16 research outputs found

    Regulatory T cells and their role in rheumatic diseases: a potential target for novel therapeutic development

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    Regulatory T cells have an important role in limiting immune reactions and are essential regulators of self-tolerance. Among them, CD4+CD25high regulatory T cells are the best-described subset. In this article, we summarize current knowledge on the phenotype, function, and development of CD4+CD25high regulatory T cells. We also review the literature on the role of these T cells in rheumatic diseases and discuss the potential for their use in immunotherapy

    Mammalian sex determination—insights from humans and mice

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    Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models

    Carbonate xenoliths hosted by the Mesoproterozoic Siddanpalli Kimberlite Cluster (Eastern Dharwar craton): Implications for the geodynamic evolution of southern India and its diamond and uranium metallogenesis

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    A number of limestone and metasomatised carbonate xenoliths occur in the 1,090 Ma Siddanpalli kimberlite cluster, Raichur kimberlite Field, Eastern Dharwar craton, southern India. These xenoliths are inferred to have been derived from the carbonate horizons of the Kurnool (Palnad) and Bhima Proterozoic basins and provide evidence for a connection between these basins in the geological past. A revised Mesoproterozoic age is proposed for the Bhima and Kurnool (Palnad) basins based on this kimberlite association and is in agreement with similar proposals made recently for the Chattisgarh and Upper Vindhyan sediments in Central India. The observed Bhima–Kurnool interbasinal uplift may have been caused by: (1) extension- or plume-related mafic alkaline magmatism that included the emplacement of the southern Indian kimberlites at *1.1 Ga, (2) mantle plume-related doming of the peninsular India during the Cretaceous, or (3) Quaternary differential uplift in this region. It is not possible, with the currently available geological information to constrain the exact timing of this uplift. The deep erosion of primary diamond sources in the Raichur kimberlite Field in the upper reaches of the Krishna River caused by this uplift could be the elusive source of the alluvial diamonds of the Krishna valley. Mesoproterozoic sedimentary basins can host world class unconformity-type uranium deposits. In light of its inferred Mesoproterozoic age, a more detailed stratigraphic and metallogenic analysis of the Kurnool basin is suggested for uranium exploration

    Tracing environmental markers of autoimmunity: introducing the infectome

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    We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of adaptive mechanisms in the body. These studies complement genome-wide association studies, which establish the genetic predisposition to disease. The infectome is a component which spans the whole life and may begin at the earliest stages right up to the time when the first symptoms manifest, and may thus contribute to the understanding of the pathogenesis of autoimmunity at the prodromal/asymptomatic stages. We provide practical examples and research tools as to how we can investigate disease-specific infectomes, using laboratory approaches employed from projects studying the "immunome" and "microbiome". It is envisioned that an understanding of the infectome and the environmental factors that affect it will allow for earlier patient-specific intervention by clinicians, through the possible treatment of infectious agents as well as other compounding factors, and hence slowing or preventing disease development

    Immunopathogenesis of Hepatitis C Virus Infection: Multifaceted Strategies Subverting Innate and Adaptive Immunity

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