A new study published in the open-access journal PLoS
Pathogens has found that replication of coronaviruses – such
as SARS – depends on two factors within the early secretory pathway.

As the cause of several respiratory and enteric (referring to the
intestines) infections in both humans and animals, coronaviruses have
been a recent focus of pathology research. The infection cycle of this
class of viruses, as with all viruses, highly depends on cellular
factors related to the host. After making its way into cells,
coronaviruses begin systematic RNA replication in factory-like
complexes that are linked to newly induced, double membrane vesicles.
Researchers have not yet revealed the cellular pathways used by these
plus-strand RNA viruses in creating these “factories.”

A team of Dutch researchers, led by Cornelis A. M. de Haan,
has demonstrated that the drug brefeldin A inhibits RNA
replication of mouse hepatitis coronavirus (MHV). It achieves this by
interfering with the central station of the cell’s secretory pathway -
called the Golgi complex. The authors were able to show consistent
depletion of both the cellular target of brefeldin A and two factors
that negatively affect infection the coronavirus’s infection: one
factor called GBF1 and a second downstream called ARF1.

“An intimate association exists between the early secretory pathway and
MHV replication,” write the researchers. Though GBF1 and ARF1 are not
involved in forming the viral replication factories, the researchers
suggest that the two factors affect their maturation or functioning.
Their research specifically dealt with the mouse hepatitis coronavirus,
and they call for further researcher studying the impact of GBF1 and
ARF1 in the replication of other coronaviruses.

Mouse Hepatitis Coronavirus RNA Replication Depends on
GBF1-Mediated ARF1 Activation
Verheije MH, Raaben M, Mari M, te Lintelo EG, Reggiori F, et al.
PLoS Pathogens (2008). 4(6):e1000088.
doi:10.1371/journal.ppat.1000088
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Here to View Article

About PLoS Pathogens

PLoS Pathogens (www.plospathogens)
publishes outstanding original articles that significantly advance the
understanding of pathogens and how they interact with their host
organisms. All works published in PLoS Pathogens
are open
access. Everything is immediately available subject only to the
condition that the original authorship and source are properly
attributed. Copyright is retained by the authors. The Public Library of
Science uses the Creative Commons Attribution License.

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization
of scientists and physicians committed to making the world’s
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For more information, visit plos

: Peter M Crosta

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On June 9 California sent letters to 13 genetic-testing companies ordering them to “cease and desist performing genetic testing without licensure or physician order.” Some of the companies have since stopped offering direct-to-consumer tests to Californians, while others insist that they are already in compliance with the law and continue to operate in the state. New York State similarly warned companies this spring that they need licenses to accept DNA samples from the state’s residents. (The Center summarizes the companies’ responses here.)

GPPC has long advocated for comprehensive federal oversight of genetic testing, and disparate state laws and state enforcement actions are clearly consequences of the void at the federal level. The confusion will only grow if and when more states attempt to fill the role the federal government has shirked – a situation that will benefit no one. As California Department of Public Health official Karen Nickel said in a conference call with members of the Clinical Laboratories Advisory Committee, “We’re looking for some kind of federal action.” Similarly, DNATraits founding partner Bennett Greenspan told GenomeWeb Daily News, “I’d rather there be a federal solution than a state solution, just as a matter of efficiency.” For 50 states to each create and enforce their own potentially disparate regulations for genetic tests, and for companies to comply with them, would indeed create massive inefficiencies. State resources would be diverted from other programs, and innovation in the genetic testing industry could be stifled as labs struggle to discern and comply with variable state laws and regulations.

Several companies recently announced plans to team up to devise guidelines for the genetic-testing industry. These standards will tap into considerable scientific and technical expertise, and potentially will be flexible and readily updated as the science progresses. However, they will be voluntary, leaving bad actors free to continue offering deceptively-marketed, inaccurate, or unhelpful tests. Furthermore, having genetic testing companies devise the guidelines creates a potential conflict of interest and may not bolster consumer confidence.

At the same June roundtable where the guidelines plan was announced, a representative from the Federal Trade Commission (FTC) acknowledged that the FTC has the authority to prohibit direct-to-consumer genetic-testing companies from making misleading claims, and said the agency is investigating two such companies. Meantime, some companies are still making the kinds of patently deceptive claims that in 2006 led Sen. Smith to label their products “snake oil.”

We’ve said it before, and we’ll say it again: the most sensible, effective way to ensure the reliability of genetic tests is for the federal government to create and enforce stronger regulations for genetic tests and the laboratories that perform them. – Kathy Hudson, director, Genetics & Public Policy Center

Factsheet – Summary of New York and California Correspondence with Health-Related
Direct-to-Consumer Genetic Testing Businesses

Issue brief – Direct-to-consumer genetic testing: empowering or endangering the public?

Chart – Direct-to-consumer genetic testing companies

Article – Advisory committee recommends improvements to genetic testing oversight

Genetics & Public Policy Center – Johns Hopkins Unversity Read the rest of this entry »

When fruit flies lack a receptor for the inhibitory neurotransmitter gamma aminobutyric acid (GABA), their ability to learn or remember is enhanced, the first time scientists have been able to induce this effect in the insects, said Baylor College of Medicine researchers in a report that appears in the journal Neuron.

“We now know that the neurotransmitter GABA is a neurotransmitter that inhibits learning,” said Xu Liu, a graduate student in the laboratory of Dr. Ronald Davis, professor of molecular and cellular biology at BCM. Liu is first author of the report and Davis is senior author.

“One of the exciting things about this is that normal learning might occur by inhibiting the inhibition of GABA,” said Davis.

In this study, Liu, Davis and their colleagues studied the effects of the GABA receptor called Resistance to dieldrin (Rdl), which is expressed or activated in the mushroom bodies of Drosophila melanogaster or the fruit fly most commonly studied in the laboratory. Mushroom bodies are key to learning and memory related to odors in the fruit fly.

When Liu overexpressed or caused too much of the receptor to be present in the mushroom body, the flies had a learning defect. But when he reduced the expression of the receptor, the flies learned better than normal.

Using a special temperature-sensitive “switch” developed by a former student in Davis’ lab, Liu raised fruit flies in which the overexpression of the receptor occurred only at higher temperatures. The flies were raised in cooler temperatures, but when they were adults, he moved them into higher temperatures for days at a time.

The flies learned less quickly in the higher temperature, when the overexpression was turned on. When they were moved back to lower temperatures, their learning ability returned to normal.

“It looks as though this affects only memory acquisition but not memory stability,” said Liu. “Flies that overexpress the receptor can’t learn as fast, but once they learn, they remember it as well as those who do not have the overexpression.”

Dr. William C. Krause of BCM also took part in this study.

Funding for this study came from the National Institutes of Health, the G. Harold and Leila Y. Mathers Charitable Foundation and the R. P. Doherty-Welch Chair in Science at the Baylor College of Medicine.

The article can be found at neuron/.

Source: Dipali Pathak

Baylor College of Medicine Read the rest of this entry »

New research could explain why females of many species have multiple partners. Published on Friday 21 November 2008 in leading journal Science, the study was carried out by a team from the Universities of Exeter (UK), Okayama (Japan) and Liverpool (UK).

Females of most species, including many mammals, mate with multiple partners. The driving forces for this practice, known as ‘polyandry’, have been a mystery for evolutionary biologists for decades. This research suggests that polyandry could be the result of females adapting to avoid producing offspring carrying selfish genetic elements that reduce male fertility.

The research team based the study on the fruitfly Drosophila pseudoobscura, which they bred over ten generations. Some males of this species carry a ‘selfish gene’ on their X chromosome that causes sperm carrying the Y-chromosome to fail. This means that males carrying this gene can only produce daughters, all of which carry the sperm damaging gene.

In this study females evolved to mate with more partners when they were exposed to males carrying this selfish gene. There was no way for the females to tell whether or not a potential mate carried the gene, but they evolved to re-mate more quickly. After ten generations, they re-mated after an average of 2.75 days, compared with 3.25 days among the original population. By mating more frequently, females ensure sperm from different males compete. This competition favours males without the sperm-damaging selfish genes, allowing females to bias paternity against these males.

Corresponding author Dr Nina Wedell of the University of Exeter said: “Multiple mating by females has puzzled biologists for decades. It’s more risky and costs precious time and energy for females. Our study suggests that these significant costs are worthwhile because the female increases her chances of producing healthy offspring of both sexes that do not carry the selfish gene.”

Selfish genes occur at random as a result of mutations. They spread quickly through populations because they subvert normal patterns of inheritance, increasing their presence in the next generation.

The researchers believe the findings have relevance for a range of species with polyandrous females, including some primates. Dr Nina Wedell explains: “Selfish genetic elements exist in all living organisms and many compromise male fertility. Our study could provide a new explanation for why polyandry is so remarkably widespread.”

At this stage the researchers do not know what implications these findings might have for understanding human reproduction. However, it is possible that some types of male fertility disorder are caused by the manipulation of selfish genes.

This study was funded by the Natural Environment Research Council.

Source: Sarah Hoyle

University of Exeter Read the rest of this entry »

A Mayo Clinic-led international consortium has found a mechanism that may help explain Parkinson’s and other neurological disorders.

Studying just eight families worldwide, the international team of researchers have discovered a genetic defect that results in profound depression and parkinsonism in a disorder known as Perry syndrome. Although this syndrome is exceedingly rare, the mechanism implicated in it may help explain the origins of a variety of neurodegenerative disorders, such as Parkinson’s and amyotrophic lateral sclerosis diseases, and even common depression and sleep disorders that are also hallmarks of the disorder, the researchers say.

In the study, to be published in the February issue of Nature Genetics (online January 11), the researchers report that people with Perry syndrome have mutations in a subunit of the dynactin complex (DCTN1; p150glued), which is essential to the movement of molecular “cargo” inside brain cells, or neurons. In this case, the mutations meant that the cargo was being driven on a “train” that essentially had faulty brakes. And because Perry syndrome resembles many other neurodegenerative diseases, the findings suggest breakdowns along the cell’s interior transportation grid may be a common mechanism underlying neurodegeneration.

“Understanding why distinct neurons are selectively vulnerable to neurodegeneration in different brain disorders is one of the greatest puzzles in neuroscience,” says the study’s lead investigator, Matthew J. Farrer, Ph.D., a professor of neuroscience at Mayo Clinic. “These findings suggest that trafficking of specific cargoes inside brain cells may be a general problem in a variety of neurodegenerative diseases, depression, and other disorders.”

“It points us to a unified theory of what is going wrong in many of them,” says the study’s senior author, Zbigniew K. Wszolek, M.D., professor of neurology at Mayo Clinic.

Molecules, vesicles and organelles within a cell are constantly carried via a network of crisscrossing microtubules that act like the tracks of an elaborate railroad system. Because, for the most part, neurons do not regenerate or divide as do other cells in the body, trafficking cargo efficiently over the lifetime of a neuron is fundamentally important, says Dr. Farrer.

Disruptions in this railroad system have been seen in many neurodegenerative diseases, but these problems have been generally regarded as byproducts of the disorder rather than the cause, the researchers say. These new findings may change that view, they say.

For example, in amyotrophic lateral sclerosis (ALS), a motor neuron disease also known as Lou Gehrig’s disease, the molecular motors (for example, dynein, dynactin and kinesin) that drive transport from distant nerve terminals to the cell body may become defective. In some forms of Parkinson’s disease, growing evidence indicates that the cargoes being trafficked are also misdirected by faulty signaling, due to pathogenic mutations in the leucine-rich repeat kinase 2(LRRK2) gene, Dr. Farrer says.

The findings may also shed light on other neurodegenerative disorders, the researchers say. In Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy, for instance, the “spikes,” comprised of microtubule associated protein tau (MAPT), that normally stabilize and secure these rails tend to fall apart.

This discovery would not have been possible without a consortium of international researchers including co-authors from Canada, France, Japan, Turkey, and the United Kingdom, says Dr. Wszolek, who established the collaborative network of scientists.

Perry syndrome was first described in two unrelated Canadian families in 1975. In a study published in 2007, Dr. Wszolek, along with Swiss neurologist and visiting fellow Christian Wider, M.D., summarized the clinical features of the disease, which include early-onset parkinsonism (stiffness, slowness and rigidity), depression, severe weight loss, and increasing difficulty in breathing. Once symptoms occur, typically in the patient’s mid-40s, the disease is rapidly progressive and fatal.

In a subsequent study published in August 2008, the consortium reported that eight patients who died from the disease had substantial loss of neurons in the midbrain area known as the substantia nigra. They also found a molecular signature of Perry syndrome – “inclusions,” or clumps, of a protein known as TDP-43 – which is found in patients with frontotemporal dementia or with motor neuron disease. What these clumps represent is not known, says co-author and neuropathologist Dennis Dickson, M.D. “But they are clearly a marker of the disease process in all of these disorders, suggesting a common process is perturbed,” he says.

