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February 1, 2010, 7:42 AM CT

HIV researchers solve key puzzle

HIV researchers solve key puzzle
Scientists have made a breakthrough in HIV research that had eluded researchers for over 20 years, potentially leading to better therapys for HIV, as per a research findings published recently in the journal Nature

The researchers, from Imperial College London and Harvard University, have grown a crystal that reveals the structure of an enzyme called integrase, which is found in retroviruses like HIV. When HIV infects someone, it uses integrase to paste a copy of its genetic information into their DNA.

Previous to the newly released study, which was funded by the Medical Research Council and the US National Institutes of Health, a number of scientists had tried and failed to work out the three-dimensional structure of integrase bound to viral DNA. New antiretroviral drugs for HIV work by blocking integrase, but researchers did not understand exactly how these drugs were working or how to improve them.

Scientists can only determine the structure of this kind of molecular machinery by obtaining high quality crystals. For the newly released study, scientists grew a crystal using a version of integrase borrowed from a little-known retrovirus called Prototype Foamy Virus (PFV). Based on their knowledge of PFV integrase and its function, they were confident that it was very similar to its HIV counterpart.........

Posted by: Mark      Read more         Source


January 29, 2010, 8:24 AM CT

Stopping Schizophrenia Before It Starts?

Stopping Schizophrenia Before It Starts?
Adult "schizophrenic" rats (middle) have larger lateral ventricles than those of normal rats (left), but become smaller after preventive treatment with clozapine in adolescence (right).
The onset of schizophrenia is not easy to predict. Eventhough it is linked to as a number of as 14 genes in the human genome, the previous presence of schizophrenia in the family is not enough to determine whether one will succumb to the mind-altering condition. The disease also has a significant environmental link.

As per Prof. Ina Weiner of Tel Aviv University's Department of Psychology, the developmental disorder, which commonly manifests in early adulthood, can be triggered in the womb by an infection. But unlike developmental disorders such as autism, it takes a number of years for the symptoms of schizophrenia to develop.

"Pharmacological therapys for schizophrenia remain unsatisfactory, so clinicians and scientists like myself have started to dig in another direction," says Prof. Weiner. "The big question asked in recent years is if schizophrenia can be prevented".

Revolutionizing the therapy

In their study, recently reported in Biological Psychiatry, Prof. Weiner and her colleagues Dr. Yael Piontkewiz and Dr. Yaniv Assaf sought to discover biological cues that would help trace the progression of the disease before symptoms manifested. "If progressive brain changes occur as schizophrenia is emerging, it is possible that these changes could be prevented by early intervention," she says. "That would revolutionize the therapy of the disorder.........

Posted by: Daniel      Read more         Source


January 21, 2010, 8:22 AM CT

Older brains make good use of 'useless' information

Older brains make good use of 'useless' information
Toronto A newly released study has observed promising evidence that the older brain's weakened ability to filter out irrelevant information may actually give aging adults a memory advantage over their younger counterparts.

A long line of research has already shown that aging is linked to a decreased ability to tune out irrelevant information. Now researchers at Baycrest's world-renowned Rotman Research Institute have demonstrated that when elderly adults "hyper-encode" extraneous information and they typically do this without even knowing they're doing it they have the unique ability to "hyper-bind" the information; essentially tie it to other information that is appearing at the same time.

The study, which appears online this week in the journal Psychological Science, was led by Karen Campbell, a PhD student in psychology at the University of Toronto, with supervision from Rotman senior scientist Dr. Lynn Hasher, a leading authority in attention and inhibitory functioning in younger and elderly adults.

"We observed that older brains are not only less likely to suppress irrelevant information than younger brains, but they can link the relevant and irrelevant pieces of information together and implicitly transfer this knowledge to subsequent memory tasks," said Campbell.........

Posted by: Daniel      Read more         Source


January 15, 2010, 8:06 AM CT

Trial of new osteoporosis drug

Trial of new osteoporosis drug
Endocrinologists at the University of Pittsburgh School of Medicine and UPMC are launching a human trial of a new drug that their research indicates holds great promise for building bones weakened by osteoporosis.

For the study, 105 participants will be randomly assigned to receive either teriparitide ( Forteo), a drug that already is FDA-approved for osteoporosis therapy, or an experimental agent called parathyroid hormone-related protein (PTHrP), explained principal investigator Mara J. Horwitz, M.D., an assistant Professor of Medicine in the Division of Endocrinology and Metabolism, Pitt School of Medicine, and a practicing metabolic bone specialist at UPMC.

"We are very eager to find out how this new drug compares to a treatment that is currently available," Dr. Horwitz said. "Our prior studies suggest that it may increase bone density more dramatically with fewer side effects, but this is the first head-to-head comparison".

On the cellular level, bone is constantly being broken down, a process known as resorption, and then rebuilt. In osteoporosis, this balancing act is off-kilter, leaving bones less dense and more vulnerable to fracture. A number of drugs, such as alendronate (Fosamax), and raloxifene (Evista), work by decreasing bone resorption. They can improve bone density by two to 10 percent over several years to a decade and reduce fractures, but a number of patients' bone density already has been reduced by half when therapy begins.........

Posted by: Scott      Read more         Source


January 13, 2010, 8:15 AM CT

How Melanoma Ivades Immune System

How Melanoma Ivades Immune System
Melanoma, if not detected in its early stages, transforms into a highly deadly, therapy-resistant cancer. Eventhough the immune system initially responds to melanoma and mounts anti-tumor attacks, these assaults are generally ineffective, allowing more advanced melanomas to win the battle and spread beyond the primary site. Now, scientists at Children's Hospital Boston and Brigham and Women's Hospital (BWH) shed light on how melanomas stimulate, yet ultimately evade, a patient's immune system. Their work, published online January 12 by the journal Cancer Research, also suggests ways drugs might block these tactics.

In 2008, the same team, led by Markus Frank, MD, of the Transplantation Research Center of Children's and BWH, and George Murphy, MD, chief of Dermatopathology at BWH, showed in the journal Nature that a key reason for melanoma virulence is a small group of tumor stem cells that are able to grow despite chemotherapy drugs, allowing the tumor to re-grow and progress. They also showed that targeting these cells (identifiable by a molecule on their surface known as ABCB5) could successfully inhibit tumor growth in mice. (The ABCB5 technology has been licensed and is currently in clinical drug development.)

In their new paper, first author Tobias Schatton, PhD, of the Transplantation Research Center, and his colleagues show that these ABCB5-positive cells also produce molecules that inhibit the body's natural immune attack, known as PD-1 and B7.2. These molecules work, they found, by triggering white blood cells known as regulatory T cells (T-regs), to dampen the normal anti-melanoma response. The T-regs are thus tricked into protecting the deadly melanoma stem cells from the body's own defenses.........

Posted by: George      Read more         Source


January 12, 2010, 8:56 AM CT

ADHD: Disconnect Between Brain Regions

ADHD: Disconnect Between Brain Regions
This research provides the first direct evidence that brain connectivity is missing in people with ADHD.
Two brain areas fail to connect when children with attention deficit hyperactivity disorder attempt a task that measures attention, as per scientists at the UC Davis Center for Mind and Brain and M.I.N.D. Institute.

"This is the first time that we have direct evidence that this connectivity is missing in ADHD," said Ali Mazaheri, postdoctoral researcher at the Center for Mind and Brain. Mazaheri and colleagues made the discovery by analyzing the brain activity in children with ADHD. The paper appears in the current online issue of the journal Biological Psychiatry.

The scientists measured electrical rhythms from the brains of volunteers, particularly the alpha rhythm. When part of the brain is emitting alpha rhythms, it shows that it is disengaged from the rest of the brain and not receiving or processing information optimally, Mazaheri said.

In the experiments, children with diagnosed ADHD and normal children were given a simple attention test while their brain waves were measured. The test consisted of being shown a red or blue image, or hearing a high or low sound, and having to react by pressing a button. Immediately before the test, the children were shown either a letter "V" to alert them that the test would involve a picture (visual), or an inverted "V" representing the letter "A" to alert them that they would hear a sound (auditory).........

Posted by: JoAnn      Read more         Source


January 11, 2010, 8:16 AM CT

Calcium and taste perception

Calcium and taste perception
Kokumi taste foods contain various compounds that have no taste themselves, but can enhance the basic sweet, salty and umami taste sensation they co-exist with. Kokumi compounds, such as calcium, protamine (found in milt), L-histidine (an amino acid) and glutathione (found in yeast extract) have now been shown to activate calcium-sensing channels in humans.

Credit: Ajinomoto Co. Inc.

Calcium may not come to mind when you think of tasty foods, but in a study appearing in the January 8 issue of JBC, Japanese scientists have provided the first demonstration that calcium channels on the tongue are the targets of compounds that can enhance taste.

In addition to molecules that directly trigger specific taste buds (salty, sweet etc.), there are other substances which have no flavor of their own but can enhance the flavors they are paired with (known as kokumi taste in Japanese cuisine).

Exploiting this enhancement could have practical uses in food modulation; for example, creating healthy foods that contain minimal sugar or salt but still elicit strong taste. At the moment, though, the mode of action for these substances is poorly understood.

However, Yuzuru Eto and his colleagues examined whether calcium channels which sense and regulate the levels of calcium in the body might be the mechanism involved; they noted that calcium channels are closely correlation to the receptors that sense sweet and umami (savory) tastes and that glutathione (a common kokumi taste element) is known to interact with calcium channels.

To test their possibility, they created several small molecules that resembled glutathione and analyzed how well these compounds activated calcium channels in cell samples. Next, they diluted the same test substances in flavored water (salt water, sugar water, etc.) and asked volunteers (all trained in discriminating tastes) to rate how strong the flavors were.........

