A universal nonlinear relation among boundary states in closed string field theory

We show that the boundary states satisfy a nonlinear relation (the idempotency equation) with respect to the star product of closed string field theory. This relation is universal in the sense that various D-branes, including the infinitesimally deformed ones, satisfy the same equation, including the coefficient. This paper generalizes our analysis (hep-th/0306189) in the following senses. (1) We present a background-independent formulation based on conformal field theory. It illuminates the geometric nature of the relation and allows us to more systematically analyze the variations around the D-brane background. (2) We show that the Witten-type star product satisfies a similar relation but with a more divergent coefficient. (3) We determine the coefficient of the relation analytically. The result shows that the alpha parameter can be formally factored out, and the relation becomes universal. We present a conjecture on vacuum theory based on this computation.Comment: 35 pages, 7 figures, references added, v3:PTPTeX, typos correcte

Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review

Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children

Reactions to insanity : a study of stigma, discrimination and labelling in relation to present and former psychiatric patients

The thesis is organised around an empirical investigation of the relationship between residents of a Hertfordshire village and people who are, or who have been, patients at a nearby psychiatric hospital, some of whom regularly venture into the village to use local facilities. The research employs the method of participant observation and draws upon the discourse analytic approach of Potter and Wetherell, together with the rhetorical perspective of Michael Billig. In particular, the research focuses upon the discursive practices of local people, practices which function to sustain, amplify or minimise difference between themselves and others who are patients. The critical theory of Jürgen Habermas is drawn upon to complement and extend the discourse analysis approach, which receives critical evaluation. In addition, the time-geography of Alan Pred is employed as an heuristic for the representation of journeys of patients in the village. The historical dimension of the relationship between village and hospital is addressed by drawing upon Parish Council minutes and local newspaper reports. The thesis contains a conceptual investigation of public anxieties concerning mental disorder, an overview and discussion of the contemporary relevance of the labelling perspective, and a review of relevant literature. In addition it provides an exploration of methodological and textual issue

Vitamin D deficiency associated with neurodevelopmental problems in 2-year-old Japanese boys

Acknowledgements The authors thank the JECS participants, as well as Nagamasa Maeda and Mikiya Fujieda of the Kochi Regional Centre of the JECS, and Ingrid Vinsa at the Gillberg Neuropsychiatry Centre. Funding information The Japan Environment and Children's Study was funded by the Ministry of Environment, JapanPeer reviewe

Pre-/perinatal reduced optimality and neurodevelopment at 1 month and 3 years of age : Results from the Japan Environment and Children’s Study (JECS)

Acknowledgments The authors thank the JECS participants and the JECS Group as well as Nagamasa Maeda, Mikiya Fujieda, Naomi Mitsuda, and Atsuko Mori of the Kochi Regional Centre of the JECS and Sifa Marie Joelle Muchanga of the National Center for Global Health and Medicine. The members of the JECS Group as of 2022 are as follows: Michihiro Kamijima (principal investigator, Nagoya City University, Nagoya, Japan, [email protected]), Shin Yamazaki (National Institute for Environmental Studies, Tsukuba, Japan), Yukihiro Ohya (National Center for Child Health and Development, Tokyo, Japan), Reiko Kishi (Hokkaido University, Sapporo, Japan), Nobuo Yaegashi (Tohoku University, Sendai, Japan), Koichi Hashimoto (Fukushima Medical University, Fukushima, Japan), Chisato Mori (Chiba University, Chiba, Japan), Shuichi Ito (Yokohama City University, Yokohama, Japan), Zentaro Yamagata (Universit y of Yamanashi, Chuo, Japan), Hidekuni Inadera (University of Toyama, Toyama, Japan), Takeo Nakayama (Kyoto University, Kyoto, Japan), Tomotaka Sobue (Osaka University, Suita, Japan), Masayuki Shima (Hyogo Medical University, Nishinomiya, Japan), Hiroshige Nakamura(Tottori University, Yonago, Japan), Narufumi Suganuma (Kochi University, Nankoku, Japan), Koichi Kusuhara (University of Occupational and Environmental Health, Kitakyushu, Japan), and Takahiko Katoh (Kumamoto University, Kumamoto, Japan). Funding: The Japan Environment and Children’s Study (JECS) is funded by the Ministry of the Environment (MOE) of Japan, including data collection. The present study utilized part of the JECS data. However, for this particular study “Pre-/perinatal reduced optimality and neurodevelopment at 1 month and 3 years of age – Results from the Japan Environment and Children’s Study (JECS)”, the funder had no role in study design, analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy

The human histone chaperone sNASP interacts with linker and core histones through distinct mechanisms

Somatic nuclear autoantigenic sperm protein (sNASP) is a human homolog of the N1/N2 family of histone chaperones. sNASP contains the domain structure characteristic of this family, which includes a large acidic patch flanked by several tetratricopeptide repeat (TPR) motifs. sNASP possesses a unique binding specificity in that it forms specific complexes with both histone H1 and histones H3/H4. Based on the binding affinities of sNASP variants to histones H1, H3.3, H4 and H3.3/H4 complexes, sNASP uses distinct structural domains to interact with linker and core histones. For example, one of the acidic patches of sNASP was essential for linker histone binding but not for core histone interactions. The fourth TPR of sNASP played a critical role in interactions with histone H3/H4 complexes, but did not influence histone H1 binding. Finally, analysis of cellular proteins demonstrated that sNASP existed in distinct complexes that contained either linker or core histones

NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei

Trypanosoma brucei mono-allelically expresses one of approximately 1500 variant surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream. The active VSG is transcribed by RNA polymerase I in one of approximately 15 telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene expression predominantly post-transcriptionally, and how ESs are mono-allelically controlled remains a mystery. Here we identify a novel transcription regulator, which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45- to 65-fold derepression of the silent VSG221 ES. NLP is also involved in repression of transcription in the inactive VSG Basic Copy arrays, minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and 50-bp simple sequence repeats, the non-transcribed regions around rDNA and procyclin, and both active and silent ESs. Blocking NLP synthesis leads to downregulation of the active ES, indicating that NLP plays a role in regulating appropriate levels of transcription of ESs in both their active and silent state. Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control

Genome-wide computational identification of WG/GW Argonaute-binding proteins in Arabidopsis

Domains in Arabidopsis proteins NRPE1 and SPT5-like, composed almost exclusively of repeated motifs in which only WG or GW sequences and an overall amino-acid preference are conserved, have been experimentally shown to bind multiple molecules of Argonaute (AGO) protein(s). Domain swapping between the WG/GW domains of NRPE1 and the human protein GW182 showed a conserved function. As classical sequence alignment methods are poorly-adapted to detect such weakly-conserved motifs, we have developed a tool to carry out a systematic analysis to identify genes potentially encoding AGO-binding GW/WG proteins. Here, we describe exhaustive analysis of the Arabidopsis genome for all regions potentially encoding proteins bearing WG/GW motifs and consider the possible role of some of them in AGO-dependent mechanisms. We identified 20 different candidate WG/GW genes, encoding proteins in which the predicted domains range from 92aa to 654aa. These mostly correspond to a limited number of families: RNA-binding proteins, transcription factors, glycine-rich proteins, translation initiation factors and known silencing-associated proteins such as SDE3. Recent studies have argued that the interaction between WG/GW-rich domains and AGO proteins is evolutionarily conserved. Here, we demonstrate by an in silico domain-swapping simulation between plant and mammalian WG/GW proteins that the biased amino-acid composition of the AGO-binding sites is conserved