Spinal Cord Regeneration: Ready, Set, Nogo

Neurons in the peripheral nervous system (PNS) have the capability to regenerate after injury or disease while central nervous system (CNS) neurons do not. Elucidation of the reasons for this difference in regenerative ability is crucial to developing treatments for sufferers of CNS disorders, injury, and stroke. Therefore, my lab investigates molecular mechanisms underlying neuronal repair, axonal guidance, and growth cone formation and collapse. We discovered the Nogo protein and its inhibitory role in CNS repair. The Nogo protein interacts with the Nogo-66 receptor (NgR), located on the axons of CNS neurons, to inhibit axonal sprouting after injury. Blockage of this interaction by a competitive inhibitor allows limited CNS axon regeneration in vitro and in spinal cord injury model mice. During normal development and repair, axonal pathfinding is mediated by the growth cone, which is guided by extra cellular cues that repel or attract the extending axon. This extension is the result of continuous polymerization and depolymerization of the actin skeleton. My lab works to elucidate the mechanism behind how these growth cones are guided, and we have uncovered a number of important steps in this pathway. Understanding the inhibitory environment to CNS regeneration is essential to developing treatments for its disorders

NMDAR-Activated PP1 Dephosphorylates GluN2B to Modulate NMDAR Synaptic Content.

In mature neurons, postsynaptic N-methyl-D-aspartate receptors (NMDARs) are segregated into two populations, synaptic and extrasynaptic, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content. Here, we identify the phosphorylation of the PDZ-ligand of the GluN2B subunit of NMDARs (at S1480) as a critical determinant in dynamically controlling NMDAR synaptic content. We find that phosphorylation of GluN2B at S1480 maintains NMDARs at extrasynaptic membranes as part of a protein complex containing protein phosphatase 1 (PP1). Global activation of NMDARs leads to the activation of PP1, which mediates dephosphorylation of GluN2B at S1480 to promote an increase in synaptic NMDAR content. Thus, PP1-mediated dephosphorylation of the GluN2B PDZ-ligand modulates the synaptic expression of NMDARs in mature neurons in an activity-dependent manner, a process with profound consequences for synaptic and structural plasticity, metaplasticity, and synaptic neurotransmission

In Situ Fabrication and Repair (ISFR) Technologies; New Challenges for Exploration

NASA's human exploration initiative poses great opportunity and great risk for manned missions to the Moon and Mars. Engineers and Scientists at the Marshall Space Flight Center (MSFC) are continuing to evaluate current technologies for in situ resource-based exploration fabrication and repair applications. Several technologies to be addressed in this paper have technology readiness levels (TRLs) that are currently mature enough to pursue for exploration purposes. However, while many technologies offer promising applications, these technologies must be pulled along by the demands and applications of this great initiative. The In Situ Fabrication and Repair (ISFR) Element will supply and push state of the art technologies for applications such as habitat structure development, in situ resource utilization for tool and part fabrication, and repair and non-destructive evaluation W E ) of common life support elements. As an overview of the ISFR Element, this paper will address rapid prototyping technologies, their applications, challenges, and near term advancements. This paper will also discuss the anticipated need to utilize in situ resources to produce replacement parts and fabricate repairs to vehicles, habitats, life support and quality of life elements. Overcoming the challenges of ISFR development will provide the Exploration initiative with state of the art technologies that reduce risk, and enhance supportability

Cultural value orientations, internalized homophobia, and accommodation in romantic relationships

In the present study, we examined the impact of cultural value orientations (i.e., the personally oriented value of individualism, and the socially oriented values of collectivism, familism, romanticism, and spiritualism) on accommodation (i.e., voice and loyalty, rather than exit and neglect, responses to partners' anger or criticism) in heterosexual and gay relationships; and we examined the impact of internalized homophobia (i.e., attitudes toward self, other, and disclosure) on accommodation specifically in gay relationships. A total of 262 heterosexuals (102 men and 162 women) and 857 gays (474 men and 383 women) participated in the present study. Consistent with hypotheses, among heterosexuals and gays, socially oriented values were significantly and positively related to accommodation (whereas the personally oriented value of individualism was unrelated to accommodation); and among gays in particular, internalized homophobia was significantly and negatively related to accommodation. Implications for the study of heterosexual and gay relationships are discussed. © 2005 by The Haworth Press, Inc. All rights reserved

