A fully functional, fast switching and printable transistor in cheap plastic is invented by researcher Lars Herlogsson, Linkoping University in Sweden. All six articles in his doctoral thesis were published in the Advanced Materials journal.

The thesis claims that with the help of polymers, plastics, which are already manufactured on a large scale, it is possible to manufacture transistors that are fast and can run on small printed batteries, where the drive voltage is around 1 volt.

They are particularly suitable for printed electronics.

The transistor is made up of two polymers, one of which acts as a semiconductor and the other as an electrolyte; a substance containing mobile charged ions that controls the current flowing through the transistor.

Polymers consist of linked chains of molecules. Thanks to the fact that one type of charged particle in the electrolyte, be it positive or negative ions, binds to the polymer chain in the semiconducting polymer. The active layer, in which the electric field is concentrated in the electrolyte, becomes very thin (1 nanometre) irrespective of the thickness of the electrolyte layer.

Whether it is a negative or positive ion that binds depends on whether it is a transistor that is hole-conducting (p-channel) or if it is electron-conducting (n-channel).

The thin active layer permits the use of very low driving voltages. By combining p- and n-channel transistors, Lars Herlogsson has constructed complementary circuits, CMOS circuits, which reduces the power consumption.

"This is robust CMOS technology which allows for very low drive voltages, and besides that, it is well suited to printed electronics," he says.

To achieve these low drive voltages using conventional technology would require nanometre thin layers. Printing such thin layers is impossible because the printing surface on paper or plastic film is typically rough. However, printing a 100-nanometre thick layer, as in this case, is possible using conventional printing techniques.

The idea of creating a thin active layer also impressed electronics Professor Christer Svensson, now emeritus of the examining committee.

"A scientifically very neat job, an intelligent idea that he clearly showed works in reality. There may be applications for this type of electronics such as in large TV screens where silicon is unable to compete," Svensson says.

The focus of Lars Herlogssons thesis has been to produce a material system for polymer-based organic transistors that can be printed at a reasonable price. The result is a transistor that within traditional electronics is called a field-effect transistor. Four of the thesis articles are related to just that, but the other two articles are related to the following:

one addresses woven electronics where the organic electrolyte transistors are embedded in the intersections between textile microfibers.
The other shows how to produce an organic field-effect transistor with a drop of water as the electrolyte.

All of the six articles in the dissertation have been published in the scientific journal Advanced Materials.

Now, after spending years on research, Lars Herlogsson has taken a step closer to production. September 1, he began working at the company Thin Film Electronics in Linkoping to develop inexpensive printed memories.

"As scientists, our task is to push the boundaries and show what is practical and possible. Industry can produce the organic electronics better than we can and there are many talented plastic electronics companies, says Magnus Berggren, Professor of organic electronics at Linkoping University.

Thesis: Electrolyte-Gated Organic Thin-Film Transistors, Lars Herlogsson, Department of Science and Technology, Linköping University, Campus Norrköping, 2011

The above story is reprinted from materials provided by Linkoeping Universitet.

A new model of obsessive-compulsive disorder (OCD) that mirrors both symptoms of the disease and the timing of its treatment in humans has been created by University of Chicago researchers, according to a new study.

Using the model, researchers isolated a single neurotransmitter receptor in a specific brain region responsible for their model's OCD-like symptoms, offering new insight into the cause of the disorder. Further research with the model may point the way to new treatments for both OCD and autism, said Nancy Shanahan, PhD, lead author of the paper in Biological Psychiatry.

"Treatment for these people is greatly needed, and there really are very few highly valid animal models of the disorder," said Shanahan, a postdoctoral researcher at the University of Chicago. "Having one that seems to mimic the disorder so well, especially in terms of the time course of treatments that work in humans, is potentially very useful for researching novel therapeutics."

Stephanie Dulawa, PhD, assistant professor in the Department of Psychiatry and Behavioral Neuroscience at the University of Chicago Medical Center and senior author of the study, said, "Our model can make accurate predictions about what you see in OCD, and that gives us confidence that the underlying neurobiology is likely to be similar between the model and the actual disorder."

About 2.2 million people in the United States have been diagnosed with OCD, according to the National Institute of Mental Health. OCD patients struggle with repetitive rituals (such as hand-washing, counting and cleaning) and unwanted thoughts that can cause severe anxiety.

Psychiatrists have found some success treating patients with a class of drugs called serotonin reuptake inhibitors (SRIs) initially developed for depression. However, these drugs fail to reduce symptoms in as many as 60 percent of OCD patients and require four to eight weeks of treatment for therapeutic effects to begin.

"OCD is very mysterious and very prevalent," Shanahan said. "The development of OCD-specific treatments will be an extremely important step toward helping these people and preventing the disorder's cost to society."

With an animal model that replicates at least some aspects of OCD, researchers can dig deeper into the specific neurotransmitters and systems involved in the disorder. In Dulawa's laboratory, a team led by Shanahan found inspiration in a drug that activates the 1b class of receptors for the neurotransmitter serotonin. Clinically, the drug is used to treat migraines, but it is also known to have the unintended effect of increasing anxiety and compulsions in people with OCD.

When the drug was given to mice, they showed highly repetitive patterns of locomotion when placed into an open arena. The drug-treated mice also exhibited deficits in prepulse inhibition, a form of startle plasticity thought to measure the brain's ability to filter out intrusive thoughts, which plague OCD patients.

To determine whether these drug-induced behaviors reflected the neurobiology of OCD, the researchers tested the same drugs used to treat the disorder in humans. After four weeks of pre-treatment with SRIs -- the same duration required to see therapeutic effects in humans -- drug-induced OCD behaviors were reduced in the mice. Shorter SRI treatment or treatment with other antidepressant drugs that do not work in humans with OCD were unsuccessful in reducing the behaviors caused by the drug.

"We have this time course that nicely parallels or mimics the human therapeutic response," Shanahan said. "In order to study how these drugs are working and the pathophysiology of the disorder, we need a model where this delayed onset exists. So we are really excited about that."

The researchers then looked for a specific brain region where activation of 1b serotonin receptors creates OCD-like symptoms. In humans, scientists have identified a region called the orbitofrontal cortex that is more active in OCD subjects. Again matching the human data, selectively activating 1b receptors in the orbitofrontal cortex with the drug was sufficient to produce the OCD-like symptoms in the mice.

"We found that the 1b receptors in the orbitofrontal cortex were really the critical receptors," Dulawa said. "It was very affirming to our research because it is the brain region most heavily implicated in OCD throughout all of the human literature."

The results offer promising ideas about developing new treatments for OCD. A drug that blocks the serotonin 1b receptors may be effective in reducing OCD symptoms; however, no such chemical is currently available, Dulawa said. Alternatively, treating OCD patients with an activator of these receptors may exacerbate symptoms initially, but have long-term benefits as the number of serotonin 1b receptors decreases from over-stimulation.

"These treatments could potentially be much more specific and work much faster," Dulawa said. "Now that we have this model, we actually could pursue these ideas for better treatments in a disease where there is only one successful therapy."

Funding for this work was provided by the National Institute of Mental Health.

The above story is reprinted from materials provided by University of Chicago Medical Center.

Language change among our prehistoric ancestors came about via the arrival of immigrant men -- rather than women -- into new settlements, according to new research.

The claim is made by two University of Cambridge academics, Peter Forster and Colin Renfrew, in a report to be published in Science on September 9.

They studied the instances of genetic markers (the male Y chromosome and female mtDNA) from several thousand individuals in communities around the world that seem to show the emergence globally of sex-specific transmission of language.

From Scandinavian Vikings who ferried kidnapped British women to Iceland -- to African, Indian and Polynesian tribes, a pattern has emerged which appears to show that the arrival of men to particular geographic locations -- through either agricultural dispersal or the arrival of military forces -- can have a significant impact on what language is spoken there.

Professor Renfrew said: "It may be that during colonisation episodes by emigrating agriculturalists, men generally outnumber women in the pioneering groups and take wives from the local community.

"When the parents have different linguistic backgrounds, it may often be the language of the father which is dominant within the family group."

Dr Forster, of Murray Edwards College, also pointed to the fact that men have a greater variance in offspring than women -- they are more likely to father children with different mothers than vice versa. This has been recorded both in prehistoric tribes such as the 19th and 20th century Polar Eskimos from Greenland and in historic figures like Genghis Khan, who is believed to have fathered hundreds of children.

Indeed, his Y chromosome is carried by 0.5 per cent of the world's male population today.

Perhaps the most striking example of sex-biased language change however comes from a genetic study on the prehistoric encounter of expanding Polynesians with resident Melanesians in New Guinea and the neighbouring Admiralty Islands. The New Guinean coast contains pockets of Polynesian-speaking areas separated by Melanesian areas. The Polynesian mtDNA level (40-50%) is similar in these areas regardless of language, whereas the Y chromosome correlates strongly with the presence of Polynesian languages.

