Sperm depletion and sperm competition in the red-sided garter snake, Thamnophis sirtalis parietalis

Sperm competition is the post-copulatory analog of male-male combat, wherein sperm from more than one male coincide in a female’s reproductive tract and compete with one another for fertilization of a limited number of ova. Post-copulatory sexual selection, such as sperm competition, can be a powerful driving force for the evolution of many reproductive traits that can lead to rapid divergence. I investigated the effect of sperm depletion on sperm competition in a model polygynandrous mating system of the Redsided garter snake, Thamnophis sirtalis parietalis. The difference in P1 (the proportion of offspring sired by the first male to mate) between a male’s first and second matings was not statistically significant (P = 0.314). However, pooling the data to compare P1, P2, and PSS did show a statistically significant difference between PSS and P1 (P < 0.05), but not between P1 and P2 or P2 and PSS (P > 0.05). Female and male copulation durations, male masses, and interval between matings did not have any significant affect on the paternity of the offspring (All P > 0.05). Genetic bet hedging, sexual conflict, and sperm degradation/extrusions are all ideas that may help to explain our results

Factors influencing paternity in multiply mated female red-sided garter snakes and the persistent use of sperm stored over winter

In some species, sperm is stored within the female reproductive tract for months to years, and yet remains viable to fertilize eggs and produce offspring. Female red-sided garter snakes store sperm for over seven months of winter dormancy. In previous work we demonstrated that these stored sperm account for an average of 25% paternity of a litter when the female mates with a male at spring emergence. Here we tested whether last-male sperm precedence was prevalent when a female mates with two males during the spring. On average, paternity was shared equally among the first (P₁ proportion of paternity of the first male to mate) and second male (P₂) to mate in the spring, and stored sperm (P[subscript ss]), but the variance in paternity was high. Thus, last male sperm precedence may diminish when a female has more than two mates. Male size did not affect paternity, but as the interval between matings increased, P₁ increased at the expense of P[subscript ss]. Interestingly, as the second spring male’s copulation duration increased, P₁ also increased at the expense of P₂. This result suggests that female influence over sperm and/or copulatory plug transfer during matings may also affect which male fathers her offspring in response to coercive matings as we assisted females to mate for their second mating. Finally, all females were spring “virgins”, consequently sperm stored from autumn matings (and/or previous spring matings) remain competitive even when faced with two rivals in sperm competition and is likely the driver of the evolution of sperm longevity.Keywords: Sperm competition, Stored sperm, Mating interval, Sperm precedence, Mate-orde

High school drinking mediates the relationship between parental monitoring and college drinking: A longitudinal analysis

<p>Abstract</p> <p>Background</p> <p>College drinking is a significant public health problem. Although parental monitoring and supervision reduces the risk for alcohol consumption among younger adolescents, few studies have investigated the impact of earlier parental monitoring on later college drinking. This study examined whether parental monitoring indirectly exerts a protective effect on college drinking by reducing high school alcohol consumption.</p> <p>Methods</p> <p>A longitudinal cohort of 1,253 male and female students, ages 17 to 19, attending a large, public, mid-Atlantic university was studied at two time points. First, data on high school parental monitoring and alcohol consumption were gathered via questionnaire during the summer prior to college entry. Second, during the first year of college, past-year alcohol consumption was measured via a personal interview. Multiple regression models tested the relationship between parental monitoring and past year alcohol use (i.e., number of drinks per drinking day).</p> <p>Results</p> <p>Holding constant demographics, SAT score, and religiosity, parental monitoring had a significant protective effect on both high school and college drinking level. However, the association between parental monitoring and college drinking level became non-significant once high school drinking level was held constant.</p> <p>Conclusion</p> <p>While parental monitoring did not directly influence college alcohol consumption, evidence for mediation was observed, whereby parental monitoring had an indirect influence on college drinking through reductions in high school drinking. Initiatives that promote effective parenting might be an important strategy to curb high-risk drinking among older adolescents. More research is needed to understand the nature and degree of parent-child communication that is necessary to extend the protective influence of parents into the college years.</p

Shared attention for action selection and action monitoring in goal-directed reaching

Dual-task studies have shown higher sensitivity for stimuli presented at the targets of upcoming actions. We examined whether attention is directed to action targets for the purpose of action selection, or if attention is directed to these locations because they are expected to provide feedback about movement outcomes. In our experiment, endpoint accuracy feedback was spatially separated from the action targets to determine whether attention would be allocated to (a) the action targets, (b) the expected source of feedback, or (c) to both locations. Participants reached towards a location indicated by an arrow while identifying a discrimination target that could appear in any one of eight possible locations. Discrimination target accuracy was used as a measure of attention allocation. Participants were unable to see their hand during reaching and were provided with a small monetary reward for each accurate movement. Discrimination target accuracy was best at action targets but was also enhanced at the spatially separated feedback locations. Separating feedback from the reaching targets did not diminish discrimination accuracy at the movement targets but did result in delayed movement initiation and reduced reaching accuracy, relative to when feedback was presented at the reaching target. The results suggest attention is required for both action planning and monitoring movement outcomes. Dividing attention between these functions negatively impacts action performance

