New Sensor Glove May Help Stroke Patients Recover Mobility

A new sensor glove may help stroke patients recover hand mobility by playing video games. 

People who have strokes are often left with moderate to severe physical impairments. Now, thanks to a glove developed at McGill, stroke patients may be able to recover hand motion by playing video games. The Biomedical Sensor Glove was developed by four final-year McGill Mechanical Engineering undergrads under the supervision of Professor Rosaire Mongrain.

It is designed to allow patients to exercise in their own homes with minimal supervision, while at the same time permitting doctors to monitor their progress from a distance, thus cutting down on hospital visits and costs.
Patients can monitor their progress thanks to software, which will generate 3D models and display them on the screen, while at the same time sending the information to the treating physician.
The glove was developed by the students in response to a design request from the startup company Jintronix Inc. The students met with company representatives once a week for several months to develop the glove, which can track the movements of the wrist, the palm and the index finger using several Inertial Measurement Units. Although similar gloves currently exist, they costs approximately $30,000. By using more accurate and less expensive sensors, the students were able to develop a glove that currently costs $1000 to produce.
Jintronix, Inc. has submitted the project to Grand Challenges Canada, which is an independent not-for-profit organization dedicated to improving the health and well-being of people in developing countries, in the hopes that they will receive funding for further development.

Of Bugs and Brains: Gut Bacteria Affect Multiple Sclerosis

In the absence of bacteria in the intestines, pro-inflammatory Th17 cells do not develop in either the gut or the central nervous system; and animals do not develop disease (top panel). When animals are colonized with symbiotic segmented filamentous bacteria, Th17 cell differentiation is induced in the gut. Th17 cells promote experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. In this way, non-pathogenic bacteria of the microbiota promote disease by shaping the immune response in both the gut and the brain

Biologists at the California Institute of Technology (Caltech) have demonstrated a connection between multiple sclerosis (MS) -- an autoimmune disorder that affects the brain and spinal cord -- and gut bacteria.
The work -- led by Sarkis K. Mazmanian, an assistant professor of biology at Caltech, and postdoctoral scholar Yun Kyung Lee -- appears online the week of July 19-23 in the Proceedings of the National Academy of Sciences.
Multiple sclerosis results from the progressive deterioration of the protective fatty myelin sheath surrounding nerve cells. The loss of myelin hinders nerve cells from communicating with one another, leading to a host of neurological symptoms including loss of sensation, muscle spasms and weakness, fatigue, and pain. Multiple sclerosis is estimated to affect about half a million people in the United States alone, with rates of diagnosis rapidly increasing. There is currently no cure for MS.
Although the cause of MS is unknown, microorganisms seem to play some sort of role. "In the literature from clinical studies, there are papers showing that microbes affect MS," Mazmanian says. "For example, the disease gets worse after viral infections, and bacterial infections cause an increase in MS symptoms."
On the other hand, he concedes, "it seems counterintuitive that a microbe would be involved in a disease of the central nervous system, because these are sterile tissues."
And yet, as Mazmanian found when he began examining the multiple sclerosis literature, the suggestion of a link between bacteria and the disease is more than anecdotal. Notably, back in 1993, Caltech biochemist Leroy Hood -- who was then at the University of Washington -- published a paper describing a genetically engineered strain of mouse that developed a lab-induced form of multiple sclerosis known as experimental autoimmune encephalomyelitis, or EAE.
When Hood's animals were housed at Caltech, they developed the disease. But, oddly, when the mice were shipped to a cleaner biotech facility -- where their resident gut bacterial populations were reduced -- they didn't get sick. The question was, why? At the time, Mazmanian says, "the authors speculated that some environmental component was modulating MS in these animals." Just what that environmental component was, however, remained a mystery for almost two decades.
But Mazmanian -- whose laboratory examines the relationships between gut microbes, both harmful and helpful, and the immune systems of their mammalian hosts -- had a hunch that intestinal bacteria were the key. "As we gained an appreciation for how profoundly the gut microbiota can affect the immune system, we decided to ask if symbiotic bacteria are the missing variable in these mice with MS," he says.
To find out, Mazmanian and his colleagues tried to induce MS in animals that were completely devoid of the microbes that normally inhabit the digestive system. "Lo and behold, these sterile animals did not get sick," he says.
Then the researchers decided to see what would happen if bacteria were reintroduced to the germ-free mice. But not just any bacteria. They inoculated mice with one specific organism, an unculturable bug from a group known as segmented filamentous bacteria. In prior studies, these bacteria had been shown to lead to intestinal inflammation and, more intriguingly, to induce in the gut the appearance of a particular immune-system cell known as Th17. Th17 cells are a type of T helper cell -- cells that help activate and direct other immune system cells. Furthermore, Th17 cells induce the inflammatory cascade that leads to multiple sclerosis in animals.
"The question was, if this organism is inducing Th17 cells in the gut, will it be able to do so in the brain and central nervous system?" Mazmanian says. "Furthermore, with that one organism, can we restore to sterile animals the entire inflammatory response normally seen in animals with hundreds of species of gut bacteria?"
The answer? Yes on all counts. Giving the formerly germ-free mice a dose of one species of segmented filamentous bacteria induced Th17 not only in the gut but in the central nervous system and brain -- and caused the formerly healthy mice to become ill with MS-like symptoms.
"It definitely shows that gut microbes have a strong role in MS, because the genetics of the animals were the same. In fact, everything was the same except for the presence of those otherwise benign bacteria, which are clearly playing a role in shaping the immune system," Mazmanian says. "This study shows for the first time that specific intestinal bacteria have a significant role in affecting the nervous system during MS -- and they do so from the gut, an anatomical location very, very far from the brain."
Mazmanian and his colleagues don't, however, suggest that gut bacteria are the direct cause of multiple sclerosis, which is known to be genetically linked. Rather, the bacteria may be helping to shape the immune system's inflammatory response, thus creating conditions that could allow the disease to develop. Indeed, multiple sclerosis also has a strong environmental component; identical twins, who possess the same genome and share all of their genes, only have a 25 percent chance of sharing the disease. "We would like to suggest that gut bacteria may be the missing environmental component," he says.
For their part, Th17 cells are needed for the immune system to properly combat infection. Problems only arise when the cells are activated in the absence of infection -- just as disease can arise, Mazmanian and others suspect, when the species composition of gut bacteria become imbalanced, say, by changes in diet, because of improved hygiene (which kills off the beneficial bacteria as well as the dangerous ones), or because of stress or antibiotic use. One impact of the dysregulation of normal gut bacterial populations -- a phenomenon dubbed "dysbiosis" -- may be the rising rate of multiple sclerosis seen in recent years in more hygienic societies.
"As we live cleaner, we're not just changing our exposure to infectious agents, but we're changing our relationship with the entire microbial world, both around and inside us, and we may be altering the balance between pro- and anti-inflammatory bacteria," leading to diseases like MS, Mazmanian says. "Perhaps treatments for diseases such as multiple sclerosis may someday include probiotic bacteria that can restore normal immune function in the gut… and the brain."
The work was supported by funding from the California Institute of Technology, the Weston Havens Foundation, and the Edward Mallinckrodt, Jr. Foundation.

