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71.
S. Srivastava S. B. Lal D. C. Mishra U. B. Angadi K. K. Chaturvedi S. N. Rai A. Rai 《Algorithms for molecular biology : AMB》2016,11(1):27
Background
Protein structure comparison play important role in in silico functional prediction of a new protein. It is also used for understanding the evolutionary relationships among proteins. A variety of methods have been proposed in literature for comparing protein structures but they have their own limitations in terms of accuracy and complexity with respect to computational time and space. There is a need to improve the computational complexity in comparison/alignment of proteins through incorporation of important biological and structural properties in the existing techniques.Results
An efficient algorithm has been developed for comparing protein structures using elastic shape analysis in which the sequence of 3D coordinates atoms of protein structures supplemented by additional auxiliary information from side-chain properties are incorporated. The protein structure is represented by a special function called square-root velocity function. Furthermore, singular value decomposition and dynamic programming have been employed for optimal rotation and optimal matching of the proteins, respectively. Also, geodesic distance has been calculated and used as the dissimilarity score between two protein structures. The performance of the developed algorithm is tested and found to be more efficient, i.e., running time reduced by 80–90 % without compromising accuracy of comparison when compared with the existing methods. Source codes for different functions have been developed in R. Also, user friendly web-based application called ProtSComp has been developed using above algorithm for comparing protein 3D structures and is accessible free.Conclusions
The methodology and algorithm developed in this study is taking considerably less computational time without loss of accuracy (Table 2). The proposed algorithm is considering different criteria of representing protein structures using 3D coordinates of atoms and inclusion of residue wise molecular properties as auxiliary information.72.
Annamária Nádor Rajiv Sinha Árpád Magyari Sampat K. Tandon Zsófia Medzihradszky Edit Babinszki Edit Thamó-Bozsó Zoltán Unger Ashish Singh 《Palaeogeography, Palaeoclimatology, Palaeoecology》2011,299(1-2):1-14
Four drill cores and a clay pit section have been examined in the southern part of the Körös plain to understand the history and controls on alluvial sedimentation for the last ~ 40 ka. Four facies groups were identified, such as channel, channel margin, floodplain and floodbasin with seven distinctive facies. Magnetic susceptibility and mineralogy have further characterized the sedimentary facies indicating shifts in humidity conditions, variations in sediment flux and pedogenesis. Detailed pollen analysis of a 7.5 m thick clayey succession indicated climatic variability within the MIS 3 period. The spatial distribution of the different facies allowed outlining alluvial architecture of the study area. Three depositional units composed of various facies were identified based on OSL and radiocarbon data. These packages correspond to three major phases of channel activity: (F-I) pre-LGM period (> 30 ka to 24 ka), (F-II) post-LGM interstadial (18–16 ka), and (F-III) Late Glacial < 15 ka to ~ 10 ka). The pre-LGM and post-LGM “interstadial” phases are characterized by meandering river patterns, while the Late Glacial fluvial activity is characterized by a braided system in the area. Higher sediment supply feeding this braided river was probably caused by neotectonic uplift of the southern margin of the basin, documented by a significant stratigraphic gap between 25 and 14 ka. 相似文献
73.
Glucose deprivation induced upregulation of phosphoenolpyruvate carboxykinase modulates virulence in Leishmania donovani 下载免费PDF全文
Savita Saini Ayan Kumar Ghosh Ruby Singh Sushmita Das Kumar Abhishek Ajay Kumar Sudha Verma Abhishek Mandal Abul Hasan Sardar Bidyut Purkait Ashish Kumar Kislay Kumar Sinha Pradeep Das 《Molecular microbiology》2016,102(6):1020-1042
Various physiological stimuli trigger the conversion of noninfective Leishmania donovani promastigotes to the infective form. Here, we present the first evidence of the effect of glucose starvation, on virulence and survival of these parasites. Glucose starvation resulted in a decrease in metabolically active parasites and their proliferation. However, this was reversed by supplementation of gluconeogenic amino acids. Glucose starvation induced metacyclogenesis and enhanced virulence through protein kinase A regulatory subunit (LdPKAR1) mediated autophagy. Glucose starvation driven oxidative stress upregulated the antioxidant machinery, culminating in increased infectivity and greater parasitic load in primary macrophages. Interestingly, phosphoenolpyruvate carboxykinase (LdPEPCK), a gluconeogenic enzyme, exhibited the highest activity under glucose starvation to regulate growth of L. donovani by alternatively utilising amino acids. Deletion of LdPEPCK (Δpepck) decreased virulent traits and parasitic load in primary macrophages but increased autophagosome formation in the mutant parasites. Furthermore, Δpepck parasites failed to activate the Pentose Phosphate Pathway shunt, abrogating NADPH/NADP+ homoeostasis, conferring increased susceptibility towards oxidants following glucose starvation. In conclusion, this study showed that L. donovani undertakes metabolic rearrangements via gluconeogenesis under glucose starvation for acquiring virulence and its survival in the hostile environment. 相似文献
74.
Bingxi Lei Yutao Huang Zhiwei Zhou Yiying Zhao Ashish Jung Thapa Wenpeng Li Wangqing Cai Yuefei Deng 《Journal of cellular biochemistry》2019,120(4):6698-6708
Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR-181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real-time polymerase chain reaction results showed that the expression of miR-181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR-181a, and miR-181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR-181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR-181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR-181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR-181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR-181a, and SIRT1 may serve as potential therapeutic targets for glioma. 相似文献
75.
Tammy Y. Carter Swetha Gadwala Ashish B. Chougule Anh P. N. Bui Alex C. Sanders Raghothama Chaerkady Nathaly Cormier Robert N. Cole Jeffrey H. Thomas 《Genesis (New York, N.Y. : 2000)》2019,57(6)
Src64 is required for actomyosin contraction during cellularization of the Drosophila embryonic blastoderm. The mechanism of actomyosin ring constriction is poorly understood even though a number of cytoskeletal regulators have been implicated in the assembly, organization, and contraction of these microfilament rings. How these cytoskeletal processes are regulated during development is even less well understood. To investigate the role of Src64 as an upstream regulator of actomyosin contraction, we conducted a proteomics screen to identify proteins whose expression levels are controlled by src64. Global levels of actin are reduced in src64 mutant embryos. Furthermore, we show that reduction of the actin isoform Actin 5C causes defects in actomyosin contraction during cellularization similar to those caused by src64 mutation, indicating that a relatively high level of Actin 5C is required for normal actomyosin contraction and furrow canal structure. However, reduction of Actin 5C levels only slows down actomyosin ring constriction rather than preventing it, suggesting that src64 acts not only to modulate actin levels, but also to regulate the actomyosin cytoskeleton by other means. 相似文献
76.
Amy Li K. Campbell S. Lal Y. Ge A. Keogh P. S. Macdonald P. Lau John Lai W. A. Linke J. Van der Velden A. Field B. Martinac M. Grosser Cristobal dos Remedios 《Biophysical reviews》2022,14(1):369
In this review, we present our current understanding of peripartum cardiomyopathy (PPCM) based on reports of the incidence, diagnosis and current treatment options. We summarise opinions on whether PPCM is triggered by vascular and/or hormonal causes and examine the influence of comorbidities such as preeclampsia. Two articles published in 2021 strongly support the hypothesis that PPCM may be a familial disease. Using large cohorts of PPCM patients, they summarised the available genomic DNA sequence data that are expressed in human cardiomyocytes. While PPCM is considered a disease predominately affecting the left ventricle, there are data to suggest that some cases also involve right ventricular failure. Finally, we conclude that there is sufficient evidence to warrant an RNAseq investigation and that this would be most informative if performed at the cardiomyocytes level rather than analysing genomic DNA from the peripheral circulation. Given the rarity of PPCM, the combined resources of international human heart tissue biobanks have assembled 30 ventricular tissue samples from PPCM patients, and we are actively seeking to enlarge this patient base by collaborating with human heart tissue banks and research laboratories who would like to join this endeavour. 相似文献
77.
Qian Jiang Stacey Arnold Tiffany Heanue Krishna?Praneeth Kilambi Betty Doan Ashish Kapoor Albee?Yun Ling Maria?X. Sosa Moltu Guy Qingguang Jiang Grzegorz Burzynski Kristen West Seneca Bessling Paola Griseri Jeanne Amiel Raquel?M. Fernandez Joke?B.G.M. Verheij Robert?M.W. Hofstra Salud Borrego Stanislas Lyonnet Isabella Ceccherini Jeffrey?J. Gray Vassilis Pachnis Andrew?S. McCallion Aravinda Chakravarti 《American journal of human genetics》2015,96(4):581-596
Innervation of the gut is segmentally lost in Hirschsprung disease (HSCR), a consequence of cell-autonomous and non-autonomous defects in enteric neuronal cell differentiation, proliferation, migration, or survival. Rare, high-penetrance coding variants and common, low-penetrance non-coding variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret proto-oncogene (RET). We used a genome-wide association (220 trios) and replication (429 trios) study to reveal a second non-coding variant distal to RET and a non-coding allele on chromosome 7 within the class 3 Semaphorin gene cluster. Analysis in Ret wild-type and Ret-null mice demonstrates specific expression of Sema3a, Sema3c, and Sema3d in the enteric nervous system (ENS). In zebrafish embryos, sema3 knockdowns show reduction of migratory ENS precursors with complete ablation under conjoint ret loss of function. Seven candidate receptors of Sema3 proteins are also expressed within the mouse ENS and their expression is also lost in the ENS of Ret-null embryos. Sequencing of SEMA3A, SEMA3C, and SEMA3D in 254 HSCR-affected subjects followed by in silico protein structure modeling and functional analyses identified five disease-associated alleles with loss-of-function defects in semaphorin dimerization and binding to their cognate neuropilin and plexin receptors. Thus, semaphorin 3C/3D signaling is an evolutionarily conserved regulator of ENS development whose dys-regulation is a cause of enteric aganglionosis. 相似文献
78.
79.
RR Pandey A Srivastava R Malasoni A Naqvi A Jain JP Maikhuri S Paliwal G Gupta AK Dwivedi 《Bioorganic & medicinal chemistry letters》2012,22(17):5735-5738
A series of twenty two derivatives of 3-(1-alkyl/aminoalkyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one and their 2-methylene derivatives were synthesized from naturally abundant cinchonine (I). Tartarate salts of these compounds were prepared and evaluated for spermicidal activity. The most active compounds (24, 27, 34, 36, and 38) showing potent spermicidal activity were further evaluated against different strains of Trichomonas vaginalis, for antimicrobial activity, in HeLa cell lines for cytotoxicity and against Lactobacillus jensenii for eco-safety. The tartarate of 3-(1-pentyl-3-vinyl-piperidin-4-yl)-1-(quinolin-4-yl)-propan-1-one (27) was found to be more active than N-9 in spermicidal activity. 相似文献