Long-range three-body atom-diatom potential for doublet Li3{}_3

An accurate long-range {\em ab initio} potential energy surface has been calculated for the ground state ${}^2A'$ lithium trimer in the frozen diatom approximation using all electron RCCSD(T). The {\em ab initio} energies are corrected for basis set superposition error and extrapolated to the complete basis limit. Molecular van der Waals dispersion coefficients and three-body dispersion damping terms for the atom-diatomic dissociation limit are presented from a linear least squares fit and shown to be an essentially exact representation of the {\em ab initio} surface at large range

Changes in neuromuscular structure and functions of human colon during ageing are region-dependent

Objective: To determine if human colonic neuromuscular functions decline with increasing age.Design: Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35–91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35–60 years) groups.Results: With increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI ), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthaseimmunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/gtissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon.Conclusion: In ascending not descending colon, ageing impairs cholinergic function

Chiasma

Newspaper reporting on events at the Boston University School of Medicine in the 1960s

Serum phosphatidylinositol as a biomarker for bipolar disorder liability

Objectives Individuals with bipolar disorder (BPD) exhibit alterations in their phospholipid levels. It is unclear whether these alterations are a secondary consequence of illness state, or if phospholipids and illness risk overlap genetically. If the latter were true, then phospholipids might provide key insights into the pathophysiology of the illness. Therefore, we rank-ordered phospholipid classes by their genetic overlap with BPD risk in order to establish which class might be most informative in terms of increasing our understanding of illness pathophysiology. Methods Analyses were conducted in a sample of 558 individuals, unselected for BPD, from 38 extended pedigrees (average family size=14.79, range=2–82). We calculated a coefficient of relatedness for all family members of nine individuals with BPD in the sample (N=185); this coefficient was set to be zero in unrelated individuals (N=373). Then, under an endophenotype ranking value (ERV) approach, this scalar index was tested against 13 serum-based phospholipid concentrations in order to rank-order lipid classes by their respective overlap with BPD risk. Results The phosphatidylinositol class was significantly heritable (h2=0.26, P=6.71 × 10−05). It was the top-ranked class, and was significantly associated with BPD risk after correction for multiple testing (β=−1.18, P=2.10 × 10−03, ERV=0.49). Conclusions We identified a peripheral biomarker, serum-based phosphatidylinositol, which exhibits a significant association with BPD risk. Therefore, given that phosphatidylinositol and BPD risk share partially common etiology, it seems that this lipid class warrants further investigation, not only in terms of treatment, but also as a promising diagnostic and risk marker

The Lipidome in Major Depressive Disorder: Shared Genetic Influence for Ether-Phosphatidylcholines, a Plasma-Based Phenotype Related to Inflammation, and Disease Risk

Background The lipidome is rapidly garnering interest in the field of psychiatry. Recent studies have implicated lipidomic changes across numerous psychiatric disorders. In particular there is growing evidence that the concentrations of several classes of lipids are altered in those diagnosed with MDD. However, for lipidomic abnormalities to be considered potential treatment targets for MDD (rather than secondary manifestations of the disease), a shared etiology between lipid concentrations and MDD should be demonstrated. Methods In a sample of 567 individuals from 37 extended pedigrees (average size 13.57 people, range = 3–80), we used mass-spectrometry lipidomic measures to evaluate the genetic overlap between twenty-three biologically distinct lipid classes and a dimensional scale of MDD. Results We found that the lipid class with the largest endophenotype ranking value (ERV, a standardized parametric measure of pleiotropy) were ether-phosphodatidylcholines (alkylphosphatidylcholine, PC(O) and alkenylphosphatidylcholine, PC(P) subclasses). Furthermore, we examined the cluster structure of the twenty-five species within the top-ranked lipid class, and the relationship of those clusters with MDD. This analysis revealed that species containing arachidonic acid generally exhibited the greatest degree of genetic overlap with MDD. Conclusions This study is the first to demonstrate a shared genetic etiology between MDD and ether-phosphatidylcholine species containing arachidonic acid, an omega-6 fatty acid that is a precursor to inflammatory mediators, such as prostaglandins. The study highlights the potential utility of the well-characterized linoleic/arachidonic acid inflammation pathway as a diagnostic marker and/or treatment target for MDD

Seeing the way: visual sociology and the distance runner's perspective

Employing visual and autoethnographic data from a two‐year research project on distance runners, this article seeks to examine the activity of seeing in relation to the activity of distance running. One of its methodological aims is to develop the linkage between visual and autoethnographic data in combining an observation‐based narrative and sociological analysis with photographs. This combination aims to convey to the reader not only some of the specific subcultural knowledge and particular ways of seeing, but also something of the runner's embodied feelings and experience of momentum en route. Via the combination of narrative and photographs we seek a more effective way of communicating just how distance runners see and experience their training terrain. The importance of subjecting mundane everyday practices to detailed sociological analysis has been highlighted by many sociologists, including those of an ethnomethodological perspective. Indeed, without the competence of social actors in accomplishing these mundane, routine understandings and practices, it is argued, there would in fact be no social order

