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Institution

University of Texas Health Science Center at Houston

EducationHouston, Texas, United States
About: University of Texas Health Science Center at Houston is a education organization based out in Houston, Texas, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 27309 authors who have published 42520 publications receiving 2151596 citations. The organization is also known as: UTHealth & The UT Health Science Center at Houston.


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Journal ArticleDOI
TL;DR: A Bcl-6-CXCR5 axis in Treg cells that drives the development of follicular regulatory T (TFR) cells that function to inhibit the germinal center reactions is unveiled.
Abstract: Foxp3(+) regulatory T (T(reg)) cells suppress different types of immune responses to help maintain homeostasis in the body. How T(reg) cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T(reg) cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T(reg) cells depends on Bcl-6. These CXCR5(+)Bcl-6(+) T(reg) cells are absent in the thymus but can be generated de novo from CXCR5(-)Foxp3(+) natural T(reg) precursors. A lack of CXCR5(+) T(reg) cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in T(reg) cells that drives the development of follicular regulatory T (T(FR)) cells that function to inhibit the germinal center reactions.

896 citations

Journal ArticleDOI
TL;DR: It is concluded that the unusually high degree of polymorphism at class II MHC loci is caused mainly by overdominant selection (heterozygote advantage) operating in the antigen-recognition site.
Abstract: To study the mechanism of maintenance of polymorphism at major histocompatibility complex (MHC) loci, synonymous and nonsynonymous (amino acid-altering) nucleotide substitutions in the putative antigen-recognition site (included in the first domain of the MHC molecule) and other regions of human and mouse class II genes were examined. In the putative antigen-recognition site, the rate of nonsynonymous substitution was found to exceed that of synonymous substitution, whereas in the second domain the former was significantly lower than the latter. In light of a previous theoretical study and parallel findings in class I MHC loci, we conclude that the unusually high degree of polymorphism at class II MHC loci is caused mainly by overdominant selection (heterozygote advantage) operating in the antigen-recognition site.

890 citations

Journal ArticleDOI
TL;DR: An analysis of single nucleotide polymorphisms with allele frequencies that were determined in three populations provides a first generation natural selection map of the human genome and provides compelling evidence that selection has shaped extant patterns of human genomic variation.
Abstract: Natural selection, which can be defined as the differential contribution of genetic variants to future generations (Aquadro et al. 2001), is the driving force of Darwinian evolution. Despite intense research, only a relatively small number of regions and genes have been directly implicated as targets of selection in the human genome (Kitano and Saitou 1999; Rana et al. 1999; Huttley et al. 2000; Hollox et al. 2001; Hull et al. 2001; Hurst and Pal 2001; Koda et al. 2001; Sullivan et al. 2001; Tishkoff et al. 2001; Baum et al. 2002; Fullerton et al. 2002; Gilad et al. 2002; Hamblin et al. 2002). A more comprehensive and genomic understanding of how and where natural selection has shaped patterns of genetic variation may provide important insights into the mechanisms of evolutionary change (Otto 2000), guide selection of loci for inclusion in population genetic studies (Vitalis et al. 2001), facilitate the annotation of functionally significant genomic regions (Nielsen 2001), and help elucidate genotype-phenotype correlations in complex diseases (Przeworski et al. 2000; Nielsen 2001). Detecting unambiguous evidence for natural selection remains challenging because the effect of selection on the distribution of genetic variation can be mimicked by population demographic history (i.e., the size, structure, and mating pattern of a population). For instance, both adaptive hitchhiking and population expansion can cause an excess of rare variants observed in DNA sequence data compared with what is expected under a standard neutral model (Tajima 1989; Przeworski et al. 2000). Despite these difficulties, the recent deluge of publicly available single nucleotide polymorphisms (SNPs) provides an exciting opportunity to identify genome-wide signatures of selection (Sunyaev et al. 2000; Fay et al. 2001; Sachidanandam et al. 2001). To this end, examining the variation in SNP allele frequencies between populations, which can be quantified by the statistic FST, is a promising strategy for detecting signatures of natural selection (Lewontin and Krakauer 1973; Rana et al. 1999; Hollox et al. 2001; Fullerton et al. 2002; Gilad et al. 2002; Hamblin et al. 2002). Under selective neutrality, FST is determined by genetic drift, which will affect all loci across the genome in a similar and predictable fashion. On the other hand, natural selection is a locus-specific force that can cause systematic deviations in FST values for a selected gene and nearby genetic markers. For example, geographically restricted directional selection may lead to an increase in FST of a selected locus, whereas balancing or species-wide directional selection may lead to a decrease in FST compared with neutrally evolving loci (Cavalli-Sforza 1966; Bowcock et al. 1991; Andolfatto 2001). Previous studies that have attempted to identify natural selection based on patterns of population differentiation relied on simulations to obtain the expected distribution of FST under selective neutrality (Lewontin and Krakauer 1973; Bowcock et al. 1991; Beaumont and Nichols 1996). However, the simulated distribution of FST strongly depends on the assumed population demographic history, which is rarely known with any degree of certainty. As an expanding number of SNPs are genotyped across multiple populations, a complimentary approach that does not require tenuous assumptions about population demographic history is now becoming feasible. Specifically, by sampling a large number of SNPs throughout the genome, loci that have been affected by natural selection can simply be identified as outliers in the extreme tails of the empirical distribution of FST (Cavalli-Sforza 1966; Black et al. 2001; Goldstein and Chikhi 2002). Recently, this strategy has been used to infer natural selection in the CAPN10 gene; however, the empirical distribution of FST contained <100 loci (Fullerton et al. 2002). In this work, we describe an analysis of 26,530 SNPs with allele frequencies that were determined in three populations: African-American, East Asian, and European-American. The density of this SNP allele frequency map provides a unique and powerful opportunity to interrogate the genome for signatures of natural selection. Through a variety of analyses, we have found statistically significant evidence supporting the hypothesis that selection has influenced extant patterns of human genetic variation. Furthermore, we have identified 174 candidate genes that demonstrate signatures of selection when contrasted to the empirical genome-wide distribution of FST. This analysis provides the conceptual foundation for constructing a high-resolution natural selection map, which will be an important resource in understanding the recent evolutionary history of our species, and will facilitate detailed studies on the identified candidate genes.

890 citations

Journal ArticleDOI
TL;DR: It is shown that nanoporous silicon particles can successfully perform all actions when they are coated with cellular membranes purified from leukocytes, and leukolike vectors retained their functions when injected in vivo, showing enhanced circulation time and improved accumulation in a tumour.
Abstract: The therapeutic efficacy of systemic drug-delivery vehicles depends on their ability to evade the immune system, cross the biological barriers of the body and localize at target tissues. White blood cells of the immune system--known as leukocytes--possess all of these properties and exert their targeting ability through cellular membrane interactions. Here, we show that nanoporous silicon particles can successfully perform all these actions when they are coated with cellular membranes purified from leukocytes. These hybrid particles, called leukolike vectors, can avoid being cleared by the immune system. Furthermore, they can communicate with endothelial cells through receptor-ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium. Moreover, leukolike vectors retained their functions when injected in vivo, showing enhanced circulation time and improved accumulation in a tumour.

889 citations

Journal ArticleDOI
TL;DR: It is indicated that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.
Abstract: background Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. methods A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 µg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. results The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). conclusions Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.

885 citations


Authors

Showing all 27450 results

NameH-indexPapersCitations
Paul M. Ridker2331242245097
Eugene Braunwald2301711264576
Eric N. Olson206814144586
Hagop M. Kantarjian2043708210208
André G. Uitterlinden1991229156747
Gordon B. Mills1871273186451
Eric Boerwinkle1831321170971
Bruce M. Psaty1811205138244
Aaron R. Folsom1811118134044
Daniel R. Weinberger177879128450
Bharat B. Aggarwal175706116213
Richard A. Gibbs172889249708
Russel J. Reiter1691646121010
James F. Sallis169825144836
Steven N. Blair165879132929
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202342
2022231
20213,048
20202,807
20192,467
20182,224