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Long-Term, Anti-Rejection-Drug-Free Tolearance of Pancreas Islets Cells Induced by Apoptotic Donor Leukocytes in Non-Human Primates; Anti-Rejection Drugs Completely Discontinued 21 Days After Transplant

For decades, immunologists have been trying to train the transplant recipient's immune system to accept transplanted cells and organs without the long-term use of anti-rejection drugs. New University of Minnesota preclinical research shows that this is now possible. In a study published online on August 2, 2019 in Nature Communications, researchers at the University of Minnesota Medical School's Department of Surgery and Schulze Diabetes Institute, collaborating with colleagues at Northwestern University, have maintained long-term survival and function of pancreatic islet transplants despite complete discontinuation of all anti-rejection drugs on day 21 after the transplant. The open-access article is titled “Long-Term Tolerance of Islet Allografts in Nonhuman Primates Induced by Apoptotic Donor Leukocytes.” This study was performed in a stringent preclinical transplant setting in nonhuman primates, one step away from humans. For many patients with end-stage organ failure, transplantation is the only effective and remaining treatment option. To prevent transplant rejection, recipients must take medications long-term that suppress the body's immune system. These immunosuppressive drugs are effective at preventing rejection over the short term; however, because anti-rejection drugs suppress all of the immune system nonspecifically, people taking these drugs face the risk of serious infections and even cancer. Additionally, non-immunological side effects of immunosuppression, such as hypertension, kidney toxicity, diarrhea, and diabetes diminish the benefits of transplantation.

Self-Sterilizing Polymer Proves Effective Against Drug-Resistant Pathogens

Researchers from North Carolina (NC) State University have found that an elastic polymer possesses broad-spectrum antimicrobial properties, allowing it to kill a range of viruses and drug-resistant bacteria in just minutes - including methicillin-resistant Staphylococcus aureus (MRSA). "We were exploring a different approach for creating antimicrobial materials when we observed some interesting behavior from this polymer and decided to explore its potential in greater depth," says Rich Spontak, PhD, co-corresponding author of a paper on the work and Distinguished Professor of Chemical and Biomolecular Engineering at NC State. "And what we found is extremely promising as an alternate weapon to existing materials-related approaches in the fight against drug-resistant pathogens. This could be particularly useful in clinical settings - such as hospitals or doctor's offices - as well as senior-living facilities, where pathogen transmission can have dire consequences." The polymer's antimicrobial properties stem from its unique molecular architecture, which attracts water to a sequence of repeat units that are chemically modified (or functionalized) with sulfonic acid groups. "When microbes come into contact with the polymer, water on the surface of the microbes interacts with the sulfonic acid functional groups in the polymer - creating an acidic solution that quickly kills the bacteria," says Reza Ghiladi, PhD, an Associate Professor of Chemistry at NC State and co-corresponding author of the paper. "These acidic solutions can be made more or less powerful by controlling the number of sulfonic acid functional groups in the polymer." The work was published online on July 17, 2019 in Materials Horizon.

Discovery of Maturation Plasticity in Acute Myeloid Leukemia Cells May Redirect Research

Approximately 22,000 people will be diagnosed this year in the US with acute myeloid leukemia (AML), the second most common type of leukemia diagnosed in adults and children, and the most aggressive of the leukemias. Less than one third of AML patients survive five years beyond diagnosis. Researchers from Australia's Monash University have discovered a key reason why this disease is so difficult to treat and therefore cure. The study, led by Associate Professor Ross Dickins from the Australian Centre for Blood Diseases, was published online on August 1, 2019 in Cell Stem Cell. The article is titled “Interconversion Between Tumorigenic and Differentiated States in Acute Myeloid Leukemia.” The paper identifies an important new concept relevant to clinicians involved in the diagnosis and treatment of AML patients. AML is characterised by an overproduction of immature white blood cells that fail to mature properly. These leukemia cells crowd the bone marrow, preventing it from making normal blood cells. In turn this causes anemia, infections, and if untreated, death. AML remains a significant health problem, with poor outcomes despite chemotherapy and stem cell transplantation. For decades it has been thought that AML growth is driven by a sub-population of immature cancer cells called “leukemia stem cells,” which lose their cancerous properties when they mature. Hence, there has been growing international interest in developing therapies aimed at forcing immature cancer cells to “grow up.” Using genetically engineered mouse models and human AML cells, Associate Professor Dickins and his Monash-led team have found that maturation of AML cells is not unidirectional as originally thought, but can instead be reversible.

TB Mycobacteria Can Use Carbon Monoxide for Survival

Carbon monoxide is an infamous and silent killer that can cause death in minutes. But while it is deadly for us, some microorganisms actually thrive on it, by using this gas as an energy source. Associate Professor Chris Greening and his team of microbiologists from the School of Biological Sciences, Monash University in Australia have discovered that some pathogens depend on carbon monoxide to survive when other nutrients are not available. The research focused on mycobacteria, a bacterial group that causes killer diseases such as tuberculosis (TB), leprosy, and Buruli ulcer. During infection, these microbes are in a hostile environment with very few nutrients to go around, meaning that anything they can do to get extra energy can be hugely advantageous. "When microbial cells are starved of their preferred energy sources, one way they subsist is by scavenging gases such as carbon monoxide," said Monash PhD student Paul Cordero, the co-lead author of the study. "They breakdown this gas into its fundamental components, which provide the cells just enough energy to persist." The researchers showed that an enzyme called carbon monoxide dehydrogenase is what allows mycobacteria to obtain energy from this gas. While the energy gained is not enough to allow for growth, the researchers found that carbon monoxide consumption allowed mycobacteria to survive for longer periods of time. The study was published online on July 29,2019 in the ISME Journal. The open-access article is titled “Atmospheric Carbon Monoxide Oxidation Is a Widespread Mechanism Supporting Microbial Survival.” The group's findings suggest that Mycobacterium tuberculosis might be able to survive inside the human host by using carbon monoxide. Present in humans since ancient times, TB remains a major global health burden.

Study Reveals Intracellular Release Mechanism for ASCT2-Transportd Nutrient Amino Acid Glutamine; Study May Lay Groundwork for Development of Small Molecules to Inhibit Growth of Cancer Cells

In order to sustain fast growth, cancer cells need to take up nutrients at a faster rate than healthy cells. The human glutamine transporter ASCT2 allows the amino acid glutamine to enter cells and ASCT2 (image) is upregulated in many types of cancer cells, which need more glutamine. It is a potential target for new anti-cancer drugs. Researchers at the University of Groningen in the Netherlands have now elucidated a structure of the human ASCT2 that provides unprecedented insight into the workings of this protein, and may aid the development of drugs. The results were published in Nature Communications on July 31, 2019. The open-access article is titled “A One-Gate Elevator Mechanism for the Human Neutral Amino Acid Transporter ASCT2.” This work allowed the researchers to solve a long-lasting riddle. It was known that these transporters work like an elevator, where the substrate glutamine is engulfed by the protein, and then carried over a long distance through the cell membrane from the outside to the inside of the cell. While it was known how the substrate enters the elevator on the outside, it remained enigmatic what happens on the inside. This study now shows, for the first time, how the transported glutamine is released into the cytoplasm of the cell. The release mechanism is surprisingly similar to its catch mechanism on the outside of the cell. The same gate - a.k.a. elevator door - is used on either side of the membrane. "Hence, we have named the transport mechanism a 'one-gate elevator,” which sets it apart from the more commonly observed mechanisms that use two different gates for entry and release,” author Dr. Dirk Slotboom says. Senior author Dr. Cristina Paulino said, "This observation is of great fundamental interest, but also has potential implications for drug design.

