Sisemised piirangud energiakäitlusele: integratiivne uuring käitumisest, sugulise valiku ornamentidest ja seedesüsteemi tervisest rohevintidel

Väitekirja elektrooniline versioon ei sisalda publikatsiooneEvolutsioonilise ökoloogia üks peamisi eesmärke on mõista, millest tulenevad isenditevahelised erinevused ning kuidas need mõjutavad sigimisedukust ja ellujäämist. Toitainete omastamine, energia tootmine mitokondrites ja energiavarude mobiliseerimine mõjutavad organismi sisemist energiakäitlust. Looma energiavajadus varieerub sõltuvalt kellaajast, aastaajast (nt migratsioon, paljunemine) ja keskkonnatingimustest, seega on oluline tagada, et energia tootmine vastaks vajadusele. Doktoritöö eesmärgiks oli uurida organismi sisemisi piiranguid energiakäitlusele ning piirangute mõju ellujäämisele, käitumisele ja sugulise valiku signaalidele rohevindil. Sooleparasiidid võivad vähendada toitainete imendumist seedesüsteemis. Esmakordselt kasutati seedefektiivsuse hindamiseks lindudelsteatokriti meetodit, mis on laia kasutuspotentsiaaliga ökoloogilistes uuringutes. Steatokriti meetod on lihtne, odav ja mitteinvasiivne ning võimaldab hinnata rasvade hulka väljaheidetes. Organismi energiavahetuse ning stressivastuse reguleerimisel mängivad olulist rolli hormoonid. Lindude peamise glükokortikoidhormooni kortikosterooni (KORT) tase oli keskmiselt 20% madalam laboris kasvanud sulgedes kui looduses kasvanutes. Isenditel kel oli kõrgem sulgede KORT tase looduses oli see kõrgem ka laboris. Kuna KORT seostus ka ellujäämise ja käitumisega, võib KORT peegeldada energiavajaduste varieeruvust isendite vahel. Kollane ja punane karotenoidsetel pigmentidel põhinev sule- või nahavärvus on paljudel loomadel sugulise valiku tunnus. Rohevintide kollasemad suled ei olnud seotud mitte ainult toitainete imendumisega seedesüsteemis, vaid ka parema võimega karotenoide muundada või sulgedesse ladustada. Toidust omastatud karotenoidide modifitseerimine toimub arvatavalt mitokondris ning karotenoidsed signaalid võivad seega signaliseerida isendi võimekust energiat toota. Samuti on võimalik, et mikrobioomi toodetud ained võivad mitokondrite tööd mõjutades mõjutada karotenoidseid tunnuseid. Kokkuvõttes selgus, et energiakäitluse ning ellujäämist ja paljunemisedukust mõjutavate tunnuste üheaegne uurimine aitab paremini mõista isenditevaheliste erinevuste põhjuseid.Explaining the reasons why individuals differ in their performance is a central question in evolutionary and ecological research. Ability to absorb nutrients from food, produce energy in the mitochondria and energy mobilisation pose major internal constraints to energy processing. Energetic needs can vastly differ depending on the time of the day, season, individual’s life history stage and environmental conditions. Thus, organism's energy demands should be matched with energy output. The main goals of this thesis were to study the internal constraints to energy processing and its impact on survival, behaviour and production of sexually selected ornaments. Parasitic infections can reduce nutrient absorption in the digestive system. In this thesis, the application of the steatocrit method for birds was described for the first time. The steatocrit method enables to asess digestive effieciency nonivasivly and has wide potential for the use in ecological studies. Glucocorticoid hormones are important regulators of energy metabolism and stress response. Levels of the predominant glucocorticoid in birds, corticosterone (CORT), were on average 20% lower in lab-grown feathers than in wild-grown feathers, and birds who deposited more CORT into the feathers in one situation did the same in another, despite vastly different environmental conditions. CORT was also related to survival and behaviour. Therefore, CORT could indicate variation of energy requirements between individuals. Red and yellow carotenoid based integument coloration is sexually selected signal in many animals. Yellower feathers in greenfinches were not only related to absorption of nutrients in the gut, but also to carotenoid modification and deposition into signals. Biotransformation of carotenoids supposedly takes place in mitochondria. Thus, carotenoid signals might indicate the individual's capacity to produce energy. It is also possible that the gut microbiome could affect carotenoid colouration via modulation of mitochondrial function. In conclusion, an integrative view that incorporates animals' energetic needs, internal constraints to energy processing, and traits related to survival and reproductive success can help to understand why individuals differ in their performance and fitness.https://www.ester.ee/record=b550731

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity . Here we use 2,009\ua0population-based studies, with measurements of height and weight in more than 112\ua0million adults, to report national, regional and global trends in mean\ua0BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in\ua0some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities\ua0in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake