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排序方式: 共有360条查询结果,搜索用时 15 毫秒
51.
A Recombinant Human Cytomegalovirus with a Large Deletion in UL97 Has a Severe Replication Deficiency 总被引:9,自引:0,他引:9
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Mark N. Prichard Ning Gao Sanju Jairath Gilbert Mulamba Paula Krosky Donald M. Coen Breck O. Parker Gregory S. Pari 《Journal of virology》1999,73(7):5663-5670
Human cytomegalovirus encodes a protein kinase (UL97) that confers sensitivity to ganciclovir by phosphorylating it to the monophosphate. The function of this unusual kinase in viral replication is unknown. We constructed two independent isolates of a recombinant virus, RCDelta97, that contain large deletions in this gene and carry a 4.8-kb insertion containing a selectable genetic marker. These mutant viruses were isolated by using a population of primary cells (HEL97) that express this gene from integrated copies of a defective retroviral vector. The recombinant viruses were severely impaired in their ability to replicate in primary fibroblasts, attaining virus titers that were 2 to 3 orders of magnitude lower than those produced by the parent virus. Despite the severe replication deficit, both of these viruses retained the ability to form small, slowly growing plaques in primary fibroblasts, demonstrating that UL97 is not absolutely essential for replication in cell culture. The replication deficit was relieved when UL97 was provided in trans in the complementing cell line, showing that the phenotype was due to a deficiency in UL97. Thus, the UL97 gene product plays a very important role in viral replication in tissue culture and may be a good target for antiviral chemotherapy. 相似文献
52.
Noureddine L Azzam R Nemer G Bielawski J Nasser M Bitar F Dbaibo GS 《Prostaglandins & other lipid mediators》2008,86(1-4):49-55
Ceramide has been implicated in regulatory processes vital for cell survival under different stressors, most notably hypoxia. Little has been done to investigate the contributions of the different ceramide species to the regulation of cell survival. This study aims to highlight the patterns of variation in total ceramide and its species in the growing and hypoxic mouse heart. Mus musculus mice were placed in a hypoxic environment at birth. Control animals remained in room air. The hearts were extracted at different time points: 1 day, 1 week, 4 weeks, and 8 weeks. The total ceramide content and the amounts of component species were assayed by a modified diacylglycerol kinase assay and high-performance liquid chromatography-tandem mass spectroscopy, respectively. Data was collected from both ventricles in hypoxic and control conditions. There was significant polycythemia in the hypoxic versus control animals with a nearly twofold increase in hematocrit levels. Hypoxic right ventricle (RV) mass significantly increased over that of controls at different age groups. When ceramide content was compared in the hypoxic versus control animals, there was a significant increase at day 1 and a significant decrease at week 4 in the left ventricle, whereas a significant decrease was found in the RV at 1 week, 4 weeks, and 8 weeks. There was also a differential involvement of the RV with regard to levels of N-palmitoyl-D-erythro-sphingosine (C16-Cer) and its synthetic precursor dihydro-N-palmitoyl-D-erythro-sphinganine (DHC-16-Cer). The decrease in C16-Cer observed in both hypoxic and control RV's over time was paralleled by a significant increase in DHC-16-Cer in hypoxic (142.1+/-15.0 pmol; p<0.05) but not control (52.8+/-4.0 pmol) RV's suggesting a role for DHC-16-Cer in the RV adaptive response to hypoxia. Another species, N-arachidoyl-D-erythro-sphingosine (C20-Cer), was specifically and significantly decreased in the hypoxic RV. These studies support the presence of distinct roles for different ceramide species and their precursors. A better assessment of cyanotic congenital heart disease in light of the mechanism and timing of cardiomyocyte death, will lead to punctual interventions and even novel cardioprotective strategies. 相似文献
53.
Background
Recent work has revealed that many biological systems keep functioning in the face of mutations and therefore can be considered genetically robust. However, several issues related to robustness remain poorly understood, such as its implications for evolvability (the ability to produce adaptive evolutionary innovations). 相似文献54.
