New biochemical discoveries into developing disease

Researchers have undertaken the most comprehensive investigation of genetic variance in human metabolism and discovered new insights into a range of common diseases. Their work has revealed 37 new variants that are associated with concentrations of metabolites in the blood. Many of these match variants associated with diseases such as chronic kidney disease, type 2 diabetes and blood clotting.

The team conducted the largest ever study of the human genome for genetic variants associated with metabolites - the biochemical compounds representing the start or end of metabolic reactions - using genome wide association analysis. They were searching for genetic influences on levels of more than 250 compounds in people's blood, including lipids, sugars, vitamins, amino acids and many others. They discovered variants that have a significant effect on the levels of these compounds, and hence on the underlying biological and disease processes.

"Our findings provide new insights for many disease-related associations that have been reported in previous studies, including cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, thrombosis and Crohn's disease," says Dr Nicole Soranzo, one of the study's researchers from the Wellcome Trust Sanger Institute. "Often the effects of variants discovered in genome wide association analyses are modest and we perhaps have a poor understanding of the biologic mechanism behind the association. Our approach can overcome these problems and possibly inform individualized therapy/treatment."

In previous studies, scientists have looked at the levels of one or a few metabolic traits; for example, cholesterol levels, or sugar in the blood, that is investigated in the doctor's surgery to help to diagnose disease. The new approach in this work was to assay a much wider range of smaller biochemical compounds, to give as complete a picture as possible of the molecules that are symptoms of disease and those that might contribute to disease.
The hope was that this more complete picture would allow researchers to better understand the function of genetic variants responsible for driving disease. This was the case.

Among the discoveries made by the team was a previously unknown association of mannose, a natural sugar, with diabetes-associated variants; this link suggests a new line of research to examine the role of mannose in diabetes, both as a diagnostic and as part of the disease process.
They also identified a possible mechanism to detoxify substances, which could affect the risk of developing kidney disease. This followed the discovery of a highly significant association with the NAT8 gene.

"These are remarkable findings powered by our method that enables researchers to identify new and potentially relevant metabolic processes and pathways," says Professor Karsten Suhre. Dr Christian Gieger adds: "To improve effectively treatment through biomedicine, we need to put genetics into its biological context. In trying to do this in our study, we have identified new molecules of interest that could be clinically significant." Both are the lead authors from the Helmholtz Center Munich, German Research Centre for Environmental Health.

Their study also discovered variants associated with blood clotting and thrombosis.
"We were able to show that variants in or near three genes are associated with a biochemical modification to peptides, a small protein that controls blood clotting. These same variants are variously associated with an increased risk for heart disease, thrombosis and other similar conditions," says Professor Tim Spector, Director of the TwinsUK twin cohort at the Department of Twin Research and Genetic Epidemiology, King's College London, which provided one of the two study samples. "We speculate that this is a new example of a mechanism that alters blood clotting. This discovery could one day lead to improved treatments."

Additionally, the researchers investigated the association of metabolite levels with drug response and treatment, including statins and thalidomide. They showed that in one case, a variant in a gene called ACE, associated with blood pressure control, could undermine treatment effects. The novel biochemical basis could help to identify possible side effects in drug trials and support development of new formulations to reduce side effects.
The data will be made publicly available as a knowledge-based resource on the internet to aid future studies, and biological, as well as clinical, interpretation of genome wide association studies.

More information: Suhre K, Shin S-Y, Petersen A-K et al. (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature Published online 31 August 2011. doi: 10.1038/Nature10354

Provided by Wellcome Trust Sanger Institute

How to tell when someone's lying

How to tell when someone's lying

May 10, 2011

The ability to effectively detect deception is crucial to public safety, particularly in the wake of renewed threats against the U.S. following the killing of Osama bin Laden.

UCLA professor of psychology R. Edward Geiselman has been studying these questions for years and has taught investigative interviewing techniques to detectives and intelligence officers from the FBI, the Department of Homeland Security, the Marines, the Los Angeles police and sheriff's departments, and numerous international agencies.

He and three former UCLA undergraduates — Sandra Elmgren, Chris Green and Ida Rystad —analyzed some 60 studies on detecting deception and have conducted original research on the subject. They present their findings and their guidance for how to conduct effective training programs for detecting deception in the current (April) issue of the American Journal of Forensic Psychiatry, which is published this week.

Geiselman and his colleagues have identified several indicators that a person is being deceptive. The more reliable red flags that indicate deceit, Geiselman said, include:

• When questioned, deceptive people generally want to say as little as possible. Geiselman initially thought they would tell an elaborate story, but the vast majority give only the bare-bones. Studies with college students, as well as prisoners, show this. Geiselman's investigative interviewing techniques are designed to get people to talk.

• Although deceptive people do not say much, they tend to spontaneously give a justification for what little they are saying, without being prompted.

• They tend to repeat questions before answering them, perhaps to give themselves time to concoct an answer.

• They often monitor the listener's reaction to what they are saying. "They try to read you to see if you are buying their story," Geiselman said.

• They often initially slow down their speech because they have to create their story and monitor your reaction, and when they have it straight "will spew it out faster," Geiselman said. Truthful people are not bothered if they speak slowly, but deceptive people often think slowing their speech down may look suspicious. "Truthful people will not dramatically alter their speech rate within a single sentence," he said.

• They tend to use sentence fragments more frequently than truthful people; often, they will start an answer, back up and not complete the sentence.

• They are more likely to press their lips when asked a sensitive question and are more likely to play with their hair or engage in other "grooming" behaviors. Gesturing toward one's self with the hands tends to be a sign of deception; gesturing outwardly is not.

• Truthful people, if challenged about details, will often deny that they are lying and explain even more, while deceptive people generally will not provide more specifics.

• When asked a difficult question, truthful people will often look away because the question requires concentration, while dishonest people will look away only briefly, if at all, unless it is a question that should require intense concentration.

If dishonest people try to mask these normal reactions to lying, they would be even more obvious, Geiselman said. Among the techniques he teaches to enable detectives to tell the truth from lies are:

• Have people tell their story backwards, starting at the end and systematically working their way back. Instruct them to be as complete and detailed as they can. This technique, part of a "cognitive interview" Geiselman co-developed with Ronald Fisher, a former UCLA psychologist now at Florida International University, "increases the cognitive load to push them over the edge." A deceptive person, even a "professional liar," is "under a heavy cognitive load" as he tries to stick to his story while monitoring your reaction.

• Ask open-ended questions to get them to provide as many details and as much complete information as possible ("Can you tell me more about...?" "Tell me exactly..."). First ask general questions, and only then get more specific.

• Don't interrupt, let them talk and use silent pauses to encourage them to talk.

If someone in an airport or other public space is behaving suspiciously and when approached exhibits a majority of the more reliable red flags, Geiselman recommends pulling him or her aside for more questioning. If there are only one or two red flags, he would probably let them go.

Geiselman tested techniques for telling the truth from deception with hundreds of UCLA students, and the studies he and his co-authors analyzed involved thousands of people.

Detecting deception is difficult, Geiselman said, but training programs can be effective. Programs must be extensive, with an education phase followed by numerous video examples, and a phase in which those being trained judge video clips and simulate real-world interviewing. Training should be conducted on multiple days over a period of a week or two.

"People can learn to perform better at detecting deception," Geiselman said. "However, police departments usually do not provide more than a day of training for their detectives, if that, and the available research shows that you can't improve much in just a day."

When Geiselman conducted training with Marine intelligence officers, he found that they were impressively accurate in detecting deception even before the training began. In contrast, the average college student is only 53 percent accurate without training, and with abbreviated training, "we often make them worse," he said.

"Without training, many people think they can detect deception, but their perceptions are unrelated to their actual ability. Quick, inadequate training sessions lead people to over-analyze and to do worse than if they go with their gut reactions."

Geiselman is currently developing a training program that he hopes will effectively compress the learning curve and thus will serve to replicate years of experience.

The cognitive interview that Geiselman and Fisher developed works well with both criminal suspects and eyewitnesses of crimes. Geiselman thinks these techniques are likely to work in non-crime settings as well, but said additional research should be done in this area.

In the next year, Geiselman plans to teach police detectives techniques for investigative interviewing and spotting deception through the U.S. Department of Homeland Security's Rural Policing Institute for underserved police departments. He says this will be a perfect fit for him because he comes from Culver, Ind., a small town that has fewer residents than UCLA has psychology majors.

Later this month, Geiselman will travel to Hong Kong to provide training in investigative interviewing to the Independent Commission Against Corruption.

An instructional course Geiselman taught on investigative interviewing before the second Iraq war resulted in cognitive interviewing techniques that were used to interdict some insurgent activity in Iraq, perhaps saving many lives, he was later informed.

Geiselman also has worked with the Los Angeles County Sheriff's Department on effective techniques for interviewing children who may have been molested and has interviewed crime victims for police departments around the country in murder cases gone cold. His research has been funded by the U.S. Department of Justice and the U.S. Department of Homeland Security.

Provided by University of California - Los Angeles

Muscle Building

New Discovery Leads to Shocking Muscle Gains

A safe alternative to steroids is changing the way pro athletes and bodybuilders stay in shape.

Adam Hillbrand is a veteran Health Headlines writer specializing in sports nutrition. His professional interests include writing about healthy living, marketing strategy, consumer psychology, and technology. He lives in the Boston area with his wife and is an avid Boston sports fan. In his spare time, he loves to cook and travel. He also enjoys working out and spending as much time as possible outside.

With the recent media coverage exposing steroid use in professional sports, many everyday people are looking for an extra edge to build muscle, get stronger, and look better.

Steroids, although effective, are unhealthy and illegal to use without a prescription. Millions of dollars have been spent in sports medicine research to find a completely safe, natural alternative that produces the same results.

After years of research scientists now agree that nitric oxide supplements are a safe way to maximize your muscle gains.

UFC Champion BJ Penn started using a nitric oxide supplement called Force Factor last year. Penn recently told us, "Force Factor is the absolute best product to hit the market in years."

Other athletes like basketball Rookie of the Year Derrick Rose and professional football player Vernon Davis are just now discovering the dramatic benefits of using a nitric oxide supplement. Vernon has been an advocate of Force Factor since first taking it, telling his teammates in San Francisco, "Force Factor has proven results. I believe in results."

The Science Behind Nitric Oxide

Your body naturally produces nitric oxide to move oxygen into your muscles while you exercise. This burst of oxygen keeps your muscles functioning while lifting weights or through your cardio session.

Unfortunately, your body can only generate a limited amount of nitric oxide. When the nitric oxide runs out your muscles can no longer power through the exercise no matter how much mental determination you have.

Taking a nitric oxide supplement 30 minutes before your workout could be the push your body needs to add weight to your bench press or run that extra mile. This increased stamina results in longer, harder workouts and a better body in less time.

The Benefits of Nitric Oxide Supplements

· Drastic Muscle Gains

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· Transform Your Body

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· Supports Your Immune System

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Source: Health Headlines