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June 14th, 2019

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.

Avalon GloboCare President and CEO David Jin, MD, PhD, to Chair June 15 "Research and Application of Stem Cell Exosomes" Session at 2019 Second International Aesthetic Industry Conference in Chengdu, China

Avalon GloboCare Corp. (NASDAQ: AVCO), a leading global developer of cell-based technologies and therapeutics, announced on June 13, 2019 that the Company's President and Chief Executive Officer, David Jin. MD, PhD, will participate at the Second International Aesthetic Industry Conference in Chengdu, China, the largest meeting of its kind across all of Asia. Dr. Jin will lead the "Application of Stem Cell Exosomes" session on June 15, 3:30 pm - 6:30 pm, in the city’s Century City New International Convention and Exhibition Center (image), acting as both chair and speaker of the panel. At this time, Dr. Jin will also unveil the launch of Avalon's new exosome product commercialization plan. The company will be providing a series of skincare and wound-healing products with Avalon's Clinical-grade Tissue-specific EXosomes as additives (ACTEX). Additionally, Yu Zhou, MD, PhD, the Co-CEO of Avalon's subsidiary GenExosome Technologies, will provide the conference keynote address. GenExosome Technologies developed proprietary exosome isolation systems in order to promote implementation of exosome biotechnology in "liquid biopsies" and to provide innovative exosome products for clinical diagnosis and treatment. Dr. Zhou's keynote presentation is titled "Application of Exosome Technology in Aesthetic Industry: Isolation, Quality Control, and Exosomic Analysis." "Avalon GloboCare is dedicated to assembling and integrating the premier scientific, clinical, and regulatory resources from around the world, in order to accelerate innovative and transformative cellular and exosome-based technologies, as well as their clinical applications," stated Dr. Jin.

June 13th

Vagus Nerve Electro-Stimulation Reduces Rheumatoid Arthritis Symptoms in Pilot Study; May Also Be Effective Against Other Chronic Inflammatory Diseases

The results of a pilot study presented (abstract number: LB0009) on June 14, 2019, at the Annual European Congress of Rheumatology (EULAR 2019) (https://www.congress.eular.org/) June 12-15 in Madrid, Spain, suggest that electro stimulation of one of the nerves connecting the brain to the body (the vagus nerve) could provide a novel treatment approach for patients with rheumatoid arthritis. The abstract (http://scientific.sparx-ip.net/archiveeular/?c=a&searchfor=LB0009&view=1...) is titled “First-in-Human Study of Novel Implanted Vagus Nerve Stimulation Device to Treat Rheumatoid Arthritis,” "This is a really exciting development. For many patients suffering from rheumatoid arthritis, current treatments don't work, or aren't tolerated," said Professor Thomas Dörner, Chairperson of the Scientific Programme Committee, EULAR 2019. "These results open the door to a novel approach to treating not only rheumatoid arthritis, but other chronic inflammatory diseases. This is certainly an area for further study." The vagus nerve is the longest and the most complex of the 12 pairs of cranial nerves that originate from the brain. The name “vagus” comes from the latin word for “wandering.” This is because the vagus nerve “wanders” from the brain into the organs of the neck, chest and abdomen. Recent advances in neuroscience and immunology have mapped circuits in the brain that regulate immune responses. In one of the circuits, i.e., the “inflammatory reflex,” signals are transmitted in the vagus nerve that inhibit the production of cytokines including tumor necrosis factor (TNF), an inflammatory molecule that is a major therapeutic target in rheumatoid arthritis.

Mouse Study Shows That Existing Drugs That Inhibit the TRF1 Telomere Protein May Be Effective in Glioblastoma Treatment; Synergistic Therapeutic Effect Seen with Combinations of the TRF1 Inhibitors

Usually, scientists study the molecular biology of cancer to find new treatments, but sometimes, it is the other way round: when trying to find new treatments, scientists find key information on cancer biology. The researchers from the Telomeres and Telomerase Group at the Spanish National Cancer Research Centre (CNIO) in Madrid, Spain, have identified new drug combinations that prevent the development of therapy resistance in mice with glioblastoma, the most malignant brain tumor. The scientists also found an unexpected link between the RAS pathway, which is involved in numerous types of cancer, and telomere maintenance. This finding, which could be used in new lines of research, will be published in the medical journal EMBO Molecular Medicine. The open-acccess article is titled “Multiple Cancer Pathways Regulate Telomere Protection.” "We had a twofold result in our study," says Maria A. Blasco, PhD, Head of the Telomeres and Telomerase Group at CNIO, and CNIO Director. "We were looking for approved drugs that could block a new target, and we found them. In the process, we also found that some molecular pathways that have a role in cancer development also participate in the regulation of telomere maintenance. This is an interesting aspect of cancer biology that was unknown before." Telomeres are protective structures at the ends of chromosomes. The Telomeres and Telomerase Group at CNIO found that attacking the telomeres in cancer cells can be an effective strategy to stop cancer growth. Specifically, the researchers in this Group found that inhibiting the telomeric repeat-binding factor 1 (TRF1) telomere protein (image) impairs tumor progression in human and murine glioblastoma models.

June 12th

Transgenerational Exposure to Bisphenol A (BPA) Causes Autism-Like Behavior in Mouse Model—Unexposed Mice Descended from Great-Grandmother Exposed to BPA During Pregnancy Show Evidence of Autism-Like Behavior

Transgenerational bisphenol A (BPA) exposure may contribute to autism, according to a mouse study that was published online on June 12, 2019 in the Endocrine Society's journal Endocrinology. The article is titled “Endocrine Disrupting Chemicals (EDCs) Are Chemicals or Mixtures of Chemicals That Interfere with the Way the Body's Hormones Work.” BPA is a common EDC used in plastics and food storage material, and it is already present in most humans' urine or blood. Animal studies have linked BPA to anxiety, aggression, and poor learning and social interactions. Studies of human populations report associations between BPA and neurobehavioral issues like attention deficit hyperactivity disorder and autism. "Exposure of mouse fetuses to BPA disrupts formation of nerve cell connections in the brain, and this is a transgenerational effect," said the study's senior author, Emilie F. Rissman, PhD, of the University of Virginia School of Medicine in Charlottesville, Virginia, and North Carolina State University in Raleigh, North Carolina. "To put this in human terms, if your great-grandmother was exposed to BPA during her pregnancy and none of your other relatives ever came into contact with BPA, your brain would still show these effects." In this mouse study, researchers tested mice descended from those exposed to BPA for social recognition and found that they showed a social behavioral deficient like autistic behavior. Mice whose great-grandmothers were exposed to BPA during pregnancy were more active and took longer to habituate to strangers than other mice. More strikingly, they didn't explore the new mice that were introduced to the group. Mice are normally very social and curious, so this is an exciting finding. "Even if we ban all BPA right now, that will not change these long-term effects on the brain," Dr. Rissman said.

Existing Acne Drug (Minocycline) Found Highly Effective in Preventing/Treating Hardening of the Arteries; Finding Culminates 12 Years of Research

A team of UK scientists has identified the mechanism behind hardening of the arteries, and shown in animal studies that a generic medication normally used to treat acne could be an effective treatment for the condition. The team, led by the University of Cambridge and King's College London, found that a molecule once thought only to exist inside cells for the purpose of repairing DNA is also responsible for hardening of the arteries, which is associated with dementia, heart disease, high blood pressure, and stroke. There is no current treatment for hardening of the arteries, which is caused by build-up of bone-like calcium deposits, stiffening the arteries and restricting blood flow to organs and tissues. Supported by funding from the British Heart Foundation, the researchers found that poly(ADP ribose), or PAR, a molecule normally associated with DNA repair, also drives the bone-like calcification of arteries. Additionally, using rats with chronic kidney disease, the researchers found that minocycline -- a widely-prescribed antibiotic often used to treat acne -- could treat hardening of the arteries by preventing the build-up of calcium in the circulatory system. The study, the result of more than a decade of fundamental research, was published online on June 11, 2019 in Cell Reports. The open-access article is titled “Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization.” "Artery hardening happens to everyone as they age, and is accelerated in patients on dialysis, where even children develop calcified arteries. But, up until now, we haven't known what controls this process and therefore how to treat it," said Professor Melinda Duer, PhD, from Cambridge's Department of Chemistry, who co-led the research as part of a long-term collaboration with Professor Cathy Shanahan, PhD, from King's College London.

New-Found Vulnerability in Major Human Viruses; Rhinoviruses (e.g., Colds) and Enteroviruses (e.g., Polio) Shown to Have Functionally Key Capsid Pocket That Can Be Blocked to Likely Prevent Replication

Discovery of a new feature of a large class of pathogenic viruses may allow development of new antiviral medications for the common cold, polio, and other illnesses, according to a new study published online on June 11 in the open-access journal PLOS Biology by Rana Abdelnabi, PhD, and Johan Neyts of the University of Leuven, Belgium, and James Geraets, PhD, and Sarah Butcher, PhD, of the University of Helsinki and their colleagues. The article is titled “A Novel Druggable Interprotomer Pocket in the Capsid of Rhino- and Enteroviruses.” Picornaviruses include rhinoviruses and enteroviruses. Rhinoviruses cause millions of cases of upper respiratory infections ("colds") yearly and contribute to asthma, while enteroviruses are responsible for millions of infections including cases such as meningitis, encephalitis, and polio. There are currently no antivirals that can be used for the treatment or prevention of any of the rhino- or enteroviruses. To replicate, viruses must interact with host cells, and in doing so, often need to change shape; stabilizing the virus particle is therefore thought to be a promising strategy for preventing replication. In a search for potential antiviral candidates, the authors found a compound that stabilized a model picornavirus. The scientists performed cryo-electron microscopy (cryo-EM) of the drug-virus complex to determine how the drug exerted its effect. Cryo-EM involves combining thousands of two-dimensional images to develop a highly detailed three-dimensional image of the target. Although picornaviruses have been studied for decades, the authors discovered a previously unknown pocket, or indentation, on the surface of the virus, in which the compound had lodged, thereby stabilizing the virus against the kind of shape change that would allow interaction with host cells.