Family-based analyses reveal novel genetic overlap between cytokine interleukin-8 and risk for suicide attempt

Background: Suicide is major public health concern. It is imperative to find robust biomarkers so that at-risk individuals can be identified in a timely and reliable manner. Previous work suggests mechanistic links between increased cytokines and risk for suicide, but questions remain regarding the etiology of this association, as well as the roles of sex and BMI. Methods: Analyses were conducted using a randomly-ascertained extended-pedigree sample of 1882 Mexican-American individuals (60% female, mean age = 42.04, range = 18-97). Genetic correlations were calculated using a variance components approach between the cytokines TNF-α, IL-6 and IL-8, and Lifetime Suicide Attempt and Current Suicidal Ideation. The potentially confounding effects of sex and BMI were considered. Results: 159 individuals endorse a Lifetime Suicide Attempt. IL-8 and IL-6 shared significant genetic overlap with risk for suicide attempt (ρg = 0.49, pFDR = 7.67 × 10-03; ρg = 0.53, pFDR = 0.01), but for IL-6 this was attenuated when BMI was included as a covariate (ρg = 0.37, se = 0.23, pFDR = 0.12). Suicide attempts were significantly more common in females (pFDR = 0.01) and the genetic overlap between IL-8 and risk for suicide attempt was significant in females (ρg = 0.56, pFDR = 0.01), but not in males (ρg = 0.44, pFDR = 0.30). Discussion: These results demonstrate that: IL-8 shares genetic influences with risk for suicide attempt; females drove this effect; and BMI should be considered when assessing the association between IL-6 and suicide. This finding represents a significant advancement in knowledge by demonstrating that cytokine alterations are not simply a secondary manifestation of suicidal behavior, but rather, the pathophysiology of suicide attempts is, at least partly, underpinned by the same biological mechanisms responsible for regulating inflammatory response

Cocktail-party listening and cognitive abilities show strong pleiotropy

Introduction: The cocktail-party problem refers to the difficulty listeners face when trying to attend to relevant sounds that are mixed with irrelevant ones. Previous studies have shown that solving these problems relies on perceptual as well as cognitive processes. Previously, we showed that speech-reception thresholds (SRTs) on a cocktail-party listening task were influenced by genetic factors. Here, we estimated the degree to which these genetic factors overlapped with those influencing cognitive abilities. Methods: We measured SRTs and hearing thresholds (HTs) in 493 listeners, who ranged in age from 18 to 91 years old. The same individuals completed a cognitive test battery comprising 18 measures of various cognitive domains. Individuals belonged to large extended pedigrees, which allowed us to use variance component models to estimate the narrow-sense heritability of each trait, followed by phenotypic and genetic correlations between pairs of traits. Results: All traits were heritable. The phenotypic and genetic correlations between SRTs and HTs were modest, and only the phenotypic correlation was significant. By contrast, all genetic SRT-cognition correlations were strong and significantly different from 0. For some of these genetic correlations, the hypothesis of complete pleiotropy could not be rejected. Discussion: Overall, the results suggest that there was substantial genetic overlap between SRTs and a wide range of cognitive abilities, including abilities without a major auditory or verbal component. The findings highlight the important, yet sometimes overlooked, contribution of higher-order processes to solving the cocktail-party problem, raising an important caveat for future studies aiming to identify specific genetic factors that influence cocktail-party listening

Imaging local genetic influences on cortical folding

Recent progress in deciphering mechanisms of human brain cortical folding leave unexplained whether spatially patterned genetic influences contribute to this folding. High-resolution in vivo brain MRI can be used to estimate genetic correlations (covariability due to shared genetic factors) in interregional cortical thickness, and biomechanical studies predict an influence of cortical thickness on folding patterns. However, progress has been hampered because shared genetic influences related to folding patterns likely operate at a scale that is much more local (cm) than that addressed in prior imaging studies. Here, we develop methodological approaches to examine local genetic influences on cortical thickness and apply these methods to two large, independent samples. We find that such influences are markedly heterogeneous in strength, and in some cortical areas are notably stronger in specific orientations relative to gyri or sulci. The overall, phenotypic local correlation has a significant basis in shared genetic factors and is highly symmetric between left and right cortical hemispheres. Furthermore, the degree of local cortical folding relates systematically with the strength of local correlations, which tends to be higher in gyral crests and lower in sulcal fundi. The relationship between folding and local correlations is stronger in primary sensorimotor areas and weaker in association areas such as prefrontal cortex, consistent with reduced genetic constraints on the structural topology of association cortex. Collectively, our results suggest that patterned genetic influences on cortical thickness, measurable at the scale of in vivo MRI, may be a causal factor in the development of cortical folding

Epigenetic Age Acceleration Assessed with Human White-Matter Images

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρpheno = -0.119, p = 0.028), with evidence of shared genetic (ρgene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging