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Introduction The Ontario Brain Institute (OBI) is a provincially funded, not-for-profit organization that accelerates discovery and innovation, benefiting both patients and the economy (Stuss, 2014). OBI has established a large-scale neuroinformatics platform - Brain-CODE - to support the collection, storage, federation, sharing, and analysis of different data types across several brain disorders (Behan et al., 2023; Vaccarino et al., 2018). A privacy preserving record linkage protocol was developed to allow for the linkage of research data at Brain-CODE with health administrative data holdings at the Institute for Clinical Evaluative Sciences (ICES) (Gee et al., 2018). Objective and Approach The methodology related to an ongoing crosswalk linkage between OBI and ICES, to allow for more seamless integration between the respective data holdings, has been previously presented (Behan et al., 2020). This methodology has since been operationalized leading to the establishment of an ongoing crosswalk linkage that is updated on an annual basis. Results Since the initial development of this ongoing crosswalk, two updates have been successfully completed leading to the linkage of over 7,000 study participants between the two platforms. This has led to a more efficient utilization of human and computational resources, compared to earlier data linkage projects completed on a project-by-project basis. Analysis projects in the areas of neurodegeneration, concussion, and neurodevelopmental disorders have already leveraged this crosswalk linkage process. Conclusions/Implications The establishment of this ongoing crosswalk linkage has supported a more streamlined approach of data linkage activities between OBI and ICES allowing for enhanced neuroscience-focused research activities.

With more than 130 clinical trials and 8 approved gene therapy products, adeno-associated virus (AAV) stands as one of the most popular vehicles to deliver therapeutic DNA in vivo. One critical quality attribute analyzed in AAV batches is the presence of residual DNA, as it could pose genotoxic risks or induce immune responses. Surprisingly, the presence of small cell-derived RNAs, such as microRNAs (miRNAs), has not been investigated previously. In this study, we examined the presence of miRNAs in purified AAV batches produced in mammalian or in insect cells. Our findings revealed that miRNAs were present in all batches, regardless of the production cell line or capsid serotype (2 and 8). Quantitative assays indicated that miRNAs were co-purified with the recombinant AAV particles in a proportion correlated with their abundance in the production cells. The level of residual miRNAs was reduced via an immunoaffinity chromatography purification process including a tangential flow filtration step or by RNase treatment, suggesting that most miRNA contaminants are likely non-encapsidated. In summary, we demonstrate, for the first time, that miRNAs are co-purified with AAV particles. Further investigations are required to determine whether these miRNAs could interfere with the safety or efficacy of AAV-mediated gene therapy.

Abstract This study shows that we can use synthetic cohorts created from medical risk calculators to gain insights into how risk estimations, clinical reasoning, data-driven subgrouping, and the confidence in risk calculator scores are connected. When prediction variables aren't evenly distributed in these synthetic cohorts, they can be used to group similar cases together, revealing new insights about how cohorts behave. We also found that the confidence in predictions made by these calculators can vary depending on patient characteristics. This suggests that it might be beneficial to include a "normalized confidence" score in future versions of these calculators for healthcare professionals. We plan to explore this idea further in our upcoming research.

Abstract YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the p73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using HCT116 cells, we show here that oxaliplatin treatment led to core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of p73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed antagonistic effects with oxaliplatin in co-treatments. Importantly, using several colorectal cell lines, we show that the sensitizing action of TAZ to oxaliplatin is dependent on the p53 status of the cells. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and p53 activity pushes cells towards apoptosis.

Abstract Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse ‘use conditions’. We report a core lexicon of terms that are atomic, non-directional ‘concepts of use’, called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility. Seventy-six concepts were initially identified from diverse real-world settings, and via iterative rounds of deliberation and user-testing these were optimised and condensed down to 20 items. To validate utility, support software and training information was provided to biobanks and registries who were asked to create Sharing Policy Profiles. This succeeded and involved adding standardised directionality and scope annotations to the employed terms. The addition of free-text parameters was also explored. The approach is now being adopted by several real-world projects, enabling this standard to evolve progressively into a universal basis for representing and managing conditions of use.

