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71.
Chaitra Prabhakara Rashmi Godbole Parijat Sil Sowmya Jahnavi Shah-e-Jahan Gulzar Thomas S. van Zanten Dhruv Sheth Neeraja Subhash Anchal Chandra Akshatha Shivaraj Patricia Panikulam Ibrahim U Vijay Kumar Nuthakki Theja Parassini Puthiyapurayil Riyaz Ahmed Ashaq Hussain Najar Sai Manoz Lingamallu Snigdhadev Das Bhagyashri Mahajan Praveen Vemula Sandip B. Bharate Parvinder Pal Singh Ram Vishwakarma Arjun Guha Varadharajan Sundaramurthy Satyajit Mayor 《PLoS pathogens》2021,17(7)
Many viruses utilize the host endo-lysosomal network for infection. Tracing the endocytic itinerary of SARS-CoV-2 can provide insights into viral trafficking and aid in designing new therapeutic strategies. Here, we demonstrate that the receptor binding domain (RBD) of SARS-CoV-2 spike protein is internalized via the pH-dependent CLIC/GEEC (CG) endocytic pathway in human gastric-adenocarcinoma (AGS) cells expressing undetectable levels of ACE2. Ectopic expression of ACE2 (AGS-ACE2) results in RBD traffic via both CG and clathrin-mediated endocytosis. Endosomal acidification inhibitors like BafilomycinA1 and NH4Cl, which inhibit the CG pathway, reduce the uptake of RBD and impede Spike-pseudoviral infection in both AGS and AGS-ACE2 cells. The inhibition by BafilomycinA1 was found to be distinct from Chloroquine which neither affects RBD uptake nor alters endosomal pH, yet attenuates Spike-pseudovirus entry. By screening a subset of FDA-approved inhibitors for functionality similar to BafilomycinA1, we identified Niclosamide as a SARS-CoV-2 entry inhibitor. Further validation using a clinical isolate of SARS-CoV-2 in AGS-ACE2 and Vero cells confirmed its antiviral effect. We propose that Niclosamide, and other drugs which neutralize endosomal pH as well as inhibit the endocytic uptake, could provide broader applicability in subverting infection of viruses entering host cells via a pH-dependent endocytic pathway. 相似文献
72.
1. Use of electron transport system (ETS) activity in a single leg for estimating whole‐body ETS activity was explored in the noble crayfish Astacus astacus. Oxygen consumption and ETS activity of the whole body and of a walking leg were measured in different‐sized animals at 10 °C to compare the size scaling of oxygen consumption, whole‐body ETS activity and the ratio of whole‐body ETS activity to oxygen consumption (ETS/R). 2. Electron transport system activity of a leg and the ratio of ETS activity of a whole crayfish to that of a leg were correlated with wet mass of animals. Therefore, metabolic potential in whole noble crayfish can be estimated on the basis of the measured ETS activity in a single leg and crayfish mass. This approach provides a valuable tool for determining metabolic characteristics of crayfish without killing them. 3. Mass‐specific oxygen consumption decreased with increasing wet mass, while ETS activity of whole crayfish showed no significant correlation with wet mass. Both oxygen consumption and ETS activity correlated significantly with protein mass. 4. The increase in ETS/R with increasing wet mass of the noble crayfish indicates that small organisms exploit a greater proportion of their metabolic potential for standard metabolism than larger ones. This is the first report on ETS/R in crayfish. 相似文献
73.
Wajid Waheed Bhat Surrinder K. Lattoo Satiander Rana Sumeer Razdan Niha Dhar Rekha S. Dhar Ram A. Vishwakarma 《In vitro cellular & developmental biology. Plant》2012,48(3):295-303
Picrorhiza kurroa Royle ex. Benth. is a medicinal herb of immense therapeutic value with restricted geographic distribution. Efficient plant regeneration via direct organogenesis and Agrobacterium tumefaciens-mediated genetic transformation was developed for this plant. Multiple shoot bud induction was achieved from leaf explants cultured in Gamborg??s B5 medium containing 3?% (w/v) sucrose, 3?mg/l kinetin and 1?mg/l indole-3-butyric acid. More than 90?% of leaf explants formed shoot buds leading to whole plant regeneration. An Agrobacterium-mediated genetic transformation protocol was developed using A. tumefaciens strain GV3101 harboring binary vector pCAMBIA1302 containing the green fluorescent protein and hygromycin phosphotransferase genes. Leaf explants precultured for 2?d were the most suitable for co-cultivation with Agrobacterium and transformation efficiency was enhanced with 200???M acetosyringone. Putative transformants were selected using media containing 15?mg/l hygromycin. Transformation was verified by detection of the green fluorescent protein using fluorescence microscopy and by polymerase chain reaction. Approximately 56?% of the explants were transformed with an average of 3.4?±?0.4 transgenic plantlets per explant. An efficient regeneration and transformation protocol thus developed enabling a fresh perspective of metabolic engineering in P. kurroa using an Agrobacterium-mediated transformation. This is the first report of direct organogenesis from leaf explants and genetic transformation of P. kurroa. 相似文献
74.
Lohar MV Mundada R Bhonde M Padgaonkar A Deore V Yewalkar N Bhatia D Rathos M Joshi K Vishwakarma RA Kumar S 《Bioorganic & medicinal chemistry letters》2008,18(12):3603-3606
We herein report the design and synthesis of furoquinoline based novel molecules (16-36) and their in vitro multiple targeted inhibitory potency against PI3K/Akt phosphorylation and mTOR using cell based and cell-free kinase assay. In particular, compound 23 in addition to PI3K-mTOR inhibitory potency, it has shown potent inhibition of hypoxia-induced accumulation of HIF-1alpha protein in U251-HRE cell line. The inhibitory activities of compound 23 were confirmed by Western blot analysis, using human non-small cell lung carcinoma H-460 cell line and glioblastoma U251 cell lines. 相似文献
75.
Loknath Gidijala Roel AL Bovenberg Paul Klaassen Ida J van der Klei Marten Veenhuis Jan AKW Kiel 《BMC biotechnology》2008,8(1):29
Background
β-Lactams like penicillin and cephalosporin are among the oldest known antibiotics used against bacterial infections. Industrially, penicillin is produced by the filamentous fungus Penicillium chrysogenum. Our goal is to introduce the entire penicillin biosynthesis pathway into the methylotrophic yeast Hansenula polymorpha. Yeast species have the advantage of being versatile, easy to handle and cultivate, and possess superior fermentation properties relative to filamentous fungi. One of the fundamental challenges is to produce functionally active enzyme in H. polymorpha. 相似文献76.
Abstract: An early Cenozoic shark fauna, comprising at least 16 taxa, is described from Paleocene sedimentary rocks on the South Island of New Zealand. Although representing a remote Southern Hemisphere location, the fauna includes forms closely comparable to contemporary species from the Northern Hemisphere, in addition to the new species Chlamydoselachus keyesi and Centroselachus goordi. Comparison with closely related extant species suggests the fauna may be interpreted as a deep water one, typical of the outer continental shelf and upper slope. However, after palaeogeography, sedimentology and mineralogy of the enclosing rock, and the nature of similar faunas from elsewhere are taken into consideration, the fauna is interpreted to have occupied a mid‐shelf environment. 相似文献
77.
Ibidapo S. Williams Prashant Joshi Linda Gatchie Mohit Sharma Naresh K. Satti Ram A. Vishwakarma Bhabatosh Chaudhuri Sandip B. Bharate 《Bioorganic & medicinal chemistry letters》2017,27(16):3683-3687
Inhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC50 of ~0.2 μM in Sacchrosomes? and CYP1B1-expressing live human cells. However, compound 3j which inhibited both CYP1A1 and CYP1B1 with an IC50 of ~0.9 µM, using the same systems, also potently antagonized B[a]P-mediated induction of AhR signaling in yeast (IC50, 1.5 µM), fully protected human cells from B[a]P toxicity and completely reversed cisplatin resistance in human cells that overexpress CYP1B1 by restoring cisplatin’s cytotoxicity. Molecular modeling studies were performed to rationalize the observed potency and selectivity of enzyme inhibition by compounds 3j and 3n. 相似文献
78.
A mathematical model has been developed for predicting the performance and simulation of a packed bed immobilized enzyme reactor performing lactose hydrolysis, which follows Michaelis‐Menten kinetics with competitive product (galactose) inhibition. The performance characteristics of a packed bed immobilized enzyme reactor have been analyzed taking into account the effects of various diffusional phenomena like axial dispersion and external mass transfer limitations. The model design equations are then solved by Galerkin's method and orthogonal collocation on finite elements. The effects of external mass transfer and axial dispersion have been studied and their effects were shown to reduce the external effectiveness factor. The effects of product inhibition have been investigated at different operating conditions correlated at different regimes using dimensionless moduli (St, γ, θ, Da)1). The product inhibition was shown to reduce the substrate conversion, and, additionally, to decrease the effectiveness factor when Da > Daxo, however, it increases the effectiveness factor when Da < Daxo. The effectiveness factor is found to be independent of the product inhibition at a crossover point at which Daxo is defined. Effects of St and Pe have been investigated at different kinetic regimes and the results show that their effects have a strong dependency on the kinetic parameters θ, γ (i.e., Km/Kp), and Daxo. 相似文献
79.
在中国应用垂直波束雷达监测褐飞虱和其他水稻害虫迁飞的可行性 总被引:1,自引:0,他引:1
J.R.Riley A.D.Smith D.R.Reynolds 《Entomologia Sinica》2003,10(1):1-19
近年来,可用于昆虫迁飞研究且可自动运行的垂直波束雷达(vertical-looking radar,VLR)的发展使得对迁飞性害虫的周年长期自动监测成为可能。本文提供了我们对能否将这种雷达应用于中国的褐飞虱和其他水稻害虫的监测与预测体系以改善其综合治理的可行性研究结果。以往的研究已经表明,这些害虫一般在300—2000m高度迁飞;而我们根据褐飞虱的雷达和射有效截面的计算结果表明,目前使用的3.2cm波长的VLR对褐飞虱个体目标的最大可检测高度仅约240m;虽然建造一部8.8mm波长的VLR即可覆盖褐飞虱迁飞高度的绝大部分,但其造价和维护费用均过于昂贵。为此,一个更可行的解决方案是,以3.2cm波长的VLR作为包括大多数水稻害虫在内的个体较大的迁飞性害虫的监测工具。 相似文献
80.
Om Prakash Dinesh K. Vishwakarma 《Journal of plant biochemistry and biotechnology.》2001,10(2):147-149
Urease from the seeds of water melon was found to be inhibited by heavy metal ions like copper, lead, nickel and cobalt. The order of effectiveness of these metals as inhibitors was Cu2+ > Pb2+ > Ni2+ > Co2+. The inhibition by these ions was noncompetitive. Time — dependent interaction of urease with nickel and cobalt exhibited a biphasic inhibition behaviour in which approximately half of the initial activity was lost rapidly (within 2 min) and remainder in a slow phase. The inhibition was largely irreversible, hence could not be reversed by dialysis. These observations are suggestive of half-and-half distribution of — SH groups on the native enzyme resulting urease into asymmetric oligomeric molecule. 相似文献