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Schizophrenia: Adolescence Is Game-Changer--Researchers Discover That Development of Hippocampus Is Severely Impacted in Adolescence at Time of First Psychotic Symptoms

Schizophrenia causes hallucinations and memory or cognition problems in those who have it. This psychiatric illness affects 0.5% of the general population, and it can be related to genetic abnormalities of chromosome 22, known as 22q11 deletion syndrome. However, not everyone who has this deletion syndrome necessarily develops psychotic symptoms. So, what triggers the illness? Researchers at the University of Geneva (UNIGE), Switzerland, have provided an initial answer after observing and analyzing several years of patients with deletion syndrome. The scientists found that the size of the hippocampus (image), the area of the brain responsible for memory and emotions, was smaller than normal but followed the same developmental curve as in healthy subjects. Yet, when the first psychotic symptoms appear - generally in adolescence - the hippocampus atrophies dramatically. The new results, which were reported online on June 4, 2019 in Molecular Psychiatry, open up new avenues for understanding the causes of schizophrenia. The article is titled “Positive Psychotic Symptoms Are Associated with Divergent Developmental Trajectories of Hippocampal Volume During Late Adolescence in Patients With 22q11ds.” 22q11 deletion syndrome is a neurogenetic disorder that targets chromosome 22. Thirty percent of people affected by the syndrome end up developing psychotic symptoms specific to schizophrenia, such as auditory hallucinations, memory problems, disorders affecting their perception of reality, and difficulties in social interactions characterized by strong paranoia.

Large Elk Populations in Yellowstone Elk Have Means to Adapt Their Migration Times to Changing Climate Cues; Migratory Shifts May Have Unknown Ripple Effects Throughout the Region

Every spring, tens of thousands of elk follow a wave of green growth up onto the high plateaus in and around Yellowstone and Grand Teton national parks, where they spend the summer calving and fattening on fresh grass. And every fall, the massive herds migrate back down into the surrounding valleys and plains, where lower elevations provide respite from harsh winters. These migratory elk rely primarily on environmental cues, including a retreating snowline and the greening grasses of spring, to decide when to make these yearly journeys, shows a new study led by University of California (UC), Berkeley, researchers. The study combined GPS tracking data from more than 400 animals in nine major Yellowstone elk populations with satellite imagery to create a comprehensive model of what drives these animals to move. "We found that the immediate environment is a very effective predictor of when migration occurs," said Gregory Rickbeil, PhD, who conducted the analysis as a postdoctoral researcher in Dr. Arthur Middleton's lab at UC Berkeley. This is in contrast with some other species, such as migratory birds, which rely on changing day length to decide when to move, Dr. Rickbeil pointed out. The results, published in the July 2019 issue of Global Change Biology, suggest that, as climate change reshapes the weather and environment of the park, elk should have the means to adjust their migratory patterns to match the new conditions.

Non-Invasive Prenatal Diagnosis for Fetal Sickle Cell Disease (SCD) Moves a Step Closer; Researchers Develop Test to Detect SCD by Next-Generation Sequencing of Cell-Free Fetal DNA in Mother’s Bloodstream

Sickle cell disease (SCD) is a form of anemia that is inherited when both parents are carriers of a mutation in the hemoglobin gene. Currently, this disease can only be diagnosed in pregnancy by carrying out an invasive test that has a small risk of miscarriage and is therefore sometimes declined by parents. Now, researchers from Guy's and St Thomas' NHS Foundation Trust and Viapath Analytics, London, UK, in collaboration with non-invasive healthcare company Nonacus Ltd., Birmingham, UK, have developed a non-invasive prenatal test for the disease, and this test was described on June 16, 2019 at the annual conference of the European Society of Human Genetics (ESHG) (https://2019.eshg.org/) (June 15-18). The abstract (C08.5) of this presentation is titled “Non-Invasive Prenatal Diagnosis of Sickle Cell Disease by Next-Generation Sequencing of Cell-Free DNA.” Julia van Campen, PhD, research scientist at Guy's and St Thomas', explains: “We have developed a method of testing for SCD using cell-free fetal DNA -- DNA from the fetus that circulates in the maternal bloodstream. Although cell-free fetal DNA testing is already available for some disorders, technical difficulties have hampered the development of such a test for SCD, despite it being one of the most commonly requested prenatal tests in the UK.” In couples that are at risk of having a baby with SCD, each partner carries a mutation in the hemoglobin gene, which means that any fetus has a one in four chance of inheriting both mutations and therefore being affected by SCD. Non-invasive prenatal diagnosis (NIPD) of conditions that are inherited in this way is difficult. "The development of a non-invasive prenatal assay for sickle cell disease has been attempted before and, until now, has not been successful, "says Dr.

