Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour

The five-subunit WASH complex generates actin networks that participate in endocytic trafficking, migration and invasion in various cell types. Loss of one of the two subunits WASH or strumpellin in mice is lethal, but little is known about their role in mammals in vivo. We explored the role of strumpellin, which has previously been linked to hereditary spastic paraplegia, in the mouse melanocytic lineage. Strumpellin knockout in melanocytes revealed abnormal endocytic vesicle morphology but no impairment of migration in vitro or in vivo and no change in coat colour. Unexpectedly, WASH and filamentous actin could still localize to vesicles in the absence of strumpellin, although the shape and size of vesicles was altered. Blue native PAGE revealed the presence of two distinct WASH complexes, even in strumpellin knockout cells, revealing that the WASH complex can assemble and localize to endocytic compartments in cells in the absence of strumpellin

The HSV-1 Latency-Associated Transcript Functions to Repress Latent Phase Lytic Gene Expression and Suppress Virus Reactivation from Latently Infected Neurons

open access articleHerpes simplex virus 1 (HSV-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein coding RNA that has been strongly implicated in the epigenetic regulation of HSV-1 gene expression. We have investigated LAT-mediated control of latent gene expression using chromatin immunoprecipitation analyses and LAT-negative viruses engineered to express firefly luciferase or β-galactosidase from a heterologous lytic promoter. Whilst we were unable to determine a significant effect of LAT expression upon heterochromatin enrichment on latent HSV-1 genomes, we show that reporter gene expression from latent HSV-1 genomes occurs at a greater frequency in the absence of LAT. Furthermore, using luciferase reporter viruses we have observed that HSV-1 gene expression decreases during long-term latent infection, with a most marked effect during LAT-negative virus infection. Finally, using a fluorescent mouse model of infection to isolate and culture single latently infected neurons, we also show that reactivation occurs at a greater frequency from cultures harbouring LAT-negative HSV-1. Together, our data suggest that the HSV-1 LAT RNA represses HSV-1 gene expression in small populations of neurons within the mouse TG, a phenomenon that directly impacts upon the frequency of reactivation and the maintenance of the transcriptionally active latent reservoir

Evaluation Of Pilgrims Hospices Rapid Response Hospice At Home Service: Summary of findings March 2015

When faced with a life-limiting illness, most people say they would prefer to spend the end of their lives and die at home. However, we know that about half the people with cancer or long-term illnesses still die in hospital. Fewer than a quarter die in their own home. Patients are often admitted to hospital because of a crisis such as uncontrolled symptoms, carer fear or stress, or not having medication available when needed. Community based palliative care teams can help in such situations. In 2008 Pilgrims Hospices commissioned a review of the literature to understand what kinds of home care services provide the most benefit to patients at the end of their lives and their families. Though good quality evidence was scarce, the findings of the review suggested that successful services are able to respond rapidly, focus on supporting family carers at home and are available 24 hours a day seven days a week. Following these conclusions, Pilgrims Hospices developed the Rapid Response Hospice at Home service (Hospice at Home) to support people who are at the end of life and would like to die at home. The Hospice at Home service operates in addition to established hospice community services and is staffed by healthcare assistants (HCAs) who have been trained at the hospice. The HCAs are available day and night at four hours' notice to support patients in the last days of their lives or when they experience a crisis

Comparative Population Genomics and Biophysical Modeling of Shrimp Migration in the Gulf of Mexico Reveals Current-Mediated Connectivity

The Gulf of Mexico experiences frequent perturbations, both natural and anthropogenic. To better understand the impacts of these events, we must inventory natural variability within the ecosystem, communities, species, and populations, and contextualize these findings in relation to physical features. Here, we present an integrated study of comparative population genomics and biophysical oceanography. Targeting three species of mesopelagic shrimp common to the Gulf of Mexico midwater (Acanthephyra purpurea, Systellaspis debilis, and Robustosergia robusta), we analyzed genetic diversity and population connectivity as proxies for species health and resilience, respectively. We also simulated a range of vertical migratory behaviors for the shrimp to infer the relationship between diel vertical migration and horizontal transmission between the Gulf of Mexico and the greater Atlantic Ocean. This study aims to establish biological baselines and characterize these values in terms of the prevailing oceanographic feature of the midwater: the Gulf Loop Current. Generally, the oplophorid species (A. purpurea and S. debilis) exhibit lower genetic diversity and higher interpopulation homogeneity compared to the sergestid (R. robusta). Biophysical simulations suggest the differences in vertical migratory regimes between these two groups have important implications for horizontal transport out of the Gulf of Mexico. Because of the difference in vertical migration patterns, access to the Gulf Loop Current varies across taxa and impacts inter-basin migration. Our findings suggest a negative correlation between surface abundance and genetic diversity in these three shrimp species. We hypothesize that this correlation may be due to the relationships between surface abundance and access to the fastest moving waters of the Gulf Loop Current

Government responses to gender-based violence during COVID-19

Gender-based violence (GBV) significantly and substantially threatens women's health. The COVID-19 pandemic has exacerbated existing risks and patterns of GBV. The impact of COVID-19 on GBV is not inevitable, however, and can be mediated by the policies of governments. In this study we developed the Government GBV Response Index to systematically examine how countries (N = 60) performed in response to the pandemic with respect to the government 1) enacting specific national-level GBV policy; 2) making dedicated COVID-19 specific funding available; and 3) adapting existing GBV responses to COVID-19 related restrictions and challenges. Most countries (N = 33) delivered fewer than two policy responses. We also performed rapid case study analyses to investigate what might contribute to countries having more comprehensive government policy. We find that civil society organizations played a key role in facilitating GBV policy during the pandemic, especially if they are well-funded and well-connected to the government, and if the country has a high-level government official responsible for gender issues

A critical analysis of gender-based violence reporting and evidence building applications (GBVxTech) for capturing memory reports

Introduction: Gender-based violence (GBV) is under-reported to the authorities owing to the stigma, shame, and fear of reprisal that surrounds these crimes. To address this, there has been an influx of technologies, including mobile phone and online applications that allow victim-survivors (hereafter, victims) to document and report GBV (hereafter referred to as GBVxTech). We critically analysed the extent to which GBVxTech applications align with the scientific knowledge base on gathering accounts of crimes from victims and witnesses.Methods: We identified 41 reporting and evidence building applications from around the world but found many (n = 19) were no longer accessible. A total of 13 applications met the study criteria and were available for download. We evaluated each application on how well its design and features align with established minimum best practice standards for gathering complete and accurate accounts from witnesses and victims, such as the pre-interview instructions (e.g., setting ground rules), questioning approach (e.g., using open-ended questions), and the adequacy of security features (e.g., password protection).Results and Discussion: We found most applications employ open questions, encourage victims to report information in an independent voice, and seek to elicit information pertinent to a criminal investigation. None of the applications use leading questions. However, most applications do not establish ground rules, and many use forced-choice questions, do not time stamp the information gathered, or document when users change their answers. Many applications have limited security features, potentially compromising users’ safety. Further, some applications do not provide information about how to use the app, an informed consent procedure, or data usage information. We discuss the findings and offer recommendations for future GBVxTech development

Hubble Space Telescope Near-IR Transmission Spectroscopy of the Super-Earth HD 97658b

Recent results from the Kepler mission indicate that super-Earths (planets with masses between 1-10 times that of the Earth) are the most common kind of planet around nearby Sun-like stars. These planets have no direct solar system analogue, and are currently one of the least well-understood classes of extrasolar planets. Many super-Earths have average densities that are consistent with a broad range of bulk compositions, including both water-dominated worlds and rocky planets covered by a thick hydrogen and helium atmosphere. Measurements of the transmission spectra of these planets offer the opportunity to resolve this degeneracy by directly constraining the scale heights and corresponding mean molecular weights of their atmospheres. We present Hubble Space Telescope near-infrared spectroscopy of two transits of the newly discovered transiting super-Earth HD 97658b. We use the Wide Field Camera 3's scanning mode to measure the wavelength-dependent transit depth in thirty individual bandpasses. Our averaged differential transmission spectrum has a median 1 sigma uncertainty of 23 ppm in individual bins, making this the most precise observation of an exoplanetary transmission spectrum obtained with WFC3 to date. Our data are inconsistent with a cloud-free solar metallicity atmosphere at the 10 sigma level. They are consistent at the 0.4 sigma level with a flat line model, as well as effectively flat models corresponding to a metal-rich atmosphere or a solar metallicity atmosphere with a cloud or haze layer located at pressures of 10 mbar or higher.Comment: ApJ in press; revised version includes an updated orbital ephemeris for the plane

Small Food Store Retailers’ Willingness to Implement Healthy Store Strategies in Rural North Carolina

Access to supermarkets is lacking in many rural areas. Small food stores are often available, but typically lack healthy food items such as fresh produce. We assessed small food store retailer willingness to implement 12 healthy store strategies to increase the availability, display, and promotion of healthy foods and decrease the availability, display, and promotion of tobacco products. Interviews were conducted with 55 small food store retailers in three rural North Carolina counties concurrently with store observations assessing current practices related to the strategies. All stores sold low-calorie beverages, sugar-sweetened beverages, candy and cigarettes. Nearly all sold smokeless tobacco and cigars/cigarillos, and 72% sold e-cigarettes. Fresh fruits were sold at 30.2% of stores; only 9.4% sold fresh vegetables. Retailers reported being most willing to stock skim/low-fat milk, display healthy snacks near the register, and stock whole wheat bread. About 50% were willing to stock at least three fresh fruits and three fresh vegetables, however only 2% of stores currently stocked these foods. Nearly all retailers expressed unwillingness to reduce the availability of tobacco products or marketing. Our results show promise for working with retailers in rural settings to increase healthy food availability in small food stores. However, restrictions on retail tobacco sales and marketing may be more feasible through local tobacco control ordinances, or could be included with healthy foods ordinances that require stores to stock a minimum amount of healthy foods

Sociodemographic Disparities in Proximity of Schools to Tobacco Outlets and Fast-Food Restaurants

Objectives. To examine the association of school sociodemographic characteristics with tobacco outlet and fast-food restaurant availability near schools in a national study