Life Science Report

MicroRNAs hold promise for treating diseases in blood vessels

2009-07-06T12:07:00.000-07:00

A newly discovered mechanism controls whether muscle cells in blood vessels hasten the development of both atherosclerosis and Alzheimer's disease, according to an article published online today in the journal Nature.

The study was led by the Gladstone Institute of Cardiovascular Disease (GICD) in San Francisco, with key contributions from the Aab Cardiovascular Research Institute at the University of Rochester School of Medicine and Dentistry.

Thanks to stem cells, humans develop from a single cell embryo into a complex being with about 250 unique cell types. As the fetus develops, cells divide and multiply (proliferate) in many generations and specialize (differentiate) with each generation until millions of functional cells result (bone, nerve, blood, skin, muscle, etc.). To serve specific roles in the body, some stem cells also switch back and forth between primitive, rapidly proliferating precursors and their mature, functioning, non-proliferating counterparts, a quality called "plasticity."

Among the most "plastic" of cells are vascular smooth muscle cells (VSMC), which form in layers around blood vessels, and by contracting or relaxing, regulate blood pressure. Because VSMC surround blood vessels that are continually becoming clogged by atherosclerosis, they must be ever ready to grow along with the vessel as it attempts, by growing, to remain open to blood flow despite fatty deposits and inflammation. If these efforts fail, heart attack or stoke may occur. Each time a vessel grows to avoid a clog, the VSMC surrounding it must grow too by reverting to their high-growth precursor form. Once a vessel reaches its growth limit, however, the growth that once kept vessels open begins adding to clogs by thickening vessel walls.

Past studies in Rochester have shown that transition of VSMC from fast-proliferating stem cells to mature cells and back is largely controlled by two proteins, myocardin and serum response factor (SRF), as part of a regulatory network that influences many genes. SRF anchors to certain snippets of DNA, while myocardin turns on the genes to which SRF sticks. Most of the genes turned on by myocardin/SRF in VSMC are needed for normal function. When levels of myocardin decrease, as they do for some reason in vascular diseases like atherosclerosis, VSMC no longer work normally and vessel thickening ensues. For this reason the field has sought urgently to learn how myocardin levels are controlled, but without success.

Enter a research team led by Deepak Srivastava, M.D, director of GICD, world leaders in the characterization of microRNAs (miRNAs). These small, single-stranded molecules of ribonucleic acid (RNA), discovered in the Victor Ambros lab in 1993, fine-tune protein levels in all cells of the body. The GICD team discovered that miRNAs control VSMC differentiation and growth.

Gene expression is the process where information encoded in genes is converted into proteins, the workhorse molecules that make up the body's structures and carry its signals. While genes are encoded in chains of deoxyribonucleic acids (DNA), they are copied into chains of messenger ribonucleic acids (mRNA) that are "read" by cellular machines that build proteins. microRNAs bind to messenger RNAs, usually targeting them for breakdown or rendering them unfit to serve as templates for protein production.

The current study found that two miRNAs in particular, miR-143 and miR-145, are part of a molecular switch that determines whether VSMC persist as high-growth precursors or mature into functioning muscle cells. miR-143 was found to block the expression of factors that promote proliferation by VSMC precursors. Surprisingly, miR-145 activated the expression of myocardin, which maintains VSMC in their mature form over their high-growth form.

In a mouse model, expression of miR-143 and miR-145 was reduced to almost nothing where disease-related proliferation of VSMC had thickened blood vessel walls. These findings suggest that miR-143 and miR-145 – in partnership with myocardin – maintain the normal balance between mature VSMC and their precursors. Thus, researchers believe the drop in miR-143 and miR-145 levels seen in disease settings contributes greatly to vessel wall thickening, but that theory will need to be confirmed by further studies.

In addition, Rochester investigators found that myocardin and SRF activate genes that may influence the rate at which the brain can remove amyloid beta, the toxic protein that builds up in blood vessels in the brains of patients with Alzheimer's disease. In a February 2009 article in Nature Cell Biology, University of Rochester investigator, Berislav Zlokovic, M.D., Ph.D. found that when SRF and myocardin are active, amyloid beta accumulates in VSMC lining blood vessels. The discovery that miR-145 encourages the expression of myocardin could explain why myocardin may occur in higher levels in Alzheimer's disease, which is turning out to be a problem of "vascular plumbing."

"The finding that a microRNA controls levels of myocardin, the master regulator of VSMC identity and function, forms the starting point in efforts to design new classes of treatment for vascular diseases that represent leading causes of death," said Joseph M. Miano, Ph.D., associate professor within the Aab Cardiovascular Research Institute at the University of Rochester Medical Center, and a study author. He and Srivastava trained together under the direction of renowned muscle biologist Eric Olson at M.D. Anderson Cancer Center in the early 1990s. Miano was also a co-author of the paper on Alzheimer's with Zlokovic. "One of the most important of potential applications for this work would be to deliver miR-145 into vessel walls as a way to normalize levels of myocardin, which would counter vessel wall thickening."

Rochester provided GICD with samples of blood vessels containing lesions with dramatically reduced levels of myocardin. GICD then looked at levels of miR-143 and miR-145 in this disease setting. The team in Rochester also did experiments to show that local delivery of miR-145 in mouse blood vessels leads to elevated expression of myocardin and its target genes.

Little it takes to tip the balance of p53

2009-07-06T12:04:00.000-07:00

A tightly controlled system of checks and balances ensures that a powerful tumor suppressor called p53 keeps a tight lid on unchecked cell growth but doesn't wreak havoc in healthy cells. In their latest study, scientists at the Salk Institute for Biological Studies suggest just how finely tuned the system is and how little it takes to tip the balance.

When unprovoked, at least two negative regulators—the related proteins Mdm2 and Mdmx—prevent p53 from unleashing its power to kill. But just slightly increasing the amount of available Mdmx, which grips p53 and renders it inactive, the Salk researchers discovered, made mice remarkably resistant to the harmful effects of radiation but very susceptible to the development of oncogene-induced lymphomas.

"Our experiments emphasize how subtle and precarious the balance is," says postdoctoral researcher and first author Yunyuan V. Wang. "A slight shift of balance and the mice survive the equivalent of Chernobyl but are in big trouble when an oncogene is activated."

Their findings, to be published in the July issue of the journal Cancer Cell, could explain why some tumors don't respond to radiation or chemotherapy, and provide novel routes for the development of new anti-cancer therapies.

As a powerful tumor suppressor, p53 turns on genes that either halt cell division to allow time for repair of damaged DNA or, when all rescue attempts prove futile, to prevent cells with genetic defects from dividing, as this would fuel the development of cancer. Consequently, before any tumor cell can start proliferating willfully, it needs to escape from p53's iron fist.

"One way or another, p53 function is compromised in all cancers. Either p53 itself is mutated or there is a problem with one of the proteins that regulate p53's activity," says the study's leader Geoffrey M. Wahl, Ph.D., a professor in the Gene Expression Laboratory. "Our hope is that we can develop small molecule drugs that will activate p53 in those tumors where it is still functional but inactivated by one of its negative regulators."

In an earlier study, Wahl and his team discovered that Mdm2 and Mdmx cooperate to prevent p53 from being activated, with Mdm2 being primarily responsible for degrading p53, while Mdmx is more effective at preventing p53 from turning on genes. But how p53 shakes off its negative regulators when cells experience one of the myriad stresses that activate p53 has been the topic of much discussion.

One view holds that after DNA damage occurs, enzymes directly modify p53 and that those modifications change the structure of p53 in such a way that neither Mdm2 nor Mdmx are able to bind. In an alternative scenario the same enzymes—kinases that attach phosphate groups to proteins—modify the negative regulators, accelerating their degradation and freeing p53 of their antagonists. Of course, it may well be that both views are correct, but the extent to which each contributes to p53 control remains an important unanswered question.

To get to the bottom of the dispute, Wang genetically engineered mice to eliminate three key phosphorylation sites in Mdmx. "The mutations stabilize Mdmx and as a result we saw consistently lower basal activity of p53. Surprisingly, we observed no increase in spontaneous tumor formation " she says. "In the absence of catastrophic DNA damage these low levels of p53 were enough to suppress tumorigenesis."

But in order to put cells on notice or commandeer them to commit suicide in the face of irreparable damage, these animals need to activate p53, which in turn activates a whole range of target genes. "Levels of active p53 still go up," says Wang, "but they never reach the critical threshold that's required to elicit a biological response."

As a result, these animals became very resistant to the deleterious effects of high doses of radiation. When blasted with 10 Gy of irradiation—enough to wipe out all blood stem cells in the bone marrow of normal mice—mutant mice that were unable to fully activate p53 experienced only a modest blood count drop. The other noticeable effect was a premature graying of their coat.

"Both radiation and chemotherapy are commonly used for the treatment of cancer and act by inducing DNA damage and subsequent cell death through p53. As such, tumors that retain normal p53 are more likely to respond to treatment while tumors carrying a defective p53 pathway are often less responsive ," says Wahl. Ideally, we want to find a therapeutic target, such as MDM2 or MDMX, that would increase p53 activity in tumor cells while minimally impacting other vital functions such as hematopoiesis."

Since p53 also protects against wayward cell proliferation caused by oncogenes such as c-myc, the researchers permanently activated c-myc in the B cell lineage to mimic human endemic Burkitt's lymphomas. They observed that mice with defective Mdmx developed very aggressive lymphomas at a very young age. Thus, control by Mdmx is critical to balance the severity of the response to DNA damaging agents, while also preventing induction of cancer by activated oncogenes.

New targeted therapy finds and eliminates deadly leukemia stem cells

2009-07-02T13:40:00.000-07:00

New research describes a molecular tool that shows great promise as a therapeutic for human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer. The study, published in Cell Stem Cell, describes exciting preclinical studies in which a new therapeutic approach selectively attacks human cancer cells grown in the lab and in animal models of leukemia.

AML is a cancer of the white blood cells that has an extremely poor prognosis and does not respond well to conventional chemotherapy. "The cellular and molecular basis for this dismal picture is unclear," offers senior study author Associate Professor Richard Lock from the Children's Cancer Institute Australia and the University of New South Wales. "However, previous research has suggested that leukemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance." LSCs are cells that can initiate AML and are critical for its long-term growth.

Associate Professor Lock and colleagues exploited the fact that the molecule CD123 is expressed at very high levels on LSCs but not on normal blood cells. CD123 is part of the interleukin-3 receptor, a protein that interacts with a growth factor (called a cytokine) that influences cell survival and proliferation. The researchers created a therapeutic antibody that recognized and bound to CD123 with the hope that this antibody would selectively interfere with AML-LSC survival.

When AML-LSCs from human patients were transplanted into mice treated with the antibody, called 7G3, cytokine signaling in the tumor cells was blocked. Further, 7G3 impaired migration of the AML-LSCs to bone marrow and activated the innate immune system of the host mouse to destroy the AML-LSCs. Overall, treatment with 7G3 substantially improved mouse survival when compared with control groups. The researchers go on to report that a CD123-targeting antibody is currently being used in phase 1 clinical trials of advanced AML and that there are no signs of treatment-related toxicity.

These results hold substantial promise for future cancer therapeutics. "The recent characterization of defined populations of cancer stem cells in a range of human malignancies, as well as their relative resistance to conventional chemotherapy and radiotherapy, supports the broad applicability of our approach and provides rationale for the progression of AML-LSC-targeted therapeutics from preclinical evaluation to clinical trials," concludes Associate Professor Lock.

New clue into how brain stem cells develop into cells which repair damaged tissue

2009-07-01T15:28:00.001-07:00

Multiple sclerosis is an autoimmune disease which is caused by the body's immune system attacking nerve fibres and their protective insulation, the myelin sheath, in the central nervous system. This damage prevents the nerves from 'firing' properly, and then leads to their destruction, resulting in physical and intellectual disabilities.

