Papers by Sonja Entringer
International Journal of Obesity, 2016
Background/Objectives: Elevated pre-pregnancy BMI (pBMI) and excess gestational weight gain (GWG)... more Background/Objectives: Elevated pre-pregnancy BMI (pBMI) and excess gestational weight gain (GWG) constitute important prenatal exposures which may program adiposity and disease risk in offspring. However, the biological mechanisms underlying these fetal programming pathways remain unclear. The objective of this study is to investigate the influence of pBMI and GWG on the maternal metabolomic profile across pregnancy trimesters, and to identify potential causal pathways for offspring adiposity. Subjects/Methods: This is a longitudinal prospective study of 167 non-diabetic women carrying a singleton pregnancy. Women were recruited between March 2011-December 2013 from antenatal clinics affiliated to the University of California Medical Center in Orange County, California. Seven women were excluded from analyses due to a diagnosis of diabetes during their pregnancies. A total of 254 plasma metabolites known to be related to obesity in non-pregnant populations were analyzed in each trimester using targeted metabolomics. The effects of pBMI and GWG on these metabolites were tested through linear regression and principle component analysis, adjusting for maternal diet, maternal insulin resistance, age, and race/ethnicity. A Bonferroni correction was applied for multiple comparison testing. Results: pBMI was significantly associated with 40 metabolites. Non-esterified fatty acids (NEFA) showed a strong positive association with pBMI, with specificity for mono-unsaturated and omega-6 NEFA. Among phospholipids, sphingomyelins with two double bonds and phosphatidylcholines containing 20:3 fatty acid chain, indicative of omega-6 NEFA, were positively associated with pBMI. Few associations between GWG, quality and quantity of the diet, insulin resistance and the maternal metabolome throughout gestation were detected. Conclusion: Pre-conception obesity appears to have a stronger influence on the maternal metabolic milieu than gestational factors such as weight gain, dietary intake and insulin resistance, highlighting the critical importance of pre-conception health. Mono-unsaturated and omega-6 fatty acids represent key metabolites for a potential mechanism of intergenerational transfer of obesity risk.
Our conceptual model proposes that (a) intrauterine life represents a particularly sensitive time... more Our conceptual model proposes that (a) intrauterine life represents a particularly sensitive time period when the effects of maternal conditions, states and exposures around conception and across pregnancy may be transmitted to the developing embryo/fetus; (b) transmission occurs primarily via the effects of various maternal states and conditions on stress-related maternal-placental-fetal (MPF) oxidative, immune/inflammatory, endocrine and metabolic pathways that participate in the process of developmental programming of health and disease risk; (c) the initial setting and function of the offspring mitochondrial biology system exhibits developmental plasticity and represents a key cellular target of such programming; (d) this initial setting of offspring mitochondrial biology has important implications for health, aging and susceptibility for common age-related disorders; and (e) in addition to the prenatal period exposures during the maternal pre-conception and during grandmaternal...
Research on mechanisms underlying the phenomenon of developmental programming of health and disea... more Research on mechanisms underlying the phenomenon of developmental programming of health and disease has focused primarily on processes that are specific to cell types, organs and phenotypes of interest. However, the observation that exposure to suboptimal or adverse developmental conditions <i>concomitantly</i> influences a broad range of phenotypes suggests that these exposures may additionally exert effects through cellular mechanisms that are common, or shared, across these different cell and tissue types. It is in this context that we focus on cellular bioenergetics and propose that mitochondria, bioenergetic and signalling organelles may represent a key cellular target underlying developmental programming. In this review, we discuss empirical findings in animals and humans that suggest key structural and functional features of mitochondrial biology exhibit developmental plasticity; are influenced by the same physiological pathways that are implicated in susceptibili...
The Journal of Clinical Endocrinology & Metabolism, 2020
Context Variation in fetal liver blood flow influences fetal growth and postnatal body compositio... more Context Variation in fetal liver blood flow influences fetal growth and postnatal body composition. Placental corticotrophin-releasing hormone has been implicated as a key mediator of placental-fetal perfusion. Objective To determine whether circulating levels of placental corticotrophin-releasing hormone across gestation are associated with variations in fetal liver blood flow. Design Prospective cohort study. Methods Fetal ultrasonography was performed at 30 weeks’ gestation to characterize fetal liver blood flow (quantified by subtracting ductus venosus flow from umbilical vein flow). Placental corticotrophin-releasing hormone was measured in maternal circulation at approximately 12, 20, and 30 weeks’ gestation. Multiple regression analysis was used to determine the proportion of variation in fetal liver blood flow explained by placental corticotrophin-releasing hormone. Covariates included maternal age, parity, pre-pregnancy body mass index, gestational weight gain, and fetal se...
Diet, Nutrition, and Fetal Programming, 2017
A substantial body of evidence suggests that suboptimal conditions in intrauterine and early post... more A substantial body of evidence suggests that suboptimal conditions in intrauterine and early postnatal life play a critical role in subsequent health and susceptibility for a range of complex, common disorders that confer a major, global burden of disease (i.e., the concept of fetal or developmental programming of health and disease). The elucidation of biological mechanisms underlying these observed effects is an area of active interest and intense investigation. We advance the hypothesis that telomere biology may represent a common mechanism underlying the observed effects of a disparate set of suboptimal intrauterine exposures on various health and disease risk phenotypes of interest. Moreover, in this chapter we summarize available data from animal and human studies reporting on the consequences of maternal (mal)nutrition, obstetric risk conditions during pregnancy, and suboptimal birth outcomes on the offspring telomere biology system. We propose that these factors during the intrauterine period of development may alter or program the telomere biology system in a manner that accelerates cellular dysfunction, aging, and disease susceptibility over the life span.
American Journal of Reproductive Immunology, 2020
The immune system represents a leading pathway of interest in the pathophysiology of preterm birt... more The immune system represents a leading pathway of interest in the pathophysiology of preterm birth. The majority of human clinical studies interrogating this pathway have utilized circulating immune biomarkers; however, these concentrations typically reflect only basal production but not key functional properties of the immune system, particularly variation in the pro‐inflammatory response to antigen challenge and the regulation of this response. Thus, in this study, we utilized an ex vivo stimulation protocol that quantifies these processes, and we examined their prospective association with the gestation length and risk of preterm birth.
There is a major resurgence of interest in brown adipose tissue (BAT) biology, particularly regar... more There is a major resurgence of interest in brown adipose tissue (BAT) biology, particularly regarding its determinants and consequences in newborns and infants. Reliable methods for non-invasive BAT measurement in human infants have yet to be demonstrated. The current study first validates methods for quantitative BAT imaging of rodents post mortem followed by BAT excision and re-imaging of excised tissues. Identical methods are then employed in a cohort of in vivo infants to establish the reliability of these measures and provide normative statistics for BAT depot volume and fat fraction. Using multi-echo water-fat MRI, fatand water-based images of rodents and neonates were acquired and ratios of fat to the combined signal from fat and water (fat signal fraction) were calculated. Neonatal scans (n = 22) were acquired during natural sleep to quantify BAT and WAT deposits for depot volume and fat fraction. Acquisition repeatability was assessed based on multiple scans from the same n...
Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the orig... more Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placentalfetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice.
Research on mechanisms underlying the phenomenon of developmental programming of health and disea... more Research on mechanisms underlying the phenomenon of developmental programming of health and disease has focused primarily on processes that are specific to cell types, organs and phenotypes of interest. However, the observation that exposure to suboptimal or adverse developmental conditions <i>concomitantly</i> influences a broad range of phenotypes suggests that these exposures may additionally exert effects through cellular mechanisms that are common, or shared, across these different cell and tissue types. It is in this context that we focus on cellular bioenergetics and propose that mitochondria, bioenergetic and signalling organelles may represent a key cellular target underlying developmental programming. In this review, we discuss empirical findings in animals and humans that suggest key structural and functional features of mitochondrial biology exhibit developmental plasticity; are influenced by the same physiological pathways that are implicated in susceptibility for complex, common age-related disorders; and that these targets of mitochondrial developmental programming exhibit long-term temporal stability. We conclude by articulating current knowledge gaps and propose future research directions to bridge these gaps.
Psychological Medicine, 2021
Background Prenatal loss which occurs in approximately 20% of pregnancies represents a well-estab... more Background Prenatal loss which occurs in approximately 20% of pregnancies represents a well-established risk factor for anxiety and affective disorders. In the current study, we examined whether a history of prenatal loss is associated with a subsequent pregnancy with maternal psychological state using ecological momentary assessment (EMA)-based measures of pregnancy-specific distress and mood in everyday life. Method This study was conducted in a cohort of N = 155 healthy pregnant women, of which N = 40 had a history of prenatal loss. An EMA protocol was used in early and late pregnancy to collect repeated measures of maternal stress and mood, on average eight times per day over a consecutive 4-day period. The association between a history of prenatal loss and psychological state was estimated using linear mixed models. Results Compared to women who had not experienced a prior prenatal loss, women with a history of prenatal loss reported higher levels of pregnancy-specific distress...
Brain, Behavior, and Immunity, 2021
Background: Health disparities in children of immigrants are prevalent from birth and are hypothe... more Background: Health disparities in children of immigrants are prevalent from birth and are hypothesized toin partemerge as a biological consequence of migration's unfavorable social and psychological sequelae. The aim of this study was to examine whether maternal migrant background is associated with inflammation during pregnancy -a key pathway by which maternal states and conditions during pregnancy may influence fetal development and subsequent pregnancy, birth, and child developmental and health outcomes. Material and methods: Data was available from 126 pregnant women who participated in a population based multi-site prospective birth cohort study in Bielefeld and Berlin, Germany. The study included two study visits in mid-and late pregnancy. At each visit, a composite maternal pro-inflammatory score was derived from circulating levels of plasma inflammatory markers (IL-6, CRP). Migrant background was defined by country of origin of participants and their parents' (Turkey or other) and generation status (1st or 2nd generation). We applied hierarchical linear models (HLM) in order to quantify the relationship between different migrant background variables and inflammation during pregnancy after adjustment for potential confounders (including socioeconomic status). Results: Migrant background was significantly associated with inflammation during pregnancy. When compared to women without migrant background, levels of inflammation were increased in 1) pregnant women with migrant background in general (B = 0.35, SE = 0.12, p < .01); 2) 1st (B = 0.28, SE = 0.15, p < .10) and 2nd generation (B = 0.40, SE = 0.15, p < .01); 3) women with a Turkish migrant background (B = 0.28, SE = 0.14, p < .10) and women with another migrant background (B = 0.42, SE = 0.15, p < .01); and 4) 2nd generation Turkish origin women (B = 0.38, SE = 0.20, p < .10), 1st generation women with other migrant background (B = 0.44, SE = 0.26, p < .10), and 2nd generation women with other migrant background (B = 0.43, SE = 0.17, p < .05). Discussion: Our findings support a role for maternal inflammation as a pathway of intergenerational transmission of migration-related health inequalities, suggest that the effect seems to persist in 2nd generation immigrants, and highlight the need for future research and targeted interventions in this context.
Clinical Epigenetics, 2021
Background Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment wi... more Background Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enh...
Journal of Psychiatry and Neuroscience, 2021
Background: Genetic variation in the guidance cue DCC gene is linked to psychopathologies involvi... more Background: Genetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume. Methods: We filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual's genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume. Results: Higher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function. Limitations: The relatively small sample size and age differences between the main and replication cohorts were limitations. Conclusion: Our findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment.
