ARHGEF18/p114RhoGEF Coordinates PKA/CREB Signaling and Actomyosin Remodeling to Promote Trophoblast Cell-Cell Fusion During Placenta Morphogenesis

Coordination of cell-cell adhesion, actomyosin dynamics and gene expression is crucial for morphogenetic processes underlying tissue and organ development. Rho GTPases are main regulators of the cytoskeleton and adhesion. They are activated by guanine nucleotide exchange factors in a spatially and temporally controlled manner. However, the roles of these Rho GTPase activators during complex developmental processes are still poorly understood. ARHGEF18/p114RhoGEF is a tight junction-associated RhoA activator that forms complexes with myosin II, and regulates actomyosin contractility. Here we show that p114RhoGEF/ARHGEF18 is required for mouse syncytiotrophoblast differentiation and placenta development. In vitro and in vivo experiments identify that p114RhoGEF controls expression of AKAP12, a protein regulating protein kinase A (PKA) signaling, and is required for PKA-induced actomyosin remodeling, cAMP-responsive element binding protein (CREB)-driven gene expression of proteins required for trophoblast differentiation, and, hence, trophoblast cell-cell fusion. Our data thus indicate that p114RhoGEF links actomyosin dynamics and cell-cell junctions to PKA/CREB signaling, gene expression and cell-cell fusion

Evaluation of Oryza sativa x O. glaberrima derived progenies for resistance to rootknot nematode and identification of introgressed alien chromosome segments using SSR markers

The genus Oryza has two cultivated species, Asian rice (Oryza sativa L.) and African rice (Oryza glaberrima Steud.) and 22 wild species. O. glaberrima is low yielding but has useful genes for resistance to biotic and abiotic stresses. Introgression lines derived from backcrossing of O. sativa x O. glaberrima, using O. sativa as recurrent parent, were evaluated for tolerance to root-knot nematode (Meloidogyne graminicola). Testing in sick plots infested with nematodes showed reduction in plant height, shoot and root biomass and leaf area index compared to the control. Based on gall rating and the ratio of the final population to the initial population of nematodes (Pf/Pi ratio), three introgression lines were found to be resistant to nematodes (IR80311-9-B-B-1-2 and IR80311-2-B-B-1-2 under screenhouse and IR80311-48-BB- 1 under phytotron conditions). Gall rating and the Pf/Pi ratio showed positive correlation (r = 0.61). Analysis of 122 introgression lines using simple sequence repeat (SSR) markers detected introgression of O. glaberrima segments into O. sativa

Visual population receptive fields in people with schizophrenia have reduced inhibitory surrounds

People with schizophrenia (SZ) experience abnormal visual perception on a range of visual tasks, which have been linked to abnormal synaptic transmission and an imbalance between cortical excitation and inhibition. However differences in the underlying architecture of visual cortex neurons, which might explain these visual anomalies, have yet to be reported in vivo. Here, we probe the neural basis of these deficits by using functional MRI (fMRI) and population receptive field (pRF) mapping to infer properties of visually responsive neurons in people with SZ. We employed a Difference-of-Gaussian (DoG) model to capture the centre-surround configuration of the pRF, providing critical information about the spatial scale of the pRFs inhibitory surround. Our analysis reveals that SZ is associated with reduced pRF size in early retinotopic visual cortex as well as a reduction in size and depth of the inhibitory surround in V1, V2 and V4. We consider how reduced inhibition might explain the diverse range of visual deficits reported in SZ. SIGNIFICANCE STATEMENT: People with schizophrenia (SZ) experience abnormal perception on a range of visual tasks, which has been linked to abnormal synaptic transmission and an imbalance between cortical excitation/inhibition. However associated differences in the underlying architecture of visual cortex neurons have yet to be reported in vivo. We used fMRI and population receptive field (pRF) mapping to demonstrate that the fine-grained functional architecture of visual cortex in people with SZ differs from unaffected controls. SZ is associated with reduced pRF size in early retinotopic visual cortex, largely due to reduced inhibitory surrounds. An imbalance between cortical excitation and inhibition could drive such a change in the centre-surround pRF configuration, and ultimately explain the range of visual deficits experienced in SZ

Avoid, Delay, Shorten. Results of Radiation Oncology’s COVID19 Patient Exposure Risk Mitigation Guidelines

We implemented evidence-based COVID19 guidelines on 3/16/20 to minimize patient exposure risks by avoiding, delaying, and shortening patient treatments when possible. We analyzed the effectiveness of our COVID guidelines by comparing the number of new patient starts and number of treatments before and after implementation. Our department successfully decreased patient exposure risk by reducing new prescription starts, rates of longer treatment courses, and overall number of treatment encounters in an evidence-based approach

PreImplantation Factor (PIF) promotes HLA-G, -E, -F, -C expression in JEG-3 choriocarcinoma cells and endogenous progesterone activity

BACKGROUND: Pregnancy success requires mandatory maternal tolerance of the semi/allogeneic embryo involving embryo-derived signals. Expression levels of PreImplantation Factor (PIF), a novel peptide secreted by viable embryos, correlate with embryo development, and its early detection in circulation correlates with a favourable pregnancy outcome. PIF enhances endometrial receptivity to promote embryo implantation. Via the p53 pathway, it increases trophoblast invasion, improving cell survival / immune privilege. PIF also reduces spontaneous and LPS-induced foetal death in immune naïve murine model. AIMS: To examine if PIF affects gene expression of human leukocyte antigen (HLA)-G, -E -F and -C in JEG-3 choriocarcinoma cells, and to examine the influence of PIF on local progesterone activity. Methods: PIF and progesterone (P4) effects on JEG-3 cells surface and intracellular HLA molecules was tested using monoclonal antibodies, flow cytometry, and Western blotting. PIF and IL17 effects on P4 and cytokines secretion was determined by ELISA. PIF and P4 effects on JEG-3 cells proteome was examined using 2D gel staining followed by spot analysis, mass spectrometry and bioinformatic analysis. RESULTS: In cytotrophoblastic JEG-3 cells PIF increased intracellular expression of HLA-G, HLA-F, HLA-E and HLA-C and surface expression of HLA-G, HLA-E and HLA-C in dose and time dependent manner. In case of HLA-E, F confirmed also by Western blotting. Proteome analysis confirmed an increase in HLA-G, pro-tolerance FOXP3+ regulatory T cells (Tregs), coagulation factors and complement regulator. In contrast, PIF reduced PRDX2 and HSP70s to negate oxidative stress and protein misfolding. PIF enhanced local progesterone activity, increasing steroid secretion and the receptor protein. It also promoted the secretion of the Th1/Th2 cytokines (IL-10, IL-1β, IL-8, GM-CSF and TGF-β1), resulting in improved maternal signalling. CONCLUSION: PIF can generate a pro-tolerance milieu by enhancing the expression of HLA molecules and by amplifying endogenous progesterone activity. A Fast-Track clinical trial for autoimmune disease has been satisfactorily completed. The acquired data warrants PIF use for the treatment of early pregnancy disorders

An Accurate Data Preparation Approach for the Prediction of Mortality in ACLF Patients using the CANONIC Dataset

The incidence of chronic liver disease has increased in Europe and can lead to Acute on Chronic Liver Failure (ACLF) which is associated with high levels of mortality due to multisystem organ failure. The characteristics of the ACLF patients can change very rapidly within a short period of time. Continuous assessment of their recovery status is critical for clinicians to adjust and deliver effective treatment. The aim of this paper is to validate the usefulness of a data preparation approach by combining different criteria to replace missing values, balance target-class variables, select useful patient characteristics and optimise hyperparameters of machine learning models for the prediction of ACLF associated mortality rates. A key step in the data preparation is a feature selection Mutual Information (MI) based multivariate approach to build smaller, and yet equally and in some cases more informative, subsets of patient characteristics than those frequently proposed for the prediction of mortality, from patients with ACLF in the CANONIC dataset. The usefulness of the data preparation approach proposed to predict mortality was evaluated by training the XGBoost and Logistic Regression models with the prepared data. Evaluations of the models trained using a test set provided evidence of an overall high accuracy in the prediction of the mortality rates of patients for days after their diagnosis, and in some cases even higher when reduced and more informative subsets of patient characteristics were found

Nonlinear Supersymmetry as a Hidden Symmetry

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Social norms for e-cigarettes and smoking: associations with initiation of e-cigarette use, intentions to quit smoking and quit attempts: findings from the EUREST-PLUS ITC Europe Surveys

Background: Social norms have received little attention in relation to electronic cigarettes (EC). The current study examine social norms for EC use and smoking tobacco, and their associations with (i) initiation of EC use, (ii) intention to quit smoking and (iii) attempts to quit smoking. Methods: Cross-sectional and longitudinal data analysis from Waves 1 and 2 of the ITC 6 European Country Survey and corresponding waves from England (the ITC Four Country Smoking and Vaping Survey). Current smokers at baseline, who heard of ECs and provided data at both waves were included (n = 3702). Complex samples logistic regression examined associations between the outcomes and descriptive (seeing EC use in public, close friends using ECs/smoking) and injunctive (public approves of ECs/smoking) norms, adjusting for country, demographics, EC use and heaviness of smoking. Results: In longitudinal analyses, seeing EC use in public at least some days was the only social norm that predicted initiation of EC use between waves (OR = 1.66, 95%CI = 1.08–2.56). In the cross-sectional analysis, having an intention to quit was associated with seeing EC use in public (OR = 1.37, 95%CI = 1.04–1.81) and reporting fewer than three close friends smoke (OR = 0.59, 95%CI = 0.44–0.80). There was no association between any social norm and making a quit attempt between waves. Conclusions: Initiation of EC use is predicted by seeing EC use in public, which was also associated with greater intention to quit smoking. Friends’ smoking was associated with lower intention to quit. These findings may allay concerns that increased visibility of ECs is renormalizing smoking amongst current smokers