Swine Flu Outbreak Illuminated By Avian Flu Research

A new study by University of Maryland researchers suggests that the potential for an avian influenza virus to cause a human flu pandemic is greater than previously thought. Results also illustrate how the current swine flu outbreak likely came about. As of now, avian flu viruses can infect humans who have contact with birds, but these viruses tend not to transmit easily between humans. However, in research recently published in the Proceedings of the National Academy of Sciences, Associate Professor Daniel Perez from the University of Maryland showed that after reassortment with a human influenza virus, a process that usually takes place in intermediary species like pigs, an avian flu virus requires relatively few mutations to spread rapidly between mammals by respiratory droplets.

"This is similar to the method by which the current swine influenza strain likely formed," said Perez, program director of the University of Maryland-based Prevention and Control of Avian Influenza Coordinated Agricultural Project, AICAP. "The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus. After mutating to be able to spread by respiratory droplets and infect humans, it is now spreading between humans by sneezing and coughing."

In his study, Perez used the avian H9N2 influenza virus, one that is on the list of candidates for human pandemic potential. Using reverse genetics, a technique whereby individual genes from viruses are separated, selected, and put back together, Perez and his team created a hybrid human-avian virus. Their research hybrid has internal human flu genes and surface avian flu genes from the H9N2 virus. Though it comes from a different strain of avian flu than the one that contributed to the hybrid virus now causing the swine flu outbreak, Perez's research virus is similar in origin to the swine flu virus, in that both involved a combination of avian and human influenza viruses.

Perez infected ferrets (considered a good model for human influenza transmission) with the virus he created, and allowed the virus to mutate in the species. Before long, healthy ferrets that shared air space but not physical space with the infected ferret had the virus, showing that the virus had mutated to spread by respiratory droplets.

When the genetic sequences of the mutant virus and original hybrid virus were compared, the only differences were five amino acid mutations, three on the surface, and two internally. Two of the surface mutations were determined to be solely responsible for supporting respiratory droplet transmission. Because so few mutations were necessary to make the hybrid H9N2 transmissible this way, they concluded that after an animal-human hybrid influenza virus forms in nature, a human pandemic of this virus is potentially just a few mutations away.

"We do not know if the mutations we saw in the lab are the same that have made the H1N1 swine flu transmissible by respiratory droplets," Perez said. "We will be doing more research on the current swine flu strain to study its specific genetic mutations."

Perez found that one of the two of the genetic mutations in his lab strain that enabled respiratory transmission between mammals was on the tip of the HA surface protein, one of the sites where human antibodies created in response to current vaccines would bind.

"Because the binding site of the mutant virus is different from the virus upon which the vaccine is modeled, it may mean that current vaccine stocks would not be as effective against the H9N2 mutant strain as previously anticipated," said Perez. "We should keep this in mind when designing vaccines for an avian flu pandemic in humans."

However, scientists cannot predict what the actual mutations will look like if and when they occur in nature, or even which strain of avian influenza will mutate to infect mammals.

"This is just the tip of the iceberg," said Perez. "Many more studies have to be done to see which combinations of mutations cause this type of transmission before we can design the appropriate vaccines."

Perez will be talking this week with the NIH and the CDC to discuss his team's role in researching the current swine flu virus strain. Perez will likely do studies related to vaccine development, virus transmission between humans and animals, and the pathogenesis of the virus.

A virus vaccine is derived from the virus itself. The vaccine consists of virus components or killed viruses that mimic the presence of the virus without causing disease. These prime the body's immune system to recognize and fight against the virus. The immune system produces antibodies against the vaccine that remain in the system until they are needed. If that virus, or in some cases a closely similar one is later introduced into the system, those antibodies attach to viral particles and remove them before they have time to replicate, preventing or lessening symptoms of the virus.

The immune system also retains antibodies to a virus after being infected with it, so humans have general immunity to human strains of avian influenza strains. But humans do not generally have immunity to avian flu strains because they have not been infected by them before. The surface proteins are sufficiently different to escape the human immune response. Avian flu strains are therefore more dangerous for humans because the human immune system cannot recognize the virus or protect against it.

Half A Glass Of Wine A Day May Boost Life Expectancy By Five Years

Drinking up to half a glass of wine a day may boost life expectancy by five years—at least in men, suggests research published ahead of print in the Journal of Epidemiology and Community Health.The Dutch authors base their findings on a total of 1,373 randomly selected men whose cardiovascular health and life expectancy at age 50 were repeatedly monitored between 1960 and 2000.

The researchers looked into how much alcohol the men drank, what type it was, and over what period, in a bid to assess whether this had any impact on the risks of their dying from cardiovascular disease, cerebrovascular disease, and from all causes.

They also tracked weight and diet, whether the men smoked, and for how long, and checked for the presence of serious illness.

During the 40 years of monitoring, 1,130 of the men died. Over half the deaths were caused by cardiovascular disease.

The proportion of men who drank alcohol almost doubled from 45% in 1960 to 86% in 2000, with the proportion of those drinking wine soaring from 2% to 44% during that period.

The researchers found that light long term alcohol consumption of all types—up to 20 g a day— extended life by around two extra years compared with no alcohol at all. Extended life expectancy was slightly less for those who drank more than 20 g.

And men who drank only wine, and less than half a glass of it a day, lived around 2.5 years longer than those who drank beer and spirits, and almost five years longer than those who drank no alcohol at all.

Drinking wine was strongly associated with a lower risk of dying from coronary heart disease, cerebrovascular disease, and death from all causes.

These results held true, irrespective of socioeconomic status, dietary and other lifestyle habits, factors long thought to influence the association between wine drinking and better health.

Turmeric: India's 'Holy Powder' Finally Reveals Its Centuries-old Secret

Scientists in Michigan are reporting discovery of the secret behind the fabled healing power of the main ingredient in turmeric — a spice revered in India as "holy powder."In the study, Ayyalusamy Ramamoorthy and colleagues point out that turmeric has been used for centuries in folk medicine to treat wounds, infections, and other health problems. Although modern scientific research on the spice has burgeoned in recent years, scientists until now did not know exactly how curcumin works inside the body.

Using a high-tech instrument termed solid-state NMR spectroscopy, the scientists discovered that molecules of curcumin act like a biochemical disciplinarian. They insert themselves into cell membranes and make the membranes more stable and orderly in a way that increases cells' resistance to infection by disease-causing microbes.

First Broad-spectrum Anti-microbial Paint To Kill 'Superbugs'

Scientists in South Dakota are reporting development of the first broad-spectrum antimicrobial paint, a material that can simultaneously kill not just disease-causing bacteria but mold, fungi, and viruses. Designed to both decorate and disinfect homes, businesses, and health-care settings, the paint is the most powerful to date, according to their new study.The paint shows special promise for fighting so-called "superbugs," antibiotic-resistant microbes that infect hospital surfaces and cause an estimated 88,000 deaths annually in the United States, the researchers say.

In the study, Yuyu Sun and Zhengbing Cao note in the antimicrobial paints already on are store shelves. These paints, however, are only effective against a narrow range of disease-causing microorganisms, limiting their usefulness.

The scientists already were aware of research on the germ-killing effects of that N-halamines, bleach-like substances already in wide use. They developed a new antimicrobial polymer that includes a type of N-halamine. It has no undesirable effects on the quality of latex paints. Laboratory tests showed that the new polymer kills a wide range of disease-causing microbes including those resistant to multiple antibiotics. The paint retains an anti-microbial punch for extended periods, and it can be easily "recharged" with a simple chlorination process, the researchers note.

Omega-3 Fatty Acids May Benefit Cancer Patients Undergoing Major Operations

New research from Trinity College Dublin published in this month’s Annals of Surgery points to a potentially significant advance in the treatment of patients undergoing major cancer surgery. The study was carried out by the oesophageal research group at Trinity College Dublin and St James’s Hospital. A randomised controlled trial showed omega-3 fatty acids given as part of an oral nutritional supplement resulted in the preservation of muscle mass in patients undergoing surgery for oesopahageal cancer, a procedure normally associated with significant weight loss and quality of life issues.The trial was designed by Professor John V Reynolds, Professor of Surgery at Trinity College Dublin and St James’s Hospital, Dublin, and Dr Aoife Ryan PhD, a research dietitian at St James’s Hospital, Dublin*.

Omega 3 fats are essential fats found naturally in oily fish, with highest concentrations in salmon, herring, mackerel, and sardines. Recently food manufacturers have begun to add omega 3 to foods such as yogurt, milk, juice, eggs and infant formula in light of a body of scientific evidence which suggests that they reduce cardiovascular disease risk, blood pressure, clot formations, and certain types of fat in the blood.

Previous studies had found that nutritional supplements containing one form of omega 3 fat, eicosapentaenoic acid (EPA), significantly reduced weight loss among inoperable cancer patients. The researchers hypothesised that a nutritional supplement rich in calories and a high dose of EPA would stem the debilitating weight loss seen in patients following oesophageal surgery. The group chose to study patients undergoing surgery for oesophageal cancer as this surgery is one of the most stressful and serious operations a patient can undergo.

Professor John V Reynolds, Professor of Surgery at TCD and St James’s Hospital and the lead researcher on the study said: “There are almost 450 new cases of oesophageal cancer diagnosed every year in Ireland and Ireland has one of the highest rates of oesophageal cancer in Europe. An increasing number of patients are treated with chemotherapy alone or in combination with radiation therapy before they undergo surgery. The surgery is a serious operation lasting several hours and can take weeks to recover from surgery and up to six months to recover pre-illness quality of life. Weight loss is extremely common both before and especially after this type of surgery, and any approach that can preserve weight, in particular muscle weight and strength, may represent a real advance”.

In a double-blinded randomised control trial, the gold standard in medical research, patients awaiting oesophagectomy surgery were randomly assigned to treatment and control groups. While both groups received a 240ml nutritional supplement twice daily starting five days before surgery (which was identical in calories, protein, micronutrients and flavor), patients in the treatment group received an enriched formula with omega 3 (2.2 gram EPA/day). Immediately following surgery, the supplement was given through a feeding tube for 14 days while patients recovered in hospital. Once patients could resume oral feeding, they continued drinking the supplement until 21 days post surgery.

The oesophageal research group at Trinity College Dublin and St James’s Hospital found that patients given the standard feed (without omega 3) suffered clinically severe weight loss post surgery – losing an average of 4 lbs of muscle mass post surgery, where as in the omega 3 group patients maintained all aspects of their body composition

Commenting on the significance of the results, Dr Aoife Ryan said: “The results were extraordinary in the sense that no previous nutritional formulation had revealed such an outcome, with supplemented patients maintaining all aspects of their body composition in the three weeks following surgery. Patients given the standard supplement without omega 3 lost a significant amount of weight comprising 100% muscle mass. In fact 68% of patients suffered ‘clinically severe’ weight loss post surgery in the standard group (without omega 3) versus only 8% in the omega 3 group. The significant finding was that the patients did not lose just fat, as one would expect with weight loss, but instead they depleted their muscle stores significantly. Research has shown that a loss of 5lbs of weight produces significant effects on quality of life and a patient’s ability to mobilise and perform simple activities of daily living. Losing 4 lbs of muscle is even more significant”.

Professor John Reynolds said: “Omega 3 enriched nutrition appears to prevent loss of muscle mass by reducing the amount of inflammatory markers in the blood – this means the metabolism is not as stressed as it usually is post surgery. We also saw that the omega 3 group was less likely to have a fever in the first week post surgery which points to the ability of omega 3 to suppress inflammation. Looking at their blood tests omega 3 fed patients had much lower ‘inflammatory compounds’ circulating in their blood which points to the ability of omega 3 to reduce inflammation”.

Using specialised nutritional feeds with a highly purified form of EPA, the researchers were able to administer a dose of omega 3 that was much higher than that typically found in food. They noted that treatment with omega 3 enriched supplement is only slightly more expensive than traditional nutritional therapy, and previous studies have yielded significant cost-savings in the form of fewer complications following surgery using immuno-nutrition feeds similar to this. “Initial treatments like this may be cost-effective for our cash-strapped health care system”, said Dr Ryan.

Commenting in an accompanying editorial in the Annals of Surgery Dr Michael Meguid, Professor of Surgery at State University of New York noted: “This study is a significant step forward because it underscores the message to surgeons of the importance of using omega 3 based nutrition as an adjunct therapy started at least 5 days before surgery. It should no longer be a surgeon’s preference, but the standard of expected norm for the practice of elective complex gut cancer surgery”.

In conclusion, Professor John Reynolds said: “This study has provided an interesting insight into how nutritional therapy can positively impact on the major stress of cancer surgery. More studies need to be done, in particular to address whether such approaches lead to more rapid recovery of quality of life, reduce complications, and improve outcomes. Throughout cancer care, many patients undergoing therapy nowadays have a combination of surgery, chemotherapy and radiation therapy, and studies addressing whether nutritional supplementation with omega 3 for the entire duration of treatment should be considered. Finally, we do not expect these findings are unique to cancer surgery, and similar benefits may accrue to patients needing complex surgical care for non-cancer problems, for instance liver transplantation or major cardiac surgery.”

This trial was supported by a research grant from Abbott Laboratories

Specific Lung Cancer Susceptibility Gene Identified

University of Cincinnati (UC) cancer cell biologists have identified a distinct gene linked to increased lung cancer susceptibility and development. They say this gene—known as RGS17—could result in a genetic predisposition to develop lung cancer for people with a strong family history of the disease.With further investigation, they believe the gene could be used to identify high-risk patients who may benefit from earlier, more aggressive lung cancer screening.

Marshall Anderson, PhD, and his colleagues report their findings in the April 15, 2009, issue of the journal Clinical Cancer Research.

“Understanding how the RGS17 gene impacts cancer development could change clinical diagnosis and treatment as radically as discovery of the breast cancer genes (BRCA1 and BRCA2) did,” explains Anderson, who has led the multi-institutional Genetic Epidemiology of Lung Cancer Consortium (GELCC) studying the genetic basis of lung cancer since 1997. “A proven genetic test could help us identify people at risk before the disease progresses.”

According to the American Cancer Society, lung cancer is the leading cause of cancer related disease and death. Although tobacco smoke is the primary environmental cause of the disease, science has shown there is also a strong genetic component to the disease.

“This study represents a significant contribution to our understanding of lung cancer susceptibility and is another step toward to the goal of preventive medicine,” says David Christiani, MD, MPH, a professor of occupational medicine and environmental health at the Harvard School of Public Health, whose two-page commentary on the study is published in conjunction with the GELCC team’s scientific findings. “The authors undertook a daunting challenge of performing a family-based study of lung cancer in an effort to identify specific causal genes.”

Genes, which are located in fixed positions on the cell's chromosomes, carry the DNA code that determines inherited characteristics, including a risk of certain diseases.

For this study, Anderson and his multi-institutional team collected biological samples from numerous multigenerational families with five or more members who were affected by lung cancer. Through a combination of what is known as “fine mapping”—where genetic information is dissected and analyzed—and genetic association studies, researchers identified RGS17 as a major candidate susceptibility gene for familial lung cancers.

Research has shown that lung cancer can occur sporadically—where people have no known risk factors or family history—or hereditarily, occurring in multiple members of the same family. In 2004, Anderson’s team reported the first genetic evidence of a major lung cancer “susceptibility locus” on chromosome 6, and evidence of a susceptibility region on three other chromosomes.

The region of the original chromosome where the lung cancer markers were found contained about 100 genes, including several genes suspected to be involved in tumor suppression and cell growth.

Using a genetically altered mouse model, researchers determined that when RGS17 was suppressed, lung tumors shrank, proving the gene was involved in cancer development and must be present for cancer growth.

“What was most interesting is that this same gene was over-expressed in 60 percent of the samples from non-hereditary lung tumors,” explains Anderson. “This suggests that perhaps epigenetic factors may be contributing to abnormal genetic development.”

The UC-led team will conduct additional research to investigate how environmental factors may influence familial cancer development.

Funding for this research comes from the National Institutes of Health through the Genetic Epidemiology of Lung Cancer Consortium, a collaborative research effort established in 1997 to research the genetic origins of familial lung cancers. Anderson serves as principal investigator. Collaborating institutions include Washington University-St. Louis, Mayo Clinic-Rochester, University of Colorado, University of Texas Southwestern Medical Center, Louisiana State University, Saccomanno Research Institute, National Cancer Institute, National Human Genome Research Institute, Karmanos Cancer Institute, University of Toledo and M.D. Anderson Cancer Center-Houston.