Posted by: Scott      Read more         Source


January 11, 2010, 7:49 AM CT

Repairing a defective alcohol metabolism enzyme

Repairing a defective alcohol metabolism enzyme
An experimental compound repaired a defective alcohol metabolism enzyme that affects an estimated 1 billion people worldwide, as per research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The findings, published Jan. 10, 2010 in the advance online edition of Nature Structural and Molecular Biology, suggest the possibility of a therapy to reduce the health problems linked to the enzyme defect.

"This intriguing finding could have broad public health implications," said NIAAA Acting Director Kenneth R. Warren, Ph.D. "We look forward to further research aimed at translating these laboratory discoveries into possible therapys for people".

"We recently identified a molecule called Alda-1 that activates the defective enzyme, and in the current study, we determined how this activation is achieved," said the study's senior author, Thomas D. Hurley, Ph.D., professor and associate chairman of biochemistry and molecular biology at Indiana University School of Medicine in Indianapolis. Initial investigations of Alda-1 were led by co-author Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology at Stanford University School of Medicine.

After alcohol is consumed, it is first metabolized, or broken down, into acetaldehyde, a toxic chemical that causes DNA damage. Aldehyde dehydrogenase 2 (ALDH2) is the main enzyme responsible for breaking down acetaldehyde into acetate, a nontoxic metabolite in the body. It also removes other toxic aldehydes that can accumulate in the body.........

Posted by: Scott      Read more         Source


January 11, 2010, 7:47 AM CT

Genetic research related to ankylosing spondylitis

Genetic research related to ankylosing spondylitis
John D. Reveille, M.D., is the principal investigator of a new study on a disabling form of arthritis.

Credit: The University of Texas Health Science Center at Houston

Work done in part by scientists at The University of Texas Health Science Center at Houston has led to the discovery of two new genes that are implicated in ankylosing spondylitis (AS), an inflammatory and potentially disabling disease. In addition, the international research team pinpointed two areas along stretches of DNA that play an important role in regulating gene activity linked to the arthritic condition.

The findings, a critical milestone in the understanding of AS, are reported in the recent issue of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases. "This helps us better understand what is driving this disease and gives us direction for new therapys and diagnostic tests," said John D. Reveille, M.D., the study's principal investigator and professor and director of the Division of Rheumatology and Clinical Immunogenetics at The University of Texas Medical School at Houston.

Reveille, the university's Linda and Ronny Finger Foundation Distinguished Chair in Neuroimmunologic Disorders, and Matthew A. Brown, M.D., professor of immunogenetics at Australia's University of Queensland, led the research by the Triple "A" Spondylitis Consortium Genetic Study (i.e. the TASC or Australo-Anglo-American Spondylitis Consortium). Based on work from a genome-wide association scan, the team identified genes ANTXR2 and IL1R2 as well as two gene deserts, segments of DNA between genes on chromosomes 2 and 21 that are linked to ankylosing spondylitis. Importantly, the study also confirmed the Triple "A" Australo-Anglo-American Spondylitis Consortium's previously reported associations of genes IL23R and ERAP1, formerly known as ARTS1.........

Posted by: Mark      Read more         Source


January 5, 2010, 9:04 AM CT

Nano Cocktail to Target Tumors

Nano Cocktail to Target Tumors
Doxorubicin-loaded liposomes are designed to kill tumors.
A team of scientists in California and Massachusetts has developed a "cocktail" of different nanometer-sized particles that work in concert within the bloodstream to locate, adhere to and kill malignant tumors.

"This study represents the first example of the benefits of employing a cooperative nanosystem to fight cancer," said Michael Sailor, a professor of chemistry and biochemistry at the University of California, San Diego and the primary author of a paper describing the results, which is being published in a forthcoming issue of the Proceedings of the National Academy of Sciences. An early online version of the paper appeared last week.

In their study, the UC San Diego chemists, bioengineers at MIT and cell biologists at UC Santa Barbara developed a system containing two different nanomaterials the size of only a few nanometers, or a thousand times smaller than the diameter of a human hair, that can be injected into the bloodstream. One nanomaterial was designed to find and adhere to tumors in mice, while the second nanomaterial was fabricated to kill those tumors.

These researchers and others had previously designed nanometer-sized devices to attach to diseased cells or deliver drugs specifically to the diseased cells while ignoring healthy cells. But the functions of those devices, the scientists discovered, often conflicted with one another.........

Posted by: Janet      Read more         Source



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Did you know?
Scientists at Yale have brought to light a mechanism that regulates the way an internal organelle, the Golgi apparatus, duplicates as cells prepare to divide, according to a report in Science Express.Graham Warren, professor of cell biology, and colleagues at Yale study Trypanosoma brucei, the parasite that causes Sleeping Sickness. Like a number of parasites, it is exceptionally streamlined and has only one of each internal organelle, making it ideal for studying processes of more complex organisms that have a number of copies in each cell.

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