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In this review, we summarize and discuss the most relevant molecular and clinical data on the role of the p53 family in gastric cancer and enumerate potential therapeutic innovative strategies.Effects of feeding levels below maintenance requirements of metabolizable energy (MER) and of feed supplementation on fecal nutrient and microbial C concentrations were evaluated. In experiment 1, Rhodes grass hay only was offered to Boran steers at 80%, 60%, and 40% of individual MER, while steers at 100% MER additionally received a concentrated mixture. This reduction in MER decreased N, increased fungal C but did not affect bacterial C concentrations in feces. In experiment 2, Holstein × Boran heifers were offered a poor-quality roughage diet without supplement, with sweet potato vine silage or with a urea-molasses block. These two supplements did not affect the fecal chemical composition or fungal C but increased bacterial C concentrations in feces. Across all data, the fungal C/bacterial C ratio was positively related to N and negatively to neutral detergent fiber concentrations in feces, indicating diet-induced shifts in the fecal microbial community.Phosphatases are hydrolytic enzymes that cleave the phosphoester bond of numerous substrates containing phosphorylated residues. The typical classification divides them into acid or alkaline depending on the pH at which they have optimal activity. The histidine phosphatase (HP) superfamily is a large group of functionally diverse enzymes characterized by having an active-site His residue that becomes phosphorylated during catalysis. HP enzymes are relevant biomolecules due to their current and potential application in medicine and biotechnology. Entamoeba histolytica, the causative agent of human amoebiasis, contains a gene (EHI_146950) that encodes a putative secretory acid phosphatase (EhHAPp49), exhibiting sequence similarity to histidine acid phosphatase (HAP)/phytase enzymes, i.e., branch-2 of HP superfamily. To assess whether it has the potential as a biocatalyst in removing phosphate groups from natural substrates, we studied the EhHAPp49 structural and functional features using a computational-experimental approach. Although the combined outcome of computational analyses confirmed its structural similarity with HP branch-2 proteins, the experimental results showed that the recombinant enzyme (rEhHAPp49) has negligible HAP/phytase activity. Nonetheless, results from supplementary activity evaluations revealed that rEhHAPp49 exhibits Mg2+-dependent alkaline pyrophosphatase activity. To our knowledge, this study represents the first computational-experimental characterization of EhHAPp49, which offers further insights into the structure-function relationship and the basis for future research.General practitioners (GPs) play a key role in the early identification and management of suicide risk in young people. B022 However, little is known about the processes involved in how, when and why a young person decides to seek help from their GP. Eight young people, aged 17-23, took part in semi-structured interviews exploring their experiences of help seeking when feeling suicidal. Data were analysed using framework analysis. The analysis identified three main themes and seven subthemes. The main themes explored were understanding when to seek help from a GP, barriers and facilitating factors at the GP consultation, and help seeking as a non-linear and dynamic process. The processes involved in how, when and why young people seek help from a GP when feeling suicidal were found to be dynamic and to fluctuate over time. Help seeking was initially related to how young people were able to understand and articulate their distress, the availability of informal support networks, and their perception of the GP as a source of help. During a GP consultation, help seeking was influenced by how safe and supported the young people felt. Perceived GP training, communication and validation of young people's concerns were important factors to help facilitate this process. Subsequent help seeking was influenced by prior experience of GP consultations and the availability of alternative support.Middle East respiratory syndrome is a severe respiratory illness caused by an infectious coronavirus. This virus is associated with a high mortality rate, but there is as of yet no effective vaccine or antibody available for human immunity/treatment. Drug design relies on understanding the 3D structures of viral proteins; however, arriving at such understanding is difficult for intrinsically disordered proteins, whose disorder-dependent functions are key to the virus's biology. Disorder is suggested to provide viral proteins with highly flexible structures and diverse functions that are utilized when invading host organisms and adjusting to new habitats. To date, the functional roles of intrinsically disordered proteins in the mechanisms of MERS-CoV pathogenesis, transmission, and treatment remain unclear. In this study, we performed structural analysis to evaluate the abundance of intrinsic disorder in the MERS-CoV proteome and in individual proteins derived from the MERS-CoV genome. Moreover, we detected disordered protein binding regions, namely, molecular recognition features and short linear motifs. Studying disordered proteins/regions in MERS-CoV could contribute to unlocking the complex riddles of viral infection, exploitation strategies, and drug development approaches in the near future by making it possible to target these important (yet challenging) unstructured regions.A novel and innovative solution addressing wind turbines' main bearing failure predictions using SCADA data is presented. This methodology enables to cut setup times and has more flexible requirements when compared to the current predictive algorithms. The proposed solution is entirely unsupervised as it does not require the labeling of data through work orders logs. Results of interpretable algorithms, which are tailored to capture specific aspects of main bearing failures, are merged into a combined health status indicator making use of Ensemble Learning principles. Based on multiple specialized indicators, the interpretability of the results is greater compared to black-box solutions that try to address the problem with a single complex algorithm. The proposed methodology has been tested on a dataset covering more than two year of operations from two onshore wind farms, counting a total of 84 turbines. All four main bearing failures are anticipated at least one month of time in advance. Combining individual indicators into a composed one proved effective with regard to all the tracked metrics.
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