Title: National Coronavirus Testing Strategy Announced as States Reopen
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: LA First Major U.S. City to Offer Free Coronavirus Tests
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: NIH Launches $500 Million Contest to Produce Best COVID-19 Test
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Interest in Unproven COVID Drugs Soared After Trump Gave Thumbs Up
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Company Selling Direct-to-Consumer Coronavirus Antibody Test
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: Out-of-Hospital Cardiac Arrests On the Rise During COVID-19 Crisis
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: Best Ways to Help Kids Through the Pandemic
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: What Works Best to Ease the Pain of Sciatica?
Category: Health News
Created: 3/18/2020 12:00:00 AM
Last Editorial Review: 3/19/2020 12:00:00 AM

Title: Screen Time for Tiniest Tots Linked to Autism-Like Symptoms
Category: Health News
Created: 4/20/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

A roundup of the latest news about COVID-19

A new consensus document provides guidance on the safe reintroduction of cardiovascular procedures and testing derailed by the COVID-19 pandemic.

These are the coronavirus stories you need to know about today.

The new coronavirus is disproportionately striking minority populations—particularly urban blacks and Navajo Indians living on their reservation. Experts say social and economic factors that predate the COVID-19 crisis may help explain why.

A roundup of the latest news about COVID-19

When pleas for protective equipment failed to produce results, individuals decided to take matters in their own hands and set up a distribution channel, now the most centralized platform in the US.

Calls to relax social distancing policies emphasize the need for increased testing, but a closer look at current SARS-CoV-2 tests leaves Anish Koka, MD, doubtful that more tests will be the solution.

A roundup of the latest news about COVID-19

Title: Americans' Cholesterol Levels Decline: Study
Category: Health News
Created: 11/12/2019 12:00:00 AM
Last Editorial Review: 11/13/2019 12:00:00 AM

Title: Especially in the Young, Cholesterol Is No Friend to the Heart
Category: Health News
Created: 12/4/2019 12:00:00 AM
Last Editorial Review: 12/4/2019 12:00:00 AM

Title: Health Tip: Should I Get a Cholesterol Test?
Category: Health News
Created: 12/10/2019 12:00:00 AM
Last Editorial Review: 12/10/2019 12:00:00 AM

Title: HDL vs. LDL Cholesterol (Good and Bad)
Category: Diseases and Conditions
Created: 7/14/2017 12:00:00 AM
Last Editorial Review: 12/11/2019 12:00:00 AM

Title: New Cholesterol Drug Approved by FDA
Category: Health News
Created: 2/24/2020 12:00:00 AM
Last Editorial Review: 2/24/2020 12:00:00 AM

Title: Fewer Americans Have High Cholesterol
Category: Health News
Created: 4/22/2020 12:00:00 AM
Last Editorial Review: 4/23/2020 12:00:00 AM

PMC marked its 10th anniversary in 2010 with a celebratory event at its annual Advisory Committee meeting, held at the National Library of Medicine last June. This milestone event was recently featured in the February 17th edition of NLM In Focus, in an article NLM Milestones: The Hits Just Keep on Coming. For more information on the ten years of PMC, see the article in the May-June issue of the NLM Technical Bulletin.

Title: Obesity Is Biggest Type 2 Diabetes Risk Factor
Category: Health News
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: New Polio Vaccine Promising in Early Test
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Modern Livestock Farming Can Pose Public Health Risk
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Low Testosterone (Low-T)
Category: Diseases and Conditions
Created: 12/14/2009 12:00:00 AM
Last Editorial Review: 12/2/2019 12:00:00 AM

Title: Testosterone Supplements Won't Help Most Men, Doctors' Group Says
Category: Health News
Created: 1/6/2020 12:00:00 AM
Last Editorial Review: 1/7/2020 12:00:00 AM

Title: Your Best Bet Against Heart Attack, Stroke? Lower Blood Pressure
Category: Health News
Created: 2/20/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Up Your Steps to Lower Blood Pressure, Heart Study Suggests
Category: Health News
Created: 3/26/2020 12:00:00 AM
Last Editorial Review: 3/27/2020 12:00:00 AM

Title: 24 Best Foods for Blood Circulation
Category: Health and Living
Created: 4/9/2020 12:00:00 AM
Last Editorial Review: 4/9/2020 12:00:00 AM

Title: Want Fewer UTIs? Go Vegetarian, Study Suggests
Category: Health News
Created: 1/30/2020 12:00:00 AM
Last Editorial Review: 1/31/2020 12:00:00 AM

