Huangfallon3482

Plants are exposed to an ever-changing environment to which they have to adjust accordingly. Their response is tightly regulated by complex signaling pathways that all start with stimulus perception. Pralsetinib Here, we give an overview of the latest developments on perception of various abiotic stresses, including drought, salinity, flooding, and temperature stress. We discuss whether proposed perception mechanisms are true sensors, which is well established for some abiotic factors whereas for others not fully elucidated yet. In addition, we review the downstream cellular responses, many of which are shared by various stresses, but result in stress-specific physiological and developmental output. New sensing mechanisms have been identified, including heat sensing by the photoreceptor phyB, salt sensing by GIPC sphingolipids, and drought sensing by the specific calcium influx channel OSCA1. The simultaneous occurrence of multiple stress conditions shows characteristic downstream signaling signatures, which were previously considered general signaling responses. The integration of sensing multiple stress conditions and subsequent signaling responses is a promising venue for future research to improve the understanding of plant abiotic stress perception. copyright, serif 2020 American Society of Plant Biologists. All rights reserved.Keratinocyte carcinomas (KC), including basal and squamous cell carcinomas, are the most common human cancers worldwide. While 75% of all KC (4 million annual cases in the US) are treated with conventional excision, this surgical modality has much lower cure rates than Mohs micrographic surgery, likely due to the bread-loaf histopathological assessment that visualizes less then 1% of the tissue margins. A quenched protease-activated fluorescent probe 6qcNIR, which produces a signal only in the protease-rich tumor microenvironment, was topically applied to ninety specimens ex vivo immediately following excision. "Puzzle-fit" analysis was used to correlate the fluorescent images with histology. Probe-dependent fluorescent images correlated with cancer determined by conventional histology. Point-of-care fluorescent detection of skin cancer had a clinically relevant sensitivity of 0.73 and corresponding specificity of 0.88. Importantly, clinicians were effectively trained to read fluorescent images within 15 minutes with reliability and confidence resulting in sensitivities of 62-78% and specificities of 92-97%. Fluorescent imaging using 6qcNIR allows 100% tumor margin assessment by generating en face images that correlate with histology and may be used to overcome the limitations of conventional bread-loaf histology. The utility of 6qcNIR was validated in a busy real-world clinical setting, and clinicians were trained to effectively read fluorescent margins with a short guided instruction, highlighting clinical adaptability. When used in conventional excision, this approach may result in higher cure rates at a lower cost by allowing same-day re-excision when needed, reducing patient anxiety and improving compliance by expediting post-surgical specimen assessment. Copyright ©2020, American Association for Cancer Research.Skeletal muscle wasting is a devastating consequence of cancer that contributes to increased complications and poor survival, but is not well understood at the molecular level. Herein we investigated the role of Myocilin (Myoc), a skeletal muscle hypertrophy-promoting protein that we showed is downregulated in multiple mouse models of cancer cachexia. Loss of Myoc alone was sufficient to induce phenotypes identified in mouse models of cancer cachexia, including muscle fiber atrophy, sarcolemmal fragility and impaired muscle regeneration. By 18 months of age, mice deficient in Myoc showed significant skeletal muscle remodeling, characterized by increased fat and collagen deposition compared to wild type mice-thus also supporting Myoc as a regulator of muscle quality. In cancer cachexia models, maintaining skeletal muscle expression of Myoc significantly attenuated muscle loss, while mice lacking Myoc showed enhanced muscle wasting. Further, we identified the Myocyte enhancer factor 2 C (MEF2C) transcription factor as a key upstream activator of Myoc whose gain-of-function significantly deterred cancer-induced muscle wasting and dysfunction in a pre-clinical model of pancreatic ductal adenocarcinoma (PDAC). Lastly, compared to non-cancer control patients MYOC was significantly reduced in skeletal muscle of PDAC patients defined as cachectic and correlated with MEF2c. These data therefore identify disruptions in MEF2c-dependent transcription of Myoc as a novel mechanism of cancer-associated muscle wasting that is similarly disrupted in muscle of cachectic cancer patients. Copyright ©2020, American Association for Cancer Research.Thousands of epigenomic data sets have been generated in the past decade, but it is difficult for researchers to effectively use all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for validated systematic integration of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic features and transcriptomes from many sources, including individual laboratories and consortia, to produce a comprehensive view of the regulatory landscape of differentiating hematopoietic cell types in mouse. By using IDEAS as our integrative and discriminative epigenome annotation system, we identified and assigned epigenetic states simultaneously along chromosomes and across cell types, precisely and comprehensively. Combining nuclease accessibility and epigenetic states produced a set of more than 200,000 candidate cis-regulatory elements (cCREs) that efficiently capture enhancers and promoters. The transitions in epigenetic states of these cCREs across cell types provided insights into mechanisms of regulation, including decreases in numbers of active cCREs during differentiation of most lineages, transitions from poised to active or inactive states, and shifts in nuclease accessibility of CTCF-bound elements. Regression modeling of epigenetic states at cCREs and gene expression produced a versatile resource to improve selection of cCREs potentially regulating target genes. These resources are available from our VISION website to aid research in genomics and hematopoiesis. © 2020 Xiang et al.; Published by Cold Spring Harbor Laboratory Press.