10 research outputs found

    Sepsis target validation for repurposing and combining complement and immune checkpoint inhibition therapeutics

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    Introduction: Sepsis is a disease that occurs due to an adverse immune response to infection by bacteria, viruses and fungi and is the leading pathway to death by infection. The hallmarks for maladapted immune reactions in severe sepsis, which contribute to multiple organ failure and death, are bookended by the exacerbated activation of the complement system to protracted T-cell dysfunction states orchestrated by immune checkpoint control. Despite major advances in our understanding of the condition, there remains to be either a definitive test or an effective therapeutic intervention. Areas covered: The authors consider a combinational drug therapy approach using new biologics, and mathematical modeling for predicting patient responses, in targeting innate and adaptive immune mediators underlying sepsis. Special consideration is given for emerging complement and immune checkpoint inhibitors that may be repurposed for sepsis treatment. Expert opinion: In order to overcome the challenges inherent to finding new therapies for the complex dysregulated host response to infection that drives sepsis, it is necessary to move away from monotherapy and promote precision for personalized combinatory therapies. Notably, combinatory therapy should be guided by predictive systems models of the immune-metabolic characteristics of an individual’s disease progression

    Probing the surface chemistry of different oxidized MWCNT for the improved electrical wiring of cytochrome c nitrite reductase

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    This work reports the evaluation of a set of multi-walled carbon nanotubes (MWCNT) presenting different surface chemistries, as interfaces for the direct electrochemistry of the multihemic nitrite reductase (ccNiR) from Desulfovibrio desulfuricans ATCC27774 (Dd). The carbon nanotubes (CNT) dispersions were prepared in aqueous media and deposited on pyrolytic graphite macroelectrodes, following a layer-by-layer methodology. The resulting MWCNT bed was coated with ccNiR and studied by cyclic voltammetry. Interestingly, although small non-catalytic cathodic waves were detected in all CNT bioconjugates, the complexity of these electrochemical signals was partially deconvoluted in some materials, the less acidic ones emphasizing the contribution of the catalytic centre. Consistently, these MWCNT were the most favourable for enzyme catalysis, highlighting the importance of the surface oxide functionalities to enzyme reactivity. Keywords: Multi-walled carbon nanotubes, Surface oxides, Nitrite reductase, Direct electrochemistr

    Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

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    International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora
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