Clune J Misevic D Ofria C Lenski RE Elena SF Sanjuán R 《PLoS computational biology》2008,4(9):e1000187
The rate of mutation is central to evolution. Mutations are required for adaptation, yet most mutations with phenotypic effects are deleterious. As a consequence, the mutation rate that maximizes adaptation will be some intermediate value. Here, we used digital organisms to investigate the ability of natural selection to adjust and optimize mutation rates. We assessed the optimal mutation rate by empirically determining what mutation rate produced the highest rate of adaptation. Then, we allowed mutation rates to evolve, and we evaluated the proximity to the optimum. Although we chose conditions favorable for mutation rate optimization, the evolved rates were invariably far below the optimum across a wide range of experimental parameter settings. We hypothesized that the reason that mutation rates evolved to be suboptimal was the ruggedness of fitness landscapes. To test this hypothesis, we created a simplified landscape without any fitness valleys and found that, in such conditions, populations evolved near-optimal mutation rates. In contrast, when fitness valleys were added to this simple landscape, the ability of evolving populations to find the optimal mutation rate was lost. We conclude that rugged fitness landscapes can prevent the evolution of mutation rates that are optimal for long-term adaptation. This finding has important implications for applied evolutionary research in both biological and computational realms. 相似文献
55.
56.
Steven A. Safren Katie B. Biello Laura Smeaton Matthew J. Mimiaga Ann Walawander Javier R. Lama Aadia Rana Mulinda Nyirenda Virginia M. Kayoyo Wadzanai Samaneka Anjali Joglekar David Celentano Ana Martinez Jocelyn E. Remmert Aspara Nair Umesh G. Lalloo Nagalingeswaran Kumarasamy James Hakim Thomas B. Campbell for the PEARLS Study Team 《PloS one》2014,9(8)
57.
Nili Raz Yael Danin-Poleg Ryan B. Hayman Yudi Bar-On Alex Linetsky Michael Shmoish Eva Sanjuán Carmen Amaro David R. Walt Yechezkel Kashi 《PloS one》2014,9(12)
Vibrio vulnificus is an aquatic bacterium and an important human pathogen. Strains of V. vulnificus are classified into three different biotypes. The newly emerged biotype 3 has been found to be clonal and restricted to Israel. In the family Vibrionaceae, horizontal gene transfer is the main mechanism responsible for the emergence of new pathogen groups. To better understand the evolution of the bacterium, and in particular to trace the evolution of biotype 3, we performed genome-wide SNP genotyping of 254 clinical and environmental V. vulnificus isolates with worldwide distribution recovered over a 30-year period, representing all phylogeny groups. A custom single-nucleotide polymorphism (SNP) array implemented on the Illumina GoldenGate platform was developed based on 570 SNPs randomly distributed throughout the genome. In general, the genotyping results divided the V. vulnificus species into three main phylogenetic lineages and an additional subgroup, clade B, consisting of environmental and clinical isolates from Israel. Data analysis suggested that 69% of biotype 3 SNPs are similar to SNPs from clade B, indicating that biotype 3 and clade B have a common ancestor. The rest of the biotype 3 SNPs were scattered along the biotype 3 genome, probably representing multiple chromosomal segments that may have been horizontally inserted into the clade B recipient core genome from other phylogroups or bacterial species sharing the same ecological niche. Results emphasize the continuous evolution of V. vulnificus and support the emergence of new pathogenic groups within this species as a recurrent phenomenon. Our findings contribute to a broader understanding of the evolution of this human pathogen. 相似文献
58.
59.
Annarita Poli Vincenzo Schiano Moriello Enrico Esposito Licia Lama Agata Gambacorta Barbara Nicolaus 《Biotechnology letters》2005,26(21):1635-1638
A haloalkalophilic Halomonas strain CRSS, isolated from salt sediments in Antarctica, produced exocellular polysaccharides (EPS) up to 2.9gg-1 dry cells. Acetate was the most efficient carbon source for EPS production. The composition of media strongly affected the nature of the polymers; a mannan and a xylo-mannan, were obtained when cells were grown on complex media. Acetate was the most efficient carbon source for EPS production and in presence of this substrate, a new polysaccharide, a fructo-glucan, was produced. The EPS fraction was composed by glucose, fructose, glucosamine and galactosamine in relative proportions of 1:0.7:0.3:trace.Revisions requested; Revisions received 6 September 2004 相似文献
60.
Joo Sang Lee Nishanth Ulhas Nair Gal Dinstag Lesley Chapman Youngmin Chung Kun Wang Sanju Sinha Hongui Cha Dasol Kim Alexander V. Schperberg Ajay Srinivasan Vladimir Lazar Eitan Rubin Sohyun Hwang Raanan Berger Tuvik Beker Ze’ev Ronai Sridhar Hannenhalli Eytan Ruppin 《Cell》2021,184(9):2487-2502.e13
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