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91.
A novel intrinsically fluorescent probe for study of uptake and trafficking of 25-hydroxycholesterol
92.
93.
Agata Jacewicz Lidia Chico Paul Smith Beate Schwer Stewart Shuman 《RNA (New York, N.Y.)》2015,21(3):401-414
Saccharomyces cerevisiae Msl5 orchestrates spliceosome assembly by binding the intron branchpoint sequence 5′-UACUAAC and, with its heterodimer partner protein Mud2, establishing cross intron-bridging interactions with the U1 snRNP at the 5′ splice site. Here we define the central Msl5 KH-QUA2 domain as sufficient for branchpoint RNA recognition. The 1.8 Å crystal structure of Msl5-(KH-QUA2) bound to the branchpoint highlights an extensive network of direct and water-mediated protein–RNA and intra-RNA atomic contacts at the interface that illuminate how Msl5 recognizes each nucleobase of the UACUAAC element. The Msl5 structure rationalizes a large body of mutational data and inspires new functional studies herein, which reveal how perturbations of the Msl5·RNA interface impede the splicing of specific yeast pre-mRNAs. We also identify interfacial mutations in Msl5 that bypass the essentiality of Sub2, a DExD-box ATPase implicated in displacing Msl5 from the branchpoint in exchange for the U2 snRNP. These studies establish an atomic resolution framework for understanding splice site selection and early spliceosome dynamics. 相似文献
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95.
Wujec M Plech T Siwek A Rajtar B Polz-Dacewiczb M 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(7-8):333-339
2-[(4-Methyl-4H-1,2,4-triazol-3-yl)sulfanyl]acetamide derivatives were synthesized and their structures were confirmed by 1H NMR, IR, and elemental analysis. Cytotoxicity of the compounds towards HEK-293 and GMK cells was evaluated. Moreover, the antiviral and virucidal activities of these compounds against human adenovirus type 5 and ECHO-9 virus were assessed. Some of the newly synthesized derivatives have the potential to reduce the viral replication of both tested viruses. 相似文献
96.
Olszak AM van Essen D Pereira AJ Diehl S Manke T Maiato H Saccani S Heun P 《Nature cell biology》2011,13(7):799-808
97.
Budkowska A Kakkanas A Nerrienet E Kalinina O Maillard P Horm SV Dalagiorgou G Vassilaki N Georgopoulou U Martinot M Sall AA Mavromara P 《PloS one》2011,6(1):e15871
The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T>C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of anti-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection. 相似文献
98.
Molecular Ecology Resources Primer Development Consortium Agata K Alasaad S Almeida-Val VM Alvarez-Dios JA Barbisan F Beadell JS Beltrán JF Benítez M Bino G Bleay C Bloor P Bohlmann J Booth W Boscari E Caccone A Campos T Carvalho BM Climaco GT Clobert J Congiu L Cowger C Dias G Doadrio I Farias IP Ferrand N Freitas PD Fusco G Galetti PM Gallardo-Escárate C Gaunt MW Ocampo ZG Gonçalves H Gonzalez EG Haye P Honnay O Hyseni C Jacquemyn H Jowers MJ Kakezawa A Kawaguchi E Keeling CI Kwan YS 《Molecular ecology resources》2011,11(3):586-589
This article documents the addition of 238 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Alytes dickhilleni, Arapaima gigas, Austropotamobius italicus, Blumeria graminis f. sp. tritici, Cobitis lutheri, Dendroctonus ponderosae, Glossina morsitans morsitans, Haplophilus subterraneus, Kirengeshoma palmata, Lysimachia japonica, Macrolophus pygmaeus, Microtus cabrerae, Mytilus galloprovincialis, Pallisentis (Neosentis) celatus, Pulmonaria officinalis, Salminus franciscanus, Thais chocolata and Zootoca vivipara. These loci were cross-tested on the following species: Acanthina monodon, Alytes cisternasii, Alytes maurus, Alytes muletensis, Alytes obstetricans almogavarii, Alytes obstetricans boscai, Alytes obstetricans obstetricans, Alytes obstetricans pertinax, Cambarellus montezumae, Cambarellus zempoalensis, Chorus giganteus, Cobitis tetralineata, Glossina fuscipes fuscipes, Glossina pallidipes, Lysimachia japonica var. japonica, Lysimachia japonica var. minutissima, Orconectes virilis, Pacifastacus leniusculus, Procambarus clarkii, Salminus brasiliensis and Salminus hilarii. 相似文献
99.
3D in vitro models have been used in cancer research as a compromise between 2-dimensional cultures of isolated cancer cells
and the manufactured complexity of xenografts of human cancers in immunocompromised animal hosts. 3D models can be tailored
to be biomimetic and accurately recapitulate the native in vivo scenario in which they are found. These 3D in vitro models
provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations.
Approaches to create more biomimetic 3D models of cancer include, but are not limited to, (i) providing the appropriate matrix
components in a 3D configuration found in vivo, (ii) co-culturing cancer cells, endothelial cells and other associated cells
in a spatially relevant manner, (iii) monitoring and controlling hypoxia- to mimic levels found in native tumours and (iv)
monitoring the release of angiogenic factors by cancer cells in response to hypoxia. This article aims to overview current
3D in vitro models of cancer and review strategies employed by researchers to tackle these aspects with special reference
to recent promising developments, as well as the current limitations of 2D cultures and in vivo models. 3D in vitro models
provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations.
Here we review current strategies in the field of modelling cancer, with special reference to advances in complex 3D in vitro
models. 相似文献
100.
Maillard P Walic M Meuleman P Roohvand F Huby T Le Goff W Leroux-Roels G Pécheur EI Budkowska A 《PloS one》2011,6(10):e26637
A distinctive feature of HCV is that its life cycle depends on lipoprotein metabolism. Viral morphogenesis and secretion follow the very low-density lipoprotein (VLDL) biogenesis pathway and, consequently, infectious HCV in the serum is associated with triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) hydrolyzes TRL within chylomicrons and VLDL but, independently of its catalytic activity, it has a bridging activity, mediating the hepatic uptake of chylomicrons and VLDL remnants. We previously showed that exogenously added LPL increases HCV binding to hepatoma cells by acting as a bridge between virus-associated lipoproteins and cell surface heparan sulfate, while simultaneously decreasing infection levels. We show here that LPL efficiently inhibits cell infection with two HCV strains produced in hepatoma cells or in primary human hepatocytes transplanted into uPA-SCID mice with fully functional human ApoB-lipoprotein profiles. Viruses produced in vitro or in vivo were separated on iodixanol gradients into low and higher density populations, and the infection of Huh 7.5 cells by both virus populations was inhibited by LPL. The effect of LPL depended on its enzymatic activity. However, the lipase inhibitor tetrahydrolipstatin restored only a minor part of HCV infectivity, suggesting an important role of the LPL bridging function in the inhibition of infection. We followed HCV cell entry by immunoelectron microscopy with anti-envelope and anti-core antibodies. These analyses demonstrated the internalization of virus particles into hepatoma cells and their presence in intracellular vesicles and associated with lipid droplets. In the presence of LPL, HCV was retained at the cell surface. We conclude that LPL efficiently inhibits HCV infection by acting on TRL associated with HCV particles through mechanisms involving its lipolytic function, but mostly its bridging function. These mechanisms lead to immobilization of the virus at the cell surface. HCV-associated lipoproteins may therefore be a promising target for the development of new therapeutic approaches. 相似文献