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Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood. As technology in genome sequencing progressed, scientific efforts were made to explain and predict asthma's complexity and heterogeneity, and genome-wide association studies (GWAS) quickly became the preferred study method. Several gene markers and loci associated with asthma susceptibility, atopic and childhood-onset asthma were identified during the last few decades. Markers near the ORMDL3/GSDMB genes were associated with childhood-onset asthma, interleukin (IL)33 and IL1RL1 SNPs were associated with atopic asthma, and the Thymic Stromal Lymphopoietin (TSLP) gene was identified as protective against the risk to TH2-asthma. The latest efforts and advances in identifying and decoding asthma susceptibility are focused on epigenetics, heritable characteristics that affect gene expression without altering DNA sequence, with DNA methylation being the most described mechanism. Other less studied epigenetic mechanisms include histone modifications and alterations of miR expression. Recent findings suggest that the DNA methylation pattern is tissue and cell-specific. Several studies attempt to describe DNA methylation of different types of cells and tissues of asthmatic patients that regulate airway remodeling, phagocytosis, and other lung functions in asthma. In this review, we attempt to briefly present the latest advancements in the field of genetics and mainly epigenetics concerning asthma susceptibility.Host plant preference during the larval stage may help shape not only phenotypic plasticity but also behavioral isolation. We assessed the effects of diet on population parameters and mate choice in Spodoptera litura. We raised larvae fed on tobacco, Chinese cabbage, or an artificial diet, and we observed the shortest developmental time and highest fecundity in individuals fed the artificial diet. However, survival rates were higher for larvae on either of the natural diets. Population parameters including intrinsic rate of increase and finite rate of increase were significantly higher with the artificial diet, but this diet led to a lower mean generation time. Copulation duration, copulation time, and number of eggs reared significantly differed between diets. In terms of mate choice, females on the artificial diet rarely mated with males fed on a natural host. Our results support the hypothesis that different diets may promote behavioral isolation, affecting mating outcomes. Thus, findings for populations fed an artificial diet may not reflect findings for populations in the field.Z-pinned/bonded joints are great potential connection components that have been used in the 2D C/SiC composite structures; however, the hybrid joints present complex failure mechanism considering the secondary deposited SiC matrix in the clearance. Therefore, the mechanical performance and failure mechanism of the joints are investigated through experimental and numerical methods in this paper. Experiment results show that two peaks exist in the load-displacement curves. The first load peak is 2891-4172 N with the corresponding displacement of 0.10-0.15 mm, and the second load peak is 2670-2919 N with the corresponding displacement of 0.21-0.25 mm. Besides that, the secondary deposited SiC matrix exhibits discrete distribution, and it has significant effects on the failure mechanism. Validated by experimental data, the proposed three-dimensional numerical model based on modified Hashin's criterion and fastener element can predict the mechanical performance and failure process. The numerical results indicate that the first load peak is dominated by the deposited SiC matrix near the edge, while the second peak is dominated by the z-pin and the SiC matrix near the z-pin. Moreover, the effects of the deposited SiC matrix's strength and distribution are discussed, which is meaningful to the optimal design of C/SiC composite z-pinned/bonded hybrid single-lap joints.
One of the most studied molecular models of gene-environment interactions is that of FKBP5, which has been shown to interact with childhood adversity to increase the risk of psychiatric disorders, and has been implicated in schizophrenia. While the model predicts up-regulation of FKBP5, previous brain samples gene expression studies yielded inconsistent results.
We performed a systematic gene expression meta-analysis of FKBP5 and NR3C1, a glucocorticoid receptor inhibited by FKBP5, in cerebellum samples of patients with schizophrenia. The gene expression databases GEO, SMRI and those of NIMH were searched, and out of six screened datasets, three were eligible for the meta-analysis (overall 69 with schizophrenia and 78 controls).
We detected up-regulation of FKBP5 and down-regulation of NR3C1 in schizophrenia, and a negative correlation between their expression patterns. Correlation analysis suggested that the detected differential expression did not result from potential confounding factors.
Our results give significant support to the FKBP5 gene-environment interaction model for schizophrenia, which provides a molecular mechanism by which childhood adversity is involved in the development of the disorder. To explore FKBP5's potential as a therapeutic target, a mapping of its differential expression patterns in different brain regions of schizophrenia patients is needed.
Our results give significant support to the FKBP5 gene-environment interaction model for schizophrenia, which provides a molecular mechanism by which childhood adversity is involved in the development of the disorder. To explore FKBP5's potential as a therapeutic target, a mapping of its differential expression patterns in different brain regions of schizophrenia patients is needed.Dynamic studies in time course experimental designs and clinical approaches have been widely used by the biomedical community. These applications are particularly relevant in stimuli-response models under environmental conditions, characterization of gradient biological processes in developmental biology, identification of therapeutic effects in clinical trials, disease progressive models, cell-cycle, and circadian periodicity. Despite their feasibility and popularity, sophisticated dynamic methods that are well validated in large-scale comparative studies, in terms of statistical and computational rigor, are less benchmarked, comparing to their static counterparts. To date, a number of novel methods in bulk RNA-Seq data have been developed for the various time-dependent stimuli, circadian rhythms, cell-lineage in differentiation, and disease progression. Here, we comprehensively review a key set of representative dynamic strategies and discuss current issues associated with the detection of dynamically changing genes. We also provide recommendations for future directions for studying non-periodical, periodical time course data, and meta-dynamic datasets.Among many contaminants in wastewater, organic phenol compounds presented a major concern to endanger the water resources safety. In the present study, blend nanofiltration (NF) membranes comprising polyphenylsulfone (PPSU) and polyethersulfone (PES) were prepared via the non-induced phase separation and their performance was examined against 4-Nitrophenol (4-NP). The PES ratio in the dope solution was varied from 6 to 9 wt.% to probe the impact of PES on the retention and permeation characteristics of the final membranes. A series of experimental tools were employed to estimate the characteristics of the membranes, including surface and cross-section, hydrophilicity, pore size and pore size distribution. Performance evaluation of the NF membranes was conducted considering two operational variables; pH and initial feed solution. About 99% removal of 4-NP along with 6.2 L/m2.h.bar was achieved at the optimum operating conditions as revealed by optimization and mathematical modelling.Colorectal cancer (CRC) represents one of the most widespread forms of cancer in the population and, as all malignant tumors, often develops resistance to chemotherapies with consequent tumor growth and spreading leading to the patient's premature death. For this reason, a great challenge is to identify new therapeutic targets, able to restore the drugs sensitivity of cancer cells. In this review, we discuss the role of TRIpartite Motifs (TRIM) proteins in cancers and in CRC chemoresistance, focusing on the tumor-suppressor role of TRIM8 protein in the reactivation of the CRC cells sensitivity to drugs currently used in the clinical practice. Since the restoration of TRIM8 protein levels in CRC cells recovers chemotherapy response, it may represent a new promising therapeutic target in the treatment of CRC.Acrylamide can be carcinogenic to humans. However, the association between the acrylamide and the risks of renal cell, prostate, and bladder cancers in Asians has not been assessed. We aimed to investigate this association in the Japan Public Health Center-based Prospective Study data in 88,818 Japanese people (41,534 men and 47,284 women) who completed a food frequency questionnaire in the five-year follow-up survey in 1995 and 1998. A validated food frequency questionnaire was used to assess the dietary acrylamide intake. Cox proportional hazard regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). During a mean follow-up of 15.5 years (15.2 years of prostate cancer), 208 renal cell cancers, 1195 prostate cancers, and 392 bladder cancers were diagnosed. Compared to the lowest quintile of acrylamide intake, the multivariate hazard ratios for the highest quintile were 0.71 (95% CI 0.38-1.34, p for trend = 0.294), 0.96 (95% CI 0.75-1.22, p for trend = 0.726), and 0.87 (95% CI 0.59-1.29, p for trend = 0.491) for renal cell, prostate, and bladder cancers, respectively, in the multivariate-adjusted model. No significant associations were observed in the stratified analyses based on smoking. Dietary acrylamide intake was not associated with the risk of renal cell, prostate, and bladder cancers.Higher fruit and vegetable intake has been associated with improved mood, greater vitality, and lower stress. Metabolism inhibitor Although the nutrients driving these benefits are not specifically identified, one potentially important micronutrient is vitamin C, an important co-factor for the production of peptide hormones, carnitine and neurotransmitters that are involved in regulation of physical energy and mood. The aim of our study was to investigate the cross-sectional relationship between blood plasma vitamin C status and mood, vitality and perceived stress. A sample of 419 university students (aged 18 to 35; 67.8% female) of various ethnicities (49.2% European, 16.2% East Asian, 8.1% Southeast/Other Asian, 9.1% Māori/Pasifika, 11.5% Other) provided a fasting blood sample to determine vitamin C status and completed psychological measures consisting of the Profile of Mood States Short Form (POMS-SF), the vitality subscale of the Rand 36-Item Short Form (SF-36), and the Perceived Stress Scale (PSS). Participants were screened for prescription medication, smoking history, vitamin C supplementation, fruit/juice and vegetable consumption, kiwifruit allergies, excessive alcohol consumption and serious health issues, and provided age, gender, ethnicity, and socioeconomic status information, which served as covariates. There were no significant associations between vitamin C status and the psychological measures for the sample overall. However, associations varied by ethnicity. Among Māori/Pasifika participants, higher vitamin C was associated with greater vitality and lower stress, whereas among Southeast Asian participants, higher vitamin C was associated with greater confusion on the POMS-SF subscale. These novel findings demonstrate potential ethnicity-linked differences in the relationship between vitamin C and mental states. Further research is required to determine whether genetic variation or cultural factors are driving these ethnicity differences.
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