Radiation-induced multiorgan dysfunction is thought to result primarily from damage to the endothelial system, leading to a systemic inflammatory response that is mediated by the recruitment of leukocytes. The Eph-ephrin signaling pathway in the vascular system participates in various disease developmental processes, including cancer and inflammation. In this study, we demonstrate that radiation exposure increased intestinal inflammation via endothelial dysfunction, caused by the radiation-induced activation of EphA2, an Eph receptor tyrosine kinase, and its ligand ephrinA1. Barrier dysfunction in endothelial and epithelial cells was aggravated by vascular endothelial-cadherin disruption and leukocyte adhesion in radiation-induced inflammation both in vitro and in vivo. Among all Eph receptors and their ligands, EphA2 and ephrinA1 were required for barrier destabilization and leukocyte adhesion. Knockdown of EphA2 in endothelial cells reduced radiation-induced endothelial dysfunction. Furthermore, pharmacological inhibition of EphA2-ephrinA1 by the tyrosine kinase inhibitor dasatinib attenuated the loss of vascular integrity and leukocyte adhesion in vitro. Mice administered dasatinib exhibited resistance to radiation injury characterized by reduced barrier leakage and decreased leukocyte infiltration into the intestine. Taken together, these data suggest that dasatinib therapy represents a potential approach for the protection of radiation-mediated intestinal damage by targeting the EphA2-ephrinA1 complex.Terrestrial plants are known to "garden" the microbiota of their rhizosphere via released metabolites (that can attract beneficial microbes and deter pathogenic microbes). Such a "gardening" capacity is also known to be dynamic in plants. Although microbial "gardening" has been recently demonstrated for seaweeds, we do not know whether this capacity is a dynamic property in any aquatic flora like in terrestrial plants. Here, we tested the dynamic microbial "gardening" capacity of seaweeds using the model invasive red seaweed Agarophyton vermiculophyllum. Following an initial extraction of surface-associated metabolites (immediately after field collection), we conducted a long-term mesocosm experiment for 5 months to test the effect of two different salinities (low = 8.5 and medium = 16.5) on the microbial "gardening" capacity of the alga over time. We tested "gardening" capacity of A. vermiculophyllum originating from two different salinity levels (after 5 months treatments) in settlement assays against threetained production of healthy A. vermiculophyllum in farms.The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional recurrences after EBRT. We performed a structured review of data published from 2010. Although no relevant new data from prospective trials or meta-analyses were identified, 14 analyses of cancer registry data from the United States or Europe, focusing predominantly on the endpoint for overall survival, were identified, four of them using propensity-score matching to compare subgroups treated with vs. without radiotherapy. Although stage-by-stage data are rare, the registry analyses support the idea of a beneficial effect, especially of VBT, on overall survival in International Federation of Gynecology and Obstetrics (FIGO) stage IA patients (to a lesser extent in stage IB). For stages II to III, the data sets indicate the largest effects on overall survival for the combination of EBRT and VBT. In all stages, survival effects of radiotherapy apparently persist when given in addition to chemotherapy. Whereas some studies see the strongest survival effects in patients with positive lymph nodes, propensity-score matched data indicate an overall survival effect of radiotherapy (EBRT + VBT or VBT alone) in FIGO stages I to III regardless of lymph node surgery.
  Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF).
 
  JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots.
 
  In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression.  https://www.selleckchem.com/products/blebbistatin.html  Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice.
 
  JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.
 JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.Human health and wellbeing and the health of the biosphere are inextricably linked. The state of Earth's life-support systems, including freshwater, oceans, land, biodiversity, atmosphere, and climate, affect human health. At the same time, human activities are adversely affecting natural systems. This review paper is the outcome of an interdisciplinary workshop under the auspices of the Future Earth Health Knowledge Action Network (Health KAN). It outlines a research agenda to address cross-cutting knowledge gaps to further understanding and management of the health risks of these global environmental changes through an expert consultation and review process. The research agenda has four main themes (1) risk identification and management (including related to water, hygiene, sanitation, and waste management); food production and consumption; oceans; and extreme weather events and climate change. (2) Strengthening climate-resilient health systems; (3) Monitoring, surveillance, and evaluation; and (4) risk communication.