Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4+ lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4+ T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R–deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.

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SUMMARY Autism spectrum disorder (ASD) is a disorder of brain development. Most cases lack a clear etiology or genetic basis, and the difficulty of reenacting human brain development has precluded understanding of ASD pathophysiology. Here we use three-dimensional neural cultures (organoids) derived from induced pluripotent stem cells (iPSCs) to investigate neurodevelopmental alterations in individuals with severe idiopathic ASD. While no known underlying genomic mutation could be identified, transcriptome and gene network analyses revealed upregulation of genes involved in cell proliferation, neuronal differentiation, and synaptic assembly. ASD-derived organoids exhibit an accelerated cell cycle and overproduction of GABAergic inhibitory neurons. Using RNA interference, we show that overexpression of the transcription factor FOXG1 is responsible for the overproduction of GABAergic neurons. Altered expression of gene network modules and FOXG1 are positively correlated with symptom severity. Our data suggest that a shift towards GABAergic neuron fate caused by FOXG1 is a developmental precursor of ASD.

Impervious surface area (ISA) from the Landsat TM-based NLCD 2001 dataset and land surface temperature (LST) from MODIS averaged over three annual cycles (2003)(2004)(2005) are used in a spatial analysis to assess the urban heat island (UHI) skin temperature amplitude and its relationship to development intensity, size, and ecological setting for 38 of the most populous cities in the continental United States. Development intensity zones based on %ISA are defined for each urban area emanating outward from the urban core to the nonurban rural areas nearby and used to stratify sampling for land surface temperatures and NDVI. Sampling is further constrained by biome and elevation to insure objective intercomparisons between zones and between cities in different biomes permitting the definition of hierarchically ordered zones that are consistent across urban areas in different ecological setting and across scales. We find that ecological context significantly influences the amplitude of summer daytime UHI (urban-rural temperature difference) the largest (8°C average) observed for cities built in biomes dominated by temperate broadleaf and mixed forest. For all cities combined, ISA is the primary driver for increase in temperature explaining 70% of the total variance in LST. On a yearly average, urban areas are substantially warmer than the non-urban fringe by 2.9°C, except for urban areas in biomes with arid and semiarid climates. The average amplitude of the UHI is remarkably asymmetric with a 4.3°C temperature difference in summer and only 1.3°C in winter. In desert environments, the LST's response to ISA presents an uncharacteristic "U-shaped" horizontal gradient decreasing from the urban core to the outskirts of the city and then increasing again in the suburban to the rural zones. UHI's calculated for these cities point to a possible heat sink effect. These observational results show that the urban heat island amplitude both increases with city size and is seasonally asymmetric for a large number of cities across most biomes. The implications are that for urban areas developed within forested ecosystems the summertime UHI can be quite high relative to the wintertime UHI suggesting that the residential energy consumption required for summer cooling is likely to increase with urban growth within those biomes.Published by Elsevier Inc.

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Unraveling the drivers of community structure and succession in response to environmental change is a central goal in ecology. Although the mechanisms shaping community structure have been intensively examined, those controlling ecological succession remain elusive. To understand the relative importance of stochastic and deterministic processes in mediating microbial community succession, a unique framework composed of four different cases was developed for fluidic and nonfluidic ecosystems. The framework was then tested for one fluidic ecosystem: a groundwater system perturbed by adding emulsified vegetable oil (EVO) for uranium immobilization. Our results revealed that groundwater microbial community diverged substantially away from the initial community after EVO amendment and eventually converged to a new community state, which was closely clustered with its initial state. However, their composition and structure were significantly different from each other. Null model analysis indicated that both deterministic and stochastic processes played important roles in controlling the assembly and succession of the groundwater microbial community, but their relative importance was time dependent. Additionally, consistent with the proposed conceptual framework but contradictory to conventional wisdom, the community succession responding to EVO amendment was primarily controlled by stochastic rather than deterministic processes. During the middle phase of the succession, the roles of stochastic processes in controlling community composition increased substantially, ranging from 81.3% to 92.0%. Finally, there are limited successional studies available to support different cases in the conceptual framework, but further well-replicated explicit time-series experiments are needed to understand the relative importance of deterministic and stochastic processes in controlling community succession.community assembly | disturbances | metagenomics | GeoChip | remediation

This study examines whether differences in proxies for audit quality between Big 4 and non-Big 4 audit firms could be a reflection of their respective clients’ characteristics. In our analyses, we use three audit-quality proxies—discretionary accruals, the ex ante cost-of-equity capital, and analyst forecast accuracy—and employ propensity-score and attribute-based matching models in attempt to control for differences in client characteristics between the two auditor groups while estimating the audit-quality effects. Using these matching models, we find that the effects of Big 4 auditors are insignificantly different from those of non-Big 4 auditors with respect to the three audit-quality proxies. Our results suggest that differences in these proxies between Big 4 and non-Big 4 auditors largely reflect client characteristics and, more specifically, client size. We caution the reader that this study has not resolved the question, although we hope that it encourages other researchers to explore alternative methodologies that separate client characteristics from audit-quality effects.