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nificant interest in this area. Radiation oncology residents are expected and desire to teach in a multitude of settings across a wide variety of audiences. However, a significant proportion of radiation oncology residents lack formal training and rarely receive feedback for their teaching skills. The results of this national survey support the development of a residents-as-teachers curriculum for radiation oncology residents that would address the needs for and significant interest in this area. Intensity modulated proton therapy (IMPT) could yield high linear energy transfer (LET) in critical structures and increased biological effect. For head and neck cancers at the skull base this could potentially result in radiation-associated brain image change (RAIC). The purpose of the current study was to investigate voxel-wise dose and LET correlations with RAIC after IMPT. For 15 patients with RAIC after IMPT, contrast enhancement observed on T1-weighted magnetic resonance imaging was contoured and coregistered to the planning computed tomography. Monte Carlo calculated dose and dose-averaged LET (LET ) distributions were extracted at voxel level and associations with RAIC were modelled using uni- and multivariate mixed effect logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve and precision-recall curve. An overall statistically significant RAIC association with dose and LET was found in both the uni- and multivariate analysis. Pahould therefore be taken into consideration.Uterine artery endothelium undergoes a form of functional adaptation during pregnancy because of an increase in Cx43 communication, resulting in increased Ca2+/IP3 exchange and more synchronous and sustained vasodilator production. We have shown previously that acute exposure to growth factors and TNF can block this adaptation through ERK and/or Src-mediated Cx43 phosphorylation. In preeclampsia such adapted function is already missing, but while elevated TNF is associated with this condition, particularly after 28 weeks (late PE), elevated circulating VEGF165 is not. Given PE is a long term condition emerging in the second half of pregnancy, and is often associated with added edema, we now compare the chronic effects of these two factors on the cell monolayer in order to establish if the breakdown of junctional adherens and tight junctional assemblies in which Cx43 resides could also explain loss of vasodilatory function. We report that while TNF can degrade monolayer integrity even in the 0.1-1 ng/ml physiologic range, VEGF up to 10 ng/ml does not. In addition, the progressive action of TNF is mediated through Src and ERK signaling to promote internalization and destruction of VE-Cadherin (VE-Cad) and ZO-1, as well as the expression and secretion of a variety of proteases. At least one protein degraded from the extracellular space is VE-Cad, resulting in release of a shed VE-Cad protein product, and consistent with monolayer breakdown being sensitive to both Src and MEK/ERK kinase inhibitors and the general protease inhibitor GM6001. We conclude that the greater association of TNF with 'late' PE is as much due to its longer term destabilizing effects on junctional assemblies as it is to acute closure of Cx43 channels themselves. New therapies aimed at stabilizing these junctional assemblies may help treat this hypertensive condition.The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo, besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses.Soluble resistance-related calcium-binding protein (sorcin), a 22 kDa penta-EF-hand protein, has been intensively studied in cancers and multidrug resistance over a prolonged period. Sorcin is widely distributed in tissues and participates in the regulation of Ca2+ homeostasis and Ca2+-dependent signaling. Protein-protein interactions (PPIs) are essential for regulating protein functions in almost all biological processes. Sorcin interaction partners tend to vary in type, including Ca2+ receptors, Ca2+ transporters, endoplasmic reticulum stress markers, transcriptional regulatory elements, immunomodulation-related factors, and viral proteins. https://www.selleckchem.com/products/nms-p937-nms1286937.html Recent studies have shown that sorcin is involved in a broad range of pathological conditions, such as cardiomyopathy, type 2 diabetes mellitus, neurodegenerative diseases, liver diseases, and viral infections. As a multifunctional cellular protein, in these diseases, sorcin has a role by interacting with or regulating the expression of other proteins, such as sarcoplasmic reticulum/endoplasmic reticulum Ca2+ ATPase, ryanodine receptors, presenilin 2, L-type Ca2+ channels, carbohydrate-responsive element-binding protein, tau, α-synuclein, signal transducer and activator of transcription 3, HCV nonstructural 5A protein, and viral capsid protein 1.
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