http://www.sciencecodex.com/scientists_learn_...h_imaging_technique-86425

[...] X-ray crystallography [...] has revealed the structure and function of many biological molecules, including vitamins, drugs, proteins and nucleic acids such as DNA. However, in order to obtain good data, large single crystals are required. These are often nearly impossible to grow. There also is the problem that X-rays damage delicate biological samples. "From the beginning, the resolution of images recorded by biologists has been limited by damage due to the radiation used," said physicist John C. H. Spence, a Regents' Professor in physics at Arizona State University. "But what happens if a pulse of imaging radiation is used that terminates before damage begins, yet contains sufficient photons to generate a useful scattering pattern?" Indeed, results of such a method are being reported [...] serial snapshot femtosecond (10-15 of a second) diffraction (SFX) from nanocrystals using the world's first hard X-ray laser. [...] "These are early days for femtosecond diffractive imaging," [...]

http://www.sciencecodex.com/vaccines_for_hiv_a_new_design_strategy-86675

Analysis of collective coevolution in HIV proteins suggests strategies for rational vaccine design

[...] researchers sought to identify independently evolving groups of amino acids where, within each group, amino acids mutate in tandem (meaning that they rely on one another to maintain the viability of the virus). In particular, they looked for groups of amino acids within which combinations of mutations would have a greater chance of making the virus unviable. By staging a multi-pronged attack against these regions of HIV, the researchers reasoned, they might be able to trap the virus between two bad choices: be destroyed by the immune system, or mutate and destroy itself.

With a mathematical tool called random matrix theory, the team searched for high-order evolutionary constraints in the so-called Gag region of HIV. The researchers were looking for collectively co-evolving groups of amino acids with a high number of negative correlations (meaning multiple mutations would destroy the virus) and a low number of positive correlations (meaning the virus could survive multiple mutations). They found this combination in a region, which they call Gag sector 3, that is involved in stabilizing the protein shell of the virus: too many mutations here, and the virus' structure would collapse.

Interestingly, when the team studied HIV-infected individuals whose bodies are naturally able to fend off the virus' attacks – so-called "elite controllers" – they found that these individuals' immune systems preferentially targeted Gag sector 3 over other proteins. [...]

I wonder if these Scripps Research scientists plan to leverage the World Community Grid?

http://www.bio-medicine.org/biology-news-1/Sc...y-news+%28Biology+News%29

"Date:2/24/2012

Scripps Florida team awarded nearly $1.5 million to develop potent new HIV inhibitors

JUPITER, FL A Scripps Florida team has been awarded nearly $1.5 million by the National Institutes of Health to identify and develop novel potent inhibitors of the human immunodeficiency virus (HIV), the cause of AIDS.

A. Donny Strosberg, a professor on the Florida campus of The Scripps Research Institute, is the principal investigator for the new three-year study.

Current treatments of HIV-infected patients are based on combinations of drugscalled cocktailsthat target several critical key steps in the early and late stages of the viral replication cycle. While these combinations have proven effective in controlling the infection in many patients, the continuous emergence of new multi-resistant viral strains requires the development of new classes of drugs that can be aimed at different targets on HIV.

Strosberg's target is the capsid protein or CA, the primary component of the HIV virion the infectious particle responsible for transporting the viral genome to host cells. This viral protein forms a cone-shaped shell around the HIV genome, and plays a critical role in the lifecycle of the virus by packaging and organizing the viral genome so that HIV can replicate efficiently.

"Because of the growing resistance of HIV against current treatments, a new, differently targeted approach to treating the disease is urgently needed," Strosberg said. "We expect to use the HIV capsid protein as a new high-throughput screening target for the discovery of novel anti-HIV/AIDS agents."

Identifying new compounds that could target the CA protein might make it possible to prevent the protein's assembly into capsid shells in the first place, blocking the virus's infectivity, and adding a potent complement to existing treatments, he said. This strategy has worked well for Strosberg's group, which has in the past years discovered several potent inhibitors of the hepatitis C virus.

Strosberg and his colleagues, who include Susana Valente, PhD, an assistant professor at Scripps Florida, and Massimo Caputi, PhD, an associate professor of biomedical science at the Florida Atlantic University Charles E. Schmidt College of Medicine, plan to perform an initial screening of some 350,000 compounds in the Molecular Libraries Probe Centers Network at Scripps Research; Scripps Research is one of only four such large probe centers nationwide."

http://www.eurekalert.org/pub_releases/2012-02/uoc--tlh021012.php

"Public release date: 10-Feb-2012

Tenofovir, leading HIV medication, linked with risk of kidney damage

Risk remains after drug use ends, say researchers, who call for patient monitoring

Tenofovir, one of the most effective and commonly prescribed antiretroviral medications for HIV/AIDS, is associated with a significant risk of kidney damage and chronic kidney disease that increases over time, according to a study of more than 10,000 patients led by researchers at the San Francisco VA Medical Center and the University of California, San Francisco (UCSF).

The researchers call for increased screening for kidney damage in patients taking the drug, especially those with other risk factors for kidney disease.

In their analysis of comprehensive VA electronic health records, the study authors found that for each year of exposure to tenofovir, risk of protein in urine – a marker of kidney damage – rose 34 percent, risk of rapid decline in kidney function rose 11 percent and risk of developing chronic kidney disease (CKD) rose 33 percent. The risks remained after the researchers controlled for other kidney disease risk factors such as age, race, diabetes, hypertension, smoking and HIV-related factors.

For individual patients, the differences in risk between users and non-users of tenofovir for each year of use were 13 percent vs. 8 percent for protein in urine, 9 percent vs. 5 percent for rapidly declining kidney function and 2 percent vs. 1 percent for CKD. "However, these numbers are based on the average risks in our study population, and patients with more risk factors for kidney disease would be put at proportionately higher risk," said principal investigator Michael G. Shlipak, MD, MPH, chief of general internal medicine at SFVAMC and professor of medicine and epidemiology and biostatistics at UCSF.

Patients were tracked for an average of 1.2 years after they stopped taking tenofovir. They remained at elevated risk for at least six months to one year compared with those who never took the drug, suggesting that the damage is not quickly reversible, said Shlipak. "We do not know the long-term prognosis for these patients who stop tenofovir after developing kidney disease," he cautioned.

The implications for patients already on or starting antiretroviral therapy are "mixed," said Shlipak. "The best strategy right now is to work with your health care provider to continually monitor for kidney damage. Early detection is the best way to determine when the risks of tenofovir begin to outweigh the benefits..."

http://www.washingtonpost.com/national/health.../21/gIQAyJ9aeR_print.html

[AIDS originated around 1908 in Kinshasha, capital city of the Democratic Republic of the Congo, as a result of the organized large-scale removal of African natural resources by European colonial authorities]