Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 248 serum proteins relevant to cardiometabolic processes in 2893 individuals. Meta-analyzing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = 1356; 22.5× WGS) and Pomak (n = 1537; 18.4× WGS), we detect 301 independently associated pQTL variants for 170 proteins, including 12 rare variants (minor allele frequency < 1%). We additionally find 15 pQTL variants that are rare in non-Finnish European populations but have drifted up in the frequency in the discovery cohorts here. We identify proteins causally associated with cardiometabolic traits, including Mep1b for high-density lipoprotein (HDL) levels, and describe a knock-out (KO) Mep1b mouse model. Our findings furnish insights into the genetic architecture of the serum proteome, identify new protein-disease relationships and demonstrate the importance of isolated populations in pQTL analysis.

• MeSH
• Genome-Wide Association Study MeSH
• Diabetes Mellitus, Type 2 * MeSH
• Phenotype MeSH
• Cardiovascular Diseases * MeSH
• Blood Proteins genetics   MeSH
• Mice MeSH
• Whole Genome Sequencing MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Neurogenesis in the adult hippocampus contributes to learning and memory in the healthy brain but is dysregulated in metabolic and neurodegenerative diseases. The molecular relationships between neural stem cell activity, adult neurogenesis, and global metabolism are largely unknown. Here we applied unbiased systems genetics methods to quantify genetic covariation among adult neurogenesis and metabolic phenotypes in peripheral tissues of a genetically diverse family of rat strains, derived from a cross between the spontaneously hypertensive (SHR/OlaIpcv) strain and Brown Norway (BN-Lx/Cub). The HXB/BXH family is a very well established model to dissect genetic variants that modulate metabolic and cardiovascular diseases and we have accumulated deep phenome and transcriptome data in a FAIR-compliant resource for systematic and integrative analyses. Here we measured rates of precursor cell proliferation, survival of new neurons, and gene expression in the hippocampus of the entire HXB/BXH family, including both parents. These data were combined with published metabolic phenotypes to detect a neurometabolic quantitative trait locus (QTL) for serum glucose and neuronal survival on Chromosome 16: 62.1-66.3 Mb. We subsequently fine-mapped the key phenotype to a locus that includes the Telo2-interacting protein 2 gene (Tti2)-a chaperone that modulates the activity and stability of PIKK kinases. To verify the hypothesis that differences in neurogenesis and glucose levels are caused by a polymorphism in Tti2, we generated a targeted frameshift mutation on the SHR/OlaIpcv background. Heterozygous SHR-Tti2+/- mutants had lower rates of hippocampal neurogenesis and hallmarks of dysglycemia compared to wild-type littermates. Our findings highlight Tti2 as a causal genetic link between glucose metabolism and structural brain plasticity. In humans, more than 800 genomic variants are linked to TTI2 expression, seven of which have associations to protein and blood stem cell factor concentrations, blood pressure and frontotemporal dementia.

• MeSH
• Phenotype MeSH
• Glucose * genetics   metabolism   MeSH
• Hippocampus metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Neurogenesis * genetics   MeSH
• Rats, Inbred BN MeSH
• Rats, Inbred SHR MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Dôležitosť sledovania pracovného stresu a jeho následkov na duševné zdravie zdôrazňuje rastúca prevalencia absencií v práci z dôvodu pracovnej neschopnosti zapríčinenej ochoreniami zo stresu. Cieľom práce bolo preskúmať osobné zdroje ako mediačné faktory pri rozvoji úzkosti a depresie v dôsledku pracovného stresu v rizikových profesiách. Skúmaný súbor tvorilo 208 pracovníkov z radov policajtov, väzenských dozorcov a colníkov (78,8 % mužov, priemerný vek 36,5 rokov), ktorí poskytli sociodemografické a pracovné údaje. Použité boli Inventórium zamestnaneckého stresu, z neho dotazníky zamestnaneckých rolí a osobných zdrojov (OSI- -R), Dotazník na meranie úzkosti a úzkostlivosti, z toho aktuálna úzkosť (STAI X-1) a Zungov dotazník depresie (SDS). Zamestnanecké roly tu predstavujú mieru pracovného stresu. Na štatistickú analýzu bolo využité štrukturálne modelovanie. Výsledný model, ktorý tvorili pracovný čas (pohotovosť, nadčasy, nočná práca), zamestnanecké roly a osobné zdroje, predikoval 35 % variability aktuálnej úzkosti a 42 % variability depresívnej symptomatiky. Signifikantnými prediktormi úzkosti boli roly preťaženia a nejednoznačnosti, ktoré boli mediované prostredníctvom osobných zdrojov rekreácie a racionálno- kognitívnych stratégií. Signifikantnými prediktormi depresie boli roly preťaženia, nedostatočnosti a nejednoznačnosti mediované prostredníctvom osobných zdrojov rekreácie, sociálnej opory a racionálno-kognitívnych stratégií. Nočná práca, nadčasy, ani pohotovosť v tomto súbore nepôsobili na úzkosť a depresiu, hoci predikovali zamestnanecké roly. Efekt pracovného stresu ako preťaženie, roly nedostatočnosti a nejednoznačnosti na úzkostnú a depresívnu symptomatiku bol štatisticky významný prostredníctvom redukovania osobných zdrojov, i keď nepriamo. Osobné zdroje sú významné mediačné faktory medzi pracovným stresom a úzkosťou a depresiou v sledovaných profesiách. Štúdia má prierezový charakter, kauzálne vzťahy môžu byť v budúcnosti overované pomocou intervenčných programov.

Background. The importance of monitoring work-related stress and its consequences for mental health is underlined by the increasing prevalence of absence from work due to stress-related illnesses. Objectives. The aim of the study was to examine personal resources as mediating factors in the development of anxiety and depression from work-related stress in high-risk professions. Sample and methods. The sample comprised a total of 208 police officers, prison guards and customs officers (78.8% men, an average age of 36.5) who provided socio-demographic and job-related information. The Occupational Stress Inventory was used (OSI-R), in particular Occupational Roles Questionnaire and Personal Resources Questionnaire, State Trait Anxiety Inventory (STAI X-1), and Zung Self-Rating Depression Scale (SDS). Occupational roles represent measurement of occupational stress. Statistical analysis. Structural modelling was used for statistical analysis. Results. The final model, comprising working time (emergency care, overtime, night shifts), occupational roles and personal resources, predicted 35% of variability of anxiety, and 42% of variability of depression. Significant predictors of anxiety were the roles of overload and ambiguity, which were mediated by recreation and rational-cognitive coping strategies. Significant predictors of depression were the roles of overload, insufficiency and ambiguity, which were mediated by recreation, social support and rational-cognitive coping strategies. Night shifts, overtime and emergency care did not predict anxiety and depression although they predicted occupational roles. The effect of occupational roles including overload, insufficiency and ambiguity on anxiety and depression was statistically significant, yet indirectly, by reducing personal resources. Personal resources are considerable mediating factors between stress, anxiety and depression in the studied professions. Limits. The study was cross-sectional. Causal relationships can be further tested using interventional studies.

• MeSH
• Adaptation, Psychological MeSH
• Mediation Analysis MeSH
• Depression MeSH
• Adult psychology   MeSH
• Correlation of Data MeSH
• Humans MeSH
• Workforce MeSH
• Occupational Stress * MeSH
• Cross-Sectional Studies MeSH
• Surveys and Questionnaires MeSH
• Risk Factors MeSH
• Professional Role MeSH
• Anxiety MeSH
• Occupations MeSH
• Check Tag
• Adult psychology   MeSH
• Humans MeSH

Genetic data has become an essential part of ecological studies, because the analyses of diversity within and among natural populations may grant access to previously overlooked ecological and evolutionary causalities, especially among cryptic species. Here, we present an example of how phylogenetic analysis of molecular data obtained within a DNA barcoding study, in combination with morphological and ecological data from the field and laboratory experiments, unraveled a striking predator-prey interaction between aquatic organisms. The "crown of thorns," a conspicuous morphological feature among water fleas of the Daphnia atkinsoni species complex (Crustacea: Cladocera), is considered to represent a species-specific trait. However, our study, initiated by the analysis of sequence variation in 2 mitochondrial genes, shows that this feature is phenotypically plastic and is induced by chemical cues released by Triops cancriformis, the tadpole shrimp (Notostraca). The trait acts as an effective antipredator defense, and is found in several Daphnia lineages coexisting with notostracans. These facts suggest that the "crown of thorns" evolved in coexistence with this ancient predator group.

• MeSH
• Models, Anatomic MeSH
• Biological Evolution MeSH
• Models, Biological MeSH
• Cell Lineage MeSH
• Cladocera MeSH
• Daphnia anatomy & histology   physiology   metabolism   MeSH
• Ecology MeSH
• Phenotype MeSH
• Financing, Organized MeSH
• Phylogeny MeSH
• Humans MeSH
• DNA, Mitochondrial metabolism   MeSH
• Food Chain MeSH
• Predatory Behavior MeSH
• Electron Transport Complex IV metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH

Parents affect offspring fitness by propagule size and quality, selection of oviposition site, quality of incubation, feeding of dependent young, and their defence against predators and parasites. Despite many case studies on each of these topics, this knowledge has not been rigorously integrated into individual parental care traits for any taxon. Consequently, we lack a comprehensive, quantitative assessment of how parental care modifies offspring phenotypes. This meta-analysis of 283 studies with 1805 correlations between egg size and offspring quality in birds is intended to fill this gap. The large sample size enabled testing of how the magnitude of the relationship between egg size and offspring quality depends on a number of variables. Egg size was positively related to nearly all studied offspring traits across all stages of the offspring life cycle. Not surprisingly, the relationship was strongest at hatching but persisted until the post-fledging stage. Morphological traits were the most closely related to egg size but significant relationships were also found with hatching success, chick survival, and growth rate. Non-significant effect sizes were found for egg fertility, chick immunity, behaviour, and life-history or sexual traits. Effect size did not depend on whether chicks were raised by their natural parents or were cross-fostered to other territories. Effect size did not depend on species-specific traits such as developmental mode, clutch size, and relative size of the egg, but was larger if tested in captive compared to wild populations and between rather than within broods. In sum, published studies support the view that egg size affects juvenile survival. There are very few studies that tested the relationship between egg size and the fecundity component of offspring fitness, and no studies on offspring survival as adults or on global fitness. More data are also needed for the relationships between egg size and offspring behavioural and physiological traits. It remains to be established whether the relationship between egg size and offspring performance depends on the quality of the offspring environment. Positive effect sizes found in this study are likely to be driven by a causal effect of egg size on offspring quality. However, more studies that control for potential confounding effects of parental post-hatching care, genes, and egg composition are needed to establish firmly this causal link.

• MeSH
• Longevity physiology   MeSH
• Genetic Fitness MeSH
• Ovum cytology   physiology   MeSH
• Birds physiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• MeSH
• Behavior MeSH
• Psychology, Applied MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Psychologie
• NML Fields
• psychologie, klinická psychologie

There is some urgency in the necessity to incorporate physiological data into mechanistic, trait-based, demographic climate change models. Physiological responses at the individual level provide the mechanistic link between environmental changes and individual performances and hence population dynamics. Here we consider the causal relationship between ambient temperature (Ta) and metabolic rate (MR), namely, the Arrhenius effect, which is directly affected by global warming through increases in average global air temperatures and the increase in the frequency and intensity of extreme climate events. We measured and collated data for several small, free-ranging tropical arboreal mammals and evaluated their vulnerability to Arrhenius effects and putative heat stress associated with climate change. Skin temperatures (Tskin) were obtained from free-ranging tarsiers (Tarsius syrichta) on Bohol Island, Philippines. Core body temperature (Tb) was obtained from the greater hedgehog tenrec (Setifer setosus) and the gray brown mouse lemur (Microcebus ravelobensis) from Ankarafantsika, Madagascar. Tskin for another mouse lemur, Microcebus griseorufus, was obtained from the literature. All four species showed evidence of hyperthermia during the daytime rest phase in the form of either Tskin or Tb that was higher than the normothermic Tb during the nighttime active phase. Potentially, tropical arboreal mammals with the lowest MRs and Tb, such as tarsiers, are the most vulnerable to sustained heat stress because their Tb is already close to Ta. Climate change may involve increases in MRs due to Arrhenius effects, especially during the rest phase or during torpor and hibernation. The most likely outcome of increased Arrhenius effects with climate change will be an increase in energy expenditure at the expense of other critical functions such as reproduction or growth and will thus affect fitness. However, we propose that these hypothetical Arrhenius costs can be, and in some species probably are, offset by the use of hyperthermic daily torpor, that is, hypometabolism at high Ta.

• MeSH
• Basal Metabolism * MeSH
• Cheirogaleidae physiology   MeSH
• Eulipotyphla physiology   MeSH
• Climate Change MeSH
• Heat-Shock Response * MeSH
• Torpor * MeSH
• Tarsiidae physiology   MeSH
• Temperature MeSH
• Tropical Climate MeSH
• Body Size * MeSH
• Conservation of Natural Resources MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Philippines MeSH
• Madagascar MeSH

In natural populations, individuals experience daily fluctuations in environmental conditions that synchronise endogenous biorhythms. Artificial alterations of environmental fluctuations can have negative consequences for life history traits, including lifespan. In laboratory studies of aging, the role of fluctuating temperature is usually overlooked and we know little of how thermal fluctuation modulates senescence in vertebrates. In this longitudinal study we followed individually-housed turquoise killifish, Nothobranchius furzeri, from two thermal regimes; ecologically relevant diel fluctuations (20 °C - 35 °C) and stable temperature (27.5 °C), and compared their survival, growth and reproduction. Fish experiencing fluctuating temperatures had a longer median lifespan but reached smaller asymptotic body size. Within-treatment variation indicated that extended lifespan in fluctuating temperatures was not causally linked to decreased growth rate or smaller body size, but occurred solely due to the effect of thermal fluctuations. Male body size was positively associated with lifespan in stable temperatures but this relationship was disrupted in fluctuating thermal regimes. Females exposed to fluctuating temperatures effectively compensated egg production for their smaller size. Thus, there was no difference in absolute fecundity between thermal regimes and body-size corrected fecundity was higher in females in fluctuating temperatures. Overall, despite a brief exposure to sub-optimal thermal conditions during fluctuations, fluctuating temperature had a positive effect on survival and reproduction. These results suggest that the expression of life history traits and their associations under stable temperatures are a poor representation of the relationships obtained from ecologically relevant thermal fluctuations.

• MeSH
• Longevity MeSH
• Fundulidae * MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Reproduction MeSH
• Temperature MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies.NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.

• MeSH
• Biomarkers metabolism   MeSH
• Diabetes Mellitus, Type 2 * metabolism   MeSH
• Insulin Resistance * MeSH
• Humans MeSH
• Obesity, Morbid * metabolism   MeSH
• Intra-Abdominal Fat metabolism   MeSH
• Obesity metabolism   MeSH
• Subcutaneous Fat metabolism   MeSH
• Proteins metabolism   MeSH
• Proteomics MeSH
• Cross-Sectional Studies MeSH
• Adipose Tissue metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH