication followed by two rounds of division, resulting in haploid cells called gametes. Each gamete contains one complete set of chromosomes, or half of the genetic content of the original cell. These resultant haploid cells can fuse with other haploid cells of the opposite sex or mating type during fertilization to create a new diploid cell, or zygote. Thus, the division mechanism of meiosis is a reciprocal process to the joining of two genomes that occurs at fertilization. Because the chromosomes of each parent undergo genetic recombination during meiosis, each gamete, and thus each zygote, will have a unique genetic blueprint encoded in its DNA. In other words, meiosis and sexual reproduction produce genetic variation.

Meiosis uses many of the same biochemical mechanisms employed during mitosis to accomplish the redistribution of chromosomes. There are several features unique to meiosis, most importantly the pairing and genetic recombination between homologous chromosomes

Occurrence of meiosis in eukaryotic life cycles

Meiosis occurs in all eukaryotic life cycles involving sexual reproduction, comprising of the constant cyclical process of meiosis and fertilization. This takes place alongside normal mitotic cell division. In multicellular organisms, there is an intermediary step between the diploid and haploid transition where the organism grows. The organism will then produce the germ cells that continue in the life cycle. The rest of the cells, called somatic cells, function within the organism and will die with it.

The organism phase of the life cycle can occur between the haploid to diploid transition or the diploid to haploid transition. Some species are diploid, grown from a diploid cell called the zygote. Others are haploid instead, spawned by the proliferation and differentiation of a single haploid cell called the gamete. Humans, for example, are diploid creatures. Human stem cells undergo meiosis to create haploid gametes, which are spermatozoa for males or ova for females. These gametes then fertilize in the Fallopian tubes of the female, producing a diploid zygote. The zygote undergoes progressive stages of mitosis and differentiation, turns into a blastocyst and then gets implanted in the uterus endometrium to create an embryo.

There are three types of life cycles that utilize sexual reproduction, differentiated by the location of the organisms stage.

In the gametic life cycle, of which humans are a part, the living organism is diploid in nature. Here, we will generalize the example of human reproduction stated previously. The organism's diploid germ-line stem cells undergo meiosis to create haploid gametes, which fertilize to form the zygote. The diploid zygote undergoes repeated cellular division by mitosis to grow into the organism. Mitosis is a related process to meiosis that creates two cells that are genetically identical to the parent cell. The general principle is that mitosis creates somatic cells and meiosis creates germ cells.

In the zygotic life cycle, the living organism is haploid. Two organisms of opposing gender contribute their haploid germ cells to form a diploid zygote. The zygote undergoes meiosis immediately, creating four haploid cells. These cells undergo mitosis to create the organism. Many fungi and many protozoa are members of the zygotic life cycle.

Finally, in the sporic life cycle, the living organism alternates between haploid and diploid states. Consequently, this cycle is also known as the alternation of generations. The diploid organism's germ-line cells undergo meiosis to produce gametes. The gametes proliferate by mitosis, growing into a haploid organism. The haploid organism's germ cells then combine with another haploid organism's cells, creating the zygote. The zygote undergoes repeated mitosis and differentiation to become the diploid organism again. The sporic life cycle can be considered a fusion of the gametic and zygotic life cycles, and indeed its diagram supports this conclusion.

Process

Because meiosis is a "one-way" process, it cannot be said to engage in a cell cycle as mitosis does. However, the preparatory steps that lead up to meiosis are identical in pattern and name to the interphase of the mitotic cell cycle.

Interphase is divided into three phases:
Growth 1 (G1) phase: Characterized by increase in cell size due to accelerated manufacture of organelles, proteins, and other cellular matter.
Synthesis (S) phase: The genetic material is replicated: each of its chromosomes duplicates. The cell is still diploid, however, because it still contains the same number of centromeres.
Growth 2 (G2) phase: The cell continues to grow.

Interphase is immediately followed by meiosis I and meiosis II. Meiosis I consists of segregating the homologous chromosomes from each other, then dividing the tetraploid cell into two diploid cells each containing one of the segregates. Meiosis II consists of decoupling each chromosome's sister strands (chromatids), segregating the DNA into two sets of strands (each set containing one of each homolog), and dividing both diploid cells to produce four haploid cells. Meiosis I and II are both divided into prophase, metaphase, anaphase, and telophase subphases, similar in purpose to their analogous subphases in the mitotic cell cycle. Therefore, meiosis encompasses the interphase (G1, S, G2), meiosis I (prophase I, metaphase I, anaphase I, telophase I), and meiosis II (prophase II, metaphase II, anaphase II, telophase II).

Meiosis I
Prophase I

The first stage of prophase I is the leptotene stage, also known as leptonema, from Greek words meaning "thin threads." During this stage, individual chromosomes begin to condense into long strands within the nucleus. However the two sister chromatids are still so tightly bound that they are indistinguishable from one another.

The zygotene stage, also known as zygonema, from Greek words meaning "paired threads,
occurs as the chromosomes approximately line up with each other into homologous chromosomes. The combined homologous chromosomes are said to be bivalent. They may also be referred to as a tetrad, a reference to the four sister chromatids. The two chromatids become "zipped" together, forming the synaptonemal complex, in a process known as synapsis.

The pachytene stage, also known as pachynema, from Greek words meaning "thick threads," heralds crossing over. Nonsister chromatids of homologous chromosomes randomly exchange segments of genetic information over regions of homology. (Sex chromosomes, however, are not identical, and only exchange information over a small region of homology.) Exchange takes place at sites where recombination nodules have formed. The exchange of information between the non-sister chromatids results in a recombination of information; each chromosome has the complete set of information it had before, and there are no gaps formed as a result of the process. Because the chromosomes cannot be distinguished in the synaptonemal complex, the actual act of crossing over is not perceivable through the microscope.

During the diplotene stage, also known as diplonema, from Greek words meaning "two threads," the synaptonemal complex degrades and homologous chromosomes separate from one another a little. The chromosomes themselves uncoil a bit, allowing some transcription of DNA. However, the homologous chromosomes of each bivalent remain tightly bound at chiasmata, the regions where crossing over occurred.

Chromosomes condense further during the diakinesis stage, from Greek words meaning "moving through." This is the first point in meiosis where the four parts of the tetrads are actually visible. Sites of crossing over entangle together, effectively overlapping, making chiasmata clearly visible. Other than this observation, the rest of the stage closely resembles prometaphase of mitosis; the nucleoli disappears, the nuclear membrane disintegrates into vesicles, and the mitotic spindle begins to form.