Researchers' Discovery Could Lead to Improved Therapies for Duchenne Muscular Dystrophy; Administration of Sarcospan Protein May Strengthen Heart

A new multi-institution study spearheaded by researchers at Florida State University (FSU) and the University of California, Los Angeles (UCLA) suggests a tiny protein could play a major role in combating heart failure related to Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder among children. In collaboration with scientists from across the nation, FSU researchers found that increased levels of the protein sarcospan improve cardiac function by reinforcing cardiac cell membranes, which become feeble in patients with DMD. Their findings were published online on April 30, 2019 in JCI Insight. The article is titled “Stabilization of the Cardiac Sarcolemma by Sarcospan Rescues DMD-Associated Cardiomyopathy.” The condition, which typically afflicts young boys, is caused by a mutation that prevents the body from producing dystrophin, a protein crucial to the health of skeletal, respiratory, and cardiac muscles. Advances in treatment for certain types of DMD-related muscle degradation have helped to prolong patients' lifespans. However, as DMD patients age, their heart function declines dramatically. "Patients typically live to 20 or 30 years of age," said lead author Michelle Parvatiyar (photo), PhD, an Assistant Professor in the Department of Nutrition, Food and Exercise Sciences in FSU's College of Human Sciences. "There have been important improvements in respiratory care, which used to be what a majority of patients would succumb to. Now, in their 20s and 30s, they're often succumbing to cardiomyopathy. The heart is functioning with a major component of the cell membrane missing. Over time, it wears out."

Researchers Gain Useful Vaccination Clues from Studying Mother’s Transfer of Antibodies Across Placenta to Fetus

One of the most successful interventions in reducing infectious disease worldwide, vaccination still has limited effectiveness in protecting one group of patients - newborn infants. Now a study based at the Ragon Institute of MGH, MIT and Harvard has determined how a pregnant woman's vaccine-induced immunity is transferred to her child, which has implications for the development of more effective maternal vaccines. The report will be published in the June 27 issue of Cell and, receiving early online release on June 13, 2019. The article is titled “Fc Glycan-Mediated Regulation of Placental Antibody Transfer” "Newborns arrive into the world on the first day of life with brand-new immune systems that, like the children themselves, need to learn to cope with both helpful and harmful microbes in their environment," says Galit Alter (photo), PhD, of the Ragon Institute and the Massachusetts General Hospital (MGH) Department of Medicine, co-senior author of the Cell paper. "To help the newborn immune system learn to discriminate between friend and foe, mothers transfer antibodies to their infants via the placenta. The rules by which the placenta performs this absolutely essential function have been unknown but, if decoded, could hold the key to generating more powerful vaccines to protect these most precious patients." While maternal antibodies against some diseases such as measles can be transferred from mother to infant, providing some protection until the child is old enough for individual vaccination, antibodies to other serious diseases like polio are less efficiently transferred. To investigate the mechanisms by which antibodies are transferred from mother to child, Dr.

