Hindu nationalism operates on a global scale today. Evinced by the transnational networks of the Sangh Parivar and the replication of strategies such as amending textbooks and patriotic rewriting of ...history, politics and discourse of Hindu nationalism are not solely contained to the territorial boundary of the nation. In this globalized battle for and against Hindu nationalism, the United States of America serves as an important site. In light of this, this article puts together existing scholarship on diasporic Hindu nationalism with late nineteenth-and early twentieth-century deterritorial history of Indian nationalism to present a broader framework for historicizing Indian activism in the US. It argues that while long-distance Hindu nationalism in the US cannot be traced before the 1970s, examining the early experiences of Indian activists in the US offers useful insights with which to evaluate the ongoing battles of Hindu nationalism in the US and opens another field of enquiry: Hindutva’s counterpublic.
Autosomal dominant gain-of-function mutations in human stimulator of interferon genes (STING) lead to a severe autoinflammatory disease called STING-associated vasculopathy with onset in infancy that ...is associated with enhanced expression of interferon-stimulated gene transcripts.
The goal of this study was to analyze the phenotype of a new mouse model of STING hyperactivation and the role of type I interferons in this system.
We generated a knock-in model carrying an amino acid substitution (V154M) in mouse STING, corresponding to a recurrent mutation seen in human patients with STING-associated vasculopathy with onset in infancy. Hematopoietic development and tissue histology were analyzed. Lymphocyte activation and proliferation were assessed in vitro. STING V154M/wild-type (WT) mice were crossed to IFN-α/β receptor (IFNAR) knockout mice to evaluate the type I interferon dependence of the mutant Sting phenotype recorded.
In STING V154M/WT mice we detected variable expression of inflammatory infiltrates in the lungs and kidneys. These mice showed a marked decrease in survival and developed a severe combined immunodeficiency disease (SCID) affecting B, T, and natural killer cells, with an almost complete lack of antibodies and a significant expansion of monocytes and granulocytes. The blockade in B- and T-cell development was present from early immature stages in bone marrow and thymus. In addition, in vitro experiments revealed an intrinsic proliferative defect of mature T cells. Although the V154M/WT mutant demonstrated increased expression of interferon-stimulated genes, the SCID phenotype was not reversed in STING V154M/WT IFNAR knockout mice. However, the antiproliferative defect in T cells was rescued partially by IFNAR deficiency.
STING gain-of-function mice developed an interferon-independent SCID phenotype with a T-cell, B-cell, and natural killer cell developmental defect and hypogammaglobulinemia that is associated with signs of inflammation in lungs and kidneys. Only the intrinsic proliferative defect of T cells was partially interferon dependent.
The amino acid tyrosine is the precursor to the catecholamine neurotransmitters dopamine and norepinephrine. Increasing tyrosine uptake may positively influence catecholamine-related psychological ...functioning. We conducted a systematic review to examine the effects of tyrosine on behavior and cognition. Fifteen studies were reviewed. All studies except one involved tyrosine loading during a single test session. In most behavioral studies, there were no significant effects of tyrosine on exercise performance. In contrast, cognitive studies employing neuropsychological measures found that tyrosine loading acutely counteracts decrements in working memory and information processing that are induced by demanding situational conditions such as extreme weather or cognitive load. The buffering effects of tyrosine on cognition may be explained by tyrosine's ability to neutralize depleted brain catecholamine levels. There is evidence that tyrosine may benefit healthy individuals exposed to demanding situational conditions. For future research we recommend moving from studying the acute effects of a single tyrosine load in small samples to studying the behavioral and cognitive effects of tyrosine in larger groups over multiple weeks.
•Tyrosine is the dietary precursor to dopamine and norepinephrine.•We reviewed 15 studies on the effects of tyrosine on human behavior or cognition.•Cognitive improvements can be observed after a single tyrosine load.•Behavioral changes may only appear after repeated tyrosine supplementation.•Future studies should focus on the longer-term effects of tyrosine intake.
The field of primary immunodeficiencies (PIDs) is rapidly evolving. Indeed, the number of described diseases is constantly increasing thanks to the rapid identification of novel genetic defects by ...next-generation sequencing. PIDs are now rather referred to as "inborn errors of immunity" due to the association between a wide range of immune dysregulation-related clinical features and the "prototypic" increased infection susceptibility. The phenotypic spectrum of PIDs is therefore very large and includes several orofacial features. However, the latter are often overshadowed by severe systemic manifestations and remain underdiagnosed. Patients with impaired innate immunity are predisposed to a variety of oral manifestations including oral infections (e.g., candidiasis, herpes gingivostomatitis), aphthous ulcers, and severe periodontal diseases. Although less frequently, they can also show orofacial developmental abnormalities. Oral lesions can even represent the main clinical manifestation of some PIDs or be inaugural, being therefore one of the first features indicating the existence of an underlying immune defect. The aim of this review is to describe the orofacial features associated with the different PIDs of innate immunity based on the new 2019 classification from the International Union of Immunological Societies (IUIS) expert committee. This review highlights the important role played by the dentist, in close collaboration with the multidisciplinary medical team, in the management and the diagnostic of these conditions.
Background LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency caused by biallelic mutations in LRBA that abolish LRBA protein expression. Objective We sought to ...report the extended phenotype of LRBA deficiency in a cohort of 22 LRBA-deficient patients. Methods Clinical criteria, protein detection, and genetic sequencing were applied to diagnose LRBA deficiency. Results Ninety-three patients met the inclusion criteria and were considered to have possible LRBA deficiency. Twenty-four patients did not express LRBA protein and were labeled as having probable LRBA deficiency, whereas 22 were genetically confirmed as having definitive LRBA deficiency, with biallelic mutations in LRBA . Seventeen of these were novel and included homozygous or compound heterozygous mutations. Immune dysregulation (95%), organomegaly (86%), recurrent infections (71%), and hypogammaglobulinemia (57%) were the main clinical complications observed in LRBA-deficient patients. Although 81% of LRBA-deficient patients had normal T-cell counts, 73% had reduced regulatory T (Treg) cell numbers. Most LRBA-deficient patients had low B-cell subset counts, mainly in switched memory B cells (80%) and plasmablasts (92%), with a defective specific antibody response in 67%. Of the 22 patients, 3 are deceased, 2 were treated successfully with hematopoietic stem cell transplantation, 7 are receiving immunoglobulin replacement, and 15 are receiving immunosuppressive treatment with systemic corticosteroids alone or in combination with steroid-sparing agents. Conclusion This report describes the largest cohort of patients with LRBA deficiency and offers guidelines for physicians to identify LRBA deficiency, supporting appropriate clinical management.
Primary immunodeficiencies (PIDs) represent a group of mostly monogenic disorders caused by loss- or gain-of-function mutations in over 340 known genes that lead to abnormalities in the development ...and/or the function of the immune system. However, mutations in different genes can affect the same cell-signaling pathway and result in overlapping clinical phenotypes. In particular, mutations in the genes encoding for members of the phosphoinositide3-kinase (PI3K)/AKT/mTOR/S6 kinase (S6K) signaling cascade or for molecules interacting with this pathway have been associated with different PIDs that are often characterized by the coexistence of both immune deficiency and autoimmunity. The serine/threonine kinase mechanistic/mammalian target of rapamycin (mTOR), which acts downstream of PI3K and AKT, is emerging as a key regulator of immune responses. It integrates a variety of signals from the microenvironment to control cell growth, proliferation, and metabolism. mTOR plays therefore a central role in the regulation of immune cells' differentiation and functions. Here, we review the different PIDs that share an impairment of the PI3K/AKT/mTOR/S6K pathway and we propose to name them "immune TOR-opathies" by analogy with a group of neurological disorders that has been originally defined by PB Crino and that are due to aberrant mTOR signaling (1). A better understanding of the role played by this complex intracellular cascade in the pathophysiology of "immune TOR-opathies" is crucial to develop targeted therapies.
Abstract Background To review how daily symptom ratings have been used in research into premenstrual dysphoric disorder (PMDD), and to discuss opportunities for the future. Methods PsycINFO and ...Medline were systematically searched, resulting in the inclusion of 75 studies in which (1) participants met the diagnostic criteria for late luteal phase dysphoric disorder (LLPDD) or PMDD and (2) diaries were used to study LLPDD/PMDD. Results To date, diaries have been used to gain insight into the aetiology and phenomenology of PMDD, to examine associated biological factors, and to assess treatment efficacy. We found low consistency among the diaries used, and often only part of the menstrual cycle was analysed instead of the whole menstrual cycle. We also observed that there was substantial variability in diagnostic procedures and criteria. Limitations This review excluded diary studies conducted in women with premenstrual syndrome, women seeking help for premenstrual complaints without a clear diagnosis, and women without premenstrual complaints. Conclusions Prospective daily ratings of symptoms and related variables provide a valuable and important tool in the study of PMDD. This paper addresses some options for improving the use of diaries and proposes the use of experience sampling and ecological momentary assessment to investigate within-person variability in symptoms in more detail.
This special issue consists of six articles initially presented at a conference titled ‘(Un)Making the Nation’, held at the University of Cambridge on the 10th and 11th of September in 2015. With ...papers ranging across temporal, geographical and thematic boundaries, this international and interdisciplinary conference explored various new engagements with the concepts of nations and nationalism. The introduction traces the ways historians have sought to insert ‘the nation’ into their work in spite of the methodological challenges brought by the global turn. The goal is neither to bury the nation nor to resurrect it, but is rather to introduce some useful approaches through which the making and unmaking of nations in world history can be better understood. This article then concludes by offering a brief synopsis of the articles that constitute the wider issue.
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