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February 13, 2007, 7:51 PM CT

Protein targets antibiotic-resistant bacteria

Protein targets antibiotic-resistant bacteria
A new type of protein discovered by Queens University scientists may be useful in developing therapys for antibiotic-resistant bacteria, such as those that cause food poisoning and typhoid.

By solving the structure and activity of the protein called YihE or RdoA a team of professors and students from the departments of Biochemistry and Microbiology & Immunology has opened up possibilities for new drug development.

Our group is the first to solve the structure and to begin to understand the function of this particular protein, says Dr. Nancy Martin (Microbiology & Immunology), who coordinated the study with Dr. Zongchao Jia (Biochemistry). It turns out to be a potentially good target in a wide range of bacteria that cause infectious diseases. Because of the increasing number of antibiotic-resistant strains of a number of different types of bacteria, such as salmonella, she notes, new approaches to antibiotic treatment are needed.

The Queens findings appear in the on-line edition of the journal Molecular Microbiology.

Also on the team, from Biochemistry, are PhD student Jimin Zheng and post-doctoral fellow Vinay Singh; and Microbiology & Immunology Masters student Chunhua He.

The group is studying sensory pathways used by bacteria that enter our bodies and move from the stomach into the gastro-intestinal tract. If we can block the sensory pathway, then the bacteria cant adapt to that change in their environment, and wont be able to infect, says Dr. Martin.........

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February 9, 2007, 4:33 AM CT

New Model for Testing and Discovery of Anti-HIV Drugs

New Model for Testing and Discovery of Anti-HIV Drugs
Scientists at the University of Pennsylvania School of Medicine are the first to show that a mouse protein, whose human equivalent is correlation to defense against HIV-1, inhibits the infection and spread of a mouse tumor virus. The study, which appeared online January 28 in advance of its print publication in Nature, provides a new model for the discovery and evaluation of anti-HIV drugs. HIV-1, like the mouse tumor virus, is a retrovirus which infects immune system cells. However, unlike HIV-1, the mouse virus causes breast cancer in mice.

"Our study is the first to show that the mouse equivalent to the human protein, called APOBEC3, actually inhibits a retrovirus in a live animal," says lead author Susan R. Ross, PhD, Professor of Microbiology. The study is based on a mouse strain that does not have the gene for mouse APOBEC3, developed by co-author Boris Matija Peterlin, PhD, University of California at San Francisco.

In this study, normal mice and mutant mice were injected with mouse mammary tumor virus (MMTV). Using a sensitive test for virus infection, the scientists observed that lymph nodes from mutant mice were more infected than normal mice. At six days after injection, the lymph nodes near the injection site in mutant mice had four times more of the breast cancer-causing virus. By 18 days after infection, the virus had spread to other sites in the mice, and spleen cells from the mutant mice were seven-fold more infected by MMTV than spleen cells from normal mice. The research team is currently waiting to see if mutant mice develop breast cancer at a greater rate than normal mice.........

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February 7, 2007, 9:12 PM CT

Better Control Of Hemorrhagic Fever Viruses

Better Control Of Hemorrhagic Fever Viruses
Scientists report discovering the receptor through which a group of life-threatening hemorrhagic fever viruses enter and attack the body's cells, and show that infection can be inhibited by blocking this receptor. The findings, would be published online by the journal Nature on February 7, give a clue to the high lethality of New World arenaviruses, suggest a way of reducing the severity of infection, and point the way toward a sorely needed therapy strategy.

The four viruses, known as the Machupo, Guanarito, Junin and Sabia viruses, cause Bolivian, Venezuelan, Argentine and Brazilian hemorrhagic fever, respectively, with mortality rates of about 30 percent. No vaccine is available, though a weakened form of Junin virus has been given to Argentinean farmers with some success. In addition to causing occasional disease outbreaks, mostly in poor, rural areas of South America, the viruses are of U.S. government interest because of their potential as bioterrorism agents. All four are classified as NIAID Category A Priority Pathogens and must be handled in Biosafety Level 4 containment facilities.

The researchers, led by Hyeryun Choe, PhD, of Children's Hospital Boston's Pulmonary Division, and Michael Farzan, PhD, of Harvard Medical School (HMS), first investigated the Machupo virus. To identify its cellular receptor, they made copies of the "spike" protein, used by the virus to gain entry into cells, and added it to cells from African green monkeys, known to be highly susceptible to Machupo virus infection. Later, they broke the cells open and isolated the spike protein and the cellular protein to which it had attached itself. Then, using a technique called mass spectrometry, they analyzed this attached cellular protein to determine its identity.........

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February 6, 2007, 9:46 PM CT

AIDS vaccines demonstrate potential to protect

AIDS vaccines demonstrate potential to protect
GeoVax Labs, Inc, an Atlanta-based biotechnology company, today reported successful results from a preclinical trial using GeoVax's vaccines for the therapeutic therapy and prevention of Acquired Immunodeficiency Disease Syndrome ("AIDS") in non-human primates. The data demonstrate the effectiveness of GeoVax's DNA/MVA vaccines in controlling the Simian ("SIV") AIDS virus through immune responses raised by the vaccines. These promising results have resulted in preliminary plans to conduct human therapeutic studies utilizing GeoVax's vaccines.