Mayo geneticists hypothesized that Perry syndrome may be caused by mutations within the same gene, even though families afflicted with this disorder are unrelated, and come from different continents. The disease is autosomal dominant, meaning that the chance of inheriting the disease is 50 percent if one parent carries a copy of a mutant gene. With the help and participation of eight families with Perry syndrome, the Mayo-led team set out to find the defective gene.

They determined that each family had one of five novel mutations in the DCTN1 gene, whose protein produces a large subunit of the dynactin complex known as p150glued. This protein is essential to the movement of cargo along the microtubule rails. “Curiously, the mutations all cluster in the p150glued cytoskeleton-associated protein glycine-rich domain and its ‘GKNDG’ binding motif,” Dr. Farrer says. “This region acts like a parking brake, so Perry mutations in p150glued mean that this brake is affected. It would be analogous to driving that train with faulty brakes.”

What amazed the researchers are the similarities that Perry syndrome shares with other neurodegenerative diseases. Perry mutations in DCTN1 are physically very close to a mutation previously reported in familial motor neuron disease, they say.

The deposits of TDP43 are also the same as found in motor neuron disease and in some forms of frontotemporal dementia, although they are in a different part of the brain. “With the discovery of mutations in Perry syndrome, researchers have a new means to explore the breakdown in the microtubule transport system in each of these diseases,” says Dr. Farrer. “The insides of neurons are very dynamic. Molecules and organelles are constantly being moved to where they are needed, so it makes sense that these disorders, with aging, may be caused by a progressive breakdown in this transport system.”

Understanding Perry syndrome may shed light on depression as well as metabolic syndromes, says Dr. Wszolek. Many of the patients have profound depression and about one-third of those commit suicide. Many of the patients also experience severe weight loss and sleep deprivation.

The study was funded by the Pacific Alzheimer Research Foundation of British Columbia, Canada, and the National Institute of Neurological Disorders and Strokes, which funds the Morris K. Udall Parkinson’s Disease Research Center of Excellence at Mayo Clinic, Jacksonville.

Source: Kevin Punsky

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Researchers have identified a new cancer gene – one that is common to many cancers and affects the most basic regulation of our genes. The new example – a gene on the X chromosome called UTX – is found in 10% of cases of multiple myeloma and 8% of esophageal cancers.

UTX plays a role in overall regulation of the activity of many genes and it is possible that other genes with similar roles will also be found to be involved in different tumor types. This is the first example of mutations in a gene of this functional class. The finding arose from a study of mutations in 4000 genes in kidney cancer.

“UTX is an important component of the transcriptional control machinery – it influences some of the most fundamental mechanisms controlling gene activity in our cells,” explains Dr Andy Futreal, co-leader of the Cancer Genome Project at the Wellcome Trust Sanger Institute. “Unlike many cancer genes, UTX does not appear to be directly involved in cell division or cell death but in basic gene regulation and shows the depths to which cancers will plumb in order to get themselves ready to go.”

The normal UTX protein modifies part of the structure holding DNA together in our cells. The composite DNA-protein structure, called chromatin, is not simply a scaffold, but plays an active role in controlling gene activity. The UTX protein alters a key organising subunit component of chromatin, called a histone. The protein is likely to be involved in both turning genes on and off, making it a key regulator of the yin-yang of gene control.

In the massive DNA sequencing study, the team found rare mutations of the UTX gene in clear cell renal cancer – a type of kidney cancer. When they expanded the search they found mutations in many cancer types – including one in ten multiple myeloma and one in twelve esophageal cancer cases.

“This work shows that mutations in genes with different functions can be found in human cancer through systematic approaches. These results indicate that cancer genes are not restricted to ‘classical’ roles of survival and cell proliferation, but can affect a variety of other cellular mechanisms,” explains Professor Victor Velculescu, Associate Professor of Oncology and Director of Cancer Genetics from the Ludwig Center at Johns Hopkins and co-Director of Cancer Biology, at Johns Hopkins Kimmel Cancer Center. “UTX wouldn’t have been found without this high-throughput type of study and indicates the type of novel findings we might expect from the International Cancer Genome Consortium.”

The International Cancer Genome Consortium (ICGC) seeks to catalogue genetic abnormalities in 50 different tumour types. The possibility of uncovering new regulatory genes – like UTX – along with continued efforts to catalog cancer genes, will boost researchers’ attempts to comprehensively describe different cancers which will to lead to expanding opportunities to reduce the global cancer burden.

The team showed that the biology of the mutation fitted their prediction. Cells that lacked a functional UTX gene showed notable slowing of growth when a copy of normal UTX was reintroduced. As well, substantial changes in gene transcription were noted. Genes with the most significant changes in expression were highly enriched in those most susceptible to control by UTX mediated histone modification.

The work identifies a new class of cancer genes that researchers can now pursue. These are genes that occupy the central control position of gene activity and act to keep cells from turning cancerous. When such ‘tumor suppressor genes’ are inactivated, other genes can run riot.

The consequence of mutation in UTX is to bring about changes in activity of other genes through epigenetic changes – their activity is changed by modification, not of their DNA code, but of their associated proteins and chemical tags.

“This is a genetic change with consequences at the level of epigenetic regulation,” explains Professor Mike Stratton, co-leader of the Cancer Genome Project at the Sanger Institute. “When we look at cancers, a substantial proportion of the epigenetic disregulation may well have a genetic basis.”

Notes:

Histone biology

DNA is not simply dissolved in our cells, but interacts with many proteins in structures that influence gene activity. Chromatin, the most-studied DNA-protein structure, consists largely of DNA in association with five classes of proteins called histones.

Histones bind strongly to DNA and interact with one another to produce the compact structure of chromatin. The strength of the association of histones with DNA can be modified by the addition or removal of simple chemical groups (such as methyl or acetyl groups) to or from the DNA.

Enzymes, such as the protein specified by the UTX gene, alter the levels of histone modification and so can alter activity of many genes.

Publication details

Van Haaften G et al. (2009) Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer. Nature Genetics Published online before print as doi:10.1038/ng. 349

Funding

This work was funded by the Wellcome Trust. Individual participants were supported by the European Molecular Biology Laboratory, the Kay Kendall Leukaemia Fund, the Robert A. and Renee E. Belfer Foundation for Innovative Cancer Science and the Leukaemia and Lymphoma Society.

Participating Centres
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, U.K.

Laboratory of Cancer Genetics, Van Andel Institute, Grand Rapids, MI, USA

Department of Pathology, University of Cambridge, Cambridge, UK

Departments of Surgery and Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong

Center for Applied Cancer Science of the Belfer Institute for Innovative Cancer Science, Departments of Medical Oncology, Medicine and Genetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Lebow Insitute for Myeloma Therapeutics and Lipper Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, USA

Department of Urology, Spectrum Health Hospital, Grand Rapids, MI, USA

Institute of Cancer Research, Sutton, Surrey, UK

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around ??650 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

Source:
Don Powell

Wellcome Trust Sanger Institute Read the rest of this entry »

Researchers report that a single-stranded DNA-binding protein (SSB), once thought to be a static player among the many molecules that interact with DNA, actually moves back and forth along single-stranded DNA, gradually allowing other proteins to repair, recombine or replicate the strands.

Their study, of SSB in the bacterium Escherichia coli, appears in the journal Nature.

Whenever the double helix of DNA unravels, exposing each strand to the harsh environment of the cell, SSB is usually first on the scene, said University of Illinois physics professor and Howard Hughes Medical Institute investigator Taekjip Ha, who led the study.

Although DNA unwinding is necessary for replication or recombination, it is normally a transient process, he said. Exposed single-stranded DNA (ssDNA) can be damaged or degraded by enzymes in the cell. Damaged DNA may also come unwound, and ssDNA can bond to itself, forming hairpin loops and other problematic structures.

“If you have lots of single-stranded DNA in the cell, basically it’s a sign of trouble,” Ha said. “SSB needs to come and bind to it to protect it from degradation and to control what kind of proteins have access to the single-stranded DNA.”

Although other proteins are known to travel along double-stranded DNA, this is the first study to find a protein that migrates back and forth randomly on single-stranded DNA, Ha said.

Other researchers had assumed that SSB simply bound to DNA where it was needed and then fell off when its job was done. But a collaborator on the new study who has studied SSB for two decades, Timothy Lohman, of Washington University School of Medicine, suspected that the protein’s interaction with DNA was more dynamic. That hunch turned out to be true, Ha said.

