Proliferation-Stimulating Effect of Colony Stimulating Factor 2 on Porcine Trophectoderm Cells Is Mediated by Activation of Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase

Colony-stimulating factor 2 (CSF2), also known as granulocyte macrophage colony-stimulating factor, facilitates mammalian embryonic development and implantation. However, biological functions and regulatory mechanisms of action of porcine endometrial CSF2 in peri-implantation events have not been elucidated. The aim of present study was to determine changes in cellular activities induced by CSFs and to access CSF2-induced intracellular signaling in porcine primary trophectoderm (pTr) cells. Differences in expression of CSF2 mRNA in endometrium from cyclic and pregnant gilts were evaluated. Endometrial CSF2 mRNA expression increases during the peri-implantation period, Days 10 to 14 of pregnancy, as compared to the estrous cycle. pTr cells obtained in Day 12 of pregnancy were cultured in the presence or absence of CSF2 (20 ng/ml) and LY294002 (20 µM), U0126 (20 µM), rapamycin (20 nM), and SB203580 (20 µM). CSF2 in pTr cell culture medium at 20 ng/ml significantly induced phosphorylation of AKT1, ERK1/2, MTOR, p70RSK and RPS6 protein, but not STAT3 protein. Also, the PI3K specific inhibitor (LY294002) abolished CSF2-induced increases in p-ERK1/2 and p-MTOR proteins, as well as CSF2-induced phosphorylation of AKT1. Changes in proliferation and migration of pTr cells in response to CSF2 were examined in dose- and time-response experiments. CSF2 significantly stimulated pTr cell proliferation and, U0126, rapamycin and LY294002 blocked this CSF2-induced proliferation of pTr cells. Collectively, during the peri-implantation phase of pregnancy in pigs, endometrial CSF2 stimulates proliferation of trophectoderm cells by activation of the PI3K-and ERK1/2 MAPK-dependent MTOR signal transduction cascades

Sex-specific expression of CTNNB1 in the gonadal morphogenesis of the chicken

BACKGROUND: Beta-catenin (CTNNB1), as a key transcriptional regulator in the WNT signal transduction cascade, plays a pivotal role in multiple biological functions such as embryonic development and homeostasis in adults. Although it has been suggested that CTNNB1 is required for gonad development and maintenance of ovarian function in mice, little is known about the expression and functional role of CTNNB1 in gonadal development and differentiation in the chicken reproductive system. METHODS: To examine sex-specific, cell-specific and temporal expression of CTNNB1 mRNA and protein during gonadal development to maturation of reproductive organs, we collected left and right gonads apart from mesonephric kidney of chicken embryos on embryonic day (E) 6, E9, E14, E18, as well as testes, oviduct and ovaries from 12-week-old and adult chickens and performed quantitative PCR, in situ hybridization, and immunohistochemical analyses. In addition, localization of Sertoli cell markers such as anti-Müllerian hormone (AMH), estrogen receptor alpha (ESR1), cyclin D1 (CCND1) and N-cadherin (CDH2) during testicular development was evaluated. RESULTS: Results of the present study showed that CTNNB1 mRNA and protein are expressed predominantly in the seminiferous cords on E6 to E14 in the male embryonic gonad, and are mainly localized to the medullary region of female embryonic gonads from E6 to E9. In addition, CTNNB1 mRNA and protein are abundant in the Sertoli cells in the testes and expressed predominantly in luminal epithelial cells of the oviduct, but not in the ovaries from 12-week-old and adult chickens. Concomitant with CTNNB1, AMH, ESR1, CCND1 and CDH2 were detected predominantly in the seminiferous cord of the medullary region of male gonads at E9 (after sex determination) and then maintained or decreased until hatching. Interestingly, AMH, ESR1, CCND1 and CDH2 were located in seminiferous tubules of the testes from 12-weeks-old chickens and ESR1, CCND1 and CDH2 were expressed predominantly in the Sertoli cells within seminiferous tubules of adult testes. CONCLUSIONS: Collectively, these results revealed that CTNNB1 is present in gonads of both sexes during embryonic development and it may play essential roles in differentiation of Sertoli cells during formation of seminiferous tubules during development of the testes

Depression and suicide risk prediction models using blood-derived multi-omics data

