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41.
42.
Mansour S. Alturki Ngolui Rene Fuanta Madison A. Jarrard Judith V. Hobrath Douglas C. Goodwin Thankhoe A. Rantso Angela I. Calderón 《Bioorganic & medicinal chemistry letters》2018,28(4):802-808
Single dose high-throughput screening (HTS) followed by dose-response evaluations is a common strategy for the identification of initial hits for further development. Early identification and exclusion of false positives is a cost-saving and essential step in early drug discovery. One of the mechanisms of false positive compounds is the formation of aggregates in assays. This study evaluates the mechanism(s) of inhibition of a set of 14 compounds identified previously as actives in Mycobacterium tuberculosis (Mt) cell culture screening and in vitro actives in Mt shikimate kinase (MtSK) assay. Aggregation of hit compounds was characterized using multiple experimental methods, LC-MS, 1HNMR, dynamic light scattering (DLS), transmission electron microscopy (TEM), and visual inspection after centrifugation for orthogonal confirmation. Our results suggest that the investigated compounds containing oxadiazole-amide and aminobenzothiazole moieties are false positive hits and non-specific inhibitors of MtSK through aggregate formation. 相似文献
43.
J Mangion N Rahman S Mansour G Brice J Rosbotham A H Child V A Murday P S Mortimer R Barfoot A Sigurdsson S Edkins M Sarfarazi K Burnand A L Evans T O Nunan M R Stratton S Jeffery 《American journal of human genetics》1999,65(2):427-432
Lymphedema-distichiasis (LD) is a dominantly inherited syndrome with onset of lymphedema at or just after puberty. Most affected individuals have distichiasis-fine hairs arising inappropriately from the eyelid meibomian glands-which is evident from birth. A study of three families with LD has shown linkage to chromosome 16q24.3, and subsequent analysis of the region for recombinant genes places the locus between D16S422 and D16S3074, a distance of approximately 16 cM. Possible candidate genes in this interval include the N-proteinase for type 3 collagen, PCOLN3; the metalloprotease PRSM1; and the cell matrix-adhesion regulator, CMAR. 相似文献
44.
Rajesh Abraham Jacob Cassandra R. Edgar Jrmie Prvost Steven M. Trothen Antony Lurie Mitchell J. Mumby Alexa Galbraith Frank Kirchhoff S.M. Mansour Haeryfar Andrs Finzi Jimmy D. Dikeakos 《The Journal of biological chemistry》2021,297(3)
Prolonged immune activation drives the upregulation of multiple checkpoint receptors on the surface of virus-specific T cells, inducing their exhaustion. Reversing HIV-1-induced T cell exhaustion is imperative for efficient virus clearance; however, viral mediators of checkpoint receptor upregulation remain largely unknown. The enrichment of checkpoint receptors on T cells upon HIV-1 infection severely constrains the generation of an efficient immune response. Herein, we examined the role of HIV-1 Nef in mediating the upregulation of checkpoint receptors on peripheral blood mononuclear cells. We demonstrate that the HIV-1 accessory protein Nef upregulates cell surface levels of the checkpoint receptor T-cell immunoglobulin mucin domain-3 (Tim-3) and that this is dependent on Nef''s dileucine motif LL164/165. Furthermore, we used a bimolecular fluorescence complementation assay to demonstrate that Nef and Tim-3 form a complex within cells that is abrogated upon mutation of the Nef dileucine motif. We also provide evidence that Nef moderately promotes Tim-3 shedding from the cell surface in a dileucine motif–dependent manner. Treating HIV-1-infected CD4+ T cells with a matrix metalloprotease inhibitor enhanced cell surface Tim-3 levels and reduced Tim-3 shedding. Finally, Tim-3-expressing CD4+ T cells displayed a higher propensity to release the proinflammatory cytokine interferon-gamma. Collectively, our findings uncover a novel mechanism by which HIV-1 directly increases the levels of a checkpoint receptor on the surface of infected CD4+ T cells. 相似文献
45.
Mansour S. Alsaid Mostafa M. Ghorab Saleh I. Alqasoumi Maged S. Abdel-Kader 《Russian Journal of Bioorganic Chemistry》2016,42(5):567-573
A novel series of thiourea and carbamimidothioic acid derivatives was synthesized using natural alkaloid L-norephedrine as a starting material. Structures of the newly synthesized compounds were confirmed by analytical and spectral data. The synthesized compounds were evaluated in vitro for anticancer activity against the human breast (MCF-7), human liver (HEPG2), and human colon (HCT116) cancer cell lines. Best activity of the synthesized compounds was expressed against HEPG2, however, none of the compounds exceeded the IC50 of doxorubicin. The corresponding N-(1-(2-chloroacetoxy)-1-phenylpropan-2-yl)-N′-p-tolylcarbamimidothioic acid was the most potent compound and exhibited higher cytotoxic activity against the human colon cancer cell line (HCT116) when compared with the reference drug doxorubicin. Also, this compound was the most active against the MCF-7 cell line but less active than the positive control. 相似文献
46.
47.
Twelve randomly-selected isolates of Fusarium graminearum that produce 3-acetyl-deoxynivalenol (3-ADON) or 15-acetyl-deoxynivalenol (15-ADON) were screened by thin-layer chromatography
(TLC) for their ability to produce ADON and zearalenone (ZEA) mycotoxins when grown on water agar containing different concentrations
of sucrose. The results showed the ability of the F. graminearum 3-ADON chemotype population to produce DON and ZEA at a lower concentration range of sucrose (5-7%) compared with the 15-ADON
chemotype (30-40%). The former distinction allows for sucrose-water agar to be employed as a rapid and simple differential
medium, where two separate sucrose-gradient concentrations discriminate 3-ADON from 15-ADON populations. In the light of the
shift in sugar concentrations occurring during the process of grain formation and maturation, the difference in mycotoxin
production between the two populations is discussed with respect to predicting Fusarium head blight (FHB) epidemiology and
accumulation of DON and ZEA. 相似文献
48.
Green HC Dick LK Gilpin B Samadpour M Field KG 《Applied and environmental microbiology》2012,78(2):503-510
Avian feces contaminate waterways but contribute fewer human pathogens than human sources. Rapid identification and quantification of avian contamination would therefore be useful to prevent overestimation of human health risk. We used subtractive hybridization of PCR-amplified gull fecal 16S RNA genes to identify avian-specific fecal rRNA gene sequences. The subtracters were rRNA genes amplified from human, dog, cat, cow, and pig feces. Recovered sequences were related to Enterobacteriaceae (47%), Helicobacter (26%), Catellicoccus (11%), Fusobacterium (11%), and Campylobacter (5%). Three PCR assays, designated GFB, GFC, and GFD, were based on recovered sequence fragments. Quantitative PCR assays for GFC and GFD were developed using SYBR green. GFC detected down to 0.1 mg gull feces/100 ml (corresponding to 2 gull enterococci most probable number [MPN]/100 ml). GFD detected down to 0.1 mg chicken feces/100 ml (corresponding to 13 Escherichia coli MPN/100 ml). GFB and GFC were 97% and 94% specific to gulls, respectively. GFC cross-reacted with 35% of sheep samples but occurred at about 100,000 times lower concentrations in sheep. GFD was 100% avian specific and occurred in gulls, geese, chickens, and ducks. In the United States, Canada, and New Zealand, the three markers differed in their geographic distributions but were found across the range tested. These assays detected four important bird groups contributing to fecal contamination of waterways: gulls, geese, ducks, and chickens. Marker distributions across North America and in New Zealand suggest that they will have broad applicability in other parts of the world as well. 相似文献
49.
Mohamed-Elamir F. Hegazy Tarik A. Mohamed Fathy F. Abdel-Latif Mansour S. Alsaid Abdelaaty A. Shahat Paul W. Paré 《Phytochemistry letters》2013,6(3):383-386
Chemical investigations of the soft coral Sarcophyton trocheliophorum, has led to the isolation of six cembranoids, two of which are new, Trochelioid A (1) and B (2), and one, 16-oxosarcophytonin E (3) isolated from nature for the first time. Additionally, two have been isolated from S. trocheliophorum for the first time (4 and 6). Structures were elucidated by employing extensive NMR and HR-FAB-MS experimentation. 相似文献
50.