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Using MicroRNA from Exosomes to Detect Early Signs of Type 2 Diabetes in Teens-- Hyperglycemic Obese Teens Have Different Exosomes Than Normoglycemic Obese Teens, with MicroRNAs Targeting Carbohydrate Metabolism & Visceral Fat

Researchers know that exosomes, tiny subcellular membrane-bound nanoparticles released from fat cells (and all cells studied), travel through the bloodstream and body, regulating a variety of processes, from growth and development to metabolism. The exosomes are important in lean, healthy individuals in maintaining homeostasis, but when fat gets “sick,” the most common reason for this is too much weight gain—the exosomes from fat cells show an altered phenotype, becoming inflammatory, and they can disrupt how our organs function, from how our skeletal muscle and liver metabolize sugar to how our blood vessels process cholesterol. Robert J. Freishtat (photo), MD, MPH, the Chief of Emergency medicine at Children's National Health System and a Professor of Precision Medicine and Genomics at the George Washington University School of Medicine and Health Sciences, and Sheela N. Magge MD, MSCE, who is now the Director of Pediatric Endocrinology and an Associate Professor of Medicine at the Johns Hopkins School of Medicine, were curious about what this process looked like in teens who fell in the mid-range of obesity. Obesity is a major risk factor for insulin resistance and type 2 diabetes, but Dr. Freishtat and Dr. Magge wanted to know: Why do some teens with obesity develop type 2 diabetes over others? Why are some teens in this mid-range of obesity metabolically healthy while others have metabolic syndrome? Can fat in obese people become sick and drive disease? To test this, Dr. Freishtat and Dr. Magge worked with 55 obese adolescents, ages 12 to 17, as part of a study at Children's National Health System. The participants (32 obese normoglycemic youth and 23 obese hyperglycemic youth) were similar in age, sex, race, pubertal stage, body mass index, and overall fat mass.

Hepatitis C Virus (HCV) Inhibits Normal Immune Response by Triggering Suppressor of Cytokine Signaling (SOCS) Regulator Molecule

Scientists from Trinity College Dublin have discovered how the highly infectious and sometimes deadly hepatitis C virus (HCV) "ghosts" our immune system and remains undiagnosed in many people. The rsearchers reported their findings on June 5, 2019 in The FASEB Journal. The article is titled “The Hepatitis C Virus (HCV) Protein, P7, Suppresses Inflammatory Responses to Tumor Necrosis Factor (TNF)-α Via Signal Transducer and Activator of Transcription (STAT)3 and Extracellular Signal-Regulated Kinase (ERK)–Mediated Induction of Suppressor of Cytokine Signaling (SOCS)3.” HCV's main route of transmission is via infected blood, but over the past 40 years, the virus has accidentally been given to many patients across the world via infected blood products. The virus replicates particularly well in the liver, and the damage it causes makes it a leading cause of liver disease worldwide. Even though HCV can be deadly, initial infection is rarely accompanied by any obvious clinical symptoms for reasons that have, until now, remained unknown. As a result, it often goes undiagnosed for the first 6-12 months following infection. If left untreated, HCV spreads throughout the liver, stimulating a low-level inflammatory response. Over several months, these mild responses, accompanied by subsequent liver repair, result in fibrotic scarring of the liver. The liver's main job is to filter out toxins, but during HCV infection the build-up of fibrotic, non-functioning liver tissue, results in reduced liver function. Without a fully functioning liver, one major side-effect is the build-up of toxins, often manifest as "jaundice.” If patients do not realize they are infected with HCV, their first noticeable symptoms are the side-effects of liver fibrosis (such as jaundice).

Scientists Edge Closer to Root Causes of Multiple Sclerosis; Study of 32 Families Having Multiple Members with MS Demonstrates 12 Different Disease-Associated Candidate Genes; These Genes May Offer Guideposts to Development of Effective MS Treatment

An international team of researchers led by the University of British Columbia scientists has made a scientific advance they hope will lead to the development of preventative treatments for multiple sclerosis (MS). In a study published online on June 6, 2019 in PLOS Genetics, researchers found mutations in 12 genes believed to be largely responsible for the onset of MS in families with multiple members diagnosed with the disease. The open-access article is titled “Exome Sequencing in Multiple Sclerosis Families Identifies 12 Candidate Genes and Nominates Biological Pathways for the Genesis ff Disease.” "These genes are like a lighthouse illuminating where the root cause of MS is," said lead author Carles Vilariño-Güell, PhD, Assistant Professor in the UBC Faculty of Medicine's Department of Medical Genetics and a Michael Smith Scholar. MS is a disease that affects the central nervous system, in which cells from the immune system attack and damage the nerve cells' protective myelin sheath (see larger image at end). The disease often results in disability and can have a significant impact on quality of life. For this study, researchers sequenced all known genes in three or more MS patients from 34 families and examined the genetic variants in family members both affected by and unaffected by MS. By looking at the genes of 132 patients, they identified 12 genetic mutations that can lead to an overactive autoimmune system that attacks myelin, the insulating layer around nerves in the brain and spinal cord. Of people diagnosed with MS, only 13 per cent are believed to have a genetic form of the disease, but those presenting the mutations identified in this new study were estimated to have an up to 85 per cent chance of developing MS in their lifetime. Dr.

Novel Gene Therapy--Japanese Researchers Develop Modified Anti-Sense Oligo (ASO) for Possible Treatment & Prevention of Parkinson’s Disease; ASO Is Targeted Against mRNA for α-Synuclein

An Osaka University-led research team has recently published findings that provide a ray of hope for the millions of Parkinson's disease (PD) sufferers worldwide. Although more common in those aged over sixty, PD can strike at any age, with an estimated prevalence of 41 per 100,000 people in their forties. And, while not fatal in and of itself, the progressive neurodegeneration that is characteristic of PD can often cause secondary effects that lead to death. The exact cause of PD is still a mystery, but researchers believe that both genetics and the environment are likely to play a part. Importantly though, all PD patients show a loss of dopaminergic neurons in the brain and increased levels of a protein called α-synuclein (image), which accumulates in Lewy bodies. Lewy bodies are a pathological feature of both familial and sporadic forms of the disease, as well as some types of dementia. In the study published online on May 21, 2019 in Scientific Reports, the team led by researchers from Osaka University's Graduate School of Medicine focused on α-synuclein as a target for a novel PD treatment. The open-access article is titled "Amido-Bridged Nucleic Acid (AmNA)-Modified Antisense Oligonucleotides Targeting α-Synuclein As A Novel Therapy for Parkinson's Disease.” "Although there are drugs that treat the symptoms associated with PD, there is no fundamental treatment to control the onset and progression of the disease," explains lead author Takuya Uehara, PhD. "Therefore, we looked at ways to prevent the expression of α-synuclein and effectively eliminate the physiological cause of PD." To do this, the researchers designed short fragments of DNA that are mirror images of sections of the α-synuclein gene mRNA. The constructs were stabilized by the addition of amido-bridging.

Scientists Resolve Genetic Origins of Persian Walnut

Prized worldwide for its high-quality wood and rich flavor of delicious nuts, the Persian walnut (Juglans regia) is an important economic crop. The Persian walnut is one of 22 species in the genus Juglans, which includes black and white walnuts and butternuts, grown across Europe, the Americas, and Asia. China leads world production, followed by California, Turkey, and Iran. But until now, the evolutionary history of walnuts has been unknown. Walnuts have a rich fossil record, which suggest an origin of walnuts and initial divergence into black walnuts and butternuts (white walnuts) in North America some 35-45 million years ago. With this high age, both walnut lineages would have had ample opportunity to migrate into the Old World via the Bering and North Atlantic land bridges, yet only butternuts have been detected in the fossil records of Europe and Asia, and no ancient fossils of the Persian walnut are known. Using genomic data analyzed with phylogenetic and population genetic approaches, researchers have now cracked this mystery, showing that the Persian walnut is the result of hybridization between two long-extinct species approximately 3.45 million years ago. Past analyses by the team based on some 2900 single-copy nuclear genes from 19 species of walnuts were unable to sort out the relationships among North American, Asian, and Persian walnut species. However, the researchers excluded incomplete lineage sorting as the cause of the phylogenetic uncertainty. "This led us to speculate that ancient hybridization might be involved in the origin of the Persian walnut and the American butternut," said Da-Yong Zhang, PhD, Peking University, a population geneticist who is one of the senior authors.

ExoFest 2019 Will Describe Latest Exosome and Extracellular Vesicle Research--Annual One-Day Event Hosted by System Biosciences (SBI) & UCSF Features Experts in the Field; Will Be Held June 6 at UCSF’s Genentech Hall

On June 5, 2019, System Biosciences (SBI), a leading provider of exosome research tools and services, announced that the 2nd Annual Exosome Research Festival – ExoFest™ 2019 – will be held June 6, 2019 at the University of California, San Francisco (UCSF) in Byers Auditorium, Genentech Hall, from 8:30 am to 5 pm. ExoFest is a one-day meeting to bring together scientists with an interest in exosome and extracellular vesicle research. This year’s symposium is co-organized by SBI and Dr. Lynn Pulliam and Dr. Sharanjot Saini of the UCSF Veterans Affairs Medical Center. “We are excited to bring together leading experts in the field of exosome research for our second annual ExoFest conference, where we’ll celebrate the latest exosome discoveries and share information about new tools and techniques, which is a core focus of our work at SBI.” Once thought to be little more than a way for cells to off-load waste, exosomes (small extracellular vesicles ranging in size from 30 – 200 nm) are a rapidly expanding area of study in basic research, biomarker discovery, and therapeutic delivery. These extracellular vesicles function as signal carriers and tissue re-shapers through their cargo of RNA, proteins, and lipids, and are involved in a wide range of healthy, as well as pathogenic processes such as cancer, inflammation, immunity, CNS function, and cardiac cell function. Exosomes are found in a wide range of biofluids, including serum, plasma, ascites fluid, urine, saliva, and tissue culture media, and are considered a rich source of material for biomarker discovery, for example in liquid biopsy diagnostic development.

Exosome-Based Screening Analysis of Cervical Mucus May Enable Early Diagnosis of Ovarian Cancer, Leading to Earlier Intervention & Increased Survival; Clemson-Led Collaboration Employs Special Chromatography Method for Rapid Isolation of Exosomes

A team of researchers from Clemson University and Prisma Health–Upstate, both in South Carolina, are working to create a screening process to detect ovarian cancer in the early or pre-cancerous stages, according to a June 4, 2019 release from Clemson University. Their goal of the researchers is to make this screening as simple and easy for women as getting a pap smear. The idea is to identify the pre-cancerous changes by analyzing the makeup of the cervical mucus. Dr. Larry Puls (right in photo), the Director of Gynecologic Oncology at Prisma Health Cancer Institute; Terri Bruce (center in photo), Director of the Clemson University Light Imaging Facility and Research Assistant Professor of Bioengineering, and Ken Marcus (left in photo), PhD, Professor of Chemistry at Clemson and 2019 University Researcher of the Year, have been working together for more than a year to create this process. Through their research of cervical mucus, exosomes, and chromatography, the scientists are working to find a way to detect and identify pre-cancerous changes in a diagnostic setting. And now they are putting their screening tool to the test through trials. According to the Centers for Disease Control and Prevention (CDC), there is no simple, reliable way to screen for ovarian cancer, especially in women who do not show symptoms. And none of the usual cancer exams work as a screening tool to catch the disease in the pre-cancerous stage, Dr. Puls said. “People have looked at pelvic exams, blood tests, and transvaginal ultrasonography as screening tools and none of it has worked as we would like,” Dr. Puls said. “To this day, there is no adequate screening protocol for ovarian cancer and that’s part of the reason why it’s such a lethal disease. We can’t find it early enough.”

Oncologist & Cancer Survivor David Johnson, MD, of UT Southwestern Honored As “Giant of Cancer Care” by OncLive at ASCO 2019

When David Johnson, MD, talks about his part in cancer drug development, he says, “I played a small role.” Others don’t use the word “small” to describe his contributions. They use the word “giant.” According to a June 3, 2019 release from the University of Texas (UT) Southwestern, Dr. Johnson was honored as one of 15 Giants of Cancer Care (https://www.giantsofcancercare.com/recipients/2019) recognized at the American Society of Clinical Oncology (ASCO) conference in Chicago on Friday, May 30. The award was given by OncLive, the website for the Oncology Specialty Group (https://www.onclive.com/publications/obtn/2010/april2010/oncology_specia...). Past inductees have included leading cancer experts from Harvard Medical School, Stanford, Yale, and the National Cancer Institute. Dr. John Minna, Professor and Director of the Hamon Center for Therapeutic Oncology Research at UT Southwestern Medical Center, was among the oncologists honored as a Giant of Cancer Care in 2015. The honor comes as Dr. Johnson prepares to step down after nine years of service as UT Southwestern’s Chair of Internal Medicine. He holds the Donald W. Seldin Distinguished Chair in Internal Medicine. He is an oncologist who has been on all sides of cancer: he’s an attending physician, a leading expert in clinical trials, an enthusiastic supporter of cancer research, and a former cancer patient himself. Dr. Johnson was in his early 40s, treating cancer patients in Tennessee, when he was diagnosed with lymphoma. “It came as somewhat of a shock to say the least,” he said. He soon had the chemotherapy he had prescribed for hundreds of patients in the past. He lost his hair and was hit with every side effect: neuropathy, neutropenia, fever, infections, and more.

“Only the Stressed Die Young”* Molecular Switch in Flies Is Decisive for Long Life and Stress Resilience; Transcription Factor Must Be Tightly Controlled As Too Little Leads to Longer Life, But Reduced Stress Resistance; Too Much Leads to Early Aging

The survival and fitness of multi-cellular organisms have been tightly associated with their capacity to renew their tissues. This is particularly important for tissues that are permanently exposed to and challenged by the external environment, such as the epithelium, which lines our digestive tract. Researchers led by Professor Dr. Mirka Uhlirova from CECAD (Cluster of Excellence for Aging Research at the University of Cologne) collaborated with the laboratory of Dr. Tony Southall from Imperial College London to identify the transcription factor Ets21c as a vital regulator of the regenerative program in the adult intestine of the fruit fly Drosophila. Moreover, their work highlighted the existence of trade-off mechanisms between stress resilience and longevity. The results were published online on June 4, 2019 in Cell Reports. The open-access article is titled “Ets21c Governs Tissue Renewal, Stress Tolerance, and Aging in the Drosophila Intestine.” While primarily involved in nutrient absorption and digestion, the intestinal epithelium also serves as a selective barrier that restricts the passage of pathogens and toxic substances. The renewal of the intestine is accomplished by stem cells which proliferate and differentiate to maintain tissue integrity and it functions throughout an organism's lifetime. In contrast, stem cell malfunctions have been linked to tissue degeneration or cancer development. The new research contributes to a better understanding of the molecular underpinnings of the regenerative processes under favorable as well as stress conditions.

Dogma-Shattering Work Shows That One Cell Type Can Change into Another Cell Type After Development; Key Incisive Observation Comes in Long-Studied Zebrafish (“Secret Hiding in Plain Sight”); Finding May Have Major Implications for Regenerative Medicine

A new study by researchers at the University of Virginia (UVA) and other institutions has revealed the existence of a type of pigment cell in zebrafish that can transform after development into another cell type. The work was reported online on May 28, 2019 in PNAS in an open-access article titled “Fate Plasticity and Reprogramming in Genetically Distinct Populations of Danio leucophores.” David Parichy, PhD, the Pratt-Ivy Foundation Distinguished Professor of Morphogenesis in UVA's Department of Biology, said that researchers in his lab noticed that some black pigment cells on zebrafish became gray and then eventually white. When they looked more closely, they found dramatic changes in gene expression and pigment chemistry. "We realized that the cells have a secret history hiding in plain sight," he said. "Zebrafish have been studied closely for more than 30 years - we know a lot about them - but this is the first time this transformation has been noticed. It's a very surprising discovery." The unique cell population sheds the pigment melanin, changing in color from black to white during the life cycle of an individual fish. These special cells are found at the edges of the fins, where they seem to act as a signal to other zebrafish. The ability of a developed cell to differentiate directly into another type of cell is exceptionally rare. Normally such a change requires experimental intervention, returning the cell to a stem-cell state in a dish, before it can differentiate, or transform, as something else. The new finding suggests that some developed cells might be more amenable to change than generally believed.

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