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Vasoactive intestinal peptide (VIP), acting on both VPAC1 and VPAC2 receptors, is a key modulator of hippocampal synaptic transmission, pyramidal cell excitability and long-term depression (LTD), exerting its effects partly through modulation GABAergic disinhibitory circuits. Yet, the role of endogenous VIP and its receptors in modulation of hippocampal LTP and the involvement of disinhibition in this modulation have scarcely been investigated. We studied the modulation of CA1 LTP induced by TBS via endogenous VIP release in hippocampal slices from young-adult Wistar rats using selective VPAC1 and VPAC2 receptor antagonists, evaluating its consequence for the phosphorylation of CamKII, GluA1 AMPA receptor subunits and Kv4.2 potassium channels in total hippocampal membranes obtained from TBS stimulated slices. Endogenous VIP, acting on VPAC1 (but not VPAC2) receptors, inhibited CA1 hippocampal LTP induced by TBS in young adult Wistar rats and this effect was dependent on GABAergic transmission and relied on the integrity of NMDA and CaMKII-dependent LTP expression mechanisms but not on PKA and PKC activity. Furthermore, it regulated the autophosphorylation of CaMKII and the expression and Ser438 phosphorylation of Kv4.2 potassium channels responsible for the A-current while inhibiting phosphorylation of Kv4.2 on Thr607. Altogether, this suggests that endogenous VIP controls the expression of hippocampal CA1 LTP by regulating disinhibition through activation of VPAC1 receptors in interneurons. This may impact the autophosphorylation of CaMKII during LTP, as well as the expression and phosphorylation of Kv4.2 K+ channels at hippocampal pyramidal cell dendrites.Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately affected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). https://www.selleckchem.com/products/ggti-298.html Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes. They are known drivers of cancer and have been identified in 20% of cancers. Improvements in genomics technologies such as RNA-sequencing coupled with better algorithms for prediction of fusion genes has added to our knowledge of specific gene fusions in cancers. At present AA are underrepresented in genomic studies of prostate cancer. The primary goal of this study was to examine molecular differences in predicted fusion genes in a cohort of AA and EA men in the context of prostate cancer using computational approaches. RNA was purified from prostate tissue specimens obtained at surgery from subjects enrolled in the study. Fusion gene predictions were performed using four different fusion gene detection programs. This identified novel putative gene fusions unique to AA and suggested that the fusion gene burden was higher in AA compared to EA men.Regular physical exercise has shown great benefits in preventing age-related functional losses and in improving the perception of health-related quality of life (HRQoL) in older people. To optimize these benefits, it would be interesting to evaluate what type of exercise is better. Therefore, the purpose of this study was to assess the effects of heavy-resistance training on mobility and HRQoL in older women. Forty healthy, untrained older women (60-75 years) were randomly assigned to three groups circuit resistance training (CRT, n = 15), traditional resistance training (TRT, n = 15) or the control group (CG, n = 10). During the 12-week training period, both experimental groups performed training with heavy loads, twice a week. Before and after the training period, the Timed Up and Go test, as a proxy of mobility, and the perception of HRQoL were evaluated. TRT and CRT resulted in a statistically significant improvement in the Timed Up and Go test (-5.4 and -10.3%, respectively; p < 0.05), but only the improvement after CRT was significantly greater than changes in the CG (p < 0.001). Only CRT elicited improvements in several dimensions of the perception of the HRQoL questionnaire, such as physical functioning (13%, p < 0.001), general health (8.1%; p = 0.048), vitality (17.7%; p < 0.001), role emotional (6.7%; p = 0.044) and physical component summary (6.3%; p = 0.001). The change in the CRT group was greater than in the CG (p < 0.001) in the physical functioning score. The present findings show that CRT might be a time- (and hence cost-) effective alternative to trigger multiple positive functional and psychological adaptations in older women.Antibiotic resistance is a major emerging issue in the health care sector, as highlighted by the WHO. Filamentous Thermosensitive mutant Z (Fts-Z) is gaining significant attention in the scientific community as a potential anti-bacterial target for fighting antibiotic resistance among several pathogenic bacteria. The Fts-Z plays a key role in bacterial cell division by allowing Z ring formation. Several in vitro and in silico experiments have demonstrated that inhibition of Fts-Z can lead to filamentous growth of the cells, and finally, cell death occurs. Many natural compounds that have successfully inhibited Fts-Z are also studied. This review article intended to highlight the structural-functional aspect of Fts-Z that leads to Z-ring formation and its contribution to the biochemistry and physiology of cells. The current trend of natural inhibitors of Fts-Z protein is also covered.Brain-derived neurotrophic factor (BDNF) is abundantly expressed in brain regions involved in both homeostatic and hedonic feeding, and it circulates at reduced levels in patients with anorexia nervosa (AN). A single nucleotide polymorphism in the gene encoding for BDNF (Val66Met) has been associated with worse outcomes in patients with AN, and it is shown to promote anorectic behaviour in a mouse model of caloric restriction paired with social isolation stress. Previous animal models of the Val66Met polymorphism have been in mice because of the greater ease in modification of the mouse genome, however, the most widely-accepted animal model of AN, known as activity-based anorexia (ABA), is most commonly conducted in rats. Here, we examine ABA outcomes in a novel rat model of the BDNF Val66Met allelic variation (Val68Met), and we investigate the role of this polymorphism in feeding, food choice and sucrose preference, and energy expenditure. We demonstrate that the BDNF Val68Met polymorphism does not influence susceptibility to ABA or any aspect of feeding behaviour. The discrepancy between these results and previous reports in mice may relate to species-specific differences in stress reactivity.Holothuria mammata is one of the most valuable species of sea cucumber, as well as one of the main target species harvested in the Mediterranean and NE-Atlantic regions. This study aims to describe the reproductive cycle of H. mammata in a coastal area of southwest Portugal. Monthly samplings were carried out for 19 months, with the concomitant collection of environmental data and biometric data. H. mammata had a sex ratio of 11.2 (malefemale) and a size at first maturity of 142 mm for males and 167 mm for females. The gonadosomatic index (GI) peaked between April and May for both sexes. Gonad development started when days had a shorter photoperiod (9 to 13 h of sunlight) and lower seawater temperature (<15 °C), and spawning occurred later, with longer photoperiod (13 to 15 h of sunlight) and higher seawater temperature (>15 °C) and chlorophyll-a concentrations. The development of new studies to increase the biological and ecological knowledge of the populations of H. mammata is essential to create conditions for the domestication of broodstock in captivity, to allow the development of fishing regulations based on informed decisions and to create precise measures for the conservation of ecosystems.Biosensors have globally been considered as biomedical diagnostic tools required in abundant areas including the development of diseases, detection of viruses, diagnosing ecological pollution, food monitoring, and a wide range of other diagnostic and therapeutic biomedical research. Recently, the broadly emerging and promising technique of plasmonic resonance has proven to provide label-free and highly sensitive real-time analysis when used in biosensing applications. In this review, a thorough discussion regarding the most recent techniques used in the design, fabrication, and characterization of plasmonic biosensors is conducted in addition to a comparison between those techniques with regard to their advantages and possible drawbacks when applied in different fields.Land use and cover changes (LUCC) have a fundamental impact on the terrestrial carbon cycle. The abandonment of cropland as a result of the collapse of the Soviet Union offers a typical case of the conversion from cropland to natural vegetation, which could have a significant effect on the terrestrial carbon cycle. Due to the inaccuracy of LUCC records, the corresponding impact on the terrestrial carbon cycle has not been well quantified. In this study, we estimated the carbon flux using the Vegetation-Global-Atmosphere-Soil (VEGAS) model over the region of Russia, Belarus and Ukraine during 1990-2017. We first optimized the LUCC input data by adjusting the Food and Agriculture Organization (FAO) data by Russian statistical data and redistributing the spatiotemporal input data from the Historical Database of the Global Environment (HYDE) to the original model. Between 1990 and 2017, the area of cropland abandonment was estimated to be 36.82 Mha, compared to 11.67 Mha estimated by FAO. At the same time, the carbon uptake from the atmosphere to the biosphere was 9.23 GtC (vs fixed cropland 8.24 and HYDE 8.25 GtC) during 1990-2017, which means by optimizing the cropland distribution data, the total carbon absorption during the abandonment process increased by 0.99 GtC. Meanwhile, the growth of the vegetation carbon pool was significantly higher than that of the soil carbon pool. Therefore, we further highlight the importance of accurate cropland distribution data in terrestrial carbon cycle simulation.Cefoperazone/sulbactam (CPZ/SUL) is a β-lactam and β-lactamase inhibitor combination therapy for the treatment of respiratory tract infections. Using data from a prospective, multiple-center, open-label clinical trial in 54 patients with hospital-acquired pneumonia or ventilator-associated pneumonia caused by multidrug-resistant Acinetobacter baumannii (Ab), we showed that a combined PK/PD index %(T > MICcpz*T > MICsul) is a more appropriate PK/PD index against Ab, compared to the PK/PD index (%T > MIC) for a single drug. For a 2 h infusion, the PK/PD cutoff of CPZ/SUL (2 g/1 g, q8h) for clinical and microbiological efficacy was 4/2 and 1/0.5 mg/L, respectively. The corresponding cumulative fraction of response was 46.5% and 25.3%, respectively. Results based on the combined PK/PD index were quite similar to that based on the joint probability of target attainment. The two drugs have interaction from the viewpoint of PK/PD. When the dose of one drug was too high, the PK/PD cutoff was often determined by another drug in which the dose was maintained.
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