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71.
Predominance of HLA-Restricted Cytotoxic T-Lymphocyte Responses to Serotype-Cross-Reactive Epitopes on Nonstructural Proteins following Natural Secondary Dengue Virus Infection 总被引:5,自引:1,他引:4
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Anuja Mathew Ichiro Kurane Sharone Green Henry A. F. Stephens David W. Vaughn Siripen Kalayanarooj Saroj Suntayakorn Dasnayanee Chandanayingyong Francis A. Ennis Alan L. Rothman 《Journal of virology》1998,72(5):3999-4004
We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive. 相似文献
72.
Rates and patterns of evolution in partial sequences of five mitochondrial
genes (cytochrome b, ATPase 6, NADH dehydrogenase subunit 5, tRNA(Glu), and
the control region) were compared among taxa in the passerine bird genera
Fringilla and Carduelis. Rates of divergence do not vary significantly
among genes, even in comparisons with the control region. Rate variation
among lineages is significant only for the control region and NADH
dehydrogenase subunit 5, and patterns of variation are consistent with the
expectations of neutral theory. Base composition is biased in all genes but
is stationary among lineages, and there is evidence for directional
mutation pressure only in the control region. Despite these similarities,
patterns of substitution differ among genes, consistent with alternative
regimes of selective constraint. Rates of nonsynonymous substitution are
higher in NADH dehydrogenase subunit 5 than in other protein-coding genes,
and transitions exist in elevated proportions relative to transversions.
Transitions appear to accumulate linearly with time in tRNA(Glu), and
despite exhibiting the highest overall rate of divergence among species,
there are no transversional changes in this gene. Finally, for resolving
phylogenetic relationships among Fringilla taxa, the combined
protein-coding data are broadly similar to those of the control region in
terms of phylogenetic informativeness and statistical support.
相似文献
73.
BiP and calreticulin form an abundant complex that is independent of endoplasmic reticulum stress 总被引:5,自引:1,他引:4
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BiP is found in association with calreticulin, both in the presence and absence of endoplasmic reticulum stress. Although the BiP-calreticulin complex can be disrupted by ATP, several properties suggest that the calreticulin associated with BiP is neither unfolded nor partially or improperly folded. (1) The complex is stable in vivo and does not dissociate during 8 hr of chase. (2) When present in the complex, calreticulin masks epitopes at the C terminus of BiP that are not masked when BiP is bound to an assembly-defective protein. And (3) overproduction of calreticulin does not lead to the recruitment of more BiP into complexes with calreticulin. The BiP-calreticulin complex can be disrupted by low pH but not by divalent cation chelators. When the endoplasmic reticulum retention signal of BiP is removed, complex formation with calreticulin still occurs, and this explains the poor secretion of the truncated molecule. Gel filtration experiments showed that BiP and calreticulin are present in distinct high molecular weight complexes in which both molecules interact with each other. The possible functions of this complex are discussed. 相似文献
74.
Cytokinesis and Midzone Microtubule Organization in Caenorhabditis elegans Require the Kinesin-like Protein ZEN-4 总被引:2,自引:1,他引:1
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William B. Raich Adrienne N. Moran Joel H. Rothman Jeff Hardin 《Molecular biology of the cell》1998,9(8):2037-2049
Members of the MKLP1 subfamily of kinesin motor proteins localize to the equatorial region of the spindle midzone and are capable of bundling antiparallel microtubules in vitro. Despite these intriguing characteristics, it is unclear what role these kinesins play in dividing cells, particularly within the context of a developing embryo. Here, we report the identification of a null allele of zen-4, an MKLP1 homologue in the nematode Caenorhabditis elegans, and demonstrate that ZEN-4 is essential for cytokinesis. Embryos deprived of ZEN-4 form multinucleate single-celled embryos as they continue to cycle through mitosis but fail to complete cell division. Initiation of the cytokinetic furrow occurs at the normal time and place, but furrow propagation halts prematurely. Time-lapse recordings and microtubule staining reveal that the cytokinesis defect is preceded by the dissociation of the midzone microtubules. We show that ZEN-4 protein localizes to the spindle midzone during anaphase and persists at the midbody region throughout cytokinesis. We propose that ZEN-4 directly cross-links the midzone microtubules and suggest that these microtubules are required for the completion of cytokinesis. 相似文献
75.