Past studies have shown similar findings in the Indian subcontinent among the speakers of Tibeto-Burman and among the immigrant Indo-European languages as opposed to indigenous Dravidian languages.

In the Americas, too, language replacement in the course of postulated farming dispersal has also been found to correlate for the Uto-Aztecan language family.

Added Forster: "Whether in European, Indian, Chinese or other languages, the expression 'mother tongue' and its concept is firmly embedded in popular imagination -- perhaps this is the reason why for so many years the role of fathers, or more likely, specific groups of successful males, in determining prehistoric language switches has not been recognised by geneticists."

"Prehistoric women may have more readily adopted the language of immigrant males, particularly if these newcomers brought with them military prowess or a perceived higher status associated with farming or metalworking."

The above story is reprinted from materials provided by University of Cambridge.

Older individuals' complaints about memory lapses such as having trouble remembering recent events may indicate that they are experiencing cognitive problems that are greater than typical age-related changes. These findings, which are published September 15 in the Journal of the American Geriatrics Society, indicate that primary care clinicians, who are often the first to see patients who are worried about their memory, should be aware that such complaints might be indicative of something serious and warrant a further cognitive assessment.


Because the number of U.S. adults aged 65 years and older is projected to nearly double over the next two decades, the incidence of Alzheimer's disease and other dementias is also expected to rise. In response, clinicians are incorporating cognitive screening tests as part of annual wellness visits for older people, and researchers are looking for simple ways to identify older individuals who may benefit from additional cognitive evaluations.

To see if certain memory complaints might be linked with potentially serious problems related to memory and thinking, investigators telephoned 16,964 older women (average age of 74 years) and asked them seven questions related to memory complaints, followed by various questions that assessed cognitive function.

Investigators found that, in general, the more memory complaints older individuals have, the worse off their cognitive functioning is. However, not all complaints are related to cognitive decline. For example, a "yes" answer to the question "Do you have much more trouble remembering things from one second to the next?" did not relate to cognitive impairment but was associated with normal aging. By contrast, a "yes" to the question "Do you have trouble finding your way around familiar streets?" was highly associated with cognitive impairment.

"These findings suggest that clinicians may need to differentiate between the types of memory complaints their patients have, as some are likely due to normal aging whereas others are worrisome for possible cognitive decline," said Dr. Rebecca Amariglio of Brigham and Women's Hospital and Harvard Medical School, one of the study authors.

This will be particularly important as the incidence of Alzheimer's disease increases and therapies for the disease become available.

The above story is reprinted from materials provided by Wiley-Blackwell.

When lung cancer strikes, it often spreads silently into more advanced stages before being detected. In a new article published in Nature Nanotechnology, biological engineers and medical scientists at the University of Missouri reveal how their discovery could provide a much earlier warning signal.

"Early detection can save lives, but there is currently no proven screening test available for lung cancer," said Michael Wang, MD, PhD, assistant professor of pathology and anatomical sciences at MU and a corresponding author for the article. "We've developed highly sensitive technology that can detect a specific molecule type in the bloodstream when lung cancer is present."

Worldwide and in the United States, lung cancer is the most common cause of cancer-related death. In the U.S., more than 221,000 people will be newly diagnosed with lung cancer in 2011, and more than 155,000 people will die from the disease this year.

MU researchers used blood plasma samples to detect a change in a specific small ribonucleic acid (microRNA) molecule that is often elevated in lung cancer patients. The scientists put an extract of blood plasma through a protein-based nanopore, which is a tiny hole in a thin membrane that is just big enough for a single molecule to pass through. By applying an ionic current to the nanopore, the scientists measured changes in the current that occur when the microRNA molecule associated with lung cancer is present.

"That altered current acts as a signal or bio-signature that is related to lung cancer," said Li-Qun Gu, PhD, an associate professor of biological engineering at MU and a corresponding author for the article. "Our new nanopore sensor is selective and sensitive enough to detect microRNAs at the single molecular level in plasma samples from lung cancer patients.

"While there are many research labs that focus on nanopore applications, this is the first time that nanopore technology has been used to detect lung cancer," Gu added. "This technology could possibly be used in the future to detect other cancer types as well as other types of diseases with specific DNA or RNA in the blood."

MU research published in the article was partially supported by grants from the National Science Foundation, National Institutes of Health and University of Missouri Intellectual Property Fast Track Initiative. The authors are associated with MU's College of Engineering, School of Medicine, Ellis Fischel Cancer Center and Dalton Cardiovascular Research Center.

The above story is reprinted from materials provided by University of Missouri School of Medicine.

Stanford University School of Medicine researchers have predicted the inherited health risks of a four-person family by analyzing their whole genome sequences. With the DNA sequences of both parents and children, the team was able to better check for sequencing errors and more accurately predict how individual genetic variants affect each family member's risk for disease.

The project improved computational tools that provide medical interpretation of genomes, which includes disease-risk prediction and how an individual would respond to common medications. "With the continuing decline in the cost of genome sequencing, routine genome analysis could be the future of medicine," said Euan Ashley, MD, assistant professor of cardiovascular medicine and senior author of the study.

The study, published Sept. 15 in PLoS Genetics, will be the second reported analysis of a four-person family of genomes, but the first to include a whole-genome interpretation of a family's medical risks. The previous report, by another group of researchers, focused on the genetic cause of a rare disorder affecting the children of that family. Ashley also published a study last year that involved the first whole-genome medical risk assessment for an individual, and the methods developed in that paper provide the basis for this new study.

"This work pushes the boundaries of our understanding of personal genomes by adding the strength of family genetics to the technology of genomics," said Rochelle Long, PhD, director of the National Institutes of Health Pharmacogenomics Research Network. "The advance promises a new era of personalized medicine in which people will be able to make informed decisions about medical treatment based on their individual genetic risks."

Human genomes carry two copies of each gene -- one inherited from each parent. With a family of genomes, the researchers could determine exactly which parent had donated a given copy of a gene to their offspring, allowing them to better calculate the severity of health risks when many variants were found together.

"Sequencing families leads to better genetic data and will be an important part of analyzing genomes for medicine," said lead author Frederick Dewey, MD, cardiology fellow and postdoctoral researcher.

The related set of genome sequences also allowed the scientists to locate, with the most precision reported to date, where along the DNA strand the parents' chromosomes had mixed together before being passed to the next generation -- a diversity-generating process known as genetic recombination. The daughter of the family, who, along with her father, is a co-author of the study, initiated the genetic recombination analysis as an at-home project.

A familial predisposition to blood clotting led the West family of Cupertino, Calif., to explore their genetics, initially on their own. In 2003, father John West suffered two pulmonary embolisms (blood clots in the lung) and he wondered if he had passed any clotting risks to his children. Genotyping analysis from the personal genomics company 23andMe revealed that the daughter, Anne, had inherited the same risks. Now armed with the much more extensive knowledge of her genetic risks derived from whole-genome sequencing, she can avoid the problems experienced by her father with some simple lifestyle changes at this time and perhaps a drug like aspirin later in life.

As a high school student, Anne West calculated the frequency of genetic recombination in her family, first with snippets of genetic information from the 23andMe data and then with the family's full genome sequences from biotechnology company Illumina. "The amount of data is vast and intimidating but if you analyze the data question by question, the next step in the investigation usually reveals itself," she said. She also identified the origin and implications of some disease variants in the family's genomes and presented her work at a national scientific conference, which landed her an internship in a genetics lab at Harvard.

Still, the family wanted to know more than one busy teenager armed with Excel spreadsheets could manage. So John West approached Stanford cardiologist Ashley and colleagues for help. Last year, Ashley led a team to publish the first medical interpretation of a complete human genome and the tools developed in that study had been significantly enhanced to explore the West family's disease risks. One important component of the genomic analyses is the large, hand-curated databases that link genetic information with health. The lab of Atul Butte, MD, PhD, associate professor of systems medicine in pediatrics, developed Varimed, a database of genetic variants associated with diseases, and the lab of Russ Altman, MD, PhD, professor of genetics and of bioengineering, developed PharmGKB, a database of genetic variants associated drug response. Butte and Altman are co-authors of the paper.

To make the best use of those databases, the authors created new reference genomes against which an individual's genome can be compared.

Typically, human genetic information is checked against the human reference genome, a composite of several anonymous donors' DNA that does not have the most common DNA sequence at every position. In fact, the reference genome lacks the most common variant at 1.6 million genomic positions, 4,000 of which affect disease risk. "Because the reference-genome donors are real people, they have some genetic risks," said Ashley. "If you compare a new genome against that reference genome, you will miss the places where that reference genome and the new genome have the same risk variants."

