LMDA Review, volume 8, issue 2

Contents include: Head to Head 1997 Annual Conference, LMDA\u27s Statement of Principle Regarding Rent Lawsuit, A Letter from Canada, My Involvement with Rent, A Dramaturg Changes Hats: Tim Sanford on Career Flexibility, Regional News, The Advocacy Caucus Needs You, Mid-Atlantic/D.C. Metropolitan Regional Report, Dramaturgy Northwest, New York Regional, Regional Vice Presidents.https://soundideas.pugetsound.edu/lmdareview/1016/thumbnail.jp

LMDA Review, volume 8, issue 2

Contents include: Head to Head 1997 Annual Conference, LMDA\u27s Statement of Principle Regarding Rent Lawsuit, A Letter from Canada, My Involvement with Rent, A Dramaturg Changes Hats: Tim Sanford on Career Flexibility, Regional News, The Advocacy Caucus Needs You, Mid-Atlantic/D.C. Metropolitan Regional Report, Dramaturgy Northwest, New York Regional, Regional Vice Presidents.https://soundideas.pugetsound.edu/lmdareview/1016/thumbnail.jp

Positive Selection of B Cells Expressing Low Densities of Self-reactive BCRs

B cell tolerance or autoimmunity is determined by selective events. Negative selection of self-reactive B cells is well documented and proven. In contrast, positive selection of conventional B cells is yet to be firmly established. Here, we demonstrate that developing self-reactive B cells are not always highly sensitive to the deletion mechanisms imposed by membrane-bound self-antigens. At low amounts, membrane-bound antigens allow survival of B cells bearing a single high affinity self-reactive B cell receptor (BCR). More importantly, we show that forced allelic inclusion modifies B cell fate; low quantities of self-antigen induce the selection and accumulation of increased numbers of self-reactive B cells with decreased expression of antigen-specific BCRs. By directly measuring antigen binding by intact B cells, we show that the low amounts of self-antigen select self-reactive B cells with a lower association constant. A fraction of these B cells is activated and secretes autoantibodies that form circulating immune complexes with self-antigen. These findings demonstrate that conventional B cells can undergo positive selection and that the fate of a self-reactive B cell depends on the quantity of self-antigen, the number of BCRs engaged, and on its overall antigen-binding avidity, rather than on the affinity of individual BCRs

Effects of Trauma in Adulthood and Adolescence on Fear Extinction and Extinction Retention: Advancing Animal Models of Posttraumatic Stress Disorder

Evidence for and against adolescent vulnerability to posttraumatic stress disorder (PTSD) is mounting, but this evidence is largely qualitative, retrospective, or complicated by variation in prior stress exposure and trauma context. Here, we examine the effects of development on trauma vulnerability using adult post-natal (PN) day 61, early adolescent (PN23) and mid adolescence (PN34) rats and two types of trauma: an established animal model of PTSD, single prolonged stress (SPS), and a novel composite model—SPS predation (SPSp) version. We demonstrate that early and mid adolescent rats are capable of fear conditioning and fear extinction, as well as extinction retention. Our results also demonstrate that both types of trauma induced a deficit in the retention of fear extinction in adulthood, a hallmark of PTSD, but not after early or mid adolescence trauma, suggesting that adolescence might convey resilience to SPS and SPSp traumas. Across all three life stages, the effects of SPS exposure and a novel predation trauma model, SPSp, had similar effects on behavior suggesting that trauma type did not affect the likelihood of developing PTSD-like symptoms, and that SPSp is a predation-based trauma model worth exploring

Análise do impacto da Carta Portuguesa para a Diversidade nas organizações signatárias

A diversidade aumentou na força de trabalho nas últimas tanto nos Estados Unidos (US Bureau of Labor Statistics, 2012) como internacionalmente (Mor Barak, 2011), e a tendência é que continue a crescer (Jackson et al. 2003, Triandis et al.1994, Williams & O’Reilly 1998). Um fenómeno que tem vindo a originar novos e complexos desafios políticos e organizacionais, que têm sido descritos na literatura (Phillimore, 2015; Vertovec, 2007). A iniciativa europeia das Cartas para a Diversidade nasceu com o intuito de estimular e potenciar a diversidade nas organizações. Assim, a Carta Portuguesa para a Diversidade (CPD), aplicou um questionário de monitorização, no ano de 2017, e outro no final de ano de 2018. O presente estudo pretendeu analisar os resultados dos mesmos, no sentido de uma reflexão sobre os impactos da assinatura da CPD. Deste modo, pretende servir como ferramenta de reflexão sobre a gestão da diversidade nas organizações signatárias. Com uma amostra de 52 organizações na primeira vaga, e de 45 na segunda, enquadrando-se num estudo exploratório. Apesar de não ter sido possível inferir uma melhoria nos impactos da CPD, dado que apenas 16 organizações responderam em ambas as vagas, foi exequivel concluir que a diversidade foi descrita como uma mais-valia pelas organizações, e que foram incluidas nas suas iniciativas as várias dimensões da diversidade. Os resultados são discutidos à luz da literatura sobre diversidade organizacional. Por fim, são apresentadas sugestões para futuras pesquisas e uma proposta de otimização do instrumento de monitorização.Diversity has increased in terms of the workforce in the recent decades, both in the United States (US Bureau of Labor Statistics, 2012) and internationally (Mor Barak, 2011), and the trend is for this to continue to grow (Jackson et al. 2003, Triandis et al. .1994, Williams & O'Reilly 1998). A phenomenon giving place to new and complex political and organisational challenges have been added to the literature (Phillimore, 2015; Vertovec, 2007). The European Charters for Diversity initiative was created to stimulate and enhance diversity in associations. Thus, the Portuguese Charter for Diversity (CPD) applied a monitoring survey in 2017, and another at the end of 2018. This study aimed to analyse results and to reflect on the impact of the CPD signature. Serving as a reflection tool on the coordination of diversity in the signatory associations. With 52 associations in the first wave, and 45 in the second, they fit into an exploratory study. Although it was impossible to determine an improvement in the impacts of CPD, given that only 16 organisations feedback was obtained in both waves, it was concluded that diversity was considered an added value by these organisations, and them including various forms of diversity in their initiatives. These results are discussed in light of the literature on organisational diversity standpoint of view. Finally, there are suggestions for future research and a proposal for optimising the monitoring tools