International OCD Foundation (IOCDF) Holds 26th Annual OCD Conference (2019) in Austin, Texas, July 19-21; Over 2,000 Attend from 49 States and 24 Countries

The 26th Annual OCD Conference was held in Austin, Texas, July 19-21. Organized by the International OCD Foundation (IOCDF), headquartered in Boston, the Conference informs and empowers members of the obsessive compulsive disorder community by bringing together health professionals, researchers, individuals with OCD, and their loved ones, with the goal of educating all attendees about the latest treatments, research, and practice in OCD and related disorders. This year, attendance broke 2,000, with attendees coming from 49 states and 24 different countries to learn more about how to help friends, families, or patients who are struggling with this troubling and variable problem. A warm welcoming statement was made to meeting attendees by Susan Boaz, President, Board of Directors, IOCDF. “One of the most unique things about the Conference is the experience of having so many diverse groups mingling, all of whom help each other find hope and support for OCD. Our researchers have the opportunity to share their latest discoveries about the causes and treatment of OCD and they value the opportunity to hear from the front lines about what is really occurring in the community of OCD sufferers. Parents meet each other and form lifetime friendships. Kids and adults with OCD learn that they are not alone. Everyone is willing to answer questions, provide information, make friends, and share hope. Our wish is that you experience kindness and inspiration at our Annual OCD Conference.” The IOCDF’s Annual OCD Conference is the only international event focused solely on serving the OCD and related disorders community.

Compound (Resveratrol) Found In Red Wine and Grape & Berry Skins & Seeds May Open Door to New Treatments for Depression & Anxiety; Research Lays Groundwork for Use of Resveratrol in Novel Anti-Depressants

Like to unwind with a glass of red wine after a stressful day? Don't give alcohol all the credit. New research has revealed that the plant compound resveratrol, which is found in red wine, displays anti-stress effects by blocking the expression of an enzyme related to the control of stress in the brain, according to a University at Buffalo (UB)-led study. The findings shed light onto how resveratrol impacts neurological processes. According to the Anxiety and Depression Association of America, depression and anxiety disorders affect 16 and 40 million people respectively in the United States. "Resveratrol may be an effective alternative to drugs for treating patients suffering from depression and anxiety disorders," says Ying Xu, MD, PhD, co-lead author and research associate professor in the UB School of Pharmacy and Pharmaceutical Sciences. The study, published in the July 15, 2019 issue of the journal Neuropharmacology, was also led by Xiaoxing Yin, PhD, Professor at Xuzhou Medical University in China. The article is titled “The antidepressant- and anxiolytic-like effects of resveratrol: Involvement of phosphodiesterase-4D inhibition.” Resveratrol, which has been linked to a number of health benefits, is a compound found in the skin and seeds of grapes and berries. While research has identified resveratrol to have antidepressant effects, the compound's relationship to phosphodiesterase 4 (PDE4), an enzyme influenced by the stress hormone corticosterone, was unknown. Corticosterone regulates the body's response to stress. Too much stress, however, can lead to excessive amounts of the hormone circulating in the brain and, ultimately, to the development of depression and/or other mental disorders.

Discovery of Alpha-Synclein DNA Repair Function Could Lead to New Treatments for Parkinson's & Other Brain Diseases

A small protein previously associated with cell dysfunction and death in fact serves a critical function in repairing breaks in DNA, according to new research led by scientists at Oregon Health & Science University (OHSU). The discovery, published online on July 29, 2019 in Scientific Reports, marks the first demonstration of the role that alpha-synuclein plays in preventing the death of neurons in brain diseases such as Parkinson's, which affects 1.5 million people in the United States alone. The findings suggest that it may be possible to design new therapies to replace alpha-synuclein's function or boost it in people with Parkinson's disease and other neurodegenerative disorders. Aggregates of alpha-synuclein, known as Lewy bodies, have long been connected to Parkinson's and other forms of dementia. The study published today casts a new light on that process. The open-access article is titled “Alpha-Synuclein Is a DNA Binding Protein That Modulates DNA Repair with Implications for Lewy Body Disorders.” The findings suggest that Lewy bodies are problematic because they pull alpha-synuclein protein out of the nucleus of brain cells. The study, which examined the cells of living mice and postmortem brain tissue in humans, reveals that these proteins perform a crucial function by repairing breaks that occur along the vast strands of DNA present in the nucleus of every cell of the body. Alpha-synuclein's role in DNA repair may be crucial in preventing cell death. This function may be lost in brain diseases such as Parkinson's, leading to the widespread death of neurons. "It may be the loss of that function that's killing that cell," said senior author Vivek Unni, MD, PhD, an Associate Professor of Neurology in the OHSU School of Medicine.

