Damsgaardbell3079

Myeloid cells are known mediators of hypertension, but their role in initiating renin-induced hypertension has not been studied. Vitamin D deficiency causes pro-inflammatory macrophage infiltration in metabolic tissues and is linked to renin-mediated hypertension. We tested the hypothesis that impaired vitamin D signaling in macrophages causes hypertension using conditional knockout of the myeloid vitamin D receptor in mice (KODMAC). These mice develop renin-dependent hypertension due to macrophage infiltration of the vasculature and direct activation of renal juxtaglomerular (JG) cell renin production. Induction of endoplasmic reticulum stress in knockout macrophages increases miR-106b-5p secretion, which stimulates JG cell renin production via repression of transcription factors E2f1 and Pde3b. Moreover, in wild-type recipient mice of KODMAC/miR106b-/- bone marrow, knockout of miR-106b-5p prevents the hypertension and JG cell renin production induced by KODMAC macrophages, suggesting myeloid-specific, miR-106b-5p-dependent effects. These findings confirm macrophage miR-106b-5p secretion from impaired vitamin D receptor signaling causes inflammation-induced hypertension.Although tobacco smoking is the world's most important preventable cause of many chronic diseases (including COPD and asthma) and premature death, many physicians do not routinely apply smoking cessation in the daily health care of their patients. Two widely felt important concerns of physicians are that smoking cessation as part of a treatment is time-consuming and may jeopardize their relationship with patients. Dexketoprofentrometamol Very Brief Advice (VBA) is a non-confrontational method, which could assist general practitioners (GPs) as a simple, quick first step in getting patients to stop smoking. In this study, we investigated the opinions and experiences of GPs with VBA in their routine care in two rounds of telephone interviews with 19 GPs. The interviews were recorded and transcribed and subsequently analysed with NVivo12. We observed that the GPs had a very positive experience with using VBA. They found the method to be efficient as to the time involved, patient-friendly and easy to implement.Surface solar radiation is an indispensable parameter for numerical models, and the diffuse component contributes to the carbon uptake in ecosystems. We generated a 12-year (2007-2018) hourly dataset from Multi-functional Transport Satellite (MTSAT) satellite observations, including surface total solar radiation (Rs) and diffuse radiation (Rdif), with 5-km spatial resolution through deep learning techniques. The used deep network tacks the integration of spatial pattern and the simulation of complex radiation transfer by combining convolutional neural network and multi-layer perceptron. Validation against ground measurements shows the correlation coefficient, mean bias error and root mean square error are 0.94, 2.48 W/m2 and 89.75 W/m2 for hourly Rs and 0.85, 8.63 W/m2 and 66.14 W/m2 for hourly Rdif, respectively. The correlation coefficient of Rs and Rdif increases to 0.94 (0.96) and 0.89 (0.92) at daily (monthly) scales, respectively. The spatially continuous hourly maps accurately reflect regional differences and restore the diurnal cycles of solar radiation at fine resolution. This dataset can be valuable for studies on regional climate changes, terrestrial ecosystem simulations and photovoltaic applications.Insertion of atoms into aromatic carbon-nitrogen bonds is an appealing method for the synthesis of nitrogen-containing molecules and it has the advantage of the availability and abundance of anilines. However, the direct cleavage of aromatic carbon-nitrogen bonds is challenging due to the particularly inert and stable nature of these bonds. Here we report a formal, enantioselective one-carbon insertion into an aromatic carbon-nitrogen bond via an aromaticity dissembly-reconstruction process to directly convert anilines to chiral α-branched benzylic amines. The process involves oxidative dearomatization of para-substituted anilines, chiral sulfur ylide-mediated asymmetric aziridination, and subsequent rearrangement. Chiral sulfur ylides serve as one-carbon insertion units.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.Migrating cells move across diverse assemblies of extracellular matrix (ECM) that can be separated by micron-scale gaps. For membranes to protrude and reattach across a gap, actin filaments, which are relatively weak as single filaments, must polymerize outward from adhesion sites to push membranes towards distant sites of new adhesion. Here, using micropatterned ECMs, we identify T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promotes membrane protrusions and enables bridging of ECM gaps. We show that T-Plastin widens and lengthens protrusions and is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity. Together, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migration when adhesion is spatially-gapped.