More than 300 million people worldwide experience depression; annually, ~800,000 people die by suicide. Unfortunately, conventional interview-based diagnosis is insufficient to accurately predict a psychiatric status. We developed machine learning models to predict depression and suicide risk using blood methylome and transcriptome data from 56 suicide attempters (SAs), 39 patients with major depressive disorder (MDD), and 87 healthy controls. Our random forest classifiers showed accuracies of 92.6% in distinguishing SAs from MDD patients, 87.3% in distinguishing MDD patients from controls, and 86.7% in distinguishing SAs from controls. We also developed regression models for predicting psychiatric scales with R2 values of 0.961 and 0.943 for Hamilton Rating Scale for Depression???17 and Scale for Suicide Ideation, respectively. Multi-omics data were used to construct psychiatric status prediction models for improved mental health treatment

Capric Acid Inhibits NO Production and STAT3 Activation during LPS-Induced Osteoclastogenesis

Capric acid is a second medium-chain fatty acid, and recent studies have shown that fatty acids are associated with bone density and reduce bone turnover. In this study, we investigated the effects of capric acid on lipopolysaccharide (LPS)-induced osteoclastogenesis in RAW264.7 cells. After treatment with capric acid (1 mM), the number of tartrate resistant acid phosphatase (TRAP)-positive cells decreased significantly. Capric acid reduced LPS-induced TRAP expression, an osteoclast differentiation marker, without inhibiting cell viability. LPS strongly upregulated inducible nitric oxide synthase (iNOS) mRNA levels and nitric oxide (NO) production, whereas capric acid inhibited them. Furthermore, capric acid also inhibited monocyte chemoattractant protein-1 (MCP-1) mRNA expression. Subsequently, we investigated various intracellular signaling proteins, including nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 1 (STAT1) and STAT3 associated with osteoclastogenesis. Capric acid had no effects on LPS-induced activation of the NF-κB, JNK, ERK1/2, and STAT1 pathways. However, capric acid inhibited LPS-induced phosphorylation of Ser727 in STAT3. Additionally, stattic (a STAT3 inhibitor) inhibited LPS-induced iNOS and MCP-1 gene expression. In conclusion, we demonstrated that capric acid inhibited LPS-induced osteoclastogenesis by suppressing NO production via the STAT3 pathway. These results suggest that capric acid has important therapeutic implications for treating bone diseases associated with excessive osteoclastogenesis

Distinct Expression Pattern and Post-Transcriptional Regulation of Cell Cycle Genes in the Glandular Epithelia of Avian Ovarian Carcinomas

The cell cycle system is controlled in a timely manner by three groups of cyclins, cyclin dependent kinases and cyclin dependent kinase inhibitors. Abnormal alterations of cell cycle regulatory mechanisms are a common feature of many diseases including numerous tumor types such as ovarian cancer. Although a variety of cell cycle regulatory genes are well known in mammalian species including human and mice, they are not well studied in avian species, especially in laying hens which are recognized as an excellent animal model for research relevant to human ovarian carcinogenesis. Therefore, in the present study, we focused on comparative expression and regulation of expression of candidate genes which might be involved in the cell cycle program in surface epithelial ovarian cancer in laying hens. Our current results indicate that expression levels of cell cycle gene transcripts are greater in cancerous as compared to normal ovaries. In particular, cyclin A2 (CCNA2), CCND1, CCND2, CCND3, CCNE2, cyclin dependent kinase 1 (CDK1), CDK3, CDK5, cyclin dependent kinases inhibitor 1A (CDKN1A) and CDKN1B were upregulated predominantly in the glandular epithelia of cancerous ovaries from laying hens. Further, several microRNAs (miRs), specifically miR-1798, miR-1699, miR-223 and miR-1744 were discovered to influence expression of CCND1, CCNE2, CDK1, and CDK3 mRNAs, respectively, via their 3'-UTR which suggests that post-transcriptional regulation of gene expression influences their expression in laying hens. Moreover, miR-1626 influenced CDKN1A expression and miR-222, miR-1787 and miR-1812 regulated CDKN1B expression via their 3'-UTR regions. Collectively, results of the present study demonstrate increased expression of cell cycle-related genes in cancerous ovaries of laying hens and indicate that expression of these genes is post-transcriptionally regulated by specific microRNAs

Organic light emitting board for dynamic interactive display

Interactive displays involve the interfacing of a stimuli-responsive sensor with a visual human-readable response. Here, we describe a polymeric electroluminescence-based stimuli-responsive display method that simultaneously detects external stimuli and visualizes the stimulant object. This organic light-emitting board is capable of both sensing and direct visualization of a variety of conductive information. Simultaneous sensing and visualization of the conductive substance is achieved when the conductive object is coupled with the light emissive material layer on application of alternating current. A variety of conductive materials can be detected regardless of their work functions, and thus information written by a conductive pen is clearly visualized, as is a human fingerprint with natural conductivity. Furthermore, we demonstrate that integration of the organic light-emitting board with a fluidic channel readily allows for dynamic monitoring of metallic liquid flow through the channel, which may be suitable for biological detection and imaging applications.

Mentides a les xarxes : ens ho empassem tot, a internet?

The reproductive system of chickens undergoes dynamic morphological and functional tissue remodeling during the molting period. The present study identified global gene expression profiles following oviductal tissue regression and regeneration in laying hens in which molting was induced by feeding high levels of zinc in the diet. During the molting and recrudescence processes, progressive morphological and physiological changes included regression and re-growth of reproductive organs and fluctuations in concentrations of testosterone, progesterone, estradiol and corticosterone in blood. The cDNA microarray analysis of oviductal tissues revealed the biological significance of gene expression-based modulation in oviductal tissue during its remodeling. Based on the gene expression profiles, expression patterns of selected genes such as, TF, ANGPTL3, p20K, PTN, AvBD11 and SERPINB3 exhibited similar patterns in expression with gradual decreases during regression of the oviduct and sequential increases during resurrection of the functional oviduct. Also, miR-1689* inhibited expression of Sp1, while miR-17-3p, miR-22* and miR-1764 inhibited expression of STAT1. Similarly, chicken miR-1562 and miR-138 reduced the expression of ANGPTL3 and p20K, respectively. These results suggest that these differentially regulated genes are closely correlated with the molecular mechanism(s) for development and tissue remodeling of the avian female reproductive tract, and that miRNA-mediated regulation of key genes likely contributes to remodeling of the avian reproductive tract by controlling expression of those genes post-transcriptionally. The discovered global gene profiles provide new molecular candidates responsible for regulating morphological and functional recrudescence of the avian reproductive tract, and provide novel insights into understanding the remodeling process at the genomic and epigenomic levels

Ultrasensitive biosensing platform for Mycobacterium tuberculosis detection based on functionalized graphene devices

Tuberculosis (TB) has high morbidity as a chronic infectious disease transmitted mainly through the respiratory tract. However, the conventional diagnosis methods for TB are time-consuming and require specialists, making the diagnosis of TB with point-of-care (POC) detection difficult. Here, we developed a graphene-based field-effect transistor (GFET) biosensor for detecting the MPT64 protein of Mycobacterium tuberculosis with high sensitivity as a POC detection platform for TB. For effective conjugation of antibodies, the graphene channels of the GFET were functionalized by immobilizing 1,5-diaminonaphthalene (1,5-DAN) and glutaraldehyde linker molecules onto the graphene surface. The successful immobilization of linker molecules with spatial uniformity on the graphene surface and subsequent antibody conjugation were confirmed by Raman spectroscopy and X-ray photoelectron spectroscopy. The GFET functionalized with MPT64 antibodies showed MPT64 detection with a detection limit of 1 fg/mL in real-time, indicating that the GFET biosensor is highly sensitive. Compared to rapid detection tests (RDT) and enzyme-linked immunosorbent assays, the GFET biosensor platform developed in this study showed much higher sensitivity but much smaller dynamic range. Due to its high sensitivity, the GFET biosensor platform can bridge the gap between time-consuming molecular diagnostics and low-sensitivity RDT, potentially aiding in early detection or management of relapses in infectious diseases

Combined Analysis of the Time-Resolved Transcriptome and Proteome of Plant Pathogen Xanthomonas oryzae pv. oryzae

Xanthomonas oryzae pv. oryzae (Xoo) is a plant pathogen responsible for causing bacterial blight in rice. The immediate alterations in Xoo upon initial contact with rice are essential for pathogenesis. We studied time-resolved genome-wide gene expression in pathogenicity-activated Xoo cells at the transcriptome and proteome levels. The early response genes of Xoo include genes related to cell motility, inorganic ion transport, and effectors. The alteration of gene expression is initiated as early as few minutes after the initial interaction and changes with time. The time-resolved comparison of the transcriptome and proteome shows the differences between transcriptional and translational expression peaks in many genes, although the overall expression pattern of mRNAs and proteins is conserved. The discrepancy suggests an important role of translational regulation in Xoo at the early stages of pathogenesis. The gene expression analysis using time-resolved transcriptome and proteome provides unprecedented valuable information regarding Xoo pathogenesis