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Healthy Surgery as well as the Intestine Microbiome in kids.
Smooth muscle cells (SMCs) are characterized by a high degree of phenotypic plasticity. Contractile differentiation is governed by myocardin-related transcription factors (MRTFs), in particular myocardin (MYOCD), and when their drive is lost, the cells become proliferative and synthetic with an expanded endoplasmic reticulum (ER). ER is responsible for assembly and folding of secreted proteins. When the load on the ER surpasses its capacity, three stress sensors (activating transcription factor 6 [ATF6], inositol-requiring enzyme 1α [IRE1α]/X-box binding protein 1 [XBP1], and PERK/ATF4) are activated to expand the ER and increase its folding capacity. This is referred to as the unfolded protein response (UPR). Here, we hypothesized that there is a reciprocal relationship between SMC differentiation and the UPR. Tight negative correlations between SMC markers (MYH11, MYOCD, KCNMB1, SYNPO2) and UPR markers (SDF2L1, CALR, MANF, PDIA4) were seen in microarray data sets from carotid arterial injury, partial bladder outlet obstruction, and bladder denervation, respectively. The UPR activators dithiothreitol (DTT) and tunicamycin (TN) activated the UPR and reduced MYOCD along with SMC markers in vitro. The IRE1α inhibitor 4μ8C counteracted the effect of DTT and TN on SMC markers and MYOCD expression. Transfection of active XBP1s was sufficient to reduce both MYOCD and the SMC markers. EGFR inhibitor MRTFs also antagonized the UPR as indicated by reduced TN and DTT-mediated induction of CRELD2, MANF, PDIA4, and SDF2L1 following overexpression of MRTFs. The latter effect did not involve the newly identified MYOCD/SRF target MSRB3, or reduced production of either XBP1s or cleaved ATF6. The UPR thus counteracts SMC differentiation via the IRE1α/XBP1 arm of the UPR and MYOCD repression. © 2020 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc.Immunotherapies have emerged as highly promising approaches to treat cancer patients. Allogeneic haematopoietic cell transplantation (HCT) is the most validated tumour immunotherapy available to date but its clinical efficacy is limited by toxicities, such as graft-versus-host disease (GVHD) and treatment resistance leading to relapse. The problems with new cellular therapies and checkpoint inhibitors are similar. However, development of biomarkers post-HCT, particularly for toxicities, has taken off in the last decade and has expanded greatly. Thanks to the advances in genomics, transcriptomics, proteomics and cytomics technologies, blood biomarkers have been identified and validated in promising diagnostic tests, prognostic tests stratifying for future occurrence of GVHD, and predictive tests for responsiveness to GVHD therapy and non-relapse mortality. These biomarkers may facilitate timely and selective therapeutic intervention. This review outlines a path from biomarker discovery to first clinical correlation, focusing on soluble STimulation-2 (sST2) - the interleukin (IL)-33-decoy receptor - which is the most validated biomarker. © 2020 British Society for Haematology and John Wiley & Sons Ltd.OBJECTIVES More people with dementia also fall into the category of high vascular risk, for which a statin is usually prescribed. However, these recommendations are based on studies in people without dementia. We aimed to evaluate the evidence for the long-term effectiveness and harm of statin therapy in patients with dementia. DESIGN Systematic review of randomized controlled trials and observational research. SETTING Publications from developed countries indexed in the PubMed, Web of Science, and Cochrane trial database between 2007 and 2019. PARTICIPANTS Trials including people with all types of dementia with a mean age older than 65 years. INTERVENTION Treatment with a statin for 6 months or longer. MEASUREMENTS Major adverse cardiovascular events, dementia progression, and general health at 2 years, or medication adverse events (AEs) at any time. Each article was assessed for bias using the Newcastle-Ottawa or Cochrane Collaboration tools. A narrative synthesis and pooled analyses are reported. RESULTS Ftional studies to inform prescribing decisions. J Am Geriatr Soc 68650-658, 2020. © 2020 The American Geriatrics Society.The European river lamprey Lampetra fluviatilis and the European brook lamprey Lampetra planeri (Block 1784) are classified as a paired species, characterized by notably different life histories but morphological similarities. Previous work has further shown limited genetic differentiation between these two species at the mitochondrial DNA level. Here, we expand on this previous work, which focused on lamprey species from the Iberian Peninsula in the south and mainland Europe in the north, by sequencing three mitochondrial marker regions of Lampetra individuals from five river systems in Ireland and five in southern Italy. Our results corroborate the previously identified pattern of genetic diversity for the species pair. We also show significant genetic differentiation between Irish and mainland European lamprey populations, suggesting another ichthyogeographic district distinct from those previously defined. Finally, our results stress the importance of southern Italian L. planeri populations, which maintain several private alleles and notable genetic diversity. © 2020 The Fisheries Society of the British Isles.Photosynthetic phenology is an important indicator of annual gross primary productivity (GPP). Assessing photosynthetic phenology remotely is difficult for evergreen conifers as they remain green year-round. Carotenoid-based vegetation indices such as the photochemical reflectance index (PRI) and chlorophyll/carotenoid index (CCI) are promising tools to remotely track the invisible phenology of photosynthesis by assessing carotenoid pigment dynamics. PRI, CCI and the near-infrared reflectance of vegetation (NIRV ) index may act as proxies of photosynthetic efficiency (ɛ), an important parameter in light-use efficiency models, or direct proxies of photosynthesis. To understand the physiological mechanisms reflected by PRI and CCI and the ability of vegetation indices to act as proxies of photosynthetic activity for estimating GPP, we measured leaf pigment composition, PRI, CCI, NIRV and photosynthetic activity at the leaf and canopy scales over 2 years in an evergreen and mixed deciduous forest. PRI and CCI captured the large seasonal carotenoid/chlorophyll ratio changes and good relationships were observed between PRI-ɛ and CCI-photosynthesis and NIRV -photosynthesis.
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