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Archive for October 30th, 2006

New Protective Action For Powerful Anti-HIV Factor Identified

Posted by tumicrobiology on October 30, 2006

Scientists at the Gladstone Institute of Virology and Immunology (GIVI) have identified a previously unknown function of APOBEC3G (A3G), a protein that acts against HIV, a finding that may lead to new approaches for controlling HIV infection.

The work is published today, Oct. 2, 2006, in Proceedings of the National Academy of Sciences, USA.

The research, conducted by scientists in the laboratory of GIVI Director Warner C. Greene, MD, PhD, explains why CD4 T cells — the immune system cells targeted by HIV — are sometimes so susceptible to HIV infection and at other times are highly resistant.

Scientists have known that resistant CD4 T cells, called “resting cells,” are made up predominantly of CD4+ T cells that are in an inactive state, awaiting a stimulus to move into action. In these cells, A3G blocks HIV at an early step in its life cycle. However, when resting CD4 T cells are stimulated by a foreign protein or other signal, A3G is rapidly recruited into large RNA protein complexes within the cells. This change neutralizes the anti-HIV properties of A3G, opening the door to HIV infection.

In the current study, the researchers set out to decipher the protein and RNA components of the A3G RNA protein complexes. In so doing, Ya-Lin Chiu, PhD, a postdoctoral fellow in Greene’s laboratory, determined that the complexes help to prevent a threat within cells posed by a class of “jumping genes,” or retro-elements, which are sequences of DNA that change position within the genome, causing mutations, activating or inactivating other genes, or duplicating themselves, thereby increasing the quantity of DNA in each cell.

As with HIV, the replication and movement of these retro-elements to new chromosomal sites with potentially damaging effect involves copying DNA into RNA and then back into DNA again. The A3G RNA protein complex, Chiu determined, interrupts this retro-element replication cycle by binding the retro-element RNAs and sequestering them in the cytoplasm away from the nuclear machinery required for copying the RNA back into DNA and inserting the retro-element at a new chromosomal site.

Understanding A3G’s role in activated CD4 T cells could lead to a new strategy against HIV.

“If we can find a way to partially block A3G assembly into the large complexes during CD4 T cell activation, we could both preserve the potent anti-HIV effect of the small form of A3G and the protective function of the large A3G complex against select mobile genetic elements,” Greene said. Gladstone scientists are now exploring various ways to achieve this desired balance.

Other authors on the study were Gladstone postdoctoral fellows Mario Santiago PhD, and Vanessa B. Soros, PhD, and H. Ewa Witkowska and Steven C. Hall of the University of California, San Francisco, and Cécile Esnault and Thierry Heidmann from the Institut Gustave Roussy in Villejuif, France. Funding for the study came from the National Institutes of Health, San Francisco Women’s HIV Interdisciplinary Network, the American Foundation for AIDS Research, UCSF-GIVI Center for AIDS Research, Ligue Nationale Contre le Cancer, Sandler Family Foundation and the J. David Gladstone Institutes. The Gladstone Institute of Virology and Immunology is one of three research institutes of The J. David Gladstone Institutes, a private, nonprofit biomedical research institution. It is affiliated with UCSF, a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the health professions and life sciences, and providing complex patient care.

Source: University of California – San Francisco
Date: October 30, 2006

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Headway Against Hepatitis C: Study Shows Liver Damage Can Be Reversed

Posted by tumicrobiology on October 30, 2006

Saint Louis University Liver Center scientists are presenting research today on a more effective way to treat hepatitis C patients who have been unresponsive to current drug therapies.

They have shown that a cocktail of ribavirin and Infergen, a highly potent Interferon, is nearly twice as effective at controlling hepatitis C than standard treatments.

They are sharing their findings at the annual American Association for the Study of Liver Diseases meeting in Boston.

“The results are promising,” says Bruce R. Bacon, M.D., principal investigator and director of the division of gastroenterology and hepatology at Saint Louis University School of Medicine. “This group of non-responders is a very challenging population to treat, and we found that patients who followed through with the therapy had a response nearly twice that of previous trials looking at this population.”

Saint Louis University Liver Center researchers led a study of more than 500 patients with hepatitis C at 40 sites, 77 percent of whom had advanced fibrosis. Fourteen percent of patients taking 9mcg of Infergen daily and 20 percent taking 15 mcg were virus negative after six months.

A quarter of the non-cirrhotic patients receiving Infergen were also virus negative after 24 weeks. The optimal response to antiviral therapy is for the hepatitis C viral RNA to become undetectable on treatment and to remain undetectable for at least another six months off therapy; this is referred to as a sustained virologic response, essentially a cure of the disease. Rates of sustained virologic response are still to be determined in this ongoing study.

Infergen is a highly potent type of interferon currently used for adult patients with chronic hepatitis C three times a week, Bacon says. This trial is expected to be completed in 2007.

An estimated 3.9 million Americans have hepatitis C. About 250,000 who have been offered therapy are unresponsive to current drug therapies, and the number is growing by 50,000 annually, according to the CDC.

Second Study Shows Liver Damage Can Be Reversed

In another study being presented at the AASLD conference, SLU researchers found that liver damage may be able to be reversed in patients with chronic hepatitis C who have undergone successful therapy.

“They are not only at a very low risk for relapse but may also see improvements to their liver,” says lead author Adrian Di Bisceglie, M.D., professor in the division of gastroenterology and hepatology at Saint Louis University School of Medicine.

Researchers studied the long-term effects in 150 patients with chronic hepatitis C following therapy. The level of liver damage in 79 percent of patients with stage 2 or worse fibrosis greatly improved and was unchanged in the rest of the patients.

“Little is known about how these patients fare after their treatment,” says Di Bisceglie, M.D., also acting chair of the department of internal medicine at SLU. “This is the largest study of its kind to examine just how much improvement patients with hepatitis C have five years after a sustained virologic response, and the results are very encouraging.”

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Oldest Complex Organic Molecules Found In Ancient Fossils

Posted by tumicrobiology on October 30, 2006

Ohio State University geologists have isolated complex organic molecules from 350-million-year-old fossil sea creatures — the oldest such molecules yet found.

The molecules may have functioned as pigments, but the study offers a much bigger finding: an entirely new way to track how species evolved.

Christina O’Malley, a doctoral student in earth sciences at Ohio State, found orange and yellow organic molecules inside the fossilized remains of several species of sea creatures known as crinoids. The oldest fossils in the study date back to the Mississippian period.

She reported the find Wednesday at the meeting of the Geological Society of America in Philadelphia.

Crinoids still exist today. Though they resemble plants, they are marine animals. They cling to the seafloor and feast on plankton that float by.

The crinoids in this study had flower-like fronds capping skinny stalks about six inches high — a look resembling “starfish on a stick,” said William Ausich, professor of earth sciences and O’Malley’s co-advisor with Yu-Ping Chin, also a professor of earth sciences.

Today’s crinoids display a range of colors, some variegated shades of red, orange, and yellow, so the geologists weren’t surprised that some of those colors turned up in the 350-million-year-old crinoids, Ausich said.

“People have suspected for a long time that organic molecules could be found inside fossils,” he added. “This is just the first time that scientists have succeeded in finding them.”

Though the organic molecules could be classified as pigments, nobody can be sure that they functioned as pigments inside these ancient animals, the geologists emphasized. They may have served some other purpose besides coloration — perhaps to defend the animal from predators by making it less palatable.

Because the molecules appear to be a little different for each species of crinoid, scientists can now use the pigments as biomarkers to map relationships on the creatures’ family tree. Until now, they could only infer crinoid lineage based on the size and shape of key features on the animals’ skeletons.

“This could be a new tool for figuring out how long-dead creatures became so prolific and successful. We can’t travel back in time, but now we can look for clues about these creature’s lives in a way that hasn’t been attempted or taken advantage of before,” O’Malley said.

Scientists can only view fossilized plants and animals in the grays and tans of sedimentary rock, such as the limestone fossils in this study. Rock is inorganic, and replaces organic molecules such as pigments during fossilization. What O’Malley and her colleagues discovered is that some organic molecules occasionally survive the process.

“Crinoid skeleton is very porous, and we think that when inorganic molecules filled in the spaces of the skeleton during preservation, some of the organic molecules were trapped inside the fossil,” she said.

O’Malley found pigments in every crinoid specimen that she sampled from three fossil sites, one in Switzerland and two in Indiana.

The Indiana samples date back to 350 million years ago, during the Mississippian period, when much of North America was covered by a shallow inland sea. The Switzerland fossils date back to 60 million years ago, during the Jurassic period. The sites preserved the crinoids exceptionally well, probably because a sudden storm buried them in sediment.

Should pigments be found in other fossils, the technique could prove to be a reliable way to trace species’ evolution. So far, the crinoid biomarkers mesh well with scientists’ concepts of how those species are related.

O’Malley isolated the pigments by grinding up small bits of fossil and dissolving the organic molecules into a solution. Then she injected a tiny sample of the solution into a machine called a gas chromatograph mass spectrometer. The machine vaporized the solution so that a magnet could separate individual molecules based on electric charge and mass. Computer software then identified the molecules.

Orange and yellow organic molecules emerged, along with several other molecules that the geologists have yet to identify. The off-the-shelf software was only designed to identify common laboratory compounds, O’Malley explained. She would like to generate her own database of fossil organic molecules, and also extract pigments from other marine fossils, including some from sites in Iowa.

Source: Ohio State University

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Social Amoebas’ Family Tree Reveals Evolutionary Clues

Posted by tumicrobiology on October 30, 2006

The full family tree of the species known as social amoebas has been plotted for the first time – a breakthrough which will provide important clues to the evolution of life on earth.

Researchers, headed by evolutionary biologist Professor Sandie Baldauf, of the University of York, and biochemist Professor Pauline Schaap, of the University of Dundee, have produced the first molecular ‘dictionary’ of the 100 or so known species of social amoeba.

Using this family tree, they have devised a model system to establish how single cell organisms communicate and interact to create multi-cellular structures in response to changing environmental conditions. Previously, there was almost no molecular data for social amoeba – Dictyostelia – which are a hugely diverse and ancient group.

Social amoebas are a group of organisms with a genetic diversity that is greater than that of fungi and similar to that of all animals. They offer an excellent experimental system for studying aspects of evolution and communication that are not easy to study in more complex multi-cellular organisms.

The York and Dundee teams have worked with field biologists in Germany, the US and Japan, and their research is published today (Friday 27 October 2006) in the prestigious international journal Science.

The published paper shows for the first time the family tree of all known social amoeba species and the evolution of their multicellular life style.

“This provides a starting point in allowing us to examine what happens at the molecular level as species evolve and mutate,” said Professor Schaap, of the Division of Cell and Developmental Biology in the College of Life Sciences at Dundee.

“The availability of a family tree allows us to reconstruct the evolution of the signalling mechanisms that generate multicellularity. It also provides a powerful tool to identify core ancestral processes that regulate the most basic aspects of development.”

Professor Baldauf, of the Department of Biology at York, said: “We have investigated the evolution of plants and animals for a very long time but our whole eco-system depends on single cell organisms. If we want to look at the fundamentals of life we have to look at single cell organisms.

“Amoebas are some of the closest single cell relatives of animals so understanding how they work and evolve is important because it helps us to understand how animals evolve. We have developed a new model system for the study of the evolution of forms.

“We have written the dictionary. Now we know what the words are – but we still have to construct the sentences.”

The research teams were able to build the family tree by amplifying and comparing highly conserved genes from all known species of social amoeba.

The existing family tree of the social amoeba was based on how the multicellular structures of each species look on the outside. However, this tree was completely uprooted by the molecular data gathered by the researchers in Dundee and York.

By plotting all existing information of the amoebas’ cellular and multi-cellular shapes and behaviour to the molecular tree, it appeared that increased cell specialization and organism size is a major trend in the evolution of social amoeba.

Professor Schaap and her team are now working to establish how the regulation and function of genes with important roles in development was altered and elaborated during the course of evolution to generate novel cell-types and morphological features.

The next step for Professor Baldauf and her team will be to investigate the origin of these amoebas, and also to search for new species and to establish their position on the family tree. Meanwhile, a number of research projects, including teams in the USA and Germany, have won sponsorship to sequence the genomes of social amoeba species identified by the work in York and Dundee.

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Enzyme involved in allergic diseases found

Posted by tumicrobiology on October 30, 2006

A U.S. research team says it has identified an enzyme involved in allergic reactions, possibly providing a new target for the treatment of such maladies.

The scientists from Virginia Commonwealth University, the Hospital for Special Surgery and Weill Cornell Medical College in New York note allergic diseases such as asthma and hay fever afflict about 30 percent of people in the developed world — and allergic reactions are the sixth leading cause of chronic disease in the United States.

The team has demonstrated, for the first time, the role of a proteolytic enzyme called ADAM10 that releases a major allergy regulatory protein from the surface of cells and, thereby, promotes a stronger allergic response.

“Our research, for the first time, may represent a treatment strategy to prevent, rather than simply control, IgE-mediated allergy,” said VCU Professor Daniel Conrad. IgE is an antibody known to trigger Type I allergic disease. “Understanding ADAM10’s role in allergic disease makes it a potential target for the design of drugs to treat asthma and allergic disease.”

The research appears online in the journal Nature Immunology.

Copyright 2006 by United Press International. All Rights Reserved.

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Study: Biofuel cells without the bio cells

Posted by tumicrobiology on October 30, 2006

U.S. scientists say proteins rendered portable from the organisms that spawned them might make miniature bioreactor cells feasible.

Researchers at the U.S. Department of Energy’s Pacific Northwest National Laboratory say they have become the first to measure electrical charges shuttled by proteins removed from living cells.

The scientists say some proteins are enzymes that taxi electrons to chemicals outside the cell, to discharge excess energy generated during metabolism. That maintains energy flow in the cell and, in turn, keeps the cell alive.

Now, the scientists say for the first time they have observed that electricity-shuttling process taking place sans cells, in purified proteins removed from the outer membrane of the versatile, metal-altering soil bacterium Shewanella oneidensis.

“We show that you can directly transfer electrons to a mineral using a purified protein and I don’t think anyone had shown that before,” said Thomas Squier, senior author of the study.

The research appears in the current issue of the Journal of the American Chemical Society.

Copyright 2006 by United Press International. All Rights Reserved.

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New microscope used for nano research

Posted by tumicrobiology on October 30, 2006

U.S. scientists are using a new form of scanning microscopy to simultaneously study physical and electronic profiles of metal nanostructures.

Researchers at the National Institute of Standards and Technology and University of Colorado-Boulder say the new instrument — the scanning photoionization microscope — is expected to be particularly useful for analyzing the make-up and properties of nanoscale electronics and nanoparticles.

The scientists said the instrument combines the high spatial resolution of optical microscopy with the high sensitivity to subtle electrical activity made possible by detecting the low-energy electrons emitted by a material as it is illuminated with laser pulses.

The technique potentially could be used to make pictures of both electronic and physical patterns in devices such as nanostructured transistors or electrode sensors, or to identify chemicals or even elements in such structures.

“You make images by virtue of how readily electrons are photoejected from a material,” said NIST fellow David Nesbitt, leader of the research group. “The method is in its infancy, but nevertheless it really does have the power to provide a new set of eyes for looking at nanostructured metals and semiconductors.”

The instrument is described in the journal Chemical Physics.

Copyright 2006 by United Press International. All Rights Reserved.

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