In this trial, two monkeys were infected with the SIV AIDS virus and then placed on drug treatment. Thereafter, once early drug treatment had temporarily reduced virus levels, the monkeys were vaccinated with the SIV version of GeoVax's DNA/MVA vaccines. Six weeks after vaccination, drug therapy was discontinued. The SIV virus levels temporarily rose in the vaccinated individuals, but were later "controlled" (reduced to much lower levels) by immune responses raised by the vaccines.

The reduction of virus levels in the blood stream of these AIDS virus-infected non-human primates has continued for more than a year to date. Vaccination with the GeoVax DNA/MVA vaccines has curtailed the development of AIDS and its associated debilitating effects, resulting in healthy, asymptomatic individuals. The monkeys have gained weight and have not mandatory any additional drug treatment.........

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February 5, 2007, 7:41 PM CT

Secret Of 1918 Influenza Virus

Secret Of 1918 Influenza Virus
In a study of non-human primates infected with the influenza virus that killed 50 million people in 1918, an international team of researchers has found a critical clue to how the virus killed so quickly and efficiently. The group was led by University of Wisconsin-Madison virologist Yoshihiro Kawaoka, and includes Michael Katze, professor of microbiology at the University of Washington, and colleagues here.

Writing in the Jan. 18 issue of the journal Nature, the team reports how the virus -- modern history's most savage influenza strain -- unleashes an immune response that destroys the lungs in a matter of days leading to death.

The finding is important because it provides insight into how the virus that swept the world in the closing days of World War I was so efficiently deadly, claiming as a number of of its victims people in the prime of life. The work suggests that it may be possible in future outbreaks of highly pathogenic flu to stem the tide of death through early intervention, and it proves that the virus was different from all of the other flu viruses currently studied.

The new study, conducted at the Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba, utilized the 1918 flu virus, which has been reconstructed by scientists using genes obtained from the tissues of victims of the great pandemic in a reverse genetics process that enables researchers to make fully functioning viruses. The research gives clues into the longstanding mystery of why the 1918 flu was so deadly, and it will help researchers better understand all influenza viruses and their ability to cause pandemics.........

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January 31, 2007, 8:30 PM CT

Promise In Halting HIV Spread

Promise In Halting HIV Spread
A new compound has shown promise in halting the spread of HIV by preventing the virus from replicating. Developed by Temple University researchers, 2-5AN6B could someday work as an effective therapy for HIV particularly in conjunction with current drug therapys. Their work is reported in the recent issue of AIDS Research and Human Retroviruses.

A nucleic acid, 2-5AN6B inhibited HIV replication in white blood cells from a group of 18 HIV infected patients by up to 80 percent, regardless of the patients' therapy regimens.

"A cure for HIV infection remains an elusive goal despite the significant impact of current therapys because of the virus' ability to adapt to and resist those therapys, and bypass the immune system's natural defenses," said Robert J. Suhadolnik, Ph.D., prinicipal investigator and professor of biochemistry at Temple University School of Medicine. "This compound prompts the body to restore its natural antiviral defense systems against the invading virus."

Current drugs for HIV work by blocking one of the steps toward virus replication.

"This new anti-HIV compound works by a very different mechanism, and would appear to offer the promise of someday being combined with existing anti-viral therapies for a much more effective therapy. It is also very important that this compound is much less likely to be defeated by the ability of the virus to mutate, a problem often encountered with existing anti-viral drugs," said Thomas Rogers, Ph.D., co-author and professor of pharmacology at Temple.........

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January 16, 2007, 8:12 PM CT

Antivirals Fights Influenza Virus

Antivirals Fights Influenza Virus
Two antiviral drugs, oseltamivir and zanamivir, are highly effective when given as a preventive measure to reduce the spread of the influenza virus, as per an analysis of household-based studies by scientists at Fred Hutchinson Cancer Research Center, University of Michigan and University of Virginia, reported in the current print edition of the American Journal of Epidemiology. The analysis also suggests that therapy with oseltamivir may reduce the infectiousness of influenza patients, eventhough further studies are needed to provide a definitive conclusion.

"Preventing the spread of influenza within families is an essential part of influenza management, regardless of the strain. This study shows that there is a clear benefit to be gained by giving antivirals to people who have been exposed to the virus to prevent the onset of symptomatic illness," said lead author M. Elizabeth (Betz) Halloran, M.D., D.Sc., a Hutchinson Center-based biostatistician.

"While the efficacy of antivirals to protect against influenza is critical, the effect of these drugs on infectiousness also has important public-health consequences. Further studies to determine antiviral efficacy for reducing infectiousness would therefore be of great value," said Halloran, a member of the Hutchinson Center's Public Health Sciences Division and a professor of biostatistics at the University of Washington School of Public Health and Community Medicine.........

