Thrombospondin-3 augments injury-induced cardiomyopathy by intracellular integrin inhibition and sarcolemmal instability.

Thrombospondins (Thbs) are a family of five secreted matricellular glycoproteins in vertebrates that broadly affect cell-matrix interaction. While Thbs4 is known to protect striated muscle from disease by enhancing sarcolemmal stability through increased integrin and dystroglycan attachment complexes, here we show that Thbs3 antithetically promotes sarcolemmal destabilization by reducing integrin function, augmenting disease-induced decompensation. Deletion of Thbs3 in mice enhances integrin membrane expression and membrane stability, protecting the heart from disease stimuli. Transgene-mediated overexpression of α7β1D integrin in the heart ameliorates the disease predisposing effects of Thbs3 by augmenting sarcolemmal stability. Mechanistically, we show that mutating Thbs3 to contain the conserved RGD integrin binding domain normally found in Thbs4 and Thbs5 now rescues the defective expression of integrins on the sarcolemma. Thus, Thbs proteins mediate the intracellular processing of integrin plasma membrane attachment complexes to regulate the dynamics of cellular remodeling and membrane stability

The killer within: Endogenous bacteria accelerate oyster mortality during sustained anoxia

16 pages, 5 figures, 2 tablesSustained periods of anoxia, driven by eutrophication, threaten coastal marine systems and can lead to mass mortalities of even resilient animals such as bivalves. While mortality rates under anoxia are well-studied, the specific mechanism(s) of mortality are less clear. We used a suite of complementary techniques (LT50, histology, 16S rRNA amplicon sequencing, and valvometry) to show that the proliferation of anaerobic bacteria within eastern oysters (Crassostrea virginica) accelerates mortality rate under anoxic conditions. Manipulative laboratory experiments revealed that oyster survival under anoxic conditions was halved when bacteria were present compared to when they were excluded by the broad-spectrum antibiotic chloramphenicol. Histological assessments supported this mechanism and showed infiltration of bacteria in oysters that were not treated with antibiotics compared to a general lack of bacteria when oysters were treated with antibiotics. 16S rRNA amplicon sequencing failed to identify any particular genera of bacteria responsible for mortality, rather a diversity of endogenous anaerobic and/or sulfate-reducing bacteria were common among oysters. In addition, monitoring of oyster valve gaping behavior in the field revealed that oysters showed remarkable valve closure synchrony when first exposed to anoxia. However, oysters periodically opened throughout anoxia/hypoxia in both the lab and field, suggesting that the infiltration of exogenous bacteria from the environment may also influence mortality rates under natural settings. Coupled with previous studies, we posit that mass mortality events in a wide range of coastal bivalves are likely the result of co-morbidity from asphyxiation and bacterial processesThis study was funded by L'Étang Ruisseau Bar Ltd. in partnership with the Department of Fisheries and Oceans of Canada (Aquaculture Collaborative Research and Development Program, project 17-G-02 led by M.R.S.C.), a NSERC Discovery Grant to R.F. (RGPIN-2017-04294), and a Total Development Fund from the New Brunswick Department of Agriculture, Aquaculture and Fisheries to R.F.Peer reviewe

Diurnal Rhythms Result in Significant Changes in the Cellular Protein Complement in the Cyanobacterium Cyanothece 51142

Cyanothece sp. ATCC 51142 is a diazotrophic cyanobacterium notable for its ability to perform oxygenic photosynthesis and dinitrogen fixation in the same single cell. Previous transcriptional analysis revealed that the existence of these incompatible cellular processes largely depends on tightly synchronized expression programs involving ∼30% of genes in the genome. To expand upon current knowledge, we have utilized sensitive proteomic approaches to examine the impact of diurnal rhythms on the protein complement in Cyanothece 51142. We found that 250 proteins accounting for ∼5% of the predicted ORFs from the Cyanothece 51142 genome and 20% of proteins detected under alternating light/dark conditions exhibited periodic oscillations in their abundances. Our results suggest that altered enzyme activities at different phases during the diurnal cycle can be attributed to changes in the abundance of related proteins and key compounds. The integration of global proteomics and transcriptomic data further revealed that post-transcriptional events are important for temporal regulation of processes such as photosynthesis in Cyanothece 51142. This analysis is the first comprehensive report on global quantitative proteomics in a unicellular diazotrophic cyanobacterium and uncovers novel findings about diurnal rhythms

Preparing for the health impacts of climate change in Indigenous communities: The role of community-based adaptation

Climate change presents substantial risks to the health of Indigenous peoples. Research is needed to inform health policy and practice for managing risks, with community based adaptation (CBA) emerging as one approach to conducting research to support such efforts. Few, if any, studies however, have critically examined the application of CBA in a health or Indigenous peoples context. We examine the strengths, challenges, and opportunities of health-related CBA research in Indigenous community settings, drawing on the experiences of the multi-nation interdisciplinary Indigenous Health Adaptation to Climate Change (IHACC) project. Data collection was guided by a framework developed to evaluate CBA projects. Semi-structured interviews (n = 114) and focus groups (n = 23, 177 participants) were conducted with faculty-based researchers, institutional partners, community members, students, and trainees involved in the IHACC project in Canada, Uganda, and Peru. Results illustrate the importance of CBA in co-generating knowledge on climate-health vulnerability and adaptation options, capacity building, and informing decision choices. There are also significant challenges of conducting CBA which can have unintended negative consequences, with results emphasizing the importance of managing the tension between health research and tangible and immediate benefits; developing a working architecture for collective impact, including team building, identification of common goals, and meaningful engagement of knowledge users; and the need to continuously monitor and evaluate progress. CBA holds significant promise in a health adaptation context, but only in the ‘right’ circumstances, where considerable time is spent developing the work with partners

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Is the United Nations framework convention on climate change an effective (or appropriate) institution for supporting indigenous peoples' adaptation to climate change?

