Forging the Association for Clinical and Translational Science (ACTS)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91162/1/j.1752-8062.2012.00404.x.pd

Genetic and environmental influences on eating behavior - a study of twin pairs reared apart or reared together

This study examined the relative influence of genetic versus environmental factors on specific aspects of eating behavior. Adult monozygotic twins (22 pairs and 3 singleton reared apart, 38 pairs and 9 singleton reared together, age 18-76 years, BMI 17-43 kg/m2) completed the Three Factor Eating Questionnaire. Genetic and environmental variance components were determined for the three eating behavior constructs and their subscales using model-fitting univariate and multivariate analyses. Unique environmental factors had a substantial influence on all eating behavior variables (explaining 45-71% of variance), and most strongly influenced external locus for hunger and strategic dieting behavior of restraint (explaining 71% and 69% of variance, respectively). Genetic factors had a statistically significant influence on only 4 variables: restraint, emotional susceptibility to disinhibition, situational susceptibility to disinhibition, and internal locus for hunger (heritabilities were 52%, 55%, 38% and 50%, respectively). Common environmental factors did not statistically significantly influence any variable assessed in this study. In addition, multivariate analyses showed that disinhibition and hunger share a common influence, while restraint appears to be a distinct construct. These findings suggest that the majority of variation in eating behavior variables is associated with unique environmental factors, and highlights the importance of the environment in facilitating specific eating behaviors that may promote excess weight gain.R01 AR046124 - NIAMS NIH HHS; R01 MH065322 - NIMH NIH HHS; T32 HL069772 - NHLBI NIH HHS; R37 DA018673 - NIDA NIH HHS; R01 DK073321 - NIDDK NIH HHS; R01 DA018673 - NIDA NIH HH

Coulomb correlation and magnetic ordering in double-layered manganites: LaSr2_2Mn2_2O7_7

A detailed study of the electronic structure and magnetic configurations of the 50 % hole-doped double layered manganite LaSr$_2$Mn$_2$O$_7$ is presented. We demonstrate that the on-site Coulomb correlation (U) of Mn d electrons {\it (i)} significantly modifies the electronic structure, magnetic ordering (from FM to AFM), and interlayer exchange interactions, and {\it (ii)} promotes strong anisotropy in electrical transport, reducing the effective hopping parameter along the {\it c} axis for electrically active $e_g$ electrons. This findng is consistent with observations of anisotropic transport -- a property which sets this manganite apart from conventional 3D systems. A half-metallic band structure is predicted with both the LSDA and LSDA+U methods. The experimentally observed A-type AFM ordering in LaSr$_2$Mn$_2$O$_7$ is found to be energetically more favorable with U $\geq$ 7 eV. A simple interpretation of interlayer exchange coupling is given within double and super-exchange mechanisms based on the dependencies on U of the effective exchange parameters and $e_g$ state sub-band widths.Comment: 10 pages, 5 figure

The Relationship Between Central Auditory Tests and Neurocognitive Domains in Adults Living With HIV

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV– controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally. Method: Subjects were recruited from an ongoing study in Dar es Salaam, Tanzania. Central auditory measures included the Gap Detection Test (Gap), Hearing in Noise Test (HINT), and Triple Digit Test (TDT). Cognitive measures included variables from the Test of Variables of Attention (TOVA), Cogstate neurocognitive battery, and Kiswahili Montreal Cognitive Assessment (MoCA). The measures represented three cognitive domains: processing speed, learning, and working memory. Bootstrap resampling was used to calculate the mean and standard deviation of the proportion of variance explained by the individual central auditory tests for each cognitive measure. The association of cognitive measures with central auditory variables taking HIV status and age into account was determined using regression models. Results: Hearing in Noise Tests and TDT were significantly associated with Cogstate learning and working memory tests. Gap was not significantly associated with any cognitive measure with age in the model. TDT explained the largest mean proportion of variance and had the strongest relationship to the MoCA and Cogstate tasks. With age in the model, HIV status did not affect the relationship between central auditory tests and cognitive measures. Age was strongly associated with multiple cognitive tests. Conclusion: Central auditory tests were associated with measures of learning and working memory. Compared to the other central auditory tests, TDT was most strongly related to cognitive function. These findings expand on the association between auditory processing and cognitive domains seen in other studies and support evaluating these tests for tracking brain health in HIV and other neurocognitive disorders

Angptl4 Protects against Severe Proinflammatory Effects of Saturated Fat by Inhibiting Fatty Acid Uptake into Mesenteric Lymph Node Macrophages

SummaryDietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and lethal phenotype characterized by fibrinopurulent peritonitis, ascites, intestinal fibrosis, and cachexia. These abnormalities are preceded by a massive acute phase response induced by saturated but not unsaturated fat or medium-chain fat, originating in mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid-laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced foam cell formation, inflammatory gene expression, and chyle-induced activation of ER stress. Induction of macrophage Angptl4 by fatty acids is part of a mechanism that serves to reduce postprandial lipid uptake from chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled saturated fat-induced inflammation

Two-site dynamical mean-field theory

It is shown that a minimum realization of the dynamical mean-field theory (DMFT) can be achieved by mapping a correlated lattice model onto an impurity model in which the impurity is coupled to an uncorrelated bath that consists of a single site only. The two-site impurity model can be solved exactly. The mapping is approximate. The self-consistency conditions are constructed in a way that the resulting ``two-site DMFT'' reduces to the previously discussed linearized DMFT for the Mott transition. It is demonstrated that a reasonable description of the mean-field physics is possible with a minimum computational effort. This qualifies the simple two-site DMFT for a systematic study of more complex lattice models which cannot be treated by the full DMFT in a feasible way. To show the strengths and limitations of the new approach, the single-band Hubbard model is investigated in detail. The predictions of the two-site DMFT are compared with results of the full DMFT. Internal consistency checks are performed which concern the Luttinger sum rule, other Fermi-liquid relations and thermodynamic consistency.Comment: LaTeX, 14 pages, 8 eps figures included, Phys. Rev. B (in press

Prevalence of sustainable and unsustainable use of wild species inferred from the IUCN Red List of Threatened Species

Unsustainable exploitation of wild species represents a serious threat to biodiversity and to the livelihoods of local communities and Indigenous peoples. However, managed, sustainable use has the potential to forestall extinctions, aid recovery, and meet human needs. We analyzed species-level data for 30,923 species from 13 taxonomic groups on the International Union for Conservation of Nature Red List of Threatened Species to investigate patterns of intentional biological resource use. Forty percent of species (10,098 of 25,009 species from 10 data-sufficient taxonomic groups) were used. The main purposes of use were pets, display animals, horticulture, and human consumption. Intentional use is currently contributing to elevated extinction risk for 28–29% of threatened or near threatened (NT) species (2752–2848 of 9753 species). Intentional use also affected 16% of all species used (1597–1631 of 10,098). However, 72% of used species (7291 of 10,098) were least concern, of which nearly half (3469) also had stable or improving population trends. The remainder were not documented as threatened by biological resource use, including at least 172 threatened or NT species with stable or improving populations. About one-third of species that had use documented as a threat had no targeted species management actions to directly address this threat. To improve use-related red-list data, we suggest small amendments to the relevant classification schemes and required supporting documentation. Our findings on the prevalence of sustainable and unsustainable use, and variation across taxa, can inform international policy making, including the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, the Convention on Biological Diversity, and the Convention on International Trade in Endangered Species.Fil: Marsh, Sophie M. E.. Colegio Universitario de Londres; Reino UnidoFil: Hoffmann, Michael. The Zoological Society of London; Reino UnidoFil: Burgess, Neil D.. Universidad de Copenhagen; Dinamarca. United Nations Environment Programme World Conservation Monitoring Centre; DinamarcaFil: Brooks, Thomas M.. University of the Philippines; Filipinas. University of Tasmania; Australia. International Union for Conservation of Nature; SuizaFil: Challender, Daniel W. S.. University of Oxford; Reino UnidoFil: Cremona, Patricia J.. International Union for Conservation of Nature; Reino UnidoFil: Hilton Taylor, Craig. International Union for Conservation of Nature; Reino UnidoFil: de Micheaux, Flore Lafaye. Universite de Lausanne; Suiza. Institut Francais de Pondichery; India. International Union For Conservation Of Nature And Natural Resources; SuizaFil: Lichtenstein, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; ArgentinaFil: Roe, Dilys. International Institute For Environment And Development; Reino UnidoFil: Böhm, Monika. Zoological Society Of London Institute Of Zoology; Reino Unid

Mothers' views on feeding infants around the time of weaning

OBJECTIVE: To describe women's views about aspects of infants' diets around the time of weaning, making comparisons with national guidelines. DESIGN: A survey of women with a 9-month-old child. SETTING: Adelaide, South Australia. SUBJECTS: Five hundred and five women who joined a longitudinal study during pregnancy. RESULTS: Sources of information varied, with written material most commonly used (37%). Cows' milk was considered suitable as the main drink for weaned infants by 14% of women. There were divergent views about the suitability of eggs, with many women concerned about allergy. The majority of women (84%) viewed fruit juice as suitable although many qualified their response, often by stating that fruit juice should be diluted. Almost all women considered the amount of sugar mattered, primarily because of tooth decay, and that salt mattered although the reason was often uncertain. It was widely believed (77%) that additives in food could cause health problems, in particular hyperactivity and allergies, and half of the women reported avoiding specific foods because of concerns about allergies. Many women thought that giving their child food that was high in fat would encourage a liking for ‘junk’ food or lead to fatness in adulthood. CONCLUSIONS: There is considerable diversity in the views women express about aspects of infant feeding that have been the subject of guidelines. Further health promotion efforts are needed to achieve greater consistency with recommendations and to address other concerns women have. This will entail greater engagement with parents and shared development of responses.Ruth B Walker, Jennifer A Conn, Michael J Davies and Vivienne M Moor

Everolimus rescues multiple cellular defects in laminopathy-patient fibroblasts

LMNA encodes the A-type lamins that are part of the nuclear scaffold. Mutations in LMNA can cause a variety of disorders called laminopathies, including Hutchinson-Gilford progeria syndrome (HGPS), atypical Werner syndrome, and Emery-Dreifuss muscular dystrophy. Previous work has shown that treatment of HGPS cells with the mTOR inhibitor rapamycin or with the rapamycin analog everolimus corrects several of the phenotypes seen at the cellular level—at least in part by increasing autophagy and reducing the amount of progerin, the toxic form of lamin A that is overproduced in HGPS patients. Since other laminopathies also result in production of abnormal and potentially toxic lamin proteins, we hypothesized that everolimus would also be beneficial in those disorders. To test this, we applied everolimus to fibroblast cell lines from six laminopathy patients, each with a different mutation in LMNA. Everolimus treatment increased proliferative ability and delayed senescence in all cell lines. In several cell lines, we observed that with treatment, there is a significant improvement in nuclear blebbing, which is a cellular hallmark of HGPS and other lamin disorders. These preclinical results suggest that everolimus might have clinical benefit for multiple laminopathy syndromes

Most Reported Genetic Associations with General Intelligence Are Probably False Positives

General intelligence (g) and virtually all other behavioral traits are heritable. Associations between g and specific single-nucleotide polymorphisms (SNPs) in several candidate genes involved in brain function have been reported. We sought to replicate published associations between g and 12 specific genetic variants (in the genes DTNBP1, CTSD, DRD2, ANKK1, CHRM2, SSADH, COMT, BDNF, CHRNA4, DISC1, APOE, and SNAP25) using data sets from three independent, well-characterized longitudinal studies with samples of 5,571, 1,759, and 2,441 individuals. Of 32 independent tests across all three data sets, only 1 was nominally significant. By contrast, power analyses showed that we should have expected 10 to 15 significant associations, given reasonable assumptions for genotype effect sizes. For positive controls, we confirmed accepted genetic associations for Alzheimer’s disease and body mass index, and we used SNP-based calculations of genetic relatedness to replicate previous estimates that about half of the variance in g is accounted for by common genetic variation among individuals. We conclude that the molecular genetics of psychology and social science requires approaches that go beyond the examination of candidate genes.Economic