126 research outputs found

    Interiors

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    Mitochondrial function in heart failure: The impact of ischemic and non-ischemic etiology

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    Background Although cardiac mitochondrial dysfunction is associated with heart failure (HF), this is a complex syndrome with two predominant etiologies, ischemic HF (iHF) and non-ischemic HF (niHF), and the exact impact of mitochondrial dysfunction in these two distinct forms of HF is unknown. Methods and results To determine the impact of HF etiology on mitochondrial function, respiration was measured in permeabilized cardiac muscle fibers from patients with iHF (n = 17), niHF (n = 18), and healthy donor hearts (HdH). Oxidative phosphorylation capacity (OXPHOS), assessed as state 3 respiration, fell progressively from HdH to niHF, to iHF (Complex I + II: 54 ± 1; 34 ± 4; 27 ± 3 pmol·s− 1·mg− 1) as did citrate synthase activity (CSA: 206 ± 18; 129 ± 6; 82 ± 6 nmol·mg− 1·min− 1). Although still significantly lower than HdH, normalization of OXPHOS by CSA negated the difference in mass specific OXPHOS between iHF and niHF. Interestingly, Complex I state 2 respiration increased progressively from HdH, to niHF, to iHF, whether or not normalized for CSA (0.6 ± 0.2; 1.1 ± 0.3; 2.3 ± 0.3; pmol·mg− 1·CSA), such that the respiratory control ratio (RCR), fell in the same manner across groups. Finally, both the total free radical levels (60 ± 6; 46 ± 4 AU) and level of mitochondrial derived superoxide (1.0 ± 0.2; 0.7 ± 0.1 AU) were greater in iHF compared to niHF, respectively. Conclusions Thus, the HF-related attenuation in OXPHOS actually appears to be independent of etiology when the lower mitochondrial content of iHF is taken into account. However, these findings provide evidence of deleterious intrinsic mitochondrial changes in iHF, compared to niHF, including greater proton leak, attenuated OXPHOS efficiency, and augmented free radical levels

    Impacts of meeting minimum access on critical earth systems amidst the Great Inequality

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    The Sustainable Development Goals aim to improve access to resources and services, reduce environmental degradation, eradicate poverty and reduce inequality. However, the magnitude of the environmental burden that would arise from meeting the needs of the poorest is under debate—especially when compared to much larger burdens from the rich. We show that the ‘Great Acceleration’ of human impacts was characterized by a ‘Great Inequality’ in using and damaging the environment. We then operationalize ‘just access’ to minimum energy, water, food and infrastructure. We show that achieving just access in 2018, with existing inequalities, technologies and behaviours, would have produced 2–26% additional impacts on the Earth’s natural systems of climate, water, land and nutrients—thus further crossing planetary boundaries. These hypothetical impacts, caused by about a third of humanity, equalled those caused by the wealthiest 1–4%. Technological and behavioural changes thus far, while important, did not deliver just access within a stable Earth system. Achieving these goals therefore calls for a radical redistribution of resources

    In vitro and in vivo antifungal profile of a novel and long acting inhaled azole, PC945, on Aspergillus fumigatus infection

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    The profile of PC945, a novel triazole antifungal, designed for administration via inhalation, hasbeen assessed in a range of in vitro and in vivo studies. PC945 was characterized as a potent, tight-binding inhibitor of Aspergillus fumigatus sterol 14α-demethylase (CYP51A and CYP51B)activity.In addition, when A. fumigatus hyphae or human bronchial cells were treated with PC945, and thenwashed, PC945 was found to be quickly absorbed into both target and non-target cells and toproduce persistent antifungal effects. In temporarily neutropenic immunocompromised miceinfected with A. fumigatus intranasally, 50% of the animals survived until day 7 when treatedintranasally with PC945 at 0.56 Όg/mouse, while posaconazole showed similar effects (44%) at14 Όg/mouse. This profile affirms that topical treatment with PC945 should provide potentantifungal activity in the lung

    Environmentally sustainable food consumption : a review and research agenda from a goal-directed perspective

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    The challenge of convincing people to change their eating habits toward more environmentally sustainable food consumption (ESFC) patterns is becoming increasingly pressing. Food preferences, choices and eating habits are notoriously hard to change as they are a central aspect of people's lifestyles and their socio-cultural environment. Many people already hold positive attitudes toward sustainable food, but the notable gap between favorable attitudes and actual purchase and consumption of more sustainable food products remains to be bridged. The current work aims to (1) present a comprehensive theoretical framework for future research on ESFC, and (2) highlight behavioral solutions for environmental challenges in the food domain from an interdisciplinary perspective. First, starting from the premise that food consumption is deliberately or unintentionally directed at attaining goals, a goal-directed framework for understanding and influencing ESFC is built. To engage in goal-directed behavior, people typically go through a series of sequential steps. The proposed theoretical framework makes explicit the sequential steps or hurdles that need to be taken for consumers to engage in ESFC. Consumers need to positively value the environment, discern a discrepancy between the desired versus the actual state of the environment, opt for action to reduce the experienced discrepancy, intend to engage in behavior that is expected to bring them closer to the desired end state, and act in accordance with their intention. Second, a critical review of the literature on mechanisms that underlie and explain ESFC (or the lack thereof) in high-income countries is presented and integrated into the goal-directed framework. This contribution thus combines a top-down conceptualization with a bottom-up literature review; it identifies and discusses factors that might hold people back from ESFC and interventions that might promote ESFC; and it reveals knowledge gaps as well as insights on how to encourage both short- and long-term ESFC by confronting extant literature with the theoretical framework. Altogether, the analysis yields a set of 33 future research questions in the interdisciplinary food domain that deserve to be addressed with the aim of fostering ESFC in the short and long term

    Achieving a nature- and people-positive future

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    Despite decades of increasing investment in conservation, we have not succeeded in “bending the curve” of biodiversity decline. Efforts to meet new targets and goals for the next three decades risk repeating this outcome due to three factors: neglect of increasing drivers of decline; unrealistic expectations and time frames of biodiversity recovery; and insufficient attention to justice within and between generations and across countries. Our Earth system justice approach identifies six sets of actions that when tackled simultaneously address these failings: (1) reduce and reverse direct and indirect drivers causing decline; (2) halt and reverse biodiversity loss; (3) restore and regenerate biodiversity to a safe state; (4) raise minimum wellbeing for all; (5) eliminate over-consumption and excesses associated with accumulation of capital; and (6) uphold and respect the rights and responsibilities of all communities, present and future. Current conservation campaigns primarily address actions 2 and 3, with urgent upscaling of actions 1, 4, 5, and 6 needed to help deliver the post-2020 global biodiversity framework

    Safe and just Earth system boundaries

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    The stability and resilience of the Earth system and human well-being are inseparably linked 1-3, yet their interdependencies are generally under-recognized; consequently, they are often treated independently 4,5. Here, we use modelling and literature assessment to quantify safe and just Earth system boundaries (ESBs) for climate, the biosphere, water and nutrient cycles, and aerosols at global and subglobal scales. We propose ESBs for maintaining the resilience and stability of the Earth system (safe ESBs) and minimizing exposure to significant harm to humans from Earth system change (a necessary but not sufficient condition for justice) 4. The stricter of the safe or just boundaries sets the integrated safe and just ESB. Our findings show that justice considerations constrain the integrated ESBs more than safety considerations for climate and atmospheric aerosol loading. Seven of eight globally quantified safe and just ESBs and at least two regional safe and just ESBs in over half of global land area are already exceeded. We propose that our assessment provides a quantitative foundation for safeguarding the global commons for all people now and into the future

    Safe and just Earth system boundaries

    Get PDF
    The stability and resilience of the Earth system and human well-being are inseparably linked1-3, yet their interdependencies are generally under-recognized; consequently, they are often treated independently4,5. Here, we use modelling and literature assessment to quantify safe and just Earth system boundaries (ESBs) for climate, the biosphere, water and nutrient cycles, and aerosols at global and subglobal scales. We propose ESBs for maintaining the resilience and stability of the Earth system (safe ESBs) and minimizing exposure to significant harm to humans from Earth system change (a necessary but not sufficient condition for justice)4. The stricter of the safe or just boundaries sets the integrated safe and just ESB. Our findings show that justice considerations constrain the integrated ESBs more than safety considerations for climate and atmospheric aerosol loading. Seven of eight globally quantified safe and just ESBs and at least two regional safe and just ESBs in over half of global land area are already exceeded. We propose that our assessment provides a quantitative foundation for safeguarding the global commons for all people now and into the future
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