Mass Spec Technique Analyzes Defensive Chemicals On Seaweed Surfaces For Potential Drugs

A new analytical technique is helping scientists learn how organisms as simple as seaweed can mount complex chemical defenses to protect themselves from microbial threats such as fungus. Known as desorption electrospray ionization mass spectrometry (DESI-MS), the technique for the first time allows researchers to study unique chemical activity taking place on the surfaces of these organisms.Understanding this surface chemistry could one day allow scientists to borrow and adapt some of those defensive chemical compounds for use against cancer, HIV, malaria, drug-resistant bacteria and other diseases of humans. In a paper scheduled to be published online in the journal Proceedings of the National Academy of Sciences, researchers from the Georgia Institute of Technology describe a sophisticated chemical defense system that uses 28 different compounds to protect a species of seaweed against a single fungus.

"Plants and animals in the wild use chemistry as way to fight with one another," said Julia Kubanek, a professor in Georgia Tech's School of Biology. "Using this new technology, scientists can listen in on this fight to perhaps learn from what's going on and steal some of the strategies for human biomedical applications."

As part of a long-term project sponsored by the Natural Institutes of Health, Georgia Tech scientists have been cataloging and analyzing natural compounds from more than 800 species found in the waters surrounding the Fiji Islands. They have been particularly interested in Callophycus serratus, an abundant species of red seaweed that seems particularly successful – and adept at fighting off microbial infections.

Using the DESI-MS technique, the researchers analyzed recently-collected samples of the seaweed and found groups of potent anti-fungal compounds in light-colored microscopic surface patches covering what may be wounds on the surface of the seaweed. In laboratory testing, these bromophycolide compounds and callophycoic acids effectively inhibited the growth of Lindra thalassiae, a common marine fungus.

"It is possible that the alga is marshalling its defenses and displaying them in a way that blocks the entry points for microbes that might invade and cause disease," Kubanek said. "Seaweeds don't have B cells, T cells and immune responses like humans do. But instead they have some chemical compounds in their tissues to protect them."

Though all the seaweed they studied was from a single species, the researchers were surprised to find two distinct groups of anti-fungal chemicals. From one seaweed subpopulation, dubbed the "bushy" type for its appearance, 18 different anti-fungal compounds were identified. In a second group of seaweed, the researchers found 10 different anti-fungal compounds – all different from the ones seen in the first group.

"This species is producing some unique chemical compounds that other seaweeds don't produce, and it is producing a large number of compounds, each of which has a role to play in the overall defense against the fungus," Kubanek noted. "We think the compounds work together in an additive way."

Though chemically different, the compounds are structurally related and seem to arise from a similar metabolic pathway in the seaweed. Why one species of simple organism would produce 28 different anti-fungal compounds remains a mystery, though Kubanek believes the chemicals may also have other uses that are not yet understood.

The compounds have been tested for potential activity against drug-resistant bacteria, cancer, HIV, malaria and other human health threats. So far, preliminary testing suggests they have anti-malarial effects.

The DESI-MS technique allowed the researchers for the first time to analyze chemical activity occurring on the surface of the seaweed. Earlier techniques allowed identification of chemicals in the organism's tissue, but being able to confirm their location on the surface – the first line of defense against infection – confirms the role they play as defensive chemicals.

In DESI-MS, a charged stream of polar solvent is directed at the surface of a sample under study at ambient pressure and temperature. The spray desorbs molecules, which are then ionized and delivered to the mass spectrometer for analysis.

"This technique allows us to examine intact organisms and see how the chemical compounds are distributed," Kubanek explained. "For our research with seaweed, this is important because we'd like to understand how an organism distributes these compounds to protect itself from enemies."

In addition to Kubanek, others researchers contributing to the study included Leonard Nyadong, Asiri Galhena, Tonya Shearer, E. Paige Stout, R. Mitchell Parry, Mark Kwasnik, May Wang, Mark Hay, and Facundo Fernandez – all from Georgia Tech – and Amy Lane, now at Scripps Institution of Oceanography. Beyond the National Institutes of Health support, the research has also been sponsored by the National Science Foundation.

For the future, Kubanek and a graduate student are working to modify the most promising of the anti-malarial compounds, replacing some oxygen atoms for nitrogen atoms and bromine for chlorine and fluorine. The hope is to create a compound more potent against the malaria organism with less toxicity for humans.

"We are doing reaction chemistry using these 28 compounds as a starting point," she explained. "Learning about how other species avoid diseases may give us something we can use to avoid or treat our own diseases."

Molecule Prompts Damaged Heart Cells To Repair Themselves After A Heart Attack

A protein that the heart produces during its early development reactivates the embryonic coronary developmental program and initiates migration of heart cells and blood vessel growth after a heart attack, researchers at UT Southwestern Medical Center have found.The molecule, Thymosin beta-4 (TB4), is expressed by embryos during the heart's development and encourages migration of heart cells. The new findings in mice suggest that introducing TB4 systemically after a heart attack encourages new growth and repair of heart cells. The research findings indicate that the molecule affects developmental gene expression as early as 24 hours after systemic injection. The UT Southwestern study is online and will appear in an upcoming issue of the Journal of Molecular and Cellular Cardiology.

"This molecule has the potential to reprogram cells in the body to get them to do what you want them to do," said Dr. J. Michael DiMaio, associate professor of cardiothoracic surgery at UT Southwestern and senior author of the study. Obviously, the clinical implications of this are enormous because of the potential to reverse damage inflicted on heart cells after a heart attack."