Psychoneuroendocrinology, 2021
BACKGROUND The association of acculturation with health among immigrant populations is believed t... more BACKGROUND The association of acculturation with health among immigrant populations is believed to be mediated, in part, by acculturation-related stress and stress biology. OBJECTIVES To review and qualitatively synthesize empirical findings on the relationship of acculturation with stress-related inflammatory and endocrine biomarkers and composite allostatic load (AL) scores. METHODS A literature search was performed in the PubMed and PsycInfo databases. Article titles, abstracts or full-texts were screened and checked for match with the search criteria. Studies were eligible if they empirically tested the relationship between acculturation and inflammatory/endocrine stress biomarkers or composite AL scores, and were published in the English language. RESULTS Among the 41 articles identified as relevant and included in this review, the majority were published after 2010, included adult Hispanic U.S.-based populations, used cross-sectional study designs, operationalized acculturation as a unidimensional construct, and varied considerably in the selection of covariates in the analyses. Acculturation was significantly associated with stress biomarkers in 29 studies, but the direction of effects varied across studies. Specifically, acculturation, operationalized as a higher orientation towards the host culture, was associated with inflammatory biomarkers in 10 of 14 studies, with endocrine stress biomarkers in 12 of 20 studies, and with composite AL scores in 7 of 8 studies. Overall, language-based proxy measures of acculturation were related to higher levels of stress-related inflammatory and endocrine biomarkers and to lower levels of AL scores, whereas nativity-, generation status- and length of stay-based proxy measures of acculturation were related to higher levels of inflammatory biomarkers and AL score. DISCUSSION The majority of studies reported associations between measures of acculturation and stress biomarkers, however the directions of effects varied across studies. We suggest this heterogeneity may, in part, be a function of limitations imposed by cross-sectional research designs and unidimensional measures of acculturation measures, and we highlight the need for longitudinal studies and use of multidimensional measures of acculturation to better uncover the biobehavioral mechanisms and pathways linking acculturation with health outcomes.
Neurobiology of Stress, 2021
Background: Studies reporting accelerated ageing in children with affective disorders or maltreat... more Background: Studies reporting accelerated ageing in children with affective disorders or maltreatment exposure have relied on algorithms for estimating epigenetic age derived from adult samples. These algorithms have limited validity for epigenetic age estimation during early development. We here use a pediatric buccal epigenetic (PedBE) clock to predict DNA methylation-based ageing deviation in children with and without internalizing disorder and assess the moderating effect of maltreatment exposure. We further conduct a gene set enrichment analysis to assess the contribution of glucocorticoid signaling to PedBE clock-based results. Method: DNA was isolated from saliva of 158 children [73 girls, 85 boys; mean age (SD) = 4.25 (0.8) years] including children with internalizing disorder and maltreatment exposure. Epigenetic age was estimated based on DNA methylation across 94 CpGs of the PedBE clock. Residuals of epigenetic age regressed against chronological age were contrasted between children with and without internalizing disorder. Maltreatment was coded in 3 severity levels and entered in a moderation model. Genome-wide dexamethasone-responsive CpGs were derived from an independent sample and enrichment of these CpGs within the PedBE clock was identified. Results: Children with internalizing disorder exhibited significant acceleration of epigenetic ageing as compared to children without internalizing disorder (F 1,147 = 6.67, p = .011). This association was significantly moderated by maltreatment severity (b = 0.49, 95% CI [0.073, 0.909], t = 2.322, p = .022). Children with internalizing disorder who had experienced maltreatment exhibited ageing acceleration relative to children with no internalizing disorder (1-2 categories: b = 0.50, 95% CI [0.170, 0.821], t = 3.008, p = .003; 3 or more categories: b = 0.99, 95% CI [0.380, 1.593], t = 3.215, p = .002). Children with internalizing disorder who were not exposed to maltreatment did not show epigenetic ageing acceleration. There was significant enrichment of dexamethasoneresponsive CpGs within the PedBE clock (OR = 4.36, p = 1.65*10-6). Among the 94 CpGs of the PedBE clock, 18 (19%) were responsive to dexamethasone. Conclusion: Using the novel PedBE clock, we show that internalizing disorder is associated with accelerated epigenetic ageing in early childhood. This association is moderated by maltreatment severity and may, in part, be driven by glucocorticoids. Identifying developmental drivers of accelerated epigenetic ageing after maltreatment will be critical to devise early targeted interventions.
American Journal of Reproductive Immunology, 2021
OBJECTIVE Inflammation as a risk factor for preterm birth is well-established. The primary object... more OBJECTIVE Inflammation as a risk factor for preterm birth is well-established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of mid-pregnancy inflammation are significantly associated with risk for adverse birth outcomes. STUDY DESIGN A multi-site prospective study was conducted in a socio-demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks' gestation, low-grade inflammation was measured via log-transformed serum concentrations of the biomarkers IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC). RESULTS PCA analysis yielded a two-factor solution, with the first factor (IF1) composed of IL-8, IL-10, IL-13, IFN-ɣ, and TNF-α, and the second factor (IF2) containing IL-6 and CRP. When adjusted for race, education, BMI, smoking status, gestational age at time of blood draw, and study site, a one standard deviation (SD) increase in IF1 remained significantly associated with a decrease in standardized gestational age (β = -0.13, 95% CI: -0.21, -0.05) and an increase in odds of preterm delivery (OR = 1.46, 95% CI: 1.13, 1.88) (Table 3). A one SD increase in IF2 was similarly associated with a decrease in standardized gestational age at delivery (β = -0.13, 95% CI: -0.23, -0.04) and an increase in odds of preterm delivery (OR: 1.46, 95% CI: 1.04, 2.05). Neither IF1 nor IF2 was associated with measures of fetal growth. AIC identified that IL-6 was a slightly better fit for length of gestation compared to either composite measure, though all performed similarly. CONCLUSION Independent of known sociodemographic risk factors, an elevated mid-pregnancy inflammatory profile was associated with a nearly 50% increase in odds of preterm delivery. The composite performed similarly to IL-6. These results suggest that maternal low-grade inflammation is a risk factor for preterm delivery, and that mid-pregnancy inflammatory biomarkers may be useful in predicting risk for preterm delivery. This article is protected by copyright. All rights reserved.
Neurobiology of Stress, 2021
Childhood maltreatment (CM) is an established major risk factor for a number of negative health o... more Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities, often experienced by these children, converge on similar DNAm changes. Here, we calculated a cumulative adversity score, which additionally to CM includes socioeconomic status (SES), other life events, parental psychopathology and epigenetic biomarkers of prenatal smoking and alcohol consumption. We investigated the effects of CM alone as well as the adversity score on longitudinal DNAm trajectories in the Berlin Longitudinal Child Study. This is a cohort of 173 children aged 3-5 years at baseline of whom 86 were exposed to CM. These children were followed-up for 2 years with extensive psychometric and biological assessments as well as saliva collection at 5 time points providing genome-wide DNAm levels. Overall, only a few DNAm patterns were stable over this timeframe, but less than 10 DNAm regions showed significant changes. At baseline, neither CM nor the adversity score associated with DNAm changes. However, in 6 differentially methylated regions (DMRs), CM and the adversity score significantly moderated DNAm trajectories over time. A number of these DMRs have previously been associated with adverse prenatal exposures. In our study, children exposed to CM also presented with epigenetic signatures indicative of increased prenatal exposure to tobacco and alcohol, as compared to non-CM exposed children. These epigenetic signatures of prenatal exposure strongly correlate with DNAm regions associated with CM and the adversity score. Finally, weighted correlation network analysis revealed a module of CpGs exclusively associated with CM. While our study identifies DNAm loci specifically associated with CM, especially within long non-coding RNAs, the majority of associations were found with the adversity score with convergent association with indicators of adverse prenatal exposures. This study highlights the importance of mapping not only of the epigenome but also the exposome and extending the observational timeframe to well before birth.
Development and Psychopathology, 2020
Exposure to child maltreatment increases the risk for psychiatric and physical diseases. Inflamma... more Exposure to child maltreatment increases the risk for psychiatric and physical diseases. Inflammation has been proposed as a mechanism through which early adverse experiences become biologically embedded. However, most studies providing evidence for the link between early adverse exposures and inflammation have been retrospective or cross-sectional in design, or did not assess inflammation immediately after maltreatment in young children. In the present study we investigated the association between childhood maltreatment and salivary C-reactive protein (CRP) concentrations in a population of N = 173 children, 3–5 years of age, who were recruited in the immediate aftermath of maltreatment and followed-up longitudinally every 6 months over a period of 2 years. We found that the association between maltreatment and CRP concentrations was significantly moderated by child sex, such that in girls, CRP concentrations were higher in the maltreated compared to the control group, and this dif...
Psychoneuroendocrinology, 2020
Currently, data centers energy consumption in the cloud is attracting a lot of interest. One of t... more Currently, data centers energy consumption in the cloud is attracting a lot of interest. One of the most approaches to optimize energy and cost in data centers is virtualization. Recently, a new type of container-based virtualization has appeared, containers are considered very light and modular virtual machines, they offer great flexibility and the possibility of migration from one environment to another, which allows optimizing applications for the cloud. Another approach to saving energy is to consolidate the workload, which is the amount of processing that the computer has to perform at any given time. In this article, we will study the container placement algorithm that takes into account the QoS requirements of different users in order to minimize energy consumption. Thus, we proposed a Hybrid approach for managing resources and workload based on ant colony optimization (ACO) and the first-fit decreasing (FFD) algorithm to avoid unnecessary power consumption. The results of the experiment indicate that using the first-fit decreasing algorithm (FFD) for container placement is better than ant colony optimization especially in a homogeneous systems. On the other hand the ant colony optimization shows very satisfying results in the case of workload management.
Der Gynäkologe, 2020
Hintergrund Das Forschungsgebiet „Fetale Programmierung von Krankheit und Gesundheit“ untersucht,... more Hintergrund Das Forschungsgebiet „Fetale Programmierung von Krankheit und Gesundheit“ untersucht, inwieweit die individuelle Anfälligkeit für die Entstehung verschiedenster Erkrankungen über die Lebensspanne bereits während der intrauterinen Entwicklung geprägt wird. Von besonderem Interesse sind die molekularen Mechanismen, die es ermöglichen, dass Umweltbedingungen im frühen Leben langfristige, gravierende Effekte auf das Krankheitsrisiko im späteren Leben ausüben können. Fragestellung und Befunde Erläutert wird das Konzept der fetalen Programmierung, diskutiert werden Veränderungen in Zellalterungsprozessen, insbesondere der Telomerbiologie, als möglicher Mechanismus, über den Krankheitsvulnerabilität durch intrauterine Einflussfaktoren vermittelt werden können. Auf der einen Seite belegen Befunde aus Tier- und Humanstudien, dass verschiedene pränatale Faktoren, z. B. ungünstige Ernährung, psychosozialer Stress, medizinische Risikofaktoren während der Schwangerschaft, mit Veränderungen im Telomersystem der Nachkommen einhergehen. Andererseits sind Veränderungen im Telomersystem mit erhöhtem Risiko für altersbedingte Erkrankungen assoziiert. Einige Studien legen nahe, dass Mind-Body-Interventionen die Telomerbiologie positiv beeinflussen können. Schlussfolgerung Die aufgeführten Forschungsarbeiten erlauben Einblicke in die molekularbiologischen Mechanismen, welche den Zusammenhang zwischen intrauterinen Umweltfaktoren und dem Krankheitsrisiko im späteren Leben vermitteln. Es existiert ein erheblicher Mangel an Translation zwischen diesen Erkenntnissen und ihrer Anwendung in der klinischen Versorgung. Eine Risikoidentifizierung – so früh wie möglich – kann dazu beitragen, dass Interventionen präventiv ansetzen und maximal wirksam sein können, um die fetale Programmierung von Krankheitsrisiken zu verhindern bzw. rückgängig zu machen. Background The research field of “fetal programming of health and disease risk” investigates how intrauterine factors can shape individual vulnerability for disease risk in later life. The search for molecular mechanisms that mediate biological embedding of fetal environmental exposures and thereby disease susceptibility is an area of active interest and investigation. Objectives The present article introduces the concept of fetal programming of disease vulnerability and advances the hypothesis that telomere biology may represent a common mechanism underlying the observed effects of a disparate set of suboptimal intrauterine exposures on various health and disease risk phenotypes of interest. Findings from animal and human studies are presented regarding the effects of prenatal conditions (e.g., unfavorable maternal [mal]nutrition, maternal stress and obstetric risk conditions during pregnancy) on the offspring telomere biology system, as well as on the association between alterations in the telomere system and increased risk for aging-related disorders. Some studies suggest that “mind–body” interventions may have a positive impact on telomere biology. Conclusion The studies and findings summarized here provide insights into potential molecular mechanisms underlying the association between intrauterine exposures and disease risk in later life. However, there is currently a lack of translation of research findings related to fetal programming to clinical applications. Early risk identification (during pregnancy) could contribute to the development of strategies to improve the precision of current clinical diagnostic tools and the success of interventions to prevent or reverse fetal programming of disease risk and thereby contribute to the health and well-being of the next generation.
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Papers by Sonja Entringer