Detection of closely linked QTLs and candidate genes controlling germination indices in response to drought and salinity stresses in barley.

The aim of current study was to identify closely linked QTLs and candidate genes related to germination indices under control, salinity and drought conditions in barley. A total of nine (a major), 28 (eight major) and 34 (five major) closely linked QTLs were mapped on the seven chromosomes in response to control, drought and salinity conditions using genome-wide composite interval mapping, respectively. The major QTLs can be used in marker-assisted selection (MAS) projects to increase tolerance to drought and salinity stresses during the germination. Overall, 422 unique candidate genes were associated with most major QTLs. Moreover, gene ontology analysis showed that candidate genes mostly involved in biological process related to signal transduction and response to stimulus in the pathway of resistance to drought and salinity stresses. Also, the protein-protein interaction network was identified 10 genes. Furthermore, 10 genes were associated with receptor-like kinase family. In addition, 16 transcription factors were detected. Three transcription factors including B3, bHLH, and FAR1 had the most encoding genes. Totally, 60 microRNAs were traced to regulate the target genes. Finally, the key genes are a suitable and reliable source for future studies to improve resistance to abiotic stress during the germination of barley.

Bioinformatics and pathway enrichment analysis identified hub genes and potential biomarker for gastric cancer prognosis.

Introduction: Gastric cancer is one of the most common cancers in the world. This study aimed to identify genes, biomarkers, and metabolic pathways affecting gastric cancer using bioinformatic analysis and meta-analysis. Methods: Datasets containing gene expression profiles of tumor lesions and adjacent non-tumor mucosa samples were downloaded. Common differentially expressed genes between data sets were selected to identify hub genes and further analysis. Gene Expression Profiling and Interactive Analyses (GEPIA) and the Kaplan-Meier method were used to further validate the expression level of genes and plot the overall survivalcurve, respectively. Results and disscussion: KEGG pathway analysis showed that the most important pathway was enriched in ECM-receptor interaction. Hub genes includingCOL1A2, FN1, BGN, THBS2, COL5A2, COL6A3, SPARC and COL12A1 wereidentified. The top interactive miRNAs including miR-29a-3p, miR-101-3p,miR-183-5p, and miR-15a-5p targeted the most hub genes. The survival chart showed an increase in mortality in patients with gastric cancer, which shows the importance of the role of these genes in the development of the disease and can be considered candidate genes in the prevention and early diagnosis of gastric cancer.

Identification of Key Genes and Potential Pathways Associated with Mastitis Induced by E. coli.

Mastitis is one of the most important diseases of dairy cattle. It is an infectious disease leading to an inflammatory reaction in the cow's mammary gland. Escherichia coli is one of the common bacteria which induce mastitis in cows. The aim of this study was to identify key genes and potential pathways associated with mastitis induced by E. coli in dairy cattle using bioinformatics analysis. The gene expression profile of ten samples including five adjacent tissues from a quarter infected with Escherichia coli and five tissues from a healthy quarter of dairy cattle was assessed using GEO2R. Gene ontology and pathway analysis were performed using bioinformatics tools. A total of 156 differentially expressed genes were detected which 95 genes were upregulated and 61 genes were downregulated in adjacent tissue of quarter infected compared with healthy tissue. Cellular oxidant detoxification and oxidation-reduction process were the most significant biological process terms in gene ontology analysis. The most important pathways of DEGs were the biosynthesis of amino acids, p53 signaling pathway, and Metabolic pathways. Three important modules were identified and their path enrichment analysis was performed. There are 10 core genes, among which SOD2, COL1A2, COL3A1, POSTN, ALDH18A1, and CBS may be the main genes associated with mastitis, which can be considered as candidate genes in the prevention and carly diagnosis program of mastitis.

Transcriptome Analysis of Breast Muscle Reveals Pathways Related to Protein Deposition in High Feed Efficiency of Native Turkeys.

Feed efficiency is important due to the high cost of food, which accounts for about 70% of the total cost of a turkey breeding system. Native poultry are an important genetic resource in poultry breeding programs. This study aimed to conduct a global transcriptome analysis of native male turkeys which have been phenotyped for high and low feed efficiency. Feed efficiency traits were recorded during the experimental period. After slaughter, the three most efficient and three least efficient male turkeys were selected for RNA-Seq analysis. A total of 365 genes with different expressions in muscle tissue were identified between turkeys with a high feed efficiency compared to turkeys with a low feed efficiency. In the pathway analysis of up-regulated genes, major pathways included the "metabolism of glycine, serine, and threonine"; the "adipocytokine signaling pathway" and the "biosynthesis of amino acids". In the pathway analysis of down-regulated genes, the major pathways included "dorso-ventral axis formation" and "actin cytoskeleton regulation". In addition, gene set enrichment analyses were performed, which showed that high feed efficiency birds exhibit an increased expression of genes related to the biosynthesis of amino acids and low feed efficiency birds an increased expression of genes related to the immune response. Furthermore, functional analysis and protein network interaction analysis revealed that genes including GATM, PSAT1, PSPH, PHGDH, VCAM1, CD44, KRAS, SRC, CAV3, NEDD9, and PTPRQ were key genes for feed efficiency. These key genes may be good potential candidates for biomarkers of feed efficiency in genetic selection in turkeys.

Oncogenic Role of Connective Tissue Growth Factor Is Associated with Canonical TGF-ß Cascade in Colorectal Cancer.

TGF-ß signaling pathways promote tumour development and control several downstream genes such as CTGF and MMPs. This study aimed to investigate the association between CTGF and MMP-1 mRNA expressions with clinicopathological status and survival rate in colorectal cancer patients. We investigated expression levels of CTGF and MMP-1 genes in paraffin-embedded tumours and adjacent normal tissue blocks (ADJ) by Real Time-PCR. Then, the expression of Smad2 and Smad4 proteins in the TGF-ß canonical pathway was evaluated by immunohistochemistry. Finally, the correlation between CTGF, MMP-1, and the canonical TGF-ß-signalling pathway with the clinicopathological features was investigated. Expression levels of MMP-1and CTGF were higher in tumours compared with adjacent normal tissues. Overexpression levels of MMP-1 and CTGF were associated with lymph node metastasis, distant metastasis, tumour histopathological grading, advanced stage, and poor survival (p < 0.05). Additionally, a significant association between the upregulation of MMP-1 and tumour location was noted. Upregulation of Smad2 and Smad4 proteins were also significantly correlated with lymph node metastasis, distant metastasis, advanced stage, and poor survival (p < 0.0001). This study showed that canonical TGF-ß signalling regulates both CTGF and MMP-1 expression and CRC progression. Moreover, TGF-ß signalling and its downstream genes could be used as novel biomarkers and novel approaches for targeted therapy in CRC.

A linkage between effectual genes in progression of CRC through canonical and non-canonical TGF-ß signaling pathways.

Different molecular signaling pathways have been involved in the incidence and progression of CRC. We aimed to examine the correlation between eight candidate genes, including TFGß, SMAD2, SMAD4, RhoA, EGFR, MAP2K1, MTA1, and LEF1 in the progression of colorectal cancer (CRC) and their association with clinicopathological variables and CRC patients prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) analysis 2-ΔΔct, were performed to assess the expression of eight genes in 64 and 122 patients with CRC, respectively and 20 normal samples were added for verification. We showed a positive correlation between SMAD2 and MAP2K1 (r = 0.337, P < 0.001), MAP2K1 and LEF1 (r = 0.187, P = 0.03), SMAD4 and RhoA (r = 0.214, P = 0.01) and as well, a negative correlation between SMAD2 and TGFß (r = - 0.197, P = 0.02), and RhoA and LEF1 (r = - 0.180, P = 0.04) in tumor tissues. A decrease in RhoA mRNA expression was associated with the advanced TNM stage (P = 0.01), while the EGFR and SMAD2 mRNA expression upregulated in advanced stages (P = 0.03, P = 0.03), respectively. Also, an increase in EGFR and SMAD4 protein expression was significantly associated with the advanced TNM stage (P = 0.000) (P = .002), respectively. Perceiving the connections between canonical and non-canonical Transforming growth factor (TGF-ß) signaling pathway along with the epidermal growth factor receptor (EGFR) and WNT cascades may trigger the development of novel approaches for CRC prediction.

Identification of hub genes involved in apparent metabolizable energy of chickens.

Feed efficiency is one of the most economically significant traits in a breeding program. Apparent metabolizable energy is the most used method to evaluate energy utilization for feed efficiency. The purpose of this study was to identify candidate genes of chickens with divergent apparent metabolizable energy by bioinformatics analysis. The gene expression profile of duodenal of the highest and lowest apparent metabolizable energy-ranked birds were analyzed. Differentially expressed genes were picked out using GEO2R tool. Gene ontology and pathway analysis were performed using bioinformatics tools. Cytoscape software was used to visualize protein-protein network. There were 201 DEGs, including 99 up-regulated genes enriched in metabolic pathways, Cellular senescence and Focal adhesion, and 102 down-regulated genes enriched in metabolic pathways, Regulation of actin cytoskeleton, Neuroactive ligand-receptor interaction, Calcium signaling pathway and Focal adhesion. Two important modules were detected and pathway enrichment analysis showed that they were mainly associated with Focal adhesion, Regulation of actin cytoskeleton and RNA transport. Fifteen hub genes were selected and among them, ITGA8, CDC42 and GSK3B might be the core genes related to apparent metabolizable energy of chickens. These hub genes can be used as biomarkers for apparent metabolizable energy and feed efficiency in breeding program of chickens.

Fast school closures correspond with a lower rate of COVID-19 incidence and deaths in most countries.

School closures have been used as one of the main nonpharmaceutical interventions to overcome the spread of SARS-CoV-2. Different countries use this intervention with a wide range of time intervals from the date of the first confirmed case or death. This study aimed to investigate whether fast or late school closures affect the cumulative number of COVID-19 cases or deaths. A worldwide population-based observational study has been conducted and a range of attributes were weighted using 10 attribute weighting models against the normalized number of infected cases or death in the form of numeric, binominal and polynomial labels. Statistical analysis was performed for the most weighted and the most common attributes of all types of labels. By the end of March 2021, the school closure data of 198 countries with at least one COVID-19 case were available. The days before the first school closure were one of the most weighted factors in relation to the normalized number of infected cases and deaths in numeric, binomial, and quartile forms. The average of days before the first school closure in the lowest quartile to highest quartile of infected cases (Q1, Q2, Q3 and Q4) was -6.10 [95% CI, -26.5 to 14.2], 9.35 [95% CI, 2.16 to 16.53], 17.55 [95% CI, 5.95 to 29.15], and 16.00 [95% CI, 11.69 to 20.31], respectively. In addition, 188 countries reported at least one death from COVID-19. The average of the days before the first school closure in the lowest quartile of death to highest quartile (Q1, Q2, Q3 and Q4) was -49.4 [95% CI, -76.5 to -22.3], -10.34 [95% CI, -30.12 to 9.44], -18.74 [95% CI, -32.72 to -4.77], and -12.89 [95% CI, -27.84 to 2.06], respectively. Countries that closed schools faster, especially before the detection of any confirmed case or death, had fewer COVID-19 cases or deaths per million of the population on total days of involvement. It can be concluded that rapid prevention policies are the main determinants of the countries' success.

Insights into the Role of Matrix Metalloproteinases in Precancerous Conditions and in Colorectal Cancer.

Colorectal cancer (CRC) is the third and second cancer for incidence and mortality worldwide, respectively, and is becoming prevalent in developing countries. Most CRCs derive from polyps, especially adenomatous polyps, which can gradually transform into CRC. The family of Matrix Metalloproteinases (MMPs) plays a critical role in the initiation and progression of CRC. Prominent MMPs, including MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, MMP-14, and MMP-21, have been detected in CRC patients, and the expression of most of them correlates with a poor prognosis. Moreover, many studies have explored the inhibition of MMPs and targeted therapy for CRC, but there is not enough information about the role of MMPs in polyp malignancy. In this review, we discuss the role of MMPs in colorectal cancer and its pathogenesis.

Increased Expression of VANGL1 is Predictive of Lymph Node Metastasis in Colorectal Cancer: Results from a 20-Gene Expression Signature.

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I-IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression.

In silico analysis of different signal peptides to discover a panel of appropriate signal peptides for secretory production of Interferon-beta 1b in Escherichia coli.

Signal peptides (SPs) are one of the most important factors for suitable secretion of the recombinant  heterologous proteins in Escherichia coli (E. coli). The objective of this study was to identify a panel of signal peptides (among the 90 biologically active SPs) required for the secretory production of interferon-beta 1b (IFN-beta 1b) recombinant protein into the periplasmic space of E. coli host. In the initial step, after predicting the accurate locations of the cleavage sites of signal peptides and their discrimination scores using SignalP 4.1 server, 31 SPs were eliminated from further analysis because their discrimination scores were less than 0.5 or their cleavage sites were inappropriately located. Therefore, only 59 SPs could be theoretically applied to secrete IFN-beta 1b into the periplasmic space of E. coli. The physico-chemical and the solubility properties, which are necessary parameters for selecting appropriate SPs, were predicted using ProtParam and SOLpro servers using the 59 remaining signal peptides. The final subcellular localization of IFN-beta 1b in combination with different SPs was predicted using ProtComB server. Consequently, according to the ranking of 59  confirmed SPs, the obtained results revealed that SPs Flagellar P-ring protein (flgI), Glucan 1,3-beta-glucosidase I/II (EXG1) and outer membrane protein C (OmpC) were theoretically the most potent and desirable SPs for secretion of recombinant IFN-beta 1b into the periplasmic space of E. coli. For further studies in the future, the experimental investigations on the obtained results will be considered.