116 research outputs found

    Genomic signatures in the coral holobiont reveal host adaptations driven by Holocene climate change and reef specific symbionts

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    Genetic signatures caused by demographic and adaptive processes during past climatic shifts can inform predictions of species’ responses to anthropogenic climate change. To identify these signatures in Acropora tenuis, a reef-building coral threatened by global warming, we first assembled the genome from long reads and then used shallow whole-genome resequencing of 150 colonies from the central inshore Great Barrier Reef to inform population genomic analyses. We identify population structure in the host that reflects a Pleistocene split, whereas photosymbiont differences between reefs most likely reflect contemporary (Holocene) conditions. Signatures of selection in the host were associated with genes linked to diverse processes including osmotic regulation, skeletal development, and the establishment and maintenance of symbiosis. Our results suggest that adaptation to post-glacial climate change in A. tenuis has involved selection on many genes, while differences in symbiont specificity between reefs appear to be unrelated to host population structure

    A genome-centric view of the role of the Acropora kenti microbiome in coral health and resilience

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    Microbial diversity has been extensively explored in reef-building corals. However, the functional roles of coral-associated microorganisms remain poorly elucidated. Here, we recover 191 bacterial and 10 archaeal metagenome-assembled genomes (MAGs) from the coral Acropora kenti (formerly A. tenuis) and adjacent seawater, to identify microbial functions and metabolic interactions within the holobiont. We show that 82 MAGs were specific to the A. kenti holobiont, including members of the Pseudomonadota, Bacteroidota, and Desulfobacterota. A. kenti-specific MAGs displayed significant differences in their genomic features and functional potential relative to seawater-specific MAGs, with a higher prevalence of genes involved in host immune system evasion, nitrogen and carbon fixation, and synthesis of five essential B-vitamins. We find a diversity of A. kenti-specific MAGs encode the biosynthesis of essential amino acids, such as tryptophan, histidine, and lysine, which cannot be de novo synthesised by the host or Symbiodiniaceae. Across a water quality gradient spanning 2° of latitude, A. kenti microbial community composition is correlated to increased temperature and dissolved inorganic nitrogen, with corresponding enrichment in molecular chaperones, nitrate reductases, and a heat-shock protein. We reveal mechanisms of A. kenti-microbiome-symbiosis on the Great Barrier Reef, highlighting the interactions underpinning the health of this keystone holobiont

    Evaluating an Integrated Local System Response to the COVID-19 Pandemic: Case Study of East Toronto Health Partners

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    Introduction: East Toronto Health Partners (ETHP) is a network of organizations that serve residents of East Toronto, Ontario, Canada. ETHP is a newly formed integrated model of care in which hospital, primary care, community providers and patients/families work together to improve population health. We describe and evaluate the evolution of this emerging integrated care system as it responded to a global health crisis. Description: This paper begins by describing ETHP’s pandemic response mapping out over two years of data. To evaluate the response, semi-structured interviews were conducted with 30 decision makers, clinicians, staff, and volunteers who were part of the response. The interviews were thematically analyzed, and emergent themes mapped onto the nine pillars of integrated care. Discussion: The ETHP pandemic response evolved rapidly. Early siloed responses gave way to collaborative efforts and equity emerged as a central priority. New alliances formed, resources were shared, leaders emerged, and community members stepped forward to contribute. Interviewees identified positives as well as many opportunities for improvement post-pandemic. Conclusion: The pandemic was a catalyst for change in East Toronto that accelerated existing initiatives to achieve integrated care. The East Toronto experience may serve as a useful guide for other emerging integrated care systems

    Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells

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    We are grateful to Custodio Borrego for giving us free use of the photograph he took of EVOO and olive trees in Granada (Spain), which have been included in Figure 7. This work has been awarded with the IV Premio Internacional Castillo de Canena de Investigación Oleícola ‘LUIS VAÑÓ’(IV Edition of Castillo de Canena LUIS VAÑÓ Award for Research on Olive Cultivation and Olive Oil; UC Davis Olive Center, Castillo de Canena, and Universidad de Jaén).The authors would like to thank Dr Kenneth McCreath for editorial support. We are greatly indebted to Prof Robert A. Weinberg (Whitehead Institute for Biomedical Research, Cambridge, MA) for providing the HMLERshCntrol/HMLERshEcad cells used in this work.Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target subpopulations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24−/low CSC. DOA could potently block the formation of multicellular tumorspheres generated from single-founder stem-like cells in a panel of genetically diverse BC models. Pretreatment of BC populations with noncytotoxic doses of DOA dramatically reduced subsequent tumor-forming capacity in vivo. Mice orthotopically injected with CSC-enriched BC-cell populations pretreated with DOA remained tumor-free for several months. Phenotype microarray-based screening pointed to a synergistic interaction of DOA with the mTOR inhibitor rapamycin and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine. In silico computational studies indicated that DOA binds and inhibits the ATP-binding kinase domain site of mTOR and the S-adenosyl-l-methionine (SAM) cofactorbinding pocket of DNMTs. FRET-based Z-LYTE™ and AlphaScreen-based in vitro assays confirmed the ability of DOA to function as an ATP-competitive mTOR inhibitor and to block the SAM-dependent methylation activity of DNMTs. Our systematic in vitro, in vivo and in silico approaches establish the phenol-conjugated oleoside DOA as a dual mTOR/DNMT inhibitor naturally occurring in EVOO that functionally suppresses CSC-like states responsible for maintaining tumorinitiating cell properties within BC populations.This work was supported by grants from the Ministerio de Ciencia e Innovación (Grant SAF2016-80639-P to J.A.M.), Plan Nacional de I+D+I, Spain, the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR; Grant 2014 SGR229 to J.A.M.), Departament d’Economia i Coneixement, Catalonia, Spain, the Andalusian Regional Government Council of Innovation and Science (Grant P11-CTS-7625 to A.S.-C.), the Ministerio de Economía, Industria y Competitividad, Spain (Grants AGL2015- 67995-C2-3-R and AGL2015-67995-C3-1-R to A.S.-C. and V.M.) and Conselleria d’Educació, Investigació, Cultura I Esport, Generalitat Valenciana, Spain (Grant PROMETEO/2016/006 to V.M). E.C. is supported by the Sara Borrell post doctoral contract (CD15/00033) from the Ministerio de Sanidad y Consumo, Fondo de Investigación Sanitaria (FIS), Spain

    A nanostructural view of the cell wall disassembly process during fruit ripening and postharvest storage by atomic force microscopy

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    Background: The mechanical properties of parenchyma cell walls and the strength and extension of adhesion areas between adjacent cells, jointly with cell turgor, are main determinants of firmness of fleshy fruits. These traits are modified during ripening leading to fruit softening. Cell wall modifications involve the depolymerisation of matrix glycans and pectins, the solubilisation of pectins and the loss of neutral sugars from pectin side chains. These changes weaken the cell walls and increase cell separation, which in combination with a reduction in cell turgor, bring about textural changes. Atomic force microscopy (AFM) has been used to characterize the nanostructure of cell wall polysaccharides during the ripening and postharvest storage of several fruits. This technique allows the imaging of individual polymers at high magnification with minimal sample preparation. Scope and approach: This paper reviews the main features of the cell wall disassembly process associated to fruit softening from a nanostructural point of view, as has been provided by AFM studies. Key findings and conclusions: AFM studies show that pectin size, ramification and complexity is reduced during fruit ripening and storage, and in most cases these changes correlate with softening. Postharvest treatments that improve fruit quality have been proven to preserve pectin structure, suggesting a clear link between softening and pectin metabolism. Nanostructural characterization of cellulose and hemicellulose during ripening has been poorly explored by AFM and the scarce results available are not conclusive. Globally, AFM could be a powerful tool to gain insights about the bases of textural fruit quality in fresh and stored fruits

    Correlation between DNA damage responses of skin to a test dose of radiation and late adverse effects of earlier breast radiotherapy

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    Aim: To correlate residual double strand breaks (DSB) 24 h after 4 Gy test doses to skin in vivo and to lymphocytes in vitro with adverse effects of earlier breast radiotherapy (RT). Patients and methods: Patients given whole breast RT P5 years earlier were identified on the basis of moderate/marked or minimal/no adverse effects despite the absence (‘RT-Sensitive’, RT-S) or presence (‘RT-Resistant’, RT-R) of variables predisposing to late adverse effects. Residual DSB were quantified in skin 24 h after a 4 Gy test dose in 20 RT-S and 15 RT-R patients. Residual DSB were quantified in lymphocytes irradiated with 4 Gy in vitro in 30/35 patients. Results: Mean foci per dermal fibroblast were 3.29 (RT-S) vs 2.80 (RT-R) (p = 0.137); 3.28 (RT-S) vs 2.60 (RT-R) in endothelium (p = 0.158); 2.50 (RT-S) vs 2.41 (RT-R) in suprabasal keratinocytes (p = 0.633); 2.70 (RT-S) vs 2.35 (RT-R) in basal epidermis (p = 0.419); 12.1 (RT-S) vs 10.3 (RT-R) in lymphocytes (p = 0.0052). Conclusions: Residual DSB in skin following a 4 Gy dose were not significantly associated with risk of late adverse effects of breast radiotherapy, although exploratory analyses suggested an association in severely affected individuals. By contrast, a significant association was detected based on the in vitro response of lymphocytes

    Conversion of biomass platform molecules into fuel additives and liquid hydrocarbon fuels

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    [EN] In this work some relevant processes for the preparation of liquid hydrocarbon fuels and fuel additives from cellulose, hemicellulose and triglycerides derived platform molecules are discussed. Thus, it is shown that a series of platform molecules such as levulinic acid, furans, fatty acids and polyols can be converted into a variety of fuel additives through catalytic transformations that include reduction, esterification, etherification, and acetalization reactions. Moreover, we will show that liquid hydrocarbon fuels can be obtained by combining oxygen removal processes (e.g. dehydration, hydrogenolysis, hydrogenation, decarbonylation/descarboxylation etc.) with the adjustment of the molecular weight via C C coupling reactions (e.g. aldol condensation, hydroxyalkylation, oligomerization, ketonization) of the reactive platform molecules.This work has been supported by the Spanish Government-MINECO through Consolider Ingenio 2010-Multicat and CTQ.-2011-27550, ITQ thanks the "Program Severo Ochoa" for financial support.Climent Olmedo, MJ.; Corma Canós, A.; Iborra Chornet, S. (2014). Conversion of biomass platform molecules into fuel additives and liquid hydrocarbon fuels. Green Chemistry. 16(2):516-547. https://doi.org/10.1039/c3gc41492bS51654716

    2018 Research & Innovation Day Program

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    A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1005/thumbnail.jp
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