Alzheimer’s disease-associated peptide Aβ₄₂ mobilizes ER Ca²⁺ via InsP₃R-dependent and -independent mechanisms

Dysregulation of Ca2+ homeostasis is considered to contribute to the toxic action of the Alzheimer’s Disease (AD) associated Amyloid β-peptide (Aβ). Ca2+ fluxes across the plasma membrane and release from intracellular stores have both been reported to underlie the Ca2+ fluxes induced by Aβ42. Here, we investigated the contribution of Ca2+ release from the endoplasmic reticulum (ER) to the effects of Aβ42 upon Ca2+ homeostasis and the mechanism by which Aβ42 elicited these effects. Consistent with previous reports, application of soluble oligomeric forms of Aβ42 exhibited Ca2+ mobilizing properties. The Aβ42-stimulated Ca2+ signals persisted in the absence of extracellular Ca2+ indicating a significant contribution of Ca2+ release from the ER Ca2+ store to the generation of these signals. Moreover, inositol 1,4,5-trisphosphate (InsP3) signaling contributed to Aβ42-stimulated Ca2+ release. The Ca2+ mobilizing effect of Aβ42 was also observed when applied to permeabilized cells deficient in InsP3 receptors revealing an additional direct effect of internalized Aβ42 upon the ER, and a mechanism for induction of toxicity by intracellular Aβ42

Investigating Graduate Education and Undergraduate Research Intentions of College Science Students

The current study examined predictors of undergraduate science students’ intentions to attend graduate school and participate in undergraduate research. We used social cognitive career theory to test our hypothesized model using a sample (N ¼ 411) of life science and physical science majors and examined basic interests in these disciplines as mediating variables. Among life science majors, results of structural equation modeling indicated that microbiology interest mediated the relationship between scientific self-efficacy (SSE) and graduate education intentions (GEIs) and the latter variable also mediated the relationship between microbiology interest and undergraduate research intentions (URIs). The model for physical science majors did not provide a good fit to the data, therefore path coefficients associated with this model were not interpreted. Implications for counseling interventions based on patterns of career intention formation in the life and physical sciences are discussed

Association of a Workplace Sales Ban on Sugar-Sweetened Beverages With Employee Consumption of Sugar-Sweetened Beverages and Health.

ImportanceReductions in sugar-sweetened beverage (SSB) intake can improve health, but are difficult for individuals to achieve on their own.ObjectivesTo evaluate whether a workplace SSB sales ban was associated with SSB intake and cardiometabolic health among employees and whether a brief motivational intervention provides added benefits to the sales ban.Design, setting, and participantsThis before-after study and additional randomized trial conducted from July 28, 2015, to October 16, 2016, at a Northern California university and hospital assessed SSB intake, anthropometrics, and cardiometabolic biomarkers among 214 full-time English-speaking employees who were frequent SSB consumers (≥360 mL [≥12 fl oz] per day) before and 10 months after implementation of an SSB sales ban in a large workplace, with half the employees randomized to receive a brief motivational intervention targeting SSB reduction.InterventionsThe employer stopped selling SSBs in all workplace venues, and half the sample was randomized to receive a brief motivational intervention and the other half was a control group that did not receive the intervention. This intervention was modeled on standard brief motivational interventions for alcohol used in the workplace that promote health knowledge and goal setting.Main outcomes and measuresOutcomes included changes in SSB intake, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and measures of abdominal adiposity. The primary associations tested were the correlation between changes in SSB intake and changes in HOMA-IR.ResultsAmong the 214 study participants, 124 (57.9%) were women, with a mean (SD) age of 41.2 (11.0) years and a baseline mean (SD) body mass index of 29.4 (6.5). They reported a mean daily intake of 1050 mL (35 fl oz) of SSBs at baseline and 540 mL (18 fl oz) at follow-up-a 510-mL (17-fl oz) (48.6%) decrease (P < .001). Reductions in SSB intake correlated with improvements in HOMA-IR (r = 0.16; P = .03). Those not randomized to receive the brief intervention reduced their SSB intake by a mean (SD) of 246.0 (84.0) mL (8.2 [2.8] fl oz), while those also receiving the brief intervention reduced SSB intake by 762.0 (84.0) mL (25.4 [2.8] fl oz). From baseline to follow-up, there were significant reductions in mean (SE) waist circumference (2.1 [2.8] cm; P < .001).Conclusions and relevanceThis study's findings suggest that the workplace sales ban was associated with a reduction in SSB intake and a significant reduction in waist circumference among employees within 10 months. The randomized clinical trial portion of this study found that targeting those at high risk with a brief motivational intervention led to additional improvements. Workplace sales bans may offer a promising new private-sector strategy for reducing the health harms of SSB intake.Trial registrationClinicalTrials.gov identifier: NCT02585336

Food supply confers calcifiers resistance to ocean acidification

Invasion of ocean surface waters by anthropogenic CO emitted to the atmosphere is expected to reduce surface seawater pH to 7.8 by the end of this century compromising marine calcifiers. A broad range of biological and mineralogical mechanisms allow marine calcifiers to cope with ocean acidification, however these mechanisms are energetically demanding which affect other biological processes (trade-offs) with important implications for the resilience of the organisms against stressful conditions. Hence, food availability may play a critical role in determining the resistance of calcifiers to OA. Here we show, based on a meta-analysis of existing experimental results assessing the role of food supply in the response of organisms to OA, that food supply consistently confers calcifiers resistance to ocean acidification.This work was funded by grants from the Danish Environmental Protection Agency within the Danish 486 Cooperation for Environment in the Arctic (DANCEA), ASSEMBLE grant agreement no. 227799 from European Community and from the Spanish Ministry of Economy and Competitiveness (ESTRESX, number CTM2012-32603). N.A.L. acknowledges support from grants Fondecyt 1140938 and NC 1200286 (Millennium Nucleus Project MUSELS) and L.R. was supported by BECAS CHILE fellowship program from Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT)Peer Reviewe

Editorial: Positive youth development, mental health, and psychological well-being in diverse youth

This is an editorial commentary on the Research Topic entitled: Editorial: Positive youth development, mental health, and psychological well-being in diverse youth. One impetus behind this Research Topic was to examine the ways in which positive development intersects with problematic aspects of development and behavior, with an emphasis on connections to indicators of mental health problems. The second impetus was to take an international approach, including youth from diverse countries and settings who were studied using a variety of etic and emic methods that correspondingly consider cross-culturally common features and features that vary across cultures

Planning, implementation and scientific goals of the Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field mission

The Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field mission based at Ellington Field, Texas, during August and September 2013 employed the most comprehensive airborne payload to date to investigate atmospheric composition over North America. The NASA ER-2, DC-8, and SPEC Inc. Learjet flew 57 science flights from the surface to 20 km. The ER-2 employed seven remote sensing instruments as a satellite surrogate and eight in situ instruments. The DC-8 employed 23 in situ and five remote sensing instruments for radiation, chemistry, and microphysics. The Learjet used 11 instruments to explore cloud microphysics. SEAC4RS launched numerous balloons, augmented AErosol RObotic NETwork, and collaborated with many existing ground measurement sites. Flights investigating convection included close coordination of all three aircraft. Coordinated DC-8 and ER-2 flights investigated the optical properties of aerosols, the influence of aerosols on clouds, and the performance of new instruments for satellite measurements of clouds and aerosols. ER-2 sorties sampled stratospheric injections of water vapor and other chemicals by local and distant convection. DC-8 flights studied seasonally evolving chemistry in the Southeastern U.S., atmospheric chemistry with lower emissions of NOx and SO2 than in previous decades, isoprene chemistry under high and low NOx conditions at different locations, organic aerosols, air pollution near Houston and in petroleum fields, smoke from wildfires in western forests and from agricultural fires in the Mississippi Valley, and the ways in which the chemistry in the boundary layer and the upper troposphere were influenced by vertical transport in convective clouds

Nuclear variants of bone morphogenetic proteins

<p>Abstract</p> <p>Background</p> <p>Bone morphogenetic proteins (BMPs) contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts.</p> <p>Results</p> <p>In all three proteins, a bipartite nuclear localization signal (NLS) was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5) containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle.</p> <p>Conclusions</p> <p>The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.</p

What is animal happiness?

Today, we see a growing concern for the quality of life of nonhuman animals and an accompanying call for viable means of assessing how well animals thrive. Past research focused on minimizing negatives such as stress, while more recent endeavors strive to promote positives such as happiness. But what is animal happiness? Although often mentioned, the term lacks a clear definition. With recent advances in the study of animal emotion, current interest into positive rather than negative experiences, and the call for captive and domesticated animals to have good lives, the time is ripe to examine the concept of animal happiness. We draw from the human and animal literature to delineate a concept of animal happiness and propose how to assess it. We argue that animal happiness depends on how an individual feels generally—that is, a typical level of affect

A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab

The epidermal growth factor receptor (EGFR) monoclonal IgG1 antibody cetuximab is approved for first-line treatment of recurrent and metastatic (R/M) HNSCC as a part of the standard of care EXTREME regimen (platinum/5-fluorouracil/cetuximab). This regimen has relatively high response and disease control rates but is generally not curative and many patients will experience recurrent disease and/or metastasis. Therefore, there is a great need to identify predictive biomarkers for recurrence and disease progression in cetuximab-treated HNSCC patients to facilitate patient management and allow for treatment modification. The goal of this work is to assess the potential of activating interleukin-1 (IL-1) ligands (IL-1 alpha [IL-1α], IL-1 beta [IL-1β]) as predictive biomarkers of survival outcomes in HNSCC patients treated with cetuximab-based chemotherapy.2016 AACR-Bayer Innovation and Discovery Grant [16-80-44-SIMO]; National Institutes of Health (NIH) [R01DE024550, F99CA223062, R01 CA177669, P30 CA006973, P50 DE019032, T32 AI007511]; University of Iowa Department of Pathology Research Grant; University of Iowa Head and Neck Cancer Symposium Seed Grant; Johns Hopkins University Catalyst AwardOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood–Onset Retinal Dystrophy

PurposeTo provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.DesignNonrandomized, multicenter clinical trial.ParticipantsEight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood–onset retinal degeneration (SECORD).MethodsPatients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.Main Outcome MeasuresThe primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire.ResultsAll patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area.ConclusionsTreatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns