The Psychophysiological Responses to Social Exclusion and Affective Films

Arts and Sciences Honors Undergraduate Research ScholarshipThis research studies the effects of viewing a positive or a negative (violent) film clip on the psychophysiological responses to social exclusion. While previous research has found impressive behavioral overlap between social exclusion and violent media, these two stimuli have not been studied together. Subjects were exposed to either a positive or a negative film prior to being ostracized by a computer-based, social exclusion paradigm. Resulting psychophysiological variables, principally heart rate and heart rate variability, were compared in a between-subjects design. Surprisingly, a task effect (F(3, 33)=12.86, p<.001) and interaction for heart rate and film type (F(3,33)=3.690, p<.05) demonstrated that the positive film seemed to have a protective effect on the physiological response to social exclusion, decreasing heart rate compared to baseline measures in this film-viewing group. The underlying dynamics of this cardiovascular response show that the decreased heart rate resulted from an attenuation of autonomic nervous system activity during the social exclusion period.This project was awarded an Undergraduate Research Scholarship from the Arts and Sciences Honors Program.No embarg

The causal effect of testosterone on men’s competitive behavior is moderated by basal cortisol and cues to an opponent’s status: Evidence for a context-dependent dual-hormone hypothesis

Testosterone has been theorized to direct status-seeking behaviors, including competitive behavior. However, most human studies to date have adopted correlational designs, and findings across studies are inconsistent. This experiment (n = 115) pharmacologically manipulated men's testosterone levels prior to a mixed-gender math competition and examined basal cortisol (a hormone implicated in stress and social avoidance) and context cues related to an opponent's perceived status (an opponent's gender or a win/loss in a prior competition) as factors that may moderate testosterone's impact on competitive behavior. We test and find support for the hypothesis that testosterone given to low-cortisol men evokes status-seeking behavior, whereas testosterone given to high-cortisol men evokes status-loss avoidance. In the initial rounds of competition, testosterone's influence on competitive decisions depended on basal cortisol and opponent gender. After providing opponent-specific win-lose feedback, testosterone's influence on decisions to reenter competitions depended on basal cortisol and this objective cue to status, not gender. Compared to placebo, men given exogenous testosterone who were low in basal cortisol showed an increased tendency to compete against male and high-status opponents relative to female and low-status opponents (status-seeking). Men given exogenous testosterone who were high in basal cortisol showed the opposite pattern-an increased tendency to compete against female and low-status opponents relative to male and high-status opponents (status-loss avoidance). These results provide support for a context-dependent dual-hormone hypothesis: Testosterone flexibly directs men's competitive behavior contingent on basal cortisol levels and cues that signal an opponent's status. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

On the 3n+l Quantum Number in the Cluster Problem

It has recently been suggested that an exactly solvable problem characterized by a new quantum number may underlie the electronic shell structure observed in the mass spectra of medium-sized sodium clusters. We investigate whether the conjectured quantum number 3n+l bears a similarity to the quantum numbers n+l and 2n+l, which characterize the hydrogen problem and the isotropic harmonic oscillator in three dimensions.Comment: 8 pages, revtex, 4 eps figures included, to be published in Phys.Rev.A, additional material available at http://radix2.mpi-stuttgart.mpg.de/koch/Diss

Periodic orbit theory for realistic cluster potentials: The leptodermous expansion

The formation of supershells observed in large metal clusters can be qualitatively understood from a periodic-orbit-expansion for a spherical cavity. To describe the changes in the supershell structure for different materials, one has, however, to go beyond that simple model. We show how periodic-orbit-expansions for realistic cluster potentials can be derived by expanding only the classical radial action around the limiting case of a spherical potential well. We give analytical results for the leptodermous expansion of Woods-Saxon potentials and show that it describes the shift of the supershells as the surface of a cluster potential gets softer. As a byproduct of our work, we find that the electronic shell and supershell structure is not affected by a lattice contraction, which might be present in small clusters.Comment: 15 pages RevTex, 11 eps figures, additional information at http://www.mpi-stuttgart.mpg.de/docs/ANDERSEN/users/koch/Diss

Resting EEG periodic and aperiodic components predict cognitive decline over 10 years

Measures of intrinsic brain function at rest show promise as predictors of cognitive decline in humans, including EEG metrics such as individual alpha peak frequency (IAPF) and the aperiodic exponent, reflecting the strongest frequency of alpha oscillations and the relative balance of excitatory:inhibitory neural activity, respectively. Both IAPF and the aperiodic exponent decrease with age and have been associated with worse executive function and working memory. However, few studies have jointly examined their associations with cognitive function, and none have examined their association with longitudinal cognitive decline rather than cross-sectional impairment. In a preregistered secondary analysis of data from the longitudinal Midlife in the United States (MIDUS) study, we tested whether IAPF and aperiodic exponent measured at rest predict cognitive function (N = 235; age at EEG recording M = 55.10, SD = 10.71) over 10 years. The IAPF and the aperiodic exponent interacted to predict decline in overall cognitive ability, even after controlling for age, sex, education, and lag between data collection timepoints. Post-hoc tests showed that “mismatched” IAPF and aperiodic exponents (e.g., higher exponent with lower IAPF) predicted greater cognitive decline compared to “matching” IAPF and aperiodic exponents (e.g., higher exponent with higher IAPF; lower IAPF with lower aperiodic exponent). These effects were largely driven by measures of executive function. Our findings provide the first evidence that IAPF and the aperiodic exponent are joint predictors of cognitive decline from midlife into old age and thus may offer a useful clinical tool for predicting cognitive risk in aging

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Single Nucleotide Polymorphisms in IL1B and the Risk of Acute Coronary Syndrome: A Danish Case-Cohort Study

BACKGROUND: Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary syndrome (ACS) have not been thoroughly investigated. The aims of this study were to examine the associations between individual SNPs in and SNP haplotypes of the promoter region of IL1B and incident ACS in a prospective study. Furthermore, we wanted to explore potential interactions with other risk factors for ACS on an additive scale. METHODOLOGY/PRINCIPAL FINDINGS: The present study was based on the Danish prospective study Diet, Cancer and Health comprising more than 57 000 participants aged 50-64 at baseline. During a median follow-up of 7.2 years we identified 989 cases of incident ACS (755 men and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire cohort. Weighted Cox proportional hazard models with age as time axis were used in the statistical analyses. Individual IL1B SNPs, SNP haplotypes, or haplotype combinations were not significantly associated with incident ACS, and, likewise, we found no evidence of interaction on an additive scale between IL1B haplotypes and risk factors, respectively. CONCLUSIONS/SIGNIFICANCE: Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years

Correlating Gene Expression Variation with cis-Regulatory Polymorphism in Saccharomyces cerevisiae

Identifying the nucleotides that cause gene expression variation is a critical step in dissecting the genetic basis of complex traits. Here, we focus on polymorphisms that are predicted to alter transcription factor binding sites (TFBSs) in the yeast, Saccharomyces cerevisiae. We assembled a confident set of transcription factor motifs using recent protein binding microarray and ChIP-chip data and used our collection of motifs to predict a comprehensive set of TFBSs across the S. cerevisiae genome. We used a population genomics analysis to show that our predictions are accurate and significantly improve on our previous annotation. Although predicting gene expression from sequence is thought to be difficult in general, we identified a subset of genes for which changes in predicted TFBSs correlate well with expression divergence between yeast strains. Our analysis thus demonstrates both the accuracy of our new TFBS predictions and the feasibility of using simple models of gene regulation to causally link differences in gene expression to variation at individual nucleotides

Association between age and the host response in critically ill patients with sepsis

Background: The association of ageing with increased sepsis mortality is well established. Nonetheless, current investigations on the influence of age on host response aberrations are largely limited to plasma cytokine levels while neglecting other pathophysiological sepsis domains like endothelial cell activation and function, and coagulation activation. The primary objective of this study was to gain insight into the association of ageing with aberrations in key host response pathways and blood transcriptomes in sepsis.Methods: We analysed the clinical outcome (n=1952), 16 plasma biomarkers providing insight in deregulation of specific pathophysiological domains (n=899), and blood leukocyte transcriptomes (n=488) of sepsis patients stratified according to age decades. Blood transcriptome results were validated in an independent sepsis cohort and compared with healthy individuals. se.Results: Older age was associated with increased mortality independent of comorbidities and disease severity. Ageing was associated with lower endothelial cell activation and dysfunction, and similar inflammation and coagulation activation, despite higher disease severity scores. Blood leukocytes of patients≥70 years, compared to patients<50 years, showed decreased expression of genes involved in cytokine signaling, and innate and adaptive immunity, and increased expression of genes involved in hemostasis and endothelial cell activation. The diminished expression of gene pathways related to innate immunity and cytokine signaling in subjects≥70 years was sepsis-induced, as healthy subjects≥70 years showed enhanced expression of these pathways compared to healthy individuals<50 years.Conclusions: This study provides novel evidence that older age is associated with relatively mitigated sepsis-induced endothelial cell activation and dysfunction, and a blood leukocyte transcriptome signature indicating impaired innate immune and cytokine signaling. These data suggest that age should be considered in patient selection in future sepsis trials targeting the immune system and/or the endothelial cell response.peer-reviewe