October 2, 2009 (Newswise) - Mathematicians at Michigan Technological University have developed powerful new tools for winnowing out the genes behind some of humanity's most intractable diseases.With one, they can cast back through generations to pinpoint the genes behind inherited illness. With another, they have isolated 11 variations within genes-called single nucleotide polymorphisms, SNPs or "snips"-associated with type 2 diabetes.

"With chronic, complex diseases like Parkinson's, diabetes and ALS [Lou Gehrig's disease], multiple genes are involved," said Qiuying Sha, an assistant professor of mathematical sciences. "You need a powerful test."

That test is the Ensemble Learning Approach (ELA), software that can detect a set of SNPs that jointly have a significant effect on a disease.

With complex inherited conditions, including type 2 diabetes, single genes may precipitate the disease on their own, while other genes cause disease when they act together. In the past, finding these gene-gene combinations has been especially unwieldy, because the calculations needed to match up suspect genes among the 500,000 or so in the human genome have been virtually impossible.

ELA sidesteps this problem, first by drastically narrowing the field of potentially dangerous genes, and second, by applying statistical methods to determine which SNPs act on their own and which act in combination. "We thought it was pretty cool," Sha said.

To test their model on real data, Sha's team analyzed genes from over 1,000 people in the United Kingdom, half with type 2 diabetes and half without. They identified 11 SNPs that, singly or in pairs, are linked to the disease with a high degree of probability. Their work was published in the journal Genetic Epidemiology available online at http://www3.interscience.wiley.com/journal/117890704/abstract?CRETRY=1&S... .

ELA is used to compare the genetic makeup of unrelated individuals to sort out disease-related genes. The team has also developed another approach, which uses a two-stage association test that incorporates founders' phenotypes, called TTFP, that can examine the genomes of family members going back generations.

"In the past, researchers have dealt with the nuclear family, parents and children, but this could go back to grandparents, great-grandparents . . . as far back as you want."
The team has published their findings in the European Journal of Human Genetics. An abstract is available at www.nature.com/ejhg/journal/v15/n11/abs/5201902a.html .
Now that they've developed the software, the analysis is relatively simple, says Sha. But getting the genetic data to work on is not. "We don't have the data sets yet to work with," she says, clearly frustrated. "That's the problem with having no medical school."

Those who do have data sets, however, can use the team's software to help find the genes associated with a panoply of illnesses. ELA is available in Windows and Linux versions at www.math.mtu.edu/~shuzhang/software.html, and TTFP is available by request.

October 2, 2009 (Newswise) - Few people talk openly about having diabetes, so most of us have little understanding of what it feels like to live with diabetes every single day and how it can impact one's every waking moment. That's about to change. In recognition of World Diabetes Day on November 14th, the Making Sense of Diabetes video contest is challenging people living with diabetes to visually reveal its impact on their lives through one of the five senses: sight, hearing, taste, touch or smell. The contest is sponsored by the Diabetes Hands Foundation, a pioneering advocacy organization in social media, and made possible through support provided by Boehringer Ingelheim Pharmaceuticals, Inc."Diabetes affects people's lives in profound and unexpected ways," said Manny Hernandez, founder of the Diabetes Hands Foundation, who has been living with diabetes since 2002. "We smell insulin, savor glucose tablets, feel the poke of devices, react to our doctor's words and see the life ahead of us.

Diabetes is complex and we hope this video contest will help people express and share their diabetes experiences with the diabetes community as a whole as well as with people close to them."

To enter the Making Sense of Diabetes contest, anyone with diabetes over the age of 18 is asked to record and submit to http://www.MakingSenseOfDiabetes.org a video (up to three minutes run time) that demonstrates life with diabetes through one of the five senses. The online video submission should express creativity and originality, be truthful, and convey emotion in a compelling, evocative and personal way.

The contest begins on September 28 and lasts through November 1. Each week will focus on one of the five senses. Three weekly finalists will be chosen based on number of unique views, average rating received, quantity and quality of comments received, creativity and originality and the compelling nature of the video in connection to the sense it is about.

Restrictions and limitations apply. Go to http://www.MakingSenseOfDiabetes.org for the official rules and regulations, prize information, online voting of weekly winners and contest submission guidelines.

September 9, 2009 (EurekAlert) - Researchers at the Carnegie Institution's Department of Plant Biology have discovered a key missing link in the so-called signaling pathway for plant steroid hormones (brassinosteroids). Many important signaling pathways are relays of molecules that start at the cell surface and cascade to the nucleus to regulate genes. This discovery marks the first such pathway in plants for which all the steps of the relay have been identified.Since this pathway shares many similarities with pathways in humans, the discovery not only could lead to the genetic engineering of crops with higher yields, but also could be a key to understanding major human diseases such as cancer, diabetes, and Alzheimer's.

Steroids are important hormones in both animals and plants. Brassinosteroids regulate many aspects of growth and development in plants. Mutants deficient in brassinosteroids are often stunted and infertile. Brassinosteroids are similar in many respects to animal steroids, but appear to function very differently at the cellular level. Animal cells usually respond to steroids using internal receptor molecules within the cell nucleus, whereas in plants the receptors, called receptor-like kinases, are anchored to the outside surface of the cell membranes. For over a decade, scientists have tried to understand how the signal is passed from the cell surface to the nucleus to regulate gene expression. The final gaps were bridged in the study published in the advanced on-line issue of Nature Cell Biology September 6, 2009.

The research team unraveled the pathway in cells of Arabidopsis thaliana, a small flowering plant related to cabbage and mustard often used as a model organism in plant molecular biology.
"This is the first completely connected signaling pathway from a plant receptor-like kinase, which is one of the biggest gene families in plants," says Carnegie's Zhi-Yong Wang, leader of the research team. "The Arabidopsis genome encodes over 400 receptor-like kinases and in rice there are nearly 1,000. We know the functions of about a dozen or so. The completely connected brassinosteroid pathway uses at least six proteins to pass the signal from the receptor all the way to the nuclear genes expressed. This will be a new paradigm for understanding the functional mechanism of other receptor-like kinases."

Understanding the molecular mechanism of brassinosteroid signaling could help researchers develop strategies and molecular tools for genetic engineering of plants with modified sensitivity to hormones, either produced by the plant or sprayed on crops during cultivation, resulting in higher yield or improved traits. "We perhaps could engineer plants with altered sensitivity in different portions of the plant," says Wang. "For example, we could manipulate the signal pathway to increase the biomass accumulation in organs such as fruits that are important as agricultural products, an area highly relevant for food and biofuel production."

Another of the study's findings has potentially far-reaching consequences for human health. The newly identified brassinosteroid signaling pathway component shares evolutionarily conserved domains with the glycogen synthase kinase 3 (GSK3). "GSK3 is found in a wide range of organisms, including mammals," says Wang. "Our study identified a distinct mechanism for regulating GSK3 activity, different from what had been identified in earlier work. GSK3 is known to be critical in the development of health issues such as neural degeneration, cancer, and diabetes, so our finding could open up new avenues for research to understand and treat these diseases."

September 8, 2009 (UT Southwestern) - One in five patients with chronic kidney disease is depressed, even before beginning long-term dialysis therapy or developing end-stage renal disease, UT Southwestern Medical Center researchers have found. The study, based on a pool of 272 participants, is the first to examine the rate of depression among these patients using the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM IV), which is considered the gold-standard in evaluating depression.

"Because patients in the early stages of chronic kidney disease are at increased risk for clinical depression, we as nephrologists should consider screening our patients for depression in clinic," said Dr. Susan Hedayati, assistant professor of internal medicine at UT Southwestern and a staff nephrologist at the Dallas Veterans Affairs Medical Center. She is the lead author of the study, available online and in the current issue of the American Journal of Kidney Diseases.

Previous research has shown that depression rates in the general community are 2 percent to 4 percent; among diabetes patients, 11 percent; among congestive heart failure patients, 14 percent; and among coronary artery disease after heart attack patients, 16 percent.

