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Archive - Aug 2013

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August 21st

Schizophrenia Symptoms Linked to Faulty Switch in Brain

Scientists at The University of Nottingham in the UK have shown that psychotic symptoms experienced by people with schizophrenia could be caused by a faulty ‘switch’ within the brain. In a study published in an open-access article in the August 21, 2013 issue of Neuron, the researchers have demonstrated that the severity of symptoms such as delusions and hallucinations, which are typical in patients with the psychiatric disorder, is caused by a disconnection between two important regions in the brain — the insula and the lateral frontal cortex. This discovery, say the academics, could form the basis for better, more targeted treatments for schizophrenia with fewer side effects. The four-year study, led by Professor Peter Liddle and Dr. Lena Palaniyappan in the University’s Division of Psychiatry and based in the Institute of Mental Health, centered on the insula region, a segregated ‘island’ buried deep within the brain, which is responsible for seamless switching between inner and outer world. Dr. Palaniyappan, a Wellcome Trust Research Fellow, said: “In our daily life, we constantly switch between our inner, private world and the outer, objective world. This switching action is enabled by the connections between the insula and frontal cortex. This switching process appears to be disrupted in patients with schizophrenia. This could explain why internal thoughts sometime appear as external objective reality, experienced as voices or hallucinations in this condition. This could also explain the difficulties in ‘internalizing’ external material pleasures (e.g., enjoying a musical tune or social events) that result in emotional blunting in patients with psychosis.

Impaired Autophagy Associated with Age-Related Macular Degeneration

A new study published online on July 29, 2013 in the open-access journal PLOS ONE changes our understanding of the pathogenesis of age-related macular degeneration (AMD). The researchers found that degenerative changes and loss of vision are caused by impaired function of the lysosomal clean-up mechanism, or autophagy, in the fundus of the eye. The results open new avenues for the treatment of the dry form of AMD, which currently lacks an efficient treatment. The University of Eastern Finland played a leading role in the study, which also involved research groups from Italy, Germany and Hungary. AMD is the most common cause of visual impairment in the Western world, and the number of AMD patients is expected to soar in the upcoming decades. AMD is divided into the dry and wet form of the disease, and 85% of AMD patients suffer from dry AMD. Unfortunately, an efficient treatment involving injections into the eye only exists for the wet form of the disease. AMD is a storage disease in which harmful protein accumulations develop behind the retina. These accumulations are indicative of the severity of the disease. As the disease progresses, retinal sensory cells in the central vision area are damaged, leading to loss of central vision. The cell biological mechanisms underlying protein accumulations remain largely unknown. For the first time ever, the present study showed that AMD is associated with impaired lysosomal autophagy, which is an important clean-up mechanism of the fundus of the eye. This renders the cells in the fundus of the eye unable to dispose of old, deformed or otherwise faulty proteins, which, in turn, leads to the development of protein accumulations and loss of vision.

Tokyo Scientists Show Dogs Yawn More Often in Response to Owners' Yawns

Dogs yawn contagiously when they see a person yawning, and respond more frequently to their owner's yawns than to those of a stranger, according to research published online on August 7, 2013 in the open-access journal PLOS ONE by Dr. Teresa Romero and colleagues from the University of Tokyo. Pet dogs in the study watched their owner or a stranger yawn, or mimic a yawning mouth movement, but yawned significantly more in response to their owners' actions than to the strangers' yawns. The dogs also responded less frequently to the fake movements, suggesting they have the ability to yawn contagiously. Previous research has shown that dogs yawn in response to human yawns, but it was unclear whether this was a mild stress response or an empathetic response. The results of this study suggest the latter, as dogs responded more to their owners' genuine yawns than to those of a stranger. The researchers observed no significant differences in the dogs' heartbeats during the experiments, making it unlikely that their yawns were a distress response. Explaining the significance of the results, Dr. Romero says, "Our study suggests that contagious yawning in dogs is emotionally connected in a way similar to humans. Although our study cannot determine the exact underlying mechanism operative in dogs, the subjects' physiological measures taken during the study allowed us to counter the alternative hypothesis of yawning as a distress response." [Press release] [PLOS ONE article]

August 20th

Multiple Genes Determine How People Taste Sweeteners

Genetics may play a role in how people's taste receptors send signals, leading to a wide spectrum of taste preferences, according to Penn State food scientists. These varied, genetically influenced responses may mean that food and drink companies will need a range of artificial sweeteners to accommodate different consumer tastes. "Genetic differences lead to differences in how people respond to tastes of foods," said Dr. John Hayes, assistant professor, food science, and director of the sensory evaluation center at Penn State. Based on the participants' genetic profile, researchers were able to explain the reactions of subjects in a taste test when they sampled Acesulfame-K -- Ace K -- in the laboratory. Ace K is a man-made non-nutritive sweetener commonly found in carbonated soft drinks and other products. Non-nutritive sweeteners are sweeteners with minimal or no calories. While some people find Ace K sweet, others find it both bitter and sweet. The researchers, who reported their findings online on April 18, 2013 in the journal, Chemical Senses, said that variants of two bitter taste receptor genes -- TAS2R9 and TAS2R31 -- were able to explain some of the differences in Ace K's bitterness. These two taste receptor genes work independently, but they can combine to form a range of responses, said Alissa Allen, a doctoral student in food science, who worked with Dr. Hayes. Humans have 25 bitter-taste receptors and one sweet receptor that act like locks on gates. When molecules fit certain receptors like keys, a signal is sent to the brain, which interprets these signals as tastes -- some pleasant and some not so pleasant, Allen said. In another study published in July 2013 in the journal Chemosensory Perception, Allen had 122 participants taste two stevia extracts, RebA -- Rebaudioside A -- and RebD -- Rebaudioside D.

New Hypothesis for How Anthrax Toxins Escape Intracellular Endosome

A new hypothesis concerning a crucial step in the anthrax infection process has been advanced by scientists at the National Institute of Standards and Technology (NIST) and the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) at Fort Detrick, Maryland. The research teams have explored the behavior of the toxins that rapidly overwhelm the body as the often-fatal disease progresses. Their findings suggest a new possible mechanism by which anthrax bacteria deliver the protein molecules that poison victims. Anthrax is easily weaponized; the findings could help lead to a more effective cure. The results were published online on August 8, 2013 in the Journal of Chemical Physics. Anthrax bacteria kill by releasing three toxins that work in concert to destroy cells. One toxin, called PA, attaches to the cell membrane, where its surface serves as a sort of landing pad for the other two toxins, called LF and EF. Once several molecules of LF and EF have latched onto PA, the cell membrane tries to destroy these unwanted hangers-on by wrapping them up in an "endosome," a small bubble of membrane that gets pinched off and moved into the cell's interior. There, the cell attempts to destroy its contents by a process that includes making the interior of the endosome more acidic. But before the cell can fully carry out its plan, the LF and EF escape from the endosome and wreak havoc in the cell's interior. The question is: how do these toxins escape? "A recent hypothesis is that LF and EF completely unfold and then squeeze through the narrow hole that PA forms in the endosomal membrane," says NIST physical scientist Dr. John Kasianowicz.

August 19th

Novel Chinese Herbal Medicine Improves Spinal Cord Injury Outcomes in Rats

A new study, published online on June 12, 2013 in Restorative Neurology and Neuroscience, demonstrates that the Chinese herbal medicine Ji-Sui-Kang (JSK), given systemically for three weeks after injury in rats, improved locomotor function, reduced tissue damage, and preserved the structure of neural cells compared to control rats. The report also includes data showing that JSK may first act to reduce inflammation and cell apoptosis and death, and boost local oxygen supply while, later on, it appears to restore function and promote tissue regeneration. Although Chinese herbal medicines have traditionally been used for a variety of ailments, the rationale for their use relies more on anecdotal evidence than the results of modern-day controlled experiments. "A number of anecdotal reports from Chinese medicine practitioners indicate that treatment with a novel herbal formulation, JSK, for periods of one week or three months improved functional recovery," explains co-lead investigator Shucui Jiang, M.D., Ph.D., head of the Hamilton NeuroRestorative Group at McMaster University in Hamilton, Ontario, Canada. "Our present study provides an important and necessary foundation for further studies of JSK." In this study, rats began JSK treatment immediately after undergoing spinal cord injury. Within 7 days, hindlimb locomotor function was significantly better in JSK-treated rats compared to those receiving only saline. JSK-treated rats continued to have better motor function than controls throughout the 21-day test period and treated animals appeared to support their weight better and have more coordinated movements.

Mechanism Determined for How Beneficial Bacteria Persist and Thrive in GI Tract

The human body is full of tiny microorganisms—hundreds to thousands of species of bacteria collectively called the microbiome, which are believed to contribute to a healthy existence. The gastrointestinal (GI) tract—and the colon in particular—is home to the largest concentration and highest diversity of bacterial species. But how do these organisms persist and thrive in a system that is constantly in flux due to foods and fluids moving through it? A team led by California Institute of Technology (Caltech) biologist Dr. Sarkis Mazmanian believes it has found the answer, at least in one common group of bacteria: i.e., a set of genes that promotes stable microbial colonization of the gut. A study describing the researchers' findings was published as an advance online publication of the journal Nature on August 18, 2013. "By understanding how these microbes colonize, we may someday be able to devise ways to correct for abnormal changes in bacterial communities—changes that are thought to be connected to disorders like obesity, inflammatory bowel disease, and autism," says Dr. Mazmanian, a professor of biology at Caltech whose work explores the link between human gut bacteria and health. The researchers began their study by running a series of experiments to introduce a genus of microbes called Bacteriodesto into sterile, or germ-free, mice. Bacteriodes, a group of bacteria that has several dozen species, was chosen because it is one of the most abundant genuses in the human microbiome, it can be cultured in the lab (unlike most gut bacteria), and it can be genetically modified to introduce specific mutations. "Bacteriodes are the only genus in the microbiome that fit these three criteria," Dr. Mazmanian says. Lead author Dr. S. Melanie Lee, who was an M.D./Ph.D. student in Dr.

August 17th

Genome Study Assesses Genetic Overlaps Between Major Mental Disorders

The largest genome-wide study of its kind has determined how much five major mental illnesses are traceable to the same common inherited genetic variations. Researchers, funded in part by the National Institutes of Health, found that the overlap was highest between schizophrenia and bipolar disorder; moderate for bipolar disorder and depression and for ADHD and depression; and low for schizophrenia and autism. Overall, common genetic variation accounted for 17-28 percent of risk for the illnesses. "Since our study only looked at common gene variants, the total genetic overlap between the disorders is likely higher," explained Naomi Wray, Ph.D., University of Queensland, Brisbane, Australia, who co-led the multi-site study by the Cross Disorders Group of the Psychiatric Genomics Consortium (PGC), which is supported by the NIH's National Institute of Mental Health (NIMH). "Shared variants with smaller effects, rare variants, mutations, duplications, deletions, and gene-environment interactions also contribute to these illnesses." Dr. Wray, Kenneth Kendler, M.D., of Virginia Commonwealth University, Richmond, Jordan Smoller, M.D., of Massachusetts General Hospital, Boston, and other members of the PGC group report on their findings online on August 11, 2013 in the journal Nature Genetics. "Such evidence quantifying shared genetic risk factors among traditional psychiatric diagnoses will help us move toward classification that will be more faithful to nature," said Bruce Cuthbert, Ph.D., director of the NIMH Division of Adult Translational Research and Treatment Development and coordinator of the Institute's Research Domain Criteria (RDoC) project, which is developing a mental disorders classification system for research based more on underlying causes.

Elimination of Cilia Suppresses Cyst Growth in Models of Polycystic Kidney Disease (PKD)

A study by Yale researchers and colleagues has uncovered a new and unexpected molecular mechanism in the development of polycystic kidney disease (PKD). The study was published online on July 28, 2013 in Nature Genetics. PKD is a life-threatening genetic disorder that causes multiple cysts to form on the kidneys — enlarging them, cutting off proper urine flow, and causing kidney failure in half of affected people by age 60. It affects more than 12 million people worldwide. Cilia are the hair-like structures on the surface of many human cells that can either move things along – dirt out of the lungs, or an egg from the ovary to the uterus – or sense the environment, such as vision in the retina or smell in the nose. Recent research has implicated defects in the sensory cilia — often caused by genetic mutations — in many human diseases, including cancer, cardiac disease, blindness, and kidney disease. In the kidney, disruption of sensory cilia can cause kidney cysts. The polycystin-1 and polycystin-2 (also known as PC1 and PC2) proteins are key players in the normal functioning of the kidneys. Earlier research has shown that when either if these proteins is lost or mutated, cysts grow in the kidneys and cause almost all cases of autosomal dominant PKD (ADPKD) in humans. Working in mice, the Yale team and colleagues found that cysts grew when the cilia were intact but lacked polycystin protein — but, surprisingly, cysts stopped growing despite the absence of polycystins when the cilia were disrupted or eliminated. The activity of this pathway, and the timing of the loss of polycystin proteins and the cilia, determined the severity of both early- and adult-onset PKD, the researchers found.

Chemical Reverses Effects of Parkinson's-Disease Mutation in Cells

University of California-San Francisco (UCSF) scientists working in the lab used a chemical found in an anti-wrinkle cream to prevent the death of nerve cells damaged by mutations that cause an inherited form of Parkinson’s disease. A similar approach might ward off cell death in the brains of people afflicted with Parkinson’s disease, the team suggested in a study reported in the August 15, 2013 issue of the journal Cell. The achievement marks a pharmacologic milestone as the first highly specific targeting of a member of an important class of enzymes called kinases to increase rather than to inhibit their activity, according to UCSF chemist Kevan Shokat, Ph.D., the senior scientist on the study. The research raises hope that similar pharmaceutical strategies might be used for combating other diseases, including diabetes and cancer, he said. Mutations that cause malfunction of the targeted enzyme, PINK1, are directly responsible for some cases of early-onset Parkinson’s disease. Loss of PINK1 activity is harmful to the cell’s power plants, called mitochondria, best known for converting food energy into another form of chemical energy used by cells, the molecule ATP. In Parkinson’s disease, poorly performing mitochondria have been associated with the death of dopamine-producing nerve cells in a region of the brain called the substantia nigra, which plays a major role in control of movement. Loss of these cells is a hallmark of Parkinson’s disease and the cause of prominent symptoms including rigidity and tremor. A UCSF team led by Dr. Shokat, a Howard Hughes Medical Institute Investigator, used the chemical, called kinetin, to increase mutant PINK1 enzyme activity in nerve cells to near normal levels.