82 research outputs found

    Pregnancy-induced changes in cell-fate in the mammary gland

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    The protective effect of an early full-term pregnancy is a well established phenomenon; in contrast, the molecular and cell-specific mechanisms that govern parity-specific changes in the mammary gland have not been well described. Recent studies signify a dramatic advance in our understanding of this phenomenon, and indicate a 'cell fate' model for parity-related changes that lead to protection against breast cancer

    RIG-I contributes to the innate immune response after cerebral ischemia

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    BACKGROUND: Focal cerebral ischemia induces an inflammatory response that when exacerbated contributes to deleterious outcomes. The molecular basis regarding the regulation of the innate immune response after focal cerebral ischemia remains poorly understood. METHODS: In this study we examined the expression of retinoic acid-inducible gene (RIG)-like receptor-I (RIG-I) and its involvement in regulating inflammation after ischemia in the brain of rats subjected to middle cerebral artery occlusion (MCAO). In addition, we studied the regulation of RIG-I after oxygen glucose deprivation (OGD) in astrocytes in culture. RESULTS: In this study we show that in the hippocampus of rats, RIG-I and IFN-α are elevated after MCAO. Consistent with these results was an increased in RIG-I and IFN-α after OGD in astrocytes in culture. These data are consistent with immunohistochemical analysis of hippocampal sections, indicating that in GFAP-positive cells there was an increase in RIG-I after MCAO. In addition, in this study we have identified n-propyl gallate as an inhibitor of IFN-α signaling in astrocytes. CONCLUSION: Our findings suggest a role for RIG-I in contributing to the innate immune response after focal cerebral ischemia

    Association between Protective and Deleterious HLA Alleles with Multiple Sclerosis in Central East Sardinia

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    The human leukocyte antigen (HLA) complex on chromosome 6p21 has been unambiguously associated with multiple sclerosis (MS). The complex features of the HLA region, especially its high genic content, extreme polymorphism, and extensive linkage disequilibrium, has prevented to resolve the nature of HLA association in MS. We performed a family based association study on the isolated population of the Nuoro province (Sardinia) to clarify the role of HLA genes in MS. The main stage of our study involved an analysis of the ancestral haplotypes A2Cw7B58DR2DQ1 and A30Cw5B18DR3DQ2. On the basis of a multiplicative model, the effect of the first haplotype is protective with an odds ratio (OR) = 0.27 (95% confidence interval CI 0.13–0.57), while that of the second is deleterious, OR 1.78 (95% CI 1.26–2.50). We found both class I (A, Cw, B) and class II (DR, DQ) loci to have an effect on MS susceptibility, but we saw that they act independently from each other. We also performed an exploratory analysis on a set of 796 SNPs in the same HLA region. Our study supports the claim that Class I and Class II loci act independently on MS susceptibility and this has a biological explanation. Also, the analysis of SNPs suggests that there are other HLA genes involved in MS, but replication is needed. This opens up new perspective on the study of MS

    LGBTQ parenting post heterosexual relationship dissolution

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    The chapter examines parenting among sexual and gender minorities post heterosexual relationship dissolution (PHRD). Reviewing the literature around intersecting identities of LGBTQ parents, we consider how religion, race, and socioeconomic status are associated with routes into and out of heterosexual relationships and variation in the lived experience of sexual and gender identity minorities, in particular how LGBTQ parents PHRD feel about being out. Further consideration is given to examining how family relationships change and develop as parental sexual and/or gender identity changes. We also explore the impact of PHRD identity and parenthood on new partnerships and stepfamily experiences. The chapter addresses the reciprocal relationship between research on LGBTQ parenting and policy and legal influences that impact upon the experience of LGBTQ parenting PHRD when custody and access are disputed. Finally, the chapter includes future research directions and implications for practice in an area that has been revitalized in recent years

    近世の流通システムと産業組織:宿駅と酒造業の経済的機能に関する考察

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    Type-I interferon pathway in neuroinflammation and neurodegeneration: focus on Alzheimer's disease

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    Past research in Alzheimer's disease (AD) has largely been driven by the amyloid hypothesis; the accompanying neuroinflammation seen in AD has been assumed to be consequential and not disease modifying or causative. However, recent data from both clinical and preclinical studies have established that the immune-driven neuroinflammation contributes to AD pathology. Key evidence for the involvement of neuroinflammation in AD includes enhanced microglial and astroglial activation in the brains of AD patients, increased pro-inflammatory cytokine burden in AD brains, and epidemiological evidence that chronic non-steroidal anti-inflammatory drug use prior to disease onset leads to a lower incidence of AD. Identifying critical mediators controlling this neuroinflammation will prove beneficial in developing anti-inflammatory therapies for the treatment of AD. The type-I interferons (IFNs) are pleiotropic cytokines that control pro-inflammatory cytokine secretion and are master regulators of the innate immune response that impact on disorders of the central nervous system. This review provides evidence that the type-I IFNs play a critical role in the exacerbation of neuroinflammation and actively contribute to the progression of AD
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