100 research outputs found

    Intercellular Adhesion Molecule-1 Guides Naive T Cell Differentiation and Regulatory T Cell Induction

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    The outcome of naĂŻve T cell activation and differentiation is guided by cues received from the cellular microenvironment, including cytokine and costimulatory signals. NaĂŻve T cell precursors can differentiate into a variety of cellular subsets, each with a unique function in the immune response. In this Dissertation, we provide supporting evidence for the participation of costimulatory molecules in cell fate decisions. Using an in vitro differentiation system, we demonstrate that costimulation through Intercellular Adhesion Molecule-1 (ICAM-1) on the naĂŻve CD4+ T cell can promote differentiation to Foxp3hiCD25+CD127lo regulatory T (Treg) cells with suppressor function. These results add to the evidence previously published by our lab that ICAM-1 can act as a costimulatory molecule in the process of activation and differentiation of naĂŻve CD4+ T cells from younger individuals. However, when naĂŻve CD4+ T cells from older individuals were costimulated through ICAM-1, differentiation to effector and memory subsets was promoted, while differentiation to a Treg subset was impaired. These data contribute to the concept that aging may alter naĂŻve T cell activation and differentiation. Next, we examined the in vivo role of ICAM-1 using mice deficient in ICAM-1 or doubly deficient in ICAM-1 and CD28. ICAM-1-/- mice tended to have slightly increased CD8+ T cell function compared to wild-type controls, while ICAM-1-/-CD28-/- mice displayed decreased CD8+ T cell function during acute viral infection. However, a lack of both ICAM-1 and CD28 did not completely abolish CD8+ T cell IFN-gamma production or cytotoxicity. Finally, we further compared costimulation of human naĂŻve CD4+ T cells through ICAM-1 and CD28 and identified potential differences in the timing of activation, in cytokine secretion, and in kinase signaling. Together, our results suggest that costimulation through ICAM-1 can participate in the differentiation of Treg cells from naĂŻve precursors, and that differences in the costimulatory signal can influence differentiation outcome

    Association of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms with bacterial vaginosis in non-pregnant Italian women

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    Bacterial vaginosis (BV) is the most prevalent alteration of vaginal microflora worldwide. BV is a polymicrobial disorder, and its etiology is elusive. Factors predisposing to this recurrent condition are not fully characterized. We aimed to investigate whether interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) polymorphisms are associated with BV in non-pregnant white Italian women. Genomic DNA was obtained from 164 BV positive, and 406 control women. Two diallelic polymorphisms in the IL-1beta gene (IL-1B) representing C/T base transitions at - 511 and + 3954 positions and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (IL-1RN) were assessed. We demonstrated that women who were homozygous for - 511 CC or + 3954 TT of the IL-1B gene were at increased risk for BV with an odds ratio (OR) = 1.5 [95% confidence interval (CI) = 1.03-2.14, P = 0.032], and OR = 2.8 (95% CI = 1.37-5.88, P = 0.004), respectively. The haplotype - 511/ + 3954 T-C was protective for BV, with an OR = 0.7 (95% CI = 0.49-0.90, P = 0.009). The IL-1RN VNTR genotype was not associated with BV, although the rare allele 3 showed a trend towards protection (P = 0.049). These data show that host genetic variants at the IL-1beta locus predispose to BV among Caucasian non-pregnant women. Further studies will determine whether these genetic polymorphisms modulate the risk for BV recurrence, and/or BV associated severe adverse outcomes as preterm birth and human immunodeficiency virus transmission

    Choice of resident costimulatory molecule can influence cell fate in human naĂŻve CD4+ T cell differentiation

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    With antigen stimulation, naĂŻve CD4+ T cells differentiate to several effector or memory cell populations, and cytokines contribute to differentiation outcome. Several proteins on these cells receive costimulatory signals, but a systematic comparison of their differential effects on naĂŻve T cell differentiation has not been conducted. Two costimulatory proteins, CD28 and ICAM-1, resident on human naĂŻve CD4+ T cells were compared for participation in differentiation. Under controlled conditions, and with no added cytokines, costimulation through either CD3+CD28 or CD3+ICAM-1 induced differentiation to T effector and T memory cells. In contrast, costimulation through CD3+ICAM-1 induced differentiation to Treg cells whereas costimulation through CD3+CD28 did not

    Race/Ethnicity and Retention in Traumatic Brain Injury Outcomes Research: A Traumatic Brain Injury Model Systems National Database Study

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    Objective: To investigate the contribution of race/ethnicity to retention in traumatic brain injury (TBI) research at 1 to 2 years post-injury. Setting: Community. Participants: 5548 Whites, 1347 Blacks, and 790 Hispanics enrolled in the Traumatic Brain Injury Model Systems National Database with dates of injury between October 1, 2002 and March 31, 2013. Design: Retrospective database analysis. Main Measure: Retention, defined as completion of at least one question on the follow-up interview by the person with TBI or a proxy. Results: Retention rates 1-2 years post-TBI were significantly lower for Hispanic (85.2%) than for White (91.8%) or Black participants (90.5%) and depended significantly on history of problem drug or alcohol use. Other variables associated with low retention included older age, lower education, violent cause of injury, and discharge to an institution versus private residence. Conclusions: The findings emphasize the importance of investigating retention rates separately for Blacks and Hispanics rather than combining them or grouping either with other races or ethnicities. The results also suggest the need for implementing procedures to increase retention of Hispanics in longitudinal TBI researc

    Candidate gene analysis of spontaneous preterm delivery: New insights from re-analysis of a case-control study using case-parent triads and control-mother dyads

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    Background: Spontaneous preterm delivery (PTD) has a multifactorial etiology with evidence of a genetic contribution to its pathogenesis. A number of candidate gene case-control studies have been performed on spontaneous PTD, but the results have been inconsistent, and do not fully assess the role of how two genotypes can impact outcome. To elucidate this latter point we re-analyzed data from a previously published case-control candidate gene study, using a case-parent triad design and a hybrid design combining case-parent triads and control-mother dyads. These methods offer a robust approach to genetic association studies for PTD compared to traditional case-control designs. Methods: The study participants were obtained from the Norwegian Mother and Child Cohort Study (MoBa). A total of 196 case triads and 211 control dyads were selected for the analysis. A case-parent triad design as well as a hybrid design was used to analyze 1,326 SNPs from 159 candidate genes. We compared our results to those from a previous case-control study on the same samples. Haplotypes were analyzed using a sliding window of three SNPs and a pathway analysis was performed to gain biological insight into the pathophysiology of preterm delivery. Results: The most consistent significant fetal gene across all analyses was COL5A2. The functionally similar COL5A1 was significant when combining fetal and maternal genotypes. PON1 was significant with analytical approaches for single locus association of fetal genes alone, but was possibly confounded by maternal effects. Focal adhesion (hsa04510), Cell Communication (hsa01430) and ECM receptor interaction (hsa04512) were the most constant significant pathways. Conclusion: This study suggests a fetal association of COL5A2 and a combined fetal-maternal association of COL5A1 with spontaneous PTD. In addition, the pathway analysis implied interactions of genes affecting cell communication and extracellular matrix.publishedVersio

    Canada's Compassionate Care Benefit: Is it an adequate public health response to addressing the issue of caregiver burden in end-of-life care?

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    Abstract Background An increasingly significant public health issue in Canada, and elsewhere throughout the developed world, pertains to the provision of adequate palliative/end-of-life (P/EOL) care. Informal caregivers who take on the responsibility of providing P/EOL care often experience negative physical, mental, emotional, social and economic consequences. In this article, we specifically examine how Canada's Compassionate Care Benefit (CCB) - a contributory benefits social program aimed at informal P/EOL caregivers - operates as a public health response in sustaining informal caregivers providing P/EOL care, and whether or not it adequately addresses known aspects of caregiver burden that are addressed within the population health promotion (PHP) model. Methods As part of a national evaluation of Canada's Compassionate Care Benefit, 57 telephone interviews were conducted with Canadian informal P/EOL caregivers in 5 different provinces, pertaining to the strengths and weaknesses of the CCB and the general caregiving experience. Interview data was coded with Nvivo software and emerging themes were identified by the research team, with such findings published elsewhere. The purpose of the present analysis was identified after comparing the findings to the literature specific to caregiver burden and public health, after which data was analyzed using the PHP model as a guiding framework. Results Informal caregivers spoke to several of the determinants of health outlined in the PHP model that are implicated in their burden experience: gender, income and social status, working conditions, health and social services, social support network, and personal health practises and coping strategies. They recognized the need for improving the CCB to better address these determinants. Conclusions This study, from the perspective of family caregivers, demonstrates that the CCB is not living up to its full potential in sustaining informal P/EOL caregivers. Effort is required to transform the CCB so that it may fulfill the potential it holds for serving as one public health response to caregiver burden that forms part of a healthy public policy that addresses the determinants of this burden. </jats:sec

    Lista de gĂȘneros de Hymenoptera (Insecta) do EspĂ­rito Santo, Brasil

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    The first checklist of genera of Hymenoptera from Espírito Santo state, Brazil is presented. A total of 973 genera of Hymenoptera is listed, of which 555 (57%) are recorded for the first time from this state. Ichneumonoidea and Chalcidoidea are the two superfamilies with the most genera, 241 and 203 respectively. Braconidae, with 141 genera, are the richest family.The first checklist of genera of Hymenoptera from Espírito Santo state, Brazil is presented. A total of 973 genera of Hymenoptera is listed, of which 555 (57%) are recorded for the first time from this state. Ichneumonoidea and Chalcidoidea are the two superfamilies with the most genera, 241 and 203 respectively. Braconidae, with 141 genera, are the richest family.Fil: Azevedo, Celso O.. Universidade Federal do Espírito Santo; BrasilFil: Molin, Ana Dal. Texas A&M University; Estados UnidosFil: Penteado-Dias, Angelica. Universidade Federal do São Carlos; BrasilFil: Macedo, Antonio C. C.. Secretaria do Meio Ambiente do Estado de São Paulo; BrasilFil: Rodriguez-V, Beatriz. Universidad Nacional Autónoma de México; MéxicoFil: Dias, Bianca Z. K.. Universidade Federal do Espírito Santo; BrasilFil: Waichert, Cecilia. State University of Utah; Estados UnidosFil: Aquino, Daniel Alejandro. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Smith, David. Smithsonian Institution; Estados UnidosFil: Shimbori, Eduardo M.. Universidade Federal do São Carlos; BrasilFil: Noll, Fernando B.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Gibson, Gary. Agriculture and Agri-Food Canada; CanadåFil: Onody, Helena. Universidade Federal do São Carlos; BrasilFil: Carpenter, James M.. American Museum of Natural History; Estados UnidosFil: Lattke, John. Universidad Nacional de Loja; EcuadorFil: Ramos, Kelli dos S.. Universidade de Sao Paulo; BrasilFil: Williams, Kevin. Florida State Collection of Arthropods; Estados UnidosFil: Masner, Lubomir. Agriculture and Agri-Food Canada; CanadåFil: Kimsey, Lynn. University of California; Estados UnidosFil: Tavares, Marcelo T.. Universidade Federal do Espírito Santo; BrasilFil: Olmi, Massimo. Università degli Studi della Tuscia; ItaliaFil: Buffington, Matthew L.. United States Department of Agriculture; Estados UnidosFil: Ohl, Michael. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Sharkey, Michael. University of Kentucky; Estados UnidosFil: Johnson, Norman F.. Ohio State University; Estados UnidosFil: Kawada, Ricardo. Universidade Federal do Espírito Santo; BrasilFil: Gonçalves, Rodrigo B.. Universidade Federal do Paranå; BrasilFil: Feitosa, Rodrigo. Universidade Federal do Paranå; BrasilFil: Heydon, Steven. University of California; Estados UnidosFil: Guerra, Tùnia M.. Universidade Federal do Espírito Santo; BrasilFil: da Silva, Thiago S. R.. Universidade Federal do Espírito Santo; BrasilFil: Costa, Valmir. Instituto Biológico; Brasi

    Mariana serpentinite mud volcanism exhumes subducted seamount materials: implications for the origin of life

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    The subduction of seamounts and ridge features at convergent plate boundaries plays an important role in the deformation of the overriding plate and influences geochemical cycling and associated biological processes. Active serpentinization of forearc mantle and serpentinite mud volcanism on the Mariana forearc (between the trench and active volcanic arc) provides windows on subduction processes. Here, we present (1) the first observation of an extensive exposure of an undeformed Cretaceous seamount currently being subducted at the Mariana Trench inner slope; (2) vertical deformation of the forearc region related to subduction of Pacific Plate seamounts and thickened crust; (3) recovered Ocean Drilling Program and International Ocean Discovery Program cores of serpentinite mudflows that confirm exhumation of various Pacific Plate lithologies, including subducted reef limestone; (4) petrologic, geochemical and paleontological data from the cores that show that Pacific Plate seamount exhumation covers greater spatial and temporal extents; (5) the inference that microbial communities associated with serpentinite mud volcanism may also be exhumed from the subducted plate seafloor and/or seamounts; and (6) the implications for effects of these processes with regard to evolution of life.Copyright 2020 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/ by/4.0/, which permits unrestricted use, provided the original author and source are credited
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