Certain Gut Bacteria (Clostridia) Prevent Obesity in Mice; Population of These Bacteria Influenced by Immune System; Possible Clues to Human Obesity

Researchers at University of Utah Health have identified a specific class of bacteria from the gut that prevents mice from becoming obese, suggesting these same microbes may similarly control weight in people. The beneficial bacteria, called Clostridia, are part of the microbiome – collectively, trillions of bacteria and other microorganisms that inhabit the intestine. Published in the July 26, 2019 issue of Science, the study shows that healthy mice have plenty of Clostridia -- a class of 20 to 30 bacteria -- but those mice with an impaired immune system lose these microbes from their gut as they age. Even when fed a healthy diet, the mice inevitably become obese. Giving this class of microbes back to these animals allowed them to stay slim. The Science article is titled “T Cell-Mediated Regulation of the Microbiota Protects Against Obesity.” June Round, PhD, an Associate Professor of Pathology at U of U Health, is the study's co-senior author along with U of U Health Research Assistant Professor W. Zac Stephens, PhD. Charisse Petersen, PhD, a graduate student at the time, led the research. "Now that we've found the minimal bacteria responsible for this slimming effect, we have the potential to really understand what the organisms are doing and whether they have therapeutic value," Dr. Round says. Results from this study are already pointing in that direction. Dr. Petersen and colleagues found that Clostridia prevents weight gain by blocking the intestine's ability to absorb fat. Mice experimentally treated so that Clostridia were the only bacteria living in their gut were leaner with less fat than mice that had no microbiome at all. They also had lower levels of a gene, CD36, that regulates the body's uptake of fatty acids. These insights could lead to a therapeutic approach, Dr.

Bacteria Separated by Billions of Years of Evolution and Employing Different Mechanisms of Photosynthesis Share Common Photosynthetic Sites; Results Suggest New View of Evolution of Photosynthesis

Structures inside rare bacteria are similar to those that power photosynthesis in plants today, suggesting the process is older than assumed. The finding could mean the evolution of photosynthesis needs a rethink, turning traditional ideas on their head. Photosynthesis is the ability to use the Sun's energy to produce sugars via chemical reactions. Plants, algae, and some bacteria today perform “oxygenic” photosynthesis, which splits water into oxygen and hydrogen to power the process, releasing oxygen as a waste product. Some bacteria instead perform “anoxygenic” photosynthesis, a version that uses molecules other than water to power the process and does not release oxygen. Scientists have always assumed that anoxygenic photosynthesis is more “primitive,” and that oxygenic photosynthesis evolved from it. Under this view, anoxygenic photosynthesis emerged about 3.5 billion years ago and oxygenic photosynthesis evolved a billion years later. However, by analysing structures inside an ancient type of bacteria, Imperial College London researchers have suggested that a key step in oxygenic photosynthesis may have already been possible a billion years before commonly thought. The new research was published online on July 24, 2019 in Trends in Plant Science. The article is titled “Evolution of Photochemical Research Centres: More Twists?” Lead author of the study, Dr. Tanai Cardona from the Department of Life Sciences at Imperial, said: "We're beginning to see that much of the established story about the evolution of photosynthesis is not supported by the real data we obtain about the structure and functioning of early bacterial photosynthesis systems." The bacteria they studied, Heliobacterium modesticaldum, is found around hot springs, soils, and waterlogged fields, where it performs anoxygenic photosynthesis.

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