CD4 T Cell Immunity Is Critical for the Control of Simian Varicella Virus Infection in a Nonhuman Primate Model of VZV Infection

Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, albeit rarely, in children and a 2-dose regimen is now recommended. Similarly, although Zostavax results in a 50% reduction in HZ cases, a significant number of recipients remain at risk. To design more efficacious vaccines, we need a better understanding of the immune response to VZV. Clinical observations suggest that T cell immunity plays a more critical role in the protection against VZV primary infection and reactivation. However, no studies to date have directly tested this hypothesis due to the scarcity of animal models that recapitulate the immune response to VZV. We have recently shown that SVV infection of rhesus macaques models the hallmarks of primary VZV infection in children. In this study, we used this model to experimentally determine the role of CD4, CD8 and B cell responses in the resolution of primary SVV infection in unvaccinated animals. Data presented in this manuscript show that while CD20 depletion leads to a significant delay and decrease in the antibody response to SVV, loss of B cells does not alter the severity of varicella or the kinetics/magnitude of the T cell response. Loss of CD8 T cells resulted in slightly higher viral loads and prolonged viremia. In contrast, CD4 depletion led to higher viral loads, prolonged viremia and disseminated varicella. CD4 depleted animals also had delayed and reduced antibody and CD8 T cell responses. These results are similar to clinical observations that children with agammaglobulinemia have uncomplicated varicella whereas children with T cell deficiencies are at increased risk of progressive varicella with significant complications. Moreover, our studies indicate that CD4 T cell responses to SVV play a more critical role than antibody or CD8 T cell responses in the control of primary SVV infection and suggest that one potential mechanism for enhancing the efficacy of VZV vaccines is by eliciting robust CD4 T cell responses

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells

Abstract Objective Dimethyl fumarate (DMF) is an anti-inflammatory and antioxidant drug used to treat multiple sclerosis, but its mechanism(s) of action are not fully understood. In central nervous system (CNS) cells, DMF activates nuclear factor E2-related factor 2 (Nrf2), perhaps ameliorating oxidative stress-induced damage. However, it is not known whether DMF also activates Nrf2 in peripheral immune cells, which are known to participate in CNS demyelination. We conducted a single observation study to determine whether DMF can activate Nrf2 in peripheral immune cells in vitro. Results We performed enzyme-linked immunosorbent assays to measure Nrf2 activation in nuclear extracts of human peripheral blood mononuclear cells treated with DMF at time points from 0 to 6 h, initially determining that DMF did not activate Nrf2, and that the mechanism(s) of action of DMF may thus differ in the periphery compared to the CNS. However, further analyses of our data suggest that high Tmax variability is masking Nrf2 activation in individual donors. Additionally, there may be sub-populations of responders, perhaps related to genetic polymorphisms in Nrf2

MOESM1 of Donor variability may mask dimethyl fumarate’s effects on nuclear factor E2-related factor 2 in human peripheral blood mononuclear cells

Additional file 1. All raw data collected and used in analyses for this manuscript, organized by figure number

Impact of T and B cell depletion on kinetics and magnitude of B cell proliferation and IgG/IgM production following SVV infection.

<p>Frequency of proliferating (Ki67+) B cells within marginal zone-like and memory subsets in BAL (A, B) and PBMC (C, D) was measured using FCM. Data points for B cell proliferation in CD20-depleted animals are not shown 0–14 dpi as there were no B cells in circulation during this time period. Average SVV-specific IgM (E) and IgG (F) end point titers± SEM in control, CD20 depleted, CD8 depleted, and CD4 depleted animals (n = 4/group) were determined by standard ELISA.* indicates p<0.05 as compared to control animals.</p

Impact of T and B cell depletion on the kinetics and magnitude of T cell proliferation following acute SVV infection.

<p>Frequency of proliferating (Ki67+) CD4 and CD8 T cells within central and effector memory subsets was measured in BAL (A–D) and PBMC (E–H) by FCM. Data points for CD4 T cell Ki67+ frequency in CD4-depleted animals are not shown 7–21 dpi as there were no CD4 T cells in circulation during this time period. Similarly data points for Ki67+ CD8 T cell frequency are not shown 0–14 dpi as there were no CD8 T cells detected during this period. * indicates p<0.05 as compared to control animals.</p