The United Nations Framework Convention on Climate Change, the core of today's global climate change regime, is an intergovernmental institution that was established in the 1990s with the objective of bringing nations together to negotiate policies in a global effort to stabilize greenhouse gas concentrations in the atmosphere at a level that would prevent dangerous interference with the climate system. Today, with increasing scientific certainty regarding the current and future impacts of climate change, and the growing notion that some degree of change is unavoidable regardless of mitigation, the role of adaptation, and its scope, have expanded a great deal within the institution since it was first envisioned. It is unclear however what opportunities and barriers this discursive structure may create for adaptation support for vulnerable sub-national populations such as indigenous peoples. Accordingly, this study uses critical discourse analysis to examine the evolution of the embedded discourse on adaptation to the adverse effects of climate change in the institution based on the official decisions rendered by the Conference of the Parties, and seeks to expose the policy implications for indigenous peoples at different scales. Noteworthy trends identified in this study include an increasingly explicit recognition of the heightened vulnerability of indigenous peoples to climate change, and the gradual shift away from approaches that are purely scientific to approaches that value and include traditional and indigenous knowledge for adaptation where appropriate. Adaptation assistance provided by developed nations however, remains exclusively aimed at projects in developing country Parties.Maintenant au cœur du régime mondial sur les changements climatiques, la Convention-Cadre des Nations Unies sur les Changements Climatiques est une institution intergouvernementale qui fut établie au début des années 1990 sous l'objectif de rassembler les pays du monde dans le but de stabiliser les concentrations de gaz à effet de serre dans l'atmosphère à un niveau qui empêcherait une interférence dangereuse avec le climat. Considérant la progression scientifique dans le domaine des impacts, présents et futures, des changements climatiques, ainsi que la notion grandissante qu'un certain degré de changement est inévitable peu importe les efforts en mitigation, le rôle qu'occupe aujourd'hui l'adaptation et sa portée s'est beaucoup élargis à l'intérieur de l'institution depuis sa naissance. En revanche, les opportunités et les obstacles que la structure du discours peut imposer à l'accès des populations vulnérables locales ne sont pas très claires, notamment le support d'adaptation apporté aux populations indigènes. À cet effet, cette thèse utilise l'analyse de discours critique afin d'examiner l'évolution du discours intégré sur l'adaptation aux impacts des changements climatiques dans l'institution, basé sur le contenu des décisions officielles rendues par les Parties à la Convention et cherche à exposer les implications politiques pour les peuples indigènes à différentes échelles. Parmi les tendances identifiées dans la présente étude, on note la reconnaissance grandissante et explicite de la vulnérabilité accrue des peuples indigènes aux changements climatiques, ainsi que l'éloignement des approches purement scientifiques dans un contexte d'adaptation, vers des approches qui valorisent et incluent les connaissances traditionnelles et indigènes. L'assistance financière fournie par les pays développés pour investir en adaptation demeure, par contre, axée sur les projets dans les pays en voie de développement seulement

Including indigenous knowledge and experience in IPCC assessment reports : post-print version

Link to published version provided.Assessment reports of the Intergovernmental Panel on Climate Change (IPCC) play a critical role in producing global knowledge on climate change. This is not a value-neutral role. As Indigenous issues have been underrepresented in previous IPCC assessments, this review analyzes how Indigenous content is covered and framed in Assessment Report 5 Working Group II (WGII). The development of culturally relevant and appropriate adaptation policies requires a more robust, nuanced, and appropriate inclusion and framing of Indigenous issues in future assessment reports. The article outlines how this can be achieved

Adaptation and indigenous peoples in the United Nations Framework Convention on climate change : post-print version

The article catalogues the discourse of adaptation within the United Nations Framework Convention on Climate Change (UNFCCC) by reviewing decision texts from the Conference of the Parties (CP) to the UNFCCC from 1992 until CP20 in 2014 (Lima). Through critical discourse analysis, Indigenous rights, practices, and knowledge are examined as they are embodied in decision texts. Implications of discursive trends around adaptation for Indigenous peoples are presented. Since CP16 (Cancun 2010), the discursive space for incorporating the voices, needs, and priorities of Indigenous peoples has expanded. The paper outlines opportunities for greater engagement in the UNFCCC post-Paris Agreement

Indigenous Health Adaptation to Climate Change (IHACC) project : final technical report

Indigenous Health Adaptation to Climate Change (IHACC) established a multinational interdisciplinary team from Canada, Uganda, and Peru to develop an understanding of the health dimensions of climate change for Indigenous populations. Research goals underpin intervention objectives towards empowering Indigenous peoples’ capacity to adapt to the health effects of climate change. Major knowledge translation / knowledge sharing workshops were held in all project locations (Peru, Arctic, and Uganda) bringing together researchers, students, community members and leaders, partner and civil society organizations, as well as government officials and decision-makers. The report provides a bibliography of research outputs