Bengtsonaguilar8041
New High-Performance Computing architectures have been recently developed for commercial central processing unit (CPU). Yet, that has not improved the execution time of widely used bioinformatics applications, like BLAST+. This is due to a lack of optimization between the bases of the existing algorithms and the internals of the hardware that allows taking full advantage of the available CPU cores. To optimize the new architectures, algorithms must be revised and redesigned; usually rewritten from scratch. BIX 02189 in vitro BLVector adapts the high-level concepts of BLAST+ to the x86 architectures with AVX-512, to harness their capabilities. A deep comprehensive study has been carried out to optimize the approach, with a significant reduction in time execution. BLVector reduces the execution time of BLAST+ when aligning up to mid-size protein sequences (∼750 amino acids). The gain in real scenario cases is 3.2-fold. When applied to longer proteins, BLVector consumes more time than BLAST+, but retrieves a much larger set of results. BLVector and BLAST+ are fine-tuned heuristics. Therefore, the relevant results returned by both are the same, although they behave differently specially when performing alignments with low scores. Hence, they can be considered complementary bioinformatics tools.
Acute myocardial infarction (AMI), characterized by an event of myocardial necrosis, is a common cardiac emergency worldwide. However, the genetic mechanisms of AMI remain largely elusive.
A genome-wide association study dataset of AMI was obtained from the CARDIoGRAMplusC4D project. A transcriptome-wide association study (TWAS) was conducted using the FUSION tool with gene expression references of the left ventricle and whole blood. Significant genes detected by TWAS were subjected to Gene Ontology (GO) enrichment analysis. Then the TWAS results of AMI were integrated with mRNA expression profiling to identify common genes and biological processes. Finally, the identified common genes were validated by RT-qPCR analysis.
TWAS identified 1,050 genes for the left ventricle and 1,079 genes for whole blood. Upon comparison with the mRNA expression profile, 4 common genes were detected, including HP (P
= 1.22 × 10
, P
= 4.98 × 10
); CAMP (P
= 2.48 × 10
, P
= 2.36 × 10
); TNFAIP6 (P
= 1.90 × 10
, P
= 3.46 × 10
); and ARG1 (P
= 8.35 × 10
, P
= 4.93 × 10
). Functional enrichment analysis of the genes identified by TWAS detected multiple AMI-associated biological processes, including autophagy of mitochondrion (GO 0000422) and mitochondrion disassembly (GO 0061726).
This integrative study of TWAS and mRNA expression profiling identified multiple candidate genes and biological processes for AMI. Our results may provide a fundamental clue for understanding the genetic mechanisms of AMI.
This integrative study of TWAS and mRNA expression profiling identified multiple candidate genes and biological processes for AMI. Our results may provide a fundamental clue for understanding the genetic mechanisms of AMI.Rabbits are one of the most used experimental animals for investigating the mechanisms of human cardiovascular disease and lipid metabolism because they are phylogenetically closer to human than rodents (mice and rats). Cholesterol-fed wild-type rabbits were first used to study human atherosclerosis more than 100 years ago and are still playing an important role in cardiovascular research. Furthermore, transgenic rabbits generated by pronuclear microinjection provided another means to investigate many gene functions associated with human disease. Because of the lack of both rabbit embryonic stem cells and the genome information, for a long time, it has been a dream for scientists to obtain knockout rabbits generated by homologous recombination-based genomic manipulation as in mice. This obstacle has greatly hampered using genetically modified rabbits to disclose the molecular mechanisms of many human diseases. The advent of genome editing technologies has dramatically extended the applications of experimental animals including rabbits. In this review, we will update genetically modified rabbits, including transgenic, knock-out, and knock-in rabbits during the past decades regarding their use in cardiovascular research and point out the perspectives in future.Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal inflammatory disease with limited treatment options of corticosteroids, sinus surgery, or both. CRSwNP is frequently associated with allergic rhinitis and asthma, but the molecular mechanisms underlying CRSwNP inflammation are not completely understood. We obtained four gene expression profiles (GSE136825, GSE36830, GSE23552, and GSE72713) from four Gene Expression Omnibus (GEO), which collectively included 65 nasal polyp samples from CRSwNP patients and 54 nasal mucosal samples from healthy controls. Using an integrated analysis approach, we identified 76 co-differentially expressed genes (co-DEGs, including 45 upregulated and 31 downregulated) in CRSwNP patients compared with the healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses identified the terms including immune effector process, leukocyte migration, regulation of the inflammatory response, Staphylococcus aureus infection, and cytokine-cytokine receptor interaction. protein-protein interaction (PPI) network analysis and real-time quantitative PCR (RT-qPCR) showed that 7 genes might be crucial in CRSwNP pathogenesis. Repurposing drug candidates (Alfadolone, Hydralazine, SC-560, Iopamidol, Iloprost, etc) for CRSwNP treatment were identified from the Connectivity Map (CMap) database. Our results suggest multiple molecular mechanisms, diagnostic biomarkers, potential therapeutic targets, and new repurposing drug candidates for CRSwNP treatment.In Southern and Southeastern Brazil, there is a germline pathogenic variant with incomplete penetrance located in the oligomerization domain of TP53, c.1010G>A (p.Arg337His). Due to a founder effect, the variant is present in 0.3% of the general population of the region. Recently, this variant was identified in 4.4 and 8.9% of two apparently unselected, single center case series of Brazilian lung adenocarcinoma (LUAD) patients from the Southeastern and Central regions of the country, respectively. In the present study, our aim was to examine TP53 c.1010G>A allele and genotype frequencies in LUAD samples obtained from patients diagnosed in Southern Brazil. A total of 586 LUAD samples (tumor DNA) recruited from multiple centers in the region were tested, and the mutant allele was identified using TaqMan® assays in seven cases (7/586, 1.2%) which were submitted to next generation sequencing analyses for confirmation. Somatic EGFR mutations were more frequent in TP53 c.1010G>A carriers than in non-carriers (57.1 vs. 17.6%, respectively). Further studies are needed to confirm if TP53 c.1010G>A is a driver in LUAD carcinogenesis and to verify if there is a combined effect of EGFR and germline TP53 c.1010G>A. Although variant frequency was higher than observed in the general population, it is less than previously reported in LUAD patients from other Brazilian regions. Additional data, producing regional allele frequency information in larger series of patients and including cost-effectiveness analyses, are necessary to determine if TP53 c.1010G>A screening in all Brazilian LUAD patients is justified.Previous studies have reported an important role of c-kit in embryogenesis and adulthood. Activation of the SCF/KIT signal transduction pathway is customarily linked to cell proliferation, migration and survival thus influence hematopoiesis, pigmentation, and spermatogenesis. The role of c-kit in the liver is controversial, it is however argued that it is a double-edged sword in liver regeneration and diseases. First, liver c-kit+ cells, including oval cells, bile epithelial cells, and part of hepatocytes, participate in liver tissue repair by regenerating target cells according to the type of liver injury. At the same time, c-kit+ mast cells, act as immature progenitors in circulation, playing a critical role in liver fibrosis. Furthermore, c-kit is also a proto-oncogene. Notably, c-kit overexpression regulates gastrointestinal stromal tumors. Various studies have explored on c-kit and hepatocellular carcinoma, nevertheless, the intricate roles of c-kit in the liver are largely understudied. Herein, we extensively summarize previous studies geared toward providing hints for future clinical and basic research.
Atherosclerosis is a risk factor for cardiovascular diseases. However, the roles of Circular RNAs (circRNAs) in atherosclerosis is unknown. Our study aimed to explore the effects of circ_0065149 in the pathogenesis of atherosclerosis.
The expression of circ_0065149 ox-LDL-induced in human umbilical vein endothelial cells (HUVECs) was assessed by RT-PCR. Cell viability, lactate dehydrogenase leakage, apoptosis, invasion, and migration were assessed in HUVECs. Dual luciferase reporter system was carried out to determine the interaction between miR-330-5p and circ_0065149.
Our results showed that circ_0065149 was significantly lower in the ox-LDL-induced HUVECs. Overexpression of circ_0065149 promoted the cell viability and inhibited the apoptosis of ox-LDL-induced HUVECs. Overexpression of circ_0065149 also promoted the migration and invasion of ox-LDL-induced HUVECs. The expression of miR-330-5p was inhibited by overexpression of circ_0065149. Furthermore, circ_0065149 overexpression significantly inhibited the expressions of nuclear NF-κBp65 and suppressed the production of TNF-α, IL-6, and IL-1β in ox-LDL-induced HUVECs, which was rescued by the miR-330-5p mimic.
These findings suggest that circ_0065149 plays an important role in the proliferation, apoptosis, and inflammatory response of HUVECs via targeting miR-330-5p.
These findings suggest that circ_0065149 plays an important role in the proliferation, apoptosis, and inflammatory response of HUVECs via targeting miR-330-5p.[This corrects the article DOI 10.3389/fgene.2020.589076.].Parkinson's means Parkinson's disease, a chronic degenerative disease of central nervous system. The main area which is affected by this disease is motor system. Since it firstly founded by James Parkinson in his 1817 publication, nowadays, people still have lots of questions about this disease. This review mainly summarizes the epigenetics of Parkinson's. DNA methylation is one of the epigenetic mechanisms of Parkinson's. During the development of disease, global hypomethylation, and hypermethylation happen in different areas of patients. Another epigenetic mechanism is histone modification. People believe that some metals can induce Parkinson's disease by modulating epigenetic mechanisms. This review summarizes the relationships between different metals and Parkinson's disease. However, the specific roles of most metals in epigenetics are still unknown, which need further research.Accelerated development of novel CRISPR/Cas9-based genome editing techniques provides a feasible approach to introduce a variety of precise modifications in the mammalian genome, including introduction of multiple edits simultaneously, efficient insertion of long DNA sequences into specific targeted loci as well as performing nucleotide transitions and transversions. Thus, the CRISPR/Cas9 tool has become the method of choice for introducing genome alterations in livestock species. The list of new CRISPR/Cas9-based genome editing tools is constantly expanding. Here, we discuss the methods developed to improve efficiency and specificity of gene editing tools as well as approaches that can be employed for gene regulation, base editing, and epigenetic modifications. Additionally, advantages and disadvantages of two primary methods used for the production of gene-edited farm animals somatic cell nuclear transfer (SCNT or cloning) and zygote manipulations will be discussed. Furthermore, we will review agricultural and biomedical applications of gene editing technology.