For instance, the human reference genome contains versions of a clotting gene known as the Factor 5 Leiden variant, which increases the risks of blood clots. Both Anne West and her father have this variant, and if either had carried two copies of that same variant, typical genome analysis would not have identified that risk.

"We found 23 instances in the human reference genome where there were rare variants associated with large disease risk, such as the Factor 5 Leiden variant. Using the current reference genome, these variants wouldn't have been identified in any individual's sequenced genome if they had two copies of the mutation," said Dewey.

To work around this problem, Dewey used published genetic data from hundreds of unrelated people (part of the 1,000 Genomes project) to develop three, ethnicity-specific, synthetic reference genomes, which contain the most common variants for each group. Comparing an individual's genome to one that is ethnically matched and contains the most common variants aids the detection of rare disease-risk variants and reduces the number of errors in determining each person's exact genome sequence, the researchers found.

"Sequencing people of more diverse backgrounds is going to be extremely important in moving forward with the application of these genetic risk predictions to other populations," said Dewey.

Specifically for the Wests, the team identified multiple variants in genes related to clotting. They also identified the exact physician-determined dosage of anticoagulants that John West was already taking, and predicted the dosage that Anne West may one day need.

"Genome sequencing is impacting medicine right now," said Ashley. When the Wests had their genomes sequenced, it cost about $40,000 each. Now, companies offer the similar services for around $4,000 and that price is expected to fall as technologies improve. That means many more people will likely have their genomes sequenced soon, but without some analysis they won't mean much more than alphabet soup. "We believe medical genome interpretation could revolutionize medicine," said Ashley. "So many people have contacted us asking for help to analyze their genomes, but as an academic lab, we simply don't have the bandwidth. Industry will have to get involved." To that end, Ashley, Butte, Altman, John West and Stanford co-author Mike Snyder, professor and chair of genetics, have started a biotech company called Personalis through which they plan to offer management and analysis of whole-genome sequencing.

For the West family, the experience provided more than just medical information. "I think we may learn more about the results medically in the years to come as we are better able to analyze the genome, but the educational opportunity for Anne has been terrific right up front," said John West.

Other Stanford collaborators include Rong Chen, PhD, bioinformatics specialist and software developer; Pablo Sanchez-Cordero, biomedical informatics graduate student; Kelly Ormond, MS, CGC, genetics counselor and associate professor of genetics; Colleen Caleshu, MS, CGC, genetic counselor; Konrad Karczewski, biomedical informatics graduate student; Michelle Whirl-Carrillo, PhD, assistant director of PharmGKB; Matthew Wheeler, MD, PhD, cardiology fellow and postdoctoral researcher; Joel Dudley, PhD, consulting faculty of systems medicine in pediatrics; postdoctoral researchers Jake Byrnes, PhD, Omar Cornejo, PhD, and Emidio Capriotti, PhD; Joshua Knowles, MD, PhD, instructor of cardiovascular medicine; Mark Woon, software developer; Katrin Sangkuhl, PhD, Li Gong, PhD, Caroline Thorn, PhD, and Joan Hebert, all scientific curators of PharmGKB; Sean David, MD, PhD, clinical associate professor of medicine; Aleksandra Pavlovic, genetics liaison; Carlos Bustamante, PhD, professor of genetics; and Teri Klein, PhD, director of PharmGKB.

The Stanford team worked with colleagues from the Massachusetts General Hospital, the Harvard Medical School in Boston and the Institute for Systems Biology in Seattle.

The study and authors were funded by the NIH, including the National Heart, Lung and Blood Institute, the National Human Genome Research Institute and the National Institute of General Medical Sciences, and the Breetwor Family Foundation.

The above story is reprinted from materials provided by Stanford University Medical Center.

UCLA researchers have found that the hormone estrogen may help reverse advanced pulmonary hypertension, a rare and serious condition that affects 2 to 3 million individuals in the U.S., mostly women, and can lead to heart failure.

The condition causes a progressive increase in blood pressure in the main pulmonary artery, which originates in the heart's right ventricle and delivers blood to the lungs. The rise in pressure impairs heart function by enlarging the right ventricle, potentially leading to heart failure.

Published in the Sept. 15 issue of the American Journal of Respiratory and Critical Care Medicine, the preclinical study shows that in rats, estrogen treatment can reverse the progression of pulmonary hypertension to heart failure and can restore lung and ventricle structure and function.

The disease progresses slowly, so most patients don't seek treatment until major symptoms occur, such as shortness of breath, dizziness and fainting. According to researchers, current medication for pulmonary hypertension only temporarily reduces the disease's severity. For advanced pulmonary hypertension, there are fewer options, and the condition often necessitates a lung transplant.

"Unfortunately, up until now, there hasn't been an ideal pharmacological therapy to treat advanced pulmonary hypertension," said senior study author Mansoureh Eghbali, Ph.D., an assistant professor of anesthesiology at the David Geffen School of Medicine at UCLA who has a strong background in studying the role of gender and estrogen in cardiovascular diseases. "We hope that this early study may offer insight into new therapies."

The UCLA team found that by treating rats with severe pulmonary hypertension with low doses of estrogen, they were able to prevent the disease from progressing to right-ventricular heart failure; this did not happen in untreated rats.

Systolic blood pressure and ejection fraction -- the volume of blood being pumped out of the heart's right chamber with each heart beat -- also improved. Tests showed that lung weight, which can increase with the disease and resulting heart-ventricle enlargement, was also corrected. After 10 days of estrogen treatment, function returned to an almost normal state.

The researchers stopped the estrogen therapy after 10 days but continued to observe some of the treated rats. They tracked the continued improvement and found almost full restoration of systolic blood pressure and ejection fraction to normal levels after an additional 12 days.

"We were surprised to find this continued benefit, even after we stopped the estrogen treatment," said the study's first author, Dr. Soban Umar, a UCLA Department of Anesthesiology researcher who has studied pulmonary hypertension and right-ventricular heart failure and is a key member of Eghbali's laboratory team. "These findings suggest that even short-term estrogen therapy may suffice to reverse the disease."

All rats with severe pulmonary hypertension that were treated with estrogen survived by the study's end. Only 25 percent of the untreated rats survived.

The team also explored how estrogen could work in reversing the disease by studying several cellular and molecular mechanisms.

They found that the number of inflammatory cells in rats with pulmonary hypertension increased five-fold, compared with normal rats. In the animals treated with estrogen, this was reversed to normal. The team found that estrogen reduced regulation of a pro-inflammatory gene that also plays a key role in disease development caused by pulmonary hypertension. They also found that estrogen had an inhibitory effect on lung fibrosis.

In addition, the team observed that estrogen therapy restored blood vessels in the lungs and right ventricle whose loss is associated with the disease.

Further study identified that estrogen exerts its biological effects on pulmonary hypertension through a receptor called estrogen receptor beta, a protein that regulates estrogen's activity in the body.

"Estrogen appears to work through an interplay of several factors, including suppression of lung inflammation and fibrosis, as well as reversal of ventricle enlargement," Eghbali said. "We may be able to utilize estrogen receptor beta in the development of future therapies to stimulate estrogen activity to treat pulmonary hypertension."

Researchers had also tested estrogen receptor alpha, the other receptor that controls estrogen activity, but found that it wasn't as effective in treating pulmonary hypertension.

Eghbali added that estrogen receptor beta may prove to be a favorable therapeutic target, since this receptor may require only a short treatment duration and low dosage and has less pro-estrogenic effects on the breasts and uterus than estrogen receptor alpha.

Pulmonary hypertension affects mostly younger women, despite the fact that females in this age group should be under the protective benefits of natural estrogen produced by the body, Eghbali said.

"These patients may have a genetic mutation that is interfering in how estrogen receptor beta directs estrogen activity that is leading to pulmonary hypertension," she said.

Her team's next step is to explore these genetic questions. Currently, Umar and Eghbali are collaborating with UCLA pulmonary hypertension physicians to investigate gender-related issues and to define the role of estrogen in patients with this deadly disease.

The study was funded by the National Institutes of Health.

Additional authors included Andrea Lorga, Humann Matori, Rangarajan Nadadur, Jingyuan Li and Federica Maltese of the department of anesthesiology in the division of molecular medicine at the Geffen School of Medicine, and Arnoud van der Laarse of the department of cardiology at Leiden University Medical Center in the Netherlands.

The above story is reprinted from materials provided by University of California - Los Angeles Health Sciences.

When Arctic ground squirrels are getting ready to hibernate they don't just get fat -- they pack on muscle at a rate that would make a bodybuilder jealous. And they do it without suffering the harmful effects that high levels of testosterone and other anabolic steroids usually cause. University of Toronto Scarborough (UTSC) researchers have started to untangle how the squirrels manage it, and their results could someday have implications for human health.

