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fMRI Brain Scans Predict Patient Response to Anti-Psychotic Medications; First-Time Such Results “Open Door for Precision Medicine Approaches to Psychiatry”

Investigators at The Feinstein Institute for Medical Research in Manhassett, New York have discovered that brain scans can be used to predict patients' response to antipsychotic drug treatment. The findings are published online on August 28, 2015 in The American Journal of Psychiatry. The article is titled “Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment.” Psychotic disorders, such as schizophrenia and bipolar disorder, are characterized by delusions, hallucinations, and disorganized thoughts and behavior. These disorders are estimated to occur in up to three percent of the population and are a leading cause for disability worldwide. Psychotic episodes are currently treated with antipsychotic drugs, but this treatment is given without guidance from lab tests or brain scans, such as functional magnetic resonance imaging (fMRI). Doctors often use "trial-and-error" approach when choosing treatment for psychotic disorders, without knowing if patients will respond well. This lack of knowledge places a large burden on not only patients and their families, but also on healthcare professionals and healthcare systems. Led by Anil Malhotra, M.D., Director of Psychiatry Research at Zucker Hillside Hospital and an Investigator at the Feinstein Institute, and Todd Lencz, Ph.D., Associate Investigator at the Zucker Hillside Hospital and the Feinstein Institute, researchers used fMRI scans obtained before treatment to predict ultimate response to medications in patients suffering from their first episode of schizophrenia. Connectivity patterns of a region of the brain called the striatum, which tends to be atypical in patients suffering from psychotic disorders, were used to create an index. This index significantly predicted if psychotic symptoms were decreased in the studies' patients.

Plasma MicroRNAs As Biomarkers for Possible Early Detection of Pancreatic Cancer

Pancreatic cancer is the fourth most common cause of cancer-related death in the United States and has a 5-year survival rate of just 6 percent, which is the lowest rate of all types of cancer according to the American Cancer Society. This low survival rate is partially attributed to the difficulty in detecting pancreatic cancer at an early stage. According to a new “proof of principle” study published online on August 27, 2015 in Cancer Prevention Research, Moffitt Cancer Center researchers in Tampa, Florida hope to improve pancreatic cancer survival rates by identifying markers in the blood that can pinpoint patients with premalignant pancreatic lesions called intraductal papillary mucinous neoplasms (IPMNs). The article is titled “Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas.” "One promising strategy to reduce the number of people affected by pancreatic cancer is to identify and treat premalignant pancreatic lesions," said first author Jennifer Permuth-Wey, Ph.D., Assistant Member in the Departments of Cancer Epidemiology and Gastrointestinal Oncology at Moffitt. "IPMNs are established precursor lesions to pancreatic cancer that account for approximately half of all asymptomatic pancreatic cysts incidentally detected by computerized tomography (CT) scans or magnetic resonance imaging (MRI) in the U.S. each year." IPMNs can be characterized as either low- or high-risk for the development of pancreatic cancer; however, the only way to accurately characterize the severity of IPMNs is by their surgical removal that is, in itself, associated with a risk of complications, such as long-term diabetes and death.

First Nanoscale DNA Vehicle for Delivery of CRISPR/Cas9 Gene Editing System into Cells

Researchers from North Carolina State University (NCSU) and the University of North Carolina at Chapel Hill (UNC-CH) have, for the first time, created and used a nanoscale vehicle made of DNA to deliver a CRISPR/Cas9 gene-editing tool into cells in both cell culture and an animal model. The article was published online on August 27, 2015 in Angewandte Chemie. The article is titled “Self-Assembled DNA Nanoclews for the Efficient Delivery of CRISPR-Cas9 for Genome Editing." The CRISPR/Cas system, which is found in bacteria and archaea, protects bacteria from invaders such as viruses. It does this by creating small strands of RNA called CRISPR RNAs, which match DNA sequences specific to a given invader. When those CRISPR RNAs find a match, they unleash Cas9 proteins that cut the DNA. In recent years, the CRISPR/Cas9 system has garnered a great deal of attention in the research community for its potential use as a gene editing tool - with the CRISPR RNA identifying the targeted portion of the relevant DNA, and the Cas9 protein cleaving it. But for Cas9 to do its work, it must first find its way into the cell. The current work focused on demonstrating the potential of a new vehicle for directly introducing the CRISPR/Cas9 complex - the entire gene-editing tool - into a cell. "Traditionally, researchers deliver DNA into a targeted cell to make the CRISPR RNA and Cas9 inside the cell itself - but that limits control over its dosage," says Dr. Chase Beisel, co-senior author of the paper and an Assistant Professor in the Department of Chemical and Biomolecular Engineering at NC State.

Redbanded Stink Bug Now a Major Threat to Texas Soybeans

Entomologists in Texas got a whiff of a new stink bug doing economic damage to soybeans in Texas and are developing ways to help farmers combat it, according to a report in the journal Environmental Entomology. The article is titled “Stink Bug Species Composition and Relative Abundance of the Redbanded Stink Bug (Hemiptera: Pentatomidae) in Soybean in the Upper Gulf Coast Texas.” Various types of stink bugs have long been a problem for soybean crops, but when sweeps of fields in southeast Texas netted 65 percent redbanded stink bugs, entomologists realized this particular bug had become the predominant pest problem, according to Dr. Mo Way, an entomologist at the Texas A&M AgriLife Research and Extension Center in Beaumont. The problem was no one in the U.S. knew much about the redbanded stink bug or how it had been able to overcome the previously predominant southern green stink bug, green stink bug and brown stink bug, Way said. An insect's life cycle and biology have to be understood before scientists can figure out ways to control it. Texas farmers plant a little less than 200,000 acres of soybeans a year, according to the U.S. Department of Agriculture's National Agricultural Statistics Service. "The redbanded stink bug has been a serious pest of soybeans in South America since the 1960s," said Dr. Suhas Vyavhare, a postdoc at the Beaumont center, who began his work on the insect as a graduate student there."It was never a problem in the United States until around 2000.

Alternative Splicing of Single Protein (PTBP1) May Have Led to Remarkable Evolution of Mammalian Brains, the Largest and Most Complex Among Vertebrates

University of Toronto researchers have discovered that a single molecular event in our cells could hold the key to how humans evolved to become the smartest animal on the planet. Benjamin Blencowe, Ph.D., a Professor in the University of Toronto’s Donnelly Centre and Banbury Chair in Medical Research, and his team have uncovered how a small change in a protein called PTBP1 (polypyrimidine-tract-binding protein 1) (image) can spur the creation of neurons – cells that make the brain – that could have fueled the evolution of mammalian brains to become the largest and most complex among vertebrates. The study is published in the August 21, 2015 issue of Science. The article is titled “An Alternative Splicing Event Amplifies Evolutionary Differences Between Vertebrates.” Brain size and complexity vary enormously across vertebrates, but it is not clear how these differences came about. Humans and frogs, for example, have been evolving separately for 350 million years and have very different brain abilities. Yet scientists have shown that they use a remarkably similar repertoire of genes to build organs in the body. So how is it that a similar number of genes, that are also switched on or off in similar ways in diverse vertebrate species, generate a vast range of organ size and complexity? The key lies in the process that Blencowe’s group studies, known as alternative splicing (AS), whereby gene products are assembled into proteins, which are the building blocks of life. During AS, gene fragments – called exons – are shuffled to make different protein shapes from the same original gene. It’s like LEGO, where some fragments can be missing from the final protein shape.

Mayo Scientists ID Code for Turning Off Cancer; Restoring Normal miRNA Levels in Cancer Cells Eliminates Aberrant Growth; Understanding of Cell-Cell Adhesion and miRNA Biology Proves Key to Major Oncology Advance with Profound Implications

Cancer researchers dream of the day they can force tumor cells to morph back to the normal cells they once were. Now, researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy. This potential blockbuster finding, published online on August 24, 2015 in Nature Cell Biology, represents “an unexpected new biology that provides the code, the software, for turning off cancer,” says the study’s senior investigator, Panos Anastasiadis, Ph.D., Chair of the Department of Cancer Biology on the Mayo Clinic’s Florida campus. Th article is titled “Distinct E-Cadherin-Based Complexes Regulate Cell Behaviour through miRNA Processing or Src and p120-Catenin Activity.” That code was unraveled by the discovery that adhesion proteins — the glue that keeps cells together — interact with the microprocessor, a key player in the production of molecules called microRNAs (miRNAs). The miRNAs orchestrate whole cellular programs by simultaneously regulating expression of a group of genes. The investigators found that when normal cells come in contact with each other, a specific subset of miRNAs suppresses genes that promote cell growth. However, when adhesion is disrupted in cancer cells, these miRNAs are misregulated and cells grow out of control. The investigators showed, in laboratory experiments, that restoring the normal miRNA levels in cancer cells can reverse that aberrant cell growth. “The study brings together two so-far unrelated research fields — cell-to-cell adhesion and miRNA biology — to resolve a long-standing problem about the role of adhesion proteins in cell behavior that was baffling scientists,” says the study’s lead author Antonis Kourtidis, Ph.D., a research associate in Dr. Anastasiadis’ lab.

Investigational Peptide Drug Shows Potential in Countering Deadly Effects of Radiation Exposure, When Given Up to 24 Hours After Exposure

An interdisciplinary research team led by The University of Texas Medical Branch (UTMB) at Galveston reports a new breakthrough in countering the deadly effects of radiation exposure. A single injection of a regenerative peptide was shown to significantly increase survival in mice when given 24 hours after nuclear radiation exposure. The study was published online on August 17, 2015 in Laboratory Investigation, a journal in the Nature Publishing group. The article is titled “Novel Regenerative Peptide TP508 Mitigates Radiation-Induced Gastrointestinal Damage by Activating Stem Cells and Preserving Crypt Integrity.” UTMB lead author Dr. Carla Kantara, postdoctoral fellow in biochemistry and molecular biology, said that a single injection of the investigative peptide drug TP508 given 24 hours after a potentially-lethal exposure to radiation appears to significantly increase survival and delay mortality in mice by counteracting damage to the gastrointestinal system. The threat of a nuclear incident, with the potential to kill or injure thousands of people, has raised global awareness about the need for medical counter-measures that can prevent radiation-induced bodily damage and keep people alive, even if given a day or more after contact with nuclear radiation. Exposure to high doses of radiation triggers a number of potentially lethal effects. Among the most severe of these effects is the gastrointestinal, or GI, toxicity syndrome that is caused by radiation-induced destruction of the intestinal lining. This type of GI damage decreases the ability of the body to absorb water and causes electrolyte imbalances, bacterial infection, intestinal leakage, sepsis, and death.

Chestnut Leaf Extract Blocks Virulence and Pathogenesis of Staph aureus, Potentially Effective Against MRSA Also; Emory-Led Study Shows

Leaves of the European chestnut tree contain ingredients with the power to disarm dangerous staph bacteria without boosting its drug resistance, scientists have found. The open-access journal PLOS ONE published the study online on August 21, 2015. The article is titled “Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance.” The use of chestnut leaves in traditional folk remedies inspired the research, led by Dr. Cassandra Quave, an ethnobotanist at Emory University. "We've identified a family of compounds from this plant that have an interesting medicinal mechanism," Dr. Quave says. "Rather than killing staph, this botanical extract works by taking away staph's weapons, essentially shutting off the ability of the bacteria to create toxins that cause tissue damage. In other words, it takes the teeth out of the bacteria's bite." The discovery holds potential for new ways to both treat and prevent infections of methicillin-resistant S. aureus (MRSA), without fueling the growing problem of drug-resistant pathogens. Antibiotic-resistant bacteria annually cause at least two million illnesses and 23,000 deaths in the United States, according to the Centers for Disease Control and Prevention. MRSA infections lead to everything from mild skin irritations to fatalities. Evolving strains of this "super bug" bacterium pose threats to both hospital patients with compromised immune systems and young, healthy athletes and others who are in close physical contact. "We've demonstrated in the lab that our extract disarms even the hyper-virulent MRSA strains capable of causing serious infections in healthy athletes," Dr. Quave says.

“Molecular Tweezer” (CLR01) Shows Remarkable Potential Effectiveness Against HIV and Other Sexually Transmitted Viruses in Semen

An unprecedented potential "molecular tweezer" called CLR01, reported on August 18, 2015 in the open-access journal eLife, not only blocks HIV and other sexually transmitted viruses, but also breaks up proteins in semen that boost infection. The article is titled “'A Molecular Tweezer Antagonizes Seminal amyloids and HIV Infection.” Semen is the main vector for sexual HIV transmission. It contains proteins that assemble into very stable polymers called amyloid fibrils, which can enhance HIV infectivity by up to 10,000 times. Scientists, led by the University of Pennsylvania (USA) and the University of Ulm (Germany), now show that a molecule with the shape of a tweezer not only destroys HIV particles, but also blocks the infection-promoting activity of semen amyloids. The antiviral activity of CLR01 is based on the way it selectively interacts with and destroys the viral coat. Remarkably, CLR01 does not affect cell membranes, which suggests it could be safely incorporated into a vaginal or anal gel to prevent HIV infection - without the risk of side effects. The way CLR01 operates means that it is also effective against many other sexually transmitted viruses, including hepatitis C and viruses in the herpes family. It may also be effective against many other "enveloped" viruses including flu and Ebola. The use of other preventive treatments has been undermined in some countries by the stigma associated with HIV. As CLR01 is effective against many viruses besides HIV, it could be more widely acceptable as a general protective agent in communities struggling with HIV stigma. Moreover, the scientists found that CLR01 also binds to amyloid fibrils and prevents the interaction with viruses that could be exploited by HIV to boost sexual transmission.

New Data on Mechanism of Cilia Assembly; Pertinent to Polycystic Kideny Disease (PKD) and Other Ciliopathies

The group led by ICREA (Catalan Institution for Research and Advanced Studies) Research Professor Cayetano Gonzalez at IRB Institute for Research in BiomedicineBarcelona, in collaboration with the group of Professor Giuliano Callaini from the University of Siena in Italy, has published a new study online on August 20, 2015 in Current Biology that contributes to understanding how cilia are assembled. The article is titled “Loss of Centrobin Enables Daughter Centrioles to Form Sensory Cilia in Drosophila.” Many cells in human bodies present a small structure that looks like, and as a matter of fact works as an antenna, conveying to the cell information on the extracellular environment. These structures are called cilia (plural) or cilium (singular). Ciliated cells play essential functions in the human body. Thus, for instance, the monitoring of fluid flow in the kidney, the detection of hormones in the brain, or the senses of hearing and smell depend on specialized neurons equipped with chemo-sensory or mechano-sensory cilia. Moreover, besides a sensory role, beating cilia keep fluids in motion in many parts of our bodies and are critical for human health. A cilium can be regarded as a long and thin protrusion of the cell membrane that contains microtubules. Ciliary microtubules are arranged in a typical radial symmetry that is conserved through evolution and is templated by a small organelle that sits at the base of the cilium, known as a basal body. Most animal cells contain two basal body-like structures (centrioles), but only one of them can actually work as basal body. In human cells, this is always the centriole that is said to be the "mother" because it was assembled earlier than the other, called the "daughter" centriole.

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