The Influence of Corporate Front-Group Stealth Campaigns

This research examined corporate front-group stealth campaigns. An experiment was conducted to examine the influence of front-group stealth campaigns on a variety of measures. It was anticipated that corporate front-group stealth campaigns, which feature names that mask the true interests of sponsors, positively affect public opinion, unless they are exposed as intentionally misleading, in which case they boomerang against sponsors. The experiment examined the potential of the inoculation strategy to preempt the influence of corporate front-group stealth campaigns. The pattern of results supported all of these expectations. Front-group stealth campaigns proved to be effective, at least in the short term. Front-group stealth campaigns eroded public attitudes toward the issue in question and boosted perceptions of the front group, but not the corporate sponsor. However, when front-group stealth campaigns were subsequently exposed, positive effects dissipated and perceptions of corporate sponsors boomeranged. Results revealed that inoculation can protect against the influence of front-group stealth campaigns.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Friends and Enemies Within: The Roles of Subgroups, Imbalance, and Isolates in Geographically Dispersed Teams

Research regarding geographically dispersed teams (GDTs) is increasingly common and has yielded many insights into how spatio-temporal and socio-demographic factors affect GDT functioning and performance. Largely missing, however, is research on the effects of the basic geographic configuration of GDTs. In this study, we explore the impact of GDT configuration (i.e., the relative number of team members at different sites, independent of the characteristics of those members or the spatial and temporal distances among them) on GDT dynamics. In a quasi-experimental setting, we examine the effects of configuration using a sample of 62 six-person teams in four different one- and twosite configurations. As predicted, we find that configuration significantly affects team dynamics – independent of spatio-temporal distance and socio-demographic factors. More specifically, we find that teams with geographically-based subgroups (defined as two or more members per site) have significantly less shared team identity, less effective transactive memory, more conflict, and more coordination issues. Furthermore, in teams with subgroups, imbalance (i.e., the uneven distribution of members across sites) exacerbates these effects; subgroups with a numerical minority of team members report significantly poorer scores on the same four outcomes. In contrast, teams with geographically isolated members (i.e., members who have no teammates at their site) outperform both balanced and imbalanced configurations

The function of fear in institutional maintenance: Feeling frightened as an essential ingredient in haute cuisine

Fear is a common and powerful emotion that can regulate behaviour. Yet institutional scholars have paid limited attention to the function of fear in processes of institutional reproduction and stability. Drawing on an empirical study of elite chefs within the institution of haute cuisine, this article finds that the multifaceted emotion of fear characterised their experiences and served to sustain their institution. Chefs’ individual feelings of fear prompted conformity and a cognitive constriction, which narrowed their focus on to the precise reproduction of traditional practices whilst also limiting challenges to the norms underpinning the institution. Through fear work, chefs used threats and violence to connect individual experiences of fear to the violation of institutionalized rules, sustaining the conditions in which fear-driven maintenance work thrived. The study also suggests that fear is a normative element of haute cuisine in its own right, where the very experience and eliciting of fear preserved an essential institutional ingredient. In this way, emotions such as fear do not just accompany processes of institutionalization but can be intimately involved in the maintenance of institutions

Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.

OBJECTIVE: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. METHODS: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers. RESULTS: A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E-07; age-at-onset top variant: p value = 9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset. INTERPRETATION: This study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82-94

SHMT2 drives glioma cell survival in the tumor microenvironment but imposes a dependence on glycine clearance

SUMMARY Cancer cells adapt their metabolic processes to support rapid proliferation, but less is known about how cancer cells alter metabolism to promote cell survival in a poorly vascularized tumor microenvironment1–3. Here, we identify a key role for serine and glycine metabolism in the survival of brain cancer cells within the ischemic zones of gliomas. In human glioblastoma multiforme (GBM), mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci. We find that SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumor regions. GLDC inhibition impairs cells with high SHMT2 levels as the excess glycine not metabolized by GLDC can be converted to the toxic molecules aminoacetone and methylglyoxal. Thus, SHMT2 is required for cancer cells to adapt to the tumor environment, but also renders these cells sensitive to glycine cleavage system inhibition

Top 40 Priorities for Science to Inform US Conservation and Management Policy

To maximize the utility of research to decisionmaking, especially given limited financial resources, scientists must set priorities for their efforts. We present a list of the top 40 high-priority, multidisciplinary research questions directed toward informing some of the most important current and future decisions about management of species, communities, and ecological processes in the United States. The questions were generated by an open, inclusive process that included personal interviews with decisionmakers, broad solicitation of research needs from scientists and policymakers, and an intensive workshop that included scientifically oriented individuals responsible for managing and developing policy related to natural resources. The process differed from previous efforts to set priorities for conservation research in its focus on the engagement of decisionmakers in addition to researchers. The research priorities emphasized the importance of addressing societal context and exploration of trade-offs among alternative policies and actions, as well as more traditional questions related to ecological processes and functions.Keywords: Priority setting, Natural resource management, Ecosystems, Conservation, Decisionmaker