Upon infection, Mycobacterium tuberculosis (Mtb) metabolically alters the macrophage to create a niche that is ideally suited to its persistent lifestyle. Infected macrophages acquire a "foamy" phenotype characterized by the accumulation of lipid bodies (LBs), which serve as both a source of nutrients and a secure niche for the bacterium. While the functional significance of the foamy phenotype is appreciated, the biochemical pathways mediating this process are understudied. We found that Mtb induces the foamy phenotype via targeted manipulation of host cellular metabolism to divert the glycolytic pathway toward ketone body synthesis. This dysregulation enabled feedback activation of the anti-lipolytic G protein-coupled receptor GPR109A, leading to perturbations in lipid homeostasis and consequent accumulation of LBs in the macrophage. ESAT-6, a secreted Mtb virulence factor, mediates the enforcement of this feedback loop. Finally, we demonstrate that pharmacological targeting of pathways mediating this host-pathogen metabolic crosstalk provides a potential strategy for developing tuberculosis chemotherapy.
Solar energy installations in arid and semi-arid regions are rapidly increasing due to technological advances and policy support. Although solar energy provides several benefits such as reduction of greenhouse gases, reclamation of degraded land, and improved quality of life in developing countries, the deployment of large-scale renewable energy infrastructure may negatively impact land and water resources. Meeting the ever-expanding energy demand with limited land and water resources in the context of increasing demand for alternative uses such as agricultural and domestic consumption is a major challenge. The goal of this study was to explore opportunities to colocate solar infrastructures and agricultural crops to maximize the efficiency of land and water use. We investigated the energy inputs/outputs, water use, greenhouse gas emissions, and economics of solar installations in northwestern India in comparison to aloe vera cultivation, another widely promoted and economically important land use in these systems. The life cycle analyses show that the colocated systems are economically viable in some rural areas and may provide opportunities for rural electrification and stimulate economic growth. The water inputs for cleaning solar panels are similar to amounts required for annual aloe productivity, suggesting the possibility of integrating the two systems to maximize land and water use efficiency. A life cycle analysis of a hypothetical colocation indicated higher returns per m 3 of water used than either system alone. The northwestern region of India has experienced high population growth in the past decade, creating additional demand for land and water resources. In these water-limited areas, coupled solar infrastructure and agriculture could be established in marginal lands with low water use, thus minimizing the socioeconomic and environmental issues resulting from cultivation of economically important non-food crops (e.g., aloe) in prime agricultural lands.
Neuronal network topologies and connectivity patterns were explored in control and glutamate-injured hippocampal neuronal networks, cultured on planar multielectrode arrays. Spontaneous activity was characterized by brief episodes of synchronous firing at many sites in the array (network bursts). During such assembly activity, maximum numbers of neurons are known to interact in the network. After brief glutamate exposure followed by recovery, neuronal networks became hypersynchronous and fired network bursts at higher frequency. Connectivity maps were constructed to understand how neurons communicate during a network burst. These maps were obtained by analysing the spike trains using cross-covariance analysis and graph theory methods. Analysis of degree distribution, which is a measure of direct connections between electrodes in a neuronal network, showed exponential and Gaussian distributions in control and glutamate-injured networks, respectively. Although both the networks showed random features, smallworld properties in these networks were different. These results suggest that functional two-dimensional neuronal networks in vitro are not scale-free. After brief exposure to glutamate, normal hippocampal neuronal networks became hyperexcitable and fired a larger number of network bursts with altered network topology. The small-world network property was lost and this was accompanied by a change from an exponential to a Gaussian network.
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