Autonomic nervous system functioning assessed during the Still-Face Paradigm: A meta-analysis and systematic review of methods, approach and findings.

Animal and human research suggests that the development of the autonomic nervous system (ANS) is particularly sensitive to early parenting experiences. The Still-Face Paradigm (SFP), one of the most widely used measures to assess infant reactivity and emotional competence, evokes infant self-regulatory responses to parental interaction and disengagement. This systematic review of 33 peer-reviewed studies identifies patterns of parasympathetic (PNS) and sympathetic (SNS) nervous system activity demonstrated by infants under one year of age during the SFP and describes findings within the context of sample demographic characteristics, study methodologies, and analyses conducted. A meta-analysis of a subset of 14 studies with sufficient available respiratory sinus arrhythmia (RSA) data examined whether the SFP reliably elicited PNS withdrawal (RSA decrease) during parental disengagement or PNS recovery (RSA increase) during reunion, and whether results differed by socioeconomic status (SES). Across SES, the meta-analysis confirmed that RSA decreased during the still-face episode and increased during reunion. When studies were stratified by SES, low-SES or high-risk groups also showed RSA decreases during the still face episode but failed to show an increase in RSA during reunion. Few studies have examined SNS activity during the SFP to date, preventing conclusions in that domain. The review also identified multiple qualifications to patterns of SFP ANS findings, including those that differed by ethnicity, infant sex, parental sensitivity, and genetics. Strengths and weaknesses in the extant research that may explain some of the variation in findings across the literature are also discussed, and suggestions for strengthening future research are provided

A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress.

BACKGROUND:Chronic life stress, such as the stress of caregiving, can promote pathophysiology, but the underlying cellular mechanisms are not well understood. Chronic stress may induce recalibrations in mitochondria leading to changes either in mitochondrial content per cell, or in mitochondrial functional capacity (i.e., quality). METHODS:Here we present a functional index of mitochondrial health (MHI) for human leukocytes that can distinguish between these two possibilities. The MHI integrates nuclear and mitochondrial DNA-encoded respiratory chain enzymatic activities and mitochondrial DNA copy number. We then use the MHI to test the hypothesis that daily emotional states and caregiving stress influence mitochondrial function by comparing healthy mothers of a child with an autism spectrum disorder (high-stress caregivers, n = 46) with mothers of a neurotypical child (control group, n = 45). RESULTS:The MHI outperformed individual mitochondrial function measures. Elevated positive mood at night was associated with higher MHI, and nightly positive mood was also a mediator of the association between caregiving and MHI. Moreover, MHI was correlated to positive mood on the days preceding, but not following the blood draw, suggesting for the first time in humans that mitochondria may respond to proximate emotional states within days. Correspondingly, the caregiver group, which had higher perceived stress and lower positive and greater negative daily affect, exhibited lower MHI. This effect was not explained by a mismatch between nuclear and mitochondrial genomes. CONCLUSIONS:Daily mood and chronic caregiving stress are associated with mitochondrial functional capacity. Mitochondrial health may represent a nexus between psychological stress and health

Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes.

Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC) telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL) in CD4+, CD8+CD28+, and CD8+CD28- T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28- cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation

Host defense responses to infection by Mycobacterium tuberculosis. Induction of IRF-1 and a serine protease inhibitor.

Alveolar macrophages and newly recruited monocytes are targets of infection by Mycobacterium tuberculosis. Therefore, we examined the expression of interferon regulatory factor 1 (IRF-1), which plays an important role in host defense against M. tuberculosis, in undifferentiated and differentiated cells. Infection induced IRF-1 in both. IRF-1 from undifferentiated, uninfected monocytic cell lines was modified during extraction to produce specific species that were apparently smaller than intact IRF-1. After infection by M. tuberculosis or differentiation, intact IRF-1 was recovered. Subcellular fractions were assayed for the ability to modify IRF-1 or inhibit its modification. A serine protease on the cytoplasmic surface of an organelle or vesicle in the "lysosomal/mitochondrial" fraction from undifferentiated cells was responsible for the modification of IRF-1. Thus, the simplest explanation of the modification is cleavage of IRF-1 by the serine protease. Recovery of intact IRF-1 correlated with induction of a serine protease inhibitor that was able to significantly reduce the modification of IRF-1. The inhibitor was present in the cytoplasm of M. tuberculosis-infected or -differentiated cells. It is likely that induction of both IRF-1 and the serine protease inhibitor in response to infection by M. tuberculosis represent host defense mechanisms

Interparental aggression, attention skills, and early childhood behavior problems

The current study explored longitudinal associations between interparental aggression, the development of child attention skills, and early childhood behavior problems in a diverse sample of 636 families living in predominately low-income, nonmetropolitan communities. The results of latent-variable, cross-lagged longitudinal models revealed that maternal-reported interparental aggression in infancy predicted reduced observed attention skills in toddlerhood; no association was observed, however, between attention in infancy and interparental aggression during the toddler years. Further, reduced toddler attention and high interparental aggression were both associated with increased risk for attention-deficit/hyperactivity disorder symptoms and conduct problems at 3 years of age. Processes largely operated in similar ways regardless of child gender or low-income status, although a few differences were observed. Overall, the results suggest that interparental aggression undermines attention development, putting children’s early behavioral adjustment at risk

Bureaucratization in Public Research Institutions

The purpose of this paper is to analyse the nature of bureaucratization within public research bodies and its relationship to scientific performance, focusing on an Italian case-study. The main finding is that the bureaucratization of the research sector has two dimensions: public research labs have academic bureaucratization since researchers spend an increasing part of their time in administrative matters (i.e., preparing grant applications, managing grants/projects, and so on); whereas universities mainly have administrative bureaucratization generated by the increase over time of administrative staff in comparison with researchers and faculty. In addition, I show that research units with higher bureaucratization have lower scientific performance

Pathogen Recognition Receptor Signaling Accelerates Phosphorylation-Dependent Degradation of IFNAR1

An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays a central role in host's defenses. Activation of these cells through the stimulation of the pathogen-recognition receptors induces the production of a number of cytokines including Type I interferons (IFNs) that mediate the diverse mechanisms of innate immunity. Type I IFNs interact with the Type I IFN receptor, composed of IFNAR1 and IFNAR2 chains, to mount the host defense responses. However, at the same time, Type I IFNs elicit potent anti-proliferative and pro-apoptotic effects that could be detrimental for IFN-producing cells. Here, we report that the activation of p38 kinase in response to pathogen-recognition receptors stimulation results in a series of phosphorylation events within the IFNAR1 chain of the Type I IFN receptor. This phosphorylation promotes IFNAR1 ubiquitination and accelerates the proteolytic turnover of this receptor leading to an attenuation of Type I IFN signaling and the protection of activated dendritic cells from the cytotoxic effects of autocrine or paracrine Type I IFN. In this paper we discuss a potential role of this mechanism in regulating the processes of innate immunity

The Nlrp3 inflammasome regulates acute graft-versus-host disease

The success of allogeneic hematopoietic cell transplantation is limited by acute graft-versus-host disease (GvHD), a severe complication accompanied by high mortality rates. Yet, the molecular mechanisms initiating this disease remain poorly defined. In this study, we show that, after conditioning therapy, intestinal commensal bacteria and the damage-associated molecular pattern uric acid contribute to Nlrp3 inflammasome-mediated IL-1β production and that gastrointestinal decontamination and uric acid depletion reduced GvHD severity. Early blockade of IL-1β or genetic deficiency of the IL-1 receptor in dendritic cells (DCs) and T cells improved survival. The Nlrp3 inflammasome components Nlrp3 and Asc, which are required for pro-IL-1β cleavage, were critical for the full manifestation of GvHD. In transplanted mice, IL-1β originated from multiple intestinal cell compartments and exerted its effects on DCs and T cells, the latter being preferentially skewed toward Th17. Compatible with these mouse data, increased levels of active caspase-1 and IL-1β were found in circulating leukocytes and intestinal GvHD lesions of patients. Thus, the identification of a crucial role for the Nlrp3 inflammasome sheds new light on the pathogenesis of GvHD and opens a potential new avenue for the targeted therapy of this severe complication