"Chronic kidney disease patient depression numbers may be higher due to the presence of the same simultaneously occurring conditions that resulted in progressive kidney disease, such as diabetes and atherosclerotic vascular disease," Dr. Hedayati said. "Alternatively, patients such as diabetics, who are depressed, may develop progressive kidney disease because of non-adherence to medications and physicians' advice."

Earlier estimates of depression among chronic kidney disease patients were based on self-report depression scales that can emphasize symptoms such as lack of appetite, weight loss and fatigue. Such symptoms can overlap with other medical conditions, so
UT Southwestern researchers took a novel approach.

From May 2005 to November 2006, researchers invited patients at the Dallas VA Medical Center who were visiting the clinic for chronic kidney disease appointments to join the study. Patients who agreed to participate then underwent a structured clinical interview to determine if they had a current major depressive episode, based on the DSM IV definition of major depressive disorder.

Fifty-seven patients, or 21 percent, were found to be depressed. The mean age of depressed patients was about 65; two were women; and nearly 56 percent were white. All patients were veterans.

The researchers also found that diabetic patients were twice as likely to be depressed as those without diabetes; 63 percent of patients had at least three other medical conditions; and 41 percent had at least four other diseases.

Twenty-six million people in America have chronic kidney disease and millions more are at increased risk, according to the National Kidney Foundation. If treatment does not begin early, the condition progresses to end-stage renal disease. At that point, a patient's kidneys have failed to the point where dialysis - a filtering of toxic chemicals in the blood and removing fluid to help control blood pressure - or a kidney transplant is needed.

According to the U.S. Renal Data System Annual Report, expenditures for end-stage renal disease patients totaled $15.5 billion, which is approximately 6 percent of the entire Medicare budget, and are projected to consume $28 billion by 2010.

Dr. Hedayati is now conducting the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) to determine whether antidepressant medication would be tolerated in kidney-disease patients and whether such treatment can improve depression.

September 2, 2009 (Newswise) - U.S. Surgeon General Richard H. Carmona, M.D., M.P.H., F.A.C.S., will call for greater research and policy action to help prevent obesity among Latino children in a keynote address Sept. 10 at the Scientific Summit of Salud America!, the Robert Wood Johnson Foundation Research Network to Prevent Obesity Among Latino Children, based at the UT Health Science Center at San Antonio.For its inaugural summit, Salud America! will unite more than 200 researchers and community leaders from across the country to address this critical health issue.

Other guests at the summit, set for Sept. 10-11 at the Sheraton Gunter Hotel in San Antonio, include Texas Sen. Eddie Lucio Jr.; Sean Elliott, a former San Antonio Spurs player; and his wife, Claudia Zapata, a San Antonio Express-News health columnist. Champion cyclist Lance Armstrong will deliver a personal video greeting.

Although the event is by invitation only, media members are welcome to attend.

FULL SUMMIT DETAILS:
WHEN: Thursday, Sept. 10, 9 a.m. to 5:30 p.m.

• A welcome by Amelie Ramirez, Dr.P.H., of the UT Health Science Center School of Medicine, and keynote speech by Dr. Richard Carmona are scheduled from 9 to 10:35 a.m.
• Remarks by Sean Elliott and Claudia Zapata are set for 2:15 p.m.

Friday, Sept. 11, 8:30 a.m. to 2:15 p.m.

• A panel featuring Sen. Eddie Lucio Jr. is set for 8:30 a.m.

WHERE: Sheraton Gunter Hotel
205 E. Houston St.
San Antonio, Texas 78205

AGENDA: A full event description and agenda can be found at http://guest.cvent.com/EVENTS/Info/Summary.aspx?e=a1d8aaa7-f07d-48a6-81c....

September 1, 2009 (EurekAlert) - A study in the September issue of Cell Metabolism, a Cell Press publication, may give new meaning to the adage, "You are what you eat."The DNA isolated from the muscles of people with diabetes bears chemical marks not found in those who respond normally to rising blood sugar levels, according to the report. The epigenetic marks in question are specifically found on a gene that controls the amount of fuel, in the form of glucose or lipids, that cells burn. Those marks also show up in the skeletal muscle of people with prediabetes, suggesting that the DNA modification might be an early event in the development of the disease.

Those changes rapidly reprogram the gene's activity without altering the underlying DNA sequence at all. They suggest a way that environmental factors-what we eat or how active we are-may perhaps influence our genes, for better or for worse.

Indeed, the researchers show that the hypermethylation of the gene known as PGC-1? for short (peroxisome proliferator-activated receptor ? [PPAR?] coactivator-1?) also takes place in isolated muscle fiber cells when they are exposed to an inflammatory factor or to free fatty acids.

"These changes take place when you expose muscle to systemic factors that mimic the diabetic condition," said Juleen Zierath of the Karolinska Institutet in Sweden.

Such changes to the epigenetic imprint have been seen before, explain Zierath and Romain Barrès, the study's first author. For instance, chemical modification of genes are responsible for developmental changes that take place as cells differentiate. They are the reason that keratin is produced in the skin but not in blood, for instance. In contrast, the changes they've now revealed take place in cells of the body that are fully mature.

"It's a much more dynamic process than we thought," Zierath said. "The genetic causes of diabetes are important, but this shows us that epigenetic changes, which take place on top of our genes, can alter our physiology in critical ways."

Evidence that dietary factors might influence epigenetic gene control in diabetes had been suggested previously by a generational study in humans, which showed that the nutritional status of the grandparent is closely linked to an increased risk of diabetes-associated mortality in their grandkids. In mice, researchers have demonstrated the crossgenerational effects of nutrition on DNA methylation status directly.

Whether epigenetic modifications could have more immediate effects in other tissues of the body wasn't clear before now. The researchers say they don't yet know whether these epigenetic changes are reversible, but they do have evidence that they might be prevented.

They were able to block hypermethlyation of PGC-1? by silencing a gene that encodes one of a few enzymes that transfer extra methyl groups to DNA. Drugs that prevent hypermethlyation might find clinical use, they say, particularly if they could be made to work only on specific tissues.

"There's room for this in terms of drug discovery," Zierath said.

In a broader sense, the discovery shows that we are not "victims of our genes," she adds. "It's exciting because there may be ways for us to lower disease risk if physical activity or other lifestyle factors can positively influence our epigenome and improve metabolism."

Further studies are needed to see whether different diets or exercise habits can alter DNA methylation in beneficial ways, she said.

August 27, 2009 (ScienceDaily) - Kudzu, the nuisance vine that has overgrown almost 10 million acres in the southeastern United States, may sprout into a dietary supplement. Scientists in Alabama and Iowa are reporting the first evidence that root extracts from kudzu show promise as a dietary supplement for a high-risk condition - the metabolic syndrome - that affects almost 50 million people in the United States alone. Their study appears in the current issue of ACS' Journal of Agricultural and Food Chemistry.J. Michael Wyss and colleagues note in the new study that people with metabolic syndrome have obesity, high blood pressure, high blood cholesterol, and problems with their body's ability to use insulin. Those disorders mean a high risk for heart attacks, strokes, and other diseases. Scientists have been seeking natural substances that can treat the metabolic syndrome. The new study evaluated kudzu root extracts, which contain healthful substances called isoflavones. People in China and Japan long have used kudzu supplements as a health food.

The study found that a kudzu root extract had beneficial effects lab rats used as a model for research on the metabolic syndrome. After two months of taking the extract, the rats had lower cholesterol, blood pressure, blood sugar, and insulin levels that a control group not given the extract. Kudzu root "may provide a dietary supplement that significantly decreases the risk and severity of stroke and cardiovascular disease in at-risk individuals," the article notes.

August 27, 2009 (Newswise) - Persistent job insecurity poses a major threat to worker health, according to a new study published in the September issue of the peer-reviewed journal Social Science and Medicine.The study used long-term data from two nationally representative sample surveys of the U.S. population to assess the impact of chronic job insecurity apart from actual job loss.

"Dramatic changes in the U.S. labor market have weakened bonds between employers and employees and fueled perceptions of job insecurity," said University of Michigan sociologist Sarah Burgard, a research assistant professor at the U-M Institute for Social Research. "This study provides the strongest evidence to date that persistent job insecurity has a negative impact on worker health. In fact, chronic job insecurity was a stronger predictor of poor health than either smoking or hypertension in one of the groups we studied."

Burgard and colleagues Jennie Brand at the University of California, Los Angeles, and James House at U-M, analyzed data on more than 1,700 adults collected over periods from three to 10 years. By interviewing the same people at different points in time, the researchers were able to disentangle the connection between poor health and job insecurity, and to control for the impact of actual job loss and other factors. One of the studies was conducted between 1986 and 1989, the other between 1995 and 2005.

"It may seem surprising that chronically high job-insecurity is more strongly linked with health declines than actual job loss or unemployment," said Burgard, who is also affiliated with U-M's Department of Sociology and School of Public Health. "But there are a number of reasons why this is the case. Ongoing ambiguity about the future, inability to take action unless the feared event actually happens, and the lack of institutionalized supports associated with perceived insecurity are among them."

To measure feelings of job insecurity, participants in one study were asked, "How likely is that during the next couple of years you will involuntarily lose your main job?" Participants in the other study were asked, "If you wanted to stay in your present job, what are the chances you could keep it for the next two years." At any given time, as many as 18 percent of those surveyed felt insecure about their jobs. But only about 5 percent of respondents in the first survey and 3 percent of respondents in the second survey reported feeling anxious about their jobs both times they were interviewed.

To reduce the chances that underlying pessimism or negativity was responsible for the degree of job insecurity participants felt, the researchers also controlled for neuroticism, asking participants to what extent they would describe themselves as moody, a worrier, nervous and calm. They also controlled for race, marital status, education and job characteristics, including self-employment.

According to Burgard, the findings have potential implications for both policy and intervention.
"Programs designed for displaced or unemployed workers are unlikely to solve the problems faced by workers who are still employed but are persistently insecure about their jobs," she said. "When you consider that not only income but so many of the important benefits that give Americans some piece of mind---including health insurance and retirement benefits---are tied to employment for most people, it's understandable that persistent job insecurity is so stressful.

"We need to learn more about the conditions that generate or change worker perceptions of their job insecurity. Then organizations might want to intervene to reduce perceptions of insecurity or perhaps broader governmental policies might help to mitigate the degree of stress associated with perceived job insecurity. Additional acute and chronic strains at work and in other areas of life might also worsen or mitigate the health impact of long-term job insecurity.

"Certainly job insecurity is nothing new, but the numbers experiencing persistent job insecurity could be considerably higher during this global recession, so these findings could apply much more broadly today than they did even a few years ago."

August 11, 2009 (EurekAlert) - People diagnosed with type 2 diabetes often resist taking insulin because they fear gaining weight, developing low blood sugar and seeing their quality of life decline.A study recently completed at UT Southwestern Medical Center suggests that those fears are largely unfounded and that patients and physicians should consider insulin as a front-line defense, as opposed to a treatment of last resort for non-insulin-dependent diabetes.

"We found that those patients who received insulin initially did just as well, if not better, than those who didn't receive insulin," said Dr. Ildiko Lingvay, assistant professor of internal medicine at UT Southwestern and lead author of the study appearing online and in a future issue of Diabetes Care. "This reinforces the idea that insulin treatment is a viable and safe option for patients, even in the very initial stages of their diagnoses.

"There is a myth out in the community, especially among certain ethnicities, that insulin is the last resort, and that somebody started on insulin is going to die," Dr. Lingvay added. "We as physicians are responsible for teaching the patient that that's not the case."

More than 20 million Americans have type 2 diabetes. Obesity, age and lack of exercise all increase the risk for the disease, which is characterized by a progressive loss of insulin-producing beta cells. Diabetes is the single greatest independent risk factor for heart disease, as well as a contributor to a number of other medical problems, including blindness and kidney disease.

The standard initial treatment for type 2 diabetes is a single drug, often metformin, followed by the addition of more oral hypoglycemic agents as needed.

For this study, researchers evaluated the effectiveness of offering insulin-based therapy as an initial treatment option to newly diagnosed type 2 diabetes patients. They compared rates of compliance, satisfaction, effectiveness, safety and quality of life among the patients, who were randomized to receive either the standard triple oral therapy or insulin plus metformin, an oral drug that helps regulate blood sugar levels.

The patients, ranging in age from 21 to 70 years old, had been diagnosed with type 2 diabetes within the past two months. Researchers recruited study participants from Parkland Memorial Hospital or by self-referral to the Clinical Diabetes Research Clinic at UT Southwestern between November 2003 and June 2005.

After enrollment, every participant followed an insulin and metformin regimen for three months. The patients were then randomized to continue taking insulin and metformin or begin the triple oral therapy regimen. All participants were checked monthly for the first four months, at six months after randomization, and every three months thereafter for three years. Of the 58 patients randomized, 24 of the insulin-treated group and 21 of the triple oral therapy group completed the study.

The researchers found that the patients taking insulin plus metformin had fewer low-blood-sugar, or hypoglycemic, events, gained less weight and reported high satisfaction with the insulin.

Dr. Lingvay said she hopes physicians use these findings as the rationale to offer insulin-metformin as the first, rather than last, line of defense.

"Modern medicine uses insulin as a very effective and safe treatment tool," she said. "With the new devices that we're using, giving yourself an insulin shot is not much harder than taking pills."

The data represent the first three years of a six-year study still under way at UT Southwestern. The next step, Dr. Lingvay said, is to begin analyzing how the insulin plus metformin and oral triple therapy regimens affect insulin production in beta cells.

August 10, 2009 (Newswise) - Four healthy lifestyle factors-never smoking, maintaining a healthy weight, exercising regularly and following a healthy diet-together appear to be associated with as much as an 80 percent reduction in the risk of developing the most common and deadly chronic diseases, according to a report in the August 10/24 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.
Cardiovascular disease, cancer and diabetes-chronic diseases that together account for most deaths-are largely preventable, according to background information in the article. "An impressive body of research has implicated modifiable lifestyle factors such as smoking, physical activity, diet and body weight in the causes of these diseases," the authors write.

To further describe the reduction in risk associated with these factors, Earl S. Ford, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues assessed data from 23,513 German adults age 35 to 65. At the beginning of the European Prospective Investigation Into Cancer and Nutrition-Potsdam (EPIC-Potsdam) study-between 1994 and 1998-participants completed an assessment of their body weight and height, a personal interview that included questions about diseases, a questionnaire on sociodemographic and lifestyle characteristics and a food frequency questionnaire.

Their responses were assessed for adherence to four healthy lifestyle factors: never smoking, having a body mass index lower than 30, exercising for at least three and a half hours per week and following healthy dietary principles (for example, having a diet with high consumption of fruits and vegetables while limiting meat consumption). Follow-up questionnaires were administered every two to three years.

Most participants had one to three of these health factors, fewer than 4 percent had zero healthy factors and 9 percent had all four factors. Over an average of 7.8 years of follow-up, 2,006 participants developed new cases of diabetes (3.7 percent), heart attack (0.9 percent), stroke (0.8 percent) or cancer (3.8 percent).

After adjusting for age, sex, education level and occupation, individuals with more healthy lifestyle factors were less likely to develop chronic diseases. Participants who had all four factors at the beginning of the study had a 78 percent lower risk of developing any of the chronic diseases during the follow-up period than those who had none of the healthy factors. The four factors were associated with a 93 percent reduced risk of diabetes, 81 percent reduced risk of heart attack, 50 percent reduced risk of stroke and 36 percent reduced risk of cancer.

The largest reduction in risk was associated with having a BMI lower than 30, followed by never smoking, at least 3.5 hours of physical activity and then adhering to good dietary principles.

"Our results reinforce current public health recommendations to avoid smoking, to maintain a healthy weight, to engage in physical activity appropriately and to eat adequate amounts of fruits and vegetables and foods containing whole grains and to partake of red meat prudently," the authors write. "Because the roots of these factors often originate during the formative stages of life, it is especially important to start early in teaching the important lessons concerning healthy living."