Cognitive Flexibility Training Improves Extinction Retention Memory and Enhances Cortical Dopamine With and Without Traumatic Stress Exposure

Stress exposure can cause lasting changes in cognition, but certain individual traits, such as cognitive flexibility, have been shown to reduce the degree, duration, or severity of cognitive changes following stress. Both stress and cognitive flexibility training affect decision making by modulating monoamine signaling. Here, we test the role cognitive flexibility training, and high vs. low cognitive flexibility at the individual level, in attenuating stress-induced changes in memory and monoamine levels using the single prolonged stress (SPS) rodent model of traumatic stress in male Sprague-Dawley rats. Exposure to SPS can heighten fear responses to conditioned cues (i.e., freezing) after a fear association has been extinguished, referred to as a deficit in extinction retention. This deficit is thought to reflect an impairment in context processing that is characteristic of posttraumatic stress disorder (PTSD). During a cognitive flexibility training we assessed individual variability in cognitive skills and conditioned rats to discriminately use cues in their environment. We found that cognitive flexibility training, alone or followed by SPS exposure, accelerated extinction learning and decreased fear responses over time during extinction retention testing, compared with rats not given cognitive flexibility training. These findings suggest that cognitive flexibility training may improve context processing in individuals with and without traumatic stress exposure. Individual performance during the reversal phase of the cognitive flexibility training predicted subsequent context processing; individuals with high reversal performance exhibited a faster decrease in freezing responses during extinction retention testing. Thus, high reversal performance predicted enhanced retention of extinction learning over time and suggests that cognitive flexibility training may be a strategy to promote context processing. In a brain region vital for maintaining cognitive flexibility and fear suppression, the prelimbic cortex (PLC), cognitive flexibility training also lastingly enhanced dopamine (DA) and norepinephrine (NE) levels, in animals with and without traumatic stress exposure. In contrast, cognitive flexibility training prior to traumatic stress exposure decreased levels of DA and its metabolites in the striatum, a region mediating reflexive decision making. Overall, our results suggest that cognitive flexibility training can provide lasting benefits by enhancing extinction retention, a hallmark cognitive effect of trauma, and prelimbic DA, which can maintain flexibility across changing contexts

Improving Translational Relevance in Preclinical Psychopharmacology (iTRIPP)

Animal models are important in preclinical psychopharmacology to study mechanisms and potential treatments for psychiatric disorders. A working group of 14 volunteers, comprising an international team of researchers from academia and industry, convened in 2021 to discuss how to improve the translational relevance and interpretation of findings from animal models that are used in preclinical psychopharmacology. The following paper distils the outcomes of the working group’s discussions into 10 key considerations for the planning and reporting of behavioural studies in animal models relevant to psychiatric disorders. These form the iTRIPP guidelines (Improving Translational Relevance In Preclinical Psychopharmacology). These guidelines reflect the key considerations that the group thinks will likely have substantial impact in terms of improving the translational relevance of behavioural studies in animal models that are used to study psychiatric disorders and their treatment. They are relevant to the research community when drafting and reviewing manuscripts, presentations and grant applications. The iTRIPP guidelines are intended to complement general recommendations for planning and reporting animal studies that have been published elsewhere, by enabling researchers to fully consider the most appropriate animal model for the research purpose and to interpret their findings appropriately. This in turn will increase the clinical benefit of such research and is therefore important not only for the scientific community but also for patients and the lay public

Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach

Background: In this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps. Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower processing in older observers starting around 120 ms after stimulus onset. This age-related delay increased over time to reach a maximum around 190 ms, at which latency younger observers had around 50 ms time lead over older observers. Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual system sensitivity to image structure, the current study demonstrates that older observers accumulate face information more slowly than younger subjects. Additionally, the N170 appears to be less face-sensitive in older observers

Genetic and Functional Characterization of an MCR-3-Like Enzyme-Producing Escherichia coli Isolate Recovered from Swine in Brazil

A collection of 126 pigs was screened for carriage of colistin-resistant Enterobacteriaceae in a farm in Minas Gerais, Brazil. Out of this collection, eight colistin-resistant Escherichia coli isolates were recovered, including one from Minas Gerais State producing a new MCR-3 variant (MCR-3.12). Analysis of the lipopolysaccharide revealed that MCR-3.12 had a function similar to that of MCR-1 and MCR-2 as a result of the addition of a phosphoethanolamine group to the lipid A moiety. Genetic analysis showed that the mcr-3.12 gene was carried by an IncA/C2 plasmid and was embedded in an original genetic environment. This study reports the occurrence of the MCR-3-like determinant in South America and is the first to demonstrate the functionality of this group of enzymes as a phosphoethanolamine transferase