Abstract Improving patient care and advancing scientific discovery requires responsible sharing of research data, healthcare records, biosamples, and biomedical resources that must also respect applicable use conditions. Defining a standard to structure and manage these use conditions is a complex and challenging task. This is exemplified by a near unlimited range of asset types, a high variability of applicable conditions, and differing applications at the individual or collective level. Furthermore, the specifics and granularity required are likely to vary depending on the ultimate contexts of use. All these factors confound alignment of institutional missions, funding objectives, regulatory and technical requirements to facilitate effective sharing. The presented work highlights the complexity and diversity of the problem, reviews the current state of the art, and emphasises the need for a flexible and adaptable approach. We propose Digital Use Conditions (DUC) as a framework that addresses these needs by leveraging existing standards, striking a balance between expressiveness versus ambiguity, and considering the breadth of applicable information with their context of use.

Abstract Legacy radioactive waste can be defined as the radioactive waste produced during the infancy of the civil nuclear industry’s development in the mid-20th Century, a time when, unfortunately, waste storage and treatment were not well planned. The marine environment is one of the environmental compartments worth studying in this regard because of legacy waste in specific locations of the seabed. Comprising nearly 70% of the earth’s service, the oceans are the largest and indeed the final destination for contaminated fresh waters. For this reason, long-term studies of the accumulation biochemical mechanisms of metallic radionuclides in the marine ecosystem are required. In this context the brown algal compartment may be ecologically relevant because of forming large and dense algal beds in coastal areas and potential important biomass for contamination. This report presents the first step in the investigation of uranium (U, an element used in the nuclear cycle) bioaccumulation in the brown alga Ascophyllum nodosum using a multi-scale spectroscopic and imaging approach. Contamination of A. nodosum specimens in closed aquaria at 13 °C was performed with a defined quantity of U(VI) (10–5 M). The living algal uptake was quantified by ICP-MS and a localization study in the various algal compartments was carried out by combining electronic microscopy imaging (SEM), X-ray Absorption spectroscopy (XAS) and micro X-ray Florescence (μ-XRF). Data indicate that the brown alga is able to concentrate U(VI) by an active bioaccumulation mechanism, reaching an equilibrium state after 200 h of daily contamination. A comparison between living organisms and dry biomass confirms a stress-response process in the former, with an average bioaccumulation factor (BAF) of 10 ± 2 for living specimens (90% lower compared to dry biomass, 142 ± 5). Also, these results open new perspectives for a potential use of A. nodosum dry biomass as uranium biosorbent. The different partial BAFs (bioaccumulation factors) range from 3 (for thallus) to 49 (for receptacles) leading to a compartmentalization of uranium within the seaweed. This reveals a higher accumulation capacity in the receptacles, the algal reproductive parts. SEM images highlight the different tissue distributions among the compartments with a superficial absorption in the thallus and lateral branches and several hotspots in the oospheres of the female individuals. A preliminary speciation XAS analysis identified a distinct U speciation in the gametes-containing receptacles as a pseudo-autunite phosphate phase. Similarly, XAS measurements on the lateral branches (XANES) were not conclusive with regards to the occurrence of an alginate-U complex in these tissues. Nonetheless, the hypothesis that alginate may play a role in the speciation of U in the algal thallus tissues is still under consideration.

Anglers are a diverse population whose behaviours and perspectives are influenced by a myriad of factors including knowledge, expertise, management actions, and regulations. We examine similarities and differences in behaviours and perspectives amongst freshwater anglers of rainbow trout and steelhead (Oncorhynchus mykiss) in British Columbia, Canada, using an online survey. Findings from the survey suggest that subgroups or “types” of anglers are identifiable by differences in their behaviours and perspectives according to geographic area, gear type, fishery, and frequency of fishing activities. Our results indicate that angler types share many of the same motivations for engaging in fishing behaviours and similar concerns regarding threats to their preferred fishery; however, differences were evident across types of issues related to angler behaviour, as well as views on fisheries management. Overall, we argue that understanding fishery-scale angler heterogeneity can benefit fisheries management by highlighting areas of agreement and disagreement and encouraging tailored communications and relationship-building with important angler subgroups.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

As part of their third-year general chemistry program, students at the University of the Côte d'Azur are taught the basics of radioactivity. The view that third-year university students have of the periodic Table of the Elements is often reduced because it ignores the vast majority of isotopes. As part of this program, a practicum devoted to the observation of [alpha] and [beta] particles has been put in place and a table-top version of a cloud chamber of the Langsdorf type was designed, but in its simpler, static version. With a simple experiment and a source of natural uranium, concepts that normally belong to the distinct disciplines of thermodynamics, classical point physics, nuclear instability, and even chemistry are being addressed in a complementary manner. This article gives a full description of the various concepts that may be taught during the practicum, together with the basic equations. Numerical applications performed with observed data are proposed and discussed together with tabulated data. Through this practicum, students can actually observe radioactivity directly and come to understand that nuclides may be stable or unstable.

Abstract Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom‐up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre‐vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self‐organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein‐1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter‐scale beige adipose micro‐tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.

The effective sharing of health research data within the healthcare ecosystem can have tremendous impact on the advancement of disease understanding, prevention, treatment, and monitoring. By combining and reusing health research data, increasingly rich insights can be made about patients and populations that feed back into the health system resulting in more effective best practices and better patient outcomes. To achieve the promise of a learning health system, data needs to meet the FAIR principles of findability, accessibility, interoperability, and reusability. Since the inception of the Brain-CODE platform and services in 2012, the Ontario Brain Institute (OBI) has pioneered data sharing activities aligned with FAIR principles in neuroscience. Here, we describe how Brain-CODE has operationalized data sharing according to the FAIR principles. Findable—Brain-CODE offers an interactive and itemized approach for requesters to generate data cuts of interest that align with their research questions. Accessible—Brain-CODE offers multiple data access mechanisms. These mechanisms—that distinguish between metadata access, data access within a secure computing environment on Brain-CODE and data access via export will be discussed. Interoperable—Standardization happens at the data capture level and the data release stage to allow integration with similar data elements. Reusable - Brain-CODE implements several quality assurances measures and controls to maximize data value for reusability. We will highlight the successes and challenges of a FAIR-focused neuroinformatics platform that facilitates the widespread collection and sharing of neuroscience research data for learning health systems.

Background: Cancer therapies targeting actionable molecular alterations (AMA) have developed, but the clinical routine impact of high-throughput molecular profiling remains unclear. We present a monocentric experience of molecular profiling based on liquid biopsy in patients with cancer. Methods: Patients included had solid cancer and underwent cfDNA genomic profiling with FoudationOne Liquid CDx (F1LCDx) test, analyzing 324 genes. Primary endpoint was to describe patients with an AMA for whom clinical decisions were impacted by F1LCDx test results. Results: 191 patients were included, mostly with lung cancer (46%). An AMA was found in 52%. The most common molecular alterations were: TP53 (52%), KRAS (14%) and DNMT3 (11%). The most common AMA were: CHEK2 (10%), PIK3CA (9%), ATM (7%). There was no difference in progression-free survival (2.66 months vs. 3.81 months, p = 0.17), overall survival (5.3 months vs. 7.1 months, p = 0.64), or PFS2/PFS1 ratio ≥ 1.3 (20% vs. 24%, p = 0.72) between patients receiving a molecularly matched therapy (MMT) or a non-MMT, respectively. Patients with a MMT had an overall response rate of 19% and a disease control of 32%. Conclusions: Routine cfDNA molecular profiling is feasible and can lead to the access of targeted therapies. However, no notable benefit in patient’s outcomes was shown in this unselected pan-cancer study.

A seminal report by Peter H. Pearse (1988; Rising to the Challenge: A New Policy for Canada’s Freshwater Fisheries, Canadian Wildlife Federation, Ottawa) outlined 62 policy recommendations focused on the management of Canada’s inland fisheries. Over three decades later, freshwater ecosystems and inland fisheries in Canada are still facing similar challenges with many emerging ones that could not have been foreseen. Here, we reflect on the contemporary relevance of the Pearse Report and propose recommendations that policy makers should consider. Broadly, our recommendations are: (1) manage fishes, fisheries, and habitat using a holistic co-management framework, with clearly defined fishery jurisdictions and partnerships with Indigenous governments; (2) engage in transparent, inclusive, and agile research to support decision-making; (3) facilitate knowledge co-production, involving interdisciplinary projects with diverse groups of actors and sectors including Indigenous Peoples, anglers, policy makers, scientists/researchers, governments, and the public; (4) embrace technological advances to support freshwater fisheries stock assessment and management; and (5) align policy and management activities in Canada with global initiatives related to increasing the sustainability of inland fisheries. We advocate for an updated comprehensive report such as the Pearse Report to ensure that we embrace robust, inclusive, and sustainable management strategies and policies for Canada’s inland fisheries for the next 30 years. It is time to again rise to the challenge.

Ferritin is the main protein of Fe storage in eukaryote and prokaryote cells. It is a large multifunctional, multi-subunit protein consisting of heavy H and light L subunits. In the field of nuclear toxicology, it has been suggested that some actinide elements, such as thorium and plutonium at oxidation state +IV, have a comparable `biochemistry' to iron at oxidation state +III owing to their very high tendency for hydrolysis and somewhat comparable ionic radii. Therefore, the possible mechanisms of interaction of such actinide elements with the Fe storage protein is a fundamental question of bio-actinidic chemistry. We recently described the complexation of Pu(IV) and Th(IV) with horse spleen ferritin (composed mainly of L subunits). In this article, we bring another viewpoint to this question by further combining modeling with our previous EXAFS data for Pu(IV) and Th(IV). As a result, the interaction between the L subunits and both actinides appears to be non-specific but driven only by the density of the presence of Asp and Glu residues on the protein shell. The formation of an oxyhydroxide Th or Pu core has not been observed under the experimental conditions here, nor the interaction of Th or Pu with the ferric oxyhydroxide core.

Abstract Sorghum currently contributes to the species portfolio that is supporting bioenergy production including anaerobic digestion. Although agro‐morphological ideotypes maximizing biogas production have been recently proposed, there is a crucial need to refine our understanding of the impacts of the stem composition and structure on this processing trait in order to ensure genetic gains in the mid to long terms. This study aims to assess the potential of Sorghum bicolor ssp bicolor stem genetic diversity to maximize genetic gains for biogas production and define a biogas stem ideotype. In this context, a panel of 57 genotypes, encompassing most of the stem composition variability available in cultivated sorghum, was characterized over five sites. Simultaneous histological and biochemical characterizations were performed. A high broad sense heritability associated with a moderate genetic variability was detected for stem biogas potential ensuring significant genetic gains in the future. In addition, the development of a stem histological phenotyping pipeline made it possible to describe the genetic diversity available for the internode anatomy and the repartition of key cell wall components. Consistently with previous studies, moderate to high heritability was observed for stem biochemical components. Genetic correlation, hierarchical clustering, and multiple stepwise regression analyses identified soluble sugar content as the first main driver of biogas potential genetic variability. Nevertheless, breeding programs should anticipate that biogas yield improvement will also rely on the monitoring of the cell wall components and their distribution in the stem jointly with the soluble sugar content. According to the assets of sorghum in terms of adaptation to environmental stresses and the present results regarding the identification of stem ideotypes suitable for different value chains, this species will surely play a key role to optimize the economic and environmental sustainability of the agrosystems that are currently facing the effects of climate change.

Inland fisheries are complex social-ecological systems that can generate important nutritional, economic, cultural, and recreational benefits. Effective management of these systems for multiple user-groups requires an understanding of the complex natural and human dimensions interactions within them. We examine the perceptions of stakeholders, Indigenous rightsholders, and regulatory/governance groups on the current and future status of Oncorhynchus mykiss (including their resident form – rainbow trout – and their anadromous form – steelhead) populations and fisheries in British Columbia (BC), Canada from 65 qualitative interviews and 1029 quantitative survey responses. Participants generally did not believe resident rainbow trout were threatened at the provincial level but were definitive in assessing anadromous steelhead trout as threatened. Habitat alterations, water temperature extremes, and climate change, were key threats identified for all forms of O. mykiss while bycatch in commercial fisheries and predation pressure from pinnipeds were specifically identified threats for steelhead trout. Anglers did not perceive recreational fishing pressure as a key threat in contrast to regulatory and governance groups. Fisheries managers were praised for stocking programs and managing small lakes fisheries but criticized for not doing enough to protect fish populations, for an unwillingness to challenge or confront commercial and Indigenous interests which infringe on conservation, and for a lack of aquatic monitoring. Three factors identified by participants contribute to fishery mismanagement, inaction, and decision paralysis: (1) insufficient resources (funding, staff, time), (2) confusion in jurisdictional authority between provincial and federal governments, and (3) organizational structure of natural resource management agencies which are not autonomous from competing commercial and industrial objectives and directions. Despite conservation being purported as the highest priority of fisheries managers, economic, social, and political drivers are perceived as increasingly influencing conservation decisions and actions. These findings can inform fisheries management and conservation decisions, policies and practices to ensure that they are more salient, robust, legitimate, and effective.

In recent years, the utility and efficiency of automated procedures for cognitive assessment in psychology and neuroscience have been demonstrated in non-human primates (NHP). This approach mimics conventional shaping principles of breaking down a final desired behavior into smaller components that can be trained in a staircase manner. When combined with home-cage-based approaches, this could lead to a reduction in human workload, enhancement in data quality, and improvement in animal welfare. However, to our knowledge, there are no reported attempts to develop automated training and testing protocols for long-tailed macaques (Macaca fascicularis), a ubiquitous NHP model in neuroscience and pharmaceutical research. In the current work, we present the results from 6 long-tailed macaques that were trained using an automated unsupervised training (AUT) protocol for introducing the animals to the basics of a two-alternative choice (2 AC) task where they had to discriminate a conspecific vocalization from a pure tone relying on images presented on a touchscreen to report their response. We found that animals (1) consistently engaged with the device across several months; (2) interacted in bouts of high engagement; (3) alternated peacefully to interact with the device; and (4) smoothly ascended from step to step in the visually guided section of the procedure, in line with previous results from other NHPs. However, we also found (5) that animals’ performance remained at chance level as soon as the acoustically guided steps were reached; and (6) that the engagement level decreased significantly with decreasing performance during the transition from visual to acoustic-guided sections. We conclude that with an autonomous approach, it is possible to train long-tailed macaques in their social group using computer vision techniques and without dietary restriction to solve a visually guided discrimination task but not an acoustically guided task. We provide suggestions on what future attempts could take into consideration to instruct acoustically guided discrimination tasks successfully.

Social comparisons are a fundamental feature of human thinking and affect self-evaluations and task performance. Little is known about the evolutionary origins of social comparison processes, however. Previous studies that investigated performance-based social comparisons in nonhuman primates yielded mixed results. We report three experiments that aimed (a) to explore how the task type may contribute to performance in monkeys, and (b) how a competitive set-up affects monkeys compared to humans. In a co-action touchscreen task, monkeys were neither influenced by nor interested in the performance of the partner. This may indicate that the experimental set-up was not sufficiently relevant to trigger social comparisons. In a novel co-action foraging task, monkeys increased their feeding speed in competitive and co-active conditions, but not in relation to the degree of competition. In an analogue of the foraging task, human participants were affected by partner performance and experimental context, indicating that the task is suitable to elicit social comparisons in humans. Our studies indicate that specifics of task and experimental setting are relevant to draw the monkeys’ attention to a co-actor and that, in line with previous research, a competitive element was crucial. We highlight the need to explore what constitutes “relevant” social comparison situations for monkeys as well as nonhuman animals in general, and point out factors that we think are crucial in this respect (e.g., task type, physical closeness, and the species’ ecology). We discuss that early forms of social comparisons evolved in purely competitive environments with increasing social tolerance and cooperative motivations allowing for more fine-grained processing of social information. Competition driven effects on task performance might constitute the foundation for the more elaborate social comparison processes found in humans, which may involve context-dependent information processing and metacognitive monitoring.

Spleen tyrosine kinase (Syk) expression have been both positively and negatively associated with tumorigenesis. Our goal was to evaluate the contribution of Syk and its two splice variants, full length Syk (L) and short isoform Syk (S), in the tumor biology of colorectal cancer cells (CRC). The analysis of Syk expression in primary human colorectal tumors, as well as the analysis of TCGA database, revealed a high Syk mRNA expression score in colorectal cancer tumors, suggesting a tumor promotor role of Syk in CRC. Our analysis showed that Syk (L) isoform is highly expressed in the majority of the tumor tissues and that it remains expressed in tumors in which global Syk expression is downregulated, suggesting the dependence of tumors to Syk (L) isoform. We also identified a small cluster of tumor tissues, which express a high proportion of Syk (S) isoform. This specific cluster is associated with overexpressed genes related to translation and mitochondria, and down regulated genes implicated in the progression of mitosis. For our functional studies, we used short hairpin RNA tools to target the expression of Syk in CRC cells bearing the activating K-Ras (G13D) mutation. Our results showed that while global Syk knock down increases cell proliferation and cell motility, Syk (L) expression silencing affects the viability and induces the apoptosis of the cells, confirming the dependence of cells on Syk (L) isoform for their survival. Finally, we report the promising potential of compound C-13, an original non-enzymatic inhibitor of Syk isolated in our group. In vitro studies showed that C-13 exerts cytotoxic effects on Syk-positive CRC cells by inhibiting their proliferation and their motility, and by inducing their apoptosis, while Syk-negative cell lines viability was not affected. Moreover, the oral and intraperitoneal administration of C-13 reduced the tumor growth of CRC DLD-1 cells xenografts in Nude mice in vivo.

Summary: The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

Summary: Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset’s allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers’ discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.

Summary: The Global Alliance for Genomics and Health (GA4GH) supports international standards that enable a federated data sharing model for the research community while respecting data security, ethical and regulatory frameworks, and data authorization and access processes for sensitive data. The GA4GH Passport standard (Passport) defines a machine-readable digital identity that conveys roles and data access permissions (called “visas”) for individual users. Visas are issued by data stewards, including data access committees (DACs) working with public databases, the entities responsible for the quality, integrity, and access arrangements for the datasets in the management of human biomedical data. Passports streamline management of data access rights across data systems by using visas that present a data user’s digital identity and permissions across organizations, tools, environments, and services. We describe real-world implementations of the GA4GH Passport standard in use cases from ELIXIR Europe, National Institutes of Health, and the Autism Sharing Initiative. These implementations demonstrate that the Passport standard has provided transparent mechanisms for establishing permissions and authorizing data access across platforms.

Lactate, a metabolite produced when the glycolytic flux exceeds mitochondrial oxidative capacities, is now viewed as a critical regulator of metabolism by acting as both a carbon and electron carrier and a signaling molecule between cells and tissues. In recent years, increasing evidence report its key role in white, beige, and brown adipose tissue biology, and highlights new mechanisms by which lactate participates in the maintenance of whole-body energy homeostasis. Lactate displays a wide range of biological effects in adipose cells not only through its binding to the membrane receptor but also through its transport and the subsequent effect on intracellular metabolism notably on redox balance. This study explores how lactate regulates adipocyte metabolism and plasticity by balancing intracellular redox state and by regulating specific signaling pathways. We also emphasized the contribution of adipose tissues to the regulation of systemic lactate metabolism, their roles in redox homeostasis, and related putative physiopathological repercussions associated with their decline in metabolic diseases and aging.

Following a first presentation of the works performed by our project group at ICOMOS General Assembly in 2017, it was time for us to bring an update, oriented on our technological and methodological choices and implementations. This paper presents the evolution of our data management system.

Abstract Background Individual bees exhibit complex movement patterns to efficiently exploit small areas within larger plant populations. How such individual spatial behaviours scale up to the collective level, when several foragers visit a common area, has remained challenging to investigate, both because of the low resolution of field movement data and the limited power of the statistical descriptors to analyse them. To tackle these issues we video recorded all flower visits (N = 6205), and every interaction on flowers (N = 628), involving foragers from a bumblebee (Bombus terrestris) colony in a large outdoor flight cage (880 m2), containing ten artificial flowers, collected on five consecutive days, and analysed bee movements using networks statistics. Results Bee-flower visitation networks were significantly more modular than expected by chance, indicating that foragers minimized overlaps in their patterns of flower visits. Resource partitioning emerged from differences in foraging experience among bees, and from outcomes of their interactions on flowers. Less experienced foragers showed lower activity and were more faithful to some flowers, whereas more experienced foragers explored the flower array more extensively. Furthermore, bees avoided returning to flowers from which they had recently been displaced by a nestmate, suggesting that bees integrate memories of past interactions into their foraging decisions. Conclusion Our observations, under high levels of competition in a flight cage, suggest that the continuous turnover of foragers observed in colonies can led to efficient resource partitioning among bees in natural conditions.

In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.

Summary: Atrial natriuretic peptide (ANP) is a cardiac hormone controlling blood volume and pressure in mammals. It is still unclear whether ANP controls cold-induced thermogenesis in vivo. Here, we show that acute cold exposure induces cardiac ANP secretion in mice and humans. Genetic inactivation of ANP promotes cold intolerance and suppresses half of cold-induced brown adipose tissue (BAT) activation in mice. While white adipocytes are resistant to ANP-mediated lipolysis at thermoneutral temperature in mice, cold exposure renders white adipocytes fully responsive to ANP to activate lipolysis and a thermogenic program, a physiological response that is dramatically suppressed in ANP null mice. ANP deficiency also blunts liver triglycerides and glycogen metabolism, thus impairing fuel availability for BAT thermogenesis. ANP directly increases mitochondrial uncoupling and thermogenic gene expression in human white and brown adipocytes. Together, these results indicate that ANP is a major physiological trigger of BAT thermogenesis upon cold exposure in mammals.