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Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis.
Continued increase in the relevance of ABM to environmental science and management will be helped by greater integration of ABMs across these two scales. Published by Oxford University Press on behalf of the Annals of Botany Company 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.BACKGROUND AND AIMS Plants have the potential to adjust the configuration of their hydraulic system to maintain its function across spatial and temporal gradients. Species with wide environmental niches provide an ideal framework to assess intra-specific xylem adjustments to contrasting climates. We aimed at assessing how xylem structure in the widespread species Nothofagus pumilio varies across combined gradients of temperature and moisture, and to which extent within-individual variation contributes to population responses across environmental gradients. METHODS We characterized xylem configuration in branches of N. pumilio trees at five sites across an 18° latitudinal gradient in the Chilean Andes, sampling at four elevations per site. We measured vessel area, vessel density and the degree of vessel grouping. We also obtained vessel diameter distributions and estimated the xylem-specific hydraulic conductivity. Xylem traits were studied in the last five growth rings to account for within-individual variatinvironmental changes. © The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail [email protected] AND AIMS Mikania micrantha Kunth, a climbing perennial weed of the family Asteraceae, is native to Latin America and is highly invasive in the tropical belt of Asia, Oceania and Australia. This study was framed to investigate the population structure of M. micrantha at a large spatial scale in Asia and to identify how introduction history, evolutionary forces and landscape features influenced the genetic pattern of the species in this region. METHODS We assessed the genetic diversity and structure of 1052 individuals from 46 populations for 12 microsatellite loci. The spatial pattern of genetic variation was investigated by estimating the relationship between genetic distance and geographic, climatic and landscape resistances hypothesized to influence gene flow between populations. KEY RESULTS We found high genetic diversity of M. micrantha in this region, as compared with the genetic diversity parameters of other invasive species. The spatial and non-spatial clustering algorithms identified the prerm persistence of the population, thereby indicating the range expansion ability of the species. © The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail [email protected] To assess the admission prevalence of third-generation cephalosporin-resistant Enterobacterales (3GCREB) and to assess whether risk factors vary by β-lactamase genotype. METHODS Adult patients were recruited within 72 h of admission to general wards of six university hospitals in 2014 and 2015. Rectal swabs were screened for 3GCREB and isolates were analysed phenotypically and genotypically. see more Patients were questioned on potential risk factors. Multivariable analyses were performed to identify risk factors for 3GCREB colonization and for specific β-lactamases. RESULTS Of 8753 patients screened, 828 were 3GCREB positive (9.5%). Eight hundred and thirteen isolates were available for genotyping. CTX-M-15 was the most common ESBL (38.0%), followed by CTX-M-1 (22.5%), CTX-M-14 (8.7%), CTX-M-27 (7.5%) and SHV-ESBL (4.4%). AmpC was found in 11.9%. Interestingly, 18 Escherichia coli isolates were AmpC positive, 12 of which (67%) contained AmpC on a gene of plasmid origin [CMY (n = 10), DHA (n = 2)]. Risk fac please email [email protected] In the current obesogenic environment we often eat while electronic devices, such as smart phones, computers, or the television, distract us. Such "distracted eating" is associated with increased food intake and overweight. However, the underlying neurocognitive mechanisms of this phenomenon are unknown. OBJECTIVE Our aim was to elucidate these mechanisms by investigating whether distraction attenuates processing in the primary and secondary taste cortices, located in the insula and orbitofrontal cortex (OFC), respectively. METHODS Forty-one healthy, normal-weight participants received fixed amounts of higher- and lower-sweetness isocaloric chocolate milk while performing a high- or low-distracting detection task during fMRI in 2 test sessions. Subsequently, we measured ad libitum food intake. RESULTS As expected, a primary taste cortex region in the right insula responded more to the sweeter drink (P less then 0.001, uncorrected). Distraction did not affect this insular sweetness response across the group, but did weaken sweetness-related connectivity of this region to a secondary taste region in the right OFC (P-family-wise error, cluster, small-volume corrected = 0.020). Moreover, individual differences in distraction-related attenuation of taste activation in the insula predicted increased subsequent ad libitum food intake after distraction (r = 0.36). CONCLUSIONS These results reveal a mechanism explaining how distraction during consumption attenuates neural taste processing. Moreover, our study shows that such distraction-induced decreases in neural taste processing contribute to individual differences in the susceptibility for overeating. Thus, being mindful about the taste of food during consumption could perhaps be part of successful prevention and treatment of overweight and obesity, which should be further tested in these target groups. This study was preregistered at the Open Science Framework as https//bit.ly/31RtDHZ. Copyright © The Author(s) 2020.AIMS In long QT syndrome (LQTS) patients, modifier genes modulate the arrhythmic risk associated with a disease-causing mutation. Their recognition can improve risk stratification and clinical management, but their discovery represents a challenge. We tested whether a cellular-driven approach could help to identify new modifier genes and especially their mechanism of action. METHODS AND RESULTS We generated human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) from two patients carrying the same KCNQ1-Y111C mutation, but presenting opposite clinical phenotypes. We showed that the phenotype of the iPSC-CMs derived from the symptomatic patient is due to impaired trafficking and increased degradation of the mutant KCNQ1 and wild-type human ether-a-go-go-related gene. In the iPSC-CMs of the asymptomatic (AS) patient, the activity of an E3 ubiquitin-protein ligase (Nedd4L) involved in channel protein degradation was reduced and resulted in a decreased arrhythmogenic substrate. Two single-nucleotide variants (SNVs) on the Myotubularin-related protein 4 (MTMR4) gene, an interactor of Nedd4L, were identified by whole-exome sequencing as potential contributors to decreased Nedd4L activity. Correction of these SNVs by CRISPR/Cas9 unmasked the LQTS phenotype in AS cells. Importantly, the same MTMR4 variants were present in 77% of AS Y111C mutation carriers of a separate cohort. Thus, genetically mediated interference with Nedd4L activation seems associated with protective effects. CONCLUSION Our finding represents the first demonstration of the cellular mechanism of action of a protective modifier gene in LQTS. It provides new clues for advanced risk stratification and paves the way for the design of new therapies targeting this specific molecular pathway. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.The hematopoietic system is sensitive to radiation. In this research, new aryl sulfone derivatives (XH-201 and XH-202) containing a nitrogen heterocycle were designed and synthesized and their radio-protective efficacies with regard to the hematopoietic system were evaluated. XH-201 administration significantly increased the survival rate of mice after 8.0 Gy total body irradiation (TBI). The results showed that XH-201 treatment not only increased the white blood cells, platelets counts and the percentage of hematopoietic progenitor cells and hematopoietic stem cells in mice exposed to 4.0 Gy TBI but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, our data demonstrated that XH-201 decreased the mitochondrial reactive oxygen species (ROS) levels in hematopoietic cells. Overall, these data suggest that XH-201 is beneficial for the protection of the hemoatopoietic system against radiation-induced injuries. © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.Forensic entomologists usually estimate the minimum postmortem interval (PMImin) using the time required for the oldest immature insects found on the corpse to grow to its development stage and age at the time of discovery. The sheep blow fly Lucilia sericata (Meigen, 1826) is a carrion fly found nearly worldwide, and important in forensics. We studied the development time of L. sericata from egg to adult at constant temperatures of 16, 19, 22, 25, 28, 31, and 34°C, and found that the times required are 913.2 ± 19.4, 588.8 ± 35.8, 459.8 ± 15.2, 373.2 ± 15.3, 308.0 ± 9.7, 272.5 ± 9.2, and 267.5 ± 10.5 h, respectively. We established three development models to infer the age of the immature insect isomegalen diagram, isomorphen diagram, and thermal summation model. In addition, a regression analysis was performed on the relationship between body length and total development time from hatching to dispersing. The thermal summation constant during the development of L. sericata is 6023.2 degree hours and development threshold temperature is 9.19°C. The results of this experiment provide a basis for the use of L. sericata in the estimation of PMImin. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.All rights reserved. For permissions, please e-mail [email protected] Recent studies suggest that microRNAs (miRNAs) can participate in depression pathogenesis by altering a host of genes that are critical in corticolimbic functioning. The present study focuses on examining whether alterations in the miRNA network in the amygdala are associated with susceptibility or resiliency to develop depression-like behavior in rats. METHODS Amygdala-specific altered miRNA transcriptomics were determined in a rat depression model following next-generation sequencing method. Target prediction analyses (cis- and trans) and qPCR-based assays were performed to decipher the functional role of altered miRNAs. miRNA-specific target interaction was determined using in vitro transfection assay in neuroblastoma cell line. miRNA-specific findings from the rat in vivo model were further replicated in postmortem amygdala of major depressive disorder (MDD) subjects. RESULTS Changes in miRNome identified 17 significantly upregulated and 8 significantly downregulated miRNAs in amygdala of learned helpless (LH) compared with nonlearned helpless rats.
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