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January 15, 2007, 9:42 PM CT

Smoking Increases Risk Of Tuberculosis

Smoking Increases Risk Of Tuberculosis
Tuberculosis (TB) is an infectious disease that causes an estimated 2 million deaths each year. The majority of those deaths occur in developing countries, home to more than 900 million of the world's 1.1 billion smokers. In addition, about half of the world's people cook and heat their homes with coal and biomass fuels such as wood, animal dung and charcoal, which generate indoor air pollution. In a new study, scientists from the Harvard School of Public Health (HSPH) undertook a systematic review and meta-analysis of epidemiologic data to quantitatively assess the association between smoking, passive smoking and indoor air pollution and TB. They found consistent evidence that smoking is linked to an increased risk of TB; they also observed that passive smoking (secondhand smoke) and the burning of biomass fuels was linked to an increased TB risk.

The study appears online on January 16, 2007, in the open-access journal PLoS Medicine.

"The evidence suggests that, when in comparison to non-smokers, smokers have about double the risk of tuberculosis. The implication for global health is critical," said Megan Murray, associate professor of epidemiology at HSPH. "Since tobacco smoking has increased in developing countries where TB is prevalent, a considerable portion of the global burden of TB may be attributed to tobacco. Importantly, this also implies that smoking cessation might provide benefits for global TB control in addition to those for chronic diseases."........

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January 15, 2007, 9:21 PM CT

Programmed Cell Death

Programmed Cell Death Neutrophil granulocytes have trapped Shigella bacteria in NETs.
Image: Dr. Volker Brinkmann, Max Planck Institute for Infection Biolog
They are the largest group of white blood cells: neutrophil granulocytes kill microorganisms. Neutrophils catch microbes with extracellular structures nicknamed Neutrophil Extracellular Traps (NETs) that are composed of nucleic acid and aggressive enzymes. A group of researchers lead by Arturo Zychlinsky at the Max-Planck-Institute for Infectious Biology in Berlin, Gera number of discovered, how the neutrophils form this snaring network (Journal of Cell Biology, online, January 8, 2007). Once triggered, the cells undergo a novel program leading to their death. While they perish, the cells release the content of their nuclei. The nucleic acid, mingled with bactericidal enzymes, forms a lethal network outside the cell. Invading bacteria and pathogenic fungi get caught and killed in the NETs.

Every minute, several million neutrophils leave the bone marrow and are ready to defend the body of invading germs. They are the immune system's first line of defence against harmful bacteria and migrate into the tissue at the site of infection to combat pathogens. For more than hundred years it was known that neutrophil granulocytes kill bacteria very efficiently by devouring them. After eating the germs neutrophils kill tehm with antimicrobial proteins.

The group of researchers lead by Arturo Zychlinsky at the Max-Planck-Institute for Infectious Biology discovered a second killing mechanism: neutrophil granulocytes can form web-like structures outside the cells composed of nucleic acid and enzymes which catch bacteria and kill them. The researchers were able to generate impressive micrographs of these nets. But it remained a mystery how the granulocytes could mobilise the contents of their nuclei and catapult it out of the cells.........

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January 7, 2007, 9:13 PM CT

New HIV test To predict drug resistance

New HIV test To predict drug resistance The test identifies which drug-resistant strains of HIV are harbored in a patient's bloodstream.
Credit: Duke University Medical Center News Offic
Scientists at Duke University Medical Center have developed a highly sensitive test for identifying which drug-resistant strains of HIV are harbored in a patient's bloodstream.

The test may provide physicians with a tool to guide patient therapy by predicting if a patient is likely to become resistant to a particular HIV drug, said one of its developers, Feng Gao, M.D., associate professor of medicine. Drug resistance is one of the most common reasons why treatment for HIV, the virus that causes AIDS, fails.

The test, which detects genetic changes, or mutations, in HIV, also may help researchers understand how the constantly evolving virus develops drug resistance, Gao said. He said such knowledge ultimately may result in the development of new therapys designed to evade resistance.

The findings will appear online on Sunday, Jan. 7, 2007, in the journal Nature Methods, as well as in the journal's February 2007 print edition. The work was supported by the National Institutes of Health and the Duke Center for AIDS Research.

Duke has filed for a provisional patent on the technology, and the scientists are considering ways to establish a new company to pursue its development or to license the technology to an existing company, Gao said.

Because HIV genes mutate so easily and the virus reproduces so rapidly, most people who are infected have a number of different forms of the virus in their bodies. In some cases, mutated strains take on new properties that make them more resistant to the drugs used in antiretroviral treatment, the primary means of therapy for HIV infection.........

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Did you know?
Scientists at Baylor College of Medicine in Houston have found a genetic marker that may identify individuals at greater risk for life-threatening infection from the West Nile virus. Results of the study are reported in the Nov. 15 print edition of Journal of Infectious Diseases. Archives of infectious disease blog

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