567 research outputs found

    Immunity to self co-generates regulatory T cells

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    Immune responses to self are kept in check by tolerance mechanisms, including suppression by regulatory T cells (Tregs). The defective generation of Tregs specific for self-antigens may lead to autoimmune disease. We identified a novel population of human CD4^+^ Tregs, characterized by high surface expression of CD52, which is co-generated in response to autoantigen. Blood CD4^+^CD52^hi^ T cells were generated preferentially in response to low-dose autoantigen and suppressed proliferation and interferon-[gamma] production by other T cells. Depletion of resting CD4^+^CD52^hi^ T cells enhanced the T-cell response to autoantigen. CD4^+^CD52^hi^ Tregs were neither derived from nor distinguished by markers of conventional resting CD4^+^CD25^+^ Tregs. In response to the pancreatic islet autoantigens glutamic acid decarboxylase, the generation of CD4^+^CD52^hi^ Tregs was impaired in individuals with and at-risk for type 1 diabetes, compared to healthy controls and individuals with type 2 diabetes. CD4^+^CD52^hi^ Tregs co-generated to self-antigen may therefore contribute to immune homeostasis and protect against autoimmune disease

    Conservation Status of Marine Biodiversity in Oceania: An Analysis of Marine Species on the IUCN Red List of Threatened Species

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    Given the economic and cultural dependence on the marine environment in Oceania and a rapidly expanding human population, many marine species populations are in decline and may be vulnerable to extinction from a number of local and regional threats. IUCN Red List assessments, a widely used system for quantifying threats to species and assessing species extinction risk, have been completed for 1190 marine species in Oceania to date, including all known species of corals, mangroves, seagrasses, sea snakes, marine mammals, sea birds, sea turtles, sharks, and rays present in Oceania, plus all species in five important perciformfish groups. Many of the species in these groups are threatened by themodification or destruction of coastal habitats, overfishing fromdirect or indirect exploitation, pollution, and other ecological or environmental changes associated with climate change. Spatial analyses of threatened species highlight priority areas for both site- and species-specific conservation action. Although increased knowledge and use of newly available IUCN Red List assessments for marine species can greatly improve conservation priorities for marine species in Oceania,many important fish groups are still in urgent need of assessment

    Evaluation of the Efficacy and Safety of a Marine-Derived Bacillus Strain for Use as an In-Feed Probiotic for Newly Weaned Pigs

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    peer-reviewedForty eight individual pigs (8.7±0.26 kg) weaned at 28±1 d of age were used in a 22-d study to evaluate the effect of oral administration of a Bacillus pumilus spore suspension on growth performance and health indicators. Treatments (n = 16) were: (1) non-medicated diet; (2) medicated diet with apramycin (200 mg/kg) and pharmacological levels of zinc oxide (2,500 mg zinc/kg) and (3) B. pumilus diet (non-medicated diet + 1010 spores/day B. pumilus). Final body weight and average daily gain tended to be lower (P = 0.07) and feed conversion ratio was worsened (P<0.05) for the medicated treatment compared to the B. pumilus treatment. Ileal E. coli counts were lower for the B. pumilus and medicated treatments compared to the non-medicated treatment (P<0.05), perhaps as a result of increased ileal propionic acid concentrations (P<0.001). However, the medicated treatment reduced fecal (P<0.001) and cecal (P<0.05) Lactobacillus counts and tended to reduce the total cecal short chain fatty acid (SCFA) concentration (P = 0.10). Liver weights were lighter and concentrations of liver enzymes higher (P<0.05) in pigs on the medicated treatment compared to those on the non-medicated or B. pumilus treatments. Pigs on the B. pumilus treatment had lower overall lymphocyte and higher granulocyte percentages (P<0.001) and higher numbers of jejunal goblet cells (P<0.01) than pigs on either of the other two treatments or the non-medicated treatment, respectively. However, histopathological examination of the small intestine, kidneys and liver revealed no abnormalities. Overall, the B. pumilus treatment decreased ileal E. coli counts in a manner similar to the medicated treatment but without the adverse effects on growth performance, Lactobacillus counts, cecal SCFA concentration and possible liver toxicity experienced with the medicated treatment.The study was funded by the Higher Education Authority/Institutes of Technology Ireland Technological Sector Research Strand III Programme

    Phenotypic and functional characteristics of highly differentiated CD57 +NKG2C + NK cells in HIV-1- infected individuals

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    Natural killer (NK) cells are important anti-viral effector cells. The function and phenotype of the NK cells that constitute an individual’s NK cell repertoire can be influenced by ongoing and/or previous viral infections. Indeed, infection with human cytomegalovirus (HCMV) drives the expansion of a highly differentiated NK cell population characterized by expression of CD57 and the activating NKG2C receptor. This NK cell population has also been noted to occur in HIV-1-infected individuals. We evaluated the NK cells of HIV-1-infected and –uninfected individuals to determine the relative frequency of highly differentiated CD57 +NKG2C + NK cells and characterize these cells for their receptor expression and responsiveness to diverse stimuli. Highly differentiated CD57 +NKG2C + NK cells occurred at higher frequencies in HCMV-infected donors relative to HCMV-uninfected donors and were dramatically expanded in HIV-1/HCMV co-infected donors. The expanded CD57 +NKG2C + NK cell population in HIV-1-infected donors remained stable following antiretroviral therapy. CD57 +NKG2C + NK cells derived from HIV-1-infected individuals were robustly activated by antibody-dependent stimuli that contained anti-HIV-1 antibodies or therapeutic anti-CD20 antibody, and these NK cells mediated cytolysis through NKG2C. Lastly, CD57 +NKG2C + NK cells from HIV-1-infected donors were characterized by reduced expression of the inhibitory NKG2A receptor. The abundance of highly functional CD57 +NKG2C + NK cells in HIV-1-infected individuals raises the possibility that these NK cells could play a role in HIV-1 pathogenesis or serve as effector cells for therapeutic/cure strategies

    Conservation Status of Marine Biodiversity in Oceania: An Analysis of Marine Species on the IUCN Red List of Threatened Species

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    Given the economic and cultural dependence on the marine environment in Oceania and a rapidly expanding human population, many marine species populations are in decline and may be vulnerable to extinction from a number of local and regional threats. IUCN Red List assessments, a widely used system for quantifying threats to species and assessing species extinction risk, have been completed for 1190 marine species in Oceania to date, including all known species of corals, mangroves, seagrasses, sea snakes, marine mammals, sea birds, sea turtles, sharks, and rays present in Oceania, plus all species in five important perciform fish groups. Many of the species in these groups are threatened by the modification or destruction of coastal habitats, overfishing from direct or indirect exploitation, pollution, and other ecological or environmental changes associated with climate change. Spatial analyses of threatened species highlight priority areas for both site- and species-specific conservation action. Although increased knowledge and use of newly available IUCN Red List assessments for marine species can greatly improve conservation priorities for marine species in Oceania, many important fish groups are still in urgent need of assessment

    Shared Neuroanatomical Substrates of Impaired Phonological Working Memory Across Reading Disability and Autism

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    Background Individuals with reading disability and individuals with autism spectrum disorder (ASD) are characterized, respectively, by their difficulties in reading and social communication, but both groups often have impaired phonological working memory (PWM). It is not known whether the impaired PWM reflects distinct or shared neuroanatomical abnormalities in these two diagnostic groups. Methods White-matter structural connectivity via diffusion weighted imaging was examined in 64 children, age 5 to 17 years, with reading disability, ASD, or typical development, who were matched on age, gender, intelligence, and diffusion data quality. Results Children with reading disability and children with ASD exhibited reduced PWM compared with children with typical development. The two diagnostic groups showed altered white matter microstructure in the temporoparietal portion of the left arcuate fasciculus and in the occipitotemporal portion of the right inferior longitudinal fasciculus (ILF), as indexed by reduced fractional anisotropy and increased radial diffusivity. Moreover, the structural integrity of the right ILF was positively correlated with PWM ability in the two diagnostic groups but not in the typically developing group. Conclusions These findings suggest that impaired PWM is transdiagnostically associated with shared neuroanatomical abnormalities in ASD and reading disability. Microstructural characteristics in left arcuate fasciculus and right ILF may play important roles in the development of PWM. The right ILF may support a compensatory mechanism for children with impaired PWM

    Cancer negatively impacts on sexual function in adolescents and young adults: The AYA HOPE study

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    ObjectiveThis cohort study examined the impact of cancer on sexual function and intimate relationships in adolescents and young adults (AYAs). We also explored factors predicting an increased likelihood that cancer had negatively affected these outcomes.MethodsParticipants (nâ =â 465, ages 15â 39) in the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) study completed two surveys approximately 1 and 2 years postâ cancer diagnosis. We used multivariable logistic regression to determine factors negatively affected by perceptions of sexual function at 2 years postâ diagnosis.ResultsFortyâ nine percent of AYAs reported negative effects on sexual function at 1 year postâ cancer diagnosis and 70% of those persisted in their negative perceptions 2 years after diagnosis. Those reporting a negative impact at 2 years were more likely to be 25 years or older (OR, 2.53; 95% CI, 1.44â 4.42), currently not raising children (OR, 1.81; 95% CI, 1.06â 3.08), experiencing fatigue (OR, 0.99; 95% CI, 0.975â 0.998) and more likely to report that their diagnosis has had a negative effect on physical appearance (OR, 3.08; 95% CI, 1.97â 4.81). Clinical factors and mental health were not significant predictors of negative effects on sexual function.ConclusionsMany AYAs diagnosed with cancer experience a persistent negative impact on sexual life up to 2 years following diagnosis. The findings underscore the need to develop routine protocols to assess sexual function in AYAs with cancer and to provide comprehensive management in the clinical setting. Copyright © 2016 John Wiley & Sons, Ltd.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138867/1/pon4181_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138867/2/pon4181.pd

    Multidrug-Resistant Tuberculosis Treatment Outcomes in Karakalpakstan, Uzbekistan: Treatment Complexity and XDR-TB among Treatment Failures

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    BACKGROUND: A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. METHODOLOGY: This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. PRINCIPAL FINDINGS: Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. CONCLUSIONS: While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment
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