Title: 'Couch Potato' Lifestyle Poses Danger to Women's Hearts
Category: Health News
Created: 2/18/2020 12:00:00 AM
Last Editorial Review: 2/19/2020 12:00:00 AM

Title: AHA News: Domestic Abuse May Do Long-Term Damage to Women's Health
Category: Health News
Created: 2/18/2020 12:00:00 AM
Last Editorial Review: 2/19/2020 12:00:00 AM

Title: How Dangerous Is General Anesthesia?
Category: Procedures and Tests
Created: 3/5/2020 12:00:00 AM
Last Editorial Review: 4/7/2020 12:00:00 AM

Title: High Testosterone Levels Have Different Health Impact for Men and Women
Category: Health News
Created: 2/10/2020 12:00:00 AM
Last Editorial Review: 2/11/2020 12:00:00 AM

Title: AHA News: Estrogen Therapy in Early Menopause May Help Keep Arteries Clear
Category: Health News
Created: 3/3/2020 12:00:00 AM
Last Editorial Review: 3/4/2020 12:00:00 AM

Title: Back in Touch: Technology Restores Hand Sensitivity to Young Quadraplegic
Category: Health News
Created: 4/23/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM

Title: The Doctor Gap: In Areas of Greatest Need, Primary Care Is a Team Effort
Category: Health News
Created: 3/19/2020 12:00:00 AM
Last Editorial Review: 3/20/2020 12:00:00 AM

Title: U.S. Issues Highest Travel Alert for China as WHO Declares Health Emergency
Category: Health News
Created: 1/31/2020 12:00:00 AM
Last Editorial Review: 2/3/2020 12:00:00 AM

Title: Restful Romance: Smelling Your Lover's Shirt Can Help You Sleep
Category: Health News
Created: 2/14/2020 12:00:00 AM
Last Editorial Review: 2/14/2020 12:00:00 AM

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific for GIST cell labeling in vitro. Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly in vitro. The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with KIT and PDGFRA mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue ex vivo, as well as peritoneal xenografts in mice with high sensitivity. These results represent the first use of an aptamer-based method for targeted detection of GIST in vitro and in vivo.

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (^–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R^–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by ²H/¹³C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

Lipid rafts are highly ordered regions of the plasma membrane that are enriched in cholesterol and sphingolipids and play important roles in many cells. In hematopoietic stem and progenitor cells (HSPCs), lipid rafts house receptors critical for normal hematopoiesis. Lipid rafts also can bind and sequester kinases that induce negative feedback pathways to limit proliferative cytokine receptor cycling back to the cell membrane. Modulation of lipid rafts occurs through an array of mechanisms, with optimal cholesterol efflux one of the major regulators. As such, cholesterol homeostasis also regulates hematopoiesis. Increased lipid raft content, which occurs in response to changes in cholesterol efflux in the membrane, can result in prolonged receptor occupancy in the cell membrane and enhanced signaling. In addition, certain diseases, like diabetes, may contribute to lipid raft formation and affect cholesterol retention in rafts. In this review, we explore the role of lipid raft-related mechanisms in hematopoiesis and CVD (specifically, atherosclerosis) and discuss how defective cholesterol efflux pathways in HSPCs contribute to expansion of lipid rafts, thereby promoting myelopoiesis and thrombopoiesis. We also discuss the utility of cholesterol acceptors in contributing to lipid raft regulation and disruption, and highlight the potential to manipulate these pathways for therapeutic gain in CVD as well as other disorders with aberrant hematopoiesis.

ABSTRACT

Human noroviruses (HuNoVs) are the leading cause of nonbacterial gastroenteritis worldwide. Histo-blood group antigen (HBGA) expression is an important susceptibility factor for HuNoV infection based on controlled human infection models and epidemiologic studies that show an association of secretor status with infection caused by several genotypes. The fucosyltransferase 2 gene (FUT2) affects HBGA expression in intestinal epithelial cells; secretors express a functional FUT2 enzyme, while nonsecretors lack this enzyme and are highly resistant to infection and gastroenteritis caused by many HuNoV strains. These epidemiologic associations are confirmed by infections in stem cell-derived human intestinal enteroid (HIE) cultures. GII.4 HuNoV does not replicate in HIE cultures derived from nonsecretor individuals, while HIEs from secretors are permissive to infection. However, whether FUT2 expression alone is critical for infection remains unproven, since routinely used secretor-positive transformed cell lines are resistant to HuNoV replication. To evaluate the role of FUT2 in HuNoV replication, we used CRISPR or overexpression to genetically manipulate FUT2 gene function to produce isogenic HIE lines with or without FUT2 expression. We show that FUT2 expression alone affects both HuNoV binding to the HIE cell surface and susceptibility to HuNoV infection. These findings indicate that initial binding to a molecule(s) glycosylated by FUT2 is critical for HuNoV infection and that the HuNoV receptor is present in nonsecretor HIEs. In addition to HuNoV studies, these isogenic HIE lines will be useful tools to study other enteric microbes where infection and/or disease outcome is associated with secretor status.

