A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus

Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTIP) that endures for more than an hour requires both transcription and translation. The signal-transduction mechanisms that couple synaptic events to protein translational machinery during long-lasting synaptic plasticity, however, are not well understood. One signaling pathway that is stimulated by growth factors and results in the translation of specific mRNAs includes the rapamycin-sensitive kinase mammalian target of rapamycin (mTOR, also known as FRAP and RAFT-1). Several components of this translational signaling pathway, including mTOR, eukaryotic initiation factor-4E-binding proteins 1 and 2, and eukaryotic initiation factor-4E, are present in the rat hippocampus as shown by Western blot analysis, and these proteins are detected in the cell bodies and dendrites in the hippocampal slices by immunostaining studies. In cultured hippocampal neurons, these proteins are present in dendrites and are often found near the presynaptic protein, synapsin I. At synaptic sites, their distribution completely overlaps with a postsynaptic protein, PSD-95. These observations suggest the postsynaptic localization of these proteins. Disruption of mTOR signaling by rapamycin results in a reduction of late-phase LTP expression induced by high-frequency stimulation; the early phase of LTIP is unaffected. Rapamycin also blocks the synaptic potentiation induced by brain-derived neurotrophic factor in hippocampal slices. These results demonstrate an essential role for rapamycin-sensitive signaling in the expression of two forms of synaptic plasticity that require new protein synthesis. The localization of this translational signaling pathway at postsynaptic sites may provide a mechanism that controls local protein synthesis at potentiated synapses

Communicating in Complex Situations: A Normative Approach to HIV-Related Talk Among Parents Who Are HIV+

Parents with HIV/AIDS are confronted with unique challenges when discussing HIV-related information with their children. Strategies for navigating these challenges effectively have not been systematically examined. In this study, we conducted in-depth interviews with 76 parents with HIV/AIDS who had children ages 10–18 years. Guided by O\u27Keefe and Delia\u27s definition of a complex communication situation and Goldsmith\u27s normative approach to interpersonal communication, we examined parents’ goals for discussing HIV-related information, factors that made conversations challenging, and instances where these conversational purposes conflicted with one another. Our data reveal the following parent–adolescent communication predicaments: relaying safety information about HIV while minimizing child anxiety, modeling open family communication without damaging one\u27s parental identity, and balancing parent–child relational needs amid living with an unpredictable health condition. Parents also described a variety of strategies for mitigating challenges when discussing HIV-related topics. Strategies parents perceived as effective included reframing HIV as a chronic, manageable illness; keeping talk educational; and embedding HIV-related topics within more general conversations. The theoretical and practical applications of these findings are discussed with regard to their relevance to health communication scholars and HIV care professionals

Tax base diversification in Carrboro: from bedroom community to bedrock for economic stability

Carrboro, North Carolina, has the fifth-highest residential property tax rate in the state, and its homes are valued higher than the municipalities with higher tax rates. Residential use comprises 86% of Carrboro's development, meaning businesses contribute little in property and sales taxes. Housing values have increased in recent decades, while diversity and affordability have dwindled. Non-residential development has been slow in Carrboro, due to a complex combination of existing policies and political will. Whether the town should change its policies and procedures to help diversify the land uses, tax revenue sources, and family backgrounds in Carrboro depends on whether Carrboro's residents actually want more non-residential development. If they do, this Master's Project uses a case study of Arcata, California to suggest specific revisions to Carrboro's development guide, zoning map and land use ordinance that could help speed the non-residential development review process and more aggressively promote affordable housing.Master of City and Regional Plannin

Expert views - and disagreements - about the potential of energy technology R&D

Mitigating climate change will require innovation in energy technologies. Policy makers are faced with the question of how to promote this innovation, and whether to focus on a few technologies or to spread their bets. We present results on the extent to which public R&D might shape the future cost of energy technologies by 2030. We bring together three major expert elicitation efforts carried out by researchers at UMass Amherst, Harvard, and FEEM, covering nuclear, solar, Carbon Capture and Storage (CCS), bioelectricity, and biofuels. The results show experts believe that there will be cost reductions resulting from R&D and report median cost reductions around 20 % for most of the technologies at the R&D budgets considered. Although the improvements associated to solar and CCS R&D show some promise, the lack of consensus across studies, and the larger magnitude of the R&D investment involved in these technologies, calls for caution when defining what technologies would benefit the most from additional public R&D. In order to make R&D funding decisions to meet particular goals, such as mitigating climate change or improving energy security, or to estimate the social returns to R&D, policy makers need to combine the information provided in this study on cost reduction potentials with an analysis of the macroeconomic implications of these technological changes. We conclude with recommendations for future directions on energy expert elicitations

Student Connection

If there was one overarching theme from the 2009- 2010 academic year, it was community-based learning. Through volunteerism, participation in local planning events, and interactions with regional leaders in the field, Master’s students gained knowledge and strengthened professional skills that will serve them well in building sustainable communities

Green salad intake is associated with improved oral cancer survival and lower soluble CD44 levels

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p \u3c 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of “salad or other vegetables” had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients

Patient and provider experiences with virtual care during the COVID-19 pandemic: A mixed methods study

The COVID-19 pandemic prompted the rapid uptake of Virtual Care (VC). Positive patient outcomes with VC are previously reported but little is known about the experiences of patients and providers using VC during the pandemic. We aimed to describe patient and primary care provider experiences, satisfaction, perceptions, and attitudes to VC during the COVID-19 pandemic that might explain adoption of VC across the continuum of care and inform sustained uptake. We conducted a sequential explanatory mixed methods study using online surveys and virtual interviews with a convenience sample of primary care providers and patients in a Canadian province (July – December 2020). Eligible participants included patients and primary care providers using VC during the COVID-19 pandemic. Survey responses and interviews were analyzed using descriptive statistics and thematic analysis, respectively. Overall satisfaction was compared using the Mann-Whitney U test. Eighty-five patients and 94 primary care providers responded to the surveys. Patients reported higher overall satisfaction with VC than primary care providers (median [interquartile range]: 4.4 [4.0-4.7] and 3.7 [3.4-3.9] p \u3c 0.001). Ten patients and 11 primary care providers were interviewed. Both groups strongly appreciated VC’s increased access and convenience, identified the lack of compensation as a pre-pandemic barrier to providing VC, and reported willingness to continue VC post-COVID-19 pandemic. The COVID-19 pandemic provided an opportunity for patients and primary care providers to rapidly adopt VC with high satisfaction. Patients and primary care providers viewed VC positively due to its convenience and accessibility; both intend to continue using VC post-pandemic. Experience Framework This article is associated with the Staff & Provider Engagement lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens

Race and Vitamin D Binding Protein Gene Polymorphisms Modify the Association of 25-Hydroxyvitamin D and Incident Heart Failure: The ARIC (Atherosclerosis Risk in Communities) Study

Abstract Objectives This study sought to determine if low serum 25-hydroxyvitamin D (25[OH]D) is associated with incident heart failure (HF) and if the association is: 1) partly mediated by traditional cardiovascular risk factors; 2) stronger among whites than blacks; and 3) stronger among those genetically predisposed to having high levels of vitamin D binding protein (DBP).Background Suboptimal 25(OH)D is a potential cardiovascular risk factor.Methods A total of 12,215 ARIC (Atherosclerosis Risk in Communities) study participants free of HF at baseline (1990 to 1992; median age, 56; 24% black) were followed through 2010. Total serum 25(OH)D was measured at baseline using liquid chromatography–mass spectrometry. Incident HF events were identified by a hospital discharge code of ICD9-428 and parallel International Classification of Diseases codes for HF deaths.Results During 21 years of follow-up, 1,799 incident HF events accrued. The association between 25(OH)D and HF varied by race (p-interaction = 0.02). Among whites, risk was 2-fold higher for those in the lowest (≤17 ng/ml) versus highest (≥31 ng/ml) quintile of 25(OH)D. The association was attenuated but remained significant with covariate adjustment. In blacks there was no overall association. In both races, those with low 25(OH)D and the rs7041 G allele, which predisposes to high DBP, were at greater risk (p-interaction = 0.01).Conclusions Low serum 25(OH)D was independently associated with incident HF among whites, but not among blacks. However, in both races, low 25(OH)D was associated with HF risk among those genetically predisposed to high DBP. These findings provide novel insight into metabolic differences that may underlie racial variation in the association between 25(OH)D and cardiovascular risk

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts