Going beyond integration: The emerging role of HIV-1 integrase in virion morphogenesis

The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis

Unwrapping school lunch: Examining the social dynamics and caring relationships that play out during school lunch

Students are important stakeholders in school food programs. Yet children’s daily experiences and voices are often overlooked in advocacy around school food. In Canada, where the federal government recently expressed interest in creating a National School Food Program, nearly no research has documented the first-hand experiences of children during lunch. This ethnographic study draws on data collected during 36 lunchtimes in three Canadian schools during a transitional period in a school district’s lunch program. The findings unwrap the powerful role of students’ perceptions of and relationships to food in shaping their social interactions, and their sense of care, connection, and identity. Classroom observations coupled with photos of school lunches demonstrate the wide diversity of foods eaten at school and the nuanced, complex, and sometimes divergent meanings children give to food, school lunch and the people involved in preparing, serving, supervising, and sharing lunchtime experiences. Students demonstrated in-depth knowledge of the food choices and attitudes of their peers and actively marked out their identities vis-à-vis food. Students frequently talked about food as a site of care and support, and both the social relationships and care work that played out were a major part of school lunch experiences. Understanding the intricacies of children’s school lunch experiences, including the relationships, meanings, and values that shape school lunch, will be critical for creating robust school food programs and policies in Canada that better serve the needs of children and reduce rather than reproduce existing health and social inequalities.Peer reviewe

Athletes’ Perceptions of Coaches’ Emotional Intelligence Competencies

This study compared intercollegiate athletic coaches’ self-perceptions to the perceptions of their players concerning a coach’s emotional intelligence. Sixteen coaches and 223 players from two Division I softball conferences completed the Emotional Competence Inventory-2 (Boyaztis, Goleman, & Hay/McBer, 2001). Mean analysis revealed that coaches rated themselves higher on 14 of the 18 emotional intelligence competencies and on all four emotional intelligence clusters. Coaches rated themselves highest in Social Awareness (Error! Bookmark not defined.x¯ =4.27/5) while their athletes rated them highest in Self Awareness (Error! Bookmark not defined.x¯ =3.63/5). Meanwhile, athletes gave coaches their lowest rating in Relationship Management (Error! Bookmark not defined.x¯ =3.44/5). Coaches need to be aware that the self perceptions of their own behavior differ from the perceptions of their athletes. Since it is well known that the behavior of the coach affects the performance of the athlete, techniques to train coaches to recognize and overcome this difference could be beneficial and are provided

An Investigation of Student Performance, Student Satisfaction , and Learner Characteristics in Online Versus Face-to-Face Classes--RESEARCH

The purpose of this study was to investigate student performance, student satisfaction, and learner characteristics in online versus face-to-face delivery formats in accounting. Forty-four students, enrolled in either the face-to-face or online section of an accounting course, completed a survey assessing satisfaction, learning outcomes, and learner characteristics. Significant differences were found regarding satisfaction with learning and perception of the instructor. However, online learners displayed similar traits as their face-to-face counterparts. In addition, researchers compared pre-test / post-test, homework, quiz, and exam scores to determine if delivery method affected learning. A significant difference was found between face-to-face and online students in post-test performance. Overall, the results of this study suggest that students perform as well in an online course as they do in a traditional face-to-face classroom and learner characteristics are similar for both online students and face-to-face classroom students. Post-test results indicate that students in an online class do not retain the information as well as those in a face-to-face class. These results, like others, show that online instructors continue to face challenges in promoting student participation and interaction in the course and overall satisfaction with learning. There is a need to replicate this study in other online courses in different disciplines

Molecular Response of the Brain to Cross-Generational Warming in a Coral Reef Fish

Ocean warming is a threat to marine biodiversity, as it can push marine species beyond their physiological limits. Detrimental effects can occur when marine poikilotherms are exposed to conditions beyond their thermal optima. However, acclamatory mechanisms, such as plasticity, may enable compensation of detrimental effects if warming is experienced during development or across generations. Studies evaluating the molecular responses of fishes to warming have mostly focused on liver, muscle, and gonads, and little is known about the effects on other vital organs, including the brain. This study evaluated the transcriptional program of the brain in the coral reef fish Acanthochromis polyacanthus, exposed to two different warming scenarios: +1.5°C and +3.0°C, across successive generations. Fish were exposed to these conditions in both developmental (F1 and F2) and transgenerational settings (F2 only), as well as a treatment with step-wise warming between generations. The largest differences in gene expression were between individuals of the first and second generation, a pattern that was corroborated by pairwise comparisons between Control F1 and Control F2 (7,500 DEGs) fish. This large difference could be associated with parental effects, as parents of the F1 generation were collected from the wild, whereas parents of the F2 generation were reared in captivity. A general response to warming was observed at both temperatures and in developmental and transgenerational treatments included protein folding, oxygen transport (i.e., myoglobin), apoptosis and cell death, modification of cellular structure, mitochondrial activity, immunity and changes in circadian regulation. Treatments at the highest temperature showed a reduction in synaptic activity and neurotransmission, which matches previous behavioral observations in coral reef fishes. The Transgenerational +3.0°C treatment showed significant activation of the gene pls3, which is known for the development of neuro-muscular junctions under heat-stress. F2 samples exposed to step-wise warming showed an intermediate response, with few differentially expressed genes compared to developmental and transgenerational groups (except for Transgenerational +1.5°C). In combination with previous studies on liver gene expression, this study indicates that warming produces a molecular signature of stress response in A. polyacanthus that is influenced both by the intensity of warming as well as the duration of exposure

Praziquantel for the treatment of schistosomiasis during human pregnancy.

In 2014, an estimated 40 million women of reproductive age were infected with Schistosoma haematobium, S. japonicum and/or S. mansoni. In both 2003 and 2006, the World Health Organization (WHO) recommended that all schistosome-infected pregnant and breastfeeding women be offered treatment, with praziquantel, either individually or during treatment campaigns. In 2006, WHO also stated the need for randomized controlled trials to assess the safety and efficacy of such treatment. Some countries have yet to follow the recommendation on treatment and many programme managers and pregnant women in other countries remain reluctant to follow the recommended approach. Since 2006, two randomized controlled trials on the use of praziquantel during pregnancy have been conducted: one against S. mansoni in Uganda and the other against S. japonicum in the Philippines. In these trials, praziquantel treatment of pregnant women had no significant effect on birth weight, appeared safe and caused minimal side-effects that were similar to those seen in treated non-pregnant subjects. Having summarized the encouraging data, on efficacy, pharmacokinetics and safety, from these two trials and reviewed the safety data from non-interventional human studies, we recommend that all countries include pregnant women in praziquantel treatment campaigns. We identify the barriers to the treatment of pregnant women, in countries that already include such women in individual treatments and mass drug administration campaigns, and discuss ways to address these barriers

Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters

BACKGROUND: In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion) and for the day (e.g., rest and low melatonin secretion). Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition. RESULTS: Rhythm splitting was observed in wheel-running and general locomotion of Siberian and Syrian hamsters. The latter also manifest split rhythms in body temperature. Access to a running wheel was necessary neither for the induction nor maintenance of this entrainment pattern. While rhythms were only transiently split in many animals with two 5 h nights, the incidence of splitting was greater with twice daily nights of shorter duration. Removal of running wheels altered the body temperature rhythm but did not eliminate its clear bimodality. CONCLUSION: The expression of entrained, split circadian rhythms exhibits no strict dependence on access to a running wheel, but can be facilitated by manipulation of ambient lighting conditions. These circadian entrainment patterns may be of therapeutic value to human shift-workers and others facing chronobiological challenges

Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.

"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs. We chemically modified three different antiretroviral drugs, zidovudine, tenofovir, and elvitegravir, for direct conjugation to vaults. Tested in infection assays, drug-conjugated vaults inhibited HIV-1 infection of PBMC with equivalent activity to free drugs, indicating vault delivery and drug release in the cytoplasm of HIV-1-susceptible cells. The ability to deliver functional drugs via vault nanoparticle conjugates suggests their potential utility for targeted drug delivery against HIV-1

Policy Recommendations for Meeting the Grand Challenge to Reduce Extreme Economic Inequality

This brief was created forSocial Innovation for America’s Renewal, a policy conference organized by the Center for Social Development in collaboration with the American Academy of Social Work & Social Welfare, which is leading theGrand Challenges for Social Work initiative to champion social progress. The conference site includes links to speeches, presentations, and a full list of the policy briefs