The SSB protein is made up of four identical subunits. Single-stranded DNA loops around and through them in a pattern “that looks like the seam on a baseball,” Ha said. The DNA entry and exit points are very close to one another, making it possible to track the interaction of ssDNA and SSB using a technique called fluorescence resonance energy transfer (FRET).

FRET makes use of fluorescent molecules whose signals vary in intensity depending on their proximity to one another. By labeling different lengths of ssDNA with red and green dyes about 65 nucleotides apart (the length of ssDNA that threads through the SSB) and tracking the FRET signal as these single DNA molecules were exposed to SSB, the researchers were able to track the movement of SSB in relation to the single-stranded DNA.

In a series of experiments, the researchers showed that SSB diffuses randomly back and forth along single-stranded DNA, and that this movement is independent of the sequence of nucleotides that make up the DNA. They also found that an important DNA repair protein in E. coli, RecA, grows along the ssDNA in tandem with the movement of SSB. As the RecA protein extends along the DNA strand it prevents the backward movement of the SSB.

The researchers also found that SSB can “melt” small hairpin loops that appear in single-stranded DNA, straightening them so that the RecA protein can bind to and repair them. In this way SSB modulates the activity of RecA and other proteins that are involved in DNA repair, recombination and replication.

“SSB may be a master coordinator of all these important processes,” Ha said.

This research was supported by the National Science Foundation, the Howard Hughes Medical Institute and the National Institutes of Health. The study is a project of the NSF-funded Center for the Physics of Living Cells at the University of Illinois, which Ha co-directs with U. of I. physics professor Klaus Schulten. Ha also is an affiliate of the Institute for Genomic Biology.

Source:
Diana Yates

University of Illinois at Urbana-Champaign Read the rest of this entry »

A snake’s intended prey might affect the type and evolution of toxins in their venom, research published in the online open access journal BMC Evolutionary Biology shows.

In snakes, venom composition varies both between species and within a particular species. Land snakes feed on a range of animals and birds, so scientists think that these snakes need a diverse array of toxins in their venom. Sea snakes, on the other hand, tend to have a more restricted diet, feeding only on fish. The toxins in these snakes have now been shown to be less diverse than those in terrestrial snakes.

Professor R Manjunatha Kini and colleagues from the National University of Singapore examined two kinds of sea snakes. They constructed complementary DNA libraries from the venom glands of the reptiles, representing only the stretches of DNA that code for venom gland proteins, and studied two types of protein toxins. The three-finger toxins (3FTx) and the phospholipase A2 (PLA2) enzymes are the main components of sea snake venom.

Although the sea snakes studied lived in very different aquatic environments, the toxins examined were similar in both and the genes encoding the toxins were highly conserved. By contrast, the same toxins in land snakes and sea kraits (which fall between land and sea snakes) showed much greater diversity. The researchers suggest that the toxin genes in sea snakes have remained relatively unchanged because of sea snakes share the same kind of feeding behaviour and diet.

“We examine toxin genes of snakes to identify new toxins, some of which will be useful in developing new therapeutic strategies to treat human diseases,” says Prof Kini from the Department of Biological Sciences, National University of Singapore. “A new anticoagulant or a hypotensive toxin may help us develop new cardiovascular drugs to block unwanted clot formation or to lower the blood pressure.”

Article:

Expression pattern of three-finger toxin and phospholipase A2 genes in the venom glands of two sea snakes, Lapemis curtus and Acalyptophis peronii: comparison of evolution of these toxins in land snakes, sea kraits and sea snakes

Susanta Pahari, David Bickford, Bryan G Fry and R Manjunatha Kini

BMC Evolutionary Biology (in press)

Click here to view the article on the journal website. All articles are available free of charge, according to BioMed Central’s Open Access policy.

Author contact:
Wong Ching Yee (Media Relations Officer, National University of Singapore)

Source: Charlotte Webber

BioMed Central Read the rest of this entry »

A large fraction of the transcription factor Oct-1 is associated with the inner nuclear envelope, but how and why it is retained there was unknown.

As for how, Malhas et al. show – in the January 12, 2009 issue of the Journal of Cell Biology (jcb/) – that Oct-1 binds to lamin B1, a prominent intermediate filament that lines the nuclear envelope, and in cells expressing a drastically truncated mutant of lamin B1, Oct-1 was disassociated from the nuclear envelope.

This left the question, why? The authors asked whether disrupting lamin B1-Oct-1 interactions could affect the expression of genes regulated by Oct-1. Indeed, in cells with truncated lamin B1, they found that expression of several Oct-1-regulated genes was altered because more Oct-1 could bind at these genes’ promoters. Among the genes was a group involved in the oxidative stress response. As a result, these mutant cells accumulated higher levels of reactive oxygen species than wild-type cells.

It remains to be seen whether and how lamin B1-Oct-1 interactions are actively regulated in cells to help control gene expression. But, it is evident from these results that perturbation of lamin B1-Oct-1 interactions can make cells more vulnerable to oxidative stress. This could be particularly important in aging cells, where nuclear envelope integrity (and lamin B1 localization) is often perturbed, says author David Vaux. Lamins support the structure of the nucleus, and compromised nuclear structure has been a suspected cause of aging; another type of lamin, lamin A, is known to cause a premature aging disease when faulty. Increased production of reactive oxygen species – due to the perturbation of lamin B1 in mature cells – could be another way in which lamins contribute to the aging process.

About the Journal of Cell Biology

Founded in 1955, the Journal of Cell Biology (JCB) is published by the Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit jcb/.

Malhas, A.N., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200804155.

Source: Rita Sullivan

Rockefeller University Press Read the rest of this entry »

If you were dying from cancer, would you consider genetic testing? A recent study conducted by researchers from Virginia Commonwealth University Massey Cancer Center showed that most terminally ill cancer patients who were eligible for genetic testing never received it despite that it could potentially save a relative’s life.

The research, “Exploring Hereditary Cancer Among Dying Cancer Patients-A Cross-Sectional Study of Hereditary Risk and Perceived Awareness of DNA Testing and Banking,” was recently published in the Journal of Genetic Counseling, and is the first to document the prevalence of hereditary cancer risk and the need for genetic services and patient education among terminally ill cancer patients.

The study was conducted by VCU Massey researchers John M. Quillin, Ph.D., assistant professor in the Department of Human and Molecular Genetics in the VCU School of Medicine; Thomas J. Smith, M.D., professor in the Division of Hematology/Oncology in the VCU School of Medicine; Joann N. Bodurtha, M.D., professor in the Departments of Human and Molecular Genetics, Pediatrics, Obstetrics-Gynecology, and Epidemiology and Community Health in the in the VCU School of Medicine; and Laura Siminoff, Ph.D., professor and chair of the Department of Social and Behavioral Sciences in the VCU School of Medicine.

Investigators interviewed 43 dying cancer patients, nine of whom had a strong genetic risk. Significant findings included:

- Twenty-one percent of dying cancer patients qualify for genetic assessment

- None of the patients had genetic testing, even though their clinical conditions warranted it

- Patients have a limited understanding of genetic services

- Hereditary cancer is not being fully identified or tested at the time of diagnosis

“About 10 percent of patients are literally taking their DNA clues to cancer with them to the grave,” said Smith, oncology and palliative care specialist at VCU Massey Cancer Center and co-lead researcher. In general, about 5 to 10 percent of cancers have a strong hereditary component.

Current genetic tests for at-risk relatives often fail to identify certain genetic markers for cancer, and clinicians are increasingly recognizing the value of beginning genetic assessment with a person who has cancer. Because the implications of genetics extend beyond the patients to their family members, this research proposes a new way of thinking about patient care that includes the larger reach of hereditary risk.

“Our findings suggest opportunities for identifying hereditary cancer are being lost, even as the window for identifying familial risk is closing,” says Quillin, genetic counselor at VCU Massey Cancer Center and co-lead researcher. “By recognizing signs of hereditary cancer among dying patients, physicians can nurture patients’ legacies while they nurture their lives.”

Just as VCU Massey Cancer Center practices a multidisciplinary approach to treating and fighting cancer, interdepartmental collaboration was critical in this study. Researchers are now further exploring knowledge, attitudes and behaviors of palliative care oncologists with respect to genetic testing.

“Genetic testing should be completed early, shortly after diagnosis. Patients should ask their doctors if there is a genetic part to their disease, and test for it sooner rather than later,” Smith says.

Source:

Virginia Commonwealth University Read the rest of this entry »