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Background: Fruit abortion is a major limiting factor for fruit production. In flat peach, fruit abortion is present in the whole tree of some accessions during early fruit development. However, the physiological factors and genetic mechanism underlying flat fruit abortion remain largely elusive. Results: In this study, we have revealed that the fertilization process was accomplished and the reduction of sucrose and starch contents might result in flat fruit abortion. By combining association and gene expression analysis, a key candidate gene, PpSnRK1βγ, was identified. A 1.67-Mb inversion co-segregated with flat fruit shape altered the promoter activity of PpSnRK1βγ, resulting in much lower expression in aborting flat peach. Ectopic transformation in tomato and transient overexpression in peach fruit have shown that PpSnRK1βγ could increase sugar and starch contents. Comparative transcriptome analysis further confirmed that PpSnRK1βγ participated in carbohydrate metabolism. Subcellular localization found that PpSnRK1βγ was located in nucleus. Conclusions: This study provides a possible reason for flat fruit abortion and identified a critical candidate gene, PpSnRK1βγ, that might be responsible for flat fruit abortion in peach. The results will provide great help in peach breeding and facilitate gene identification for fruit abortion in other plant species. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most malignant diseases in women worldwide. Serum microRNAs (miRNAs), with the characteristics of high sensitivity and specificity, have recently attracted more attentions to serve as potential biomarkers for tumor diseases. In this study, 194 breast cancer patients’ serum samples were collected before surgery and enrolled into different groups based on their diagnostic information. To search for breast cancer diagnostic biomarkers, serum miRNAs were screened by microarray in pooled samples of healthy volunteers and breast cancer patients in different clinical stages. The miRNAs were further verified in each individual patient’s serum samples in diagnostic and predictive sets. The serum level of miR-1915-3p was upregulated and miR-455-3p was downregulated significantly in breast cancer patients compared with healthy volunteers. Furthermore, the patients with infiltrating carcinoma or lymph node metastasis had a higher serum level of miR-1915-3p and lower serum level of miR-455-3p than patients with the carcinoma in situ or patients without lymph node metastasis. ROC analysis suggested that miR-1915-3p and miR-455-3p had the potential as a promising serum diagnostic and predictive biomarkers of breast cancer. miR-1915-3p was over-expressed in certain human breast cancer cells. Functional experiments in vitro showed that miR-1915-3p enhanced cell proliferative and migrational abilities. Overexpression of miR-1915-3p repressed target gene DUSP3 and activated ERK1/2. Collectively, this study provided a new insight that miR-1915-3p might play a role in the development of breast cancer and that serum miR-1915-3p and miR-455-3p could serve as diagnostic and predictive biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

Micromonas is a unicellular marine green alga that thrives from tropical to polar ecosystems. We investigated the growth and cellular characteristics of acclimated mid-exponential phase Micromonas commoda RCC299 over multiple light levels and over the diel cycle (14:10 hour light:dark). We also exposed the light:dark acclimated M. commoda to experimental shifts from moderate to high light (HL), and to HL plus ultraviolet radiation (HL+UV), 4.5 hours into the light period. Cellular responses of this prasinophyte were quantified by flow cytometry and changes in gene expression by qPCR and RNA-seq. While proxies for chlorophyll a content and cell size exhibited similar diel variations in HL and controls, with progressive increases during day and decreases at night, both parameters sharply decreased after the HL+UV shift. Two distinct transcriptional responses were observed among chloroplast genes in the light shift experiments: i) expression of transcription and translation-related genes decreased over the time course, and this transition occurred earlier in treatments than controls; ii) expression of several photosystem I and II genes increased in HL relative to controls, as did the growth rate within the same diel period. However, expression of these genes decreased in HL+UV, likely as a photoprotective mechanism. RNA-seq also revealed two genes in the chloroplast genome, ycf2-like and ycf1-like, that had not previously been reported. The latter encodes the second largest chloroplast protein in Micromonas and has weak homology to plant Ycf1, an essential component of the plant protein translocon. Analysis of several nuclear genes showed that the expression of LHCSR2, which is involved in non-photochemical quenching, and five light-harvesting-like genes, increased 30 to >50-fold in HL+UV, but was largely unchanged in HL and controls. Under HL alone, a gene encoding a novel nitrite reductase fusion protein (NIRFU) increased, possibly reflecting enhanced N-assimilation under the 625 μmol photons m-2 s-1 supplied in the HL treatment. NIRFU’s domain structure suggests it may have more efficient electron transfer than plant NIR proteins. Our analyses indicate that Micromonas can readily respond to abrupt environmental changes, such that strong photoinhibition was provoked by combined exposure to HL and UV, but a ca. 6-fold increase in light was stimulatory. [ABSTRACT FROM AUTHOR]

Micromonas is a unicellular motile alga within the Prasinophyceae, a green algal group that is related to land plants. This picoeukaryote (<2 μm diameter) is widespread in the marine environment but is not well understood at the cellular level. Here, we examine shifts in mRNA and protein expression over the course of the day-night cycle using triplicated mid-exponential, nutrient replete cultures of Micromonas pusilla CCMP1545. Samples were collected at key transition points during the diel cycle for evaluation using high-throughput LC-MS proteomics. In conjunction, matched mRNA samples from the same time points were sequenced using pair-ended directional Illumina RNA-Seq to investigate the dynamics and relationship between the mRNA and protein expression programs of M. pusilla. Similar to a prior study of the marine cyanobacterium Prochlorococcus, we found significant divergence in the mRNA and proteomics expression dynamics in response to the light:dark cycle. Additionally, expressional responses of genes and the proteins they encoded could also be variable within the same metabolic pathway, such as we observed in the oxygenic photosynthesis pathway. A regression framework was used to predict protein levels from both mRNA expression and gene-specific sequence-based features. Several features in the genome sequence were found to influence protein abundance including codon usage as well as 3’ UTR length and structure. Collectively, our studies provide insights into the regulation of the proteome over a diel cycle as well as the relationships between transcriptional and translational programs in the widespread marine green alga Micromonas. [ABSTRACT FROM AUTHOR]

Canopy FGF signaling regulator 2 (CNPY2) is a FGF21-modulated protein containing a saposin B-type domain. In vitro studies have shown CNPY2 is able to enhance neurite outgrowth in neurons and stabilize the expression of low density lipoprotein receptor in macrophages and hepatocytes. However, no in vivo data are available on the normal expression of CNPY2 and information is lacking on which cell types express this protein in tissues. To address this, the present study examined CNPY2 expression at the mRNA and protein levels. Quantitative PCR and ELISA examination of mouse tissues showed that CNPY2 varies between organs, with the highest expression in the heart, lung and liver. Immunohistochemistry detected CNPY2 in a variety of cell types including skeletal, cardiac and smooth muscle myocytes, endothelial cells and epithelial cells. CNPY2 was also detectable in mouse blood and human and mouse uteri. These data demonstrate CNPY2 is widely distributed in tissues and suggest the protein has biological functions that have yet to be identified. Using these new observations we discuss possible functions of the protein. [ABSTRACT FROM AUTHOR]

Soluble starch synthases (SSs) play important roles in the synthesis of cassava starch. However, the expression characteristics of the cassava SSs genes have not been elucidated. In this study, the MeSSIII-1 gene and its promoter, from SC8 cassava cultivars, were respectively isolated by PCR amplification. MeSSIII-1 protein was localized to the chloroplasts. qRT-PCR analysis revealed that the MeSSIII-1 gene was expressed in almost all tissues tested, and the expression in mature leaves was 18.9 times more than that in tuber roots. MeSSIII-1 expression was induced by methyljasmonate (MeJA), abscisic acid (ABA), and ethylene (ET) hormones in cassava. MeSSIII-1 expression patterns were further confirmed in proMeSSIII-1 transgenic cassava. The promoter deletion analysis showed that the −264 bp to −1 bp MeSSIII-1 promoter has basal activity. The range from −1228 bp to −987 bp and −488 bp to −264 bp significantly enhance promoter activity. The regions from −987 bp to −747 bp and −747 bp to −488 bp have repressive activity. These findings will provide an important reference for research on the potential function and transcriptional regulation mechanisms of the MeSSIII-1 gene and for further in-depth exploration of the regulatory network of its internal functional elements. [ABSTRACT FROM AUTHOR]

