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Archive - Feb 14, 2015

New Mouse Model Suggests That Normally Functioning N17 Region of Huningtin Protein May Help Protect Neurons Against Huntington’s Disease

Scientists know that Huntington’s disease is caused by an inherited gene mutation. But research has yet to identify the specific mechanisms that trigger the disease and cause it to advance — and there is currently no way to prevent the disease or slow its progression. Now, researchers at UCLA have found that removing a specific molecular switch from a mutant protein can trigger symptoms in mice that are similar to the symptoms found in people with Huntington’s disease. The finding provides further insight into how the disease evolves. The study, led by Dt. X. William Yang, a UCLA Professor of Psychiatry, was published online on February 5, 2015 in Neuron. Huntington’s disease affects 1 in every 10,000 Americans, while another 250,000 are at risk because they carry the inherited gene mutation. That mutation leads to an abnormallylong stretch of an amino acid called glutamine in the huntingtin protein. Symptoms include chorea (jerky, uncontrollable movements), dystonia (sustained involuntary muscle contractions), and an abnormal gait that can cause frequent falls. People with Huntington’s also suffer from debilitating cognitive and psychiatric deficits and they typically die of complications from the disease about 20 years after the onset of symptoms. Most of those who have Huntington’s disease do not show symptoms until middle age, meaning that many unknowingly pass on the mutated gene to their children. In 2009, Dr. Yang and his colleagues genetically manipulated a small domain on the huntingtin protein called N17 that is a 17-amino-acid region located immediately before the mutant glutamine stretch. In doing so, they found they could dramatically suppress the disease in an earlier mouse model of Huntington’s disease they had developed.

Scientists Using X-Ray Crystallograpy & Electron Cryo-Microscopy to Create Synthetic Vaccine for Polio, Following Moddel Used Usscessfully for Foot-and-Mouth-Disease Virus

Scientists from the UK and the USA are using technology that helped in the design of a new synthetic vaccine to combat the foot-and-mouth-disease virus (FMDV) to now target the virus that causes polio. The synthetic vaccine that is currently being engineered in collaboration with Professor Dave Rowlands at the University of Leeds would provide a powerful weapon in the fight to rid the world of polio. This project is being funded by a £438,000 grant from the World Health Organization (WHO) and the Bill & Melinda Gates Foundation (http://www.gatesfoundation.org/). The research team's hope is to create a vaccine that does not contain the viral genome, but instead “mimics” the structure of the live virus. Such a vaccine would be quicker, easier, and safer to produce. Even after the apparent global elimination of poliomyelitis, it will be necessary to continue vaccination as a precaution against re-introduction of the polio virus from hidden sources, such as rare chronically infected carriers. A synthetic vaccine would fulfil this role without the inherent danger of accidental release of virus associated with the production of current vaccines. Eventually, such vaccines could pave the way to completely eliminating the necessity to vaccinate.

Declarative Memory Is “Superstar” Among Brain’s Memory & Learning Systems; New Hypothesis Suggests This Powerful System Enables Compensation in ASDs, OCD, Tourette’s, Dyslexia, and SLI; May Also Play Positive Roles in ADHD, Aphasia, and Parkinson’s

Individuals with five neurodevelopmental disorders -- autism spectrum disorder (ASDs), obsessive-compulsive disorder (OCD), Tourette syndrome, dyslexia, and Specific Language Impairment (SLI) -- appear to compensate for dysfunction by relying on a single powerful and nimble system in the brain known as declarative memory. This hypothesis, currently being proposed by a Georgetown University Medical Center neuroscientist, is based on decades of research. It is published online and will be in the April issue of Neuroscience and Biobehavioral Reviews. The proposed compensation allows individuals with autism to learn scripts for navigating social situations; helps people with obsessive-compulsive disorder or Tourette syndrome to control tics and compulsions; and provides strategies to overcome reading and language difficulties in those diagnosed with dyslexia, autism, or Specific Language Impairment, a developmental disorder of language. "There are multiple learning and memory systems in the brain, but declarative memory is the superstar," says Michael Ullman, Ph.D., Professor of Neuroscience at Georgetown and Director of the school’s Brain and Language Laboratory. He explains that declarative memory can learn explicitly (consciously), as well as implicitly (non-consciously).

The Neural Basis of “Being in the Mood”

What determines receptivity or rejection towards potential sexual partners? For people, there are many factors that play a part, appearance, culture, age, are all taken into account. But what part does the internal state of the individual play? The functioning of our bodies is maintained through a complicated system of hormonal signals. Some of these signals vary along different physiological rhythms, such as the menstrual cycle. How do changes in hormone levels affect the activity of individuals' brains and their behavior? "It is well known that the behavior of female mice changes dramatically during the different phases of their reproductive cycle, called the estrous cycle," says Dr. Susana Lima (http://neuro.fchampalimaud.org/en/person/61/), a Principal Investigator at the Champalimaud Centre for the Unknown in Lisbon, Portugal. "Responses to brief social interactions with males can result in radically different outcomes, ranging from receptivity to aggression. In this study, we investigated the question--what is the neural basis that underlies these polar behaviors?" The study results were published online on Februay 12, 2015 in Current Biology. The article is entitled, “Enhanced Male-Evoked Responses in the Ventromedial Hypothalamus of Sexually Receptive Female Mice.” The researchers chose to focus their research on the hypothalamus. "The hypothalamus regulates many instinctive behaviors, including feeding, sleeping, and sexual behavior", says Dr. Kensaku Nomoto, a post-doctoral researcher in the laboratory of Susana Lima. "We recorded the activity of neurons in an area within the hypothalamus dedicated to socio-sexual behavior. The activity of the neurons was observed while the females interacted with males or with other females."

Romantic Reunion of Two Fern Species After 60 Million Years Apart Stuns Plant Geneticists

A delicate woodland fern discovered in the mountains of France is the “love child” of two distantly-related groups of plants that haven't interbred in 60 million years, genetic analyses show. For most plants and animals, reuniting after such a long hiatus is thought to be impossible due to genetic and other incompatibilities between species that develop over time. Reproducing after such a long evolutionary breakup is akin to an elephant hybridizing with a manatee, or a human with a lemur, said co-author Kathleen Pryer, who directs the Duke University Herbarium. Led by Dr. Pryer and Dr. Carl Rothfels of the University of California, Berkeley, the study appears online on February 14, 2015 in the American Naturalist. The pale green fern was found growing wild on a forest floor in the Pyrenees and eventually made its way to a nursery, where researchers plucked several fronds and extracted the DNA to pinpoint its parentage. To their surprise, genetic analyses revealed that the fern was the result of a cross between an oak fern and a fragile fern -- two distantly related groups that co-occur across much of the northern hemisphere, but stopped exchanging genes and split into separate lineages some 60 million years ago. "To most people they just look like two ferns, but to fern researchers these two groups look really different," Dr. Rothfels said. Other studies have documented instances of tree frog species that proved capable of producing offspring after going their separate ways for 34 million years, and sunfish who hybridized after nearly 40 million years, but until now, those were the most extreme reunions ever recorded. "For most plant and animal species, reproductive incompatibility takes only a few million years at the most," Dr. Rothfels said.

Proteomics Analysis Reveals New Alzheimer’s Targets; Beyond Beta-Amyloid and Tau

Allan Levey, M.D, Ph.D, Chair of Neurology at Emory University School of Medicine and Director of the Emory Alzheimer's Disease Research Center, gave a a talk titled "Proteomics Discovery of New Alzheimer's Disease Targets," as part of the Dementia: Research Milestones and Policy Priorities session on Friday, Feb. 13, at the 2015 annual AAAS convention taking place in San Jose, California, February 12-16, 2015, The theme of this year’s AAAS meeting is “Innovations, Information, and Imaging.” Dr. Levey described a "beyond the usual suspects" approach to probing for proteins involved in Alzheimer's disease pathology. "Usual suspects" refers to beta-amyloid and tau, two proteins that accumulate in the brains of Alzheimer's patients. Some experimental approaches to Alzheimer's treatment aim at curbing beta-amyloid, but have not proven effective. Taking their proteomics approach, Dr. Levey and his team have already identified a previously unrecognized type of pathology in the brains of Alzheimer's patients, seen at early stages of the disease. They found tangle-like structures that sequester proteins critical for RNA splicing, a discovery that may have implications for the disease mechanism. A related article, entitled “U1 Small Nuclear Ribonucleoprotein Complex and RNA Splicing Alterations in Alzheimer’s Disease,” was published in the February 10, 2015 issue of PNAS. Last year, Emory was awarded a five-year, $7.2 million grant from the National Institute on Aging to extend this work in collaboration with five other Alzheimer's Disease Research Centers around the country.The image depicts the U1 small nuclear ribonucleoprotein complex.

[Press release] [PNAS articlet]