IMPORTANCE Several studies have demonstrated that secretor status is associated with susceptibility to human norovirus (HuNoV) infection; however, previous reports found that FUT2 expression is not sufficient to allow infection with HuNoV in a variety of continuous laboratory cell lines. Which cellular factor(s) regulates susceptibility to HuNoV infection remains unknown. We used genetic manipulation of HIE cultures to show that secretor status determined by FUT2 gene expression is necessary and sufficient to support HuNoV replication based on analyses of isogenic lines that lack or express FUT2. Fucosylation of HBGAs is critical for initial binding and for modification of another putative receptor(s) in HIEs needed for virus uptake or uncoating and necessary for successful infection by GI.1 and several GII HuNoV strains.

ABSTRACT

Human noroviruses (HuNoV) are a leading cause of viral gastroenteritis worldwide and a significant cause of morbidity and mortality in all age groups. The recent finding that HuNoV can be propagated in B cells and mucosa-derived intestinal epithelial organoids (IEOs) has transformed our ability to dissect the life cycle of noroviruses. Using transcriptome sequencing (RNA-Seq) of HuNoV-infected intestinal epithelial cells (IECs), we have found that replication of HuNoV in IECs results in interferon (IFN)-induced transcriptional responses and that HuNoV replication in IECs is sensitive to IFN. This contrasts with previous studies that suggested that the innate immune response may play no role in the restriction of HuNoV replication in immortalized cells. We demonstrated that inhibition of Janus kinase 1 (JAK1)/JAK2 enhanced HuNoV replication in IECs. Surprisingly, targeted inhibition of cellular RNA polymerase II-mediated transcription was not detrimental to HuNoV replication but instead enhanced replication to a greater degree than blocking of JAK signaling directly. Furthermore, we demonstrated for the first time that IECs generated from genetically modified intestinal organoids, engineered to be deficient in the interferon response, were more permissive to HuNoV infection. Taking the results together, our work revealed that IFN-induced transcriptional responses restrict HuNoV replication in IECs and demonstrated that inhibition of these responses mediated by modifications of the culture conditions can greatly enhance the robustness of the norovirus culture system.

IMPORTANCE Noroviruses are a major cause of gastroenteritis worldwide, and yet the challenges associated with their growth in culture have greatly hampered the development of therapeutic approaches and have limited our understanding of the cellular pathways that control infection. Here, we show that human intestinal epithelial cells, which represent the first point of entry of human noroviruses into the host, limit virus replication by induction of innate responses. Furthermore, we show that modulating the ability of intestinal epithelial cells to induce transcriptional responses to HuNoV infection can significantly enhance human norovirus replication in culture. Collectively, our findings provide new insights into the biological pathways that control norovirus infection but also identify mechanisms that enhance the robustness of norovirus culture.

ABSTRACT

Microbes adapt their metabolism to take advantage of nutrients in their environment. Such adaptations control specific metabolic pathways to match energetic demands with nutrient availability. Upon depletion of nutrients, rapid pathway recovery is key to release cellular resources required for survival under the new nutritional conditions. Yet, little is known about the regulatory strategies that microbes employ to accelerate pathway recovery in response to nutrient depletion. Using the fatty acid catabolic pathway in Escherichia coli, here, we show that fast recovery can be achieved by rapid release of a transcriptional regulator from a metabolite-sequestered complex. With a combination of mathematical modeling and experiments, we show that recovery dynamics depend critically on the rate of metabolite consumption and the exposure time to nutrients. We constructed strains with rewired transcriptional regulatory architectures that highlight the metabolic benefits of negative autoregulation over constitutive and positive autoregulation. Our results have wide-ranging implications for our understanding of metabolic adaptations, as well as for guiding the design of gene circuitry for synthetic biology and metabolic engineering.

IMPORTANCE Rapid metabolic recovery during nutrient shift is critical to microbial survival, cell fitness, and competition among microbiota, yet little is known about the regulatory mechanisms of rapid metabolic recovery. This work demonstrates a previously unknown mechanism where rapid release of a transcriptional regulator from a metabolite-sequestered complex enables fast recovery to nutrient depletion. The work identified key regulatory architectures and parameters that control the speed of recovery, with wide-ranging implications for the understanding of metabolic adaptations as well as synthetic biology and metabolic engineering.