Grassroots Agency: Participation and Conflict in Buenos Aires Shantytowns seen through the Pilot Plan for Villa 7 (1971–1975)

open access articleIn 1971, after more than a decade of national and municipal policies aimed at the top-down removal of shantytowns, the Buenos Aires City Council approved the Plan Piloto para la Relocalización de Villa 7 (Pilot Plan for the Relocation of Shantytown 7; 1971–1975, referred to as the Pilot Plan hereinafter). This particular plan, which resulted in the construction of the housing complex, Barrio Justo Suárez, endures in the collective memory of Argentines as a landmark project regarding grassroots participation in state housing initiatives addressed at shantytowns. Emerging from a context of a housing shortage for the growing urban poor and intense popular mobilizations during the transition to democracy, the authors of the Pilot Plan sought to empower shantytown residents in novel ways by: 1) maintaining the shantytown’s location as opposed to eradication schemes that relocated the residents elsewhere, 2) formally employing some of the residents for the stage of construction, as opposed to “self-help” housing projects in which the residents contributed with unpaid labor, and 3) including them in the urban and architectural design of the of the new housing. This paper will examine the context in which the Pilot Plan was conceived of as a way of re-assessing the roles of the state, the user, and housing-related professionals, often seen as antagonistic. The paper argues that residents’ fair participation and state intervention in housing schemes are not necessarily incompatible, and can function in specific social and political contexts through multiactor proposals backed by a political will that prioritizes grassroots agency

Environmental Report 1998

This summary provides an overview of LLNL's environmental activities in 1998, including radiological and nonradiological surveillance, effluent, and compliance monitoring, remediation, assessment of radiological releases and doses, and determination of the impact of LLNL operations on the environment and public health

Histamine Derived from Probiotic Lactobacillus reuteri Suppresses TNF via Modulation of PKA and ERK Signaling

Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases

MAP4K4 Inhibition Promotes Survival of Human Stem Cell-Derived Cardiomyocytes and Reduces Infarct Size In Vivo

Heart disease is a paramount cause of global death and disability. Although cardiomyocyte death plays a causal role and its suppression would be logical, no clinical counter-measures target the responsible intracellular pathways. Therapeutic progress has been hampered by lack of preclinical human validation. Mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) is activated in failing human hearts and relevant rodent models. Using human induced-pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs) and MAP4K4 gene silencing, we demonstrate that death induced by oxidative stress requires MAP4K4. Consequently, we devised a small-molecule inhibitor, DMX-5804, that rescues cell survival, mitochondrial function, and calcium cycling in hiPSC-CMs. As proof of principle that drug discovery in hiPSC-CMs may predict efficacy in vivo, DMX-5804 reduces ischemia-reperfusion injury in mice by more than 50%. We implicate MAP4K4 as a well-posed target toward suppressing human cardiac cell death and highlight the utility of hiPSC-CMs in drug discovery to enhance cardiomyocyte survival

Proton and zinc effects on HERG currents.

The proton and Zn2+ effects on the human ether-a-go-go related gene (HERG) channels were studied after expression in Xenopus oocytes and stable transfection in the mammalian L929 cell line. Experiments were carried out using the two-electrode voltage clamp at room temperature (oocytes) or the whole-cell patch clamp technique at 35 degrees C (L929 cells). In oocytes, during moderate extracellular acidification (pHo = 6.4), current activation was not shifted on the voltage axis, the time course of current activation was unchanged, but tail current deactivation was dramatically accelerated. At pHo < 6.4, in addition to accelerating deactivation, the time course of activation was slower and the midpoint voltage of current activation was shifted to more positive values. Protons and Zn2+ accelerated the kinetics of deactivation with apparent Kd values about one order of magnitude lower than for tail current inhibition. For protons, the Kd values for the effect on tail current amplitude versus kinetics were, respectively, 1.8 microM (pKa = 5.8) and 0.1 microM (pKa = 7.0). In the presence of Zn2+, the corresponding Kd values were, respectively, 1.2 mM and 169 microM. In L929 cells, acidification to pHo = 6.4 did not shift the midpoint voltage of current activation and had no effect on the time course of current activation. Furthermore, the onset and recovery of inactivation were not affected. However, the acidification significantly accelerated tail current deactivation. We conclude that protons and Zn2+ directly interact with HERG channels and that the interaction results, preferentially, in the regulation of channel deactivation mechanism