1,901 research outputs found
Territorial development and Community currencies
Brazilian community development banks (CDBs) have established various coordinated financial mechanisms aiming to restructure poor and peripheral local economies. Their development strategy includes an instrument to facilitate access to microfinance and a community currency, combined with the definition of vocational training programmes and support for business start- ups. Put together, these different activities constitute the endogenous and resilient territorial development strategy defined by CDBs. Little scientific literature has been devoted to the study of community currencies in this process. This article presents an overview of the symbolic meanings conveyed by the currency of Banco Palmas, the first and most prominent CDB. First, we present some historical and territorial characteristics of Banco Palmas. Second, we analyse the symbolic role of its currency: money as a bond/link (the building of the community on its territory); money as a medium for institutionalisation (of the community itself and to the exogenous actors, as to define a federative project); and finally money as a vector-catalyst (when the plasticity of money allows to explore its different formats and so, to adapt it to the new perspectives of community and territorial development)
the ethics of alternative currencies
Alternative currencies are means of payment that circulate alongside—as an alternative or complement to—official currencies. While these currencies have existed for a long time, both society and academia have shown a renewed interest in their potential to decentralize the governance of monetary affairs and to bring people and organizations together in more ethical or sustainable ways. This article is a review of the ethical and philosophical implications of these alternative monetary projects. We first discuss various classifications of these currencies before analyzing the ethical challenges linked to the way they tackle social and environmental issues. We also examine the incentive-based and coercive mechanisms used by these currencies from an ethical perspective and debate the promises and perils of monetary decentralization and democracy. We conclude by identifying an agenda for future research
Environmental Contaminants in the Lake Huron to Erie Corridor: Effects on Zebrafish
Contaminants of emerging concern (CECs) and endocrine-disrupting chemicals (EDCs) include pharmaceutical, personal care, agricultural, and industrial byproducts that enter waterways via effluent, runoff, aging infrastructure, and inadequate wastewater treatment. The Detroit River is an Area of Concern, but the drinking water source for ~4 million people, hub of >30% of Michigan’s fishing effort, and home to vital habitats. Zebrafish are advantageous for such complex issues due to short generation times and large numbers of synchronously developing fish. We investigate early development or chronic exposure of zebrafish to Detroit River water and evaluate changes in embryonic development, behavior, reproductive capacity, sex ratio, offspring survival, transcriptome, and epigenome. We also analyze water samples in the Lake Huron to Erie corridor for CECs and EDCs, and then evaluate the same endpoints in zebrafish exposed to these chemicals at environmentally-relevant levels, either singly or in mixtures. This multi-pronged approach has implications for local human and fish health, water treatment/sewage infrastructure, remediation/restoration efforts, natural resource management, public education, and community revitalization.Ope
Annual Student Exhibition 2015: Senior Capstone Gallery Guide
We are pleased to present the inaugural edition of the Senior Capstone Gallery Guide, a collaboration between the graduating Studio Art and Art History Majors. This publication and the exhibition it accompanies celebrate the achievements of the Department\u27s Class of 2015
Iron accumulation drives fibrosis, senescence, and the senescence-associated secretory phenotype
Enhanced Pathogenesis Caused by Influenza D Virus and Mycoplasma bovis Coinfection in Calves: a Disease Severity Linked with Overexpression of IFN-gamma as a Key Player of the Enhanced Innate Immune Response in Lungs
Bovine respiratory disease (BRD) is a major disease of young cattle whose etiology lies in complex interactions between pathogens and environmental and host factors. Despite a high frequency of codetection of respiratory pathogens in BRD, data on the molecular mechanisms and pathogenesis associated with viral and bacterial interactions are still limited. In this study, we investigated the effects of a coinfection with influenza D virus (IDV) and Mycoplasma bovis in cattle. Naive calves were infected by aerosol with a French IDV strain and an M. bovis strain. The combined infection shortened the incubation period, worsened the disease, and led to more severe macroscopic and microscopic lesions compared to these parameters in calves infected with only one pathogen. In addition, IDV promoted colonization of the lower respiratory tract (LRT) by M. bovis and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The gamma interferon (IFN-gamma) gene was shown to be the gene most statistically overexpressed after coinfection at 2 days postinfection (dpi) and at least until 7 dpi, which correlated with the high level of lymphocytes in the LRT. Downregulation of the PACE4 and TMPRSS2 endoprotease genes was also highlighted, being a possible reason for the faster clearance of IDV in the lungs of coinfected animals. Taken together, our coinfection model with two respiratory pathogens that when present alone induce moderate clinical signs of disease was shown to increase the severity of the disease in young cattle and a strong transcriptomic innate immune response in the LRT, especially for IFN-gamma.IMPORTANCE Bovine respiratory disease (BRD) is among the most prevalent diseases in young cattle. BRD is due to complex interactions between viruses and/or bacteria, most of which have a moderate individual pathogenicity. In this study, we showed that coinfection with influenza D virus (IDV) and Mycoplasma bovis increased the severity of the respiratory disease in calves in comparison with IDV or M. bovis infection. IDV promoted M. bovis colonization of the lower respiratory tract and increased white cell recruitment to the airway lumen. The transcriptomic analysis highlighted an upregulation of immune genes in the lungs of coinfected calves. The IFN-gamma gene in particular was highly overexpressed after coinfection, correlated with the disease severity, immune response, and white cell recruitment in the lungs. In conclusion, we showed that IDV facilitates coinfections within the BRD complex by modulating the local innate immune response, providing new insights into the mechanisms involved in severe respiratory diseases
Development of resistance to type II JAK2 inhibitors in MPN depends on AXL kinase and is targetable.
PURPOSE
Myeloproliferative neoplasms (MPN) dysregulate JAK2 signaling. Since clinical JAK2 inhibitors have limited disease-modifying effects, type II JAK2 inhibitors such as CHZ868 stabilizing inactive JAK2 and reducing MPN clones, gain interest. We studied whether MPN cells escape from type ll inhibition.
METHODS
MPN cells were continuously exposed to CHZ868. We used phosphoproteomic analyses and ATAC-/RNA-sequencing to characterize acquired resistance to type II JAK2 inhibition, and targeted candidate mediators in MPN cells and mice.
RESULTS
MPN cells showed increased IC50 and reduced apoptosis upon CHZ868 reflecting acquired resistance to JAK2 inhibition. Among >2500 differential phospho-sites, MAPK pathway activation was most prominent, while JAK2-STAT3/5 remained suppressed. Altered histone occupancy promoting AP-1/GATA binding motif exposure associated with upregulated AXL kinase and enriched RAS target gene profiles. AXL knockdown resensitized MPN cells and combined JAK2/AXL inhibition using bemcentinib or gilteritinib reduced IC50 to levels of sensitive cells. While resistant cells induced tumor growth in NSG mice despite JAK2 inhibition, JAK2/AXL inhibition largely prevented tumor progression. Since inhibitors of MAPK pathway kinases such as MEK are clinically used in other malignancies, we evaluated JAK2/MAPK inhibition with trametinib to interfere with AXL-MAPK-induced resistance. Tumor growth was halted similarly to JAK2/AXL inhibition and in a systemic cell line-derived mouse model, marrow infiltration was decreased supporting dependency on AXL-MAPK.
CONCLUSIONS
We report on a novel mechanism of AXL-MAPK-driven escape from type II JAK2 inhibition, which is targetable at different nodes. This highlights AXL as mediator of acquired resistance warranting inhibition to enhance sustainability of JAK2 inhibition in MPN
Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial – CADOT
IntroductionAmong treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines.MethodOut of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity – QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning – GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st – 3rd quartile) of 4 (1–9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11–33) months after remission.ResultsAt the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38–66%]). After DATA step 2, 37 patients were in remission (77% [65–89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78–97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62–95%]).ConclusionThese results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s)
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