Neuroimaging Evidence for Social Rank Theory

Recent advances in imaging have enabled the study of social rank, which refers generally to an individual’s social standing as either dominant or subordinate in a group, in relation to brain structure and function. From an evolutionary perspective, the mind is a modular structure from which various psychological traits and processes evolved in order to promote the success of the individual and the species. Gilbert (2000) argues that social rank theory explains responses reflecting such a system, which appears to have functional underpinnings linking limbic, prefrontal, and striatal structures (Levitan et al., 2000). Researchers argue tha

Epigenetic clock analysis of diet, exercise, education, and lifestyle factors

Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti

IgG glycosylation and DNA methylation are interconnected with smoking

Background: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. Methods: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed. Results: The overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites. Conclusion: Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures. General significance: An epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Some anemonefish lack personality: a comparative assessment of behavioral variation and repeatability in relation to environmental and social factors

Determining the extent of repeatable differences in the behavior of animals and the factors that influence behavioral expression is important for understanding individual fitness and population processes, thereby aiding in species conservation. However, little is known about the causes of variation in the repeatability of behavioral differences among species because rarely have comparative studies been undertaken to examine the repeatability of behavioral differences among individuals within their natural ecological settings. Using two species of endemic subtropical anemonefishes, Amphiprion mccullochi and A. latezonatus at Lord Howe and North Solitary Islands, Australia, we conducted an in situ comparative analysis of personality traits, examining the repeatability of boldness, sociability and aggression as well as the potential role of environmental and social factors on behavioral expression. For A. mccullochi, only boldness and aggression were highly repeatable and these behaviors formed a behavioral syndrome. For A. latezonatus, none of the three behaviors were repeatable due to low-inter-individual variation in behavior. We suggest that the harsher and more variable environmental and social conditions experienced by A. latezonatus have resulted in reduced repeatability in behavior, in contrast to A. mccullochi which typically inhabits a more stable lagoonal reef environment. Additionally, group size and size rank, rather than nearestneighbor distance and anemone size, influenced the expression of these behaviors in both species, suggesting that behavioral variation was more sensitive to social than environmental factors. Overall, differences in repeatability between these closely related species likely reflect adaptations to contrasting environmental and social conditions, although alternative explanations must be considered. The differences in behavioral consistency between these two endemic anemonefishes could lead to disparity in their resilience to environmental or social change in the future

Some anemonefish lack personality: a comparative assessment of behavioral variation and repeatability in relation to environmental and social factors

Determining the extent of repeatable differences in the behavior of animals and the factors that influence behavioral expression is important for understanding individual fitness and population processes, thereby aiding in species conservation. However, little is known about the causes of variation in the repeatability of behavioral differences among species because rarely have comparative studies been undertaken to examine the repeatability of behavioral differences among individuals within their natural ecological settings. Using two species of endemic subtropical anemonefishes, Amphiprion mccullochi and A. latezonatus at Lord Howe and North Solitary Islands, Australia, we conducted an in situ comparative analysis of personality traits, examining the repeatability of boldness, sociability and aggression as well as the potential role of environmental and social factors on behavioral expression. For A. mccullochi, only boldness and aggression were highly repeatable and these behaviors formed a behavioral syndrome. For A. latezonatus, none of the three behaviors were repeatable due to low-inter-individual variation in behavior. We suggest that the harsher and more variable environmental and social conditions experienced by A. latezonatus have resulted in reduced repeatability in behavior, in contrast to A. mccullochi which typically inhabits a more stable lagoonal reef environment. Additionally, group size and size rank, rather than nearest-neighbor distance and anemone size, influenced the expression of these behaviors in both species, suggesting that behavioral variation was more sensitive to social than environmental factors. Overall, differences in repeatability between these closely related species likely reflect adaptations to contrasting environmental and social conditions, although alternative explanations must be considered. The differences in behavioral consistency between these two endemic anemonefishes could lead to disparity in their resilience to environmental or social change in the future

Protein intake and incident frailty in the Women's Health Initiative observational study.

ObjectivesTo evaluate the association between protein intake and incident frailty.DesignProspective cohort study.SettingSubset of the Women's Health Initiative Observational Study conducted at 40 clinical centers.ParticipantsTwenty-four thousand four hundred seventeen women aged 65 to 79 who were free of frailty at baseline with plausible self-reported energy intakes (600-5,000 kcal/day) according to the Food Frequency Questionnaire (FFQ).MeasurementsBaseline protein intake was estimated from the FFQ. Calibrated estimates of energy and protein intake were corrected for measurement error using regression calibration equations estimated from objective measures of total energy expenditure (doubly labeled water) and dietary protein (24-hour urinary nitrogen). After 3 years of follow-up, frailty was defined as having at least three of the following components: low physical function (measured using the Rand-36 questionnaire), exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models estimated associations for uncalibrated and calibrated protein intake.ResultsOf the 24,417 eligible women, 3,298 (13.5%) developed frailty over 3 years. After adjustment for confounders, a 20% increase in uncalibrated protein intake (%kcal) was associated with a 12% (95% confidence interval (CI)=8-16%) lower risk of frailty, and a 20% increase in calibrated protein intake was associated with a 32% (95% CI=23-50%) lower risk of frailty.ConclusionHigher protein consumption, as a fraction of energy, is associated with a strong, independent, dose-responsive lower risk of incident frailty in older women. Using uncalibrated measures underestimated the strength of the association. Incorporating more protein into the diet may be an intervention target for frailty prevention

Protein intake and incident frailty in the Women's Health Initiative observational study.

ObjectivesTo evaluate the association between protein intake and incident frailty.DesignProspective cohort study.SettingSubset of the Women's Health Initiative Observational Study conducted at 40 clinical centers.ParticipantsTwenty-four thousand four hundred seventeen women aged 65 to 79 who were free of frailty at baseline with plausible self-reported energy intakes (600-5,000 kcal/day) according to the Food Frequency Questionnaire (FFQ).MeasurementsBaseline protein intake was estimated from the FFQ. Calibrated estimates of energy and protein intake were corrected for measurement error using regression calibration equations estimated from objective measures of total energy expenditure (doubly labeled water) and dietary protein (24-hour urinary nitrogen). After 3 years of follow-up, frailty was defined as having at least three of the following components: low physical function (measured using the Rand-36 questionnaire), exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models estimated associations for uncalibrated and calibrated protein intake.ResultsOf the 24,417 eligible women, 3,298 (13.5%) developed frailty over 3 years. After adjustment for confounders, a 20% increase in uncalibrated protein intake (%kcal) was associated with a 12% (95% confidence interval (CI)=8-16%) lower risk of frailty, and a 20% increase in calibrated protein intake was associated with a 32% (95% CI=23-50%) lower risk of frailty.ConclusionHigher protein consumption, as a fraction of energy, is associated with a strong, independent, dose-responsive lower risk of incident frailty in older women. Using uncalibrated measures underestimated the strength of the association. Incorporating more protein into the diet may be an intervention target for frailty prevention

Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative.

It is well established that protein-energy malnutrition decreases serum insulin-like growth factor (IGF)-I levels, and supplementation of 30 g of whey protein daily has been shown to increase serum IGF-I levels by 8 % after 2 years in a clinical trial. Cohort studies provide the opportunity to assess associations between dietary protein intake and IGF axis protein levels under more typical eating conditions. In the present study, we assessed the associations of circulating IGF axis protein levels (ELISA, Diagnostic Systems Laboratories) with total biomarker-calibrated protein intake, as well as with dairy product and milk intake, among postmenopausal women enrolled in the Women's Health Initiative (n 747). Analyses were carried out using multivariate linear regression models that adjusted for age, BMI, race/ethnicity, education, biomarker-calibrated energy intake, alcohol intake, smoking, physical activity and hormone therapy use. There was a positive association between milk intake and free IGF-I levels. A three-serving increase in milk intake per d (approximately 30 g of protein) was associated with an estimated average 18·6 % higher increase in free IGF-I levels (95 % CI 0·9, 39·3 %). However, total IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were not associated with milk consumption and nor were there associations between biomarker-calibrated protein intake, biomarker-calibrated energy intake, and free IGF-I, total IGF-I or IGFBP-3 levels. The findings of the present study carried out in postmenopausal women are consistent with clinical trial data suggesting a specific relationship between milk consumption and serum IGF-I levels, although in the present study this association was only statistically significant for free, but not total, IGF-I or IGFBP-3 levels