Syndicate content

Archive - 2019

November 4th

Commonly Used Diabetes Drug (Pioglitazone) Relieves Symptoms of Nicotine Withdrawal; May Provide New Strategy in Efforts to Help Individuals Stop Smoking

A drug commonly used to treat Type II diabetes abolishes the characteristic signs of nicotine withdrawal in rats and mice, according to new research published on November 4, 2019 in the Journal of Neuroscience. The finding may offer an important new strategy in the battle to end smoking. The article is titled “Activation of PPARγ attenuates the expression of physical and affective nicotine withdrawal symptoms through mechanisms involving amygdala and hippocampusneurotransmission.” Smokers trying to quit face potent side effects from nicotine withdrawal, including cravings, increased appetite, restlessness, anxiety, irritability, and depression. Even though they may want to quit, many smokers continue to smoke simply because the withdrawal experience is so unpleasant. The diabetes drug, pioglitazone, targets a specific form of the peroxisome proliferator-activated receptors in the nucleus. This receptor, PPARγ, is found in areas of the brain involved in drug addiction. In their current work, Esi Domi(photo), PhD, post-doc at the Center for Social and Affective Neuroscience-Linköping University (Sweden), and colleagues have demonstrated that direct injections of pioglitazone into the hippocampi of male mice reduced the signs of physical nicotine withdrawal, including paw tremors, chattering, and head shakes. Injecting pioglitazone into the amygdala of male mice ameliorated signs of anxiety associated with nicotine withdrawal. Nicotine abusers face a 30% higher risk of developing Type II diabetes. The researchers suggest pioglitazone may help diabetic smokers quit by lessening the physical and emotional withdrawal symptoms while reducing insulin resistance.

Simple Blood Test for Tumor-Associated Antigens My Be Effective for Early Detection of Breast Cancer; Similar Test Being Assessed in Soctland for Lung Cancer

Breast cancer could be detected up to five years before there are any clinical signs of it, using a blood test that identifies the body's immune response to substances produced by tumor cells, according to new research presented on November 3 at the 2019 National Cancer Research Institute (NCRI) Conference (November 3-5)(https://www.ncri.org.uk/events/2019-ncri-cancer-conference/) in Glasgow. The work was presented in poster #2966, entitled “Clinical Utility of Autoantibodies in Early Detection of Breast Cancer.” Cancer cells produce proteins called antigens that trigger the body to make antibodies against them - autoantibodies. Researchers at the University of Nottingham (UK) have found that these tumor-associated antigens (TAAs) are good indicators of cancer, and now the scientists have developed panels of TAAs that are known already to be associated with breast cancer to detect whether or not there are autoantibodies against them in blood samples taken from patients. In a pilot study, the researchers, who are part of the Centre of Excellence for Autoimmunity in Cancer (CEAC) group at the School of Medicine, University of Nottingham, took blood samples from 90 breast cancer patients at the time they were diagnosed with breast cancer and matched them with samples taken from 90 patients without breast cancer (the control group). The researchers used screening technology (protein microarray) that allowed them to screen the blood samples rapidly for the presence of autoantibodies against 40 TAAs associated with breast cancer, and also 27 TAAs that were not known to be linked with the disease.

November 2nd

Researchers Engineer Insulin-Producing Cells Activated by Light for Diabetes

Tufts University researchers have transplanted engineered pancreatic beta cells into diabetic mice, then caused the cells to produce more than two to three times the typical level of insulin by exposing them to light. The light-switchable cells are designed to compensate for the lower insulin production or reduced insulin response found in diabetic individuals. The study, published online on Septembr 13, 2019 in ACS Synthetic Biology, shows that glucose levels can be controlled in a mouse model of diabetes without pharmacological intervention. The article is titled “Amelioration of Diabetes in a Murine Model Upon Transplantation of Pancreatic Β-Cells with Optogenetic Control of Cyclic AMP.” Insulin is a hormone that plays a central role in precisely controlling levels of circulating glucose - the essential fuel used by cells -. Diabetes affects more than 30 million Americans according to the Centers for Disease Control and Prevention (CDC). In type II diabetes - the most common form of the disease - the cells of the body become inefficient at responding to insulin and as a consequence, glucose in circulation can become dangerously high (hyperglycemia) while the pancreas cannot produce enough insulin to compensate. In type I diabetes, the beta cells, which are the only cells in the body that produce insulin, are destroyed by the immune system resulting in complete lack of the hormone. Current treatments include the administration of drugs that enhance the production of insulin by pancreatic beta cells, or direct injection of insulin to supplement the naturally produced supply. In both cases, regulation of blood glucose becomes a manual process, with drug or insulin intervention conducted after periodic readings of glucose levels, often leading to spikes and valleys that can have harmful long-term effects.

Lymphatic System Found to Play Key Role in Hair Regeneration

Given the amount of wear and tear it's subjected to on a daily basis, the skin has a phenomenal ability to replenish itself. Spread throughout it are small reservoirs of stem cells, nested within supportive microenvironments called niches, which keep a tight rein on this repair process. Too much tissue might cause problems like cancer, while too little might accelerate aging. Until now, scientists were uncertain whether the stem cells themselves could instruct other stem cells to form new skin by reshaping their niche. But new research in Science, led by Elaine Fuchs, PhD, the Rebecca C. Lancefield Professor at the Rockefeller University, indicates that stem cells can indeed influence tissue regeneration. The open-access article, published online on October 31, 2019, is titled “Stem Cell–Driven Lymphatic Remodeling Coordinates Tissue Regeneration.” The study identifies a molecular coordination tool used by stem cells to signal across niches. The researchers also discovered a new component of the niche: a specialized type of vessel called lymphatic capillaries, which transport immune cells and drain excess fluids and toxins from tissues. These capillaries form an intimate network around the stem cell niche within each hair follicle, the study showed, thereby interconnecting all its niches. "By turning the skin completely transparent," says postdoctoral fellow Shiri Gur-Cohen, PhD, "we were able to reveal the complex architecture of this network of tubes." Hair-follicle stem cells control the behavior of lymphatic capillaries by secreting molecules that act as an on-off switch for drainage, the scientists found, enabling them to control the composition of fluids and cells in the surrounding locale and ultimately synchronize regeneration across the tissue.

November 1st

International Study Led by Harvard Scientists Reveals Surprising Amount of Gene Flow Among Butterfly Species, Even Between Some That Are Distantly Related

An international team of researchers analyzed the genomes of 20 butterfly species and discovered a surprisingly high amount of gene flow among them - even between species that are distantly related. The findings, published in the November1, 2019 issue Science, challenge conventional views about species and point to hybridization as a key process in the emergence of biological diversity. The article, which serves as the cover story of this issue of Science, is titled “Genomic Architecture and Introgression Shape A Butterfly Radiation.” Different species of passion vine butterflies (Heliconius) have similar color patterns that serve as warnings to predators. Scientists have previously found that one reason for their similarity is that they actually share parts of their DNA, thanks to hybridization that occurred at some point in their ancestry. The new findings suggest that this process of DNA sharing is far more common than previously thought. To understand how butterflies pass genes to other species by hybridizing, a process known as introgression, the researchers analyzed new genome assemblies of 20 Heliconius butterfly species. "DNA sharing had been shown in closely related species, but we wanted to probe deeper into the phylogenetic tree," said senior author James Mallet, Professor of Organismic and Evolutionary Biology in Residence and Associate of Population Genetics in the Museum of Comparative Zoology. "What we found is really astonishing: introgression even among species that are distantly related. "Species" are simply not what we thought they were, and now we have the data to show it.

October 31st

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Final Day (Day 5), Thursday, October 10

Thursday was the last day of the 2019 ASEMV meeting and a number of interesting topics were presented. Two are reported on here. Louis Laurent, MD, PhD, of the University of California-San Diego (UCSD), spoke on the “Discovery and Verfication of Extracelular miRNA Biomarkers for Non-Invasive Prediction of Preeclampsia in Asymptomatic Women.” Dr. Laurent said that she and colleagues performed small RNA-seq of maternal serum exRNAs to discover and verify miRNAs differentially expressed in patients who later developed preeclammpsia. Serum collected from 73 preeclampsia cases and 139 controls between 17-28 weeks gestational age, divided into separate Discovery and Verification cohorts, was analyzed by small RNA seq. Discovery and verification of univariate and bivariate miRNA biomarkers revealed that bivariate biomarkers verified at a markedly higher rate than univariate markers. The majority of verified biomarkers contained miR-155-5p, which has been reported to mediate the preeclampsia-associated repression of eNOS by TNF-alpha. Deconvolution analysis revealed that several verified miRNA biomarkers came from the placenta and were likely carried by placenta-specific EVs. Norman Haughey, PhD, Johns Hopkins University School of Medicine, presented a talk entitled “Astrocyte-Derived EVs Shed in Response to IL-1 Promote Stabilization of APP Translation Through Ligand-Independent Activation of the Wnt Pathway in Neurons.” In his introduction, Dr. Haughey noted that chronic inflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD) by upregulating amyloidogenic processing of APP. Based on previous findings that inflammatory stimuli modify the cargo of astrocyte-derived EVs (ADEV), Dr.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 4, Wednesday, October 9

Wednesday’s sessions of the annual ASEMV 2019 meeting at Asilomar,in Pacific Grove, California, featured multiple exciting presentations. Among the 19 talks of the day, we will focus on five of particular interest. Luis Rodriguez-Borlado, PhD, of Capricor Therapeutics, delivered as presentation titled “Extracellular Vesicles from Cardiosphere-Derived Cells (CDCs) Are Taken Up by Muscle Stem Cells and Increase Exercise Capability in a Duchenne Muscular Dystrophy Model.” Dr. Rodriguez-Borlada introduced his discussion by stating that Duchenne muscular dystrophy (DMD) patients infused with CDCs showed an improvement in PUL (pullulanase) activity, skeletal muscle activity, and a reduction in myocardial scarring when compared to placebo-treated patients. He noted that there is wide acceptance that most of the therapeutic effects observed in cell therapies using non-engrafting cells are caused by paracrine factors secreted by the delivered cells. In the current work, Dr. Rodriguez-Borlado said his group observed significant improvement in exercise capability in mdx mice (DMD model mice) treated wit CDC-EVs when compared with control-treated mice. EVs from immortal CDCs also showed immunomodulatory capabilities on macrophages and improved exercise capability in mdx mice, opening the possibility of developing consistent, robust, and affordable manufacturing process for producing clinical-grade EVs. Julia Saugstad, PhD, Oregon Health & Science University, presented work by a collaborative group and the presentation was titled “Establishing the Contributions of Extracellular miRNAs to Alzheimer’s Disease.” As background, Dr. Saugstad said that Alzheimer’s disease (AD) is the most common form of dementia, the sixth leading cause of death in the United States, and fifth-leading cause of death in those age 65 and older.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 3, Tuesday October 8

Tuesday’s sessions of the annual ASEMV 2019 meeting at Asilomar, California, featured many exciting presentations. Among the 16 talks of the day, five were of particular interest. The first was by Ryan McNamara, PhD, of University of North Carolina-Chapel Hill, whose presentation was titled “EVs from Kaposi Sarcoma-Associated Herpes Lymphoma Induce Long-Term Endothelial Cell Reprogramming.” Dr. McNamara noted that extracellular communication is critical for organismal homeostasis, and thus presents as a major network for viruses to usurp for viral pathogenesis. EVs package contents from a donor cell to communicate with its surroundings, and evolutionarily diverse viruses have been shown to hijack this communication axis to promote pathogenesis. Previously, Dr. McNamara and colleagues had showd that the oncovirus Kaposi’s Sarcoma-Associated Herpes Virus (KSHV) incorporates viral miRNA into EVs secreted from infected cells during the “latency stage” of the viral life cycle. They hypothesized that these modified EVs, termed KSHV-EVs, aid in the establishment of a more favorable niche for disease/tumor progression. Their current results demonstrate that KSHV can modify the local environment using EVs. The group currently proposes that oncoviruses such as KSHV utilize the extracellular communications network through EVs to establish a niche favorable for disease progression and tissue transformation. This allows for the virus to reshape the local environment with minimal spread of the infectious agent, and without tripping immune alarms. In a following presentation, Jeffrey Savas, PhD, from Northwestern University, spoke on how “Viral Scission Factor Alix Tunes Neuronal Communication Through EVs.” Dr. Savas began by noting that synaptic plasticity is a dynamic process facilitating adaptable and flexible communication.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 2, Monday October 7

Monday’s sessions of the annual ASEMV 2019 meeting at Asilomar, in Pacific Grove, California, featured many exciting presentations. Among the 16 talks of the day, five were of particular interest. The first, “Methamphetamine Use Disorder Alters Plasma EV MicroRNA Expression,” was presented by Ursula Sandau, PhD, of Oregon Health & Science University (OHSU) in Portland, Oregon. Dr. Sandau noted that methamphetamine has deleterious effects to both peripheral organs and the central nervous system. The rewarding properties and addictive potential of methamphetamine are correlated with increased synaptic dopamine availability following alterations in dopamine and vesicular monamine transporter function. She reported results demonstrating that EV miRNA expression in subjects with methamphetamine use disorder was significantly different than in control participants, suggesting that methamphetamine may affect EV communication among cells. Dr. Sandau further noted that the differential miRNA expression also implicates a role for EVs in behavioral and physiological effects specific to methamphetamine and suggests that there may be changes in expression of miRNAs that are relevant to specific drugs of addiction, as well as to a spectrum of drug-mediated addiction disorders. In another compelling presentation, Franklin Monzon, PhD, of Spectradyne Particle Analysis (https://nanoparticleanalyzer.com/), spoke on “The Importance of Orthogonal Techniques in Quantifying Extracellular Vesicles.” Dr. Monson noted that, as EV research matures, so must the relevant measurement technologies.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles Opened Sunday Evening, October 6, at Asilomar in Pacific Grove, California

The 2019 annual meeting of the American Society for Exosomes and Microvesicles (ASEMV) was held October 6-10 at the gorgeous Asilomar Conference Grounds in Pacific Grove, California, home of migrating monarch butterflies, steps from the Pacific Ocean, and just 120 miles south of San Francisco. The glorious natural setting was almost matched perhaps by the broad range of 60 scintillating presentations delivered by scientists from around the country and world, during the five intense days of meetings focused on one of the most exciting aspects of biology and mediicine. This year’s meeting, organized as always by Stephen Gould, PhD, of Johns Hopkins, began on Sunday evening with a brief introduction on the history of the ASEMV annual meetings by Michael Graner, PhD, University of Colorado-Denver, and this was followed by the keynote presentation, sponsored by Caris Life Sciences, and delivered by Dr. Travis Thomson of the University of Massachusetts (Worcester, MA). Dr. Thomson’s address was titled “Arc and Copia in Exosome-Mediated Information Exchange.” Dr. Thomson described Arc as a “master regulator of neuronal plasticity and as a remnant of a transposon gag region of a virus. In a 2018 article in Cell (https://www.ncbi.nlm.nih.gov/pubmed/29328915), Dr. Thomson and colleagues noted that Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. In the Cell article, Dr.