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排序方式: 共有116条查询结果,搜索用时 15 毫秒
1.
Shuilian Luo Yuhang Chen Rui He Yujun Shi Li Su 《Biochemical and biophysical research communications》2018,495(1):607-613
Objective
The decreased expression of muscle-specific microRNA-1 (miR-1) has been found in many cardiovascular diseases and is considered to contribute to heart failure (HF). Here we investigated the role of miR-1 in myocardium protection by infusion of miR-1 in a cardiac global miRNA-deficient mouse.Methods
We generated a cardiac-selective miRNA-deficient mouse by crossing Dicerflox/flox mice with mice expressing tamoxifen-inducible Cre recombinase under the control of a mouse αMHC promoter. When Dicer gene was removed following tamoxifen injection, the mice were treated with micrONTM mmu-miR-1a-3p agomir (agomir-1). The mice were subjected to echocardiography measurement, and the heart tissue specimens were stained with hematoxylin and eosin (H&E) and Sirius red. Terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling assay and Ki67 immunofluorescence were used to determine apoptosis and proliferation.Results
Dicer deletion resulted in extensive decrease in cardiac miRNAs in the mice. In echocardiography, the mice developed rapid and dramatic left ventricular enlargement. In histology, apparent cardiomyocyte hypertrophy, myofiber disarray, ventricular fibrosis, inflammatory infiltration, and severe ventricular remodeling were exhibited. When the mice were treated with agomir-1, they did not show any significant abnormalities in heart structure and histology in response to Dicer ablation.Conclusion
The proper expression of miRNAs plays vital roles in the maintenance of heart histology and function. Among these miRNAs, miR-1 is critical to inhibit myocyte hypertrophy and extracellular matrix deposition, thereby preventing cardiac remodeling in cardiac-selective Dicer deficient mice. 相似文献2.
N. Sundaraganesan G. Elango C. Meganathan B. Karthikeyan M. Kurt 《Molecular simulation》2013,39(9):705-713
Vibrational frequencies and geometrical parameters of 4-piperidone (4-PID) in the ground state have been calculated by using the Hartree–Fock (HF) and density functional methods (B3LYP) with 6-311++G(d,p) and 6-311+G(3df,2p) basis sets. These methods are proposed as a tool to be applied in the structural characterisation of 4-PID (C5H9NO). The title molecule has C s point group symmetry, thus providing useful support in the interpretation of experimental IR and Raman data. The DFT-B3LYP/6-311+G(3df,2p) calculations have been found more reliable than the ab initio HF/6-311++G(d,p) calculations for the vibrational study of 4-PID. The calculated highest occupied molecular orbital and lowest unoccupied molecular orbital energies show that charge transfer occurs within the molecule. The theoretical spectrograms for FT-IR and FT-Raman spectra of the title molecule have been constructed. 相似文献
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4.
Vinaya Mulkareddy Susan B. Racette Andrew R. Coggan Linda R. Peterson 《生物化学与生物物理学报:疾病的分子基础》2019,1865(4):735-740
Heart failure with reduced ejection fraction (HFrEF) is a deadly and disabling disease. A key derangement contributing to impaired exercise performance in HFrEF is decreased nitric oxide (NO) bioavailability. Scientists recently discovered the inorganic nitrate pathway for increasing NO. This has advantages over organic nitrates and NO synthase production of NO. Small studies using beetroot juice as a source of inorganic nitrate demonstrate its power to improve exercise performance in HFrEF. A larger-scale trial is now underway to determine if inorganic nitrate may be a new arrow for physicians' quiver of HFrEF treatments. 相似文献
5.
Molecular Mechanics Calculations of Proteins. Comparison of Different Energy Minimization Strategies
Inge Thøger Christensen Flemming Steen jørgensen 《Journal of biomolecular structure & dynamics》2013,31(3):473-488
Abstract A general strategy for performing energy minimization of proteins using the SYBYL molecular modelling program has been developed. The influence of several variables including energy minimization procedure, solvation, dielectric function and dielectric constant have been investigated in order to develop a general method, which is capable of producing high quality protein structures. Avian pancreatic polypeptide (APP) and bovine pancreatic phospholipase A2 (BP PLA2) were selected for the calculations, because high quality X-ray structures exist and because all classes of secondary structure are represented in the structures. The energy minimized structures were evaluated relative to the corresponding X-ray structures. The overall similarity was checked by calculating RMS distances for all atom positions. Backbone conformation was checked by Ramachandran plots and secondary structure elements evaluated by the length on hydrogen bonds. The dimensions of active site in BP PLA2 is very dependent on electrostatic interactions, due to the presence of the positively charged calcium ion. Thus, the distances between calcium and the calcium-coordinating groups were used as a quality index for this protein. Energy minimized structures of the trimeric PLA2 from Indian cobra (N.n.n. PLA2) were used for assessing the impact of protein-protein interactions. Based on the above mentioned criteria, it could be concluded that using the following conditions: Dielectric constant ? = 4 or 20; a distance dependent dielectric function and stepwise energy minimization, it is possible to reproduce X-ray structures very accurately without including explicit solvent molecules. 相似文献
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7.
Ferro N Bultinck P Gallegos A Jacobsen HJ Carbo-Dorca R Reinard T 《Phytochemistry》2007,68(2):237-250
An computational-biostatistical approach, supported by ab initio optimizations of auxin-like molecules, was used to find biologically meaningful relationships between quantum chemical variables and fresh bioassay's data. It is proven that the auxin-like recognition requires different molecular assembling states. We suggest that the carboxyl group is not the determining factor in explaining the biological auxin-like conduct. The biological effects depends essentially on the chemical condition of the ring system. The aim to find active molecules (quantum objects) via statistical grouping-analysis of molecular quantum similarity measures was verified by bioactivity assays. Next, this approach led to the discovery of a non-carboxylated active auxin-like molecule (2,6-dibromo-phenol). This is the first publication on structure activity relationship of auxin-like molecules, which relies on highly standardized bioassays of different auxins screened in parallel as well as analysed by multi-dimensional scaling. 相似文献
8.
Johnson EC Malito E Shen Y Pentelute B Rich D Florián J Tang WJ Kent SB 《Journal of molecular biology》2007,373(3):573-586
The human immunodeficiency virus 1 (HIV-1) protease (PR) is an aspartyl protease essential for HIV-1 viral infectivity. HIV-1 PR has one catalytic site formed by the homodimeric enzyme. We chemically synthesized fully active HIV-1 PR using modern ligation methods. When complexed with the classic substrate-derived inhibitors JG-365 and MVT-101, the synthetic HIV-1 PR formed crystals that diffracted to 1.04- and 1.2-A resolution, respectively. These atomic-resolution structures revealed additional structural details of the HIV-1 PR's interactions with its active site ligands. Heptapeptide inhibitor JG-365, which has a hydroxyethylamine moiety in place of the scissile bond, binds in two equivalent antiparallel orientations within the catalytic groove, whereas the reduced isostere hexapeptide MVT-101 binds in a single orientation. When JG-365 was converted into the natural peptide substrate for molecular dynamic simulations, we found putative catalytically competent reactant states for both lytic water and direct nucleophilic attack mechanisms. Moreover, free energy perturbation calculations indicated that the insertion of catalytic water into the catalytic site is an energetically favorable process. 相似文献
9.
V. Lyju Jose Ravi P. More Thulasi Appoothy A. Sha Arun 《Systematic and applied microbiology》2017,40(3):160-170
Rumen houses a plethora of symbiotic microorganisms empowering the host to hydrolyze plant lignocellulose. In this study, NGS based metagenomic approach coupled with bioinformatic analysis was employed to gain an insight into the deconstruction of lignocellulose by carbohydrate-active enzymes (CAZymes) in Indian crossbred Holstein-Friesian cattle. Cattle rumen metagenomic DNA was sequenced using Illumina-MiSeq and 1.9 gigabases of data generated with an average read length of 871 bp. Analysis of the assembled sequences by Pfam-based Carbohydrate-active enzyme Analysis Toolkit identified 17,164 putative protein-encoding CAZymes belonging to different families of glycoside hydrolases (7574), glycosyltransferases (5185), carbohydrate-binding modules (2418), carbohydrate esterases (1516), auxiliary activities (434) and polysaccharide lyases (37). Phylogenetic analysis of putative CAZymes revealed that a significant proportion of CAZymes were contributed by bacteria belonging to the phylum Bacteroidetes (40%), Firmicutes (30%) and Proteobacteria (10%). The comparative analysis of HF cross rumen metagenome with other herbivore metagenomes indicated that Indian crossbred cattle rumen is endowed with a battery of CAZymes that may play a central role in lignocellulose deconstruction. The extensive catalog of enzymes reported in our study that hydrolyzes plant lignocellulose biomass, can be further explored for the better feed utilization in ruminants and also for different industrial applications. 相似文献
10.
The development of heart failure (HF) is a complex process that can be initiated by multiple etiologies. Identifying common functional modules associated with HF is a challenging task. Here, we developed a systems method to identify these common functional modules by integrating multiple expression profiles, protein interactions from four species, gene function annotations, and text information. We identified 1439 consistently differentially expressed genes (CDEGs) across HF with different etiologies by applying three meta-analysis methods to multiple HF-related expression profiles. Using a weighted human interaction network constructed by combining interaction data from multiple species, we extracted 60 candidate CDEG modules. We further evaluated the functional relevance of each module by using expression, interaction network, functional annotations, and text information together. Finally, five functional modules with significant biological relevance were identified. We found that almost half of the genes in these modules are hubs in the weighted network, and that these modules can accurately classify HF patients from healthy subjects. We also identified many significantly enriched biological processes that contribute to the pathophysiology of HF, including two new ones, RNA splicing and vesicle-mediated protein transport. In summary, we proposed a novel framework to analyze common functional modules related to HF with different etiologies. Our findings provide important insights into the complex mechanism of HF. Further biological experimentations should be required to validate these novel biological processes. 相似文献