Special Fibroblasts, Antigen-Presenting Cancer-Associated Fibroblasts (apCAFs), Help Pancreatic Cancer Cells Evade Immune Detection; Further Study Might Reveal Approaches That Can Augment Diminished Immune Response

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the world. Mostly chemoresistant, PDAC so far has no effective treatment. Understanding the connective tissue, called stroma, that surrounds, nurtures, and even protects PDAC tumors, is key to developing effective therapeutics. "PDAC patients are diagnosed really late, so we don't know they're sick until the very end stages," said Ela Elyada (photo), PhD, a postdoctoral fellow in Dr. David Tuveson's lab at Cold Spring Harbor Laboratory (CSHL) in New York. "We can't diagnose patients early enough because we don't have tools, and they don't respond to drugs. One barrier to the drugs is the fibroblasts in the stroma." PDAC is characterized by an abundance of non-malignant stromal cells, and fibroblasts are one of the most common types of stromal cells. "We have a lot of fibroblasts in pancreatic cancer, unlike other cancers which are mostly cancer cells," Dr. Elyada said. These cancer-associated fibroblasts (CAFs) can help cancer cells proliferate, survive, and evade detection by the immune system. The insidious role CAFs seem to play in protecting cancer cells labels them as bad, but completely obliterating CAFs in mice also worsened their cancers. Dr. Elyada wanted to investigate the nature of CAFs: are they good or bad? To crack the case, she, Associate Professor Paul Robson at the Jackson Laboratory, and colleagues used single-cell RNA sequencing to classify the fibroblasts into three distinct sub-populations, identifying specific functions and characteristics unique to each. This includes two previously identified types of CAFs, myofibroblastic CAFs (myCAFs) and inflammatory CAFs (iCAFs), and also a new type of CAF called antigen-presenting CAFs (apCAFs). The apCAFs were present in both mice and human PDAC.

Unusual Language Use May Be Early Sign of Schizophrenia in At-Risk Individuals—Machine Learning Reveals Increased Use of Words Related to Voices & Sounds and of Words That Have Similar Meanings Is Predictive of Psychosis with 93% Accuracy

A machine-learning method discovered a hidden clue in people's language predictive of the later emergence of psychosis –-i.e., the frequent use of words associated with sound. A paper published by the Nature-published journal npj Schizophrenia published the findings by scientists at Emory University and Harvard University online on June 13, 2019. The open-access article is titled “A machine learning approach to predicting psychosis using semantic density and latent content analysis.” The researchers also developed a new machine-learning method to more precisely quantify the semantic richness of people's conversational language, a known indicator for psychosis. Their results show that automated analysis of the two language variables -- more frequent use of words associated with sound and speaking with low semantic density, or vagueness -- can predict whether an at-risk person will later develop psychosis with 93 percent accuracy. Even trained clinicians had not noticed how people at risk for psychosis use more words associated with sound than the average, although abnormal auditory perception is a pre-clinical symptom. "Trying to hear these subtleties in conversations with people is like trying to see microscopic germs with your eyes," says Neguine Rezaii, MD, first author of the paper. "The automated technique we've developed is a really sensitive tool to detect these hidden patterns. It's like a microscope for warning signs of psychosis." Dr. Rezaii began work on the paper while she was a resident at Emory School of Medicine's Department of Psychiatry and Behavioral Sciences. She is now at fellow in Harvard Medical School's Department of Neurology.

Drug Combination (FOLFIRINOX) May Make More Pancreatic Cancers Resectable & Also Extend Lifespans; Survival Time for Those with “Borderline Resectable” Tumors Nearly Doubled—from 12 Months to 22 Months

If the American Cancer Society's projections prove accurate, more people will die from pancreatic cancer than from breast, brain, ovarian, or prostate cancer this year. One reason pancreatic cancer is so lethal is its resistance to traditional chemotherapy. But surgical oncologist Brian Boone, MD, at the West Virginia University School of Medicine, is exploring whether FOLFIRINOX--a new combination of cancer drugs--can improve outcomes in patients whose pancreatic cancer is "borderline resectable," meaning that a tumor may be too close to a blood vessel to be removed safely. "The way pancreatic tumors sit, they're very close to several important blood vessels that you really can't live without. That's where chemotherapy comes into play," said Dr. Boone, an Assistant Professor in the School of Medicine's Department of Surgery. "We try to shrink the tumor off of the vein and change it from borderline resectable to resectable, or removable by surgery." In a recent meta-analysis of 24 studies, Dr. Boone and a team of researchers considered 313 cases of borderline resectable pancreatic cancer that physicians treated with FOLFIRINOX. They analyzed the patients' overall survival rates. They also evaluated how frequently tumors shrank enough to be surgically removed. The team found that FOLFIRINOX prolonged patients' lives, on average, and made surgery possible in more instances. Their findings were published online on May 14, 2019 in the Journal of the National Cancer Institute (JNCI).

Rapid, Easy-to-Use DNA Amplification Method at 37°C Developed by Japanese Scientists; Application Could Advance Molecular Diagnosis & Robotics

Scientists in Japan have developed a way of amplifying DNA on a scale suitable for use in the emerging fields of DNA-based computing and molecular robotics. By enabling highly sensitive nucleic acid detection, their method could improve disease diagnostics and accelerate the development of biosensors, for example, for food and environmental applications. Researchers from the Tokyo Institute of Technology (Tokyo Tech), Abbott Japan Co., Ltd., and the University of Electro-Communications, Japan, report a way to achieve million-fold DNA amplification and targeted hybridization that works at body temperature (37°C/98.6°F). The method, named L-TEAM (Low-TEmperature AMplification), is the result of more than five years of research and offers several advantages over traditional PCR, the dominant technique used to amplify DNA segments of interest. With its easy-to-use, “one-pot” design, L-TEAM avoids the need for heating and cooling steps and specialized equipment usually associated with PCR. That means it is an efficient, inexpensive method that can importantly prevent protein denaturation, thereby opening a new route to real-time analysis of living cells. In their study published in the June 21, 2019 issue of Organic & Biomolecular Chemistry, the researchers introduced synthetic molecules called locked nucleic acids (LNAs) into the DNA strands, as these molecules are known to help achieve greater stability during hybridization. The article is titled “Leak-Free Million-Fold DNA Amplification with Locked Nucleic Acid and Targeted Hybridization In One Pot.” The addition of LNA led to an unexpected, but beneficial, outcome.

Plant Cells Excitable Via Voltage-Dependent Two-Pore Calcium Channel Protein 1 (TPC1) Ion Channel; Central Vacuole of Plant Cells Also Excitable Via TPC1

Many plant processes are not different from humans: cells and tissues in grain plants, including maize also communicate through electrical signals. The shape and frequency of these signals tell a plant different things. For example, these signals allow the plants to respond to heat and cold, excessive light intensities or insect pests. If, for instance, a caterpillar starts to nibble on the leaves of a wild plant, an electrical signal is sent to the leaves that haven't been harmed yet, triggering a response mechanism: bitter agents or toxic substances are subsequently produced throughout the plant, causing the caterpillar to stop eating or killing it after a while. But the ability to produce bitter substances has been bred out of modern crops for reasons of taste. Therefore, chemical pesticides are sprayed on field crops to rid them of caterpillar pests. Researchers from the Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, have now shed new light on plant communication via electrical signals. The scientists found that the two-pore calcum channel protein 1 (TPC1) ion channel contributes to plant excitability. The function of this channel had been previously unknown. This discovery may pave the way to breed plants that are more resistant to pests, heat or drought in the long run - properties that are crucial in the face of climate change. The JMU scientists, led by biophysicist Professor Rainer Hedrich, PhD, published their findings online on June 14, 2019 in Nature Communications. The open-access article is titled “Voltage-Dependent Gating of SV Channel TPC1 Confers Vacuole Excitability.” It was Dr. Hedrich who had discovered the TPC1 ion channel in the mid-1980s, when he was a postdoc with Nobel Laureate Erwin Neher in Göttingen.

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