Arctic ground squirrels, it turns out, ramp up their anabolic steroid levels and keep them high not just during the spring mating season, but during the summer and fall. To avoid the damaging effects of these high levels, they seem to suppress androgen receptors in all tissues except muscle, according to Rudy Boonstra, professor of biological sciences at UTSC.

Boonstra's research will appear in an upcoming issue of Functional Ecology. It is co-authored by Brendan Delehanty, also of UTSC, and Adrian J. Bradley of the University of Queensland.

Like many other hibernators, Arctic ground squirrels go underground in winter and burn the fat they stored up during the summer and fall. But Arctic ground squirrels have a problem faced by almost no other hibernator. Other animals dig below the frost line and hibernate in a relatively warm 0° C. Because Arctic ground squirrels can't get below the permafrost, they have to spend their eight-month hibernation at temperatures as low as -23° C.

Thus to stay alive their metabolisms have to run at a higher rate than other hibernators. Stored fat provides much of the energy they need, but it can't give them the levels of glucose required by vital tissues such as the brain and heart. Only burning protein stored in muscles will provide the needed glucose.

To see what was going on, Boonstra and colleagues examined the blood of Arctic ground squirrels in Canada's northern Yukon territory over an entire active season, and compared it with blood taken from Columbian ground squirrels from southern Alberta, a species which hibernates at about 0°C.

In most ground squirrels, testosterone levels in males peak during mating season then fall drastically afterwards. In male Arctic ground squirrels, anabolic steroid levels (including testosterone) start out higher than in other species and stay elevated -- between 10 and 200 times higher than in any other ground squirrels. Females also had exceptionally high levels of androgens, between 40 and 100 times higher than in other ground squirrels.

These high levels of androgens help both males and females to increase lean body mass (i.e. muscle) by about 25 percent in the months leading up to winter hibernation -- mass which is then consumed as they hibernate.

In another portion of the study Boonstra and colleagues showed that in males these anabolic steroids were not being produced at the normal site of production, the testes. Instead, the squirrels produced them in their adrenal glands.

High doses of anabolic steroids also have negative effects, such as suppressing the immune system, and in older human males, causing prostate cancer. Men who take anabolic steroids to increase muscle mass and strength can suffer side effects like baldness, scarring acne, shrinkage of the testicles, behavioral and psychiatric problems, and increased risk of cardiovascular disease.

Arctic ground squirrels are proposed to down-regulate androgen receptors in tissues other than muscle. In other words, the androgens coursing through their bodies are invisible to all tissues except muscle, which protects them from the ill effects of too much androgen. How they do this still isn't known.

Because of the role of androgen levels on prostate cancer, understanding how Arctic ground squirrels turn off androgen receptors could someday have implications for human health, Boonstra says.

The above story is reprinted from materials provided by University of Toronto Scarborough.

Recent PET-measurements in Turku, Finland, show that the GSM mobile phone electromagnetic field suppresses glucose metabolism in temporoparietal and anterior temporal areas of the hemisphere next to the antenna.

Thirteen young healthy males were exposed to the GSM signal for 33 minutes. The study, initiated by Centre for Cognitive Neuroscience (CCN) at University of Turku, was methodologically unique combining the expertice in brain imaging (National PET-Center and CCN), measurements and modeling of radiation (Radiation and Nuclear Safety Authority in Finland, STUK) and measurements of skin temperature (Finnish Institute of Occupational Health, TTL).

No conclusions concerning health risks can be made based on the result, the researchers caution. The study was financed by Finnish Technology Agency (Tekes) as part of the national Wirecom (wireless communication) research program.

The results were published in Journal of Cerebral Blood Flow & Metabolism.

The above story is reprinted from materials provided by Academy of Finland.

Using a diversity of DNA sequencing and human genome analytic techniques, researchers led by Baylor College of Medicine have identified some cases of developmental delay or cognitive disorders associated with a sudden chromosomal catastrophe that occurred early in development, perhaps during cell division when DNA is replicated.

In a report in the journal Cell, Dr. Weimin Bi, assistant professor of molecular and human genetics, Dr. James R. Lupski, vice chair of molecular and human genetics, both at BCM, first author Pengfei Liu, a graduate student in Lupski's laboratory, and their many clinical collaborating colleagues describe the analysis of the DNA of 17 patients who were referred to BCM because they had unexplained developmental problems.

"Four were very complex," said Liu. "One had 18 rearrangements in one chromosome. It was beyond our imagination."

About that time, a group of British researchers led by the Wellcome Trust Sanger Institute published another paper in Cell describing massive genomic rearrangements in cancer that they believe emanated from a single catastrophic event.

Lupski, Bi and Liu wondered if a similar situation had occurred in their patients, whose rearrangements occurred early in the germ line -- the cells that produce eggs and sperm. The events that had occurred in the genetic code of these patients shared striking similarities to the findings in the patients with cancer.

"First, the patients have many duplications and deletions," said Lupski, a pioneer in identifying and understanding copy number variation, changes that occur in the genome that either duplicate or delete genes, changing their expression with profound effects on the individual patients.

"We used comparative genomic array hybridization, FISH (fluorescent in situ hybridization, which can tell a person how many copies of a certain chromosome exist in each cell) and other techniques to demonstrate that this 'catastrophe' phenomenon exists in the genomes of these patients," said Liu. "This chromosomal catastrophe occurs not only in cancer but can also occur in different developmental tissues. They may occur in the germ line, as in our case, or in the somatic cells. In one case, the patient had this complex rearrangement and the mother also has it, but the rearrangement occurs in only a subset of her cells. It occurred in the mother during development and she then transmitted the rearrangement to the child."

"We see extensive complexity in the rearrangement," said Lupski. The researchers who wrote the cancer paper saw even more complex changes.

However, when such extreme changes occur in the chromosomes of developing embryos, this could potentially disrupt development resulting in "death before birth." The Baylor researchers propose that this accounts for the differences in the two groups, i.e. degree of complexity observed with cancer versus in subjects with cognitive disabilities, but they provide evidence that it is likely the same mechanisms are involved in the chromosomal catastrophes. The genomic changes they describe occur early in the development. The cancer changes occur in the cells of people who are often adults.

"We are looking for the mechanisms that cause this catastrophe," said Lupski. "We are dealing with pure rearrangement. The whole body has it, not just a subset of cancerous cells within a growing tumor."

In their work, the team saw features that seemed to indicate that the catastrophe may have occurred as a result of a single event involving DNA replication -- the process during cell division in which the pattern of DNA is copied for use in the new cell. If that replication process misfires, then the DNA is not copied accurately and the resulting cell is abnormal.

The developmental disorders the BCM team studies are those that can be caused by mutation in one of many potential genes.

"A combination of effects on multiple genes may be responsible for some subset of disorders," said Lupski. "You can interrupt one gene, delete another gene, make three copies of another gene; a single mutational event, but a potential multigenic effect."

Others who took part in this research include Ayelet Erez, Sandesh C. Sreenath Nagamani, Shweta U. Dhar, Katarzyna E. Kolodziejska, Avinash V. Dharmadhikari, M. Lance Cooper, Joanna Wiszniewska, Feng Zhang, Marjorie A. Withers, Carlos A. Bacino, Seema R. Lalani, Fernando Scaglia, Lane Strathearn, Sung-Hae L. Kang, Ankita Patel, Sau Wai Cheung, P. J. Hastings, and Pawel Stankiewicz all of BCM; Luis Daniel Campos-Acevedo and Dolores Hernández-Almaguer of Departamento de Genética, Hospital Universitario, Monterrey, México; Mauricio R. Delgado of Texas Scottish Rite Hospital in Dallas; Debra Freedenberg of Vanderbilt in Nashville, TN.; Adolfo Garnica of St. Francis Hospital in Tulsa, OK.; Theresa A. Grebe of Phoenix Children's Hospital; LaDonna Immken of Specially for Children in Austin, TX.; Scott D. McLean of San Antonio Military Medical Center; Hope Northrup of The University of Texas Medical School at Houston, and Pamela Trapane of Children's Hospital of Wisconsin in Milwaukee.

Funding for this work came from the National Institute of Neurological Disorders and Stroke, the National Institutes of General Medical Science, the Baylor College of Medicine Intellectual and Developmental Disabilities Research Center, The Eunice Kennedy Shriver National Institute of Children Health & Human Development, the Osteogenesis Imperfecta Foundation and the National Urea Cycle Foundation.

Dr. Lupski holds the Cullen Endowed Chair in Molecular Genetics.

The above story is reprinted from materials provided by Baylor College of Medicine.