During these stages, centrioles are migrating to the two poles of the cell. These centrioles, which were duplicated during interphase, function as microtubule coordinating centers. Centrioles sprout microtubules, essentially cellular ropes and poles, during crossing over. They invade the nuclear membrane after it disintegrates, attaching to the chromosomes at the kinetochore. The kinetochore functions as a motor, pulling the chromosome along the attached microtubule toward the originating centriole, like a train on a track. There are two kinetochores on each tetrad, one for each centrosome. Prophase I is the longest phase in meiosis.

Microtubules that attach to the kinetochores are known as kinetochore microtubules. Other microtubules will interact with microtubules from the opposite centriole. These are called nonkinetochore microtubules.

Metaphase I

Homologous pairs move together along the phase plate: as kinetochore microtubules from both centrioles attach to their respective kinetochores, the homologous chromosomes align along an equatorial plane that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by the microtubules emanating from the two kinetochores. The physical basis of the independent assortment of chromosomes is the random orientation of each bivalent along the metaphase plate.

Anaphase I

Kinetochore microtubules shorten, severing the recombination nodules and pulling homologous chromosomes apart. Since each chromosome only has one kinetochore, whole chromosomes are pulled toward opposing poles, forming two diploid sets. Each chromosome still contains a pair of sister chromatids. Nonkinetochore microtubules lengthen, pushing the centrioles further apart. The cell elongates in preparation for division down the middle. In prophase 1 the DNA coils tightly and individual chromosomes become visible under the light microscope. Homologous chromosomes closely associated in synapsis and they exchange segments by crossing over.

Telophase I

The first meiotic division effectively ends when the centromeres arrive at the poles. Each daughter cell now has half the number of chromosomes but each chromosome consists of a pair of chromatids. This effect produces a variety of responses from the neuro-synrchromatic enzyme, also known as NSE. The microtubules that make up the spindle network disappear, and a new nuclear membrane surrounds each haploid set. The chromosomes uncoil back into chromatin. Cytokinesis, the pinching of the cell membrane in animal cells or the formation of the cell wall in plant cells, occurs, completing the creation of two daughter cells.

Cells enter a period of rest known as interkinesis or interphase II. No DNA replication occurs during this stage. Note that many plants skip telophase I and interphase II, going immediately into prophase II.

Meiosis II

Prophase II takes an inversely proportional time compared to telophase I. In this prophase we see the disappearance of the nucleoli and the nuclear envelope again as well as the shortening and thickening of the chromatids. Centrioles move to the polar regions and are arranged by spindle fibres. The new equatorial plane is rotated by 90 degrees when compared to meiosis I, perpendicular to the previous plane.

In metaphase II, the centromeres contain three kinetochores, organizing fibers from the centrosomes on each side.

This is followed by anaphase II, where the centromeres are cleaved, allowing the kinetochores to pull the sister chromatids apart. The sister chromatids by convention are now called sister chromosomes, and they are pulled toward opposing poles.

The process ends with telophase II, which is similar to telophase I, marked by uncoiling, lengthening, and disappearance of the chromosomes occur as the disappearance of the microtubules. Nuclear envelopes reform; cleavage or cell wall formation eventually produces a total of four daughter cells, each with a haploid set of chromosomes. Meiosis is now complete.

Significance of meiosis
Meiosis facilitates stable sexual reproduction. Without the halving of ploidy, or chromosome count, fertilization would result in zygotes that have twice the number of chromosomes than the zygotes from the previous generation. Successive generations would have an exponential increase in chromosome count, resulting in an unwieldy genome that would cripple the reproductive fitness of the species. Polyploidy, the state of having three or more sets of chromosomes.

Most importantly, however, meiosis produces genetic variety in gametes that propagate to offspring. Recombination and independent assortment allow for a greater diversity of genotypes in the population. As a system of creating diversity, meiosis allows a species to maintain stability under environmental changes.

Nondisjunction
The normal separation of chromosomes in Meiosis I or sister chromatids in meiosis II is termed disjunction. When the separation is not normal, it is called nondisjunction. This results in the production of gametes which have either more or less of the usual amount of genetic material, and is a common mechanism for trisomy or monosomy. Nondisjunction can occur in the meiosis I or meiosis II, phases of cellular reproduction, or during mitosis.

This is a cause of several medical conditions in humans, including:
Down's Syndrome - trisomy of chromosome 21
Patau Syndrome - trisomy of chromosome 13
Edward Syndrome - trisomy of chromosome 18
Klinefelter Syndrome - extra X chromosomes in males - ie XXY, XXXY, XXXXY
Turner Syndrome - atypical X chromosome dosage in in females - ie XO, XXX, XXXX
XYY Syndrome - an extra Y chromosome in males

Meiosis in humans
In females, meiosis occurs in precursor cells known as oogonia that divide twice into oocytes. These stem cells stop at the diplotene stage of meiosis I and lay dormant within a protective shell of somatic cells called the follicle. Follicles begin growth at a steady pace in a process known as folliculogenesis, and a small number enter the menstrual cycle. Menstruated oocytes continue meiosis I and arrest at meiosis II until fertilization. The process of meiosis in females is called oogenesis, and differs from the typical meiosis in that it features a long period of meiotic arrest known as the Dictyate stage and lacks the assistance of centrosomes.

In males, meiosis occurs in precursor cells known as spermatogonia that divide twice to become sperm. These cells continuously divide without arrest in the seminiferous tubules of the testicles. Sperm is produced at a steady pace. The process of meiosis in males is called spermatogenesis.

(Acknowledgement: Wikipedia)

Mitosis - Animated Tutorial

2007-06-26T12:50:00.000-07:00

Mitosis is the process by which a cell duplicates its chromosomes, in order to generate two, identical cells. It is generally followed immediately by cytokinesis which divides the cytoplasm and cell membrane. This results in two identical cells with a roughly equal distribution of organelles and other cellular components. Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle, the division of the mother cell into two daughter cells, each with the genetic equivalent of the parent cell. Mitosis occurs exclusively in eukaryotic cells. In multicellular organisms, the somatic cells undergo mitosis, while germ cells — cells destined to become sperm in males or ova in females — divide by a related process called meiosis. Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.
Mitosis divides genetic information during cell division.

