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81.
Suniba Shuaib Simranjeet Singh Narang Deepti Goyal Bhupesh Goyal 《Journal of cellular biochemistry》2019,120(10):17935-17950
The β-sheet breaker (BSB) peptides interfere with amyloid fibril assembly and used as therapeutic agents in the treatment of Alzheimer's disease (AD). In this regard, a simple yet effective in silico screening methodology was applied in the present study to evaluate a potential 867 pentapeptide library based on known BSB peptide, LPFFD, for destabilizing Aβ42 protofibrils. The molecular docking based virtual screening was used to filter out pentapeptides having binding affinities stronger than LPFFD. In the next step, binding free energies of the top 10 pentapeptides were evaluated using the MM-PBSA method. The residue-wise binding free energy analysis reveals that two pentapeptides, PVFFE, and PPFYE, bind to the surface of Aβ42 protofibril and another pentapeptide, PPFFE, bind in the core region of Aβ42 protofibril. By employing molecular dynamics simulation as a post filter for the top-hit peptides from MM-PBSA, the pentapeptides, PPFFE, PVFFE, and PPFYE, have been identified as potential BSB peptides for destabilizing Aβ42 protofibril structure. The conformational microstate analysis, a significant decrease in the β-sheet content of Aβ42 protofibril, a loss in the total number of hydrogen bonds in Aβ42 protofibril, Asp23-Lys28 salt bridge destabilization and analysis of the free energy surfaces highlight Aβ42 protofibril structure destabilization in presence of pentapeptides. Among three top-hit pentapeptides, PPFFE displayed the most potent Aβ42 protofibril destabilization effect that shifted the energy minima toward lowest value of β-sheet content as well as lowest number of hydrogen bonds in Aβ42 protofibril. The in silico screening workflow presented in the study highlight an alternative tool for designing novel peptides with enhanced BSB ability as potential therapeutic agents for AD. 相似文献
82.
Genetic variations play a crucial role in differential phenotypic outcomes. Given the complexity in establishing this correlation and the enormous data available today, it is imperative to design machine-readable, efficient methods to store, label, search and analyze this data. A semantic approach, FROG: “FingeRprinting Ontology of Genomic variations” is implemented to label variation data, based on its location, function and interactions. FROG has six levels to describe the variation annotation, namely, chromosome, DNA, RNA, protein, variations and interactions. Each level is a conceptual aggregation of logically connected attributes each of which comprises of various properties for the variant. For example, in chromosome level, one of the attributes is location of variation and which has two properties, allosomes or autosomes. Another attribute is variation kind which has four properties, namely, indel, deletion, insertion, substitution. Likewise, there are 48 attributes and 278 properties to capture the variation annotation across six levels. Each property is then assigned a bit score which in turn leads to generation of a binary fingerprint based on the combination of these properties (mostly taken from existing variation ontologies). FROG is a novel and unique method designed for the purpose of labeling the entire variation data generated till date for efficient storage, search and analysis. A web-based platform is designed as a test case for users to navigate sample datasets and generate fingerprints. The platform is available at http://ab-openlab.csir.res.in/frog. 相似文献
83.
Himanshi Narang Nagesh Bhat S. K. Gupta S. Santra R. K. Choudhary S. Kailash Malini Krishna 《Molecular and cellular biochemistry》2009,324(1-2):85-91
Mitogen-activated protein kinases have been shown to respond to various stimuli including cytokines, mitogens and gamma irradiation, leading to cell proliferation, differentiation, or death. The duration of their activation determines the specificity of response to each stimulus in various cells. In this study, the crucial intracellular kinases, ERK, JNK, and p38 kinase involved in cell survival, death, or damage and repair were examined for their activity in RAW 264.7 cells at various time points after irradiation with 2 Gy doses of proton ions or X-rays. This is the first report that shows that the MAPK signaling induced after heavy ion or X-ray exposure is not the same. Unlike gamma irradiation, there was prolonged but marginal activation of prosurvival ERK pathway and significant activation of proapoptotic p38 pathway in response to high LET radiation. 相似文献
84.
Jagriti Narang Nidhi Chauhan Shikha Pundir C. S. Pundir 《Bioprocess and biosystems engineering》2013,36(11):1545-1554
A method is described for the construction of a highly sensitive amperometric sensor for the detection of tyrosine, employing a magnetic nanoparticles-zinc oxide/zinc hexacyanoferrate (Fe3O4NP-ZnO/ZnHCF) hybrid film electrodeposited on the surface of a Pt electrode as working electrode. The sensor is based on electrocatalytic mechanism initiated by electrochemical oxidation of the reduced form of the hybrid film at +0.2 V vs. Ag/AgCl followed by completion of chemical oxidation of tyrosine. The sensor showed optimum response within 2 s at pH 2. The working/linear range of the sensor was 0.02–2.76 mM with a detection limit of 4 μM. The sensor measured tyrosine level in serum, a potential biomarker of phenylketonuria. The working electrode lost only 5 % of its initial activity, when stored at 4 °C, after its regular use over a period of 100 days. 相似文献
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86.
Schistosomes are blood-dwelling parasitic helminths which produce eggs in order to facilitate transmission. Intestinal schistosomes lay eggs in the mesenteries, however, it is unclear how their eggs escape the vasculature to exit the host. Using a murine model of infection, we reveal that Schistosoma mansoni exploits Peyer''s Patches (PP) gut lymphoid tissue as a preferential route of egress for their eggs. Egg deposition is favoured within PP as a result of their more abundant vasculature. Moreover, the presence of eggs causes significant vascular remodeling leading to an expanded venule network. Egg deposition results in a decrease in stromal integrity and lymphoid cellularity, including secretory IgA producing lymphocytes, and the focal recruitment of macrophages. In mice lacking PP, egg excretion is significantly impaired, leading to greater numbers of ova being entrapped in tissues and consequently, exacerbated morbidity. Thus, we demonstrate how schistosomes directly facilitate transmission from the host by targeting lymphoid tissue. For the host, PP-dependency of egg egress represents a trade-off, as limiting potentially life-threatening morbidity is balanced by loss of PP structure and perturbed PP IgA production. 相似文献
87.
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89.
Synthesis of human insulin gene. Part I. Development of reversed-phase chromatography in the modified triester method. Its application in the rapid and efficient synthesis of eight deoxyribooligonucleotides fragments constituting human insulin A DNA. 总被引:10,自引:7,他引:3 下载免费PDF全文
Preparative reversed-phase thin layer chromatography on silanized silica-gel (RP-2 and RP-18) has been developed to purify triester deoxyribooligonucleotides prepared by the modified triester method. The effectiveness of this technique has been demonstrated in the rapid synthesis of eight pure deoxyribooligonucleotides constituting the sequence of human insulin A DNA. The sequence of each of the deoxyribooligonucleotides was confirmed by the two-dimensional mobility-shift method of finger-printing. 相似文献
90.
S. K. Narang T. A. Klein O. P. Perera José Bento Lima Amazonia Toda Tang 《Biochemical genetics》1993,31(1-2):97-112
Allozyme and mitochondrial DNA (mtDNA) restriction studies were undertaken to determine the extent of genetic divergence among
field populations ofAnopheles albitarsis in Brazil. Two sympatric species,An. deaneorum andAn. marajoara, were identified in collections from Costa Marques (CM), Rondonia. Genetic evidence includes (1) the presence of two types
of individuals, each with diagnostic allelic clusters (forHad-1, Pgi-1, Pep-1, Mpi-1, andIdh-1), (2) a deficiency of heterozygotes, and (3) characteristic mtDNA haplotypes. In addition, two allopatric cryptic species
ofAn. marajoara were identified, one from Iguape (An. marajoara form IG), Sao Paulo state, and the other from the Island of Marajo (An. marajoara form MA). Though form IG and form-MA resemble form CM in wing spot morphology, they differ from it in diagnostic allozymes
and mtDNA haplotypes.An. marajoara form CM had a higher variability (mean heterozygosity,H=0.22, and percentage of polymorphic loci,P=66.7) than did form IG and form MA (H=0.08 in both, andP=25.0 and 33.3, respectively). Form MA and form IG are genetically more similar to each other than both are to form CM. Based
on wing morphology, estimates ofF statistics, and genetic similarities, we propose thatAn. albitarsis in Brazil is a species complex. It comprises at least two morphologically distinguishable species: (1)An. deaneorum (currently one taxon) and (2) theAn. marajoara species complex, which further consists of at least three cryptic forms,marajoara form MA,marajoara form IG, andmarajoara form CM.
The views of the authors do not purport to reflect the position of the Department of the Army or the Department of Defense
of the United States.
This research was conducted when the senior author was on the staff of the USDA-ARS Laboratory in Gainesville, Florida. 相似文献