Nanoparticles Shrink Tumors in Mice

The application of nanotechnology in the field of drug delivery has attracted much attention in recent years. In cancer research, nanotechnology holds great promise for the development of targeted, localized delivery of anticancer drugs, in which only cancer cells are affected.

A dorsal view of a mouse showing accumulation of nanoparticles in a tumor four hours after intravenous administration. Bright fluorescence is observed predominantly in the tumor.

Such targeted-therapy methods would represent a major advance over current chemotherapy, in which anticancer drugs are distributed throughout the body, attacking healthy cells along with cancer cells and causing a number of adverse side effects.
By carrying out comprehensive studies on mice with human tumors, UCLA scientists have obtained results that move the research one step closer to this goal. In a paper published July 8 in the journal Small, researchers at UCLA's California NanoSystems Institute and Jonsson Comprehensive Cancer Center demonstrate that mesoporous silica nanoparticles (MSNs), tiny particles with thousands of pores, can store and deliver chemotherapeutic drugs in vivo and effectively suppress tumors in mice.
The researchers also showed that MSNs accumulate almost exclusively in tumors after administration and that the nanoparticles are excreted from the body after they have delivered their chemotherapeutic drugs.
The study was conducted jointly in the laboratories of Fuyu Tamanoi, a UCLA professor of microbiology, immunology and molecular genetics and director of the signal transduction and therapeutics program at UCLA's Jonsson Comprehensive Cancer Center, and Jeffrey Zink, a UCLA professor of chemistry and biochemistry. Tamanoi and Zink are researchers at the California NanoSystems Institute (CNSI) and are two of the co-directors of the CNSI's Nano Machine Center for Targeted Delivery and On-Demand Release. The lead investigator on the research is Jie Lu, a postdoctoral fellow in Tamanoi's lab. Monty Liong and Zongxi Li, researchers from Zink's lab, also contributed to this work.
In the study, researchers found that MSNs circulate in the bloodstream for extended periods of time and accumulate predominantly in tumors. The tumor accumulation could be further improved by attaching a targeting moiety to MSNs, the researchers said.
The treatment of mice with camptothecin-loaded MSNs led to shrinkage and regression of xenograft tumors. By the end of the treatment, the mice were essentially tumor free, and acute and long-term toxicity of MSNs to the mice was negligible. Mice with breast cancer were used in this study, but the researchers have recently obtained similar results using mice with human pancreatic cancer.
"Our present study shows, for the first time, that MSNs are effective for anticancer drug delivery and that the capacity for tumor suppression is significant," Tamanoi said.
"Two properties of these nanoparticles are important," Lu said. "First, their ability to accumulate in tumors is excellent. They appear to evade the surveillance mechanism that normally removes materials foreign to the body. Second, most of the nanoparticles that were injected into the mice were excreted out through urine and feces within four days. The latter results are quite interesting and might explain the low toxicity observed in the biocompatabilty experiments we conducted."
Researchers at the Nano Machine Center for Targeted Delivery and On-Demand Release are modifying MSNs -- which are easily modifiable -- so that the nanoparticles can be equipped with nanomachines. For example, nanovalves are being attached at the opening of the pores to control the release of anticancer drugs. In addition, the interior of the pores is being modified so that the light-induced release of anticancer drugs can be achieved.
"We can modify both the particles themselves and also the attachments on the particles in a wide variety of ways, which makes this material particularly attractive for engineering drug-delivery vehicles," Zink said.
The team is now planning future research that involves testing MSNs in a variety of animal-model systems and carrying out extensive studies on the safety of MSNs.
"Comprehensive investigation with practical dosages which are adequate and suitable for in vivo delivery of anticancer drugs is needed before MSNs can reach clinics as a drug-delivery system," Tamanoi said.
The research received support from National Institutes of Health and the National Science Foundation. In addition, NanoPacific Holdings Inc. provided critical support for the animal experiments.

Scientists 'Boot Up' a Bacterial Cell With a Synthetic Genome

Scientists have developed the first cell controlled by a synthetic genome. They now hope to use this method to probe the basic machinery of life and to engineer bacteria specially designed to solve environmental or energy problems.

Scanning electron micrographs of M. mycoides JCVI-syn1. Samples were post-fixed in osmium tetroxide, dehydrated and critical point dried with CO2 , then visualized using a Hitachi SU6600 scanning electron microscope at 2.0 keV.

The study will be published online by the journal Science, at the Science Express website, on May 20.
The research team, led by Craig Venter of the J. Craig Venter Institute, has already chemically synthesized a bacterial genome, and it has transplanted the genome of one bacterium to another. Now, the scientists have put both methods together, to create what they call a "synthetic cell," although only its genome is synthetic.
"This is the first synthetic cell that's been made, and we call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer," said Venter.
"This becomes a very powerful tool for trying to design what we want biology to do. We have a wide range of applications [in mind]," he said.
For example, the researchers are planning to design algae that can capture carbon dioxide and make new hydrocarbons that could go into refineries. They are also working on ways to speed up vaccine production. Making new chemicals or food ingredients and cleaning up water are other possible benefits, according to Venter.
In the Science study, the researchers synthesized the genome of the bacterium M. mycoides and added DNA sequences that "watermark" the genome to distinguish it from a natural one.
Because current machines can only assemble relatively short strings of DNA letters at a time, the researchers inserted the shorter sequences into yeast, whose DNA-repair enzymes linked the strings together. They then transferred the medium-sized strings into E. coli and back into yeast. After three rounds of assembly, the researchers had produced a genome over a million base pairs long.
The scientists then transplanted the synthetic M. mycoides genome into another type of bacteria, Mycoplasm capricolum. The new genome "booted up" the recipient cells. Although fourteen genes were deleted or disrupted in the transplant bacteria, they still looked like normal M. mycoides bacteria and produced only M. mycoides proteins, the authors report.
"This is an important step we think, both scientifically and philosophically. It's certainly changed my views of the definitions of life and how life works," Venter said.
Acknowledging the ethical discussion about synthetic biology research, Venter explained that his team asked for a bioethical review in the late 1990s and has participated in variety of discussions on the topic.
"I think this is the first incidence in science where the extensive bioethical review took place before the experiments were done. It's part of an ongoing process that we've been driving, trying to make sure that the science proceeds in an ethical fashion, that we're being thoughtful about what we do and looking forward to the implications to the future," he said.
This research was funded by Synthetic Genomics, Inc. Three of the authors and the J. Craig Venter Institute hold Synthetic Genomics, Inc. stock. The J. Craig Venter Institute has filed patent applications on some of the techniques described in this paper.

How Ducks Host Influenza Unharmed: Could Findings Shield Humans from Bird Flu Viruses?

A University of Alberta-led research team has discovered an influenza detector gene that could potentially prevent the transmission of the virus to humans.

Mallard duck with fifteen ducklings. Researchers have identified the genetic detector that allows ducks to live, unharmed, as the host of influenza. 

Katharine Magor, a U of A associate professor of biology, has identified the genetic detector that allows ducks to live, unharmed, as the host of influenza. The duck's virus detector gene, called retinoic acid inducible gene -- I, or RIG-I, enables a duck's immune system to contain the virus, which typically spreads from ducks to chickens, where it mutates and can evolve to be a human threat like the H5N1 influenza virus. The first human H5N1 cases were in Hong Kong in 1997. Eighteen people with close contact to chickens became infected and six died.
Magor's research shows chickens do not have a RIG-I gene. A healthy chicken can die within 18 hours after infection, but researchers have successfully transferred the RIG-I gene from ducks to chicken cells. The chicken's defenses against influenza were augmented and RIG-I reduced viral replication by half.
One potential application of this research could affect the worldwide poultry industry by production of an influenza-resistant chicken created by transgenesis.
The work of Katharine Magor, her U of A PhD candidate Megan Barber, and researchers from the United States (Jerry Aldridge and Robert Webster) was published March 22, in the online, early edition of Proceedings from the National Academy of Sciences.

Life on Saturn's Moon Titan: Stand Well Back and Hold Your Nose!

Research by astrobiologist William Bains suggests that if life has evolved on the frozen surface of Saturn's moon, Titan, it would be strange, smelly and explosive compared to life on Earth.

Dr Bains will present his work at the National Astronomy Meeting in Glasgow on April 13.
"Hollywood would have problems with these aliens" says Dr. Bains. "Beam one onto the Starship Enterprise and it would boil and then burst into flames, and the fumes would kill everyone in range. Even a tiny whiff of its breath would smell unbelievably horrible. But I think it is all the more interesting for that reason. Wouldn't it be sad if the most alien things we found in the galaxy were just like us, but blue and with tails?"
Dr Bains, whose research is carried out through Rufus Scientific in Cambridge, UK, and MIT in the USA, is seeking to work out just how extreme the chemistry of life can be. Life on Titan, Saturn's largest moon, represents one of the more bizarre scenarios being studied. Titan is twice as large as our Moon and has a thick atmosphere of frozen, orange smog. At ten times our distance from the Sun, it is a frigid place, with a surface temperature of -180 degrees Celsius. Water is permanently frozen into ice and the only liquid available is liquid methane and ethane, which the Cassini/Huygens mission has shown is present in ponds and lakes on the surface of the moon.
"Life needs a liquid; even the driest desert plant on Earth needs water for its metabolism to work. So, if life were to exist on Titan, it must have blood based on liquid methane, not water. That means its whole chemistry is radically different. The molecules must be made of a wider variety of elements than we use, but put together in smaller molecules. It would also be much more chemically reactive," said Dr Bains.
The solubility of chemicals in liquid methane is very limited, and strongly dependent on molecular weight. With a few exceptions, molecules with more than 6 heavy (non-hydrogen) atoms are essentially insoluble. So a metabolism running in liquid methane will have to be built of smaller molecules than terrestrial biochemistry, which is typically built of modules of around 10 heavy atoms. However you can only build around 3400 molecules from such a small number of atoms if you are limited to the chemistry that terrestrial life uses i.e. carbon, nitrogen, oxygen, and sulphur and phosphorus in very limited chemical contexts.
Dr Bains explained, "Terrestrial life uses about 700 molecules, but to find the right 700 there is reason to suppose that you need to be able to make 10 million or more. The issue is not how many molecules you can make, but whether you can make the collection you need to assemble a metabolism. It is like trying to find bits of wood in a lumber-yard to make a table. In theory you only need 5. But you may have a lumber-yard full of offcuts and still not find exactly the right five that fit together. So you need the potential to make many more molecules than you actually need. Thus the 6-atom chemicals on Titan would have to include much more diverse bond types and probably more diverse elements, including sulphur and phosphorus in much more diverse and (to us) unstable forms, and other elements such as silicon."
Energy is another factor that would affect the type of life that could evolve on Titan. With Sunlight a tenth of a percent as intense on Titan's surface as on the surface of Earth, energy is likely to be in short supply.
"Rapid movement or growth needs a lot of energy, so slow-growing, lichen-like organisms are possible in theory, but velociraptors are pretty much ruled out," said Bains.

Experts say U.S. doctors overtesting, overtreating

Too much cancer screening, too many heart tests, too many cesarean sections. A spate of recent reports suggest that too many Americans — maybe even President Obama — are being overtreated.

Is it doctors practicing defensive medicine? Or are patients so accustomed to a culture of medical technology that they insist on extensive tests and treatments?

