Evolutionary and in silico analysis of the antiviral TRIM22 gene

Tripartite motif protein 22 (TRIM22) is an evolutionarily ancient interferon-induced protein that been shown to potently inhibit human immunodeficiency virus (HIV), hepatitis B virus (HBV), and influenza A virus (IAV) replication. Altered TRIM22 expression levels have also been linked to autoimmune disease, cancer, and cellular proliferation. Despite its important role in a number of biological processes, the factors that influence TRIM22 expression and/or antiviral activity remain largely unknown. To identify key functional sites in TRIM22, we performed extensive evolutionary and in silico analyses on the TRIM22 coding region. These tools allowed us to pinpoint multiple sites in TRIM22 that have evolved under positive selection during mammalian evolution, including one site that coincides with the location of a common non-synonymous SNP (nsSNP) in the human TRIM22 gene (TRIM22 rs1063303:G\u3eC). Remarkably, we found that the frequency of TRIM22 rs1063303:G\u3eC varied considerably among different ethnic populations and African (AFR), American (AMR), and European (EUR) populations contained an excess of intermediate frequency TRIM22 rs1063303:G\u3eC alleles when compared to a neutral model of evolution. The latter is typically indicative of balancing selection, a non-neutral selective process that maintains polymorphism in a population. Interestingly, we also found that the TRIM22 nsSNP rs1063303:G\u3eC had an inverse impact on TRIM22 function. TRIM22 rs1063303:G\u3eC increased TRIM22 expression levels, but decreased its anti-HIV activity and altered its subcellular localization pattern. In addition to these studies, we used a variety of in silico methods to prioritize and delineate other functional sites in TRIM22. We showed that the majority of positively selected sites in the C-terminal B30.2 domain of TRIM22 are located in one of four surface-exposed variable loops that are critical for the anti-HIV effects of the closely-related TRIM5α protein. Moreover, we used six different in silico nsSNP prediction programs to screen all of the nsSNPs in the TRIM22 gene and identified 14 high-risk nsSNPs that are predicted to be highly deleterious to TRIM22 function. Finally, to examine the TRIM22 nsSNP rs1063303:G\u3eC in a more isolated population, we genotyped this nsSNP in two Inuit populations (Canadian and Greenlandic Inuit). We found that the TRIM22 rs1063303:C allele is inordinately prevalent in the Inuit compared to non-Inuit populations and that these two populations do not contain an excess of intermediate frequency TRIM22 rs1063303:G\u3eC alleles compared to a neutral model of evolution, indicating that site TRIM22 rs1063303:G\u3eC has not evolved under balancing selection in the Inuit. Lastly, we found an interesting association between the TRIM22 rs1063303:C allele and serum levels of triglycerides (TG) and high-density lipoprotein (HDL). Taken together, the results presented here identify a number of pertinent sites in the TRIM22 protein that likely influence its biological and/or antiviral functions

Equal but Inequitable: Who Benefits from Gender-Neutral Tenure Clock Stopping Policies?

Many skilled professional occupations are characterized by an early period of intensive skill accumulation and career establishment. Examples include law firm associates, surgical residents, and untenured faculty at research-intensive universities. High female exit rates are sometimes blamed on the inability of new mothers to survive the sustained negative productivity shock associated with childbearing and early childrearing in these environments. Gender-neutral family policies have been adopted in some professions in an attempt to "level the playing field." The gender-neutral tenure clock stopping policies adopted by the majority of research-intensive universities in the United States in recent decades are an excellent example. But to date, there is no empirical evidence showing that these policies help women. Using a unique data set on the universe of assistant professor hires at top-50 economics departments from 1985-2004, we show that the adoption of gender-neutral tenure clock stopping policies substantially reduced female tenure rates while substantially increasing male tenure rates

Meat-Wise Eating Habits

Whether from a cow, pig, bird, fish, or other domestic or game animal, meat is universally enjoyed as part of the cultural culinary experience. It is also an excellent source of protein, which is important for a healthy body. Many people who eat meat, however, are not aware of the impact their consumption has on the environment. This guide provides a set of quick facts and action tools to make wiser choices concerning meat consumption

Betta Less Motivated: Effects of Fluoxetine on Betta Splendens

Previous studies have demonstrated that the selective serotonin reuptake inhibitor (SSRI) Fluoxetine reduces aggression in Siamese fighting fish (Betta splendens). While this finding has been replicated across multiple studies, the behavioral mechanism of Fluoxetine\u27s action upon aggression is not known. Betta splendens are great candidates for Fluoxetine exposure based on their well documented seratonergic activity as well as their choice for agressive opportunities. In particular, Fluoxetine may produce its anti-aggressive effects by altering the motivational component of aggressive responding in Betta splendens or through the sedation of motoric activity. To examine this hypothesis a maze swimming task for access to aggressive oppurtunities was designed. Results from this task indicated that Fluoxetine exposures reduce the appetitive properties of the aggressive encounters and provide evidence for a role of serotonin in the control of motivational processes. The results leave room for discussion of the impacts of antidepressant medications used by humans

The Effects of Mandala Coloring on Reducing Stress in Corporate Employees: A Quasi-Experimental Pilot Study

Job demands and extended hours contribute to chronic employee stress, leading to physical and psychological health problems. Workplace wellness programs (WWPs) strive to improve employee’s physical health and wellbeing, but lack holistic options addressing stress reduction for the mind, body, and spirit. The purpose of this project is to describe the effects mandala coloring has on reducing objective and subjective stress levels in corporate employees. This empirical, quasi-experimental pilot study sampled 14 employees (n = 6 experimental, n = 8 control) measuring blood pressure, pulse, and perceived stress levels over a course of three weeks of coloring. Participants of this convenience sample were randomly sorted into the control or experimental group. Data was analyzed and interpreted using IBM SPSS Statistics 24. An RMANOVA showed no statistical significance between coloring mandalas versus coloring sheets in reducing objective and subjective stress levels in corporate employees over a three week time period. Our pilot study provides a starting point for future research and possible implications for WWPs. Our suggestions for future research include: recruiting a larger sample size to represent the population as a whole, increasing both the duration of the study and time spent coloring for participants, incorporating qualitative data, and testing cortisol levels as another determinant of stress reduction. Furthermore, as the demands of corporate employees continue to cause chronic stress to rise, it is necessary to provide more evidence for stress reduction encompassing holistic modalities, such as mandala coloring, in a workplace setting

The dynamics of three-forms in thick branes

In this work, we investigate thick brane models with a single three-form field. We find novel solutions for thick braneworlds where only three-forms exist and interact gravitationally in the bulk, both with and without matter fields. We use an additional scalar field as proxy for the matter fields. As an initial study, we consider the results here in contrast to the single scalar field thick braneworld case. The properties of the specific three-form parameterisation limits the freedom we have to choose the form of the warp factor, leading to a closed system of equations with nontrivial yet unstable solutions. The stability of the gravitational sector for thick brane three-forms is investigated and the models are shown to be unstable against small perturbations of the metric, further indicating that three-forms cannot exist stably in thick braneworld settings

Bilateral attentional advantage on elementary visual tasks

We examined interactions between and within the left and right visual hemifields using elementary visual tasks. Each trial required identifying a letter at fixation and then either discriminating the orientation of (experiment I) or detecting (experiment 2) peripheral Gabor targets. On half the trials Gabor distracters were presented between the Gabor targets, and were either restricted to one lateral hemifield (unilateral condition) or presented across the left and right hemifields (bilateral condition). Orientation discrimination and detection each exhibited bilateral superiority only when distracters were present. The results confirm bilateral superiority in attentional selection, even on these most elementary visual tasks. (C) 2009 Elsevier Ltd. All rights reserved

The Effects of Substance Use and Depressive Symptoms on High-Risk Sexual Behaviors in Sexually Active Vermont Adolescents

Background: There is a high prevalence of substance use, depressive symptoms, and high-risk sexual behaviors (HRSB) among adolescents, but the relationships between these variables is less clear. Objective: To identify associations between these behaviors and outcomes, this study aims to address how depressive symptoms paired with substance use impacts HRSB in adolescents. Methods: Adolescent self-reported depressive and suicidal symptoms, substance use, and HRSB were obtained from the 2015 Vermont Youth Risk Behavior Survey (YRBS) (n= 17,041). The associations between exposures (substance use and depressive symptoms) with HRSB were studied. Variables were calculated using prevalence ratios with 95% confidence intervals (CI) and logistic regression to determine adjusted odds ratios (OR). Results: Adolescents who attempted suicide more than once were \u3e5 times more likely to engage in 4+ HRSB (OR=5.19, P\u3c.001). Low-level drug users were 1.76 times more likely to engage in 4+ HRSB (p=\u3c0.05) and high-level users 6.69 times more likely (p\u3c.001). Reporting sexual intercourse with same sex partners was significantly associated with HRSB, while reported sexual orientation was not. Conclusions: There are associations between both self-reported depressive symptoms and substance use with high-risk sexual behavior in adolescents