The Canadian Open Neuroscience Platform-An open science framework for the neuroscience community.

The Canadian Open Neuroscience Platform (CONP) takes a multifaceted approach to enabling open neuroscience, aiming to make research, data, and tools accessible to everyone, with the ultimate objective of accelerating discovery. Its core infrastructure is the CONP Portal, a repository with a decentralized design, where datasets and analysis tools across disparate platforms can be browsed, searched, accessed, and shared in accordance with FAIR principles. Another key piece of CONP infrastructure is NeuroLibre, a preprint server capable of creating and hosting executable and fully reproducible scientific publications that embed text, figures, and code. As part of its holistic approach, the CONP has also constructed frameworks and guidance for ethics and data governance, provided support and developed resources to help train the next generation of neuroscientists, and has fostered and grown an engaged community through outreach and communications. In this manuscript, we provide a high-level overview of this multipronged platform and its vision of lowering the barriers to the practice of open neuroscience and yielding the associated benefits for both individual researchers and the wider community.

Data and Tools Integration in the Canadian Open Neuroscience Platform.

We present the Canadian Open Neuroscience Platform (CONP) portal to answer the research community's need for flexible data sharing resources and provide advanced tools for search and processing infrastructure capacity. This portal differs from previous data sharing projects as it integrates datasets originating from a number of already existing platforms or databases through DataLad, a file level data integrity and access layer. The portal is also an entry point for searching and accessing a large number of standardized and containerized software and links to a computing infrastructure. It leverages community standards to help document and facilitate reuse of both datasets and tools, and already shows a growing community adoption giving access to more than 60 neuroscience datasets and over 70 tools. The CONP portal demonstrates the feasibility and offers a model of a distributed data and tool management system across 17 institutions throughout Canada.

Participation in the Global Corporate Challenge®, a Four-Month Workplace Pedometer Program, Reduces Psychological Distress.

BACKGROUND: Psychological distress (stress) has been linked to an increased risk of chronic diseases and is exacerbated by a range of workplace factors. Physical activity has been shown to alleviate psychological distress. Previous pedometer-based intervention evaluations have tended to focus on physical health outcomes. This study aimed to investigate the immediate and long-term changes in psychological distress in employees based in Melbourne, Australia after their participation in a four-month pedometer-based program in sedentary workplaces. METHODS: At baseline, 716 adults (aged 40 ± 10 years, 40% male) employed in primarily sedentary occupations, voluntarily enrolled in the Global Corporate Challenge© (GCC©), recruited from 10 Australian workplaces to participate in the GCC® Evaluation Study, completed the Kessler 10 Psychological Distress Scale (K10). Of these, 422 completed the K10 at baseline, 4 months and 12 months. RESULTS: Psychological distress reduced after participation in a four-month workplace pedometer-based program, which was sustained eight months after the program ended. Participants achieving the program goal of 10,000 steps per day or with higher baseline psychological distress had the greatest immediate and sustained reductions in psychological distress. Demographic predictors of immediate reduced psychological distress (n = 489) was having an associate professional occupation, younger age, and being 'widowed, separated or divorced'. CONCLUSIONS: Participation in a workplace pedometer-based program is associated with a sustained reduction in psychological distress. Low-impact physical health programs conducted in groups or teams that integrate a social component may be an avenue to improve both physical and psychological health in the workplace.

Dynein-mediated microtubule translocation powering neurite outgrowth in chick and Aplysia neurons requires microtubule assembly.

Previously, we have shown that bulk microtubule (MT) movement correlates with neurite elongation, and blocking either dynein activity or MT assembly inhibits both processes. However, whether the contributions of MT dynamics and dynein activity to neurite elongation are separate or interdependent is unclear. Here, we investigated the underlying mechanism by testing the roles of dynein and MT assembly in neurite elongation of Aplysia and chick neurites using time-lapse imaging, fluorescent speckle microscopy, super-resolution imaging and biophysical analysis. Pharmacologically inhibiting either dynein activity or MT assembly reduced neurite elongation rates as well as bulk and individual MT anterograde translocation. Simultaneously suppressing both processes did not have additive effects, suggesting a shared mechanism of action. Single-molecule switching nanoscopy revealed that inhibition of MT assembly decreased the association of dynein with MTs. Finally, inhibiting MT assembly prevented the rise in tension induced by dynein inhibition. Taken together, our results suggest that MT assembly is required for dynein-driven MT translocation and neurite outgrowth.

Temporomandibular joint osteoarthritis at Chelechol ra Orrak, Palau.

OBJECTIVE: To explore the frequency and severity of temporomandibular joint osteoarthritis (TMJ-OA) and its causative factors in a skeletal assemblage from the prehistoric site of Chelechol ra Orrak, Palau, western Micronesia. MATERIALS: 50 temporomandibular joint surfaces (mandibular condyles and articular eminences), representing a minimum of 22 adult individuals, 17 of which retain teeth. METHODS: Joint surfaces were macroscopically evaluated for characteristics associated with TMJ-OA and joint morphology. Dental remains were scored for tooth wear and staining. RESULTS: Nine individuals (40.1 %) displayed lesions typical of TMJ-OA. The strongest associations were between tooth wear and TMJ-OA. CONCLUSIONS: Indirect effects of parafunctional dental activity appear to be a factor in TMJ-OA frequency at Chelechol ra Orrak. While betel nut chewing may be one of those activities, it does not appear to be solely driving the presence of TMJ-OA. SIGNIFICANCE: This study highlights the association between a specific parafunctional use of the temporomandibular joint and the potential pathological consequences. It also reinforces the need to carefully evaluate the archaeological context of skeletal remains in order to evaluate specific etiological factors in the presence of TMJ-OA in present and past populations. LIMITATIONS: Sample sizes are limited in this study. This will increase as excavations continue. SUGGESTIONS FOR FURTHER RESEARCH: Because dental occlusion appears to be associated with TMJ-OA, focus on dental conditions affecting occlusal patterns, such as third molar agenesis, antemortem tooth loss, and malocclusion, and their relationship to TMJ-OA frequency, are recommended.

Reevaluating human colonization of the Caribbean using chronometric hygiene and Bayesian modeling.

Human settlement of the Caribbean represents the only example in the Americas of peoples colonizing islands that were not visible from surrounding mainland areas or other islands. Unfortunately, many interpretive models have relied on radiocarbon determinations that do not meet standard criteria for reporting because they lack critical information or sufficient provenience, often leading to specious interpretations. We have collated 2484 radiocarbon determinations, assigned them to classes based on chronometric hygiene criteria, and constructed Bayesian colonization models of the acceptable determinations to examine patterns of initial settlement. Colonization estimates for 26 islands indicate that (i) the region was settled in two major population dispersals that likely originated from South America; (ii) colonists reached islands in the northern Antilles before the southern islands; and (iii) the results support the southward route hypothesis and refute the "stepping-stone model."

Craniofacial plasticity in ancient Peru.

Numerous studies have utilized craniometric data to explore the roles of genetic diversity and environment in human cranial shape variation. Peru is a particularly interesting region to examine cranial variation due to the wide variety of high and low altitude ecological zones, which in combination with rugged terrain have created isolated populations with vastly different physiological adaptations. This study examines seven samples from throughout Peru in an effort to understand the contributions of environmental adaptation and genetic relatedness to craniofacial variation at a regional scale. Morphological variation was investigated using a canonical discriminant analysis and Mahalanobis D(2) analysis. Results indicate that all groups are significantly different from one another with the closest relationship between Yauyos and Jahuay, two sites that are located geographically close in central Peru but in very different ecozones. The relationship between latitude/longitude and face shape was also examined with a spatial autocorrelation analysis (Moran's I) using ArcMap and show that there is significant spatial patterning for facial measures and geographic location suggesting that there is an association between biological variation and geographic location.

Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) potentiates cardiac contractility via activation of the ryanodine receptor.

Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is the most recently identified phosphoinositide, and its functions have yet to be fully elucidated. Recently, members of our muscle group have shown that PI(3,5)P2 plays an important role in skeletal muscle function by altering Ca(2+) homeostasis. Therefore, we hypothesized that PI(3,5)P2 may also modulate cardiac muscle contractility by altering intracellular Ca(2+) ([Ca(2+)](i)) in cardiac myocytes. We first confirmed that PI(3,5)P2 was present and increased by insulin treatment of cardiomyocytes via immunohistochemistry. To examine the acute effects of PI(3,5)P2 treatment, electrically paced left ventricular muscle strips were incubated with PI(3,5)P2. Treatment with PI(3,5)P2 increased the magnitude of isometric force, the rate of force development, and the area associated with the contractile waveforms. These enhanced contractile responses were also observed in MIP/Mtmr14(-/-) mouse hearts, which we found to have elevated levels of PI(3,5)P2. In cardiac myocytes loaded with fura-2, PI(3,5)P2 produced a robust elevation in [Ca(2+)](i). The PI(3,5)P2-induced elevation of [Ca(2+)](i) was not present in conditions free of extracellular Ca(2+) and was completely blocked by ryanodine. We investigated whether the phosphoinositide acted directly with the Ca(2+) release channels of the sarcoplasmic reticulum (ryanodine receptors; RyR2). PI(3,5)P2 increased [(3)H]ryanodine binding and increased the open probability (P(o)) of single RyR2 channels reconstituted in lipid bilayers. This strongly suggests that the phosphoinositide binds directly to the RyR2 channel. Thus, we provide inaugural evidence that PI(3,5)P2 is a powerful activator of sarcoplasmic reticulum Ca(2+) release and thereby modulates cardiac contractility.

Symptoms of sleep-disordered breathing in children with nocturnal enuresis.

OBJECTIVES: There is an association between sleep-disordered breathing (SDB) and nocturia in adults, raising the question as to whether SDB could play a role in the aetiology of nocturnal enuresis (NE) in children. The aim of this study was to determine whether there is an association between these two conditions. METHODS: The study group comprised 40 patients, aged 5-15 years, with enuresis and the control group 40 children undergoing routine day-case surgery. Subjects completed a Pediatric Sleep Questionnaire (PSQ) and a questionnaire assessing lower tract symptoms. Categorical variables were analysed using Pearson's Xi(2) test, and group differences for continuous variables using Mann-Whitney and Kruskal-Wallis tests or t-tests according to the distribution of data. RESULTS: The groups were well matched. Patients with NE had significantly higher total PSQ scores (P<0.001). PSQ subscales relating to daytime sleepiness (P<0.003) and daytime behaviour (P<0.000) were significantly worse in NE patients. The snoring subscale was not statistically different (P<0.051), but a comparison of females alone showed a highly significant difference (P<0.001) with higher snoring subscale scores in girls with NE. CONCLUSION: Children with NE had significantly higher PSQ scores. The data suggest an association between NE and SDB in girls. The significantly higher level of reports of daytime sleepiness and behavioural problems in all NE children warrants further study to determine the potential causative pathways and clinical relevance of these findings. SDB could be usefully assessed in children with NE, particularly when they do not respond to standard treatment.

Differentiation and growth inhibition mediated via the RXR:PPARgamma heterodimer in colon cancer.

This study evaluated the anti-tumor efficacy of combining the RXR agonist, bexarotene, with the PPARgamma agonist, rosiglitazone, in colon cancer. Moser, a human colon cancer cell line, was treated with bexarotene and rosiglitazone alone or in combination and the effect on growth and differentiation were examined. The data demonstrated that the bexarotene/rosiglitazone combination produced greater efficacy in growth inhibition than either single agent. Furthermore, combination treatment acted cooperatively to decrease COX-2 expression and PGE2 synthesis while increasing expression of the differentiation marker, CEA. These findings were confirmed in vivo in a Moser xenograft tumor model. Collectively, our data suggest a potential role for utilizing a combination regimen of a RXR and PPARgamma agonist in the treatment of colon cancer.