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71.
72.
Background
Pichia stipitis xylose reductase (Ps-XR) has been used to design Saccharomyces cerevisiae strains that are able to ferment xylose. One example is the industrial S. cerevisiae xylose-consuming strain TMB3400, which was constructed by expression of P. stipitis xylose reductase and xylitol dehydrogenase and overexpression of endogenous xylulose kinase in the industrial S. cerevisiae strain USM21. 相似文献73.
Zinkernagel AS Timmer AM Pence MA Locke JB Buchanan JT Turner CE Mishalian I Sriskandan S Hanski E Nizet V 《Cell host & microbe》2008,4(2):170-178
Interleukin-8 (IL-8) promotes neutrophil-mediated host defense through its chemoattractant and immunostimulatory activities. The Group A Streptococcus (GAS) protease SpyCEP (also called ScpC) cleaves IL-8, and SpyCEP expression is strongly upregulated in vivo in the M1T1 GAS strains associated with life-threatening systemic disease including necrotizing fasciitis. Coupling allelic replacement with heterologous gene expression, we show that SpyCEP is necessary and sufficient for IL-8 degradation. SpyCEP decreased IL-8-dependent neutrophil endothelial transmigration and bacterial killing, the latter by reducing neutrophil extracellular trap formation. The knockout mutant lacking SpyCEP was attenuated for virulence in murine infection models, and SpyCEP expression conferred protection to coinfecting bacteria. We also show that the zoonotic pathogen Streptococcus iniae possesses a functional homolog of SpyCEP (CepI) that cleaves IL-8, promotes neutrophil resistance, and contributes to virulence. By inactivating the multifunctional host defense peptide IL-8, the SpyCEP protease impairs neutrophil clearance mechanisms, contributing to the pathogenesis of invasive streptococcal infection. 相似文献
74.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
75.
Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks 下载免费PDF全文
Shin‐ichiro Hiraga Chandre Monerawela Yuki Katou Sophie Shaw Kate RM Clark Katsuhiko Shirahige Anne D Donaldson 《EMBO reports》2018,19(9)
Despite its evolutionarily conserved function in controlling DNA replication, the chromosomal binding sites of the budding yeast Rif1 protein are not well understood. Here, we analyse genome‐wide binding of budding yeast Rif1 by chromatin immunoprecipitation, during G1 phase and in S phase with replication progressing normally or blocked by hydroxyurea. Rif1 associates strongly with telomeres through interaction with Rap1. By comparing genomic binding of wild‐type Rif1 and truncated Rif1 lacking the Rap1‐interaction domain, we identify hundreds of Rap1‐dependent and Rap1‐independent chromosome interaction sites. Rif1 binds to centromeres, highly transcribed genes and replication origins in a Rap1‐independent manner, associating with both early and late‐initiating origins. Interestingly, Rif1 also binds around activated origins when replication progression is blocked by hydroxyurea, suggesting association with blocked forks. Using nascent DNA labelling and DNA combing techniques, we find that in cells treated with hydroxyurea, yeast Rif1 stabilises recently synthesised DNA. Our results indicate that, in addition to controlling DNA replication initiation, budding yeast Rif1 plays an ongoing role after initiation and controls events at blocked replication forks. 相似文献
76.
Tanya Marchant Ritgak Dimka Tilley-Gyado Tsegahun Tessema Kultar Singh Meenakshi Gautham Nasir Umar Della Berhanu Simon Cousens Joanna RM Armstrong Schellenberg 《PloS one》2015,10(5)
BackgroundFamilies in high mortality settings need regular contact with high quality services, but existing population-based measurements of contacts do not reflect quality. To address this, in 2012, we designed linked household and frontline worker surveys for Gombe State, Nigeria, Ethiopia, and Uttar Pradesh, India. Using reported frequency and content of contacts, we present a method for estimating the population level coverage of high quality contacts.ConclusionsMeasuring content of care to reflect the quality of contacts can reveal missed opportunities to deliver best possible health care. 相似文献
77.
Bradley RD; Adkins RM; Honeycutt RL; McDonald JH 《Molecular biology and evolution》1998,15(6):709-717
Using the strictly neutral model as a null hypothesis, we tested for
deviations from expected levels of nucleotide polymorphism at the alcohol
dehydrogenase locus (Adh-1) within and among four species of pocket gophers
(Geomys bursarius major, G. knoxjonesi, G. texensis llanensis, and G.
attwateri). The complete protein-encoding region was examined, and 10
unique alleles, representing both electromorphic and cryptic alleles, were
used to test hypotheses (e.g., the neutral model) concerning the
maintenance of genetic variation. Nineteen variable sites were identified
among the 10 alleles examined, including 9 segregating sites occurring in
synonymous positions and 10 that were nonsynonymous. Several statistical
methods, including those that test for within-species variation as well as
those that examine variation within and among species, failed to reject the
null hypothesis that variation (both within and between species of Geomys)
at the Adh locus is consistent with the neutral theory. However, there was
significant heterogeneity in the ratio of polymorphism to divergence across
the gene, with polymorphisms clustered in the first half of the coding
region and fixed differences clustered in the second half of the gene. Two
alternative hypotheses are discussed as possible explanations for this
heterogeneity: an old balanced polymorphism in the first half of the gene
or a recent selective sweep in the second half of the gene.
相似文献
78.
Markus Huemer Srikanth Mairpady Shambat Silvio D Brugger Annelies S Zinkernagel 《EMBO reports》2020,21(12)
Antimicrobial resistance (AMR) and persistence are associated with an elevated risk of treatment failure and relapsing infections. They are thus important drivers of increased morbidity and mortality rates resulting in growing healthcare costs. Antibiotic resistance is readily identifiable with standard microbiological assays, and the threat imposed by antibiotic resistance has been well recognized. Measures aiming to reduce resistance development and spreading of resistant bacteria are being enforced. However, the phenomenon of bacteria surviving antibiotic exposure despite being fully susceptible, so‐called antibiotic persistence, is still largely underestimated. In contrast to antibiotic resistance, antibiotic persistence is difficult to measure and therefore often missed, potentially leading to treatment failures. In this review, we focus on bacterial mechanisms allowing evasion of antibiotic killing and discuss their implications on human health. We describe the relationship between antibiotic persistence and bacterial heterogeneity and discuss recent studies that link bacterial persistence and tolerance with the evolution of antibiotic resistance. Finally, we review persister detection methods, novel strategies aiming at eradicating bacterial persisters and the latest advances in the development of new antibiotics. 相似文献
79.
Reduced natural selection associated with low recombination in Drosophila melanogaster 总被引:8,自引:1,他引:7
Synonymous codons are not used equally in many organisms, and the extent of
codon bias varies among loci. Earlier studies have suggested that more
highly expressed loci in Drosophila melanogaster are more biased,
consistent with findings from several prokaryotes and unicellular
eukaryotes that codon bias is partly due to natural selection for
translational efficiency. We link this model of varying selection intensity
to the population-genetics prediction that the effectiveness of natural
selection is decreased under reduced recombination. In analyses of 385 D.
melanogaster loci, we find that codon bias is reduced in regions of low
recombination (i.e., near centromeres and telomeres and on the fourth
chromosome). The effect does not appear to be a linear function of
recombination rate; rather, it seems limited to regions with the very
lowest levels of recombination. The large majority of the genome apparently
experiences recombination at a sufficiently high rate for effective natural
selection against suboptimal codons. These findings support models of the
Hill-Robertson effect and genetic hitchhiking and are largely consistent
with multiple reports of low levels of DNA sequence variation in regions of
low recombination.
相似文献
80.
Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions 总被引:2,自引:0,他引:2
We have determined the nucleotide sequence of a 1,200-base pair (bp)
genomic fragment that includes the kappa-chain constant-region gene (C
kappa) from two species of native Australian rodents, Rattus leucopus
cooktownensis and Rattus colletti. Comparison of these sequences with each
other and with other rodent C kappa genes shows three surprising features.
First, the coding regions are diverging at a rate severalfold higher than
that of the nearby noncoding regions. Second, replacement changes within
the coding region are accumulating at a rate at least as great as that of
silent changes. Third, most of the amino acid replacements are localized in
one region of the C kappa domain--namely, the carboxy-terminal "bends" in
the alpha-carbon backbone. These three features have previously been
described from comparisons of the two allelic forms of C kappa genes in R.
norvegicus. These data imply the existence of considerable evolutionary
constraints on the noncoding regions (based on as yet undetermined
functions) or powerful positive selection to diversify a portion of the
constant-region domain (whose physiological significance is not known).
These surprising features of C kappa evolution appear to be characteristic
only of closely related C kappa genes, since comparison of rodent with
human sequences shows the expected greater conservation of coding regions,
as well as a predominance of silent nucleotide substitutions within the
coding regions.
相似文献