It is currently thought that two components determine clinical outcomes in MS. First, it is important to stop ongoing damage (mainly achieved by controlling inflammation in the central nervous system). The second is to repair the damage that has occurred to the protective myelin sheaths surrounding the nerve fibres (this involves a regenerative process called remyelination in which new myelin sheaths are restored to nerve fibres).

While there exist several effective treatments to reduce inflammatory damage, no treatments are available to augment remyelination to repair the damage to nerve fibres. Critical to the development of such repair therapies is to understand how the brain's own stem cells can replace the myelin forming cells (oligodendrocytes) lost in the disease. During early stages of the disease the brains own stem cells are surprisingly good at repairing damage in MS. However, for reasons that until now have not been well explained, they become less efficient as the disease progresses.

In this study the researchers have identified the Wnt pathway, which plays an active role in the maintenance and proliferation of stem cells, as a crucial determinant of whether oligodendrocytes can efficiently make myelin. Their studies demonstrate that if the Wnt pathway is abnormally active, then the process is inhibited. This opens up the exciting possibility that the repair can be enhanced in MS patients by drugs that block the Wnt pathway.

Professor Robin Franklin from the University of Cambridge, a co-senior author of the study, explained the significance of their findings: "The pathway we identified plays a critical role in whether repair to the damaged cells will or will not occur. Interestingly, mutations in this particular pathway are also involved in several cancers. In this regard, drugs that inhibit this pathway from signaling have been sought which might suppress tumour growth. These same drugs may also find a role in promoting repair in MS."

Lead author of the study, Stephen Fancy, PhD, a postdoctoral fellow in the lab of co-senior author David Rowitch, MD, PhD, a Howard Hughes Medical Institute Investigator at the University of California, San Francisco, said: "We believe we have made a significant step forward in understanding why repair might fail in neurological diseases such as MS by identifying a pathway which inhibits the myelin repair process," said the

MS Society Director of Research, Jayne Spink, said: "We are delighted with the outcome of this outstanding research, which gives us greater knowledge of the mechanics of MS. This works opens up new avenues of research and lends itself to more study. Being able to uncover the secrets behind the damage caused in MS will take us forward in our understanding of this debilitating condition."

"Our studies work have implications for other diseases," said UCSF's Rowitch. "In a condition called periventricular leukomalacia (PVL), which can lead to cerebral palsy in extremely premature infants, recent studies show a similar inability of oligodendrocytes to perform their important repair function. In respect to failed myelin repair, we see a parallel between the chronic demyelinated plaques of multiple sclerosis and the lesions of PVL."

New test detects genetic and chromosomal abnormalities in embryos

2009-06-30T10:17:00.000-07:00

One-step screening for both genetic and chromosomal abnormalities has come a stage closer as scientists announced that an embryo test they have been developing has successfully screened cells taken from spare embryos that were known to have cystic fibrosis.

They told at the 25th annual meeting of the European Society of Human Reproduction and Embryology that, as a result, they would be able to offer clinical trials to couples seeking fertility treatment later this year.

The researchers based in the USA and the UK have been able to prove that the technique, known as genome-wide karyomapping, was capable of not only detecting diseases caused by a specific gene mutation, in this case cystic fibrosis, but that it was also capable of detecting aneuploidy (an abnormal number of any of the 23 pairs of chromosome) at the same time. This is the first time they have been able to demonstrate that the test can work in cells taken from embryos that have already been diagnosed with the cystic fibrosis gene mutation using conventional preimplantation genetic diagnosis (PGD).

Gary Harton, PGD scientific director of the Genetics & IVF Institute in Fairfax, Virginia (USA) told a news briefing: "Karyomapping is a universal method for analysing the inheritance of genetic defects in the preimplantation embryo without any prior patient or disease specific test development, which often delays patient treatment. For the first time, the inheritance of both single gene defects and chromosomal abnormalities can be detected simultaneously at the single cell level. Unlike other methods, this is achieved entirely by analysing the DNA sequence at over 300,000 locations genome-wide in parents and appropriate family members, often children already affected by a disease, and comparing their sequence with that inherited by the embryo. This can be achieved very rapidly using current microchip technology known as microarray."

With karyomapping it is not necessary to know the exact DNA mutation that is being sought; the scientists just need to take the relevant chunk of DNA from the parent that carries the mutation somewhere along its length, and if it matches a chunk of DNA from the embryo, then they know the embryo has inherited the mutation. As karyomapping involves analysing chromosomes, it also detects the existence of aneuploidy at the same time.

"The range of applications is broad", says Dr Harton

"The range of applications is broad and includes single gene defects, abnormal chromosome number, structural chromosome abnormalities and HLA [human leukocyte antigen] matching in 'saviour sibling' cases," said Mr Harton.

Karyomapping was developed by Professor Alan Handyside of the London Bridge Fertility Gynaecology and Genetics Centre in London (UK), and Mr Harton has been providing samples and DNA information in order to test the method and validate it for use in the clinic.

"The hope is that clinicians will be able to test embryos for specific genetic diseases and know that, with one test, they are transferring chromosomally normal embryos. This will be a step forward from current technology that is mostly limited to choosing one test or the other," explained Prof Handyside.

Karyomapping would also be quicker and cheaper. Currently, developing a PGD test for a single gene defect can take weeks or months, as scientists have to identify the exact patient or disease-specific genetic mutation first before screening for it, which is labour-intensive and costly. By contrast, karyomapping can be carried out without such extended pre-test development; at present, it takes about three days, but Mr Harton and his colleagues believe this could be reduced to 18-24 hours.

In this most recent stage of their research they examined cells from five embryos that had been donated for medical research by a couple who had received successful fertility treatment, including PGD for cystic fibrosis. The embryos had developed to the blastocyst stage, which is about five days after fertilisation. Conventional PGD had already identified which embryos were unaffected, affected or were carriers of the disease. Karyomapping of cells from the donated embryos confirmed these diagnoses, but, in addition, it was able to identify which parent carried the affected chunk of DNA. Karyomapping also revealed two aneuploidies in two embryos, which had not been detected by the earlier PGD.

New cell analysis system from Fluxion

2009-06-30T10:10:00.000-07:00

Fluxion Biosciences now provides the BioFlux 1000 Workstation – a cell analysis system that integrates the company’s Well Plate Microfluidic™ technology with automated microscopy for high-throughput shear flow assays. The 1000 workstation delivers higher throughput and unattended operation with integrated microscopy and an automated stage that enables fast scanning of the BioFlux plates.

The BioFlux systems bridge the gap between in vitro and in vivo experiments by enabling physiologically relevant shear flow assays in a standard well-plate format. Assays are performed on the BioFlux platform under conditions that mimic those in the human body. This delivers a higher content data set to help ensure that only the most promising compounds move forward into animal and clinical trials. The BioFlux Controller delivers programmable shear flow to the plates while the Fluxion Montage software provides analysis and single-point control of all systems components. Ideal applications include research in cell and platelet adhesion, cancer biology, microbiology and biofilms.

Commentary: This bloody Swine flu thing - how annoying!

2009-06-29T14:01:00.000-07:00

I have to admit that Im quite frustrated about this whole swine flu thing. Everybody talked about it, the media hyped it and now it is almost over, isnt it?

Not quite, of course. We are still hoping that the flu doesnt get worse, will be more or less contained and furthermore, wont come back in autumn - maybe this time round in a more deadly version. Swine flu is all bad - I got that - and I hate to see people dying from any sort of disease.

But there is one thing that I find really annoying. While we are having loads of money for flu vaccines and the stockpiles of medicines, others are simply less fortunate: the poor.

As wikipedia explains, "each year, there are approximately 350–500 million cases of malaria, killing between one and three million people". Now compare this with the 30,000 confirmed cases of swine flu so far.

I dont know how much we are spending on research on malaria as compared to flu, but I have a certain feeling about this. It is somehow understandable that pharma is not too interested in developing a vaccine or medication against a disease, for which nobody can pay the bill. But I believe, there still must be a different solution than just ignoring the problem (and focusing on flu)?

To be honest, I dont have a solution myself. I just think, we cant continue like that - from moral grounds, but also because of selfishness: one day, these poor countries could be the launching pad for a new pandemic of a disease we dont know about today. If this happens, we can simply through away our stockpiles and prepardness plans and all the millions that we could have put in other prevention measures for the poor.

Breakthrough in combating side effects of malaria drug quinine

2009-06-29T13:04:00.000-07:00

Discovered back in the 1600s quinine was the first effective treatment in the fight against malaria – and it continues to be a commonly used treatment against this devastating disease. But the drug is associated with a long list of side effects which can range from sickness and headaches to blindness, deafness and in rare cases death — and until now no one knew why.

Scientists at The University of Nottingham have made a discovery that may explain many of the adverse side-effects associated with the drug and as a result have potentially found a way of combating them.

Their research, funded by The Sir Halley Stewart Trust, found that quinine can block a cell's ability to take up the essential amino acid tryptophan. The findings, published today in the Journal of Biological Chemistry, suggest that dietary tryptophan supplements could be a cheap and simple way to improve the performance of this important drug.

Dr Simon Avery and colleagues in the School of Biology used yeast genetics to examine the effects of quinine on a collection of 6000 yeast mutants, each one lacking exactly one of the yeast's 6000 genes. While quite different from humans, yeast is comparable on a cellular level and yeast is frequently, and successfully, used as a front-line agent in testing chemicals and small molecule drugs.

This detailed screening process revealed that strains of yeast unable to make tryptophan were extremely susceptible to quinine poisoning, which led them to identify a tryptophan transporter as a key quinine target (yeast that cannot make their own tryptophan have to rely exclusively on external sources, and thus die if tryptophan transport is blocked).

This discovery fits in well with evidence that quinine reactions are more severe in malnourished individuals. Tryptophan is an essential amino acid which means the human body cannot produce it — we have to get it from the food we eat. Tryptophan is abundant in meat but limited in yams, a staple food crop in the tropics where malaria is prevalent. If quinine severely reduces tryptophan uptake, then it follows that people with preexisting tryptophan deficiency, a common occurrence in undernourished populations, would be especially at risk from this drug.

Each year there are an estimated 350 to 500 million cases of malaria — and every year it kills between one and three million people. In Africa, malaria is a leading cause of death in children. Estimates are that worldwide over three billion people are at risk of contracting the disease.

Dr Simon Avery said: "This finding could be a key step towards making quinine side-effects a thing of the past, so improving the quality of treatment for millions of malaria sufferers. It also highlights the benefits of collaborative research, in this case between my yeast group and the parasite immunology group of Dr. Richard Pleass."

The body uses tryptophan to make the brain chemical serotonin — which is thought to produce healthy sleep and a stable mood - so a lack of tryptophan induced by quinine could also explain why many of quinine's side effects are localized to the head region.

The researchers postulate that the toxic effects of quinine could be averted simply by taking dietary tryptophan supplements in conjunction with quinine treatments. Scientists now have to find out if tryptophan affects quinine action against the malaria parasite.

Over 6,100 antibodies from Sigma

2009-06-29T12:52:00.000-07:00

Sigma-Aldrich released over 2,300 antibody additions to its Prestige Antibodies, bringing the total number of highly validated antibodies to over 6,100. Developed by the Human Proteome Resource, these antibodies are available to customers immediately through an exclusive partnership between Sigma-Aldrich and Atlas Antibodies. Prestige Antibodies can provide significant time and cost savings for researchers because they are optimized on a single protocol, resulting in efficient and effective applications.

This addition to the Prestige Antibodies product line is a step toward the Human Proteome Resource's goal to develop at least one antibody to all 22,000 non-redundant human proteins by 2015.

Prestige Antibodies are supported by the publicly available data of the Human Protein Atlas (HPA), part of HUPO's Human Antibody Initiative. Multiple quality assurance testing steps ensure that Prestige Antibodies are highly specific to their targets. Each Prestige Antibody is also associated with over 500 tissue immunohistochemistry (IHC) images, over 100 cell/line immunocytochemistry (ICC) images, immunofluorescence (IF) and western blotting (WB) data, all publicly accessible via the Human Protein Atlas (www.proteinatlas.org).

In August 2008, Sigma-Aldrich added over 2,000 Prestige Antibodies to the existing antibody product line. The rapid expansion of the Sigma-Aldrich Prestige Antibodies gives an increasing number of scientists the ability to save resources and facilitate high-throughput applications in proteomics and cell biology research.

Poor mice: Genetic engineering made them autistic

2009-06-25T11:44:00.000-07:00

Engineering autism: Mice with extra chromosome region show many autistic signs
Mice who inherit a particular chromosomal duplication from their fathers show many behaviors associated with human autism, researchers report in the June 26th issue of the journal Cell, a Cell Press Publication. The duplicated chromosomal region in mice is the equivalent of human chromosome 15q11-13, the most frequent cytogenetic abnormality observed in autism, accounting for some five percent of all cases.

The engineered mice validate the human chromosome abnormality as one cause of the disease, the researchers said. They will also serve as an invaluable tool for therapeutic development.

"We know several mice as 'putative' models of autism, which show face validity that they are similar to human patients," said Toru Takumi of Hiroshima University in Japan. "In addition to these similar phenotypes, our mice have construct validity," meaning that their symptoms are traced to the same biological cause.

Scientists have studied many gene candidates, and mice carrying some of those mutations do show some signs. Still the molecular pathways underlying autism remain largely mysterious.

Chromosomal abnormalities are thought to account for 10 to 20 percent of cases and duplication of chromosome 15q11-13 is the only recurrent aberration so far linked to the disease.

In the new study, the scientists generated mice with a duplication of a region on their chromosome 7, mirroring the autism-linked abnormality seen in humans. Mice who inherit that abnormality from their fathers show poor social interaction, behavioral inflexibility, abnormal ultrasonic vocalizations and indications of anxiety, the results of extensive behavioral testing now show.

For instance, when given the option of spending time alone or in the presence of a stranger mouse, normal mice will often choose to hang out with the stranger. Mice with the chromosomal abnormality, on the other hand, more often choose to spend time with inanimate objects over fellow mice.

In tests of spatial memory, in which mice are trained to swim to a hidden platform, animals with the paternally inherited duplication were less able to adapt to changes in the platform's location than normal mice were. Another test, in which mice have to locate the correct hole to exit a box, showed similar results.

The scientists were "honestly surprised to see behavioral inflexibility in two different reversal tests of learning and two different backgrounds. Higher ultrasonic calls from pups with paternal duplication were unexpected" too. It's also hard to say exactly what those unusual calls mean for the mice, given scientists' limited understanding of mouse communication.

In other tests, the mice showed more signs of fear or anxiety, a feature common in autistic individuals.

The researchers also found molecular-level evidence that the duplication can lead to changes in a receptor for serotonin, a nerve messenger that acts as a growth factor in the immature brain. Those changes stem from different levels of one brain-specific small nucleolar RNA (snoRNA), known as MBII52, a molecule that is known to be involved in physiologically important "edits" to the receptor.

Because the gene that encodes MBII52 is "maternally imprinted," its expression in mice with the inherited duplication from their father was double that of normal mice or those who inherited the same abnormality from their mothers, they report. (Imprinted genes are chemically modified to prevent their expression.) Studies in cultured neurons showed that those changes to MBII52 are associated with an altered neural response, suggesting that changes in serotonin signals might underlie the aberrant behaviors exhibited by the animals.

MicroRNAs help control HIV life cycle

2009-06-25T11:41:00.000-07:00

Scientists at Burnham Institute for Medical Research have discovered that specific microRNAs, non-coding RNAs that interfere with gene expression, reduce HIV replication and infectivity in human T-cells. In particular, miR29 plays a key role in controlling the HIV life cycle. The study suggests that HIV may have co-opted this cellular defense mechanism to help the virus hide from the immune system and antiviral drugs. The research was published today in the journal Molecular Cell.

The scientists found that the microRNA miR29 suppresses translation of the HIV-1 genome by transporting the HIV mRNA to processing-bodies (P-bodies), where they are stored or destroyed. This results in a reduction of viral replication and infectivity. The study also showed that inhibition of miR29 enhances viral replication and infectivity. The scientists further demonstrated that strains of HIV-1 with mutations in the region of the genome that interact with miR29 are not inhibited by miR29.

The scientists looked at miR29 expression levels in infected and uninfected cells and found that miR29 expression was enhanced by HIV-1 infection. Blocking the activity of miR29 with interfering RNA resulted in increased replication and infectivity of the virus. The scientists tested the association of miR29 and HIV-1 by mutating both miR29 and its target region on the HIV virus. When either was altered, miR29s suppression of HIV replication and infectivity was reduced or eliminated. In addition, the team suppressed P-bodies in the cells and noted a similar effect. This suggests that HIV may use miRNAs to become dormant and escape immune response.

Molecule-size capsules can deliver drugs

2009-06-25T11:35:00.000-07:00

Like burrs on your clothes, molecule-size capsules can deliver drugs by sticking to targeted cells
It is now possible to engineer tiny containers the size of a virus to deliver drugs and other materials with almost 100 percent efficiency to targeted cells in the bloodstream.

According to a new Cornell study, the technique could one day be used to deliver vaccines, drugs or genetic material to treat cancer and blood and immunological disorders.

"This study greatly extends the range of therapies," said Michael King, Cornell associate professor of biomedical engineering, who co-authored the study with lead author Zhong Huang, a former Cornell research associate who is now an assistant professor at the Shenzhen University School of Medicine in China. "We can introduce just about any drug or genetic material that can be encapsulated, and it is delivered to any circulating cells that are specifically targeted," King added.

The king of nanoscale capsules

The technique involves filling the tiny lipid containers, or nanoscale capsules, with a molecular cargo and coating the capsules with adhesive proteins called selectins that specifically bind to target cells. A shunt coated with the capsules is then inserted between a vein and an artery. Much as burrs attach to clothing in a field, the selectin-coated capsules adhere to targeted cells in the bloodstream.

After rolling along the shunt wall, the cells break free from the wall with the capsules still attached and ingest their contents.

The technique mimics a natural immune response that occurs during inflammation, which stimulates cells on blood vessel walls to express selectins, which quickly form adhesive bonds with passing white blood cells. The white blood cells then stick to the selectins and roll along the vessel wall before leaving the bloodstream to fight disease or infection.

Selectin proteins may be used to specifically target nucleated (cells with a nucleus) cells in the bloodstream.

The study shows that since only the targeted cells ingest the contents of the nanocapsules, the technique could greatly reduce the adverse side effects caused by some drugs.

The current study demonstrates that genetic material can be delivered to targeted cells to turn off specific genes and interfere with processes that lead to disease. The researchers filled nanocapsules with a small-interfering RNA (siRNA) and targeted them to specific circulating cells. When the targeted cells ingested the capsules, the siRNA turned off a gene that produces an enzyme that contributes to the degradation of cartilage in arthritis.

In a similar manner, the method could be used to target the delivery of chemotherapy drugs, vaccine antigens to white blood cells, specific molecules that mitigate auto-immune disorders and more, King said.

New UHPLC instrument from Agilent

2009-06-24T11:58:00.000-07:00

Agilent introduced the 1290 Infinity Liquid Chromatography System, designed to deliver significantly greater power, speed and sensitivity for enhanced performance in the high-end Ultra High Performance Liquid Chromatography (UHPLC) market.

The instrument delivers the industry’s largest analytical power range, enabling users to deploy any particle type, any column dimensions or any mobile and stationary phases. This range provides the highest separation power per time for sub-two-micron and other advanced particle columns. It is the first system that delivers the foundations for method transferability from and to any vendor’s UHPLC and HPLC systems.

The Agilent 1290 Infinity LC is designed to drive even higher levels of performance from Agilent LC/MS systems. The lowest possible delay volume, exceptionally low sample carryover, integrated control and operation with Agilent’s MassHunter MS software, and the ability to perform fast, ultrahigh resolution LC separations contribute to this performance.

Human share experience with baboons on Malaria

2009-06-24T11:48:00.000-07:00

Evolutionarily speaking, baboons may be our more distant cousins among primates. But when it comes to our experiences with malaria over the course of time, it seems the stories of our two species have followed very similar plots.

In humans, subtle variation in one particular gene that controls whether a protein on the surface of red blood cells gets made or not literally spells the difference between susceptibility or resistance to one form of malaria. That's because the blood protein serves as the entry point for Plasmodium vivax, one of several malaria-causing parasites that infect humans.

Now, researchers at the Duke Institute for Genome Sciences & Policy report that variation in precisely the same regulatory gene also influences baboons' chances of getting sick, by ratcheting their susceptibility to another, closely related parasite up or down.

Some baboons are just too similar

"It's a nice example of how – in the vastness of the genome – the same gene was modified in the same way in two different species to produce the same kind of resistance," says Greg Wray, director of the IGSP's Center for Evolutionary Genomics. "That's a pretty remarkable thing when you think of all the different ways malaria resistance might have evolved."

The findings, which appeared online in Nature on June 24, also mark a turning point in primate research: they are the first to connect any functionally important genetic variation in wild primates to complex, real-life consequences for the animals.

The yellow baboons in question live in Kenya's Amboseli National Park and have been the subject of ongoing observation for nearly 40 years, making them one of the best-studied wild mammal populations in the world from a behavioral and life history standpoint.

"It used to be that our work was limited to 'skin-out' biology," says Susan Alberts, an associate professor of biology and IGSP member who has been recording the habits of the baboons for the last 25 years. Today, thanks to a growing library of sequenced primate genomes including our own, scientists can begin to delve deeper.

Graduate student Jenny Tung spent three summers out on the East African savanna, watching the baboons, collecting their DNA-laden feces, and with the help of an expert team of Kenyan field assistants, very carefully drawing blood from darted animals. Successfully darting baboons is no small feat, Tung said. You have to be within meters of the animal you are targeting, and at the same time make sure that none of the baboons catch you in the act. If they did, it would send the troop running and screaming and, in technical terms, "really mess up the field data." In the evenings, Tung processed and stored her hard-won samples in a makeshift refrigerator before shipping them off to Duke.

Once back at the lab, Tung found something in those blood samples that came as a surprise despite all the years of study. More than half of the Amboseli baboons -- some 60 percent -- were infected with the malaria-like parasite known as Hepatocystis.

"We had no idea so many of them were carrying this parasite," Alberts says. For years, researchers have tracked the baboons for any signs of injury or illness. But although the infection probably compromises the animals, they don't develop cyclical fever spikes or other immediately obvious symptoms like humans with malaria do.

In search of a genetic basis for differences in the baboons' vulnerability to infection, the researchers zeroed in on the DNA sequence surrounding the DARC gene, the same region that has been traced to malaria protection among people. Although the specifics differ from those in humans, they found that a single letter change to the genetic code -- a switch from an A to a G -- lends some baboons the ability to better fend off infection. In fact, they show, one G is good, but two are even better.

Further analysis of the baboons' blood and in cell culture confirmed that the variants influence infection rates through changes in the activity of the DARC gene. Comparison of the Amboseli baboon sequences to two other populations also showed that the DNA sequence has undergone a relatively rapid rate of evolutionary change, the mark of natural selection for malaria resistance.

The newfound parallels between baboons and humans bring the long history of conflict between parasite and host into high relief. "It's a struggle out there," Alberts says. "We often think of malaria as a contemporary problem, but it's a deep part of our history."

The study also shows the power of coupling genomics with dedicated fieldwork. "Part of what we want to do is push the envelope and show that this is doable," Wray says. With the proof of principle in hand, the next big challenge is to begin to unravel the genomic differences that may be responsible for fuzzier behavioral traits, such as social status or aggression, he added.

"It's getting easier and easier to generate genetic data," Tung says. "But it's never going to be easy to have long-term field data -- especially for primates. It takes years and years before you see the fruit of those labors. We're just at the point where it's going to really start paying off."

$1,560,000 grant support for NYU

2009-06-24T11:46:00.000-07:00

Two NYU Langone Medical Center researchers have received $1,560,000 in grant support for their first year of studies focused on microbiome and psoriasis and on microbiome and esophageal cancer from the National Institutes of Health (NIH). The studies being conducted at NYU Langone Medical Center are two of several projects being conducted through the NIH Roadmap for Medical Research as part of the Human Microbiome Project (HMP) taking place at institutions across the country.

Since 2007, the HMP has awarded more than $70 million to expand its exploration of how the trillions of microscopic organisms that live in and on our bodies affect our health. The human microbiome is all the microorganisms that reside in or on the human body, as well as all their DNA, or genomes.

In the new round of funding, the HPM will support pilot demonstration projects by researchers that will sample the microbiomes of healthy volunteers and volunteers with specific diseases over the next year.

In the first phases of the HMP, jumpstart funding was awarded to create a framework and data resources. Funding has also previously been awarded for the development of innovative technologies and computational tools, coordination of data analysis, and an examination of some of the ethical, legal and social implications of human microbiome research. The HMP plans to award more than $115 million in research grants during the project to sequence up to 600 microbial genomes and for selected demonstration projects that will examine the relationship between the microbiome in a specific niche of the body with a particular disease. The goal is to determine whether individuals share a core microbiome, and to examine how changes in microbial populations correlate with changes in human health.

Need something? Talk to my right ear!

2009-06-23T11:50:00.000-07:00

We humans prefer to be addressed in our right ear and are more likely to perform a task when we receive the request in our right ear rather than our left. In a series of studies, looking at ear preference in communication between humans, Dr. Luca Tommasi and Daniele Marzoli from the University "Gabriele d'Annunzio" in Chieti, Italy, show that a natural side bias, depending on hemispheric asymmetry in the brain, manifests itself in everyday human behavior.

One of the best known asymmetries in humans is the right ear dominance for listening to verbal stimuli, which is believed to reflect the brain's left hemisphere superiority for processing verbal information. However, until now, the majority of studies looking at ear preference in human communication have been controlled laboratory studies and there is very little published observational evidence of spontaneous ear dominance in everyday human behavior.

Tommasi and Marzoli's three studies specifically observed ear preference during social interactions in noisy night club environments. In one study, 286 clubbers were observed while they were talking, with loud music in the background. In total, 72 percent of interactions occurred on the right side of the listener. These results are consistent with the right ear preference found in both laboratory studies and questionnaires and they demonstrate that the side bias is spontaneously displayed outside the laboratory.

In another study, the researchers approached 160 clubbers and mumbled an inaudible, meaningless utterance and waited for the subjects to turn their head and offer either their left of their right ear. They then asked them for a cigarette. Overall, 58 percent offered their right ear for listening and 42 percent their left. Only women showed a consistent right-ear preference. In this study, there was no link between the number of cigarettes obtained and the ear receiving the request.

In the third study, the researchers intentionally addressed 176 clubbers in either their right or their left ear when asking for a cigarette. They obtained significantly more cigarettes when they spoke to the clubbers' right ear compared with their left.

According to the authors, taken together, these results confirm a right ear/left hemisphere advantage for verbal communication and distinctive specialization of the two halves of the brain for approach and avoidance behavior.

They conclude: "Our studies corroborate the idea of a common ancestry – in humans and other species – of lateralized behavior during social interactions, not only for species-specific vocal communication, but also for affective responses."

New Protocol for Automated DNA Purification

2009-06-23T11:41:00.000-07:00

Hamilton Robotics provides a tested and verified protocol for automation of the Promega Wizard SV 96 Plasmid DNA Purification System. Developed in collaboration with Promega, this high-throughput method purifies DNA from pelleted bacterial culture samples using Hamilton's MICROLAB® STAR liquid handling workstation. The method processes up to 96 plasmid samples in 30 minutes or less with consistent results and no detectable cross-contamination. The purified plasmid can be used directly for automated fluorescent DNA sequencing, restriction enzyme digestion and other downstream molecular biology processes.

The flexible Hamilton MICROLAB STAR workstation has a unique air displacement pipetting and performs a range of liquid handling and vacuum-based tasks. This workstation can also be used with the Promega Wizard SV 96 PCR Clean-Up System, which requires a vacuum manifold, shaker and plate gripper in addition to liquid handling.

What sharks have in common with Jack the Ripper

2009-06-22T13:11:00.000-07:00

What do great white sharks have in common with serial killers? Refined hunting skills, according to a paper published today in the Zoological Society of London's Journal of Zoology.

A team of US-based researchers have found that sharks hunt in a highly focused fashion, just like serial criminals.Using the same methods used in criminology, the authors demonstrate how geographic profiling, a mathematical technique usually used to hunt serial criminals, can be used to study the hunting patterns of great white sharks.

The authors observed the location of 340 shark attacks and used the data to locate the sharks' anchor point. Interestingly, the study also showed that younger sharks exhibited less focused search patterns and were less successful hunters, perhaps because larger sharks excluded them from the best areas.

"Geographic profiling is an interesting new way to study patterns of animal foraging, and especially predation" says Dr Steven Le Comber, an expert on geographic profiling at the School of Biological and Chemical Sciences at Queen Mary, University of London. "Shark hunting patterns are extremely difficult to study and the work here will have important implications for our understanding of the ways in which predators hunt their prey."

Toxic to some, giving orientation to other (species): Superoxide

2009-06-22T12:52:00.000-07:00

A toxic molecule known to damage cells and cause disease may also play a pivotal role in bird migration, report researchers at the University of Illinois in Chicago. The molecule, superoxide, is proposed as a key player in the mysterious process that allows birds to "see" Earth's magnetic field.

The discovery, reported this month in Biophysical Journal, occurred as a result of a "mistake" made by a collaborator, said principal investigator Klaus Schulten, who holds the Swanlund Chair in Physics at Illinois. His postdoctoral collaborator, Ilia Solov'yov, of the Frankfurt Institute for Advanced Studies, did not know that superoxide was toxic, seeing it instead as an ideal reaction partner in a biochemical process involving the protein cryptochrome in a bird's eye.

Cryptochrome is a blue-light photoreceptor found in plants and in the eyes of birds and other animals. Schulten was the first to propose (in 2000) that this protein was a key component of birds' geomagnetic sense, a proposal that was later corroborated by experimental evidence. He made this prediction after he and his colleagues discovered that magnetic fields can influence chemical reactions if the reactions occur quickly enough to be governed by pure quantum mechanics.

"Prior to our work, it was thought that this was impossible because magnetic fields interact so weakly with molecules," he said.

Such chemical reactions involve electron transfers, Schulten said, "which result in freely tumbling spins of electrons. These spins behave like an axial compass."

Changes in the electromagnetic field, such as those experienced by a bird changing direction in flight, appear to alter this biochemical compass in the eye, allowing the bird to see how its direction corresponds to north or south.

"Other researchers had found that cryptochrome, acting through its own molecular spins, recruits a reaction partner that operates at so-called zero spin. They suggested that molecular oxygen is that partner," Schulten said. "We propose that the reaction partner is not the benign oxygen molecule that we all breathe, but its close cousin, superoxide, a negatively charged oxygen molecule."

When Solov'yov showed that superoxide would work well as a reaction partner, Schulten was at first dismissive.

"But then I realized that the toxicity of superoxide was actually crucial to its role," he said. The body has many mechanisms for reducing concentrations of superoxide to prevent its damaging effects, Schulten said. But this gives an advantage, since the molecule must be present at low concentrations – but not too low – "to make the biochemical compass work effectively," he said.

Schulten and Cryptochrome

Although known primarily as an agent of aging and cellular damage, superoxide recently has been recognized for its role in cellular signaling.

However, its toxicity may also explain why humans, who also have cryptochrome in their eyes, do not have the same ability to see Earth's electromagnetic field, Schulten said.

"Our bodies try to play it safe," he said. "It might be that human evolution chose longevity over orientational ability."

New microcentrifuges

2009-06-22T12:47:00.000-07:00

Thermo Fisher Scientific has introduced two new Sorvall Micro-ultracentrifuge models, each delivering improved versatility in rapid, small volume processing of samples including viruses, cellular organelles, lipoproteins, nucleic acids and nanoparticles. According to the supplier, both new micro-ultracentrifuge models offer an expanded volume range, accommodating tubes from 0.2 mL to 30 mL. These systems use a drive system that provides maintenance-free performance and rotor imbalance protection to ensure years of reliability.

The Sorvall MTX 150 is up to 20% smaller than other benchtop models in its class and puts almost any separation within reach with a centrifugal force in excess of 1,048,000 x g. It achieves its maximum rotational speed of 150,000 rpm in just 80 seconds. A state-of-the-art, user-friendly LCD touch-screen interface simplifies operation while providing a range of operating features.

The new Sorvall MX series offers the same versatility as the Sorvall MTX 150 in the most- compact floor model configuration currently on the market, says Thermo. Available in two versions with maximum speeds of 150,000 rpm or 120,000 rpm, its small footprint of 2.3 square ft (0.21 sq M), in combination with minimal noise (below 48 dBA) enables convenient in-lab location.

New medium for purification of glycoproteins, polyschharides and glycolipids

2009-06-22T12:41:00.000-07:00

GE Healthcare now provides HiTrap™ Con A 4B, ready-to-use columns prepacked with Con A Sepharose™ 4B, a chromatography medium for separation and purification of glycoproteins, polysaccharides and glycolipids.

The HiTrap columns are made of biocompatible polypropylene and are available in 1 ml and 5 ml formats and can be operated with a syringe, a peristaltic pump, or a liquid chromatography system such as ÄKTAdesign.

Con A Sepharose 4B is an affinity chromatography medium with a lectin, concanavalin A
(Con A), coupled to Sepharose 4B. Immobilized lectins are tools for isolating and separating glycoproteins, polysaccharides and glycolipids, subcellular particles and cells, and for purifying detergent-solubilized cell membrane components. They are also useful for assessing changes in levels or composition of surface glycoproteins during cell development and in malignant or virally transformed variants.

Con A Sepharose 4B chromatography medium is also available in 5 ml and 100 ml bulk packs.

The Scientist Video Awards: Vote For Your Favorite!

2009-06-20T08:45:00.000-07:00

The Scientist 2009 Video Awards voting is open! The Finalists Video's can be viewed and and you can vote for your favorite.

The Scientist selected the top 5 finalists in both the individual and institutional categories. Now they want us to help deciding which video will receive top honors. Vote by July 1st!

There are 2 Categories:

Individual - created with funding from an individual or single research grant, or simply off the skin of one's back
Institution - created with funding from a corporation or research institution

So take a look at the 10 videos (each is just a few minutes long or less) and vote for your favorite today - voting closes July 1st.

The winners will be announced in August.

New EMBL service makes web browsing efficient for biologists

2009-06-20T08:40:00.000-07:00

The European Molecular Biology Laboratory (EMBL) now offers a new free service to help researchers, teachers and students keep up-to-date with scientific literature on the web, especially when researching unfamiliar molecules.

Researchers of EMBL's Structural and Computational Biology Unit now provide 'Reflect', a new automated document annotation service free of charge. Reflect pinpoints all genes, proteins and small molecule names on any web page.With a single click pop-up windows provide extra information on any molecule, such as domain structure, subcellular localisation, 3D structure, and interaction partners in the case of proteins, and the chemical structure and interaction partners in the case of small molecules. The information is based on biological databases comprising 1.5 million proteins from 373 organisms and 4.3 million small molecules.

Reflect was recently awarded the first prize in the Elsevier Grand Challenge, an international contest that attracted over 70 submissions that improve the way scientific information is communicated Reflect is freely available on the web at: http://reflect.ws.

BRIT-1 is more relaxing than Brit!

2009-06-19T15:30:00.000-07:00

Not only Britney is relaxing, but also BRIT-1, even though more on DNA-level: Like a mechanic popping the hood of a car to get at a faulty engine, the tumor-suppressing protein BRIT-1 allows cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.

Reporting online at Nature Cell Biology this week, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center shows that BRIT1 connects with another protein complex to relax DNA's tight packaging at the site of the damage.

"Relaxing this barrier allows two different DNA repair pathways greater access to the damage, preventing flawed DNA from being passed on as the cell divides, which causes genomic instability leading to cancer," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in M. D. Anderson's Department of Systems Biology.

BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines. Lin and colleagues previously showed that the protein plays a key role in early detection of DNA damage.

Chromosomes are made of DNA that is tightly intertwined with proteins called histones to form chromatin. Chromatin is a very condensed structure that forms a natural barrier inhibiting access to genes, said first author Guang Peng, Ph.D., a post-doctoral fellow in Systems Biology. ATP-dependent chromatin remodeling is a fundamental mechanism used by cells to relax chromatin in DNA repair, but the detailed molecular mechanism by which it is recruited to DNA lesions in response to damage signaling has been largely unknown.

"Our studies demonstrate a novel mechanism by which BRIT1 recruits chromatin remodeling factors to DNA lesions to facilitate chromatin relaxation and DNA repair," Peng said.

A series of lab experiments showed that BRIT1 accomplishes this by enhanced binding to a known chromatin remodeling complex called SWI-SNF when a specific site on the complex is phosphorylated. BRIT1 also maintains the relaxation factor at the damage site.

The team showed that normal BRIT1 aids repair of double-stranded DNA breaks by allowing access to two repair pathways: homologous recombination (HR) and non-homologous end-joining (NHEC).

DNA repair efficiency dropped by between 40 and 60 percent in cells with BRIT1 knocked down that were then exposed to ionizing radiation, allowing many damaged cells to divide and pass on their genetic defects.

Having shown that BRIT1 deficiency impairs HR repair, Peng said one solution the team is examining is to treat cancer cells lacking BRIT1 with PARP inhibitors, drugs that specifically kill HR-deficient cancer cells.

BRIT1 mutations are known to cause a neurological condition called primary microcephaly, in which the brain develops to only one third of normal size. The team showed that in experiments using cells derived from primary microcephaly patients that BRIT1 dysfunction may specifically contribute to development of the neurological disease by failing to bind to SWI-SNF to relax chromatin.

Why I drink green tea? Because it affects cancer progression...

2009-06-19T12:50:00.001-07:00

According to results of a study published in Cancer Prevention Research men with prostate cancer who consumed the active compounds in green tea demonstrated a significant reduction in serum markers predictive of prostate cancer progression.

"The investigational agent used in the trial, Polyphenon E (provided by Polyphenon Pharma) may have the potential to lower the incidence and slow the progression of prostate cancer," said James A. Cardelli, Ph.D., professor and director of basic and translational research in the Feist-Weiller Cancer Center, LSU Health Sciences Center-Shreveport.

Green tea is the second most popular drink in the world, and some epidemiological studies have shown health benefits with green tea, including a reduced incidence of prostate cancer, according to Cardelli. However, some human trials have found contradictory results. The few trials conducted to date have evaluated the clinical efficacy of green tea consumption and few studies have evaluated the change in biomarkers, which might predict disease progression.

Cardelli and colleagues conducted this open-label, single-arm, phase II clinical trial to determine the effects of short-term supplementation with green tea's active compounds on serum biomarkers in patients with prostate cancer. The biomarkers include hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and prostate specific antigen (PSA). HGF and VEGF are good prognostic indicators of metastatic disease.

Cardelli in the lab

The study included 26 men, aged 41 to 72 years, diagnosed with prostate cancer and scheduled for radical prostatectomy. Patients consumed four capsules containing Polyphenon E until the day before surgery — four capsules are equivalent to about 12 cups of normally brewed concentrated green tea, according to Cardelli. The time of study for 25 of the 26 patients ranged from 12 days to 73 days, with a median time of 34.5 days.

Findings showed a significant reduction in serum levels of HGF, VEGF and PSA after treatment, with some patients demonstrating reductions in levels of greater than 30 percent, according to the researchers.

Cardelli and colleagues found that other biomarkers were also positively affected. There were only a few reported side effects associated with this study, and liver function remained normal.

Results of a recent year-long clinical trial conduced by researchers in Italy demonstrated that consumption of green tea polyphenols reduced the risk of developing prostate cancer in men with high-grade prostate intraepithelial neoplasia (HGPIN).

"There is reasonably good evidence that many cancers are preventable, and our studies using plant-derived substances support the idea that plant compounds found in a healthy diet can play a role in preventing cancer development and progression," said Cardelli.

No single biofuel technology supreme

2009-06-19T12:36:00.000-07:00

Scientists say they are forging ahead in developing replacements for petrochemical fuels that will be cost-competitive and renewable while having a minimal impact on the environment, reports Genetic Engineering & Biotechnology News (GEN). A consensus seems to emerge that no single technology will reign supreme and that a range of current and novel methodologies will contribute to meeting biofuel needs.

"It's been estimated that fossil fuels constitute more than eighty percent of the world's main energy supply," says John Sterling, Editor in Chief of GEN. "Both economics and the concern over global warming require that technologies be used to significantly lower this number."

Edenspace Systems is working on Energy Corn™, a feedstock designed to cut the cost of producing cellulosic biofuels from corn stover. The company's technology, based on identifying promising cellulose genes, transforming crop plants with candidate genes, and evaluating the effects on growth, yield, and cellulose hydrolysis, would be applicable to a variety of energy crops including switchgrass, sorghum, and sugar cane.

Officials at Coskata say the company relies on a hybrid approach based on its Flex Ethanol™ technology, which combines gasification and fermentation in a thermo-biological pathway to produce fuel-grade ethanol that it contends can be cost-competitive with gasoline. The process reportedly is able to yield more than 100 gallons of ethanol per ton of dry biomass.

Also discussed in the GEN article is biofuel research taking place at ICM, Qteros, Synthetic Genomics, Solazyme, and the United States Department of Agriculture.

Does size matter? Well, at least it did...

2009-06-18T12:09:00.000-07:00

Oldest evidence for reproduction with giant sperm uncovered at the European Synchrotron Radiation Facility. The mystery of giant sperm present in some living animal groups today has taken on a new dimension. In one group of micro-crustaceans new evidence shows the feature is at least 100 million years old.

Renate Matzke-Karasz, from Ludwig-Maximilians-Universität Munich (Germany), has led an international team of scientists, studying specimens from the London Natural History Museum's collections. Their research has revealed fossilised evidence for reproduction using giant sperm in a group of small aquatic crustaceans, called ostracods, dating back to 100 million years ago.

Matzke-Karasz said, 'In these microfossils, we detected organs that are required for transferring giant spermatozoa. Since modern ostracods still produce giant sperm and manoeuvre them with the same organs as 100 million years ago, it's safe to say this distinctive feature evolved only once in this group. It seems to be an evolutionarily successful reproduction strategy, even though it comes at an exceedingly high price for both genders, as a lot of energy is invested in producing and carrying such enormous sperm.'

The international team analysed Harbinia micropapillosa specimens from the Cretaceous Period that had remains of the soft body intact. These fossils had been collected, investigated and then donated to the Natural History Museum in 2000 by Robin Smith. Now at the Lake Biwa Museum, Japan, Smith is a member of the research team. Eight years later, the same specimens were analysed using synchrotron X-ray holotomography at the European Synchrotron Radiation Facility (ESRF) in Grenoble, through collaboration with Paul Tafforeau, a palaeontologist at the ESRF. This method is currently the most powerful and sensitive way to investigate in three dimensions and at a microscopic scale, the internal anatomy of exceptional fossils without damaging them. "Holotomography is a non-destructive imaging technique like computer tomography (CT), but we use powerful and coherent synchrotron X-rays leading to a sensitivity thousand times higher," explains Paul Tafforeau of ESRF. "It is since very recently that palaeontologists use this technique to image fossils, but the results achieved so far show that this technique will surely lead to many important discoveries on fossils", he adds.

The X-ray examination of the fossilised ostracods revealed direct parallels with the complex reproductive apparatus of modern relatives of these Cretaceous fossils. The team also came across something of a surprise: two of the female specimens had inflated cavities that only occur in modern ostracods that have recently mated, meaning fossil evidence for an insemination had been uncovered.

The team was completed by Radka Symonová, scientist at the Charles University in Prague and Giles Miller, Micropalaeontology Curator at the Natural History Museum.

A human sperm would have to be over 17 meters long in order to measure up against one group of modern ostracods, whose sperm are up to ten times as big as the animals themselves. Roughly 34,000 of the 50 micron-long human sperm would have to line up to match the body length of a man (of 1,70m).

Zeiss: Faster FRET experiments with new software

2009-06-18T12:05:00.000-07:00

All FRET applications are now integrated into the physiology module of the AxioVision 4.7 microscopy software from Carl Zeiss. This enables cell and development biologists to use all AxioVision functionalities such as the enhancement of fluorescence signals and the suppression of image noise. Operation is very easy as only a few clicks are required.

The FRET software is used to determine the energy transfer portion between two adjacent protein molecules through fluorescence energy transfer (FRET), measure the distance between adjacent protein molecules below the microscope resolution and obtain quantitative temporal and spatial information about the bonding and interaction between proteins, lipids, enzymes, DNA and RNA in vivo.

The software offers numerous additions to existing and new methods of FRET measurement by using different corrective techniques or acceptor bleaching. Users can define their own formulas for the tasks to be performed or use pre-programmed FRET formulas to make FRET experiments even more simple. Furthermore, it is possible to modify existing FRET formulas and easily create new evaluation techniques via the formula field. AxioVision enables all microscope components and software functions to be used for processing. The dual camera module more than doubles the speed of capture. Up to 140 frames per second are available with the AxioCam HS. In addition, all required time series images (donor, acceptor and FRET) can be captured using the physiology module. However, the system can also be utilized for all standard tasks in image processing and analysis.

The benefits of the FRET software can be perfectly utilized with the motorized Axio Imager or Cell Observer microscope systems. However, suitable filter sets for FRET measurements also allow the software to be used with manual fluorescence microscopes.

Cancer-causing protein can also help fight the tumors it causes

2009-06-18T11:58:00.000-07:00

Research from Tel Aviv University is demonstrating that Ras, one of the first oncogenes discovered, has the power to heal as well as harm.

Ph.D. student Oded Rechavi and his fellow researchers at Tel Aviv University's Department of Neurobiology have found that Ras has the ability to transfer from cancer cells into immune cells — such as t-cells — a transfer that may be the key to creating new drugs to fight cancerous tumors.

Prof. Yoel Kloog, dean of the university's Faculty of Life Sciences and a renowned expert in the field, is supervising the project. He and Rechavi published the discovery in the journal Public Library of Science One and a recent review about such cell-to-cell transferring of proteins in FEBS Letters.

The idea that proteins can transfer between cells challenges the original theory of the cell, according to Rechavi. "All the energy flow, metabolism, and biochemistry of life is supposed to happen within the boundaries of an individual cell," he says. "Here we show that when cells in the immune system interact with other cells, proteins are exchanged without being secreted from the cell, and act in both the immune and original cells alike."

Oded Rechavi is a researcher at Tel Aviv University.

"When Ras transfers from one cell to another, it strengthens the immune system. The immune cell that adopts the mutated Ras gets activated and reacts against the cancerous cell that donated the Ras. This does not happen for advanced tumors, but if we could control the movement of Ras, we would have a better understanding of how immune cells react against cancer" and provide the scientific basis for an entirely new class of cancer drugs.

The researchers are working to discover the mechanisms by which the Ras protein is transferred, and initial results look promising. One current theory Rechavi is investigating is that the membranes of the cells temporarily fuse together. What is certain, however, is that once t-cells acquire mutated Ras, they are able to generate clones with the ability to respond against this specific threat.

"When immune cells scan their targets they bind to their targets," he says. "When immune cells acquire normal Ras, nothing happens. But when they acquire mutated Ras from a potential tumor, it starts a cascade. This results in the production of cytokines that help the immune system and act against the cancer."

Rechavi says that understanding the nature of this interaction between mutated Ras and immune t-cells can unlock mysteries about the nature of proteins and cells. The next step is to identify other proteins that, like Ras, are able to transfer outside of their cell of origin.

Rechavi is now conducting a scan of proteins in an attempt to identify which ones have similar characteristics and abilities to Ras, and how they might transfer in the body. The TAU researchers have developed a technology to scan hundreds of proteins and have already discovered many with transferring properties; they plan to publish their results soon.

The more researchers learn, the more they can exploit these cells to keep the human body healthy — but Rechavi warns that not all the news may be good. "It could be that a bad protein is able to transfer from cancer cells to immune cells as well, upon acquiring such protein the immune system will be less active," says Rechavi. "It's also possible that a tumor could transfer the Ras protein into cells that normally support tumor growth, like stroma cells that grow blood vessels for the tumor. This is why we have to work to understand what is happening."

Guest Commentary: Dear science marketing expert: shut up - now!

2009-06-17T11:51:00.001-07:00

Dear science marketing expert,

Have you ever read any of the product introductions on the product pages of your trade publication or on the web? It can actually get quite complicated to read this sort of thing. However, not because of the complexity of the product mentioned or the many features it might have. Nope! There is simply a clash of two worlds: marketing and science.

Just check out this one that is used over and over again:

"The company continues to execute on its strategy of providing customers a complete solution for..."

So, what does that actually mean? So, they have a strategy - good for them, but who cares when buying a couple of antibodies or a new microscope? Well, the CEO might want to hear that and feel good about having a strategy and seeing it in one way or the other implemented, but I'm not sure how you guys in the lab feel about this sort of thing. I find it not much more than marketing spiel - or should I say nonsense?

And let me have another 2 nice examples:

"With the new product, scientists now have the complete solution for..."
"...provides also the advantage of quick results."

You wish! Buy a new machine or antibody and the first thing you feel is pain. This isn't working, that ain't working, etc. It is just normal that sometimes things don't pan out as I wish, but let's not exaggerate stuff that is going to frustrate others in the lab, ok?

So, marketing gurus, just shut up for a minute, think about the benefits of the product and then talk. That would be much appreciated. Thanks!

Kind regards,
A lab worker

Research uncover virus-cancer link in HIV

2009-06-17T11:42:00.000-07:00

A research team from the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center has uncovered clues to the development of cancers in AIDS patients.

In an April article published in the journal PLoS Pathogens, Dirk Dittmer at UNC's School of Medicine demonstrated that the Kaposi sarcoma associated herpesvirus (KSHV) is not only present in every tumor cell, but that the cells also transcribe microRNAs (miRNA) from the virus.

MicroRNAs are small molecules that regulate gene expression. Scientists have hypothesized that viruses can cause cancer through a mechanism where the viral genes take over the cell and induce cancerous growth through alteration of cell miRNA, since certain kinds of miRNA are responsible for putting the 'brakes' on uncontrolled cell growth.

Dittmer's team examined samples of tissue provided with the consent of Kaposi's sarcoma patients and found that specific miRNA biomarkers accurately identify stages of tumor progression. They found that certain miRNAs were lost as the tumors progressed, effectively accelerating the cancer's growth. More aggressive tumor stages expressed higher levels of KSHV miRNA.

In second study, published June 4 in Blood, the team looked for the presence of tumor suppressor mRNAs in primary effusion lymphoma and Kaposi's Sarcoma. "We chose these two cancers because, while they are both associated with the same virus, they occur in very different types of cells," Dittmer noted.

His team found that several miRNAs known to suppress tumor activity were significantly less active in both types of cancer. "Micro RNAs are an exciting new class of cancer markers. Knowing which ones are present in a particular tumor will help us understand the biology and develop those micro RNAs as novel cancer therapy targets."

Scientists believe that finding the mechanisms through which viruses take over cellular systems, resulting in cancer, is a promising strategy for cancer prevention and treatment, since it is much more feasible to block viral infection or develop specific inhibitors of the viral genes than try to inhibit all of the genetic changes within a cancer.

3 Canabis cigarettes = 1 normal cigarette

2009-06-16T12:30:00.000-07:00

A new study published by University of Leicester researchers has found evidence that cannabis smoke damages DNA in ways that could potentially increase the risk of cancer development in humans.

Using a newly developed highly sensitive liquid chromatography-tandem mass spectrometry method, the University of Leicester scientists found clear indication that cannabis smoke damages DNA, under laboratory conditions. the findings have been published in the journal Chemical Research in Toxicology¹.

The research was carried out by Rajinder Singh, Jatinderpal Sandhu, Balvinder Kaur, Tina Juren, William P. Steward, Dan Segerback and Peter B. Farmer from the Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine and Karolinska Institute, Sweden.

Raj Singh said: "Parts of the plant Cannabis sativa, also known as marijuana, ganja, and various street names, are commonly smoked as a recreational drug, although its use for such purposes is illegal in many countries.

"There have been many studies on the toxicity of tobacco smoke. It is known that tobacco smoke contains 4000 chemicals of which 60 are classed as carcinogens. Cannabis in contrast has not been so well studied. It is less combustible than tobacco and is often mixed with tobacco in use. Cannabis smoke contains 400 compounds including 60 cannabinoids. However, because of its lower combustibility it contains 50% more carcinogenic polycyclic aromatic hydrocarbons including naphthalene, benzanthracene, and benzopyrene, than tobacco smoke."

The scientists describe the development of a mass spectrometry method that provides a clear indication that cannabis smoke damages DNA, under laboratory conditions.

The authors added: "It is well known that toxic substances in tobacco smoke can damage DNA and increase the risk of lung and other cancers. Scientists were unsure though whether cannabis smoke would have the same effect. Our research has focused on the toxicity of acetaldehyde, which is present in both tobacco and cannabis."

The researchers add that the ability of cannabis smoke to damage DNA has significant human health implications especially as users tend to inhale more deeply than cigarette smokers, which increases respiratory burden. "The smoking of 3-4 cannabis cigarettes a day is associated with the same degree of damage to bronchial mucus membranes as 20 or more tobacco cigarettes a day," the team adds.

Same-sex behaviour is universal, says study

2009-06-16T10:34:00.000-07:00

Same-sex behavior is a nearly universal phenomenon in the animal kingdom, common across species, from worms to frogs to birds, concludes a new review of existing research.

There is a caveat, however. The review also reports that same-sex behaviors are not the same across species, and that researchers may be calling qualitatively different phenomena by the same name.For example, male fruit flies may court other males because they are lacking a gene that enables them to discriminate between the sexes. But that is very different from male bottlenose dolphins, who engage in same-sex interactions to facilitate group bonding, or female Laysan Albatross that can remain pair-bonded for life and cooperatively rear young.

Female-female pair of Laysan Albatross. Females cooperatively build nests and rear young when males are scarce.

The review, published yesterday in the journal Trends in Ecology & Evolution also finds that although many studies are performed in the context of understanding the evolutionary origins of same-sex sexual behavior, almost none have considered its evolutionary consequences.

A selective force, which is a sudden or gradual stress placed on a population, affects the reproductive success of individuals in the population.

Oral drug for diabetes?

2009-06-15T13:04:00.000-07:00

Promise is held out for the development of novel oral drugs to control blood glucose levels in diabetes patients as the result of research by a Hebrew University of Jerusalem scientist.

For his groundbreaking work, Prof. Shlomo Sasson of the Hebrew University School of Pharmacy has been named one of the winners this year of the Hebrew University's Kaye Innovation Awards.

Prof. Shlomo Sasson is from the Hebrew University of Jerusalem.

Pharmacological anti-diabetic therapy aims at a strict regulation of blood glucose levels to prevent such complications. However, because current oral anti-diabetic drugs often fail, many patients need daily injections of insulin to control their glucose metabolism and reduce blood glucose levels.

Recent work on the molecular mechanisms that regulate glucose transport in skeletal muscles has identified new potential targets for anti-diabetic drugs.

In his research, Sasson, with his colleagues and students, made a unique discovery that high levels of the carbohydrate D-xylose increased the rate of glucose entry into skeletal muscle cells in a non-insulin-dependent manner. They then used it as a prototype molecule for the planning and synthesis of chemical derivatives that may act as potential drugs to lower blood glucose in type 2 diabetic patients.

Some of these derivatives increased significantly the rate of glucose transport in skeletal muscles at very low concentrations. This effect was not achieved by mimicking the classical pathway of insulin action, but by activating the enzyme AMP-activated protein kinase (AMPK). When activated, this enzyme increases the rate of glucose transport in skeletal muscles in the absence of insulin. Therefore, compounds that activate this enzyme can be effective in insulin resistant type 2 diabetic patients or in those that fail to respond to conventional drug therapy. This makes AMPK an extremely attractive target in the development of novel anti-diabetic drugs.

One of the lead compounds developed by Sasson and colleagues effectively reduced blood glucose levels in various animal models of diabetes. This discovery indicates the great potential of these novel derivatives to serve as the basis for development of new drugs to normalize blood glucose levels in diabetic patients.

Scientists say: have a purpose and you life longer...

2009-06-15T12:00:00.000-07:00

Possessing a greater purpose in life is associated with lower mortality rates among older adults according to a new study by researchers at Rush University Medical Center.

The scientists studied 1,238 community-dwelling elderly participants from two ongoing research studies, the Rush Memory and Aging Project and the Minority Aging Research Study. None had dementia. Data from baseline evaluations of purpose in life and up to five years of follow-up were used to test the hypothesis that greater purpose in life is associated with a reduced risk of mortality among community-dwelling older persons.

Purpose in life reflects the tendency to derive meaning from life's experiences and be focused and intentional, according to the scientists.

After adjusting for age, sex, education and race, a higher purpose of life was associated with a substantially reduced risk of mortality. Thus, a person with high purpose in life was about half as likely to die over the follow-up period compared to a person with low purpose. The association of purpose in life with mortality did not differ among men and women or whites and blacks, and the finding persisted even after controlling for depressive symptoms, disability, neuroticism, the number of medical conditions and income. During the study period, 151 participants died.

The researchers note that knowledge of the relationship of purpose of life with other demographic characteristics is limited and future studies are needed to examine whether the association of purpose of life with mortality might be modified by other variables not measured in this study, such as how religious a participant may be. In addition, researchers suggest that future studies should examine whether purpose in life can be enhanced in older persons with interventions.

The study, published in the June 15 issue of the journal, Psychosomatic Medicine, is available online at www.psychosomaticmedicine.org.

Want your genome for under $50,000?

2009-06-15T11:46:00.000-07:00

Personal genome sequencing is now available to everybody: Illumina annouced that their service offers a complete coverage of the human genome sequence for under $50,000. The offering includes sequencing of an individual's DNA to 30 times depth, providing information on SNP variation and other structural characteristics of the genome such as insertions, deletions and rearrangements.

Illumina intends to create a social community for the education and exchange of information for those who have had their genomes sequenced. As more information becomes available, participants will be in a position to mine their personal genome sequence data to understand their identity in ways which have never been possible.

In addition to the sequencing service, the company is establishing a protocol, infrastructure, and community to enable large-scale adoption of personal genome sequencing. This includes the creation of a network of partners to offer a variety of services. Data analysis partners, physicians and genetic counselors will play an important role in Illumina's Personal Genome Sequencing Service. A physician's network is being created as physicians will be critical to the service - to discuss the process with the consumer, order the sequencing service, collect DNA samples and deliver final sequencing data to the consumer.

Automated gel electrophoresis

2009-06-15T11:41:00.000-07:00

Lab901 now offers an automated gel electrophoresis system. It comprises the TapeStation for the liquid handling, electrophoresis and imaging and ScreenTape, a consumable that contains the pre-cast, pre-packaged gel and running buffer and software. With no gel or buffer preparation and no system priming, untrained operators can rapidly generate accurate and reproducible data.

The first ScreenTape consumables are optimised for the analysis of DNA fragments up to 800 bp. This makes the system ideal for applications such as multiplex or simplex PCR analysis, genotyping, QC of Q-PCR products and QC of DNA prior to microarray printing. Efficient and safe data storage isachieved through integrated bar-coding and the generation of secure file formats for the analysed data. Labs using gel electrophoresis can obtain full traceability and GLP compliance.

Lab901 is also developing tapes for the analysis of larger DNA fragments, proteins and RNA, and is seeking to develop collaborations with interested companies.

For Most no Antiviral in Pandemic, But Generics Can Help

2009-06-13T07:32:00.000-07:00

Almost 90 per cent of the world's population will not have timely access to affordable supplies of vaccines and antiviral agents in the current influenza pandemic, but it is possible that inexpensive generic drugs that are readily available, even in developing countries, could save millions of lives. That's the conclusion reached by an extensive review and analysis by Dr David Fedson, published online by Influenza and Other Respiratory Viruses.

The study points out that seasonal flu resistance to antiviral drugs like Tamiflu may make them ineffective in the pandemic and maintains that without effective drugs some countries will have to rely on 19th century public health measures to see them through the outbreak.

Fedson is therefore calling for urgent and sharply focused research to determine whether drugs that reduce inflammation or modify the host response - the way that the body responds to infection or injury - could be used to manage the pandemic. And he believes that a lot could be learnt from the work done on these commonly available generic drugs - which include drugs to lower cholesterol and treat diabetes - by scientists not involved in influenza research.

"Despite the best efforts of influenza scientists, pharmaceutical companies and health officials, the stark reality is that although studies of the molecular characteristics of influenza viruses have been enormously informative, they have failed to explain the system-wide effects that flu has on people who contract it."

"Most of the world's population lack realistic alternatives for confronting the next pandemic and urgent research is vital. Otherwise people everywhere might be faced with an unprecedented public health crisis."

Dr Fedson maintains that experiments by non-influenza scientists have defined common cell signalling pathways for acute lung injury caused by different agents, including the inactivated H5N1 influenza virus (bird flu).

"Research suggests that giving patients anti-inflammatory and immunomodulatory agents such as statins, fibrates and glitazones could help to regulate the cell signalling pathways in patients who have suffered acute lung injury, a common problem with influenza" he says. "They can also help to reverse the cellular dysfunction and cell damage that accompanies multi-organ failure

"Cell signalling pathways play essential roles in the ability of cells to perceive and correctly respond to their microenvironment. They form the basis of development, tissue repair, immunity and normal tissue function.

Dr Fedson, expert on flu.

"Statins are commonly used to lower cholesterol and prevent heart disease - but have also been shown to be effective in reducing hospitalisations and deaths from pneumonia. Fibrates modify fatty acid metabolism and glitazones reduce blood glucose levels in type 2 diabetes. All of these drugs modify the cell signalling pathways involved in acute lung injury and multi-organ failure. Moreover, they are affordable generic drugs that are widely available even in developing countries."

Dr Fedson points out that there is currently no logistical plan to distribute supplies of pandemic vaccines to the non-vaccine producing countries that contain 88 per cent of the world's population.

"In all likelihood, people in these countries won't be able to obtain supplies of pandemic vaccines or they will get them too late" he says

"Many health officials have placed their hopes on stockpiles of antiviral agents, but resistance to the most widely stockpiled agent, Tamiflu, in seasonal flu outbreaks, has prompted concerns that similar resistance could develop in any pandemic virus. It's estimated that countries that do not produce influenza vaccines will only have enough antivirals to treat one per cent of their combined populations."

"Swine flu has only recently emerged so we have had less time to study its effects. But any influenza pandemic is cause for great concern regardless of what strain it is."

NIH Receives 20,000 Applications for Challenge Grants

2009-06-13T07:20:00.000-07:00

The National Institutes of Health (NIH) received approximately 20,000 applications for Challenge Grants, a new program under the American Recovery and Reinvestment Act (ARRA). This large number of applications is approximately equal to the total number of applications NIH receives in one of the agency’s three major review rounds each year.

Secretary of Health and Human Services Kathleen Sebelius, commented:"President Obama is committed to supporting science and research that has the potential to improve public health and save lives. These grants and other Recovery Act investments will strengthen our scientific community and help our economy grow as we create new jobs invest in new laboratories, buildings and equipment."

President Obama and Vice President Biden believe federally funded scientific research should play an important role in advancing science and technology in the classroom and in the lab.

The Challenge Grant program is designed to spur new areas of research and trigger an influx of research dollars into communities across the nation. NIH requested applications on topics in fifteen broad scientific areas the agency believes will benefit from a jumpstart or in which scientific challenges need to be overcome. They include bioethics, translational science, genomics, health disparities, enhancing clinical trials, behavioral change and prevention, and regenerative medicine.

The Center for Scientific Review (CSR) will check the applications for compliance and review them in a two-phase process. Reviewers with expertise in the specialized topic areas were recruited to do the first phase reviews. Their reviews and the applications will be further assessed by one of about 30 study sections comprising researchers who will focus on overall significance and impact.

All Challenge Grant applications will receive a summary statement containing critiques with criterion scores from three assigned reviewers. More than 18,000 scientists are expected to be involved in the Challenge Grant peer review process.

CSR typically reviews 16,000 applications with the help of about 8,000 reviewers in each of the three main yearly review rounds. Including Challenge Grants and other ARRA grants, CSR will assess about 40,000 applications this round with about 28,000 reviewers.

The deadline for Challenge Grant applications was April 27. Scores and summary statements will be available in August 2009. Challenge Grant awards will be issued by September 30, 2009.

NIH expects to devote at least $200 million in ARRA funding to Challenge Grants. In addition to the approximately 200 Challenge Grants that will be funded by the NIH Office of the Director, it is likely that more than 200 ARRA-related grants will be funded by NIH Institutes or Centers.

GC/MS-system with low requirements on space

2009-06-13T07:08:00.000-07:00

Varian introduced the 225-MS, a benchtop GC/MS system. According to Varian, it is the world's first mass spectrometer to enclose all of its components, including the foreline vacuum pump, in one compact design. it can be used in high-throughput laboratories for applications ranging from environmental analyses to product safety.

Mass spectrometers require two pumps to achieve sufficient vacuum: a foreline pump which is typically situated on the laboratory floor and a turbomolecular pump located inside the instrument. Without increasing the size of the mass spectrometer, the 225-MS integrates both pumps inside the benchtop unit, eliminating the floor space and hose required by an external pump.

The innovative integrated pump design offers benefits, such a reduction of background signals for improved sensitivity.

Researchers develop prototype of SARS-detector

2009-06-13T06:58:00.000-07:00

USC researchers say they have made a big improvement in a new breed of electronic detectors for viruses and other biological materials - one that may be a valuable addition in the battle against epidemics.

The improvement consists of a piece of synthetic antibody attached to a nanowire that is attached to an electrical base sitting in liquid.

If the protein the antibody binds to is present in the liquid, it will bind to these antibodies, immediately creating a sharply measurable jump in current through the nanowire.

The basic principle of nanotube and nanowire biosensors for protein detection was first demonstrated in 2001, but the new design by a team headed by Chongwu Zhou of the USC Viterbi School of Engineering and USC College chemist Mark Thompson uses two new elements.

Chongwu Zhou of the USC

The innovation takes advantage of bioengineered synthetic antibodies - much smaller versions of the natural substances that are designed to bind with a specific protein and only that protein. Second, it uses indium oxide nanowires instead of silicon and other materials previously tried. Metal oxides do not, unlike silicon, develop “an insulating native oxide layer that can reduce sensitivity.”

The result, according to the paper, is a device that can detect its target molecules with a sensitivity as great as the best alternative modes and without use of chemical reagents and is also potentially cheaper than alternatives.

In addition, the system can be useful in basic research by helping to establish important parameters for two-part biological systems such as the antibody/target protein pair

Boost of translational research in Germany

2009-06-10T12:13:00.000-07:00

The chances of cure for people affected with certain diseases can only be improved, if research results are swiftly transferred from the laboratory into clinical practice. Framework conditions for this research transfer, also called translational research, will now be optimized in Germany, according to the German Research Minister Annette Schavan.

"Each year, more than 436,000 people in Germany are newly diagnosed with cancer, 210,000 patients die of cancer every year. Therefore, it is important to translate the latest findings of cancer research even more rapidly into patient care. To this end, we have founded the National Consortium for Translational Cancer Research," Schavan said. "We intend to further strengthen Germany's leading role in cancer research."

The consortium is established on the initiative of the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), German Cancer Aid (Deutsche Krebshilfe) and the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). The financial resources needed for the whole consortium over a period of ten years amount to 400 million euros.

Key tasks of the national consortium include the creation and use of effective translational research units at partnering sites within a network throughout Germany. The DKFZ in Heidelberg as the core research center will collaborate with selected partners at university hospitals at up to six sites.

Research minister Schavan also announced that the Federal Ministry of Education and Research and German Cancer Aid will jointly support the participation of a German research consortium in the International Cancer Genome Consortium (ICGC). Both partners will jointly provide funds of approximately 15 million euros over a period of five years. This is intended as a contribution to the fight against tumor diseases with particularly high mortality. The ICGC aims to analyze the genetic changes in tumors of all human organ systems in order to facilitate and customize new and better applications in the areas of diagnosis, treatment and prevention of the respective cancer types. The results will rapidly be made available to the research community as a basis for further research work. The project is planned to be launched in fall 2009. The ICGC is a large-scale biomedical project in which leading cancer researchers have joined forces.

The earlier, the better: HAART-therapy of HIV-infection

2009-06-10T11:05:00.000-07:00

A clinical trial has demonstrated that HIV-infected adults in a resource-limited setting are more likely to survive if they start antiretroviral therapy (ART) before their immune systems are severely compromised.

On May 28, 2009, an independent data and safety monitoring board (DSMB) met to conduct a planned interim review of an ongoing clinical study known as CIPRA HT 001, which is being conducted in Haiti. The comittee found overwhelming evidence that starting ART at CD4+ T cell counts—a measure of immune health—between 200 and 350 cells per cubic millimeter (mm3) improves survival compared with deferring treatment until CD4+ T cells drop below 200 cells/mm3.

In light of these results, the DSMB recommended that the trial sponsor—the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health—end the trial immediately, before its scheduled conclusion. NIAID agreed with the DSMB recommendation, and all study participants who have fewer than 350 CD4+ T cells/mm3 will be offered ART.

The study investigators say this new finding has the potential to change the standard of care for HIV infection in dozens of countries around the world where ART is initiated only when CD4+ T cell counts drop below 200 cells/mm3. Like the results of several recent epidemiologic studies in developed countries that examined the optimal time to begin ART, the new finding underscores the importance of identifying people who are HIV-infected earlier in the course of their infection and starting ART earlier.

In light of these results, the DSMB recommended that NIAID end the trial immediately and that the study team offer ART to all participants in the standard-of-care group who have fewer than 350 CD4+ T cells/mm3. The DSMB also recommended that the study team continue to follow all participants for another year and make every effort to ensure that participants receiving ART continue their therapy. NIAID concurred with these recommendations.

Commentary: Scientists, we can!

2009-06-09T13:12:00.001-07:00

Yes, we all know it - the credit crisis is here. Friends are worrying about their jobs, if it is not ourselves. PostDocs and lab heads are fired at big pharma companies that were previously a "safe haven". This crisis is in some way also a kind of bad timing for science as a whole; it just happens, when pharma companies are already dealing with diminishing pipelines and tremendous cost issues in drug discovery. Personalised medicine isnt there, gene therapy hasnt made it (yet?) and biomarker discovery is sluggish, anyway.

But, in all this doom and gloom, there are also some good news. Politicians seem to realise that science and high-tech are key to our future. Obama seems to support science, and not only GM, and other governments are following this trend. A good example is the science funding boost in Germany, as Chemistry World reported this week.

To me, it seems that it hasn't been forgotten that not only do we need the public for (financial) support, but also the public needs our support. There are major challenges, ahead of us and you can name it: from the need to develop new vaccines through to finding new medicines against cancer, schizophrenia or alzheimers. Scientist's response to the economic downturn should therefore be under the mantra:

Yes, we can!

New high-res microarray scanner

2009-06-09T12:45:00.000-07:00

Roche NimbleGen introduced a new high-resolution scanning instrument, the NimbleGen MS 200 Microarray Scanner. The MS 200 is the first scanner optimized to reveal the full potential and capture the complete picture from all NimbleGen DNA microarrays. This offering completes the NimbleGen DNA Microarray processing family, comprised of a high-resolution suite of innovative microarray technology products, supplies, equipment, and instrumentation as well as software for data analysis.

The highly sensitive scanner reproducibly acquires two-color fluorescent array image data down to 2 micron pixel resolution and generates high-quality image files for subsequent data analysis. To satisfy today’s high-throughput requirements and make high throughput genomics a reality, the MS 200 offers several key features for a completely automated system allowing for walk away scanning and overnight runs.

New Tools Aimed at Increasing Productivity in Proteomics

2009-06-09T12:30:00.000-07:00

Thermo Fisher Scientific launched two new products designed to increase the productivity of quantitative proteomics research. The products are Intelligent Selected Reaction Monitoring (iSRM), which improves the throughput of SRM assays, and Pinpoint software for automated method development and quantitative analysis of SRM-based targeted peptide assays.

One of the biggest challenges in proteomics quantitation is to simultaneously verify and quantify low-level biomarkers. iSRM, which is available on all Thermo Scientific TSQ (triple stage quadrupole) instruments, increases the sensitivity and selectivity of targeted quantitation assays for simultaneously verifying and quantifying targeted proteins.

Thermo Fisher Scientific is also introducing Pinpoint software. Pinpoint, available as a free download, is designed to simplify the transition from early-stage biomarker discovery to larger-scale, quantitative verification of putative biomarkers and general quantitative proteomics. See here for details.

New antibiotics from DNA binding compound kills bacteria in 2 minutes

2009-06-09T12:21:00.000-07:00

A synthetic DNA binding compound has proved surprisingly effective at binding to the DNA of bacteria and killing all the bacteria it touched within two minutes. The DNA binding properties of the compound were first discovered in the Department of Chemistry at the University of Warwick by Professor Mike Hannon and Professor Alison Rodger. However the strength of its antibiotic powers have now made it a compound of high interest for University of Warwick researchers working on the development of novel antibiotics. Their work has been published in in the International Journal of Antimicrobial Agents.

Dr Adair Richards from the University of Warwick said:

"This research will assist the design of new compounds that can attack bacteria in a highly effective way which gets around the methods bacteria have developed to resist our current antibacterial drugs. As this antibiotic compound operates by targeting DNA, it should avoid all current resistance mechanisms of multi-resistant bacteria such as MRSA."

The compound [Fe2L3]4+ is an iron triple helicate with three organic strands wrapped around two iron centres to give a helix which looks cylindrical in shape and neatly fits within the major groove of a DNA helix. It is about the same size as the parts of a protein that recognise and bind with particular sequences of DNA. The high positive charge of the compound enhances its ability to bind to DNA which is negatively charged.

When the iron-helicate binds to the major groove of DNA it coils the DNA so that it is no longer available to bind to anything else and is not able to drive biological or chemical processes. Initially the researchers focused on the application of this useful property for targeting the DNA of cancer cells as it could bind to, coil up and shut down the cancer cell's DNA either killing the cell or stopping it replicate. However the team quickly realised that it might also be a very clever way of targeting drug-resistant bacteria.

New research at the University of Warwick, led by Dr Adair Richards and Dr Albert Bolhuis, has now found that the [Fe2L3]4+ does indeed have a powerful effect on bacteria. When introduced to two test bacteria Bacillus subtilis and E. coli they found that it quickly bound to the bacteria's DNA and killed virtually every cell within two minutes of being introduced - though the concentration required for this is high.

The researchers will next try and understand how and why the compound can cross the bacteria cell wall and membranes. They plan to test a wide range of compounds to look for relatives of the iron helicate that have the same mechanism for action in collaboration with researchers around the world.

Collaborating in discovery of biomarkers

2009-06-08T13:01:00.000-07:00

Applied Biosystems announced that bioMérieux and researchers at the University of Lyon in France are collaborating on research to advance the discovery of biomarkers that can be used to diagnose or monitor disease. They are using next-generation, mass spectrometry technology with integrated triple quadrupole and linear accelerator trap to validate newly identified candidate biomarkers.

The scientists are deploying AB SCIEX QTRAP® 5500 Systems that rapidly quantify dozens of protein and peptide biomarkers in a single analysis. The AB SCIEX QTRAP 5500 System offers greater reproducibility and precision than other mass spectrometry platforms. According to AB, it provides faster and more specific results than the current clinical standard of antibody-based testing.

Biomarkers are indicators of the presence or progression of a disease that offer a quick and easy method for diagnosing or monitoring patients for a range of conditions, including cancers as well as infectious and degenerative diseases. Extensive research is required to clarify the exact role and significance of each newly discovered candidate biomarker, which is a process that can take several years to complete. The scientists from bioMérieux and the University of Lyon are combining their respective expertise in biomarker discovery and protein mass spectrometry to accelerate this biomarker validation process.

New Protein Research Center in Copenhagen

2009-06-08T12:47:00.000-07:00

This week, the University Copenhagen opened the doors of its new research center, The Novo Nordisk Foundation Center for Protein Research. The Center is the result of a historic donation from the Novo Nordisk Foundation, which in 2007 gave the University 80 million euros for its establishment.

The protein center will be housed in three recently renovated floors of the Panum Institute in Copenhagen. According to the unviersity, there will be over 150 international researchers with new labs and advanced instruments, and is aimed at becoming a leading center in the field of protein research.

Merkc & AstraZeneca collaborate in early stage drug discovery

2009-06-08T12:39:00.000-07:00

AstraZeneca and Merck & Co collaborate on a novel combination anticancer regimen composed of two investigational compounds, MK-2206 from Merck and AZD6244 from AstraZeneca.

Preclinical evidence indicates that combined administration of these compounds could enhance their anticancer properties. This is the first time that two large pharmaceutical companies have established a collaboration to evaluate the potential for combining candidate molecules at such an early stage of development. The collaboration will more quickly advance a potentially promising anticancer treatment. In general, such combinations would only be studied when one or both of the drugs has entered late-stage development or received marketing approval.

Under the terms of the agreement, AstraZeneca and Merck will work together to evaluate co-administration of the compounds in a Phase I clinical trial for the treatment of solid cancer tumors. All development costs will be shared jointly. Following the Phase I trial, the companies will consider opportunities for further clinical development.

Each candidate is designed to inhibit a protein known to be abnormally activated in human cancers. In preclinical studies, AZD6244 has been shown to affect MEK (Mitogen-activated protein kinase 1), an important signal that promotes cancer cell growth and survival. AZD6244 has completed Phase I evaluation, demonstrating proof of mechanism, and several Phase II monotherapy studies, which showed evidence of clinical activity. It is currently in Phase II clinical trials in a range of tumor types. Merck’s MK-2206 has demonstrated an effect on AKT, a component of the phosphatidylinositol-3 kinase pathway, an important signal promoting cancer cell survival.

New HIV microbicide -- and a way to mass produce it in plants?

2009-06-07T03:02:00.000-07:00

Research published online in The FASEB Journal (http://www.fasebj.org) describes how scientists from St George's, University of London have devised a one-two punch to stop HIV. First the report describes a new protein that can kill the virus when used as a microbicide. Then the report shows how it might be possible to manufacture this protein in quantities large enough to make it affordable for people in developing countries.

"We desperately need to control the spread of HIV, particularly in developing countries," said Julian Ma of the Department of Cellular and Molecular Medicine at St. George's and the senior researcher involved in the work. "A vaccine is still some way off, but microbicides could provide a more immediate solution, provided we can overcome major hurdles of high efficacy, low cost, and wide availability—all of which we address in this study."

In the research paper, Ma and colleagues describe how they combined two protein microbicides (b12 monoclonal antibody and cyanovirin-N) into a single "fusion" molecule and showed that this molecule is more active against HIV than either of its individual components. They designed synthetic DNA for producing this molecule and introduced this DNA into plant cells. After regenerating transgenic plants that produce the fusion molecule, they prepared the microbicide from a plant extract made by grinding the leaves.

"This study is nothing short of a breakthrough—not only does it yield a new drug to fight the spread of HIV, but it also shows us how we can produce it on the scale necessary to get it into the hands of those who need it most," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Unlike their unregulated counterparts in the dietary supplement industry, these scientists are using the engines of nature to manufacture pharmaceuticals that must undergo extensive safety and efficacy testing long before the first gel or cream is administered."

2009-06-06T15:19:00.000-07:00

Johnson & Johnson will commence a cash tender offer to purchase all outstanding shares of common stock of Cougar Biotechnology, Inc. . Johnson & Johnson reported on May 21, 2009, its intent to acquire Cougar Biotechnology.

Upon the successful closing of the tender offer, shareholders of Cougar Biotechnology will receive $43.00 in cash for each share of Cougar Biotechnology common stock tendered in the offer, without interest and less any required withholding taxes. As a subsidiary of Johnson & Johnson, following the purchase of shares in the tender offer Cougar Biotechnology will work with Ortho Biotech Oncology Research & Development, a unit of Centocor Research & Development, Inc., a Johnson & Johnson company.

Today, Johnson & Johnson will file with the Securities and Exchange Commission (SEC) a tender offer statement on Schedule TO that provides the terms of the tender offer. Cougar Biotechnology will file with the SEC a solicitation/recommendation statement on Schedule 14D-9 that includes the recommendation of Cougar Biotechnology's board of directors that Cougar Biotechnology shareholders accept the tender offer and tender their shares to Johnson & Johnson. As previously disclosed, Cougar Biotechnology's board of directors has unanimously approved the transaction.

The tender offer will expire at midnight on July 2, 2009, unless extended in accordance with the merger agreement and the applicable rules and regulations of the SEC. The closing of the tender offer is conditioned on the tender of a majority of the outstanding shares of Cougar Biotechnology's common stock on a fully diluted basis. The closing is also conditioned on clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions.

Study on deep-sea corals on the ocean floor

2009-06-06T15:10:00.000-07:00

On 8 June, World Oceans Day, a team of scientists including biologist Thomas Shirley of the Harte Research Institute at Texas A&M University in Corpus Christi will begin a 16-day 'Finding Coral' expedition off the coast of British Columbia, Canada. Shirley and other crew members will use Deep Worker mini-submersibles to study deep-sea corals on the ocean floor. Shirley tells Nature News why corals matter, why piloting the Deep Worker is like driving a sports car, and how the sea floor is like Las Vegas.

See the story in Nature magazine here.

New FT-IR Spectrophotomer

2009-06-06T14:44:00.000-07:00

PerkinElmer launched the Spectrum 100S, a new infrared (FT-IR) spectrometer offering increased productivity and enhanced sensitivity for the analysis of even the most difficult samples.

Infrared (FT-IR) is used primarily in the chemical, pharmaceutical and academic research industries to identify or validate raw materials and to examine the properties and performance of novel materials and their component parts. With a 50% increase in sensitivity over the previous Spectrum 100 model, the new Spectrum 100S spectrometer can analyze materials in applications that previously required a specialized detector. In addition, it can also increase productivity by reducing analysis time by up to 50% for most routine applications.

The 50% improved signal-to-noise performance of the Spectrum 100S delivers a sensitivity typically only associated with specialized instruments costing approximately 40% more. The instrument also benefits from the patented Advanced Atmospheric Compensation feature that removes spectral interference from water and carbon dioxide and can eliminate the need to take reference spectra before running an analysis, and the exclusive Automatic Virtual Instrument (AVI) function, which enables easy method transfer from one instrument to another.