A team of researchers at the University of California, San Diego School of Medicine has uncovered a new signaling mechanism used to activate protein kinases that are critical for the body’s inflammatory response. Their work will be published in the July 18 online edition of Science (Science Express.).
“In addition to helping explain the basic mechanisms of transmembrane receptor signaling, these results may identify a potential therapy for interfering with inflammation,” said Michael Karin, Ph.D., professor of pharmacology and pathology in UC San Diego’s Laboratory of Gene Regulation and Signal Transduction.
The tumor necrosis factor (TNF) receptor (TNFR) family codes for a large number of cell surface receptors of great biomedical importance, and its signaling mechanisms have been the subject of intense investigation during the past decade. Specific inhibitors of TNF receptor 1 (TNFR1) activation are being used in the treatment of rheumatoid arthritis, psoriasis and inflammatory bowel disease, and receptor activator of NF-κB (RANK) inhibitors were recently found to be effective in the treatment of osteoporosis and other bone loss diseases.
Now Atsushi Matsuzawa, Ph.D., and Ping-Hui Tseng, Ph.D., postdoctoral fellows in the Karin laboratory, describe how engagement of CD40, a member of the TNFR family, results in assembly of multiprotein signaling complexes at the receptor. However, according to the researchers – and contrary to previous expectations – signaling cascades that lead to activation of Jun Kinases (JNK) and p38 MAP Kinases (MAPK) are not initiated until these complexes dissociate from the receptor.
The authors found that complex translocation from the cell surface receptor to the cytoplasm, which is required for JNK and p38 activation, depends on degradation of a signaling protein called TRAF3. This process can be inhibited by a class of compounds known as Smac mimics.
“As Smac mimic compounds do not interfere with the activation of NF-κB-dependent innate immunity but do prevent the induction of JNK- and p38- dependent inflammatory mediators, they may serve as the prototypes for new anti-inflammatory therapy,” said Karin, who also noted that current drugs that work by interfering with TNFR signaling exceed $5 billion a year in revenue.
An Amazonian language with only 300 speakers has no word to express the concept of “one” or any other specific number, according to a new study from an MIT-led team.
The team, led by MIT professor of brain and cognitive sciences Edward Gibson, found that members of the Piraha tribe in remote northwestern Brazil use language to express relative quantities such as “some” and “more,” but not precise numbers.
It is often assumed that counting is an innate part of human cognition, said Gibson, “but here is a group that does not count. They could learn, but it’s not useful in their culture, so they’ve never picked it up.” … Continue Reading »
A clinical study on patients who have suffered a heart attack found that a partially purified extract of Chinese red yeast rice, Xuezhikang (XZK), reduced the risk of repeat heart attacks by 45%, revascularization (bypass surgery/angioplasty), cardiovascular mortality and total mortality by one-third and cancer mortality by two-thirds. The multicenter, randomized, double-blind study, was conducted on almost 5,000 patients, ranging in age from 18-70 over a five-year period at over 60 hospitals in the People’s Republic of China. Corresponding author David M. Capuzzi, M.D., Ph.D, director of the Cardiovascular Disease Prevention Program at Jefferson’s Myrna Brind Center of Integrative Medicine and Zonliang Lu, M.D., Ph.D, from the Fuwai Hospital at the Chinese Academy of Medical Science report their findings in the June 15th edition of the American Journal of Cardiology.
“It’s very exciting because this is a natural product and had very few adverse side effects including no abnormal blood changes,” said Capuzzi. “People in the Far East have been taking Chinese red yeast rice as food for thousands of years, but no one has ever studied it clinically in a double-blind manner with a purified product against a placebo group until now and we are pleased with the results. However, people in the United States should know that the commercially available over-the-counter supplement found in your average health food store is not what was studied here. Those over-the-counter supplements are not regulated, so exact amounts of active ingredient are unknown and their efficacy has not been studied yet.”
The study looked at patients who had suffered a heart attack in the previous year. Study participants were given two-300-milligram XZK capsules or a placebo and tracked over a five-year period. The XZK capsules contained a combination of lovastatin, lovastatin hydroxyl acid, ergosterol and other components.
“I think it is surprising that a natural product like XZK would have this great an effect,” said Capuzzi. “If further testing and study prove true, my hope is that XZK becomes an important therapeutic agent to treat cardiovascular disorders and in the prevention of disease whether someone has had a heart attack or not. But it is important to recognize the fact we do not know exactly how Chinese red yeast rice works. The exact ingredients from the XZK capsules have not been isolated and studied yet. Still the results were so profound, even out performing statins prescribed in numerous western populations, that further study should certainly be investigated.”
Many Westerners dismiss Chinese/Eastern medicine because it is not a replacement for Western medicine. While it can’t replace Western medicine, there is much to be learned and it is great to see large studies like this showing significant results. Chinese medicine also has the benefit of being much, much more affordable to the world’s populations because patents and intellectual property and usually nil.
In a world first, a University of Melbourne study has shown that topical estrogen could help prevent HIV infection by blocking entry of the virus into the human penis.
[editor's note] (Andrew): The only reason I’m not scrubbing this trash study off my website is to mock it.
First, there is no clinical application. Rather than a CONDOM, which costs nothing, works immediately, is everywhere, works for everyone, has no side effects, and prevents every STD up to and including pregnancy itself by almost 100%, I’m supposed to sagely ponder rubbing female hormones on my penis to “toughen it up” by “15%” which might increase my resistance to HIV a week later? And this is suggested as viable solution for AIDS control in countries with pervasive cultural taboos about the penis? Total, absolute bullshit.
Second, the sample size of this study is: TWO. Yes, two. Ok, eight if you include the foreskin donors. And the study only tested keratin coverage and presented some untested hypotheses regarding a couple tangential studies as conclusions regarding HIV prevention.
But good news for readers, because I’m awarding a Think Gene coffee mug to the first reader who forwards me a spam email hawking topical oestrogen as an “all natural” penis cream to “u last longr.”
The study to be published in PLoS ONE journal today reveals that application of estrogen to the human penis increased the thickness of the natural keratin layer on the skin, which could prevent HIV from infecting the male.
The epithelium of the human penis is richly supplied with estrogen receptors suggesting it could respond to topical estrogen.
Dr Andrew Pask from the Department of Zoology at the University of Melbourne analyzed the tissue samples from 12 foreskins and made the discovery.
“This suggested that estrogen could induce a thickening of the keratin layer of the foreskin epidermis in the same way as it acts in the vagina,” said Dr Pask.
“Keratin on our skin acts a barrier to viral infection. We hope to be able to enhance this protection with the use of a naturally occurring, weak estrogen,” said Professor Roger Short of the Faculty of Medicine, Dentistry and Health Sciences who lead the research.
To confirm its effect, topical estrogen was applied to the human foreskin for a two week trial. This resulted in a rapid and substantial increase in keratin thickness.
“We have found a new avenue to possibly prevent HIV infection of the penis.”
HIV is one of the greatest health crises the world has ever seen, and affects over 40 million people worldwide.
Kevin: HIV is on the rise around the world and a treatment such as this could have impact where condoms are not socially acceptable because of adverse societal influence. Estrogen on the penis would be fine, and while it’s nothing like condoms for preventing HIV (and anti-retrovirals at your local free HIV drug stand) this could mean something in terms of harm reduction.
This video has the tone of a polemic but this is an area where a strong call to action is needed. Is there anyone out there even willing to defend big corporations that are patenting naturally occurring genes and then aggressively “protecting” their IP? This is indicative of the broader problem with the US patent system which doesn’t encourage innovation in the way it was meant to.
Researchers at Columbia University Medical Center have illuminated a window into how abnormalities in microRNAs, a family of molecules that regulate expression of numerous genes, may contribute to the behavioral and neuronal deficits associated with schizophrenia and possibly other brain disorders.
In the May 11 issue of Nature Genetics, Maria Karayiorgou, M.D., professor of psychiatry, and Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center explain how they uncovered a previously unknown alteration in the production of microRNAs of a mouse modeled to have the same chromosome 22q11.2 deletions previously identified in humans with schizophrenia. … Continue Reading »
Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have found a fast and effective way to investigate important aspects of human ageing. Working at the University of Oxford and The Open University, Dr Lynne Cox and Dr Robert Saunders have discovered a gene in fruit flies that means flies can now be used to study the effects ageing has on DNA. In new work published today in the journal Aging Cell, the researchers demonstrate the value of this model in helping us to understand the ageing process. This exciting study demonstrates that fruit flies can be used to study critical aspects of human ageing at cellular, genetic and biochemical levels.
Dr Lynne Cox from the University of Oxford said: “We study a premature human ageing disease called Werner syndrome to help us understand normal ageing. The key to this disease is that changes in a single gene (called WRN) mean that patients age very quickly. Scientists have made great progress in working out what this gene does in the test tube, but until now we haven’t been able to investigate the gene to look at its effect on development and the whole body. By working on this gene in fruit flies, we can model human ageing in a powerful experimental system.” … Continue Reading »
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