A model for the regulation of cerebral oxygen delivery 总被引:3,自引:0,他引:3
Hyder Fahmeed; Shulman Robert G.; Rothman Douglas L. 《Journal of applied physiology》1998,85(2):554-564
On the basis of the assumption that oxygen delivery across theendothelium is proportional to capillary plasmaPO2, a model is presented that linkscerebral metabolic rate of oxygen utilization(CMRO2) to cerebral blood flow(CBF) through an effective diffusivity for oxygen (D) of the capillarybed. On the basis of in vivo evidence that the oxygen diffusivityproperties of the capillary bed may be altered by changes in capillaryPO2, hematocrit, and/or bloodvolume, the model allows changes in D with changes in CBF. Choice inthe model of the appropriate ratio of (D/D)/(CBF/CBF)determines the dependence of tissue oxygen delivery on perfusion.Buxton and Frank (J. Cereb. Blood Flow. Metab. 17: 64-72, 1997) recently presented alimiting case of the present model in which = 0. In contrast to thetrends predicted by the model of Buxton and Frank, in the current modelwhen > 0, the proportionality between changes in CBF andCMRO2 becomes more linear, and similardegrees of proportionality can exist at different basal values ofoxygen extraction fraction. The model is able to fit the observedproportionalities between CBF and CMRO2 for a large range ofphysiological data. Although the model does not validate any particularobserved proportionality between CBF andCMRO2, generally values of(CMRO2/CMRO2)/(CBF/CBF) close to unity have been observed across ranges of graded anesthesia inrats and humans and for particular functional activations in humans.The model's capacity to fit the wide range of data indicates that theoxygen diffusivity properties of the capillary bed, which can bemodified in relation to perfusion, play an important role in regulatingcerebral oxygen delivery in vivo. 相似文献
76.
77.
Marc Y. R. Henrion Mark P. Purdue Ghislaine Scelo Peter Broderick Matthew Frampton Alastair Ritchie Angela Meade Peng Li James McKay Mattias Johansson Mark Lathrop James Larkin Nathaniel Rothman Zhaoming Wang Wong-Ho Chow Victoria L. Stevens W. Ryan Diver Demetrius Albanes Jarmo Virtamo Paul Brennan Timothy Eisen Stephen Chanock Richard S. Houlston 《PloS one》2015,10(3)
So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (P
combined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; P
combined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation. 相似文献
78.
Mitchell T. Irwin Jean‐Luc Raharison David Raubenheimer Colin A. Chapman Jessica M. Rothman 《American journal of physical anthropology》2014,153(1):78-91
Primate field studies often identify “lean seasons,” when preferred foods are scarce, and lower‐quality, abundant foods (fallback foods) are consumed. Here, we quantify the nutritional implications of these terms for two diademed sifaka groups (Propithecus diadema) in Madagascar, using detailed feeding observations and chemical analyses of foods. In particular, we sought to understand 1) how macronutrient and energy intakes vary seasonally, including whether these intakes respond in similar or divergent ways; 2) how the amount of food ingested varies seasonally (including whether changes in amount eaten may compensate for altered food quality); and 3) correlations between these variables and the degree of frugivory. In the lean season, sifakas shifted to non‐fruit foods (leaves and flowers), which tended to be high in protein while low in other macronutrients and energy, but the average composition of the most used foods in each season was similar. They also showed dramatic decreases in feeding time, food ingested, and consequently, daily intake of macronutrients and energy. The degree of frugivory in the daily diet was a strong positive predictor of feeding time, amount ingested and all macronutrient and energy intakes, though season had an independent effect. These results suggest that factors restricting how much food can be eaten (e.g., handling time, availability, or intrinsic characteristics like fiber and plant secondary metabolites) can be more important than the nutritional composition of foods themselves in determining nutritional outcomes—a finding with relevance for understanding seasonal changes in behavior, life history strategies, competitive regimes, and conservation planning. Am J Phys Anthropol 153:78–91, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
79.
Cecilia Ferndahl Nicklas Bonander Christel Logez Renaud Wagner Lena Gustafsson Christer Larsson Kristina Hedfalk Richard AJ Darby Roslyn M Bill 《Microbial cell factories》2010,9(1):47
Background
Recombinant protein production is universally employed as a solution to obtain the milligram to gram quantities of a given protein required for applications as diverse as structural genomics and biopharmaceutical manufacture. Yeast is a well-established recombinant host cell for these purposes. In this study we wanted to investigate whether our respiratory Saccharomyces cerevisiae strain, TM6*, could be used to enhance the productivity of recombinant proteins over that obtained from corresponding wild type, respiro-fermentative strains when cultured under the same laboratory conditions. 相似文献80.
The programmed death of particular cells in Caenorhabditis elegans and Drosophila has been shown to occur by non-apoptotic programs regulated by developmental timing. Such alternative programs may be used as a general mechanism to eliminate differentiated, functional cells. 相似文献