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This effect was stronger when the currently fixated patch was isoluminant as opposed to unmodified. Our results suggest that peripheral scene information substantially affects fixation durations and are consistent with the notion of competition among the current and potential future fixation locations.Purpose Retinitis pigmentosa GTPase regulator (RPGR)-related X-linked retinitis pigmentosa is associated with one of the most severe phenotypes among inherited retinal disease. The aim of this study was to investigate Clustered Regularly Interspaced Short Palindromic Repeat/Cas9-mediated gene editing therapy in a mouse model of Rpgr. Methods The Rpgr-/yCas9+/WT male mice were used for this study. At 6 months of age, they received a single subretinal injection of adeno-associated virus vectors carrying sgRNA and donor template separately, and therapeutic effect was examined after 1, 6, and 12 months. Results Rpgr knockout mouse showed slow but progressive age-related retinal degeneration, which emulates the disease occurring in humans. Significant photoreceptor preservation was observed in the treated part of the retina, in sharp contrast to the untreated part of the retina in the same eye after 6 and 12 months. It was surprising that precise modification at the target locus as demonstrated by genomic DNA sequencing in the post-mitotic photoreceptor was observed. Moreover, the therapeutic effect lasts for up to 12 months and no off-target effects were shown. Conclusions Our study strongly demonstrates that gene editing therapy is a promising therapeutic strategy to treat inherited retinal degeneration.Purpose Meibomian glands are essential in maintaining the integrity and health of the ocular surface. Meibomian gland dysfunction (MGD), mainly induced by ductal occlusion, is considered as the major cause of dry eye disease. In this study, a novel in vitro model was established for investigating the role of inflammation in the process of MGD. https://www.selleckchem.com/products/pf-2545920.html Methods Mouse tarsal plates were removed from eyelids after dissection and explants were cultured during various time ranging from 24 to 120 hours. Meibomian gland epithelial cells were further enzymatically digested and dissociated from tarsal plates before culturing. Both explants and cells were incubated in different media with or without serum or azithromycin (AZM). Furthermore, explants were treated with IL-1β or vehicle for 48 hours. Analyses for tissue viability, histology, biomarker expression, and lipid accumulation were performed with hematoxylin and eosin (H&E) staining, immunofluorescence staining, and Western blot. Results Higher viability was preserved when explants were cultured on Matrigel with immediate addition of culture medium. The viability, morphology, biomarker expression, and function of meibomian glands were preserved in explants cultured for up to 72 hours. Lipid accumulation and peroxisome proliferator-activated receptor γ (PPARγ) expression increased in both explants and cells cultured in media containing serum or AZM. Treatment with IL-1β induced overexpression of Keratin (Krt) 1 in meibomian gland ducts. Conclusions Intervention with pro-inflammatory cytokine IL-1β induces hyperkeratinization in meibomian gland ducts in vitro. This novel organotypic culture model can be used for investigating the mechanism of MGD.Iron and zinc deficiencies are some of the most widespread micronutrient deficiencies in low- and middle-income countries (LMIC). Dietary diversification, food fortification, nutrition education, and supplementation can be used to control micronutrient deficiencies. Legumes are important staple foods in most households in LMIC. Legumes are highly nutritious (good sources of essential minerals, fiber, and low glycemic index) and offer potential benefits in addressing nutrition insecurity in LMIC. Several efforts have been made to increase micronutrient intake by use of improved legumes. Improved legumes have a higher nutrient bioavailability, lower phytate, or reduced hard-to-cook (HTC) defect. We hypothesize that consumption of improved legumes leads to optimization of zinc and iron status and associated health outcomes. Therefore, the objective of this review is to examine the evidence on the efficacy of interventions using improved legumes. Nine relevant studies are included in the review. Consumption of imes suggesting them to be a sustainable solution to improve iron status. Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.Interpreting genetic variants of unknown significance (VUS) is essential in clinical applications of genome sequencing for diagnosis and personalized care. Noncoding variants remain particularly difficult to interpret, despite making up a large majority of trait associations identified in GWAS analyses. Predicting the regulatory effects of noncoding variants on candidate genes is a key step in evaluating their clinical significance. Here we develop a machine learning algorithm, ICE (Inference of Connected eQTLs), to predict the regulatory targets of noncoding variants identified in studies of expression quantitative trait loci (eQTLs). We assemble datasets using eQTL results from the Genotype-Tissue Expression (GTEx) project and learn to separate positive and negative pairs based on annotations characterizing the variant, gene and the intermediate sequence. ICE achieves an area under the receiver operating characteristic curve (ROC-AUC) of 0.799 using random cross-validation, and 0.700 for a more stringent poermissions@oup.com.Background The coronavirus disease 2019 pandemic has or threatens to overwhelm health care systems. Many institutions are developing ventilator triage policies. Objective To characterize the development of ventilator triage policies and compare policy content. Design Survey and mixed-methods content analysis. Setting North American hospitals associated with members of the Association of Bioethics Program Directors. Participants Program directors. Measurements Characteristics of institutions and policies, including triage criteria and triage committee membership. Results Sixty-seven program directors responded (response rate, 91.8%); 36 (53.7%) hospitals did not yet have a policy, and 7 (10.4%) hospitals' policies could not be shared. The 29 institutions providing policies were relatively evenly distributed among the 4 U.S. geographic regions (range, 5 to 9 policies per region). Among the 26 unique policies analyzed, 3 (11.3%) were produced by state health departments. The most frequently cited triage criteria were benefit (25 policies [96.2%]), need (14 [53.8%]), age (13 [50.0%]), conservation of resources (10 [38.5%]), and lottery (9 [34.6%]). Twenty-one (80.8%) policies use scoring systems, and 20 of these (95.2%) use a version of the Sequential Organ Failure Assessment score. Among the policies that specify the triage team's composition (23 [88.5%]), all require or recommend a physician member, 20 (87.0%) a nurse, 16 (69.6%) an ethicist, 8 (34.8%) a chaplain, and 8 (34.8%) a respiratory therapist. Thirteen (50.0% of all policies) require or recommend those making triage decisions not be involved in direct patient care, but only 2 (7.7%) require that their decisions be blinded to ethically irrelevant considerations. Limitation The results may not be generalizable to institutions without academic bioethics programs. Conclusion Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation.SUMMARY Bulk RNA sequencing studies have demonstrated that human leukocyte antigen (HLA) genes may be expressed in a cell type-specific and allele-specific fashion. Single-cell gene expression assays have the potential to further resolve these expression patterns, but currently available methods do not perform allele-specific quantification at the molecule level. Here we present scHLAcount, a postprocessing workflow for single-cell RNA-seq data that computes allele-specific molecule counts of the HLA genes based on a personalized reference constructed from the sample's HLA genotypes. AVAILABILITY scHLAcount is available under the MIT license at https//github.com/10XGenomics/scHLAcount. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) 2020. Published by Oxford University Press.BACKGROUND We aimed to determine the prevalence of antibodies against angiotensin II type 1 receptor (AT1RAbs) in hypertensive adults and elucidate the relation of anti-hypertensive medication type to blood pressure (BP) among persons with and without AT1RAb. METHODS Sera from participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with hypertension were tested for AT1RAb using a commercial ELISA [(OneLambda; positive ≥ 17 units/ml)]. BP measurements, uncontrolled BP (systolic BP ≥140 and/or diastolic BP ≥ 90 mmHg) and effect of BP medication type were compared for AT1RAb positive (+) versus negative (-) participants using descriptive statistics and multivariable regression. RESULTS 132 (13.1%) participants were AT1RAb+. Compared to AT1RAb-, AT1RAb+ persons were more likely to be white (47 vs. 36.7%; p= 0.03) but had similar comorbid disease burden. In models adjusting for age, sex, and race, AT1RAb+ persons had higher diastolic BP (β= 2.61 mmHg; SE=1.03; p =0.01) compared to AT1RAb- participants. Rates of uncontrolled BP were similar between the groups. AT1RAb+ persons on an ARB (n=21) had a mean of 10.5 mmHg higher systolic BP (SE=4.56; p =0.02) compared to AT1RAb+ persons using other BP medications. The odds of uncontrolled BP among AT1RAb+ participants on an ARB was 2.05 times that of those on other medications. AT1RAb- persons prescribed an ACEi had 1.8 mmHg lower diastolic BP (SE=0.81; p=0.03) than AT1RAb- persons not prescribed an ACEi. CONCLUSION AT1RAb was prevalent among hypertensive adults and was associated with higher BP among persons on an ARB. © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.The response to contrast is one of the most important functions of the macaque primary visual cortex, V1, but up to now there has not been an adequate theory for it. To fill this gap in our understanding of cortical function, we built and analyzed a new large-scale, biologically constrained model of the input layer, 4Cα, of macaque V1. We called the new model CSY2. We challenged CSY2 with a three-parameter family of visual stimuli that varied in contrast, orientation, and spatial frequency. CSY2 accurately simulated experimental data and made many new predictions. It accounted for 1) the shapes of firing-rate-versus-contrast functions, 2) orientation and spatial frequency tuning versus contrast, and 3) the approximate contrast-invariance of cortical activity maps. Post-analysis revealed that the mechanisms that were needed to produce the successful simulations of contrast response included strong recurrent excitation and inhibition that find dynamic equilibria across the cortical surface, dynamic feedback between L6 and L4, and synaptic dynamics like inhibitory synaptic depression.

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