Application of Structure Equation Modeling for Inferring a Serial Transcriptional Regulation in Yeast

Revealing the gene regulatory systems among DNA and proteins in living cells is one of the central aims of systems biology. In this study, I used Structural Equation Modeling (SEM) in combination with stepwise factor analysis to infer the protein-DNA interactions for gene expression control from only gene expression profiles, in the absence of protein information. I applied my approach to infer the causalities within the well-studied serial transcriptional regulation composed of GAL-related genes in yeast. This allowed me to reveal the hierarchy of serial transcriptional regulation, including previously unclear protein-DNA interactions. The validity of the constructed model was demonstrated by comparing the results with previous reports describing the regulation of the transcription factors. Furthermore, the model revealed combinatory regulation by Gal4p and Gal80p. In this study, the target genes were divided into three types: those regulated by one factor and those controlled by a combination of two factors

Game Theoretical Interactions of Moving Agents

Game theory has been one of the most successful quantitative concepts to describe social interactions, their strategical aspects, and outcomes. Among the payoff matrix quantifying the result of a social interaction, the interaction conditions have been varied, such as the number of repeated interactions, the number of interaction partners, the possibility to punish defective behavior etc. While an extension to spatial interactions has been considered early on such as in the "game of life", recent studies have focussed on effects of the structure of social interaction networks. However, the possibility of individuals to move and, thereby, evade areas with a high level of defection, and to seek areas with a high level of cooperation, has not been fully explored so far. This contribution presents a model combining game theoretical interactions with success-driven motion in space, and studies the consequences that this may have for the degree of cooperation and the spatio-temporal dynamics in the population. It is demonstrated that the combination of game theoretical interactions with motion gives rise to many self-organized behavioral patterns on an aggregate level, which can explain a variety of empirically observed social behaviors

Developing and Validating a New Multi-Dimensional Scale for Anti-Social Behaviour in a Higher Education Setting

The purpose of this research is to construct and validate a multi-dimensional scale of Anti-social Behaviour (hereafter ASB) in a Western higher education context (i.e. USA). To achieve this, four studies, each with a different sample, were performed. Study 1 (n = 150) followed an exploratory design to generate a pool of potential items measuring ASB. Study 2 (n = 254) explored the dimensionality of the items produced in Study 1 using Exploratory Factor Analysis (EFA) and reliability measures. Study 3 (n = 654) confirmed the factorial structure from Study 2 and assessed the measurement model invariance using structural equation modelling (SEM). Finally, Study 4 (n = 287) assessed the predictive validity of the ASB measure through testing a hypothetical path model linking ASB to narcissism and Machiavellianism via an SEM procedure. In total, our research findings conclude that the ASB measurement model is a two-factor multi-dimensional structure comprising: Interpersonal Antagonistic Behaviour (six items) as well as Indirect Distractive Behaviour (four items). The research and practical implications for universities are thereafter discussed

Pelvic Chlamydial Infection Predisposes to Ectopic Pregnancy by Upregulating Integrin ?1 to Promote Embryo-tubal Attachment

Tubal ectopic pregnancies are a leading cause of global maternal morbidity and mortality. Previous infection with Chlamydia trachomatis is a major risk factor for tubal embryo implantation but the biological mechanism behind this association is unclear. Successful intra-uterine embryo implantation is associated with increased expression of endometrial “receptivity” integrins (cell adhesion molecules).We examined integrin expression in Fallopiantubes of women with previous C. trachomatis infection, in mice experimentally infected with C. trachomatis, in immortalised human oviductal epithelial cells (OE-E6/E7) and in an in vitro model of human embryo attachment (trophoblast spheroid-OE-E6/7 cell co-culture). Previous exposure with C. trachomatis increased Fallopian tube/oviduct integrin-subunit beta-1 (ITGB1) in women and mice compared to controls. C. trachomatis increased OEE6/E7 cell ITGB1 expression and promoted trophoblast attachment to OE-E6/E7 cellswhichwas negated by anti-ITGB1-antibody.We demonstrate that infection with C. trachomatis increases tubal ITGB1 expression, predisposing to tubal embryo attachment and ectopic pregnancy

Models of cognition and affect in perceptions of well-being

How do people arrive at assessments of their own life quality? A series of models was developed to provide an interpretation of the way the factors of cognition and affect operate along with evaluations of specific life concerns (domains) in the perception of well-being. Following previous research, cognition was defined operationally as a factor which accounts for the covariance among a set of assessments of life-as-a-whole after affect, as measured by Bradburn's scales, is partialled out and after allowance is made for the presence of correlated measurement errors. It was found that loadings on the cognitive factor, and hence the interpretation of this factor, changed little despite quite large changes in the models. Moreover, in all major comparisons, models that contained the cognitive factor fitted the data better than models that did not. Models that included affect as the only variable intervening between the domains and the life-as-a-whole factor led to results that were intuitively difficult to accept. In the preferred model both affect and cognition were positioned as intervening variables. In this model it was found that the domain evaluations had no direct impact on life-as-a-whole assessments — the contribution of the domains was indirect by way of their association with cognition and affect. It was hypothesised that associated with each domain was a domain-specific element of affect and a domain-specific element of cognition. The linear additive relation found by previous researchers between domain evaluations and life-as-a-whole assessments would then be explainable as a statistical result arising from the summing of the domain-specific elements of affect and cognition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43703/1/11205_2004_Article_BF00292640.pd

The influence of first generation fertility and economic status on second generation fertility

This paper examines the impact of parental economic status and family size on the actual and expected fertility of adult children using longitudinal data from two generations of families participating in the Panel Study of Income Dynamics. There was a modest positive relationship between first generation family size and second generation fertility. More importantly, the ideal family size of the parental family was more closely related to fertility behavior and plans in the second generation than was actual parental family size. In addition, the data revealed the hypothesized negative correlation between parental financial status and second generation fertility behavior and plans. Several mechanisms which could produce the correlation between parental characteristics and the fertility of their children are explored.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43511/1/11111_2005_Article_BF01253070.pd

The value of children to parents in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43479/1/11111_2004_Article_BF01277597.pd

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global burden of 87 risk factors in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk�outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk�outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk�outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95 uncertainty interval UI 9·51�12·1) deaths (19·2% 16·9�21·3 of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12�9·31) deaths (15·4% 14·6�16·2 of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253�350) DALYs (11·6% 10·3�13·1 of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0�9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10�24 years, alcohol use for those aged 25�49 years, and high systolic blood pressure for those aged 50�74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens