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41.
Amit Kumar Solanki Abhishek Acharya Himani Kaushik Bharti Bhatia Lalit C Garg 《Bioinformation》2021,17(6):628
Beta toxin from Clostridium perfringens after being secreted in gut is capable of causing necrotic enteritis in humans and several other animal species and does not respond to routinely used antibiotics. Therefore, there is a need to design an effective inhibitor for the Clostridium perfringens beta toxin (CPB) using cutting edge drug discovery technologies. Hence, potential CPB inhibitors were identified using computer aided screening of compounds from the ZINC database. Further, we document the molecular docking analysis of Clostridium perfringens beta toxin model (that revealed 4 binding pockets, A-D) with the identified potential inhibitors. We show that ZINC291192 [N-[(1-methylindol-3-yl) methyl eneamino]-7,10-dioxabicyclo[4.4.0]deca-2,4,11-triene-8- carboxamide] has optimal binding features with calculated binding energy of -10.38 kcal/mol and inhibition constant of 24.76 nM for further consideration. 相似文献
42.
Bo Hu Xiaolu Ma Peiyao Fu Qiman Sun Weiguo Tang Haixiang Sun Zhangfu Yang Mincheng Yu Jian Zhou Jia Fan Yang Xu 《基因组蛋白质组与生物信息学报(英文版)》2021,19(6):913
The aim of this study was to identify novel prognostic mRNA and microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) using methods in systems biology. Differentially expressed mRNAs, miRNAs, and long non-coding RNAs (lncRNAs) were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas (TCGA) database. Subsequently, a prognosis-associated mRNA co-expression network, an mRNA–miRNA regulatory network, and an mRNA–miRNA–lncRNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis. Seven prognosis-associated mRNA co-expression modules were obtained by analyzing these differentially expressed mRNAs. An expression module including 120 mRNAs was significantly correlated with HCC patient survival. Combined with patient survival data, several mRNAs and miRNAs, including CHST4, SLC22A8, STC2, hsa-miR-326, and hsa-miR-21 were identified from the network to predict HCC patient prognosis. Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC. Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, leading to the identification of an integrated mRNA–miRNA–lncRNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival. 相似文献
43.
Michael R. Heaven Anthony W. Herren Daniel L. Flint Natasha L. Pacheco Jiangtao Li Alice Tang Fatima Khan James E. Goldman Brett S. Phinney Michelle L. Olsen 《Molecular & cellular proteomics : MCP》2022,21(1):100180
Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAPTg;Gfap+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAPTg;Gfap+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAPTg;Gfap+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAPTg;Gfap+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAPTg;Gfap+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap+ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAPTg;Gfap+/R236H mice. Last, to determine whether the findings in GFAPTg;Gfap+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAPTg;Gfap+/R236H mice. 相似文献
44.
Anna?LewandowskaEmail author Zenon?Foltynowicz 《The International Journal of Life Cycle Assessment》2004,9(3):180-186
Goal, Scope and Background This paper is the second part of the publication which is devoted to comparative LCA analysis of the industrial pumps. The
previous paper deals with the methodological aspects concerning quality assessment and forms an independent work. This paper
uses practically only the methodological suggestions made there. The main aim of the presented study is to make a comparison
between the industrial pumps which are based on two different technologies. The Life Cycle Assessment method is used to check
whether the differences of the manufacturing processes influence the level of the potential environmental impact during the
whole life cycle of the analysed products.
Methods The Life Cycle Assessment is carried out using the Ecoindicator99 method. Additionally, an extensive quality analysis of the
LCA study is made (Part I). To make the process of an identification of the data easier and faster, they are assigned to a
special data documentation form. To ensure the credibility of the LCA results different methods of interpretation are used.
Results and Discussion The LCA analysis shows clear superiority of the pumps manufactured using modern technology. It seems that this superiority
results not only from the differences in the emissions, but also from different characteristics of effectiveness in the usage
stage. Thanks to the uncertainty analysis, each LCA result is provided with the range of uncertainty.
Conclusions The LCA results are supported by different techniques of interpretation: the sensitivity-, the contribution-, the comparative-,
the discernability- and the uncertainty analysis. There is strong evidence of the superiority of the pumps based on the modern
technology.
Recommendations and Outlook The main source of the environmental impact in the case of pumps is the usage stage and the consumption of energy. That is
why it should be the main area to improve. The LCA results show that actions taken in the usage stage and energy consumption
can lead to a considerable reduction of the environmental impacts. 相似文献
45.
Nobuhiko?NaritaEmail author Yoshifumi?Nakahara Mamoru?Morimoto Ryosuke?Aoki Shigeru?Suda 《The International Journal of Life Cycle Assessment》2004,9(6):355-359
In 1998, the Japan’s Ministry of Economy, Trade, and Industry (METI) launched a five-year national project entitled ‘Development
of Life Cycle Impact Assessment for Products’ (commonly known as ‘the LCA Project’). The purpose of the project is to develop
common LCA methodology as well as a highly reliable database that can be shared in Japan. Activities over these five years
have resulted in the supply of LCI data on some 250 products. Industrial associations voluntarily provided data. The results
of these activities are currently being made available on the Internet on a trial basis in the form of an LCA database. In
addition, a method entitled ‘Life-cycle Impact assessment Method based on Endpoint modeling (LIME)’ was developed. It is expected
that these results will be widely used in Japan in the future. This paper presents an outline of the results of the research
and development that has been conducted in the LCA Project in Japan. 相似文献
46.
Fernandez S Katsuyama AM Kashiwabara AY Madeira AM Durham AM Gruber A 《FEMS microbiology letters》2004,238(1):183-188
This study reports the development and characterization of 151 sequence characterized amplified region (SCAR) markers for the seven Eimeria species that infect the domestic fowl. From this set, 84 markers are species-specific and 67 present partial specificity. The complete nucleotide sequence was derived for all markers, revealing the presence of micro- and minisatellite repetitive units in 22 SCARs, with up to five distinct repeat units being observed per marker. Only 15 markers showed significant hits in similarity searches against public sequence databases, thus confirming their anonymous and non-coding character. Finally, a relational database of the markers (the Eimeria SCARdb) was developed and made available on the Internet, providing a valuable resource of SCAR markers that can be useful for molecular diagnosis, and also for epizootiological, genetic variability and genome mapping studies. 相似文献
47.
Vector NTI, a balanced all-in-one sequence analysis suite 总被引:6,自引:0,他引:6
Vector NTI is a well-balanced desktop application integrated for molecular sequence analysis and biological data management. It has a centralised database and five application modules: Vector NTI, AlignX, BioAnnotator, ContigExpress and GenomBench. In this review, the features and functions available in this software are examined. These include database management, primer design, virtual cloning, alignments, sequence assembly, 3D molecular viewer and internet tools. Some problems encountered when using this software are also discussed. It is hoped that this review will introduce this software to more molecular biologists so they can make better-informed decisions when choosing computational tools to facilitate their everyday laboratory work. This tool can save time and enhance analysis but it requires some learning on the user's part and there are some issues that need to be addressed by the developer. 相似文献
48.
Database searching by flexible protein structure alignment 总被引:1,自引:0,他引:1
We have recently developed a flexible protein structure alignment program (FATCAT) that identifies structural similarity, at the same time accounting for flexibility of protein structures. One of the most important applications of a structure alignment method is to aid in functional annotations by identifying similar structures in large structural databases. However, none of the flexible structure alignment methods were applied in this task because of a lack of significance estimation of flexible alignments. In this paper, we developed an estimate of the statistical significance of FATCAT alignment score, allowing us to use it as a database-searching tool. The results reported here show that (1) the distribution of the similarity score of FATCAT alignment between two unrelated protein structures follows the extreme value distribution (EVD), adding one more example to the current collection of EVDs of sequence and structure similarities; (2) introducing flexibility into structure comparison only slightly influences the sensitivity and specificity of identifying similar structures; and (3) the overall performance of FATCAT as a database searching tool is comparable to that of the widely used rigid-body structure comparison programs DALI and CE. Two examples illustrating the advantages of using flexible structure alignments in database searching are also presented. The conformational flexibilities that were detected in the first example may be involved with substrate specificity, and the conformational flexibilities detected in the second example may reflect the evolution of structures by block building. 相似文献
49.
White SH 《Protein science : a publication of the Protein Society》2004,13(7):1948-1949
The rate of membrane protein (MP) structure determination has been examined for the 18-year period following the publication of the first high-resolution crystal structure. The growth is solidly exponential, but lags behind the rate for soluble proteins during the equivalent time period. 相似文献
50.
A new hybrid approach to predict subcellular localization of proteins by incorporating gene ontology 总被引:3,自引:0,他引:3
Based on the recent development in the gene ontology and functional domain databases, a new hybridization approach is developed for predicting protein subcellular location by combining the gene product, functional domain, and quasi-sequence-order effects. As a showcase, the same prokaryotic and eukaryotic datasets, which were studied by many previous investigators, are used for demonstration. The overall success rate by the jackknife test for the prokaryotic set is 94.7% and that for the eukaryotic set 92.9%. These are so far the highest success rates achieved for the two datasets by following a rigorous cross-validation test procedure, suggesting that such a hybrid approach may become a very useful high-throughput tool in the area of bioinformatics, proteomics, as well as molecular cell biology. The very high success rates also reflect the fact that the subcellular localization of a protein is closely correlated with: (1). the biological objective to which the gene or gene product contributes, (2). the biochemical activity of a gene product, and (3). the place in the cell where a gene product is active. 相似文献