The process of mitosis is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These stages are prophase, prometaphase, metaphase, anaphase and telophase. During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatids to opposite sides of the cell. The cell then divides in cytokinesis, to produce two identical daughter cells.

Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "mitotic phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei. This occurs most notably among the fungi and slime moulds, but is found in various different groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development. Errors in mitosis can either kill a cell through apoptosis or cause mutations that may lead to cancer.

Phases

Interphase

The mitotic phase is a relatively short period of the cell cycle. It alternates with the much longer interphase, where the cell prepares itself for cell division. Interphase is divided into three phases, G1 (first gap), S (synthesis), and G2 (second gap). During all three phases, the cell grows by producing proteins and cytoplasmic organelles. However, chromosomes are replicated only during the S phase. Thus, a cell grows (G1), continues to grow as it duplicates its chromosomes (S), grows more and prepares for mitosis (G2), and divides (M).

Preprophase
In plant cells only, prophase is preceded by a pre-prophase stage. In highly vacuolated plant cells, the nucleus has to migrate into the center of the cell before mitosis can begin. This is achieved through the formation of a phragmosome, a transverse sheet of cytoplasm that bisects the cell along the future plane of cell division. In addition to phragmosome formation, preprophase is characterized by the formation of a ring of microtubules and actin filaments (called preprophase band) underneath the plasmamembrane around the equatorial plane of the future mitotic spindle and predicting the position of cell plate fusion during telophase. The cells of higher plants (such as the flowering plants) lack centrioles. Instead, spindle microtubules aggregate on the surface of the nuclear envelope during prophase. The preprophase band disappears during nuclear envelope disassembly and spindle formation in prometaphase.

Prophase
Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin. At the onset of prophase, chromatin condenses together into a highly ordered structure called a chromosome. Since the genetic material has already been duplicated earlier in S phase, the replicated chromosomes have two sister chromatids, bound together at the centromere by the cohesion complex. Chromosomes are visible at high magnification through a light microscope.

Close to the nucleus are two centrosomes. Each centrosome, which was replicated earlier independent of mitosis, acts as a coordinating center for the cell's microtubules. The two centrosomes nucleate microtubules (which may be thought of as cellular ropes or poles) by polymerizing soluble tubulin present in the cytoplasm. Molecular motor proteins create repulsive forces that will push the centrosomes to opposite side of the nucleus.

Some centrosomes contain a pair of centrioles that may help organize microtubule assembly, but they are not essential to formation of the mitotic spindle

Prometaphase
The nuclear envelope disassembles and microtubules invade the nuclear space. This is called open mitosis, and it occurs in most multicellular organisms. Fungi and some protists, such as algae or trichomonads, undergo a variation called closed mitosis where the spindle forms inside the nucleus or its microtubules are able to penetrate an intact nuclear envelope.

Each chromosome forms two kinetochores at the centromere, one attached at each chromatid. A kinetochore is a complex protein structure that is analogous to a ring for the microtubule hook; it is the point where microtubules attach themselves to the chromosome. Although the kinetochore structure and function are not fully understood, it is known that it contains some form of molecular motor. When a microtubule connects with the kinetochore, the motor activates, using energy from ATP to "crawl" up the tube toward the originating centrosome. This motor activity, coupled with polymerisation and depolymerisation of microtubules, provides the pulling force necessary to later separate the chromosome's two chromatids.

When the spindle grows to sufficient length, kinetochore microtubules begin searching for kinetochores to attach to. A number of nonkinetochore microtubules find and interact with corresponding nonkinetochore microtubules from the opposite centrosome to form the mitotic spindle. Prometaphase is sometimes considered part of prophase

Metaphase
As microtubules find and attach to kinetochores in prometaphase, the centromeres of the chromosomes convene along the metaphase plate or equatorial plane, an imaginary line that is equidistant from the two centrosome poles. This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochores, analogous to a tug-of-war between equally strong people. In certain types of cells, chromosomes do not line up at the metaphase plate and instead move back and forth between the poles randomly, only roughly lining up along the midline. Metaphase comes from the Greek μετα meaning "after."

Because proper chromosome separation requires that every kinetochore be attached to a bundle of microtubules (spindle fibers) , it is thought that unattached kinetochores generate a signal to prevent premature progression to anaphase without all chromosomes being aligned. The signal creates the mitotic spindle checkpoint

Anaphase
When every kinetochore is attached to a cluster of microtubules and the chromosomes have lined up along the metaphase plate, the cell proceeds to anaphase (from the Greek ανα meaning “up,” “against,” “back,” or “re-”).

Two events then occur; First, the proteins that bind sister chromatids together are cleaved, allowing them to separate. These sister chromatids turned sister chromosomes are pulled apart by shortening kinetochore microtubules and toward the respective centrosomes to which they are attached. Next, the nonkinetochore microtubules elongate, pushing the centrosomes (and the set of chromosomes to which they are attached) apart to opposite ends of the cell.

These two stages are sometimes called early and late anaphase. Early anaphase is usually defined as the separation of the sister chromatids, while late anaphase is the elongation of the microtubules and the microtubules being pulled farther apart. At the end of anaphase, the cell has succeeded in separating identical copies of the genetic material into two distinct populations.

Telophase
Telophase (from the Greek τελος meaning "end") is a reversal of prophase and prometaphase events. It "cleans up" the after effects of mitosis. At telophase, the nonkinetochore microtubules continue to lengthen, elongating the cell even more. Corresponding sister chromosomes attach at opposite ends of the cell. A new nuclear envelope, using fragments of the parent cell's nuclear membrane, forms around each set of separated sister chromosomes. Both sets of chromosomes, now surrounded by new nuclei, unfold back into chromatin. Mitosis is complete, but cell division is not yet complete.

Cytokinesis

Cytokinesis is often mistakenly thought to be the final part of telophase, however cytokinesis is a separate process that begins at the same time as telophase. Cytokinesis is technically not even a phase of mitosis, but rather a separate process, necessary for completing cell division. In animal cells, a cleavage furrow (pinch) containing a contractile ring develops where the metaphase plate used to be, pinching off the separated nuclei. In both animal and plant cells, cell division is also driven by vesicles derived from the Golgi apparatus, which move along microtubules to the middle of the cell. In plants this structure coalesces into a cell plate at the center of the phragmoplast and develops into a cell wall, separating the two nuclei. The phragmoplast is a microtubule structure typical for higher plants, whereas some green algae use a phycoplast microtubule array during cytokinesis. Each daughter cell has a complete copy of the genome of its parent cell. The end of cytokinesis marks the end of the M-phase.

The Biology Project > Cell Biology > Intro. to Cell Cycle & Mitosis > Tutorial

The Cell Cycle & Mitosis Tutorial Mitosis What is (and is not) mitosis? Mitosis is nuclear division plus cytokinesis, and produces two identical daughter cells during prophase, prometaphase, metaphase, anaphase, and telophase. Interphase is often included in discussions of mitosis, but interphase is technically not part of mitosis, but rather encompasses stages G1, S, and G2 of the cell cycle. Interphase & mitosis Interphase

The cell is engaged in metabolic activity and performing its prepare for mitosis (the next four phases that lead up to and include nuclear division). Chromosomes are not clearly discerned in the nucleus, although a dark spot called the nucleolus may be visible. The cell may contain a pair of centrioles (or microtubule organizing centers in plants) both of which are organizational sites for microtubules.

Prophase

Chromatin in the nucleus begins to condense and becomes visible in the light microscope as chromosomes. The nucleolus disappears. Centrioles begin moving to opposite ends of the cell and fibers extend from the centromeres. Some fibers cross the cell to form the mitotic spindle.

Prometaphase

The nuclear membrane dissolves, marking the beginning of prometaphase. Proteins attach to the centromeres creating the kinetochores. Microtubules attach at the kinetochores and the chromosomes begin moving.

Metaphase

Spindle fibers align the chromosomes along the middle of the cell nucleus. This line is referred to as the metaphase plate. This organization helps to ensure that in the next phase, when the chromosomes are separated, each new nucleus will receive one copy of each chromosome.

Anaphase

The paired chromosomes separate at the kinetochores and move to opposite sides of the cell. Motion results from a combination of kinetochore movement along the spindle microtubules and through the physical interaction of polar microtubules.

Telophase

Chromatids arrive at opposite poles of cell, and new membranes form around the daughter nuclei. The chromosomes disperse and are no longer visible under the light microscope. The spindle fibers disperse, and cytokinesis or the partitioning of the cell may also begin during this stage.

Cytokinesis

In animal cells, cytokinesis results when a fiber ring composed of a protein called actin around the center of the cell contracts pinching the cell into two daughter cells, each with one nucleus. In plant cells, the rigid wall requires that a cell plate be synthesized between the two daughter cells

(Acknowledgements:Wikipedia)

Drug Designing - Animated Methodology

2007-06-26T12:41:00.000-07:00

This is an example of an HIV Protease Inhibitor drug - Tipranavir. In this Exciting wonderful animation, you shall learn the approach used in Drug Designing Research nowadays!

(Acknowledgement: Youtube)

Stem Cells - Animated Tutorial

2007-06-26T11:43:00.000-07:00

Stem cells are primal cells common to all multi-cellular organisms that retain the ability to renew themselves through cell division and can differentiate into a wide range of specialized cell types. Research in the human stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960s

The three broad categories of mammalian stem cells are: embryonic stem cells, derived from blastocysts, adult stem cells, which are found in adult tissues, and cord blood stem cells, which are found in the umbilical cord. In a developing embryo, stem cells are able to differentiate into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells.

As stem cells can be readily grown and transformed into specialised cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed. In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates.

Characteristics of Stem Cells

Defining properties

The rigorous definition of a stem cell requires that it possesses two properties:
Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
Unlimited potency - the capacity to differentiate into any mature cell type. In a strict sense, this makes stem cells either totipotent or pluripotent, although some multipotent and/or unipotent progenitor cells are sometimes referred to as stem cells.

These properties can be illustrated in vitro, using methods such as clonogenic assays, where the progeny of single cell is characterized. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.

Potency definitions

Potency specifies the differentiation potential of the stem cell.

Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.

Pluripotent Stem cells

Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.

Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).

Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells.

Embryonic stem cells
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst. A blastocyst is an early stage embryo - approximately 4 to 5 days old in humans and consisting of 50-150 cells. ES cells are pluripotent, and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.

Embryonic stem cell

When given no stimuli for differentiation, ES cells will continue to divide in vitro and each daughter cell will remain pluripotent. The pluripotency of ES cells has been rigorously demonstrated in vitro and in vivo, thus they can be indeed classified as stem cells.

Because of their unique combined abilities of unlimited expansion and pluripotency, embryonic stem cells are a potential source for regenerative medicine and tissue replacement after injury or disease. To date, no approved medical treatments have been derived from embryonic stem cell research. This is not surprising considering that many nations currently have moratoria on either ES cell research or the production of new ES cell lines.

Adult stem cells
Adult stem cells are undifferentiated cells found throughout the body that divide to replenish dying cells and regenerate damaged tissues. Also known as somatic (from Greek Σωματικóς, of the body) stem cells, they can be found in children, as well as adults.

Adult stem cells

A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.Many adult stem cells may be better classified as progenitor cells, due to their limited capacity for cellular differentiation.

Nevertheless, specific multipotent or even unipotent adult progenitors may have potential utility in regenerative medicine. The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. In contrast with the embryonic stem cell research, more US government funding has been provided for adult stem cell research. Adult stem cells can be isolated from a tissue sample obtained from an adult. They have mainly been studied in humans and model organisms such as mice and rats.

(Acknowledgement: Wikipedia)

Immune System - Animated Introduction

2007-06-26T11:35:00.001-07:00

An Immune system is a collection of mechanisms within an organism that protects against infection by identifying and killing pathogens. It detects pathogens ranging from viruses to parasitic worms and distinguishes them from the organism's normal cells and tissues. Detection is complicated as pathogens adapt and evolve new ways to successfully infect the host organism.

To survive this challenge, several mechanisms have evolved that recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria possess enzyme systems that protect against viral infections. Other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants, fish, reptiles, and insects. These mechanisms include antimicrobial peptides called defensins, pattern recognition receptors, and the complement system. More sophisticated mechanisms, however, developed relatively recently, with the evolution of vertebrates.The immune systems of vertebrates such as humans consist of many types of proteins, cells, organs, and tissues, which interact in an elaborate and dynamic network. As part of this more complex immune response, the vertebrate system adapts over time to recognize particular pathogens more efficiently. The adaptation process creates immunological memories and allows even more effective protection during future encounters with these pathogens. This process of acquired immunity is the basis of vaccination.

Disorders in the immune system can cause disease. Immunodeficiency diseases occur when the immune system is less active than normal, resulting in recurring and life-threatening infections. Immunodeficiency can either be the result of a genetic disease, such as severe combined immunodeficiency, or be produced by pharmaceuticals or an infection, such as the acquired immune deficiency syndrome (AIDS) that is caused by the retrovirus HIV. In contrast, autoimmune diseases result from a hyperactive immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include rheumatoid arthritis, diabetes mellitus type 1 and lupus erythematosus. These critical roles of immunology in health and disease are areas of intense scientific study.

Layered defense in immunity

The immune system protects organisms from infection with layered defenses of increasing specificity. Most simply, physical barriers prevent pathogens such as bacteria and viruses from entering the body. If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response. Innate immune systems are found in all plants and animals. However, if pathogens successfully evade the innate response, vertebrates possess a third layer of protection, the adaptive immune system. Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered.

Surface barriers

Several barriers protect organisms from infection, including mechanical, chemical and biological barriers. The waxy cuticle of many leaves, the exoskeleton of insects, the shells and membranes of externally deposited eggs, and skin are examples of the mechanical barriers that are the first line of defense against infection.
However, as organisms cannot be completely sealed against their environments, other systems act to protect body openings such as the lungs, intestines, and the genitourinary tract. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the respiratory tract. The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.

Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β-defensins. Enzymes such as lysozyme and phospholipase A in saliva, tears, and breast milk are also antibacterials. Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains defensins and zinc to kill pathogens. In the stomach, gastric acid and proteases serve as powerful chemical defenses against ingested pathogens.

Within the genitourinary and gastrointestinal tracts, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, by changing the conditions in their environment, such as pH or available iron.This reduces the probability that pathogens will be able to reach sufficient numbers to cause illness. However, since most antibiotics non-specifically target bacteria and do not affect fungi, oral antibiotics can lead to an "overgrowth" of fungi and cause conditions such as a vaginal candidiasis (yeast infection). There is good evidence that re-introduction of probiotic flora, such as pure cultures of the lactobacilli normally found in yoghurt, helps restore a healthy balance of microbial populations in intestinal infections in children and encouraging preliminary data in studies on bacterial gastroenteritis, inflammatory bowel diseases, urinary tract infection and post-surgical infections.

Innate immunity

Microorganisms that successfully enter an organism will encounter the cells and mechanisms of the innate immune system. Innate immune defenses are non-specific, meaning these systems recognize and respond to pathogens in a generic way. This system does not confer long-lasting immunity against a pathogen. The innate immune system is the dominant system of host defense in most organisms

Humoral and chemical barriers

Inflammation

Inflammation is one of the first responses of the immune system to infection. The symptoms of inflammation are redness and swelling, which are caused by increased blood flow into a tissue. Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes). Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell. Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.

Complement system

he complement system is a biochemical cascade that attacks the surfaces of foreign cells. It contains over 20 different proteins and is named for its ability to "complement" the killing of pathogens by antibodies. Complement is the major humoral component of the innate immune response. Many species have complement systems, including non-mammals like plants, fish, and some invertebrates.

In humans, this response is activated by the binding of complement proteins to carbohydrates on the surfaces of microbes or by complement binding to antibodies that have attached to these microbes. This recognition signal triggers a rapid killing response. The speed of the response is a result of signal amplification that occurs following sequential proteolytic activation of complement molecules, which are also proteases. After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other complement proteases, and so on. This produces a catalytic cascade that amplifies the initial signal by controlled positive feedback. The cascade results in the production of peptides that attract immune cells, increase vascular permeability, and opsonize (coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their plasma membrane.

Adaptive immunity
The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by a signature antigen.The adaptive immune response is antigen-specific and requires the recognition of specific "non-self" antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.

Lymphocytes

The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are the major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow.B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response.

Association of a T cell with MHC class I or MHC class II, and antigen (in red)

Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a "non-self" target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a "self" receptor called a major histocompatibility complex (MHC) molecule. There are two major subtypes of T cells: the killer T cell and the helper T cell. Killer T cells only recognize antigens coupled to Class I MHC molecules, while helper T cells only recognize antigens coupled to Class II MHC molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC receptors.

In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes whole pathogens without any need for antigen processing. Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.

Killer T cells

Killer T cell are a sub-group of T cells that kill cells infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. As with B cells, each type of T cell recognises a different antigen. Killer T cells are activated when their T cell receptor (TCR) binds to this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a co-receptor on the T cell, called CD8. The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such cells, it releases cytotoxins that form pores in the target cell's plasma membrane, allowing ions, water and toxins to enter. This causes the target cell to undergo apoptosis. T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T cells.

Helper T cells

Helper T cells regulate both the innate and adaptive immune responses and help determine which types of immune responses the body will make to a particular pathogen. These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the immune response by directing other cells to perform these tasks.

Helper T cells express T cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex is also recognized by the helper cell's CD4 co-receptor, which recruits molecules inside the T cell ( e.g. Lck) that are responsible for T cell's activation. Helper T cells have a weaker association with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200�300) on the helper T cell must be bound by an MHC:antigen in order to activate the helper cell, while killer T cells can be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell. The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell's surface, such as CD40 ligand (also called CD154), which provide extra stimulatory signals typically required to activate antibody-producing B cells

(Acknowledgement: Wikipedia, Youtube)

Nano-Medicine

2007-06-26T09:10:00.001-07:00

Nanomedicine

is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials

Nanomedicine research is directly funded, with the US National Institutes of Health in 2005 funding a five-year plan to set up four nanomedicine centers. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide

In the near future, advancement in nanomedicine will deliver a valuable set of research tools and clinically helpful devices. The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that will include advanced drug delivery systems, new therapies, and in vivo imaging. The most important innovations are taking place in drug delivery which involves developing nanoscale particles or molecules to improve bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. Over 65 billion dollars is wasted every year because of poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new therapies and surgeries that are being developed might be effective in treating illnesses and diseases such as cancer. Finally, a shift from the possible to the potential will be made when nanorobots such as neuro-electronic interfaces and cell repair machines are discussed.

Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell walls and into cells. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently.

Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms, one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.

Nanorobots

The somewhat speculative claims about the possibility of using nanorobots in medicine, advocates say, would totally change the world of medicine once it is realized. Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections. A typical blood borne medical nanorobot would be between 0.5-3 micrometres in size, because that is the maximum size possible due to capillary passage requirement. Carbon would be the primary element used to build these nanorobots due to the inherent strength and other characteristics of some forms of carbon (diamond/fullerene composites). Cancer can be treated very effectively, according to nanomedicine advocates. Nanorobots could counter the problem of identifying and isolating cancer cells as they could be introduced into the blood stream. These nanorobots would search out cancer affected cells using certain molecular markers. Medical nanorobots would then destroy these cells, and only these cells. Nanomedicines could be a very helpful and hopeful therapy for patients, since current treatments like radiation therapy and chemotherapy often end up destroying more healthy cells than cancerous ones. From this point of view, it provides a non-depressed therapy for cancer patients. Nanorobots could also be useful in treating vascular disease, physical trauma , and even biological

Neuro-electronic Interfaces

Neuro-electronic interfaces are a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. The computers will be able to interpret, register, and respond to signals the body gives off when it feels sensations. The demand for such structures is huge because many diseases involve the decay of the nervous system (ALS and multiple sclerosis). Also, many injuries and accidents may impair the nervous system resulting in dysfunctional systems and paraplegia. If computers could control the nervous system through neuro-electronic interface, problems that impair the system could be controlled so that effects of diseases and injuries could be overcome. Two considerations must be made when selecting the power source for such applications. They are refuelable and nonrefuelable strategies. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, or electrical sources. A nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained.

One limitation to this innovation is the fact that electrical interference is a possibility. Electric fields, EMP pulses, and stray fields from other in vivo electrical devices can all cause interference. Also, thick insulators are required to prevent electron leakage, and if high conductivity of the in vivo medium occurs there is a risk of sudden power loss and "shorting out." Finally, thick wires are also needed to conduct substantial power levels without overheating. Little practical progress has been made even though research is happening. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system so that it is able to monitor and respond to nervous signals. The structures that will provide the interface must also be compatible with the body's immune system so that they will remain unaffected in the body for a long time. In addition, the structures must also sense ionic currents and be able to cause currents to flow backward. While the potential for these structures is amazing, there is no timetable for when they will be available.

Cell repair machines

Using drugs and surgery, doctors can only encourage tissues to repair themselves. With molecular machines, there will be more direct repairs. Cell repair will utilize the same tasks that living systems already prove possible. Access to cells is possible because biologists can stick needles into cells without killing them. Thus, molecular machines are capable of entering the cell. Also, all specific biochemical interactions show that molecular systems can recognize other molecules by touch, build or rebuild every molecule in a cell, and can disassemble damaged molecules. Finally, cells that replicate prove that molecular systems can assemble every system found in a cell. Therefore, since nature has demonstrated the basic operations needed to perform molecular-level cell repair, in the future, nanomachine based systems will be built that are able to enter cells, sense differences from healthy ones and make modifications to the structure.

The possibilities of these cell repair machines are impressive. Comparable to the size of viruses or bacteria, their compact parts will allow them to be more complex. The early machines will be specialized. As they open and close cell membranes or travel through tissue and enter cells and viruses, machines will only be able to correct a single molecular disorder like DNA damage or enzyme deficiency. Later, cell repair machines will be programmed with more abilities with the help of advanced AI systems.

Nanocomputers
will be needed to guide these machines. These computers will direct machines to examine, take apart, and rebuild damaged molecular structures. Repair machines will be able to repair whole cells by working structure by structure. Then by working cell by cell and tissue by tissue, whole organs can be repaired. Finally, by working organ by organ, health is restored to the body. Cells damaged to the point of inactivity can be repaired because of the ability of molecular machines to build cells from scratch. Therefore, cell repair machines will free medicine from reliance on self repair.

A new wave of technology and medicine is being created and its impact on the world is going to be monumental. From the possible applications such as drug delivery and in vivo imaging to the potential machines of the future, advancements in nanomedicine are being made every day. It will not be long for the 10 billion dollar industry to explode into a 100 billion or 1 trillion dollar industry, and drug delivery, in vivo imaging and therapy is just the beginning.

(Acknowledgement: Wilkepedia)

Protein Biosynthesis

2007-06-26T08:44:00.001-07:00

Protein biosynthesis (Synthesis) is the process in which cells build proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription which are then used for translation. Protein biosynthesis, although very similar, differs between prokaryotes and eukaryotes.
Amino acid synthesis

Amino acids are the monomers which are polymerized to produce proteins. Amino acid synthesis is the set of biochemical processes (metabolic pathways) which build the amino acids from carbon sources like glucose. Not all amino acids may be synthesised by every organism, for example adult humans have to obtain 8 of the 20 amino acids from their diet.

The amino acids are then loaded onto tRNA molecules for use in the process of translation.
Transcription is the process by which an mRNA template, carrying the sequence of the protein, is produced for the translation step from the genome. Transcription makes the template from one strand of the DNA double helix, called the template strand.
Transcription takes place in 3 stages.
Transcription starts with the process of Initiation. RNA
polymerase, the enzyme which produces RNA from a DNA template, binds to a
specific region on DNA that designates the starting point of transcription. This
binding region is called the promoter. As the RNA polymerase binds on to the
promoter, the DNA strands are beginning to unwind.

The second process is Elongation. RNA polymerase
travels along the template (noncoding) strand, synthesizing a ribonucleotide
polymer. RNA polymerase does not use the coding strand as a template because a
copy of any strand produces a base sequence that is complementary to the strand
which is being copied. Therefore DNA from the noncoding strand is used as a
template to copy the coding strand.

The third stage is Termination. As the polymerase
reaches the termination stage, modifications are required for the newly
transcribed mRNA to be able to travel to the other parts of the cell, including
cytoplasm and endoplasmic reticulum, for translation. A 5' cap is added to the
mRNA to protect it from degradation. In eukaryotes, poly-A-polymerase adds a
poly-A tail onto the 3' end for stabilization, protection from cytoplasmic
hydrolytic enzymes, and as a template for further processes. Also in eukaryotes
(higher organisms) the vital process of splicing occurs at this stage by the
spliceosome enzyme. It removes the introns (non-coding bits of genetic material)
and glues together the exons (the segments that code for a specific protein).
The mRNA now exits the nuclear pore to be translated.
Translation:
Protein translation involves the transfer of information from the mRNA into a peptide, composed of amino acids. This process is mediated by the ribosome, with the adaptation of the RNA sequence into amino acids mediated by transfer RNA. Numerous initation and elongation factors also play a role.

Translation requires a lot of energy, with the hydrolysis of approximately 4 NTP --> NDP per amino acid added. (This includes the aminoacylation of the tRNA. Thus, gene expression is highly regulated to ensure that only proteins that are required are translated.

Translation involves 3 processes: initiation, elongation, and termination.
Initiation in Prokaryotes

The initiation of protein translation involves the assembly of the ribosome and addition of the first amino acid, methionine.

The 30S ribosomal subunit attaches to the mRNA, mediated by IF-1 and IF-3 (initiation factors).

The 30S ribosome brings with it the P and A site, but the A site is blocked by IF-1 to prevent binding of tRNA. It aligns to the Shine-Dalgarno sequence, which positions the first codon (AUG) in the P site.

Next, the specific aminoacyl-tRNA for N-formylmethionine (F-Met) is brought into the P site by IF-2. The anticodon of this tRNA will bind to the AUG codon on the mRNA.

(Note: this is the only tRNA brought into the P site; all successive aminoacyl-tRNAs will be brought to the A site for peptide elongation).

The 50S ribosomal subunit is then brought in to complete the ribosome, and with it, IF-1, IF-2, and IF-3 come off the complex. The A and P site are completed, and the 50S subunit also brings the E (exit) site.
Initiation in Eukaryotes

The initiation of protein translation in eukaryotes is similar to that of prokaryotes with some modifications.

A complex of proteins will connect the 5'cap and 3'PolyA tail, and this complex will recruit the ribosome subunits.
There is no Shine-Dalgarno sequence in eukaryotes. Instead, the ribosome scans along the mRNA for the first methionine codon. Similarly, there is no N-formyl methionine in eukaryotic cells.
Elongation

Elongation of protein biosynthesis is fairly similar between prokaryotes and eukaryotes. The following is a description of elongation in prokaryotes:
Elongation proceeds after initiation with the binding of an aminoacyl-tRNA
to the A site, which is the next codon in the mRNA.
The aminoacyl-tRNA is brought to the ribosome through a series of
interactions with EF-Tu (an elongation factor). This step involves the
hydrolysis of GTP: EF-Tu-GTP --> EF-Tu-GDP (The hydrolyzed GDP is
switched for GTP through another series of reactions with EF-Ts.)

The next aminoacyl-tRNA binds to the codon, and the C-terminus of the
F-Met undergoes nucleophilic attack by the N-terminus of the second amino acid.
The F-Met is now connected to the second amino acid through a peptide bond.

The first tRNA (for F-Met) is now uncharged. The entire ribosome complex
moves along the mRNA through the action of another elongation factor (EF-G) and
the hydrolysis of GTP --> GDP.

The first tRNA is now in the E site and comes off from the ribosome,
while the second tRNA, with the nascent peptide chain, is in the P site.

Step 1-4 will repeat as successive amino acids are added.
Termination

Termination of protein biosynthesis occurs when the ribosome comes across a stop codon, for which there is no tRNA. At this point, protein biosynthesis halts and one of three release factors will bind to the stop codon. (Note: In eukaryotes, there is only one release factor that will bind to all three stop codons.) This induces a nucleophilic attack of the C-terminus of the nascent peptide by water - this hydrolysis releases the peptide from the ribosome. The ribosome, release factor, and uncharged tRNA then dissociates and translation is complete.
Events following Protein Translation
The events following biosynthesis include post-translational modification and protein
folding. During and after synthesis, polypeptide chains often fold to assume, so called, native secondary and tertiary structures. This is known as protein folding.

Many proteins undergo post-translational modification. This may include the formation of disulfide bridges or attachment of any of a number of biochemical functional groups, such as acetate, phosphate, various lipids and carbohydrates. Enzymes may also remove one or more amino acids from the leading (amino) end of the polypeptide chain, leaving a protein consisting of two polypeptide chains connected by disulfide bonds.

(Acknowledgement: Wikipedia)

Histone proteins

2007-06-26T08:35:00.001-07:00

Histones are the chief protein components of chromatin. They act as spools around which DNA winds and they play a role in gene regulation.

Six major histone classes are known:

H1 (sometimes called the linker histone or H5.)
H2A
H2B
H3
H4
Archaeal histones

Two each of the class H2A, H2B, H3 and H4, so-called core histones, assemble to form one octameric nucleosome core particle by wrapping 146 base pairs of DNA around the protein spool in 1.65 left-handed super-helical turn. The linker histone H1 binds the nucleosome and the entry and exit sites of the DNA, thus locking the DNA into place and allowing the formation of higher order structure. The most basic such formation is the 10 nm fiber or beads on a string conformation. This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of DNA spaced between each nucleosome (also referred to as linker DNA). Higher order structures include the 30 nm fiber (forming an irregular zigzag) and 100 nm fiber, these being the structures found in normal cells. During meiosis, through the combination of nucleosome interactions with other proteins, the chromosome is assembled. The assembled histones and DNA is called chromatin.

Structure

The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer, forming two nearly symmetrical halves by tertiary structure (C2 symmetry; one macromolecule is the mirror image of the other). The H2A-H2B dimers and H3-H4 tetramer also show pseudodyad symmetry.

The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution, all featuring a 'helix turn helix turn helix' motif (which allows the easy dimerisation). They also share the feature of long 'tails' on one end of the amino acid structure - this being the location of post-transcriptional modification

In all, histones make five types of interactions with DNA:

Helix-dipoles from alpha-helices in H2B, H3, and H4 cause a net positive charge to accumulate at the point of interaction with negatively charged phosphate groups on DNA.
Hydrogen bonds between the DNA backbone and the amine group on the main chain of histone proteins.
Nonpolar interactions between the histone and deoxyribose sugars on DNA.
Salt links and hydrogen bonds between side chains of basic amino acids (especially lysine and arginine) and phosphate oxygens on DNA.
Non-specific minor groove insertions of the H3 and H2B N-terminal tails into two minor grooves each on the DNA molecule.

The highly basic nature of histones, aside from facilitating DNA-histone interactions, contributes to the water solubility of histones.

Histones are subject to posttranslational modification by enzymes primarily on their N-terminal tails, but also in their globular domains. Such modifications include methylation, citrullination, acetylation, phosphorylation, Sumoylation, ubiquitination, and ADP-ribosylation. This affects their function of gene regulation

In general, genes that are active have less bound histone, while inactive genes are highly associated with histones during interphase. It also appears that the structure of histones have been evolutionarily conserved, as any deleterious mutations would be severely maladaptive.

Functions:

Packing proteins: Histones act as spools around which DNA winds. This enables the compaction necessary to fit the large genomes of eukaryotes inside cell nuclei: the compacted molecule is 50,000 times shorter than an unpacked molecule.
Histone modifications in chromatin regulation: Histones undergo posttranslational modifications which alter their interaction with DNA and nuclear proteins. The H3 and H4 histones have long tails protruding from the nucleosome which can be covalently modified at several places. Modifications of the tail include methylation, acetylation, phosphorylation, ubiquitination, sumoylation, citrullination, and ADP ribosylation. The core of the histones (H2A and H3) can also be modified. Combinations of modifications are thought to constitute a code, the so-called "histone code". Histone modifications act in diverse biological processes such as gene regulation, DNA repair and chromosome condensation (mitosis)

Human Genetic Resources

2007-06-26T08:24:00.001-07:00

Here you'll find quite useful links to various Human Genetic Resources along with information on Human Genome Project.

Designer Genes
This site was created by high school and junior high school students as an entry in the 1998 ThinkQuest web design contest. The site offers a remarkably clear, detailed non-technical overview of genetics.
Primer on Molecular Genetics (DOE)
The Primer on Molecular Genetics is very much like an introductory biology text, teaching the core fundamentals of genetics (DNA, gene mapping, linkage, etc).
Genlink
GenLink is a multimedia database resource for human genetics that is currently under development. GenLink will provide linkage mapping information and software tools that will facilitate the integration of physical and genetic linkage data to produce unified maps of the human genome.
Human Genome Project Information
Human Genome Project at Los Alamos National Laboratory
The LANL center's goals include assembly of complete high-resolution ( 0.1 Mb) maps of chromosome 16 and regions of chromosome 5, studies at the molecular level of chromosome structure and function, and isolation of selected genes of interest on chromosomes 5 and 16.
The Human Molecular Genetics Page at HUM MOL-GEN
Human Molecular Genetics Group
The home page for the Human Molecular Genetics Group, led by Dr. Nabeel Affara, contains a host of information regarding the human Y chromosome. An anonymous FTP site is available to their data.
Human STS vs YAC Screening Data
This site is a searchable database that lets you search for markers, YAC's and contigs. You must have a forms-capable browser to use this service.
List of the Human Genome Databases
This site is a good resource for the various databases that contain Human Genome information.
Stanford Human Genome Server
The Stanford Human Genome Center is a research facility dedicated to mapping and sequencing DNA in the human genome. Their World Wide Web (WWW) site will soon have an interface to a Sybase database of genetic information.
Classic Papers in Genetics
University of Michigan Human Genome Center
National Center for Genome Resources
The Virtual Library: Genetics

First Artificial Life in months

2007-06-06T10:32:00.000-07:00

Scientists could create the first new form of artificial life within months after a landmark breakthrough in which they turned one bacterium into another.

In a development that has triggered unease and excitement in equal measure, scientists in the US took the whole genetic makeup - or genome - of a bacterial cell and transplanted it into a closely related species.

This then began to grow and multiply in the lab, turning into the first species in the process.

The team that carried out the first "species transplant" says it plans within months to do the same thing with a synthetic genome made from scratch in the laboratory

If that experiment worked, it would mark the creation of a synthetic lifeform.

The scientists want to create new kinds of bacterium to make new types of bugs which can be used as green fuels to replace oil and coal, digest toxic waste or absorb carbon dioxide and other greenhouse gases from the atmosphere.

But this pioneering research also triggers unease about the limits of science and the inevitable fears about "playing god," as well as raising the spectre that this technology could one day be abused to create a new generation of bioweapons.

Producing living cells from synthetic genomes of lab-made DNA would require the ability to move and manipulate whole genomes.

To that end, a milestone was passed today by a team led by Craig Venter, the first person to have his entire genetic makeup read, and which included the Nobel prizewinner Ham Smith.

Dr Venter said that, in the light of this success, the culmination of a decade's work, he will be attempting the first transplant of a lab-made genome to create the first artificial life "within months."

Dr Venter said: "We would hope to have the first fuel from synthetic organisms certainly within the decade, possibly within half that time."

The breakthrough occurred at the J Craig Venter Institute in Rockville, Maryland, the team reports today in the journal Science.

One of its editors called it "a landmark in biological engineering."

Since the 1970s, scientists have moved genes - instructions to make proteins - between different organisms.

But this marks the first time that the entire instruction set, consisting of more than a million "letters" of DNA, has been transplanted, transforming one species of bacterium into another.

They are attempting to build a microbe with the minimal set of genes needed for life, with the goal of then adding other useful genes, such as ones for making biofuels.

It recently submitted broad patents for methods to create a synthetic genome from such lab-made DNA.

In anticipation, the team wanted to develop a way to move a complete genome into a living cell, chosing the simplest and smallest kind, a bacterium.

In all, of the millions of bacteria that they tried the transplant on, it only worked one time in every 150,000.

Dr Venter likened it to "changing a Macintosh computer into a PC by inserting a new piece of software" and stressed it would be more difficult in other kinds of cells, which have enzymes to snip the DNA of invaders.

But he said to achieve the feat, without adding anything more than naked DNA, "is a huge enabling step."

"This is a significant and unexpected advance," commented Robert Holt of the Michael Smith Genome Sciences Centre, Vancouver, Canada.

"It's a necessary step toward creating artificial life," added microbiologist Fred Blattner of the University of Wisconsin, Madison.

Antoine Danchin of the Pasteur Institute, Paris, calls the experiment "an exceptional technical feat."

But he told Science "many controls are missing." And that has prevented Glass's team, as acknowledged by Ham Smith, from truly understanding how the introduced DNA reprograms the host cell.

"We are one step closer to synthetic organisms," said Markus Schmidt of the Organisation for International Dialogue, Vienna.

He said the experiment will drive discussions about the safety issues related to synthetic biology and the implications for society.

Dr Venter stressed that the work had been halted for some time for a review to ensure it is ethical, though acknowledged concerns that synthetic biology could pave the way to new kinds of biowarfare.

(Source: Telegraph.co.uk)

Advertising on SISR

2007-01-21T08:23:00.000-08:00

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Dead End

2007-01-21T03:08:00.000-08:00