Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease

Therapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strains would be valuable for orienting physicians towards alternative therapies, with a combination of existing drugs or new anti-T. cruzi agents. We developed a procedure that couples the isolation of parasites by haemoculture with quantification of BZ susceptibility in the resultant epimastigote forms. BZ activity was standardized with reference strains, which showed IC50 to BZ between 7.6-32 µM. The assay was then applied to isolates from seven chronic patients prior to administration of BZ therapy. The IC50 of the strains varied from 15.6 ± 3-51.4 ± 1 µM. Comparison of BZ susceptibility of the pre-treatment isolates of patients considered cured by several criteria and of non-cured patients indicates that the assay does not predict therapeutic outcome. A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out.FAPESPCNP

Trypanosoma cruzi high infectivity in vitro is related to cardiac lesions during long-term infection in Beagledogs

Trypanosoma cruzi is a hemoflagelate parasite associated with heart dysfunctions causing serious problems in Central and South America. Beagle dogs develop the symptoms of Chagas disease in humans, and could be an important experimental model for better understanding the immunopathogenic mechanisms involved in the chagasic infection. In the present study we investigated the relation among biological factors inherent to the parasite (trypomastigote polymorphism and in vitro infectivity) and immunoglobulin production, inflammation, and fibrosis in the heart of Beagle dogs infected with either T. cruzi Y or Berenice-78 strains. In vitro infectivity of Vero cells as well as the extension of cardiac lesions in infected Beagle was higher for Y strain when compared to Berenice-78 strain. These data suggested that in vitro infectivity assays may correlate with pathogenicity in vivo. In fact, animals infected with Y strain, which shows prevalence of slender forms and high infectivity in vitro, presented cardiomegaly, inflammation, and fibrosis in heart area. Concerning the immunoglobulin production, no statistically significant difference was observed for IgA, IgM or IgG levels among T. cruzi infected animals. However, IgA together IgM levels have shown to be a good marker for the acute phase of Chagas disease

Agroecology and climate change rapid evidence review: Performance of agroecological approaches in low- and middle- income countries

Agroecology is increasingly seen as being able, or even necessary, to transform food systems (HLPE 2019). The Foreign, Commonwealth and Development Office (FCDO) and the CGIAR Research Programme on Climate Change, Agriculture and Food Security (CCAFS) commissioned this rapid evidence-based review to assess the quality and strength of evidence regarding (i) the impact of agroecological approaches on climate change mitigation and adaptation in low- and middle-income countries (LMICs) and (ii) the programming approaches and conditions supporting large-scale transitions to agroecology and transitions. The review also aims to identify knowledge gaps critical to understand and inform future public and private investment in research, development, and deployment of agroecological approaches. The focus here is on the science of agroecology at the field and landscape level, not on social movement, value chain or business aspects. We use the Food and Agriculture Organization of the United Nations (FAO) 10 elements of agroecology with the Gliessman (2016) framework to identify agroecology practices (transition level 2) and agroecology systems (transition level 3). To assess evidence related to agroecology‘s climate change outcomes we conducted a systematic literature review of i) synthesis papers and ii) primary empirical studies related to nutrient and pest and disease management. For the latter we documented the presence of evidence for climate change outcome indicators, but not the magnitude or direction of the change. We also conducted semi-structured interviews with representatives from 12 organizations supporting or implementing on-the-ground agricultural development programmes to better understand the feasibility of scaling out agroecology

Agroecology can promote climate change adaptation outcomes without compromising yield in smallholder systems

A critical question is whether agroecology can promote climate change mitigation and adaptation outcomes without compromising food security. We assessed the outcomes of smallholder agricultural systems and practices in low- and middle-income countries (LMICs) against 35 mitigation, adaptation, and yield indicators by reviewing 50 articles with 77 cases of agroecological treatments relative to a baseline of conventional practices. Crop yields were higher for 63% of cases reporting yields. Crop diversity, income diversity, net income, reduced income variability, nutrient regulation, and reduced pest infestation, indicators of adaptative capacity, were associated with 70% or more of cases. Limited information on climate change mitigation, such as greenhouse gas emissions and carbon sequestration impacts, was available. Overall, the evidence indicates that use of organic nutrient sources, diversifying systems with legumes and integrated pest management lead to climate change adaptation in multiple contexts. Landscape mosaics, biological control (e.g., enhancement of beneficial organisms) and field sanitation measures do not yet have sufficient evidence based on this review. Widespread adoption of agroecological practices and system transformations shows promise to contribute to climate change services and food security in LMICs. Gaps in adaptation and mitigation strategies and areas for policy and research interventions are finally discussed

Bulletin No. 9: Six points of Especial Botanical Interest in Connecticut

The areas described are the Barn Island Marshes, the Connecticut Arboretum, the North Haven Sand Plains, Catlin Wood, Cathedral Pines and the Bigelow Pond Hemlocks. 32 pp

The lag-phase during diauxic growth is a trade-off between fast adaptation and high growth rate

Bi-phasic or diauxic growth is often observed when microbes are grown in a chemically defined medium containing two sugars (for example glucose and lactose). Typically, the two growth stages are separated by an often lengthy phase of arrested growth, the so-called lag-phase. Diauxic growth is usually interpreted as an adaptation to maximise population growth in multi-nutrient environments. However, the lag-phase implies a substantial loss of growth during the switch-over. It therefore remains unexplained why the lag-phase is adaptive. Here we show by means of a stochastic simulation model based on the bacterial PTS system that it is not possible to shorten the lag-phase without incurring a permanent growth-penalty. Mechanistically, this is due to the inherent and well established limitations of biological sensors to operate efficiently at a given resource cost. Hence, there is a trade-off between lost growth during the diauxic switch and the long-term growth potential of the cell. Using simulated evolution we predict that the lag-phase will evolve depending on the distribution of conditions experienced during adaptation. In environments where switching is less frequently required, the lag-phase will evolve to be longer whereas, in frequently changing environments, the lag-phase will evolve to be shorter

On the Peripheries of Planetary Urbanization: Globalizing Manaus and its Expanding Impact

In this paper I argue that global urbanism produces peripherality in ways that cannot be adequately problematized without taking into account its actual extent and geographically uneven development. Therefore, planetary urbanization needs to engage scholarly traditions attuned to regional urbanization if the discourse is to move past limitations in the urban globalization canon and its narrow focus on cities. To that end, I examine research on extensive urbanization in the Amazon region. Illustrative case studies show how attempts to globalize Manaus precipitated territorial restructuring and sociospatial change far beyond the city's boundaries. Manaus is now a more unequal city. Selective metropolitan expansion to the Rio Negro's south bank has led to the simultaneous upgrading and peripheralization of Iranduba. Yet, the building of a city-centric regional network of roadways also shaped Roraima State's transformation from isolated borderland to bypassed periphery. Moreover, financial and symbolic appropriations of standing rainforests by metropolitan conservationism marginalize remote communities even in the absence of exploitative deforestation and resource extraction. Final remarks emphasize the need for further research on the hybrid (urban—rural) conditions and functional articulations of distant-yet-impacted peripheries. Such efforts may broaden the political horizons of planetary urbanization by informing extensive contestations of entrepreneurial urbanism

(Dis)entangling Barad: Materialisms and ethics

In the wake of the widespread uptake of and debate surrounding the work of Karen Barad, this article revisits her core conceptual contributions. We offer descriptions, elaborations, problematizations and provocations for those intrigued by or invested in this body of work. We examine Barad’s use of quantum physics, which underpins her conception of the material world. We discuss the political strengths of this position but also note tensions associated with applying quantum physics to phenomena at macro-scales. We identify both frictions and unacknowledged affinities with science and technology studies in Barad’s critique of reflexivity and her concept of diffraction. We flesh out Barad’s overarching position of ‘agential realism’, which contains a revised understanding of scientific apparatuses. Building upon these discussions, we argue that inherent in agential realism is both an ethics of inclusion and an ethics of exclusion. Existing research has, however, frequently emphasized entanglement and inclusion to the detriment of foreclosure and exclusion. Nonetheless, we contend that it is in the potential for an ethics of exclusion that Barad’s work could be of greatest utility within science and technology studies and beyond