114 research outputs found

    Motivated counterfactual thinking and moral inconsistency: how we use our imaginations to selectively condemn and condone

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    People selectively enforce their moral principles, excusing wrongdoing when it suits them. We identify an underappreciated source of this moral inconsistency: the ability to imagine counterfactuals, or alternatives to reality. Counterfactual thinking offers three sources of flexibility that people exploit to justify preferred moral conclusions: People can (a) generate counterfactuals with different content (e.g., consider how things could have been better or worse), (b) think about this content using different comparison processes (i.e., focus on how it is similar to or different than reality), and (c) give the result of these processes different weights (i.e., allow counterfactuals more or less influence on moral judgments). These sources of flexibility help people license unethical behavior and can fuel political conflict. Motivated reasoning may be less constrained by facts than previously assumed; people’s capacity to condemn and condone whom they wish may be limited only by their imaginations

    Polarized imagination: partisanship influences the direction and consequences of counterfactual thinking

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    Four studies examine how political partisanship qualifies previously-documented regularities in people’s counterfactual thinking (*N* = 1,186 Democrats and Republicans). First, whereas prior work finds that people generally prefer to think about how things could have been better instead of worse (i.e., entertain counterfactuals in an upward vs. downward direction), Studies 1a–2 find that partisans are more likely to generate and endorse counterfactuals in whichever direction best aligns with their political views. Second, previous research finds that the closer someone comes to causing a negative event, the more blame that person receives; Study 3 finds that this effect is more pronounced among partisans who oppose (vs. support) a leader who “almost” caused a negative event. Thus, partisan reasoning may influence which alternatives to reality people will find most plausible, will be most likely to imagine spontaneously, and will view as sufficient grounds for blame

    Influencia de especies arbóreas implantadas sobre parámetros biológicos y bioquímicos en un suelo forestal de Chubut, Argentina

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    87-92The influence of some tree species on biological and biochemical properties of a forest soil was studied with the purpose of establishing criteria to achieve a sustainable development of a forest system. The study site is a forest soil of Chubut, in the Argentinean Patagonia. Surface soil samples were taken of three plots with a dominant species each one: Oak (Quercus robur), Ash (Fraxinus excelsior L.) and Radiata Pine (Pinus radiata D. Don.). Microbial respiration, dehydrogenase and acid phosphatase activities, counts of aerobic and amylolytic bacteria, actinomyces and fungi were determined in soil samples, while phosphorous was determines in leaves. The results showed important differences of these parameters for the different species considered in the study, differences that are explained by the different chemical composition of the vegetal species

    Propiedades microbiológicas en un suelo de la Patagonia Argentina bajo la influencia de diferentes especies forestales

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    191-197In forest systems, leaf litter is usually the main source of nutrients for the vegetation and microorganisms. Leaf litter composition may vary according to the biomass and quality of the materials produced by different species. Tree roots affect the development and activity of microflora. The aim of this study was to evaluate the influence of two implanted tree species, with different composition of plant residues, on the soil characteristics. The soil is classified as an Andisol and is located in the Trevelín Forest Station, Chubut, Argentina, Lat. 43° S, Long 71°31' West. The samples were extracted from the surface soil of two forest plots with a dominant species each: Radiata Pine (Pinus radiata D. Don.) and European Oak (Quercus robur). The following analytical determinations were carried out on soil samples: organic carbon, microbial respiration, deshydrogenase activity, microbial count (bacterial communities, amilolytic, actinomyces and fungi) as well as the functional diversity of associated microbial communities. The Shannon-Weaver index (H) was calculated. The soil under Oak trees showed the highest values of microbial respiration, organic carbon and amilolytic and bacterial community counts. No significant differences were found in deshydrogenase activity, actinomyces and fungi counts between species. The principal component analysis showed significant variations in the physiology of microbial communities associated with these two tree species. The microorganism H diversity index was significantly greater for Pine. Plants residues of broadleaf species such as Oak have lower contents of recalcitrant substances than conifer species, and this fact, associated with the higher development of total and amylolytic bacteria, could result in an increase in the decomposition of plant residues in the soil and in higher organic carbon and microbial respiration values

    Requirement for Ergosterol in V-ATPase Function Underlies Antifungal Activity of Azole Drugs

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    Ergosterol is an important constituent of fungal membranes. Azoles inhibit ergosterol biosynthesis, although the cellular basis for their antifungal activity is not understood. We used multiple approaches to demonstrate a critical requirement for ergosterol in vacuolar H+-ATPase function, which is known to be essential for fungal virulence. Ergosterol biosynthesis mutants of S. cerevisiae failed to acidify the vacuole and exhibited multiple vma− phenotypes. Extraction of ergosterol from vacuolar membranes also inactivated V-ATPase without disrupting membrane association of its subdomains. In both S. cerevisiae and the fungal pathogen C. albicans, fluconazole impaired vacuolar acidification, whereas concomitant ergosterol feeding restored V-ATPase function and cell growth. Furthermore, fluconazole exacerbated cytosolic Ca2+ and H+ surges triggered by the antimicrobial agent amiodarone, and impaired Ca2+ sequestration in purified vacuolar vesicles. These findings provide a mechanistic basis for the synergy between azoles and amiodarone observed in vitro. Moreover, we show the clinical potential of this synergy in treatment of systemic fungal infections using a murine model of Candidiasis. In summary, we demonstrate a new regulatory component in fungal V-ATPase function, a novel role for ergosterol in vacuolar ion homeostasis, a plausible cellular mechanism for azole toxicity in fungi, and preliminary in vivo evidence for synergism between two antifungal agents. New insights into the cellular basis of azole toxicity in fungi may broaden therapeutic regimens for patient populations afflicted with systemic fungal infections

    Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

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    The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential

    Group membership and racial bias modulate the temporal estimation of in-group/out-group body movements

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    Social group categorization has been mainly studied in relation to ownership manipulations involving highly-salient multisensory cues. Here, we propose a novel paradigm that can implicitly activate the embodiment process in the presence of group affiliation information, whilst participants complete a task irrelevant to social categorization. Ethnically White participants watched videos of White- and Black-skinned models writing a proverb. The writing was interrupted 7, 4 or 1 s before completion. Participants were tasked with estimating the residual duration following interruption. A video showing only hand kinematic traces acted as a control condition. Residual duration estimates for out-group and control videos were significantly lower than those for in-group videos only for the longest duration. Moreover, stronger implicit racial bias was negatively correlated to estimates of residual duration for out-group videos. The underestimation bias for the out-group condition might be mediated by implicit embodiment, affective and attentional processes, and finalized to a rapid out-group categorization

    Identification of Antifungal Compounds Active against Candida albicans Using an Improved High-Throughput Caenorhabditis elegans Assay

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    Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans–C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay
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