Extended twin study of alcohol use in Virginia and Australia

Drinking alcohol is a normal behavior in many societies, and prior studies have demonstrated it has both genetic and environmental sources of variation. Using two very large samples of twins and their first-degree relatives (Australia ≈ 20,000 individuals from 8,019 families; Virginia ≈ 23,000 from 6,042 families), we examine whether there are differences: (1) in the genetic and environmental factors that influence four interrelated drinking behaviors (quantity, frequency, age of initiation, and number of drinks in the last week), (2) between the twin-only design and the extended twin design, and (3) the Australian and Virginia samples. We find that while drinking behaviors are interrelated, there are substantial differences in the genetic and environmental architectures across phenotypes. Specifically, drinking quantity, frequency, and number of drinks in the past week have large broad genetic variance components, and smaller but significant environmental variance components, while age of onset is driven exclusively by environmental factors. Further, the twin-only design and the extended twin design come to similar conclusions regarding broad-sense heritability and environmental transmission, but the extended twin models provide a more nuanced perspective. Finally, we find a high level of similarity between the Australian and Virginian samples, especially for the genetic factors. The observed differences, when present, tend to be at the environmental level. Implications for the extended twin model and future directions are discussed

Cross-cultural comparison of genetic and cultural transmission of smoking initiation using an extended twin kinship model

Background: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent–offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. Methods: We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime ‘ever’ smoking measure was obtained from twins and relatives in the ‘Virginia 30,000’ sample and the ‘Australian 25,000’. Results: Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent–offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. Conclusions: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI

Effects of diamagnetic levitation on bacterial growth in liquid

Diamagnetic levitation is a technique that uses a strong, spatially-varying magnetic field to levitate diamagnetic materials, such as water and biological cells. This technique has the potential to simulate aspects of weightlessness, on the Earth. In common with all ground-based techniques to simulate weightlessness, however, there are effects introduced by diamagnetic levitation that are not present in space. Since there have been few studies that systematically investigate these differences, diamagnetic levitation is not yet being fully exploited. For the first time, we critically assess the effect of diamagnetic levitation on a bacterial culture in liquid. We used a superconducting magnet to levitate growing bacterial cultures for up to 18 hours, in a series of experiments to determine the effect of diamagnetic levitation on all phases of the bacterial growth cycle. We find that diamagnetic levitation increases the rate of population growth in a liquid culture. The speed of sedimentation of the bacterial cells to the bottom of the container is considerably reduced. Further experiments and microarray gene analysis show that the growth enhancement is due to greater oxygen availability in the magnetically levitated sample. We demonstrate that the magnetic field that levitates the cells also induces convective stirring in the liquid, an effect not present in microgravity. We present a simple theoretical model, showing how the paramagnetic force on dissolved oxygen can cause the liquid to become unstable to convection when the consumption of oxygen by the bacteria generates an oxygen concentration gradient. We propose that this convection enhances oxygen availability by transporting oxygen around the sample. Since convection is absent in space, these results are of significant importance and timeliness to researchers considering using diamagnetic levitation to explore weightless effects on living organisms and a broad range of other topics in the physical and life sciences

Racial Differences in Genetic and Environmental Risk to Preterm Birth

Preterm birth is more prevalent in African Americans than European Americans and contributes to 3.4 times more African American infant deaths. Models of social inequity do not appreciably account for this marked disparity and molecular genetic studies have yet to characterize whether allelic differences that exist between races contribute to this gap. In this study, biometrical genetic models are applied to a large mixed-race sample consisting of 733,339 births to measure the extent that heritable factors and environmental exposures predict the timing of birth and explain differences between racial groups. Although we expected significant differences in mean gestational age between racial groups, we did not anticipate the variance of gestational age in African Americans (σ2 = 7.097) to be nearly twice that of European Americans (σ2 = 3.764). Our results show that this difference in the variance of gestational age can largely be attributed to environmental sources; which were 3.1 times greater in African Americans. Specifically, environmental factors that change between pregnancies, versus exposures that influence all pregnancies within a family, are largely responsible for the increased reproductive heterogeneity observed in African American mothers. Although the contribution of both fetal and maternal genetic factors differed between race categories, genetic studies may best be directed to understanding the differences in the socio-cultural sources of this heterogeneity, and their possible interaction with genetic differences within and between races. This study provides a comprehensive description of the relative genetic and environmental contributions to racial differences in gestational age

Clinical characteristics of familial generalized anxiety disorder

The authors seek to determine whether the clinical characteristics of generalized anxiety disorder (GAD) differ in individuals with a high vs. low familial vulnerability to illness. We identified 486 personally interviewed female twins from a population‐based register who had both an interviewed co‐twin and a lifetime history of GAD using modified DSM‐III‐R criteria which required a one‐month minimum duration of illness. We attempted to predict risk for GAD in the co‐twin from the clinical features of the GAD in the proband twin using the Cox proportional hazard model, controlling for year of birth and zygosity. Only two variables uniquely predicted an increased risk for GAD in the co‐twin: number of GAD symptoms endorsed and comorbidity with bulimia. Variables that did not uniquely predict risk of illness in the co‐twin included age at onset, duration of the longest episode and number of episodes. The familial vulnerability to GAD can be meaningfully indexed by clinical features of the syndrome. These results suggest that if the syndrome of GAD is to be narrowed, it would, from a familial perspective, be more valid to increase the minimum number of required symptoms rather than to increase the minimum duration of illness. Anxiety 1:186–191 (1994/1995). © 1995 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101797/1/3070010407_ftp.pd

Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster

<p>Abstract</p> <p>Background</p> <p>Many biological systems respond to the presence or absence of gravity. Since experiments performed in space are expensive and can only be undertaken infrequently, Earth-based simulation techniques are used to investigate the biological response to weightlessness. A high gradient magnetic field can be used to levitate a biological organism so that its net weight is zero.</p> <p>Results</p> <p>We have used a superconducting magnet to assess the effect of diamagnetic levitation on the fruit fly <it>D. melanogaster </it>in levitation experiments that proceeded for up to 22 consecutive days. We have compared the results with those of similar experiments performed in another paradigm for microgravity simulation, the Random Positioning Machine (RPM). We observed a delay in the development of the fruit flies from embryo to adult. Microarray analysis indicated changes in overall gene expression of imagoes that developed from larvae under diamagnetic levitation, and also under simulated hypergravity conditions. Significant changes were observed in the expression of immune-, stress-, and temperature-response genes. For example, several heat shock proteins were affected. We also found that a strong magnetic field, of 16.5 Tesla, had a significant effect on the expression of these genes, independent of the effects associated with magnetically-induced levitation and hypergravity.</p> <p>Conclusions</p> <p>Diamagnetic levitation can be used to simulate an altered effective gravity environment in which gene expression is tuned differentially in diverse <it>Drosophila melanogaster </it>populations including those of different age and gender. Exposure to the magnetic field <it>per se </it>induced similar, but weaker, changes in gene expression.</p

Meristematic cell proliferation and ribosome biogenesis are decoupled in diamagnetically levitated Arabidopsis seedlings

Background: Cell growth and cell proliferation are intimately linked in the presence of Earth’s gravity, but are decoupled under the microgravity conditions present in orbiting spacecraft. New technologies to simulate microgravity conditions for long-duration experiments, with stable environmental conditions, in Earth-based laboratories are required to further our understanding of the effect of extraterrestrial conditions on the growth, development and health of living matter. Results: We studied the response of transgenic seedlings of Arabidopsis thaliana, containing either the CycB1-GUS proliferation marker or the DR5-GUS auxin-mediated growth marker, to diamagnetic levitation in the bore of a superconducting solenoid magnet. As a control, a second set of seedlings were exposed to a strong magnetic field, but not to levitation forces. A third set was exposed to a strong field and simulated hypergravity (2 g). Cell proliferation and cell growth cytological parameters were measured for each set of seedlings. Nucleolin immunodetection was used as a marker of cell growth. Collectively, the data indicate that these two fundamental cellular processes are decoupled in root meristems, as in microgravity: cell proliferation was enhanced whereas cell growth markers were depleted. These results also demonstrated delocalisation of auxin signalling in the root tip despite the fact that levitation of the seedling as a whole does not prevent the sedimentation of statoliths in the root cells. Conclusions:In our model system, we found that diamagnetic levitation led to changes that are very similar to those caused by real- [e.g. on board the International Space Station (ISS)] or mechanically-simulated microgravity [e.g. using a Random Positioning Machine (RPM)]. These changes decoupled meristematic cell proliferation from ribosome biogenesis, and altered auxin polar transport

Distinct Stromal Cell Factor Combinations Can Separately Control Hematopoietic Stem Cell Survival, Proliferation, and Self-Renewal

SummaryHematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation, and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential are variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings point to the molecular basis of HSC control and expansion