Gene Expression Analysis Reveals Novel Gene Signatures Between Young and Old Adults in Human Prefrontal Cortex

Human neurons function over an entire lifetime, yet the molecular mechanisms which perform their functions and protecting against neurodegenerative disease during aging are still elusive. Here, we conducted a systematic study on the human brain aging by using the weighted gene correlation network analysis (WGCNA) method to identify meaningful modules or representative biomarkers for human brain aging. Significantly, 19 distinct gene modules were detected based on the dataset GSE53890; among them, six modules related to the feature of brain aging were highly preserved in diverse independent datasets. Interestingly, network feature analysis confirmed that the blue modules demonstrated a remarkably correlation with human brain aging progress. Besides, the top hub genes including PPP3CB, CAMSAP1, ACTR3B, and GNG3 were identified and characterized by high connectivity, module membership, or gene significance in the blue module. Furthermore, these genes were validated in mice of different ages. Mechanically, the potential regulators of blue module were investigated. These findings highlight an important role of the blue module and its affiliated genes in the control of normal brain aging, which may lead to potential therapeutic interventions for brain aging by targeting the hub genes

Whole-Genome Sequencing Identifies a Novel Variation of WAS Gene Coordinating With Heterozygous Germline Mutation of APC to Enhance Hepatoblastoma Oncogenesis

Hepatoblastoma (HB), a leading primary hepatic malignancy in children, originates from primitive hepatic stem cells. This study aimed to uncover the genetic variants that are responsible for HB oncogenesis. One family, which includes the healthy parents, and two brothers affected by HB, was recruited. Whole-genome sequencing (WGS) of germline DNA from all the family members identified two maternal variants, located within APC gene and X-linked WAS gene, which were harbored by the two brothers. The mutation of APC (rs137854573, c.C1606T, p.R536X) could result in HB carcinogenesis by activating Wnt signaling. The WAS variant (c.G3T, p.M1-P5del) could promote HB cell proliferation and inhibit T-cell-based immunity by activating PLK1 signaling and inactivating TCR signaling. Further analysis reflected that WAS deficiency might affect the antitumor activity of natural killer and dendritic cells. In summary, the obtained results imply that an APC mutant together with an X-linked WAS mutant, could lead to HB tumorigenesis by activating Wnt and PLK1 signaling, inhibiting TCR signaling, and reducing the antitumor activity of natural killer and dendritic cells

Enhanced Forest Microexpression Recognition Based on Optical Flow Direction Histogram and Deep Multiview Network

In order to recognize the instantaneous changes of facial microexpressions in natural environment, a method based on optical flow direction histogram and depth multiview network to enhance forest microexpression recognition was proposed. In the preprocessing stage, the histogram equalization of the acquired face image is performed, and then the dense key points of the face are detected. According to the coordinates of the key points and the face action coding system (FACS), the face region is divided into 15 regions of interest (ROI). In the feature extraction stage, the optical flow direction histogram feature between adjacent frames in ROI is extracted to detect the peak frame of microexpression sequence. Finally, the average optical flow direction histogram feature of the image sequence from the initial frame to the peak frame is extracted. In the classification stage, firstly, the head pose parameters under horizontal degrees of freedom are estimated to eliminate the influence of head pose motion, and a forest multiview conditional probability model based on deep multiview network is established. Conditional probability and neural connection function are introduced into the node splitting learning of random tree to improve the learning ability and distinguishing ability of the model on the limited training set. Finally, multiview-weighted voting is used to determine the categories of facial microexpressions. Experiments on CASME II microexpression dataset show that the proposed method can effectively describe the changes of microexpressions and improve the recognition accuracy compared with other new methods

Behavioral observability and reputational-preference–based rewarding mechanism promotes cooperation in spatial social dilemmas

To explore the incentive mechanisms of cooperation, inspired by preference for reputation in indirect reciprocity and the influence of behavioral observability on fitness, we present a new rewarding mechanism by incorporating these two impact factors into the evaluation of fitness in the spatial prisoner's dilemma game (PDG), under which a dynamically changing reward is established for cooperative neighbors whose reputation is higher than the average score of all neighbors. Simulation results reveal that the proposed rewarding mechanism favors the evolution of cooperation, under the joint effects of behavioral observability and reputational preference, cooperators can gradually agglomerate and form close clusters to defend the invasion of defectors. Moreover, we have investigated the characteristic snapshots and strategy transitions during the evolutionary process, which further validate the above outcome

Identification of key genes and pathways involved in response to pain in goat and sheep by transcriptome sequencing

Abstract Purpose This aim of this study was to investigate the key genes and pathways involved in the response to pain in goat and sheep by transcriptome sequencing. Methods Chronic pain was induced with the injection of the complete Freund’s adjuvant (CFA) in sheep and goats. The animals were divided into four groups: CFA-treated sheep, control sheep, CFA-treated goat, and control goat groups (n = 3 in each group). The dorsal root ganglions of these animals were isolated and used for the construction of a cDNA library and transcriptome sequencing. Differentially expressed genes (DEGs) were identified in CFA-induced sheep and goats and gene ontology (GO) enrichment analysis was performed. Results In total, 1748 and 2441 DEGs were identified in CFA-treated goat and sheep, respectively. The DEGs identified in CFA-treated goats, such as C-C motif chemokine ligand 27 (CCL27), glutamate receptor 2 (GRIA2), and sodium voltage-gated channel alpha subunit 3 (SCN3A), were mainly enriched in GO functions associated with N-methyl-d-aspartate (NMDA) receptor, inflammatory response, and immune response. The DEGs identified in CFA-treated sheep, such as gamma-aminobutyric acid (GABA)-related DEGs (gamma-aminobutyric acid type A receptor gamma 3 subunit [GABRG3], GABRB2, and GABRB1), SCN9A, and transient receptor potential cation channel subfamily V member 1 (TRPV1), were mainly enriched in GO functions related to neuroactive ligand-receptor interaction, NMDA receptor, and defense response. Conclusions Our data indicate that NMDA receptor, inflammatory response, and immune response as well as key DEGs such as CCL27, GRIA2, and SCN3A may regulate the process of pain response during chronic pain in goats. Neuroactive ligand-receptor interaction and NMDA receptor as well as GABA-related DEGs, SCN9A, and TRPV1 may modulate the process of response to pain in sheep. These DEGs may serve as drug targets for preventing chronic pain

Do investors care about auditor assignments? Evidence from last-minute changes to signing auditors

Against the background of China’s strengthening of finance and accounting supervision, this study examines the practice among listed companies of changing signing auditors at the last minute and explores whether Chinese investors can capture this information in a timely manner. We find that China’s capital market responds significantly negatively to these last-minute changes, implying that investors perceive a potential negative impact of this behavior. Cross-sectional analyses suggest that the characteristics of the change event, recent corporate events, and accounting firm capability significantly affect the stock price response. Furthermore, in terms of the individual characteristics of signing auditors, external investors appear to comprehensively consider busyness level, industry experience, and the timing of the change to determine the causes and effects of the auditor change and make different market reactions accordingly. In addition, consistent with investor perceptions, we find that last-minute changes significantly impair the quality of financial statements, indicating that external investors’ judgments based on information about changes in signing auditors are rational and effective

Selection of Reliable Reference Genes for Real-time qRT-PCR Analysis of Zi Geese () Gene Expression

Zi geese (Anser anser domestica) belong to the white geese and are excellent layers with a superior feed-to-egg conversion ratio. Quantitative gene expression analysis, such as Real-time qRT-PCR, will provide a good understanding of ovarian function during egg-laying and consequently improve egg production. However, we still don’t know what reference genes in geese, which show stable expression, should be used for such quantitative analysis. In order to reveal such reference genes, the stability of seven genes were tested in five tissues of Zi geese. Methodology/Principal Findings: The relative transcription levels of genes encoding hypoxanthine guanine phosphoribosyl transferase 1 (HPRT1), β-actin (ACTB), β-tubulin (TUB), glyceraldehyde-3-phosphate-dehydrogenase (GADPH), succinate dehydrogenase flavoprotein (SDH), 28S rRNA (28S) and 18S rRNA (18S) have been quantified in heart, liver, kidney, muscle and ovary in Zi geese respectively at different developmental stages (1 d, 2, 4, 6 and 8 months). The expression stability of these genes was analyzed using geNorm, NormFinder and BestKeeper software. Conclusions: The expression of 28S in heart, GAPDH in liver and ovary, ACTB in kidney and HPRT1 in muscle are the most stable genes as identified by the three different analysis methods. Thus, these genes are recommended for use as candidate reference genes to compare mRNA transcription in various developmental stages of geese