California Stress, Trauma, and Resilience Study (CalSTARS) protocol: A multiomics-based cross-sectional investigation and randomized controlled trial to elucidate the biology of ACEs and test a precision intervention for reducing stress and enhancing resilience.

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision.

Transcriptional evidence of HPA axis dysregulation in adolescent females: Unique contributions of chronic early-life stressor exposure and maternal depression history.

Background: Depression risk increases dramatically for adolescent females following the pubertal transition. Although chronic early-life stressor exposure and a maternal history of depression are established risk factors for depression onset in this population, we know little about the biological mechanisms underlying these associations.

Method: To investigate, we examined how chronic early-life stressor exposure and maternal depression history were associated with stress-related gene expression patterns, using a high-risk family design in 48 psychiatrically healthy adolescent females, 20 of whom had a mother with a lifetime history of depression.

Dynemicin A Derivatives as Potential Cancer Chemotherapeutics by Mutasynthesis.

The enediyne antitumor antibiotics have remarkable structures and exhibit potent DNA cleavage properties that have inspired continued interest as cancer therapeutics. Their complex structures and high reactivity, however, pose formidable challenges to their production and development in the clinic. We report here proof-of-concept studies using a mutasynthesis strategy to combine chemical synthesis of select modifications to a key iodoanthracene-γ-thiolactone intermediate in the biosynthesis of dynemicin A and all other known anthraquinone-fused enediynes (AFEs).

Structural basis for CCR6 modulation by allosteric antagonists.

The CC chemokine receptor 6 (CCR6) is a potential target for chronic inflammatory diseases. Previously, we reported an active CCR6 structure in complex with its cognate chemokine CCL20, revealing the molecular basis of CCR6 activation. Here, we present two inactive CCR6 structures in ternary complexes with different allosteric antagonists, CCR6/SQA1/OXM1 and CCR6/SQA1/OXM2.

The effects of childhood adversity on twenty-five disease biomarkers and twenty health conditions in adulthood: Differences by sex and stressor type.

Background: Although early adversity is now recognized as a major public health concern, it remains unclear if the effects of early-life stressors on disease biology and health differ by sex or stressor type. Because childhood stressors often covary, examining whether such stressors typically occur together (e.g.

Early adversity and sexual diversity: the importance of self-reported and neurobiological sexual reward sensitivity.

Work shows that sexually-diverse individuals face high rates of early life adversity and in turn increased engagement in behavioral outcomes traditionally associated with adversity, such as sexual risk taking. Recent theoretical work suggests that these associations may be attributable to heightened sexual reward sensitivity among adversity-exposed women. We aimed to test these claims using a combination of self-report and EEG measures to test the relationship between early adversity, sexual reward sensitivity (both self-reported and EEG measured) and sexual risk taking in a sexually diverse sample of cis-gender women (N = 208) (Mage = 27.

Characterizing the hierarchical depression phenotype in sexually diverse individuals.

Introduction: Sexual diverse individuals are at high risk for internalizing psychopathologies, such as depression. Understanding how symptom profiles of heterogeneous psychiatric disorders such as depression differ for sexually diverse vs. heterosexual individuals is thus critical to advance precision psychiatry and maximize our ability to effectively treat members of this population.

Multi-omics in stress and health research: study designs that will drive the field forward.

Despite decades of stress research, there still exist substantial gaps in our understanding of how social, environmental, and biological factors interact and combine with developmental stressor exposures, cognitive appraisals of stressors, and psychosocial coping processes to shape individuals' stress reactivity, health, and disease risk. Relatively new biological profiling approaches, called multi-omics, are helping address these issues by enabling researchers to quantify thousands of molecules from a single blood or tissue sample, thus providing a panoramic snapshot of the molecular processes occurring in an organism from a systems perspective. In this review, we summarize two types of research designs for which multi-omics approaches are best suited, and describe how these approaches can help advance our understanding of stress processes and the development, prevention, and treatment of stress-related pathologies.

Quantifying Cell Death Induced by the NLRC4 Inflammasome.

