Targets of Elf5 in Mouse Trophoblast Stem Cells

The Placenta is an essential organ for all mammalian embryonic development as it provides the nutritional link between maternal and foetal blood streams. The cells which go on to proliferate and contribute to all the major cell types of the embryo derived placenta have been located to the trophoblast (TE) cells overlying the Inner Cell Mass (ICM) of the embryo. Immortal cell lines have been subsequentially derived from this tissue and called Trophoblast Stem (TS) cells. In parallel with their in vivo counterparts they are also reliant on Fibroblast growth factor 4 (FgF4) (Tanaka et al., 1998) and Activin/Nodal signalling (Guzman-Ayala et al., 2004). The Ets family transcription factor, Elf5, has been shown to be specifically expressed in the early placental trophoblast and subsequent derived tissues. Mice deficient in Elf5 failed to form a placenta post implantation. Furthermore TS cells were unable to be derived from Elf5 knockout embryos (Donnison et al., 2005). This work suggested that Elf5 plays an essential role in TS cells and their differentiation. The aim of this study was to determine the downstream target genes of Elf5 in mouse TS cells. The target genes of Fgf4 and Activin/Nodal signalling in TS cells were also investigated. This work is hoped to contribute to an overall greater understanding of the molecular networks underlying TS cell maintenance and to contribute to our knowledge of early placental development. Small interfering RNA (siRNA) targeted reduction of Elf5 mRNA expression in mTS cells was achieved using two independent siRNAs; with Elf5 reduction exceeding 80%. The resulting changes in gene expression were measured in order to determine the downstream targets of Elf5. Selected genes known to be important for trophoblast differentiation and maintenance were measured using real-time PCR in a candidate gene approach .Global changes in gene expression as a consequence of Elf5 silencing were measured using an Affymetrix microarray. Global changes in gene expression due to growth factor (Fgf4 and/or Activin) removal were also measured. Expression of 22 genes was changed using either of the Elf5 siRNA oligonucleotides. Of these, 9 were also significantly changed by growth factor removal. Included in this set were Synopl, Hst3st3b1, Cyr61 and Sox2. In the overall analysis, many genes whose expression changed upon loss of Elf5 are known to play important roles in trophectoderm cell specification. Real-time PCR validation agreed closely with the up or down regulation measured using the microarray. This work has thus led to the discovery of sets of Elf5 target genes potentially involved in trophoblast stem cell function and has provided the foundation for future work exploring the molecular pathways of trophoblast development

Viewing pre‐lab gross anatomy demonstration videos correlates positively with student performance when total dissection time is limited by Covid‐19 restrictions

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic

Enhancing Attendance of the Greater Burlington YMCA Diabetes Fitness Program

Introduction: Since 1999, the Burlington YMCA has offered a free aerobics class to members of the community with diabetes. Additionally, the class regularly monitors participants’ health status. These data support the well-established benefit of exercise in diabetes. Medical Monitoring •hemoglobin A1C •blood pressure •resting pulse rate (before and after each twelve week session) About the Program •Began in 1999 •Free •Physician’s referral required •2h aerobics, twice per week: 1h land + 1h waterhttps://scholarworks.uvm.edu/comphp_gallery/1001/thumbnail.jp

Construção social dos mercados de frutos do Cerrado: entre sociobiodiversidade e alta gastronomia

Cerrado, the second largest biome in Brazil and home to an enormous biological and social diversity, is considered today as one of the world’s Hotspots due to the pressures it has been subject of, as the agribusiness frontier advances. In order to conserve these natural resources, besides creating Protected Areas, it is necessary to increase the value of products obtained through agroextractivism (agriculture coupled with extractivism). The purpose of this article is to analyze how the social construction of markets of Cerrado agroextractivism products is based on the diffusion of social and environmental values spread through the action of civil society organizations, especially by networks. The research included interviews with the main actors – agroextractivists, intermediaries, cooperatives, industries, retailers, NGOs – in addition to field excursions, among others. The results include an analysis of the actions of the networks, a presentation of the products and the description of the markets. These indicate that the evolution of the alternative markets of these products towards supermarkets, long circuits of commercialization and gastronomy runs the risk of limiting the participation of the agroextractivist producers in dominant circuits.O Cerrado, o segundo maior bioma do Brasil e lar de enorme diversidade biológica e social, é considerado hoje como um dos hotspots mundias devido às pressões que tem sofrido com o avanço da fronteira do agronegócio. Para conservar estes recursos naturais, além de áreas protegidas, é necessária a valorização dos produtos obtidos através do agroextrativismo. Este artigo tem por objetivo analisar como a construção social dos mercados de produtos do agroextrativismo do Cerrado se baseia na difusão de valores socioambientais divulgados através da ação de organizações da sociedade civil, especialmente por meio de redes. A pesquisa incluiu entrevistas com os atores principais – agroextrativistas, intermediários, cooperativas, indústrias, distribuidoras, ONGs – além de visitas a campo, entre outros. Os resultados incluem uma análise da ação das redes, uma apresentação dos produtos e a descrição dos mercados. Estes indicam que a evolução dos mercados alternativos destes produtos na direção dos supermercados, de circuitos longos de comercialização e da gastronomia corre o risco de limitar a participação dos produtores agroextrativistas em circuitos dominantes.

Building from patient experiences to deliver patient-focused healthcare systems in collaboration with patients: A call to action

Patients’ experiences of their diagnosis, condition, and treatment (including the impact on their lives), and their experiences surrounding expectations of care, are becoming increasingly important in shaping healthcare systems that meet the evolving needs and priorities of different patient communities over time; this is an ongoing goal of all healthcare stakeholders. Current approaches that capture patient experiences with data are fragmented, resulting in duplication of effort, numerous requests for information, and increased patient burden. Application of patient experience data to inform healthcare decisions is still emerging and there remains an opportunity to align diverse stakeholders on the value of these data to strengthen healthcare systems. Given the collective value of understanding patient experiences across multiple stakeholder groups, we propose a more aligned approach to the collection of patient experience data. This approach is built on the principle that the patients’ experiences are the starting point, and not just something to be considered at the end of the process. It must also be based on meaningful patient engagement, where patients are collaborators and decision makers at each step, thereby ensuring their needs and priorities are accurately reflected. The resulting data and evidence should be made available for all stakeholders, to inform their decision making and healthcare strategies in ways that meet patient priorities. We call for multi-stakeholder collaboration that will deliver healthcare systems and interventions that are better centered around and tailored to patient experiences, and that will help address patients’ unmet needs

Manual / Issue 12 / On Further Review

Manual, a journal about art and its making. On Further Review. This issue uncovers narratives once central to objects’ histories but that now have been systematically obscured, inadvertently overlooked, or otherwise lost. Softcover, 96 pages. Published 2019 by the RISD Museum.(On Further Review) contributors include Anita N. Bateman, Laurie Anne Brewer, Becci Davis, Jamie Gabbarelli, Bethany Johns, Elon Cook Lee, Kevin McBride, Walker Mettling, Jessica Rosner, Suzanne Scanlan, Nell Painter, Allison Pappas, Pamela A. Parmal, Shiyanthi Thavapalan, and Nick White.https://digitalcommons.risd.edu/risdmuseum_journals/1038/thumbnail.jp

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

First Sagittarius A* Event Horizon Telescope Results. I. The Shadow of the Supermassive Black Hole in the Center of the Milky Way

We present the first Event Horizon Telescope (EHT) observations of Sagittarius A* (Sgr A*), the Galactic center source associated with a supermassive black hole. These observations were conducted in 2017 using a global interferometric array of eight telescopes operating at a wavelength of λ = 1.3 mm. The EHT data resolve a compact emission region with intrahour variability. A variety of imaging and modeling analyses all support an image that is dominated by a bright, thick ring with a diameter of 51.8 \ub1 2.3 μas (68% credible interval). The ring has modest azimuthal brightness asymmetry and a comparatively dim interior. Using a large suite of numerical simulations, we demonstrate that the EHT images of Sgr A* are consistent with the expected appearance of a Kerr black hole with mass ∼4 7 106 M☉, which is inferred to exist at this location based on previous infrared observations of individual stellar orbits, as well as maser proper-motion studies. Our model comparisons disfavor scenarios where the black hole is viewed at high inclination (i > 50\ub0), as well as nonspinning black holes and those with retrograde accretion disks. Our results provide direct evidence for the presence of a supermassive black hole at the center of the Milky Way, and for the first time we connect the predictions from dynamical measurements of stellar orbits on scales of 103-105 gravitational radii to event-horizon-scale images and variability. Furthermore, a comparison with the EHT results for the supermassive black hole M87* shows consistency with the predictions of general relativity spanning over three orders of magnitude in central mass

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required

THEMIS: A Parameter Estimation Framework for the Event Horizon Telescope

The Event Horizon Telescope (EHT) provides the unprecedented ability to directly resolve the structure and dynamics of black hole emission regions on scales smaller than their horizons. This has the potential to critically probe the mechanisms by which black holes accrete and launch outflows, and the structure of supermassive black hole spacetimes. However, accessing this information is a formidable analysis challenge for two reasons. First, the EHT natively produces a variety of data types that encode information about the image structure in nontrivial ways; these are subject to a variety of systematic effects associated with very long baseline interferometry and are supplemented by a wide variety of auxiliary data on the primary EHT targets from decades of other observations. Second, models of the emission regions and their interaction with the black hole are complex, highly uncertain, and computationally expensive to construct. As a result, the scientific utilization of EHT observations requires a flexible, extensible, and powerful analysis framework. We present such a framework, Themis, which defines a set of interfaces between models, data, and sampling algorithms that facilitates future development. We describe the design and currently existing components of Themis, how Themis has been validated thus far, and present additional analyses made possible by Themis that illustrate its capabilities. Importantly, we demonstrate that Themis is able to reproduce prior EHT analyses, extend these, and do so in a computationally efficient manner that can efficiently exploit modern high-performance computing facilities. Themis has already been used extensively in the scientific analysis and interpretation of the first EHT observations of M87