Tremendous medical progress has been made to counter the damaging effects of heart attacks, but ordinarily, mammalian hearts are incapable of repairing themselves following damage. They are also limited in their ability to form new blood vessels. Earlier studies demonstrated that TB4 is expressed in the embryonic heart and stimulates cardiac vessels to form. It was therefore thought that introduction of TB4 might activate new vessel growth in the adult heart.

In this mouse study researchers found that TB4 initiates capillary tube formation of adult coronary endothelial cells in tissue culture. The molecule also encourages cardiac regeneration by inhibiting death in heart cells after an injury such as a heart attack and by stimulating new vessel growth.

"We observed that by injecting this protein systemically, there was increased cardiac function after a heart attack," said Dr. Ildiko Bock-Marquette, assistant professor of cardiothoracic surgery at UT Southwestern and the study's lead author. "We hope this protein can inhibit cell death that occurs during a heart attack in the short term, and that it may initiate new growth of coronary vessels by activating progenitor cells in the long term."

Researchers assessed the effect of TB4 on new vessel growth in adult mice after inducing heart attacks and then following up by introducing TB4 into the animals. An examination of the capillary smooth muscle cells following treatment with TB4 showed a significant increase in capillary density in the heart three days afterward near the site of the heart attack, the scientists reported.

Further studies will examine whether the same events occur in larger mammals and which receptors are responsible for the action of this molecule.

Other UT Southwestern researchers involved in the study were Santwana Shrivastava, research assistant; and John Shelton, senior research scientist. Study authors also included Dr. Teg Pipes, former postdoctoral fellow; Jeffrey Thatcher, a doctoral candidate in biomedical engineering; Dr. Cristi Galindo, postdoctoral research fellow; and co-senior author, Dr. Eric Olson, chairman of molecular biology.

The work was supported by the Ted Nash Long Life Foundation, the American Heart Association, and the National Institutes of Health.

How Tumor Cells Move

Researchers in Heidelberg discover new protein that is suppressed in particularly aggressive cancer cell.If cancer cells lack a certain protein, it could be much easier for them to penetrate healthy body tissue, the first step towards forming metastases. Scientists at the Pharmacology Institute of the University of Heidelberg have discovered the previously unknown cell signal factor SCAI (suppressor of cancer cell invasion), which inhibits the movement and spread of tumor cells in laboratory tests. When the factor’s functioning was disrupted, the cancer cells moved much more effectively in what are known as three-dimensional matrix systems, which imitate some of the tissue properties of the human body.

“The protein is apparently suppressed in many types of tumors, e.g. breast, lung, or thyroid,” explains Dr. Robert Grosse, head of the Emmy Noether Junior Research Group funded by the German Research Association (DFG) at the Pharmacology Institute. The new factor could be an interesting starting point for research into new mechanisms for fighting cancer. The research team’s results have now been published online in the prestigious international journal Nature Cell Biology.

Focus on particularly aggressive cancers

Tumor cells are extremely mobile and “adept” at penetrating healthy tissue to form metastases. They adapt to the consistency of the respective tissue by changing their shapes constantly and attach flexibly to surrounding tissues during movement with the help of special surface structures (receptors).

One of these receptors is what is known as b1-integrin, which is frequently formed in many tumors such as metastasizing breast cancer. “The cell signal factor SCAI controls the formation and function of b1-integrin,” says Dr. Robert Grosse. “If there is too little SCAI in tumor cells, then b1-integrin is overactive, so to speak. The cell can change more rapidly to a more aggressive form and penetrate surrounding tissue, a crucial step toward increased spreading of the tumor and the possible formation of metastases.”

In their recently published study, the Heidelberg researchers examined cells from skin cancer (melanoma) and breast cancer. In other projects, Dr. Robert Grosse’s team would like to study the function of the signal factor SCAI more closely in an animal model. “If the function of SCAI is confirmed to be decisive in the formation of especially aggressive tumor cells, this could be a promising starting point for developing new diagnostic methods or medication,” says the pharmacologist. It could also be possible to develop an agent that prevents the genetic suppression of the signal factor in cancer cells. But first the researchers need to better understand how the signal factor itself is regulated in the cell.

Dance Your Way To Successful Aging

Older people can dance their way towards improved health and happiness, according to a report from the Changing Ageing Partnership (CAP).The research, by Dr Jonathan Skinner from Queen’s University Belfast, reveals the social, mental and physical benefits of social dancing for older people. It suggests that dancing staves of illness, and even counteracts decline in ageing.

Recommendations include the expansion of social dance provision for older people in order to aid successful ageing and help older people enjoy longer and healthier lives.

Jonathan Skinner, Lecturer in Social Anthropology at the School of History and Anthropology at Queen’s, studied the effects of social dancing amongst older people in Northern Ireland, Blackpool and Sacramento, USA.

Dr Skinner said: "I have found that social dancing leads to a continued engagement with life - past, present, and future - and holds the promise for successful ageing. It contributes to the longevity of the dancers, giving them something to enjoy and focus upon - to live for. It alleviates social isolation and quite literally helps take away the aches and pains associated with older age.

“In addition to this, and especially in Northern Ireland, dancing brings people together across communities, creating solidarity, tolerance and understanding."

Sarah, a 70-year-old from Bangor and a regular ice-dancer, took part in the study. Sarah said: "My daughters brought me down to the ice rink. I have to say, after years of dancing on a Ballroom floor, I was very impressed and skating has great flow and speed. I’ve been doing it for twelve years now. We do the rumba, quickstep, foxtrot and tango. My instructor even wanted me to compete. My friends have commented that my energy is overwhelming, ‘what’s the secret?’ they ask, and I just say ‘keep dancing’.”

Dr Una Lynch, CAP Research Manager at Queen’s said: "Dr Skinner's study is the seventh piece of CAP research to be completed and we are delighted to be involved in a study that challenges stereotypical images of ageing and highlights the fact that healthy ageing can be fun."

The researcher, Jonathan Skinner, will present further findings and recommendations of the research at a research launch at the Institute of Governance at Queen’s University Belfast on Wednesday 1 April.

Red In The Face? People Use The Color Of Your Skin To Judge How Healthy You Are

People use the color of your skin to judge how healthy you are, according to researchers at the University of St Andrews. Scientists in the School of Psychology have shown that there is truth to the received wisdom that a "rosy" complexion denotes healthiness, whilst a "green" or "pale" color indicates illness.

Lead researcher Ian Stephen worked with the University's Perception Lab to determine how face color is associated with healthy looks.

Several monkey species use redness in their faces or sexual skin to advertise their health status and to attract mates. The team was keen to discover whether similar mechanisms were at work in humans.

Ian Stephen said, "Parents and doctors know that when you get ill, you can end up looking pale. Our research goes further and shows that even young, healthy university students can benefit from a complexion reflecting more blood and more oxygen in the skin."

The team from the University of St Andrews first measured how skin color varies with the amount of blood and oxygen in the blood.

These measurements were used with computer graphics to allow research participants to change the color of the faces in the photographs to look as healthy as possible. The team found that, for all faces, participants added more oxygen rich blood color to improve the healthy appearance.

Stephen continued, "Our skin contains many tiny blood vessels that carry blood laden with oxygen to the skin cells, allowing them to "breathe", and allowing us to lose heat during exercise. People who are physically fit or have higher levels of sex hormones have more of these blood vessels and flush easier than people who are unhealthy, unfit, elderly or smokers. Physically fit people also have more oxygen in their blood than people who are unfit or have heart or lung illnesses."

Professor Dave Perrett, head of the Perception Lab commented, "Our evaluators all thought that bright red blood with lots of oxygen looked healthier than darker, slightly bluer blood with lower oxygen levels. It is remarkable is that people can see this subtle difference."

"This may explain why some people with very red faces do not look so healthy; the color of their blood may be wrong. So it's not just the amount of blood that's important; it's the type of blood that determines healthy looks".

The research shows that people use the color of the blood in your skin to judge how healthy you are.

"Since your attractiveness relies upon how healthy you look, you might be able to make yourself more attractive by being kind to your heart and lungs in doing more exercise or quitting smoking," concluded Ian Stephen.

Waist Size Found To Be Predictor Of Heart Failure In Both Men And Women

Adding to the growing evidence that a person's waist size is an important indicator of heart health, a study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has found that larger waist circumference is associated with increased risk of heart failure in middle-aged and older populations of men and women.The findings, published online in the April 7 Rapid Access Report of the journal Circulation: Heart Failure, showed that increased waist size was a predictor of heart failure even when measurements of body mass index (BMI) fell within the normal range.

"Currently, 66 percent of adults in the United States are overweight or obese," explains Emily Levitan, ScD, the study's first author and a Research Fellow in the Cardiovascular Epidemiology Research Unit at BIDMC. "Knowing that the prevalence of heart failure increased between 1989 and 1999, we wanted to better understand if and how this increase in obesity was contributing to these rising figures."

A life-threatening condition that develops when the heart can no longer pump enough blood to meet the body's needs, heart failure (also known as congestive heart failure) is usually caused by existing cardiac conditions, including high blood pressure and coronary artery disease. Heart failure is the leading cause of hospitalization among patients 65 and older, and is characterized by such symptoms as fatigue and weakness, difficulty walking, rapid or irregular heartbeat, and persistent cough or wheezing.

The researchers examined two Swedish population-based studies, the Swedish Mammography Cohort (made up of 36,873 women aged 48 to 83) and the Cohort of Swedish Men (43,487 men aged 45 to 79) who responded to questionnaires asking for information about their height, weight and waist circumference. Over a seven-year period between January 1998 and December 2004 the researchers reported 382 first-time heart-failure events among the women (including 357 hospital admissions and 25 deaths) and 718 first-time heart-failure events among men (accounting for 679 hospital admissions and 39 deaths.)

Their analysis found that based on the answers provided by the study participants, 34 percent of the women were overweight and 11 percent were obese, while 46 percent of the men were overweight and 10 percent were obese.

"By any measure – BMI, waist circumference, waist to hip ratio or waist to height ratio –our findings showed that excess body weight was associated with higher rates of heart failure," explains Levitan.

Further breakdown of the numbers showed that among the women with a BMI of 25 (within the normal range), a 10-centimeter higher waist measurement was associated with a 15 percent higher heart failure rate; women with a BMI of 30 had an 18 percent increased heart failure rate. In men with a BMI of 25, a 10-centimeter higher waist circumference was associated with a 16 percent higher heart failure rate; the rate increased to 18 percent when men's BMI increased to 30.

Furthermore, adds Levitan, among the men, each one-unit increase in BMI was associated with a four percent higher heart failure rate, no matter what the man's waist size. In women, she adds, BMI was only associated with increased heart failure rates among the subjects with the largest waists. Finally, the authors found that the association between BMI and heart-failure events declined with age, suggesting that the younger the person, the greater the impact of weight to heart health.

"This study reinforces the importance of maintaining a healthy weight," says Levitan. "Previous research has looked at various types of heart disease and related health issues, and no matter the particulars of the study, they've all been pretty consistent in determining that excess body weight increases a person's risk of heart disease."

Study coauthors include BIDMC investigators Murray A. Mittleman, MD, DrPH (senior author), Amy Z. Yang, BA and Alicja Wok, DrMedSci.

The study was supported by grants from the National Institutes of Health, the Swedish Research Council and the Swedish Foundation for International Cooperation in Research and Higher Education.

Broccoli Sprouts May Prevent Stomach Cancer By Defeating Helicobacter Pylori

A small, pilot study in 50 people in Japan suggests that eating two and a half ounces of broccoli sprouts daily for two months may confer some protection against a rampant stomach bug that causes gastritis, ulcers and even stomach cancer.Citing their new "demonstration of principle" study, a Johns Hopkins researcher and an international team of scientists caution that eating sprouts containing sulforaphane did not cure infection by the bacterium Helicobacter pylori (H. pylori). They do not suggest that eating this or any amount of broccoli sprouts will protect anyone from stomach cancer or cure GI diseases.

However, the study does show that eating a daily dose of broccoli sprouts reduced by more than 40 percent the level of HpSA, a highly specific measure of the presence of components of H. pylori shed into the stool of infected people. There was no HpSA level change in control subjects who ate alfalfa sprouts. The HpSA levels returned to pretreatment levels eight weeks after people stopped eating the broccoli sprouts, suggesting that although they reduce H. pylori colonization, they do not eradicate it.

"The highlight of the study is that we identified a food that, if eaten regularly, might potentially have an effect on the cause of a lot of gastric problems and perhaps even ultimately help prevent stomach cancer," says Jed W. Fahey, M.S., Sc.D., an author of the paper who is a nutritional biochemist in the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center at the Johns Hopkins University School of Medicine.

The discovery that sulforaphane is a potent antibiotic against H. pylori was reported in 2002 by Fahey and colleagues at Johns Hopkins. "Broccoli sprouts have a much higher concentration of sulforaphane than mature heads," Fahey explains, adding that further investigation is needed to affirm the results of this clinical trial and move the research forward. The study, published April 6 in Cancer Prevention Research, builds on earlier test-tube and mouse studies at Johns Hopkins and elsewhere about the potential value of sulforaphane, a naturally occurring biochemical found in relative abundance in fresh broccoli sprouts. Sulforaphane appears to trigger cells in the body, including in the gastrointestinal tract, to produce enzymes that protect against oxygen radicals, DNA-damaging chemicals, and inflammation.

In the new report, the team also shows that when H. pylori-infected mice sipped broccoli-sprout smoothies for eight weeks, there was up to a fourfold increase in the activity of two of these key enzymes that protect cells against oxidative damage. In addition, the number of Helicobacter bacteria in the mice's stomachs decreased by almost a hundredfold it did not change in infected control animals that drank plain water. The researchers also noted a greater than 50 percent reduction in inflammation of the primary target of this bacterium – the body of the stomach – in treated mice but not in controls.

In a related experiment, the team fed the same dose of broccoli sprouts for the same amount of time to H. pylori-infected mice that had been genetically engineered to lack the Nrf2 gene that activates protective enzymes. "These knock-out mice didn't respond," Fahey says, which confirms previous findings for a role of Nrf2 in protection against H. pylori-induced inflammation and gastritis.

Classified a carcinogen by the World Health Organization, H. pylori is a gastrointestinal tract germ that manages to thrive in the lining of the stomach despite the strength of natural acids there that rival that of car batteries. Afflicting several billion people – roughly half of the world's population – this corkscrew-shaped bacterium has long been associated with stomach ulcers, which now are frequently cured by antibiotics. Research strongly suggests that the bacteria also are linked to high rates of stomach cancer in some countries, that strains resistant to standard antibiotics are prevalent, and that multiple courses of standard antibiotics do not always eliminate the infection.

Working in Japan where there is high incidence of chronic H. pylori-infection, the research team gave 25 H. pylori-infected subjects two and a half ounces (70 grams) per day of broccoli sprouts for two months. Another 25 infected people consumed an equivalent amount of alfalfa sprouts which, although rich in phytochemicals, don't contain sulforaphane.

The researchers assessed the severity of Helicobacter infection at the start of the study, after four and eight weeks of treatment, and again eight weeks after intervention was stopped. They used breath tests to assess colonization by H. pylori bacteria and blood tests to judge the severity of inflammation in the stomach lining; in addition, they looked for antigens in stool samples to help determine the extent of the infections.

"We know that a dose of a couple ounces a day of broccoli sprouts is enough to elevate the body's protective enzymes," Fahey says. "That is the mechanism by which we think a lot of the chemoprotective effects are occurring.

"What we don't know is whether it's going to prevent people from getting stomach cancer. But the fact that the levels of infection and inflammation were reduced suggests the likelihood of getting gastritis and ulcers and cancer is probably reduced."

In disclosure of a potential conflict of interest, Fahey is a cofounder of, but holds no equity in, a company that is licensed by The Johns Hopkins University to produce broccoli sprouts. A portion of the proceeds is used to help support cancer research, but no such funds were provided to support this study.

"It's exciting that a chronic bacterial infection that poses great hazards to hundreds of millions of people globally can be ameliorated by a specific dietary strategy," says Paul Talalay, M.D., John Jacob Abel Distinguished Service Professor of Pharmacology and Experimental Therapeutics and director of the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center at Johns Hopkins' Institute for Basic Biomedical Sciences.

Talalay directs the lab where, in 1992, his team discovered the health-promoting properties of sulforaphane. A longtime proponent of cancer prevention and chemoprotection, Talalay eats fresh broccoli sprouts regularly, as does Fahey.

"I like them," Fahey says. "I eat them all the time, but not every day. Variety is the spice of life: I eat blueberries on the other days."

In addition to Fahey, the authors of the paper are Akinori Yanaka, Atsushi Fukumoto, Mari Nakayama and Souta Inoue, Tokyo University of Science, Japan; Masayuki Yamamoto, Songhua Zhang, Masafumi Tauchi, Hideo Suzuki and Ichinosuke Hyodo, University of Tsukuba, Japan.

New Link In Liver Cancer

Liver damage can be triggered by various insults, including hepatitis infection or alcohol-induced cirrhosis. In severe cases, this damage can lead to cancer. A new study by researchers at the National Institutes of Health and Osaka University reveals how one protein helps decide the fate of damaged livers in mice.Liver cells rely on signals triggered by growth hormone to survive and multiply—functions that go haywire in cancer. Normally, growth hormone works by activating a signaling network inside liver cells that includes a protein called STAT5. When the researchers removed STAT5 from liver cells, cancer ensued.

The normally protective effect of STAT5 was traced to its ability to hitch itself to a damage-inducing protein called TGFbeta and trigger its destruction. Without STAT5, TGFbeta levels soared, and growth hormone activated a related protein, STAT3, which is known to promote tumor growth.

TGFbeta and STAT5 appear to be adversaries in the liver, according to the study. STAT5 protects the liver by breaking down TGFbeta. But when TGFbeta is abundant—as occurs in people with chronic liver damage—growth hormone activates the cancer-promoting STAT3 instead of the protective STAT5. These results might help explain how chronic liver damage can eventually lead to cancer.

The study will be published online on March 30th in the Journal of Experimental Medicine.

Sleep May Help Clear Brain For New Learning

A new theory about sleep's benefits for the brain gets a boost from fruit flies in the journal Science. Researchers at Washington University School of Medicine in St. Louis found evidence that sleep, already recognized as a promoter of long-term memories, also helps clear room in the brain for new learning.The critical question: How many synapses, or junctures where nerve cells communicate with each other, are modified by sleep? Neurologists believe creation of new synapses is one key way the brain encodes memories and learning, but this cannot continue unabated and may be where sleep comes in.

"There are a number of reasons why the brain can't indefinitely add synapses, including the finite spatial constraints of the skull," says senior author Paul Shaw, Ph.D., assistant professor of neurobiology at Washington University School of Medicine in St. Louis. "We were able to track the creation of new synapses in fruit flies during learning experiences, and to show that sleep pushed that number back down."

Scientists don't yet know how the synapses are eliminated. According to theory, only the less important connections are trimmed back, while connections encoding important memories are maintained.

Many aspects of fly sleep are similar to human sleep; for example, flies and humans deprived of sleep one day will try to make up for the loss by sleeping more the next day. Because the human brain is much more complex, Shaw uses the flies as models for answering questions about sleep and memory.

Sleep is a recognized promoter of learning, but three years ago Shaw turned that association around and revealed that learning increases the need for sleep in the fruit fly. In a 2006 paper in Science, he and his colleagues found that two separate scenarios, each of which gave the fruit fly's brain a workout, increased the need for sleep.

The first scenario was inspired by human research linking an enriched environment to improved memory and other brain functions. Scientists found that flies raised in an enhanced social environment—a test tube full of other flies—slept approximately 2-3 hours longer than flies raised in isolation.

Researchers also gave male fruit flies their first exposure to female fruit flies, but with a catch—the females were either already mated or were actually male flies altered to emit female pheromones. Either fly rebuffed the test fly's attempts to mate. The test flies were then kept in isolation for two days and exposed to receptive female flies. Test flies that remembered their prior failures didn't try to mate again; they also slept more. Researchers concluded that these flies had encoded memories of their prior experience, more directly proving the connection between sleep and new memories.

Scientists repeated these tests for the new study, but this time they used flies genetically altered to make it possible to track the development of new synapses, the junctures at which brain cells communicate.

"The biggest surprise was that out of 200,000 fly brain cells, only 16 were required for the formation of new memories, " says first author Jeffrey Donlea, a graduate student. "These sixteen are lateral ventral neurons, which are part of the circadian circuitry that let the fly brain perform certain behaviors at particular times of day."

When flies slept, the number of new synapses formed during social enrichment decreased. When researchers deprived them of their sleep, the decline did not occur.

Donlea identified three genes essential to the links between learning and increased need for sleep: rutabaga, period and blistered. Flies lacking any of those genes did not have increased need for sleep after social enrichment or the mating test.

Blistered is the fruit fly equivalent to a human gene known as serum response factor (SRF). Scientists have previously linked SRF to plasticity, a term for brain change that includes both learning and memory and the general ability of the brain to rewire itself to adapt to injury or changing needs.

The new study shows that SRF could offer an important advantage for scientists hoping to study plasticity: unlike other genes connected to plasticity, it's not also associated with cell survival.

"That's going to be very helpful to our efforts to study plasticity, because it removes a large confounding factor," says co-author Naren Ramanan, Ph.D., assistant professor of neurobiology. "We can alter SRF activity and not have to worry about whether the resulting changes in brain function come from changes in plasticity or from dying cells."

Shaw plans further investigations of the connections between memory and sleep, including the question of how increased synapses induce the need for sleep.

"Right now a lot of people are worried about their jobs and the economy, and some are no doubt losing sleep over these concerns," Shaw says. "But these data suggest the best thing you can do to make sure you stay sharp and increase your chances of keeping your job is to make getting enough sleep a top priority."