Forkhead box O (FOXO) transcription factors are emerging as key regulators of cell survival and growth. The transcriptional activity and subcellular localization of FOXO are tightly regulated by post-translational modifications. Here we report that IKBKE regulates FOXO3a through phosphorylation of FOXO3a-Ser644. The phosphorylation of FOXO3a resulted in its degradation and nuclear-cytoplasmic translocation. Previous studies have shown that IKBKE directly activates Akt and that Akt inhibits FOXO3a by phosphorylation of Ser32, Ser253 and Ser315. However, the activity of Akt-nonphosphorytable FOXO3a-A3 (i.e., converting 3 serine residues to alanine) was inhibited by IKBKE. Furthermore, overexpression of IKBKE correlates with elevated levels of pFOXO3a-S644 in primary lung and breast tumors. IKBKE inhibits cellular function of FOXO3a and FOXO3a-A3 but, to a much less extent, of FOXO3a-S644A. These findings suggest that IKBKE regulates FOXO3a primarily through phosphorylation of SerS644 and that IKBKE exerts its cellular function, at least to some extent, through regulation of FOXO3a. [ABSTRACT FROM AUTHOR]

Nitrogen is an important nutrient element that limits plant growth and yield formation, but excessive nitrogen has negative effects on plants and the environment. It is important to reveal the molecular mechanism of high NUE (nitrogen use efficiency) for breeding peach rootstock and variety with high NUE. In this study, two peach rootstocks, Shannong–1 (S) and Maotao (M), with different NUE were used as materials and treated with 0.1 mM KNO3 for transcriptome sequencing together with the control group. From the results of comparison between groups, we found that the two rootstocks had different responses to KNO3, and 2151 (KCL_S vs. KCL_M), 327 (KNO3_S vs. KCL_S), 2200 (KNO3_S vs. KNO3_M) and 146 (KNO3_M vs. KCL_M) differentially expressed genes (DEGs) were identified, respectively, which included multiple transcription factor families. These DEGs were enriched in many biological processes and signal transduction pathways, including nitrogen metabolism and plant hormone signal transduction. The function of PpNRT2.1, which showed up-regulated expression under KNO3 treatment, was verified by heterologous expression in Arabidopsis. The plant height, SPAD (soil and plant analyzer development) of leaf and primary root length of the transgenic plants were increased compared with those of WT, indicating the roles of PpNRT2.1 in nitrogen metabolism. The study uncovered for the first time the different molecular regulatory pathways involved in nitrogen metabolism between two peach rootstocks and provided gene reserve for studying the molecular mechanism of nitrogen metabolism and theoretical basis for screening peach rootstock or variety with high NUE. [ABSTRACT FROM AUTHOR]

In many high-dimensional microarray classification problems, an important task is to identify subsets of genes that best discriminate the classes. Nevertheless, existing gene selection methods for microarray classification cannot identify which classes are discriminable by these selected genes. In this paper, we propose an improved linear discriminant analysis (LDA) method that simultaneously selects important genes and identifies the discriminable classes. Specifically, a pairwise fusion penalty for LDA was used to shrink the differences of the class centroids in pairs for each variable and fuse the centroids of indiscriminable classes altogether. The numerical results in analyzing 2 gene expression profiles demonstrate the proposed approach help improve the interpretation of important genes in microarray classification problems. [ABSTRACT FROM PUBLISHER]

