Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study

Objectives: Single genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene-gene (G x G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and agerelated diseases would identify significant interactions with increased predictive power for depression. Design: A retrospective cohort study. Setting: A survey of participants in the Wisconsin Longitudinal Study. Participants: A total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white. Primary outcome measure: Depression as determine by the Composite International Diagnostic Interview-Short-Form. Results: Using a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G 3 G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G x G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) → (after): men: GNRH1 novel SNP: (1.43 → 1.57); women: APOC3 rs2854116: (1.28 → 1.55), ACVR2B rs3749386: (1.11 → 2.17), FTO rs1421085: (1.32 → 1.65), IL6 rs1800795: (1.12 → 1.85)). Conclusions: The results suggest that examining G x G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1 and DRD2) and neuroendocrine (GNRH1 and ACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology

Uniform regularity for the Navier-Stokes equation with Navier boundary condition

We prove that there exists an interval of time which is uniform in the vanishing viscosity limit and for which the Navier-Stokes equation with Navier boundary condition has a strong solution. This solution is uniformly bounded in a conormal Sobolev space and has only one normal derivative bounded in $L^\infty$. This allows to get the vanishing viscosity limit to the incompressible Euler system from a strong compactness argument

Oh Comrade, What Times those Were! History, Capital Punishment and the Urban Square.

From the perspective of traditional Western histories of the urban realm, public squares have been seen to represent a privileged site of urban containment expressive of a community's highest values of individual freedom, social inclusion and cultural refinement. But such views can be misleading. For what is omitted from the scope of these conventional historical visions and their ideal and conforming subjects of public spatial discourse, is an entire array of other and darker narratives that equally speak of personal choice, collective participation and cultural value. Capital punishment reflects such an example, a practice that once comprised an integral part of the political, social and cultural landscape of a Western city's squares and streets. Drawing from Michel Foucault's Discipline and Punish and its implications on how we might begin to re-read the history of the urban square, the following seeks to explore those practices and modes of rationality that underpinned the once public spectacle of executions and torture as a vital condition of urban life. In particular, this discussion will question the assumptions of an historical tradition that continues to reduce our understanding of the city and its open spaces of public appearance and action to an idealistic and illusory reality of the urban realm and its narrow framing of collective conduct, necessity and significance

The association between environmental exposures during childhood and the subsequent development of Crohn's Disease: A score analysis approach

Background Environmental factors during childhood are thought to play a role in the aetiology of Crohn's Disease (CD). In South Africa, recently published work based on an investigation of 14 childhood environmental exposures during 3 age intervals (0-5, 6-10 and 11-18 years) has provided insight into the role of timing of exposure in the future development of CD. The 'overlapping' contribution of the investigated variables however, remains unclear. The aim of this study was to perform a post hoc analysis using this data and investigate the extent to which each variable contributes to the subsequent development of CD relative to each aforementioned age interval, based on a score analysis approach. Methods Three methods were used for the score analysis. Two methods employed the subgrouping of one or more (similar) variables (methods A and B), with each subgroup assigned a score value weighting equal to one. For comparison, the third approach (method 0) involved no grouping of the 14 variables. Thus, each variable held a score value of one. Results Results of the score analysis (Method 0) for the environmental exposures during 3 age intervals (0-5, 6-10 and 11-18 years) revealed no significant difference between the case and control groups. By contrast, results from Method A and Method B revealed a significant difference during all 3 age intervals between the case and control groups, with cases having significantly lower exposure scores (approximately 30% and 40% lower, respectively). Conclusion Results from the score analysis provide insight into the 'compound' effects from multiple environmental exposures in the aetiology of CD.IS

Management of a South African family with retinitis pigmentosa—should potential therapy influence translational research protocols?

Mutation analysis of retinal candidate genes is performed as part of an ongoing research to identify the causative genetic defect in South African families with retinal degenerative disorders (RDDs). A translational research protocol has been established whereby probands are counseled and given their molecular genetic results to take back to other family members, who can then request individual diagnostic testing. A Thr17Met mutation of the rhodopsin gene was identified in a Caucasian South African family with autosomal dominant retinitis pigmentosa. Patients with this mutation appear to benefit from treatment using oral vitamin A supplementation. This family has been informed that a molecular diagnosis is available; however, one individual has refused testing and none of the younger generation has shown interest in receiving molecular results or genetic counseling. Adapting the established protocol for the translation of RDD research results and contacting mutation positive individuals may be justifiable in light of the potential benefit of therapy

Determinants of female sexual function in inflammatory bowel disease: a survey based cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Sexual function is impaired in women with inflammatory bowel disease (IBD) as compared to normal controls. We examined disease specific determinants of different aspects of low sexual function.</p> <p>Methods</p> <p>Women with IBD aged 18 to 65 presenting to the university departments of internal medicine and surgery were included. In addition, a random sample from the national patients organization was used (separate analyses). Sexual function was assessed by the Brief Index of Sexual Function in Women, comprising seven different domains of sexuality. Function was considered impaired if subscores were < -1 on a z-normalized scale. Results are presented as age adjusted odds ratios with 95% CI based on multiple logistic regression.</p> <p>Results</p> <p>336 questionnaires were included (219 Crohn's disease, 117 ulcerative colitis). Most women reported low sexual activity (63%; 17% none at all, 20% moderate or high activity). Partnership satisfaction was high in spite of low sexual interest in this group. Depressed mood was the strongest predictor of low sexual function scores in all domains. Urban residency and higher socioecomic status had a protective effect. Disease activity was moderately associated with low desire (OR 1.8, 95% CI 1.0 to 3.2). Severity of the disease course impacted most on intercourse frequency (OR 2.3, 95% CI 1.4 to 4.7). Lubrication problems were more common in smokers (OR 2.5, 95% CI 1.3 to 5.1).</p> <p>Conclusion</p> <p>Mood disturbances and social environment impacted more on sexual function in women with IBD than disease specific factors. Smoking is associated with lubrication problems.</p

Remnant radio-loud AGN in the Herschel-ATLAS field

Only a small fraction of observed active galactic nuclei (AGN) display large-scale radio emission associated with jets, yet these radio-loud AGN have become increasingly important in models of galaxy evolution. In determining the dynamics and energetics of the radio sources over cosmic time, a key question concerns what happens when their jets switch off. The resulting ‘remnant' radio-loud AGN have been surprisingly evasive in past radio surveys, and therefore statistical information on the population of radio-loud AGN in their dying phase is limited. In this paper, with the recent developments of Low-Frequency Array (LOFAR) and the Very Large Array, we are able to provide a systematically selected sample of remnant radio-loud AGN in the Herschel-ATLAS field. Using a simple core-detection method, we constrain the upper limit on the fraction of remnants in our radio-loud AGN sample to 9 per cent, implying that the extended lobe emission fades rapidly once the core/jets turn off. We also find that our remnant sample has a wide range of spectral indices (−1.5 ⩽ α1400150 ⩽ −0.5), confirming that the lobes of some remnants may possess flat spectra at low frequencies just as active sources do. We suggest that, even with the unprecedented sensitivity of LOFAR, our sample may still only contain the youngest of the remnant population

Asexuality: Classification and characterization

This is a post-print version of the article. The official published version can be obtaineed at the link below.The term “asexual” has been defined in many different ways and asexuality has received very little research attention. In a small qualitative study (N = 4), individuals who self-identified as asexual were interviewed to help formulate hypotheses for a larger study. The second larger study was an online survey drawn from a convenience sample designed to better characterize asexuality and to test predictors of asexual identity. A convenience sample of 1,146 individuals (N = 41 self-identified asexual) completed online questionnaires assessing sexual history, sexual inhibition and excitation, sexual desire, and an open-response questionnaire concerning asexual identity. Asexuals reported significantly less desire for sex with a partner, lower sexual arousability, and lower sexual excitation but did not differ consistently from non-asexuals in their sexual inhibition scores or their desire to masturbate. Content analyses supported the idea that low sexual desire is the primary feature predicting asexual identity

The aged niche disrupts muscle stem cell quiescence

SUMMARY The niche is a conserved regulator of stem cell quiescence and function. During aging, stem cell function declines. To what extent and by which means age-related changes within the niche contribute to this phenomenon are unknown. We demonstrate that the aged muscle stem cell niche, the muscle fiber, expresses FGF2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose self-renewing capacity. We show that relatively dormant aged satellite cells robustly express Sprouty1 (spry1), an inhibitor of FGF signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing spry1, results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of FGFR1 signalling or overexpression of spry1 in satellite cells prevents their depletion. These experiments identify an age-dependent change in the stem cell niche that directly influences stem cell quiescence and function