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Parkinson's disease (PD) is a neurodegenerative disease caused by aging, environmental and genetic factors, and many susceptibility genes have been found to increase the risk for PD. Lin28a, an RNA binding protein, is expressed prominently in neural progenitor cells. The expression of Lin28a is decreased gradually with neural differentiation and is implicated in oncogenesis, glucose metabolism, neurogenesis, and neurogliogenesis. However, few genetic studies have explored the association between rare variants of the LIN28A gene and PD yet. Our study recruited 3,879 PD patients and 2,931 controls, and they were divided into two cohorts, including the EOPD & FPD cohort and the LOPD cohort, separately sequenced by whole-exome sequencing and whole-genome sequencing. We found nine rare nonsynonymous variants in the coding region of the LIN28A gene, but the rare variants of this gene were not enriched in PD patients in both cohorts. Thence, our study did not support the association between the LIN28A gene and the PD risk in the Chinese mainland population.
Childhood obesity is triggered by a complex interplay of environmental, genetic, and epigenetic factors; however, the molecular mechanisms behind this disease are not completely elucidated. Thus, the aim of this study was to investigate molecular mechanisms involved in childhood obesity by implementing a systems biology approach.
Experimentally validated and computationally predicted genes related to childhood obesity were downloaded from DisGeNET database. A protein-protein interaction (PPI) network was constructed using the STRING database and analyzed at Cytoscape web-tool. Hub-bottleneck genes and functional clusters were identified through CytoHubba and MCODE plugins, respectively. Functional enrichment analyses were performed based on Gene Ontology terms and KEGG Pathways.
The DisGeNET search retrieved 191 childhood obesity-related genes. The resulting PPI network contained 12 hub-bottleneck genes (INS, LEP, STAT3, POMC, ALB, TNF, BDNF, CAT, GCG, PPARG, VEGFA, and ADIPOQ) and 4 functional clusters, with cluster 1 showing the highest interaction score. Genes at this cluster were enriched at inflammation, carbohydrate, and lipid metabolism pathways. With exception of POMC, all hub-bottleneck genes were found in cluster 1, which contains highly connected genes that possibly play key roles in obesity-related pathways.
Our systems biology approach revealed a set of highly interconnected genes associated with childhood obesity, providing comprehensive information regarding genetic and molecular factors involved in the pathogenesis of this disease.
Our systems biology approach revealed a set of highly interconnected genes associated with childhood obesity, providing comprehensive information regarding genetic and molecular factors involved in the pathogenesis of this disease.Alternative splicing (AS) selects different alternative splice sites and produces a variety of transcripts with different exon/intron combinations, which may result in multiple protein isoforms. The splicing signals include cis-elements and RNA structures; however, the mechanisms of AS regulation in plants have yet to be elucidated. Previous studies have shown that in Platanus acerifolia, the FLOWERING LOCUS T (FT) homolog PaFT has a unique and complex AS pattern, in which most of the splice forms of PaFT involve the first and/or second intron, and the FD homolog PaFDL1 produces two transcripts via AS, whereas the other FT homolog PaFTL is not regulated by AS. In this study, the regulatory mechanism of the AS of PaFT was demonstrated to be conserved in different plant species. To define the distribution of the AS regulatory signals, the intron-swap, site-directed mutagenesis of alternative splice sites, and deletion experiment were performed. For the PaFT gene, all the signals that regulate the AS of the first intron were located within this intron, while the usage of the first alternative splice site in the second intron was determined by the first intron. Marimastat molecular weight Meanwhile, the AS of PaFDL1 might be co-regulated by exons and the first intron. Additionally, the first alternative splice site and adjacent region in PaFT intron 1 might contain cis-elements and/or RNA structures that affect the use of the other sites. This study had provided a deeper insight into the distribution of AS signals in plants, namely the AS signals of different splice sites might exist in the intron where the sites were present, and might also be distributed in exons or other introns.BLAST searches previously carried out against Xenopus genome databases, using the cloned X. laevis cytosolic sulfotransferase 1 (SULT1) cDNA sequence, revealed the presence of more than a dozen members of this gene family. Among them, 11 genes composed of five sets, four pairs and a triplet, were homeologous genes in the X. laevis allotetraploid genome consisting of S- and L-subgenomes (≥83% identity within a set). Phylogenetic and synteny analyses of tetrapod SULT1 genes demonstrated that X. laevis possessed six subfamilies, four of which were related to mammalian SULT1 gene subfamilies, while two were ectothermic vertebrate-specific and amphibian-specific SULT1 gene subfamilies. Five sets of homeologous SULT1 genes were located as a gene cluster, and showed S-subgenome-biased gene expression patterns. Acetylation levels of histone H3 at lysine 9 and H4 were also higher in the homeologous SULT1 genes on the S-subgenome than those on the L-subgenome, however, methylation levels of histone H3 at lysine 9 and DNA methylation levels showed no correlation with their transcript levels. In conclusion, histone modifications such as acetylation may be a key factor that controls the S-subgenome-biased expression of the homeologous SULT1 genes.Zearalenone (ZEN), a common non-steroidal estrogenic mycotoxin of the Fusarium genus, is one of the most frequent and powerful contaminant of grains and cereal products representing a serious threat for people and livestock health. In fact, ZEN causes cytotoxicity and genotoxicity in a variety of cell types at least in part through binding to estrogen receptors (ERs). The main pathways through which ZEN induces such effects remain, however, elusive. In particular, how the mycotoxin causes DNA damage, dysregulates DNA repair mechanisms, changes epigenome of targeted cells and, not least, affects chromatin conformation and non-coding RNA (ncRNA), is unclear. In the present paper, following extensive review of the literature about such ZEN effects and our own experience in studying the effects of this compound on reproductive processes, we propose that increased production of reactive oxygen species (ROS) and consequently oxidative stress (OS) are central in ZEN genotoxicity. Besides to shed light on the action mechanisms of the mycotoxin, this notion might help to develop effective strategies to counteract its deleterious biological effects.
Evidence suggests that schizophrenia (SCZ), schizoaffective disorder (SAD) and bipolar disorder (BPD) share genetic risk variants. ZNF804A gene has been associated with these disorders in different populations. GWAS and candidate gene studies have reported association between the rs1344706 A allele with SCZ, SAD and BPD in European and Asian populations. In Mexican patients, no studies have specifically analyzed ZNF804A gene variants with these disorders. The aim of the study was to analyze the rs1344706 and identify common and rare variants in a targeted region of the ZNF804A gene in Mexican patients with SCZ, BPD and SAD compared with a control group.
We genotyped the rs1344706 in 228 Mexican patients diagnosed with SCZ, SAD and BPD, and 295 controls. Also, an additional sample of 167 patients with these disorders and 170 controls was analyzed to identify rare and common variants using the Sanger-sequence analysis of a targeted region of ZNF804A gene.
Association analysis of rs1344706 observed a higher frequency of A allele in the patients compared with the control group; however, did not show statistical differences after Bonferronís correction (χ2=5.3, p=0.0208). In the sequence analysis, we did not identify rare variants; however, we identified three common variants rs3046266, rs1366842 and rs12477430. A comparison of the three identified variants between patients and controls did not show statistical differences (p>0.0125). Finally, haplotype analysis did not show statistical differences between SCZ, SAD and BPD and controls.
Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders.
Our findings did not support the evidence suggesting that ZNF804A gene participates in the etiology of SCZ, SAD and BPD. Future studies are needed in a larger sample size to identify the effect of this gene in psychiatric disorders.
Current guidelines recommend offering epidemiological treatment to asymptomatic contacts of early syphilis. This is on the expectation that up to 60% of sexual contacts of patients with syphilis will be infected. However, the evidence for this figure is sparse. We performed a systematic review and meta-analysis, to estimate the proportion of sexual contacts of syphilis that are infected with syphilis.
Two electronic databases (Medline and Embase) were reviewed in March 2021, to identify studies that reported rates of infection in sexual contacts of syphilis.
Of 3,051 Embase and 1,828 Medline articles identified, 32 were included in the meta-analysis. In total 36,397 contacts were tested. The proportion of contacts infected varied across the studies, ranging from 10.7% to 97.5%, resulting in considerable heterogeneity (I
=98.5%). Pooling the studies gave an estimated proportion of infected contacts of 32.6% (95% confidence interval 26.2% - 39.7%).
The risk of infection in sexual contacts of syphilis reported in the literature is highly variable, with a pooled estimate of 32.6%. This will help guide decisions regarding epidemiological treatment of sexual contacts of patients with syphilis. These decisions are increasingly important in this era of antibiotic resistance, with increasing emphasis being placed on antimicrobial stewardship.
The risk of infection in sexual contacts of syphilis reported in the literature is highly variable, with a pooled estimate of 32.6%. This will help guide decisions regarding epidemiological treatment of sexual contacts of patients with syphilis. These decisions are increasingly important in this era of antibiotic resistance, with increasing emphasis being placed on antimicrobial stewardship.The assessment of skin sensitisation is a key requirement in all regulated sectors, with the European Union's regulation of cosmetic ingredients being most challenging, since it requires quantitative skin sensitisation assessment based on new approach methodologies (NAMs). To address this challenge, an in-depth and harmonised understanding of NAMs is fundamental to inform the assessment. Therefore, we compiled a database of NAMs, and in vivo (human and local lymph node assay) reference data. Here, we expanded this database with 41 substances highly relevant for cosmetic industry. These structurally different substances were tested in six NAMs (Direct Peptide Reactivity Assay, KeratinoSens™, human Cell Line Activation Test, U-SENS™, SENS-IS, Peroxidase Peptide Reactivity Assay). Our analysis revealed that the substances could be tested without technical limitations, but were generally overpredicted when compared to reference results. Reasons for this reduced predictivity were explored through pairwise NAM comparisons and association of overprediction with hydrophobicity.
Website: https://www.selleckchem.com/products/marimastat.html
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