A combination of both is at work, but now new evidence and guidelines are recommending a step back and more thorough doctor-patient conversations about risks and benefits.

As a medical journal editorial said this week about Obama's recent checkup, Americans including the commander in chief need to realize that "more care is not necessarily better care."

Obama's exam included prostate-cancer screening and a virtual colonoscopy. The PSA test for prostate cancer is not routinely recommended for any age and colon screening is not routinely recommended for patients younger than 50. Obama is 48. (PSA stands for prostate-specific antigen screening).

Earlier colon-cancer screening is sometimes recommended for high-risk groups — which a White House spokesman noted includes blacks. Doctors disagree on whether a virtual colonoscopy is the best method. But it's less invasive than traditional colonoscopies and doesn't require sedation — or the possible temporary transfer of presidential power, the White House said.

The colon exam exposed him to radiation "while likely providing no benefit to his care," Dr. Rita Redberg, editor of Archives of Internal Medicine, wrote in an online editorial. "People have come to equate tests with good care and prevention," Redberg, a cardiologist with the University of California, San Francisco, said in an interview Thursday. "Prevention is all the things your mother told you — eat right, exercise, get enough sleep, don't smoke — and we've made it into getting a new test."

This week alone, a New England Journal of Medicine study suggested that too many patients are getting angiograms — invasive imaging tests for heart disease — who don't really need them; and specialists convened by the National Institutes of Health said doctors are too often demanding repeat cesarean deliveries for pregnant women after a first C-section.

Experts dispute how much routine cancer screening saves lives.

Not all doctors and advocacy groups agree with the criticism of screening. Many argue that it can improve survival chances and that saving even a few lives is worth the cost of routinely testing tens of thousands of people.

While some patients clearly do benefit from screening, others clearly do not, said Dr. Richard Wender, former president of the American Cancer Society.

These include very old patients, who may unrealistically fear cancer and demand a screening test, when their risks are far higher of dying from something else, Wender said.

Doctors also often order tests or procedures to protect themselves against lawsuits — so-called defensive medicine — and also because the fee-for-service system compensates them for it, said Dr. Gilbert Welch, a Dartmouth University internist and health-outcomes researcher.

While many patients also demand routine tests, they're often bolstered by advertisements, medical information online — and by doctors, too, Welch said.

The new guidance from the cancer society last week on PSA testing, echoing others' advice on mammograms, is for doctors and patients to thoroughly discuss testing, including a patient's individual disease risks, general pros and cons of testing and possible harms it may cause.

Read More : seattletimes

Medical Identity Theft

     The latest addition to the world of fraud , medical identity theft. You might be wondering what really is " Medical Identity Theft" . It is in simple words , usage of ones health cards by some other person without the knowledge of its real owner. The owner of the card may come to the realization of the fraud only when his service provoder sent him bills for thousands of dollars for some surgeries that he never underwent.
                                     The irony is that most of the fraud are done by family members or close family friends. So the number of cases reported will be very rare. The hospital authorities also didn't check much details once they are provided with health cards , that also is a reason for this fraud to develop.

             To read a detailed report on Medical Identity Theft Read from here  :: Medical Identity Theft

Genetic Link Between Misery and Death Discovered; Novel Strategy Probes 'Genetic Haystack'

Interaction between nerves (red) and tumor cells (blue) in an ovary provides one way by which stress biochemistry signals can be distributed to sites of disease in the body

In ongoing work to identify how genes interact with social environments to impact human health, UCLA researchers have discovered what they describe as a biochemical link between misery and death. In addition, they found a specific genetic variation in some individuals that seems to disconnect that link, rendering them more biologically resilient in the face of adversity.
Perhaps most important to science in the long term, Steven Cole, a member of the UCLA Cousins Center for Psychoneuroimmunology and an associate professor of medicine in the division of hematology-oncology, and his colleagues have developed a unique strategy for finding and confirming gene-environment interactions to more efficiently probe what he calls the "genetic haystack."
The research appears in the current online edition of Proceedings of the National Academy of Sciences.
Using an approach that blends computational, in vivo and epidemiological studies to focus their genetic search, Cole and his colleagues looked at specific groups of proteins known as transcription factors, which regulate gene activity and mediate environmental influences on gene expression by binding to specific DNA sequences. These sequences differ within the population and may affect a gene's sensitivity to environmental activation.
Specifically, Cole analyzed transcription factor binding sequences in a gene called IL6, a molecule that is known to cause inflammation in the body and that contributes to cardiovascular disease, neurodegeneration and some types of cancer.
"The IL6 gene controls immune responses but can also serve as 'fertilizer' for cardiovascular disease and certain kinds of cancer," said Cole, who is also a member of UCLA's Jonsson Comprehensive Cancer Center and UCLA's Molecular Biology Institute. "Our studies were able to trace a biochemical pathway through which adverse life circumstances -- fight-or-flight stress responses -- can activate the IL6 gene.
"We also identified the specific genetic sequence in this gene that serves as a target of that signaling pathway, and we discovered that a well-known variation in that sequence can block that path and disconnect IL6 responses from the effects of stress."
To confirm the biochemical link between misery and death, and the genetic variation that breaks it, the researchers turned to epidemiological studies to prove that carriers of that specific genetic variation were less susceptible to death due to inflammation-related mortality causes under adverse social-environmental conditions.
They found that people with the most common type of the IL6 gene showed an increased risk of death for approximately 11 years after they had been exposed to adverse life events that were strong enough to trigger depression. However, people with the rarer variant of the IL6 gene appeared to be immune to those effects and showed no increase in mortality risk in the aftermath of significant life adversity.
This novel method of discovery -- using computer modeling and then confirming genetic relationships using test-tube biochemistry, experimental stress studies and human genetic epidemiology -- could speed the discovery of such gene and environmental relationships, the researchers say.
"Right now, we have to hunt down genetic influences on health through blind searches of huge databases, and the results from that approach have not yielded as much as expected," Cole said. "This study suggests that we can use computer modeling to discover gene-environment interactions, then confirm them, in order to focus our search more efficiently and hopefully speed the discovery process.
"This opens a new era in which we can begin to understand the influence of adversity on physical health by modeling the basic biology that allows the world outside us to influence the molecular processes going on inside our cells."
Other authors on the study were Jesusa M. G. Arevalo, Rie Takahashi, Erica K. Sloan and Teresa E. Seeman, of UCLA; Susan K. Lutgendorf, of the University of Iowa; Anil K. Sood, of the University of Texas; and John F. Sheridan, of Ohio State University. Funding was provided by the National Institutes of Health, the UCLA Norman Cousins Center and the James L. Pendleton Charitable Trust. The authors report no conflict of interest.

From Uncharted Region of Human Genome, Clues Emerge About Origins of Coronary Artery Disease

Scientists from the U.S. Department of Energy's Lawrence Berkeley National Laboratory have learned how an interval of DNA in an unexplored region of the human genome increases the risk for coronary artery disease, the leading cause of death worldwide.
Their research paints a fuller picture of a genetic risk for the disease that was discovered only three years ago and which lurks in one out of two people.
It also reinforces the tantalizing possibility that many more disease risks -- and potential therapies -- are hidden in the vast and uncharted part of the genome that doesn't contain instructions for making proteins.
The research is reported in the February 21 advance online publication of the journal Nature.
The team focused on an interval of DNA in chromosome 9p21. People who carry variations of this interval have an increased chance of developing coronary artery disease, which is an accumulation of plaque in coronary arteries that restricts blood flow to the heart and causes heart attacks.
Determining how this DNA contributes to the disease is difficult because it's in the poorly understood part of the genome that doesn't code for proteins, the workhorses of cellular function.
In groundbreaking research, the Berkeley Lab scientists found that the DNA interval regulates a pair of genes that inhibit cell division, and that bad copies of the interval reduce the genes' expression. Although more work is needed to understand how this mechanism contributes to coronary artery disease, the researchers speculate that the hobbled genes allow vascular cells to proliferate unchecked and narrow coronary arteries.
"We show that this non-coding interval affects the expression of two cell cycle inhibitor genes located almost 100,000 base pairs away. We believe that something goes awry in variants of this interval, causing vascular cells to divide and multiply more quickly than usual," says Len Pennacchio, a geneticist with Berkeley Lab's Genomics Division who conducted the research with Axel Visel and several other scientists from Berkeley Lab, as well as Jonathan Cohen of the University of Texas Southwestern Medical Center.
The link between an interval of DNA in chromosome 9p21 and a risk for coronary artery disease was established in several recent studies, one of which was published in the journal Science in 2007. In that study, led by Cohen and co-authored by several scientists including Pennacchio, the researchers scoured the human genome for differences in people who have coronary artery disease versus people who don't.
This genome-wide association analysis alighted on a stretch of DNA in chromosome 9p21 that spans 58,000 base pairs of DNA. The study found that people with bad copies of this interval have a moderately higher risk of developing coronary artery disease. In addition, 50 percent of people have one bad copy and 25 percent have two bad copies.
"The risk of coronary artery disease isn't very high in any give person with bad copies. But they are so common that population-wide the effect is significant," says Pennacchio.
Remarkably, the study also found that the DNA interval isn't associated with known risks for coronary artery disease such as diabetes, high blood pressure, and high cholesterol level. An unknown mechanism was at work.
"We landed on this risk interval and immediately said 'wow!' why doesn't it link to problems that we know cause coronary artery disease?" says Pennacchio. "So the big question became: what is this DNA doing?"
Adding to the mystery, the DNA interval is among the 98 percent of our genome that doesn't code for proteins. Most efforts to determine the function of the genome have focused on the two percent of our DNA that overlaps protein-coding genes. Scientists are just now beginning to explore the non-coding region, once referred to as "junk DNA."
As part of this effort, the Berkeley Lab scientists set out to determine the function of the DNA interval in chromosome 9p21 that's linked to coronary artery disease. They removed an analogous section of DNA from mice, then tracked what happened.
The expression level of two genes located far away, Cdkn2a and Cdkn2b, plummeted by about 90 percent in the "knock-out" mice compared to normal mice. These genes are important in controlling cell cycles and have been linked to cancer when mutated, but they had never been linked to coronary artery disease.
The scientists also studied heart tissue of the "knock-out" mice and found that the smooth muscle cells from their aortas had increased proliferation, a hallmark of coronary artery disease.
"Our research shows that the DNA interval plays a pivotal role in regulating the expression of two genes that control cell cycles. It also suggests that variants of the interval spur the progression of coronary artery disease by altering the dynamics of vascular cells," says Pennacchio.
With this mechanism identified, scientists can develop therapies that fight coronary artery disease by targeting the two genes and jumpstarting them into action, says Pennacchio. He also believes that the genetic roots of many other diseases will be unearthed as scientists learn how to decipher the function of non-coding DNA.
"Non-coding DNA is a huge area of the genome, waiting to be explored, which could have huge dividends for understanding and treating disease," says Pennacchio.

Mango can arrest growth of certain breast and colon cancer cells

ango fruit been found to prevent or stop certain colon and breast cancer cells in the lab.

Mango fruit been found to prevent or stop certain colon and breast cancer cells in the lab.
That's according to a new study by Texas AgriLife Research food scientists, who examined the five varieties most common in the U.S.: Kent, Francine, Ataulfo, Tommy/Atkins and Haden.
Though the mango is an ancient fruit heavily consumed in many parts of the world, little has been known about its health aspects. The National Mango Board commissioned a variety of studies with several U.S. researchers to help determine its nutritional value.
"If you look at what people currently perceive as a superfood, people think of high antioxidant capacity, and mango is not quite there," said Dr. Susanne Talcott, who with her husband, Dr. Steve Talcott, conducted the study on cancer cells. "In comparison with antioxidants in blueberry, acai and pomegranate, it's not even close."
But the team checked mango against cancer cells anyway, and found it prevented or stopped cancer growth in certain breast and colon cell lines, Susanne Talcott noted.
"It has about four to five times less antioxidant capacity than an average wine grape, and it still holds up fairly well in anticancer activity. If you look at it from the physiological and nutritional standpoint, taking everything together, it would be a high-ranking super food," she said. "It would be good to include mangoes as part of the regular diet."
The Talcotts tested mango polyphenol extracts in vitro on colon, breast, lung, leukemia and prostate cancers. Polyphenols are natural substances in plants and are associated with a variety of compounds known to promote good health.
Mango showed some impact on lung, leukemia and prostate cancers but was most effective on the most common breast and colon cancers.
"What we found is that not all cell lines are sensitive to the same extent to an anticancer agent," she said. "But the breast and colon cancer lines underwent apotosis, or programmed cell death. Additionally, we found that when we tested normal colon cells side by side with the colon cancer cells, that the mango polyphenolics did not harm the normal cells."
The duo did further tests on the colon cancer lines because a mango contains both small molecules that are readily absorbed and larger molecules that would not be absorbed and thus remain present in a colon.
"We found the normal cells weren't killed, so mango is not expected to be damaging in the body," she said. "That is a general observation for any natural agent, that they target cancer cells and leave the healthy cells alone, in reasonable concentrations at least."
The Talcotts evaluated polyphenolics, and more specifically gallotannins as being the class of bioactive compounds (responsible for preventing or stopping cancer cells). Tannins are polyphenols that are often bitter or drying and found in such common foods as grape seed, wine and tea.
The study found that the cell cycle, which is the division cells go through, was interrupted. This is crucial information, Suzanne Talcott said, because it indicates a possible mechanism for how the cancer cells are prevented or stopped.
"For cells that may be on the verge of mutating or being damaged, mango polyphenolics prevent this kind of damage," she said.
The Talcotts hope to do a small clinical trial with individuals who have increased inflamation in their intestines with a higher risk for cancer.
"From there, if there is any proven efficacy, then we would do a larger trial to see if there is any clinical relevance," she said.
According to the National Mango Board, based in Winter Park, Fla., most mangoes consumed in the U.S. are produced in Mexico, Ecuador, Peru, Brazil, Guatemala and Haiti. Mangoes are native to southeast Asia and India and are produced in tropical climates. They were introduced to the U.S. in the late 1800s, and a few commercial acres still exist in California and Florida.

Anti Inflammation therapy for Retinal Disease

The discovery of an inflammatory mediator key to the blinding effects of diabetic retinopathy is pointing toward a potential new treatment, Medical College of Georgia researchers said.
Interleukin-6, known to contribute to the debilitating joint inflammation of rheumatoid arthritis, also helps ignite inflammation of the retina, a first step in a disease that is the leading cause of blindness is working-age adults, MCG researchers reported online in Investigative Ophthalmology & Visual Science.
The finding has the scientists looking at whether an interleukin-6 antibody, which is showing success in treating rheumatoid arthritis, can halt inflammation in mice with diabetic retinopathy. "We expect that this neutralizing antibody can be used to treat diabetic retinopathy in the future," said Dr. Wenbo Zhang, assistant research scientist in MCG's Vascular Biology Center. Drs. Zhang and Modesto Rojas, senior postdoctoral fellow, are co-first authors on the paper.
Angiotensin II, a powerful constrictor of blood vessels, is typically associated with the kidneys where it plays a vital role in regulating blood pressure. The scientists suspect angiotensin II helps promotes wound healing and regulation of pressure within small blood vessels in the eye.
However in diabetes, angiotensin II levels increase in the eye -- probably in response to high glucose levels -- and help promote inflammation, spurring remodeling of blood vessels and tissue destruction, Dr. Rojas said. "Vascular inflammation is one of the first steps to inducing the changes in the retina."
MCG scientists have shown interleukin-6 is a needed accomplice whose previously undetectable levels in the eye also increase, said Dr. Ruth Caldwell, cell biologist a the Vascular Biology Center and the Charlie Norwood Veterans Affairs Medical Center and the study's corresponding author.
With the help of interleukin-6, angiotensin II induces white blood cells to stick to the endothelial cells lining blood vessels of the retina, which slows blood flow. The white blood cells also start producing inflammatory and vascular growth factors that cause blood vessel walls to leak and thicken, further constricting blood flow. Retinal cells start dying from the reduced blood and oxygen supplies that result. In response, the body prompts growth of new blood vessels, presumably to help but instead causing more vision impairment.
If the trigger, high glucose, was temporary, these natural responses might help clear damaged cells and protect the eye. "Inflammation is a compensatory mechanism that gets activated as a survival mechanism," Dr. Rojas said. "If it continues, the effect is bad."
"We have known for along time if patients keep their blood sugar under perfect control, they don't have these problems, but that's hard," Dr. Caldwell adds. "That is why it's such a difficult disease."
To examine interleukin-6's role in the destruction, the researchers injected angiotensin II into the vitreous portion of the eyes of mice missing the gene for the inflammatory factor as well as normal mice. The extra angiotensin did little to the retinal vessels of mice lacking interleukin-6 but vessels in the normal mouse retina mimicked the inflammatory reaction found in diabetic retinopathy. When they reintroduced interleukin-6 to the genetically altered mice, the damage mimicked that of the normal mice. "So when we knock out interleukin-6, we can block the effects of angiotensin II," Dr. Caldwell said.
The scientists want to see whether the interleukin-6 antibody can be used to prevent damage by giving it shortly after the onset of diabetes in rodents and as a treatment by using it later in the disease process.
The research was funded by the National Institutes of Health, the Department of Veterans Affairs and postdoctoral fellowship awards from the Juvenile Diabetes Research Foundation International and the American Heart Association.
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Chlamydial Infections can't be prevented by just screening girls alone

Chlamydial Inclusion Bodies

Frequent testing and treatment of infection does not reduce the prevalence of chlamydia in urban teenage girls, according to a long-term study by Indiana University School of Medicine researchers published in the January 1, 2010 issue of the Journal of Infectious Diseases.
Despite the fact they were screened every three months and treated when infected, the proportion of infected girls did not change over the course of the study. On entering the study, 10.9 percent of the young women were infected. After 18 months of participation, 10.6 percent were infected; 10.4 percent were infected at the four-year mark.
Eighty-four percent of repeated infections were reinfections. In spite of being so highly motivated that they kept diaries of their sexual encounters and interacted at least quarterly with the study staff, some of the young women had unprotected sex with either an untreated partner or a new partner and subsequent infection occurred. The researchers determined that 13 percent of repeated infections were due to failure of antibiotics to cure an earlier infection; considering all infections, antibiotic treatment was 92.1 percent effective.
"The rate of infection we found in the 365 Indianapolis girls we followed is similar to the rates reported by other researchers for girls in Denver and Baltimore, so it is likely that our important new findings on reinfection can be generalized to urban teenage girls in other cities," said Byron E. Batteiger, M.D., professor of medicine at the IU School of Medicine, an infectious disease specialist who is the first author of the study.
The researchers obtained a biological sample from as many sex partners of the study participants as possible to determine if the boys were chlamydia infected. "We were able to test 22.6 percent of all the partners that the girls named in the study. We determined that 26.2 percent of the participating boys were infected -- a very high level of infection in this pool of young men to whom young women in the study were exposed," noted Dr. Batteiger.
Current national recommendations call for routine chlamydia screening of women based on age and history of sexual activity. There is no similar recommendation for screening young men.
"The high rate of reinfection we found in our study strongly suggests there may be some real limits on what we can do to control chlamydia without doing a better job of controlling chlamydia in young men," said J. Dennis Fortenberry M.D. M.S., professor of pediatrics at the IU School of Medicine, an adolescent medicine physician who is the senior author of the study.
"We also need to make sure that sexually active teens are aware of fact that unlike some other diseases, having chlamydia and being successfully treated for it does not give the individual immunity from reoccurrence," said Dr. Fortenberry, who urges physicians to repeatedly screen adolescents for the disease.
Chlamydia is the most common bacterial sexually transmitted infection and is associated with an increased risk of pelvic inflammatory disease, ectopic pregnancy, tubal infertility, and increased susceptibility to human immunodeficiency virus infection. Chlamydia is more common in sexually active teens than in any other age group.
In addition to Dr. Batteiger and Dr. Fortenberry, co-authors of the study are IU School of Medicine faculty members Wanzhu Tu, Ph.D.; Susan Ofner, M.S.; Barbara Van Der Pol, Ph.D.; Diane R. Stothard, Ph.D.; Donald P. Orr, M.D.; and Barry P. Katz, Ph.D. In addition to their IU affiliations, Dr. Tu is a Regenstrief Institute investigator, Dr. Orr and Dr. Katz are Regenstrief Institute affiliated scientists and Dr. Van Der Pol is with the Marion County Department of Health. Dr. Stothard, formerly with the IU School of Medicine, is presently affiliated with Eli Lilly and Company. The study was funded by the National Institutes of Health.
The IU School of Medicine is located on the Indiana University-Purdue University Indianapolis campus.

Early Scents Really Do Get 'Etched' In The Brain

Common experience tells us that particular scents of childhood can leave quite an impression, for better or for worse. Now, researchers reporting the results of a brain imaging study online on November 5th in Current Biology, a Cell Press publication, show that first scents really do enjoy a "privileged" status in the brain."We found that the first pairing or association between an object and a smell had a distinct signature in the brain," even in adults, said Yaara Yeshurun of the Weizmann Institute of Science in Israel. "This 'etching' of initial odor memories in the brain was equal for good and bad smells, yet was unique to odor." Sounds did not have the same effect, the research showed.

In the study, the researchers presented adults with a visual object together with one, and later with a second, set of pleasant and unpleasant odors and sounds while their brains were imaged by functional magnetic resonance imaging (fMRI). A week later, the researchers presented the same objects inside the fMRI and tested participants' associations of those images with the scents and smells.

The researchers found that people remembered early associations more clearly when they were unpleasant, regardless of whether they were smelled or heard. The images, however, revealed a unique activation in particular brain regions in the case of their first olfactory (but not auditory) associations. That signature held regardless of whether the odors or sounds were pleasant or unpleasant. The researchers even found that they could predict what a person would remember later based on the activity in their brains on day 1.

Yeshurun explained that it makes good sense to remember unpleasant memories as a kind of evolutionary "risk management." But the findings show that there is also something particularly special about early memories of smells.

That wasn't really unexpected, Yeshurun said -- it is after all a phenomenon that has long fascinated authors, poets, and scientists alike. Still, the results did hold some surprises.

"We expected a unique representation of initial or 'first' olfactory associations but did not expect that it would materialize even in cases where the behavioral evidence did not indicate a stronger memory," Yeshurun said. "In our paradigm, initial and later olfactory associations were remembered equally well, but only first associations had the unique brain representation."

In terms of understanding the brain, the findings suggest that activity in two brain regions, known as the hippocampus and amygdala, together can render a memory "special."

Although any application of the findings would be far off, Yeshurun said the results could suggest ways to strengthen particular memories. "Perhaps more importantly, it may help us generate methods to better forget early and powerful memories, such as trauma," she said.

The researchers include Yaara Yeshurun, Hadas Lapid, Yadin Dudai, and Noam Sobel, of the Weizmann Institute of Science, in Rehovot, Israel.

Babies' Language Learning Starts From The Womb

From their very first days, newborns' cries already bear the mark of the language their parents speak, reveals a new study published online on November 5th in Current Biology, a Cell Press publication. The findings suggest that infants begin picking up elements of what will be their first language in the womb, and certainly long before their first babble or coo."The dramatic finding of this study is that not only are human neonates capable of producing different cry melodies, but they prefer to produce those melody patterns that are typical for the ambient language they have heard during their fetal life, within the last trimester of gestation," said Kathleen Wermke of the University of Würzburg in Germany. "Contrary to orthodox interpretations, these data support the importance of human infants' crying for seeding language development."

Human fetuses are able to memorize sounds from the external world by the last trimester of pregnancy, with a particular sensitivity to melody contour in both music and language, earlier studies showed. Newborns prefer their mother's voice over other voices and perceive the emotional content of messages conveyed via intonation contours in maternal speech (a.k.a. "motherese"). Their perceptual preference for the surrounding language and their ability to distinguish between different languages and pitch changes are based primarily on melody.

Although prenatal exposure to native language was known to influence newborns' perception, scientists had thought that the surrounding language affected sound production much later, the researchers said. It now appears that isn't so.

Wermke's team recorded and analyzed the cries of 60 healthy newborns, 30 born into French-speaking families and 30 born into German-speaking families, when they were three to five days old. That analysis revealed clear differences in the shape of the newborns' cry melodies, based on their mother tongue.

Specifically, French newborns tend to cry with a rising melody contour, whereas German newborns seem to prefer a falling melody contour in their crying. Those patterns are consistent with characteristic differences between the two languages, Wermke said.

The new data show an extremely early impact of native language, the researchers say. Earlier studies of vocal imitation had shown that infants can match vowel sounds presented to them by adult speakers, but only from 12 weeks on. That skill depends on vocal control that just isn't physically possible much earlier, the researchers explain.

"Imitation of melody contour, in contrast, is merely predicated upon well-coordinated respiratory-laryngeal mechanisms and is not constrained by articulatory immaturity," they write. "Newborns are probably highly motivated to imitate their mother's behavior in order to attract her and hence to foster bonding. Because melody contour may be the only aspect of their mother's speech that newborns are able to imitate, this might explain why we found melody contour imitation at that early age."

The researchers include Birgit Mampe, University of Wurzburg, Wurzburg, Germany; Angela D. Friederici, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Anne Christophe, Ecole Normale Superieure/CNRS, Paris, France; and Kathleen Wermke, University of Wurzburg, Wurzburg, Germany.

Nobel Prize In Chemistry: What Ribosomes Look Like And How They Functions At Atomic Level

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2009 jointly to Venkatraman Ramakrishnan, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom; Thomas A. Steitz, Yale University, New Haven, CT, USA; and Ada E. Yonath, Weizmann Institute of Science, Rehovot, Israel, "for studies of the structure and function of the ribosome".

The ribosome translates the DNA code into life

The Nobel Prize in Chemistry for 2009 awards studies of one of life's core processes: the ribosome's translation of DNA information into life. Ribosomes produce proteins, which in turn control the chemistry in all living organisms. As ribosomes are crucial to life, they are also a major target for new antibiotics.

This year's Nobel Prize in Chemistry awards Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for having showed what the ribosome looks like and how it functions at the atomic level. All three have used a method called X-ray crystallography to map the position for each and every one of the hundreds of thousands of atoms that make up the ribosome.

Inside every cell in all organisms, there are DNA molecules. They contain the blueprints for how a human being, a plant or a bacterium, looks and functions. But the DNA molecule is passive. If there was nothing else, there would be no life.

The blueprints become transformed into living matter through the work of ribosomes. Based upon the information in DNA, ribosomes make proteins: oxygen-transporting haemoglobin, antibodies of the immune system, hormones such as insulin, the collagen of the skin, or enzymes that break down sugar. There are tens of thousands of proteins in the body and they all have different forms and functions. They build and control life at the chemical level.

An understanding of the ribosome's innermost workings is important for a scientific understanding of life. This knowledge can be put to a practical and immediate use; many of today's antibiotics cure various diseases by blocking the function of bacterial ribosomes. Without functional ribosomes, bacteria cannot survive. This is why ribosomes are such an important target for new antibiotics.

This year's three Laureates have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity's suffering.

V Ramakrishnan wins Nobel prize for Chemistry

Tamil Nadu-born Venkatraman Ramakrishnan, a senior scientist at the MRC Laborartory of Molecular Biology at Cambridge, has won the 2009 Nobel Prize for Chemistry along with two others, the Nobel Committee announced on Wednesday.

Born in 1952 in Chidambaram, Ramakrishnan shares the Nobel prize with Thomas E Steitz (US) and Ada E Yonath (Israel) for their "studies of the structure and function of the ribosome".


Ramakrishnan earned his B.Sc. in Physics (1971) from Baroda University and his Ph.D. in Physics (1976) from Ohio University.


He moved into biology at the University of California, San Diego, where he took a year of classes, then conducted research with Dr Mauricio Montal, a membrane biochemist.



With this 5.5 Angstrom-resolution structure, Ramakrishnan's group identified key portions of the RNA and, using previously determined structures, positioned seven of the subunit's proteins.


In the 21st September 2000 issue of Nature, Ramakrishnan published two papers. In the first of these, he presents the 3 Angstrom structure of the 30S ribosomal subunit.


His second paper reveals the structures of the 30S subunit in complex with three antibiotics that target different regions of the subunit. In this paper, Ramakrishnan discusses the structural basis for the action of each of these drugs.

After his postdoctoral fellowship, Ramakrishnan joined the staff of Brookhaven National Laboratory in the US. There, he began his collaboration with Stephen White to clone the genes for several ribosomal proteins and determine their three-dimensional structures.


He was also awarded a Guggenheim fellowship during his tenure there, and he used it to make the transition to X-ray crystallography.

Ramakrishnan moved to the University of Utah in 1995 to become a professor in the Department of Biochemistry. There, he initiated his studies on protein-RNA complexes and the entire 30S subunit.

He since moved to the MRC Laboratory of Molecular Biology in Cambridge, where he is a Senior Scientist and Group Leader in the Structural Studies Division. He joins the list of several Nobel laureates who worked at the laboratory.

Keep Swine Flu away From You

Here are eight measures that Horton thinks students and families should consider as they prepare for the opening of classes.

1. Have a physical exam before starting college. Washington and Lee requires all students to have a physical, and Dr. Horton believes it’s an important part of preparing for college.

2. Talk to your doctor about recommended immunizations for adolescents and young adults and make sure all of your vaccinations are up to date. Make plans to get a flu shot in the fall. Dr. Horton cautions that this will be the year when student health centers will be doing more outreach than ever to see that students get vaccinated against the flu — both the normal seasonal shot and the H1N1 vaccine when it becomes available.

3. Have a parents-student conversation about expectations regarding alcohol, other drugs and sexual activity.

4. Check your health insurance. Families need to be aware, says Horton, of what kind of coverage the student will have on campus, including whether or not the prescription drug plan will be honored at pharmacies in the area.

5. Bring a first aid kit with common, over-the-counter medications.

6. Do what your mom always told you. Wash your hands, cover your cough, dispose of used tissues.

7. Watch your diet. Unhealthy eating habits are easy to pick up when no one is there to make sure you eat your veggies.

8. Get plenty of sleep. “For some reason, students get to college and their clock seems to shift, and they stay up too late, and they still have 8 o’clock classes,” said Horton. “They stay up talking to friends in the hall, and they don’t start their work until 11 or 12, and they’re up half the night doing their homework. Sleep deprivation among students is a very unhealthy habit.”