Coastal upwelling currents such as the California Current System (CCS) comprise some of the most productive biological systems on the planet. Diatoms dominate these upwelling events in part due to their rapid response to nutrient entrainment. In this region, they may also be limited by the micronutrient iron (Fe), an important trace element primarily involved in photosynthesis and nitrogen assimilation. The mechanisms behind how diatoms physiologically acclimate to the different stages of the upwelling conveyor belt cycle remain largely uncharacterized. Here, we explore their physiological and metatranscriptomic response to the upwelling cycle with respect to the Fe limitation mosaic that exists in the CCS. Subsurface, natural plankton assemblages that would potentially seed surface blooms were examined over wide and narrow shelf regions. The initial biomass and physiological state of the phytoplankton community had a large impact on the overall response to simulated upwelling. Following on‐deck incubations under varying Fe physiological states, our results suggest that diatoms quickly dominated the blooms by "frontloading" nitrogen assimilation genes prior to upwelling. However, diatoms subjected to induced Fe limitation exhibited reductions in carbon and nitrogen uptake and decreasing biomass accumulation. Simultaneously, they exhibited a distinct gene expression response which included increased expression of Fe‐starvation induced proteins and decreased expression of nitrogen assimilation and photosynthesis genes. These findings may have significant implications for upwelling events in future oceans, where changes in ocean conditions are projected to amplify the gradient of Fe limitation in coastal upwelling regions. [ABSTRACT FROM AUTHOR]

Trehalose-6-phosphate synthase (TPS) is essential for plant growth and development, linking trehalose-6-phosphate (T6P) to carbon metabolism. However, little is known about the TPS gene family in peaches and their potential roles in regulating carbohydrates in peach fruit. In this study, nine TPS genes were identified in the peach genome and named according to the homologous genes in Arabidopsis. Phylogenetic analysis showed that three subfamilies were identified, including TPSI, TPSII-1, and TPSII-2, which were also consistent with gene structure analysis. Considerable cis-elements were enriched in the promoters, including plant hormone-related elements. Tissue-specific analysis showed that these TPS genes were mainly expressed in leaves, stems, and fruit, showing different expression patterns for each gene. In addition, during fruit development, the content of trehalose-6-phosphate (T6P) was positively correlated with the expression of PpTPS7a and negatively with sucrose non-fermenting-1-related kinase 1 (SnRK1) activity. Transient overexpression and silencing of PpTPS7a in peach fruit validated its function in regulating T6P content and SnRK1 activity. [ABSTRACT FROM AUTHOR]

In this study, the expression of Cripto-1 and the role of macrophage polarization in immune response after allogeneic transfusion were analyzed by constructing a mouse model of allogeneic transfusion. In order to analyze the effects of miR-449a on the PI3K/AKT/NF-κB signaling pathway and the expression of downstream related regulatory factors under normal and abnormal conditions, we adopt in vitro and in vivo experiments separately. The molecular mechanism of PI3K/AKT/NF-κB signaling pathway was analyzed by blocking or activating gene expression and western blotting. Experiment in vitro has confirmed that inhibition of miR-449a increased the protein expression of Cripto-1. In vivo experiments confirmed that allogeneic transfusion reduced the expression of Cripto-1, which further inhibited NF-κB signaling pathway through AKT/PI3K phosphorylation, regulated macrophage polarization, inhibited M1 polarization of macrophages, promoted M2 polarization, and thus affected immune response of the body. [ABSTRACT FROM AUTHOR]

Nardostachyos Radix et Rhizoma (nardostachys) is the root and rhizome of Nardostachys jatamansi DC. Recent studies have shown that nardostachys may exert an anti-PD effect. In this study, the UHPLC-LTQ-Orbitrap-MS method was used to analyze the brain components of nardostachys in rats. Based on the results of UHPLC-LTQ-Orbitrap-MS analysis, nardosinone was identified to be the most effective anti-PD compound in nardostachys. To further verify this inference, a mouse PD model was established and the effect of nardosinone on PD mice was determined using classic behavioral tests. The results showed that nardosinone was indeed effective for relieving PD symptoms in mice. Moreover, network pharmacology analysis was used to elucidate the mechanism underlying the anti-PD effect of nardosinone. Dopamine receptor D2 (DRD2) was identified as the key target of nardosinone-PD interaction network, which was further verified by molecular docking and Western blotting. The results demonstrated that nardosinone and DRD2 could interact with each other. Furthermore, the expression level of DRD2 was decreased in the brain tissue of PD mice, and nardosinone could restore its expression to a certain extent. In conclusion, our findings suggest that nardosinone may reduce the motor and cognitive symptoms in the animal PD model by regulating DRD2 expression. [ABSTRACT FROM AUTHOR]

Male infertility induced by heat stress has been attracting more and more attention. Heat stress not only causes apoptosis of spermatocytes but also has adverse effects on Sertoli cells, further damaging spermatogenesis. Lycium barbarum polysaccharide (LBP) is the main bioactive component of Lycium barbarum, which has a protective effect on male reproduction, but its mechanism is still unclear. In this study, our results proved that LBP blocked the inhibitory effect on the proliferation activity of Sertoli cells after heat stress, reversed the dedifferentiation of Sertoli cells induced by heat stress, and ameliorated the structural integrity of the blood-testis barrier. In addition, it increased the expression of the androgen receptor and activated Akt signaling pathway to resist heat-stress-induced injury of Sertoli cells. [ABSTRACT FROM AUTHOR]

Male infertility induced by heat stress has been attracting more and more attention. Heat stress not only causes apoptosis of spermatocytes but also has adverse effects on Sertoli cells, further damaging spermatogenesis. Lycium barbarum polysaccharide (LBP) is the main bioactive component of Lycium barbarum, which has a protective effect on male reproduction, but its mechanism is still unclear. In this study, our results proved that LBP blocked the inhibitory effect on the proliferation activity of Sertoli cells after heat stress, reversed the dedifferentiation of Sertoli cells induced by heat stress, and ameliorated the structural integrity of the blood-testis barrier. In addition, it increased the expression of the androgen receptor and activated Akt signaling pathway to resist heat-stress-induced injury of Sertoli cells. [ABSTRACT FROM AUTHOR]

Male infertility induced by heat stress has been attracting more and more attention. Heat stress not only causes apoptosis of spermatocytes but also has adverse effects on Sertoli cells, further damaging spermatogenesis. Lycium barbarum polysaccharide (LBP) is the main bioactive component of Lycium barbarum, which has a protective effect on male reproduction, but its mechanism is still unclear. In this study, our results proved that LBP blocked the inhibitory effect on the proliferation activity of Sertoli cells after heat stress, reversed the dedifferentiation of Sertoli cells induced by heat stress, and ameliorated the structural integrity of the blood-testis barrier. In addition, it increased the expression of the androgen receptor and activated Akt signaling pathway to resist heat-stress-induced injury of Sertoli cells. [ABSTRACT FROM AUTHOR]

Herb-pairs are the basic units of composition in Chinese herbal formulae, where the bridge linking Chinese medicine and prescription consists of two Chinese medicine herbs. The Suanzaoren-Wuweizi herb-pair (SWHP) is commonly used as a sedative or tranquilizer. SWHP has been demonstrated to exert an antianxiety effect in animal models of anxiety. However, little information about its mechanism is available and the effects of SWHP have not been investigated. This study examined the effects of SWHP on ameliorating anxiety-like behaviors by regulating endocannabinoids system (ECS)—brain-derived neurotrophic factor (BDNF)—extracellular regulated protein kinases (ERK) signaling pathway expression, induced by restraint stress (RS) procedures. The antianxiety effects of SWHP on RS rats were then examined through the open-field test (OF) and the elevated plus maze test (EPM). The concentration of BNDF, ERK1/2, p-ERK1/2, cAMP-response element binding protein (CREB), and p-CREB expression in the prefrontal cortex and hippocampus of the rats was then measured by western blot. The number of positive cells of CB1 and CB2 in the rats' hippocampus CA1 region was measured by immunohistochemistry. These results gave compelling evidence that SWHP could modify anxiety-like behaviors of RS rats through regulation of the ECS-BDNF-ERK signaling pathway. Our study demonstrated that SWHP improved anxiety-like behaviors in RS rat models by regulating the ECS-BDNF-ERK signaling pathway. The findings indicate that SWHP may have a therapeutic application in the RS model of anxiety disorder, which proposes a potential new direction for research into anxiety disorders regarding mechanisms and the development of novel antianxiety drugs. [ABSTRACT FROM AUTHOR]

Objective: Recent evidence from genetic, cell biology, and animal model studies has suggested a pivotal role of autophagy in mediating systemic lupus erythematosus (SLE). However, the genetic basis has not yet been thoroughly examined. Therefore, the aim of the present study was to identify additional susceptibility variants in autophagy‐related genes along with their functional significance. Methods: First, we performed a gene family–based genetic association analysis in SLE patients with the use of ImmunoChip arrays, and then we selected the most strongly associated polymorphisms for replication in additional cohorts. To identify regulatory clues, we analyzed publicly available blood expression quantitative trait locus data and Encyclopedia of DNA Elements data on transcription factor binding sites and cell type‐specific differential expression. Functional effects were tested by luciferase reporter assays, electrophoretic mobility shift assays, and differential gene expression assays. Results: In 14,474 samples, we observed that the rare Chinese variant rs933717T was associated with susceptibility to SLE (0.11% in cases versus 0.87% in controls; P = 2.36 × 10–10, odds ratio 0.13). The rs933717 risk allele C correlated with increased MAP1LC3B expression; increased MAP1LC3B messenger RNA was observed in SLE patients and in lupus‐prone mice. In reporter gene constructs, the risk allele increased luciferase activity up to 2.7‐3.8‐fold in both HEK 293T and Jurkat cell lines, and the binding of HEK 293T and Jurkat cell nuclear extracts to the risk allele was also increased. Conclusion: We observed a likely genetic association between light chain 3B, a widely used marker for autophagy, and susceptibility to SLE. [ABSTRACT FROM AUTHOR]

Background: Axl is a receptor tyrosine kinase that is involved in many pathological conditions and carcinogenesis. Gas6 is the major ligand of Axl. Activation of Gas6/Axl pathway is essential for cancer development. However, its prognostic significance in solid tumors remains unclear. Therefore, we performed this meta-analysis to elucidate the prognostic impact of Axl. Methods: Published studies on Axl or Gas6 expression and overall survival (OS) and/or disease-free survival (DFS) were searched from databases. The outcome measurement is hazard ratio (HR) for OS or DFS related to Axl/Gas6 expression. Meta-analysis was performed using RevMan. The pooled HR was calculated by fixed-/random-effect models. Results: A total of 3,344 patients from 25 studies were included. The results of meta-analysis showed that Axl overexpression was correlated with shorter OS (HR: 2.03, p,0.0001) and DFS (HR: 1.85, p,0.0001). In subgroup analysis, Axl expression was significantly correlated with poor prognosis in hepatocellular, esophageal and lung cancer. Axl expression was associated with differentiation grade, TNM stage, lymph node and distant metastasis. Conclusion: These results suggest that Axl overexpression is correlated with poor prognosis in solid tumors. This correlation varies among different types of cancers. More studies are needed to further investigate the prognostic value of Axl. [ABSTRACT FROM AUTHOR]

Initiation of hair follicle (HF) is the first and most important stage of HF morphogenesis. However the precise molecular mechanism of initiation of hair follicle remains elusive. Meanwhile, in previous study, the more attentions had been paid to the function of genes, while the roles of non-coding RNAs (such as long noncoding RNA and microRNA) had not been described. Therefore, the roles of long noncoding RNA(LncRNA) and coding RNA in sheep skin during the initiation of sheep secondary HF were integrated and analyzed, by using strand-specific RNA sequencing (ssRNA-seq).A total of 192 significant differentially expressed genes were detected, including 67 up-regulated genes and 125 down-regulated genes between stage 0 and stage 1 of HF morphogenesis during HF initiation. Only Wnt2, FGF20 were just significant differentially expressed among Wnt, Shh, Notch and BMP signaling pathways. Further expression profile analysis of lncRNAs showed that 884 novel lncRNAs were discovered in sheep skin expression profiles. A total of 15 lncRNAs with significant differential expression were detected, 6 up-regulated and 9 down-regulated. Among of differentially expressed genes and LncRNA, XLOC002437 lncRNA and potential target gene COL6A6 were all significantly down-regulated in stage 1. Furthermore, by using RNAhybrid, XLOC005698 may be as a competing endogenous RNA ‘‘sponges” oar-miR-3955-5p activity. Gene Ontology and KEGG pathway analyses indicated that the significantly enriched pathway was peroxisome proliferator-activated receptors (PPARs) pathway (corrected P-value < 0.05), indicating that PPAR pathway is likely to play significant roles during the initiation of secondary HF.Results suggest that the key differentially expressed genes and LncRNAs may be considered as potential candidate genes for further study on the molecular mechanisms of HF initiation, as well as supplying some potential values for understanding human hair disorders. [ABSTRACT FROM AUTHOR]

Wool fiber diameter (WFD) is the most important economic trait of wool. However, the genes specifically controlling WFD remain elusive. In this study, the expression profiles of skin from two groups of Gansu Alpine merino sheep with different WFD (a super-fine wool group [FD = 18.0 ± 0.5 μm, n= 3] and a fine wool group [FD=23.0±0.5μm, n=3]) were analyzed using next-generation sequencing–based digital gene expression profiling. A total of 40 significant differentially expressed genes (DEGs) were detected, including 9 up-regulated genes and 31 down-regulated genes. Further expression profile analysis of natural antisense transcripts (NATs) showed that more than 30% of the genes presented in sheep skin expression profiles had NATs. A total of 7 NATs with significant differential expression were detected, and all were down-regulated. Among of 40 DEGs, 3 DEGs (AQP8, Bos d2, and SPRR) had significant NATs which were all significantly down-regulated in the super-fine wool group. In total of DEGs and NATs were summarized as 3 main GO categories and 38 subcategories. Among the molecular functions, cellular components and biological processes categories, binding, cell part and metabolic process were the most dominant subcategories, respectively. However, no significant enrichment of GO terms was found (corrected P-value >0.05). The pathways that were significantly enriched with significant DEGs and NATs were mainly the lipoic acid metabolism, bile secretion, salivary secretion and ribosome and phenylalanine metabolism pathways (P < 0.05). The results indicated that expression of NATs and gene transcripts were correlated, suggesting a role in gene regulation. The discovery of these DEGs and NATs could facilitate enhanced selection for super-fine wool sheep through gene-assisted selection or targeted gene manipulation in the future. [ABSTRACT FROM AUTHOR]

Alzheimer's disease ( AD) is the most common form of dementia and displays the characteristics of chronic neurodegenerative disorders; amyloid plaques ( AP) that contain amyloid β-protein (Aβ) accumulate in AD, which is also characterized by tau phosphorylation. Epidemiological evidence has demonstrated that long-term treatment with nonsteroidal anti-inflammatory drugs ( NSAIDs) markedly reduces the risk of AD by inhibiting the expression of cyclooxygenase 2 ( COX-2). Although the levels of COX-2 and its metabolic product prostaglandin ( PG) E2 are elevated in the brain of AD patients, the mechanisms for the development of AD remain unknown. Using human- or mouse-derived glioblastoma and neuroblastoma cell lines as model systems, we delineated the signaling pathways by which COX-2 mediates the reciprocal regulation of interleukin-1β ( IL-1β) and Aβ between glial and neuron cells. In glioblastoma cells, COX-2 regulates the synthesis of IL-1β in a PGE2-dependent manner. Moreover, COX-2-derived PGE2 signals the activation of the PI3- K/ AKT and PKA/ CREB pathways via cyclic AMP; these pathways transactivate the NF-κB p65 subunit via phosphorylation at Ser 536 and Ser 276, leading to IL-1β synthesis. The secretion of IL-1β from glioblastoma cells in turn stimulates the expression of COX-2 in human or mouse neuroblastoma cells. Similar regulatory mechanisms were found for the COX-2 regulation of BACE-1 expression in neuroblastoma cells. More importantly, Aβ deposition mediated the inflammatory response of glial cells via inducing the expression of COX-2 in glioblastoma cells. These findings not only provide new insights into the mechanisms of COX-2-induced AD but also initially define the therapeutic targets of AD. [ABSTRACT FROM AUTHOR]

The alterations of MicroRNAs(miRNAs) in host cell after foot-and-mouth disease virus (FMDV) infection is still obscure. To increase our understanding of the pathogenesis of FMDV at the post-transcriptional regulation level, Solexa high-throu MicroRNAs (miRNAs) play an important role both in the post-transcriptional regulation of gene expression and host-virus interactions. Despite investigations of miRNA expression ghput sequencing and bioinformatic tools were used to identify differentially expressed miRNAs and analyze their functions during FMDV infection of PK-15cells. Results indicated that 9,165,674 and 9,230,378 clean reads were obtained, with 172 known and 72 novel miRNAs differently expressed in infected and uninfected groups respectively. Some of differently expressed miRNAs were validated using stem-loop real-time quantitative RT-PCR. The GO annotation and KEGG pathway analysis for target genes revealed that differently expressed miRNAs were involved in immune response and cell death pathways. [ABSTRACT FROM AUTHOR]

In recent years, among all patients with colorectal cancer, the proportion of young patients has been gradually increasing. However, the molecular mechanisms involved in colorectal cancer in the young are largely unknown. In the present study the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas datasets were integrated to elucidate the key gene biomarkers in these patients. The GSE41657 and GSE41258 datasets were downloaded from the GEO database. By screening for differentially expressed genes, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein-protein interaction analysis, hub gene screening and survival analysis, two key genes, CXCL8 and VEGFA, which were enriched in cancer pathways, were obtained. Reverse transcription-quantitative (RT-q)PCR was performed to verify the outcome obtained by bioinformatics analysis. In conclusion, the present study identified two key genes using bioinformatics analysis and RT-qPCR validation. These results indicated that the candidate genes may be involved in the progression of colorectal cancer in young people, and these two genes may act as ideal prognostic indicators or therapeutic targets for colorectal cancer in the youth. [ABSTRACT FROM AUTHOR]

Although extensive studies have demonstrated the functional impairment of antigen-specific CD4+ and CD8+ T-cells during chronic hepatitis C virus (HCV) infection, the functional status of global CD4+ and CD8+ T-cells remains unclear. In this report, we recruited 42 long-term (~20 years) treatment-naïve chronic HCV (CHC) patients and 15 healthy donors (HDs) to investigate differences in global CD4+ and CD8+ T-cells function. We show that CD4+ and CD8+ T-cells from CHC patients underwent increased apoptosis after TCR stimulation. Furthermore, IFN-γ, IL-9 and IP-10 were elevated in CHC patients’ plasma and promoted activation-induced T-cells death. Global CD4+ and CD8+ T-cells also showed unique transcriptional profiles in the expression of apoptosis-related genes. We identified BCL2, PMAIP1, and CASP1 in CD4+ T-cells and IER3 and BCL2A1 in CD8+ T-cells from CHC patients as HCV-specific gene signatures. Importantly, the gene expression patterns of CD4+ and CD8+ T-cells from CHC patients differ from those in CD4+ and CD8+ T-cells from human immunodeficiency virus type 1 (HIV-1) or hepatitis B virus (HBV) infected individuals. Our results indicate that chronic HCV infection causes a systemic change in cytokine levels that primes T-cells for activation-induced apoptosis. Furthermore, HCV infection programs unique apoptosis-related gene expression profiles in CD4+ and CD8+ T-cells, leading to their enhanced activation-induced apoptosis. These results provide novel insights to the pathogenesis of chronic HCV infection. [ABSTRACT FROM AUTHOR]