The Omega Deformation, Branes, Integrability, and Liouville Theory

We reformulate the Omega-deformation of four-dimensional gauge theory in a way that is valid away from fixed points of the associated group action. We use this reformulation together with the theory of coisotropic A-branes to explain recent results linking the Omega-deformation to integrable Hamiltonian systems in one direction and Liouville theory of two-dimensional conformal field theory in another direction.Comment: 96 p

Natural variation in a glucuronosyltransferase modulates propionate sensitivity in a C. elegans propionic acidemia model

Mutations in human metabolic genes can lead to rare diseases known as inborn errors of human metabolism. For instance, patients with loss-of-function mutations in either subunit of propionyl-CoA carboxylase suffer from propionic acidemia because they cannot catabolize propionate, leading to its harmful accumulation. Both the penetrance and expressivity of metabolic disorders can be modulated by genetic background. However, modifiers of these diseases are difficult to identify because of the lack of statistical power for rare diseases in human genetics. Here, we use a model of propionic acidemia in the nematode Caenorhabditis elegans to identify genetic modifiers of propionate sensitivity. Using genome-wide association (GWA) mapping across wild strains, we identify several genomic regions correlated with reduced propionate sensitivity. We find that natural variation in the putative glucuronosyltransferase GLCT-3, a homolog of human B3GAT, partly explains differences in propionate sensitivity in one of these genomic intervals. We demonstrate that loss-of-function alleles in glct-3 render the animals less sensitive to propionate. Additionally, we find that C. elegans has an expansion of the glct gene family, suggesting that the number of members of this family could influence sensitivity to excess propionate. Our findings demonstrate that natural variation in genes that are not directly associated with propionate breakdown can modulate propionate sensitivity. Our study provides a framework for using C. elegans to characterize the contributions of genetic background in models of human inborn errors in metabolism

The relationship between cognitive schemas activated in sexual context and early maladaptive schemas among married women of childbearing age

Background: Healthy sex can be affected by cognitive schemas activated in the sexual context (CSASCs) and early maladaptive schemas (EMSs). Cognitive schemas are the nuclear structure of the cognitive system which facilitate the interaction between individuals and their environments. CSASCs are emotional and behavioral responses in the sexual context. EMSs are extremely stable, enduring and are developed throughout the life of the individual, beginning in childhood. The present study investigated the relationship between CSASCs and EMSs among married women of childbearing age. Methods: In a cross-sectional study, 260 married women of childbearing age participated. Using two-stage sampling , ten comprehensive urban health centers were first randomly selected and then 26 individuals from each center were invited to participate. Data collection included demographic variables, the Young Schema Questionnaire-Short Form (YSQ-SF) with 15 EMSs (emotional deprivation, abandonment, mistrust/abuse, social alienation, defectiveness, incompetence, dependency, vulnerability to harm, enmeshment, subjugation of needs, self-sacrifice, emotional inhibition , unrelenting standards, entitlement, and insufficient self-control), and the Cognitive Schema Activation in Sexual Context Questionnaires (CSASCQ) with five subscales (undesirability/rejection, incompetence, self-depreciation, difference/loneliness, and helplessness). Data analysis was performed using a uni-variable and multi-variable linear regression model with a stepwise method at a significance level of 0.05. Results: The mean age of the participants was 32.48 years and the average duration of their marriage was 10.34 years. The average score of early maladaptive schemas on the YSQ-SF was 151.5 (out of 450). Higher scores indicate more severe maladaptive schemas, although the total score has no defined cutoff point. Scores greater than 15 on each subscale constitute the internalization of that particular maladaptive schema. The highest average subscale scores were the schemas of self-sacrifice and unrelenting standards (M = 16.12, 15.90, respectively), indicating that these two schemas play important roles in the cognition of the participants. The mean score on the CSASCQ was 34.60 (SD ± 12.59; range: 25-125), with the highest mean reported on the loneliness subscale. Hypoactive sexual desire was the most common unpleasant sexual problem (6.9%) and disillusion was the most dominant feeling experienced by participants (33.3%). The results of the multivariable model showed that the following were significant predictors of the CSASC: three subscales of EMS (emotional deprivation [β = 0.28], social isolation [β = 0.31], and emotional inhibition [β = 0.14]) and two demographic variables (job [β = 0.11] and consanguineous marriage [β = 0.20]). In total, the multi-variable model explained 92% of variance of CSASCs. Conclusions: The present study found a significant and meaningful association between EMSs and CSASCs adjusting for the effect of socio-demographic characteristics. The findings indicate that the study of schemas and schema therapy should be considered in both premarital and marital counseling

Dishevelled proteins regulate cell adhesion in mouse blastocyst and serve to monitor changes in Wnt signaling

Wnt signaling is essential for the regulation of cell polarity and cell fate in the early embryogenesis of many animal species. Multiple Wnt genes and its pathway members are expressed in the mouse early embryo, raising the question whether they play any roles in preimplantation development. Dishevelled is an important transducer of divergent Wnt pathways. Here we show that three of the mouse Dishevelled proteins are not only expressed in oocytes and during preimplantation development, but also display distinct spatio-temporal localization. Interestingly, as embryos reach blastocyst stage, Dishevelled 2 becomes increasingly associated with cell membrane in trophectoderm cells, while at E4.5, Dishevelled 3 is highly enriched in the cytoplasm of ICM cells. These changes are coincident with an increase in the active form of β-catenin, p120catenin transcription and decrease of Kaiso expression, indicating an upregulation of Wnt signaling activity before implantation. When Dishevelled-GFP fusion proteins are overexpressed in single blastomeres of the 4-cell stage embryo, the progeny of this cell show reduction in cell adhesiveness and a rounded shape at the blastocyst stage. This suggests that perturbing Dvl function interferes with cell–cell adhesion through the non-canonical Wnt pathway in blastocysts