The Nod-like Receptor (NLR) apoptosis inhibitory proteins (NAIPs) are cytosolic receptors that sense cytosolic bacterial proteins. NAIP ligation induces its association with NLRC4, leading to the assembly of the NAIP/NLRC4 inflammasome, which induces the activation of the caspase-1 protease. Caspase-1 then cleaves pro-interleukin (IL)-1β, pro-IL-18, and gasdermin D and induces a form of pro-inflammatory cell death, pyroptosis.

Multi-omics approaches in psychoneuroimmunology and health research: Conceptual considerations and methodological recommendations.

The field of psychoneuroimmunology (PNI) has grown substantially in both relevance and prominence over the past 40 years. Notwithstanding its impressive trajectory, a majority of PNI studies are still based on a relatively small number of analytes. To advance this work, we suggest that PNI, and health research in general, can benefit greatly from adopting a multi-omics approach, which involves integrating data across multiple biological levels (e.

A Novel C-C Chemoattractant Cytokine (Chemokine) Receptor 6 (CCR6) Antagonist (PF-07054894) Distinguishes between Homologous Chemokine Receptors, Increases Basal Circulating CCR6 T Cells, and Ameliorates Interleukin-23-Induced Skin Inflammation.

Blocking chemokine receptor C-C chemoattractant cytokine (chemokine) receptor (CCR) 6-dependent T cell migration has therapeutic promise in inflammatory diseases. PF-07054894 is a novel CCR6 antagonist that blocked only CCR6, CCR7, and C-X-C chemoattractant cytokine (chemokine) receptor (CXCR) 2 in a -arrestin assay panel of 168 G protein-coupled receptors. Inhibition of CCR6-mediated human T cell chemotaxis by (R)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide (PF-07054894) was insurmountable by CCR6 ligand, C-C motif ligand (CCL) 20.

Associations Between Childhood Victimization, Adult Victimization, and Physical Health Among Sexually Diverse Adults at Different Stages of Life.

Research examining health disparities in sexually diverse populations is quite variable. The purpose of the present article was to shed light on the conflicting findings pertaining to minority stress and health by examining the potential impact of age, childhood victimization, and different measurements of health. The present research used data from the Generations Study, a questionnaire study of sexually diverse adults (ages 18-60) surveyed between 2016 and 2019.

Histomorphological study of hepatic lobules of adult Wistar rats administered with aqueous extracts of leaves of .

Objectives: is widely used in northern Nigeria as an herb for the treatment of enamors ailments. Nevertheless the toxicity of the herb on liver architecture; the hepatic lobule and body weight is yet to be authenticated.

Methods: A total of 24 male Wistar rats with an average weight of 150 g were randomly placed into four groups.

Social Safety Theory: Conceptual foundation, underlying mechanisms, and future directions.

Classic theories of stress and health are largely based on assumptions regarding how different psychosocial stressors influence biological processes that, in turn, affect human health and behavior. Although theoretically rich, this work has yielded little consensus and led to numerous conceptual, measurement, and reproducibility issues. Social Safety Theory aims to address these issues by using the primary goal and regulatory logic of the human brain and immune system as the basis for specifying the social-environmental situations to which these systems should respond most strongly to maximize reproductive success and survival.

Examining Heterodimerization by Aryl C-N Coupling in Dynemicin Biosynthesis.

Distinct among the enediyne antitumor antibiotics, the dynemicin subgroup is comprised of two discrete halves, an enediyne and an anthraquinone, but each is ultimately derived from the same linear β-hydroxyhexaene precursor. The linkage of these two halves by an aryl C-N bond is examined here using a variety of experimental approaches. We demonstrate that this heterodimerization is specific for anthracenyl iodide as the corresponding bromo- and amino-substituted anthracenes do not support dynemicin biosynthesis.

Rethinking minority stress: A social safety perspective on the health effects of stigma in sexually-diverse and gender-diverse populations.

For over two decades, the minority stress model has guided research on the health of sexually-diverse individuals (those who are not exclusively heterosexual) and gender-diverse individuals (those whose gender identity/expression differs from their birth-assigned sex/gender). According to this model, the cumulative stress caused by stigma and social marginalization fosters stress-related health problems. Yet studies linking minority stress to physical health outcomes have yielded mixed results, suggesting that something is missing from our understanding of stigma and health.

Mitochondrial Mass of Naïve T Cells Is Associated with Aerobic Fitness and Energy Expenditure of Active and Inactive Adults.

Purpose: Chronic exercise training is known to induce metabolic changes, but whether these adaptations extend to lymphocytes and how this may affect immune function remains largely unknown. This study was conducted to determine the extent to which mitochondrial characteristics of naïve T cells differ according to fitness status and to further examine the energy production pathways of cells from aerobically trained and inactive participants.

Methods: Blood was collected from 30 aerobically active (>6 h·wk -1 ) or inactive (<90 min·wk -1 ) men and women.

Demographic and sociocultural predictors of sexuality-related body image and sexual frequency: The U.S. Body Project I.

Body image is a critical component of an individual's sexual experiences. This makes it critical to identify demographic and sociocultural correlates of sexuality-related body image: the subjective feelings, cognitions, and evaluations related to one's body in the context of sexual experience. We examined how sexuality-related body image differed by gender, sexual orientation, race, age, and BMI.

Exercise after influenza or COVID-19 vaccination increases serum antibody without an increase in side effects.

Vaccination is an effective public health measure, yet vaccine efficacy varies across different populations. Adjuvants improve vaccine efficacy but often increase reactogenicity. An unconventional behavioral "adjuvant" is physical exercise at the time of vaccination.

Understanding the Link Between Adolescent Same-Gender Contact and Unintended Pregnancy: The Role of Early Adversity and Sexual Risk Behavior.

Past research suggests an apparent paradox: Women who engage in same-gender sexual behavior show higher rates of unintended pregnancy than women with exclusive other-gender sexual behavior. Such women also have disproportionate rates of early adversity (both harshness, such as abuse or neglect, and unpredictability, such as father absence). We used the Add Health data (N = 5,617 cisgender women) to examine the relative contributions of early adversity, adolescent same-gender sexual behavior, and general sexual risk behavior to women's risks for adult unintended pregnancy.

Exercise duration modulates upper and lower respiratory fluid cellularity, antiviral activity, and lung gene expression.

Exercise has substantial health benefits, but the effects of exercise on immune status and susceptibility to respiratory infections are less clear. Furthermore, there is limited research examining the effects of prolonged exercise on local respiratory immunity and antiviral activity. To assess the upper respiratory tract in response to exercise, we collected nasal lavage fluid (NALF) from human subjects (1) at rest, (2) after 45 min of moderate-intensity exercise, and (3) after 180 min of moderate-intensity exercise.

The Health Benefits of Sexual Expression.

Objective: Sexual activity is a fundamental human function with short-term and long-term emotional, social, and physical benefits. Yet within healthcare, sexuality has been marginalized and many HCPs are unaware of its beneficial implications for immediate and long-term health.

Methods: To challenge this assumption we combined the data that already had been collected by the authors with an extensive search of articles on the various health benefits of sexual activity.

Systemic inflammation as a driver of health disparities among sexually-diverse and gender-diverse individuals.

Sexually-diverse individuals (those who seek sexual or romantic relationships with the same and/or multiple genders) and gender-diverse individuals (those whose gender identity and/or expression differs from their birth-assigned sex/gender) have disproportionately high physical health problems, but the underlying biological causes for these health disparities remain unclear. Building on the minority stress model linking social stigmatization to health outcomes, we argue that systemic inflammation (the body's primary response to both physical and psychological threats, indicated by inflammatory markers such as C-reactive protein and proinflammatory cytokines) is a primary biobehavioral pathway linking sexual and gender stigma to physical health outcomes. Expectations and experiences of social threat (i.

Illness, Social Disadvantage, and Sexual Risk Behavior in Adolescence and the Transition to Adulthood.

This study investigated the influence of illness on sexual risk behavior in adolescence and the transition to adulthood, both directly and through moderation of the impact of social disadvantage. We hypothesized positive effects for social disadvantages and illness on sexual risk behavior, consistent with the development of faster life history strategies among young people facing greater life adversity. Using the first two waves of the National Longitudinal Study of Adolescent to Adult Health, we developed a mixed-effects multinomial logistic regression model predicting sexual risk behavior in three comparisons: risky nonmonogamous sex versus safer nonmonogamous sex, versus monogamous sex, and versus being sexually inactive, by social characteristics, illness, interactions thereof, and control covariates.