Monoamine Oxidase A is Required for Rapid Dendritic Remodeling in Response to Stress

Background: Acute stress triggers transient alterations in the synaptic release and metabolism of brain monoamine neurotransmitters. These rapid changes are essential to activate neuroplastic processes aimed at the appraisal of the stressor and enactment of commensurate defensive behaviors. Threat evaluation has been recently associated with the dendritic morphology of pyramidal cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA); thus, we examined the rapid effects of restraint stress on anxiety-like behavior and dendritic morphology in the BLA and OFC of mice. Furthermore, we tested whether these processes may be affected by deficiency of monoamine oxidase A (MAO-A), the primary enzyme catalyzing monoamine metabolism. Methods: Following a short-term (1–4h) restraint schedule, MAO-A knockout (KO) and wild-type (WT) mice were sacrificed, and histological analyses of dendrites in pyramidal neurons of the BLA and OFC of the animals were performed. Anxiety-like behaviors were examined in a separate cohort of animals subjected to the same experimental conditions. Results: In WT mice, short-term restraint stress significantly enhanced anxiety-like responses, as well as a time-dependent proliferation of apical (but not basilar) dendrites of the OFC neurons; conversely, a retraction in BLA dendrites was observed. None of these behavioral and morphological changes were observed in MAO-A KO mice. Conclusions: These findings suggest that acute stress induces anxiety-like responses by affecting rapid dendritic remodeling in the pyramidal cells of OFC and BLA; furthermore, our data show that MAO-A and monoamine metabolism are required for these phenomena

Bivalve facilitation mediates seagrass recovery from physical disturbance in a temperate estuary

Rapid global degradation of coastal habitats can be attributed to anthropogenic activities associated with coastal development, aquaculture, and recreational surface water use. Restoration of degraded habitats has proven challenging and costly, and there is a clear need to develop novel approaches that promote resilience to human-caused disturbances. Positive interactions between species can mitigate environmental stress and recent work suggests that incorporating positive interactions into restoration efforts may improve restoration outcomes. We hypothesized that the addition of a potential facultative mutualist, the native hard clam (Mercenaria mercenaria), could enhance seagrass bed recovery from disturbance. We conducted two experiments to examine the independent and interacting effects of hard clam addition and physical disturbance mimicking propeller scarring on mixed community Zostera marina and Halodule wrightii seagrass beds in North Carolina. Adding clams to seagrass beds exposed to experimental disturbance generally enhanced seagrass summer growth rates and autumn shoot densities. In contrast, clam addition to non-disturbed seagrass beds did not result in any increase in seagrass growth rates or shoot densities. Clam enhancement of autumn percent cover relative to areas without clam addition was most prominent after Hurricane Dorian, suggesting that clams may also enhance seagrass resilience to repeated disturbances. By June of the next growing season, disturbed areas with clam additions had greater percent cover of seagrass than disturbed areas without clam additions. Beds that were disturbed in April had higher percent cover than areas disturbed in June of the previous growing season. Our results suggest that the timing and occurrence of physical disturbances may modify the ability of clams to facilitate seagrass resiliency and productivity. Understanding when and how to utilize positive, interspecific interactions in coastal restoration is key for improving restoration success rates.ECU Open Access Publishing Support Fun

Effect of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men

Objective  This study was conducted to assess the effects of chronic daily methylsulfonylmethane (MSM) supplementation on known markers of oxidative stress following acute bouts of exercise in untrained healthy young men. Methods  Eighteen untrained men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into two groups: MSM (n = 9) and placebo (n = 9). The participants took supplementation or placebo daily for 10 days before running. Participants ran 14 km. The MSM supplementation was prepared in water at 50 mg/kg body weight. The placebo group received water. Serum malondialdehyde (MDA), protein carbonyl (PC) and plasma oxidized glutathione (GSSG) were measured as markers of oxidative stress. The plasma-reduced glutathione (GSH) level and the GSH/GSSG ratio were determined as markers of plasma antioxidant capacity. Key Findings  Acute exercise led to elevated levels of serum MDA, PC and plasma GSSG. MSM supplementation maintained PC, MDA and GSSG at lower levels after exercise than the placebo. The plasma level of GSH and the ratio of GSH/GSSG were significantly higher in the MSM supplemented group. Conclusions  These results suggest that chronic daily oral supplementation of MSM has alleviating effects on known markers of oxidative stress following acute bouts of exercise in healthy young men

The role of social networks in students’ learning experiences

The aim of this research is to investigate the role of social networks in computer science education. The Internet shows great potential for enhancing collaboration between people and the role of social software has become increasingly relevant in recent years. This research focuses on analyzing the role that social networks play in students’ learning experiences. The construction of students’ social networks, the evolution of these networks, and their effects on the students’ learning experience in a university environment are examined

Fundamental challenges in designing a collaborative travel app

The growing capabilities of smartphones have opened up new opportunities for travel coordination and transport is a fertile area for app development. One stream of development is apps that enable collaborative travel, either in the form of lift sharing or collaborative shopping, but despite growing interest from governmental agencies, there is little evidence of the efficacy of such apps. Based on trials of purpose built travel collaboration apps, deployed in tourism, urban and rural residential communities, and logistics, this paper analyses the fundamental challenges facing users adopting such travel apps. The findings suggest that transport practitioners, policy makers and app developers need to better understand the challenges associated with attracting users, the use of incentives and the types of communities most appropriate to implement collaborative travel concepts using such approaches. Also, how the users’ sense of time pressure and the issues around reciprocal exchange can impact on their long-term success and wider adoption

Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation–Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials

Purpose: To report the durability of voretigene neparvovec-rzyl (VN) adeno-associated viral vector–based gene therapy for RPE65 mutation–associated inherited retinal dystrophy (IRD), including results of a phase 1 follow-on study at year 4 and phase 3 study at year 2. Design: Open-label phase 1 follow-on clinical trial and open-label, randomized, controlled phase 3 clinical trial. Participants: Forty subjects who received 1.5×1011 vector genomes (vg) of VN per eye in at least 1 eye during the trials, including 11 phase 1 follow-on subjects and 29 phase 3 subjects (20 original intervention [OI] and 9 control/intervention [CI]). Methods: Subretinal injection of VN in the second eye of phase 1 follow-on subjects and in both eyes of phase 3 subjects. Main Outcome Measures: End points common to the phase 1 and phase 3 studies included change in performance on the Multi-Luminance Mobility Test (MLMT) within the illuminance range evaluated, full-field light sensitivity threshold (FST) testing, and best-corrected visual acuity (BCVA). Safety end points included adverse event reporting, ophthalmic examination, physical examination, and laboratory testing. Results: Mean (standard deviation) MLMT lux score change was 2.4 (1.3) at 4 years compared with 2.6 (1.6) at 1 year after administration in phase 1 follow-on subjects (n = 8), 1.9 (1.1) at 2 years, and 1.9 (1.0) at 1 year post-administration in OI subjects (n = 20), and 2.1 (1.6) at 1 year post-administration in CI subjects (n = 9). All 3 groups maintained an average improvement in FST, reflecting more than a 2 log10(cd.s/m2) improvement in light sensitivity at 1 year and subsequent available follow-up visits. The safety profile was consistent with vitrectomy and the subretinal injection procedure, and no deleterious immune responses occurred. Conclusions: After VN gene augmentation therapy, there was a favorable benefit-to-risk profile with similar improvement demonstrated in navigational ability and light sensitivity among 3 groups of subjects with RPE65 mutation–associated IRD, a degenerative disease that progresses to complete blindness. The safety profile is consistent with the administration procedure. These data suggest that this effect, which is nearly maximal by 30 days after VN administration, is durable for 4 years, with observation ongoing

Implementing smartphone enabled collaborative travel: Routes to success in the tourism domain.

Smartphone technology can help identify current and anticipate future patterns of behaviour and, with its social networking capabilities, allow users to imagine and organise collaborative travel opportunities, such as lift share. This has led to the development of collaborative apps designed to enable activities like lift sharing. Such apps require new norms of behaviour to establish a user base and research has yet to address the socio-cultural barriers to both the use of this technology to organise travel and the sharing of personal space that collaborative travel entails. This paper reports the findings of a study which designed, built and tested a collaborative travel app in the tourism domain. Data derived from exploratory interviews, post-trial interviews and a questionnaire reveal that user age and extent of mobile engagement play a less significant role than expected, while other aspects of the social exchange, notably social tie strength, trust and obligations play a more marked role. A conceptual framework and discussion of strategies to address these barriers provides insight into appropriate contexts and routes for implementation of collaborative travel apps

Lift-share using mobile apps in tourism: the role of trust, sense of community and existing lift-share practices

This paper explores the use of mobile technology to enable lift-share in the leisure travel domain of camping tourism. Here mobile devices can connect a user community on the move undertaking non-routine trips and reveal temporal and spatial connections suggesting lift-share opportunities. Data were derived from a questionnaire survey (n=339) administered at campsites in a rural tourism destination in Dorset, UK. Analysis focuses on the role of trust, sense of community and existing lift-share practices in willingness to engage in lift-share and other forms of share use of private vehicles using a mobile app. The findings indicate that previous experience of lift-share and sense of community both have a small effect, however, trust had no effect on the desire to lift-share. Analysis indicates trust is generated through community participation rather than being a precursor to taking part. Lift-share app developers and providers need to design strategies which build trust in the system using peer-to-peer ratings, where appropriate, and establishing user etiquette through user champions and visualising successful exchanges

Mitochondrial oxidants, but not respiration, are sensitive to glucose in adipocytes

Insulin action in adipose tissue is crucial for whole-body glucose homeostasis, with insulin resistance being a major risk factor for metabolic diseases such as type 2 diabetes. Recent studies have proposed mitochondrial oxidants as a unifying driver of adipose insulin resistance, serving as a signal of nutrient excess. However, neither the substrates for nor sites of oxidant production are known. Since insulin stimulates glucose utilisation, we hypothesised that glucose oxidation would fuel respiration, in turn generating mitochondrial oxidants. This would impair insulin action, limiting further glucose uptake in a negative feedback loop of ‘glucose-dependent’ insulin resistance. Using primary rat adipocytes and cultured 3T3-L1 adipocytes, we observed that insulin increased respiration, but notably this occurred independently of glucose supply. In contrast, glucose was required for insulin to increase mitochondrial oxidants. Despite rising to similar levels as when treated with other agents that cause insulin resistance, glucose-dependent mitochondrial oxidants failed to cause insulin resistance. Subsequent studies revealed a temporal relationship whereby mitochondrial oxidants needed to increase before the insulin stimulus to induce insulin resistance. Together, these data reveal that a) adipocyte respiration is principally fuelled from non-glucose sources, b) there is a disconnect between respiration and oxidative stress, whereby mitochondrial oxidant levels do not rise with increased respiration unless glucose is present, and c) mitochondrial oxidative stress must precede the insulin stimulus to cause insulin resistance, explaining why short-term insulin-dependent glucose utilisation does not promote insulin resistance. These data provide additional clues to mechanistically link nutrient excess to adipose insulin resistance.DEJ was supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (APP1019680) and NHMRC project grants (GNT1061122, GNT1086851). GJC was supported by a Professorial Research Fellowship from the University of Sydney Medical School. DEJ and GJC were also supported by an NHMRC project grant (GNT1086850). JRK was funded by an NHMRC Early Career Fellowship (APP1072440), Australian Diabetes Society Skip Martin Early-Career Fellowship, Diabetes Australia Research Program grant, and CPC Early-Career Seed Funding grant. DJF was funded by Medical Research Council Career Development Award (MR/S007091/1)