Antigenic variation and resistance to neutralization in poliovirus type 1.

Mutations have been identified in variants of poliovirus, type 1 (Mahoney) on the basis of their resistance to neutralization by individual monoclonal antibodies. The phenotypes of these variants were defined in terms of antibody binding; the pattern of epitopes expressed or able to be exploited for neutralization were complex. Single amino acid changes can have distant (in terms of linear sequence) and generalized effects on the antigenic structure of poliovirus and similarly constituted virions

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Psychache and Suicide Risk in the LGBTQ Community: Considering the Role of Time Perspective

In the United States, approximately 45,000 persons die by suicide annually. Members of the LGBTQ community experience heightened suicide risk; for example, suicide attempts are four times higher among gay and bisexual men, and twice as common in lesbian and bisexual women, compared to heterosexual counterparts. Experiences of stigma and discrimination may constrict one’s view of a positive future (e.g., hopelessness), thereby contributing to the development of psychache, or unbearable psychological pain and negative emotionality, and heightened risk for suicide. However, individual-level resiliency traits, such as a positive view of the future (e.g., future orientation) may contribute to reduced levels of psychological pain and suicidality. That is, whereas future orientation may ameliorate psychological pain and suicide risk, hopelessness may exacerbate such risks; yet, a comparison of the effects of these temporal constructs on psychache has not been previously examined in an LGBTQ sample. At the bivariate level, we hypothesized that hopelessness would be positively related to psychache and suicide risk, and that psychache would be positively related to suicide risk. In addition, we hypothesized that future orientation would be negatively related to hopelessness, psychache and suicide risk. At the multivariate level, we hypothesized that psychache would mediate the associations between hopelessness and suicide risk, and between positive future orientation and suicide risk. In other words, greater positive future orientation would be associated with less psychache and, in turn, to reduced suicide risk, and greater hopelessness would be linked to more psychache and suicide risk. Recruited locally, nationally, and internationally from advocacy organizations and support groups, our sample of LGBTQ individuals (N = 496) was primarily White (81.7%; n = 365), female (44.8%; n = 201), and either lesbian or gay (46.8%, n = 209). Participants completed online self-report measures, including: Beck Hopelessness Scale, Future Orientation Scale, Psychache Scale, and the Suicidal Behaviors Questionnaire-Revised. Bivariate correlations, and multivariate analyses per Hayes (2013), were conducted, covarying age, birth sex, and race/ethnicity. In bivariate correlations, all variables were significantly related in hypothesized directions (p \u3c .01). In serial mediation analyses, the total effect of future orientation on suicide risk was significant (t = -2.17, p \u3c .05), and the direct effect was nonsignificant when psychache was added to the model (t = -.879, p = .381), indicating mediation. In the second model, psychache mediated the relation between hopefulness and suicide risk; the total effect was significant (t = 3.56, p \u3c .05), and the direct effect was nonsignificant (t = 1.35, p = .181). Supporting hypotheses, our results suggest that LGBTQ individuals with a positive future orientation experience less psychache and, in turn, reduced suicide risk. On the other hand, LGBTQ persons with greater hopelessness experience greater psychache and, in turn, greater suicide risk. Therapeutic interventions designed to encourage an adaptive, positive view of the future (e.g. Future Directed Therapy), rather than a hopeless view of the future, may help to counteract the often-present stressors and distress experienced by LGBTQ persons, thereby ameliorating suicide risk

A comparison of decision-theoretic, fixed-policy and random tutorial action selection

Abstract. DT Tutor (DT), an ITS that uses decision theory to select tutorial actions, was compared with both a Fixed-Policy Tutor (FT) and a Random Tutor (RT). The tutors were identical except for the method they used to select tutorial actions: FT employed a common fixed policy while RT selected randomly from relevant actions. This was the first comparison of a decision-theoretic tutor with a non-trivial competitor (FT). In a two-phase study, first DT’s probabilities were learned from a training set of student interactions with RT. Then a panel of judges rated the actions that RT took along with the actions that DT and FT would have taken in identical situations. DT was rated higher than RT and also higher than FT both overall and for all subsets of scenarios except help requests, for which DT’s and FT’s ratings were equivalent.