Complementary Immune Roles for Infected and Uninfected Cells During Legionella Pneumophila infection

The innate immune system responds to virulent pathogens, yet many pathogens manipulate host-signaling pathways, which should limit immune activation. The intracellular bacterium Legionella pneumophila is the cause of the severe pneumonia Legionnaire\u27s disease. L. pneumophila encodes a type IV secretion system (T4SS) to translocate bacterial proteins into the cytosol of infected host cells. Several of these bacterial effectors (Lgt1, Lgt2, Lgt3, SidI, SidL, Pkn5, and Lpg1489) inactivate host cell elongation factors involved in protein translation. Despite the ability of L. pneumophila to block host protein translation, inflammatory cytokines are still made during infection both in vivo and in vitro. It is unclear how infected cells can mount a cytokine response when host protein synthesis is blocked. By creating a fluorescence resonance energy transfer-based system to track the activity of the T4SS in infected host cells, this study investigates how innate immune cells produce cytokines during L. pneumophila infection. In vitro, cells targeted by the T4SS of L. pneumophila are poor producers of cytokines critical for control of infection, such as TNF, IL-6, IL-12, and do not express CD86 in response to infection. Instead, uninfected, bystander cells produce these cytokines. Infected host cells do produce IL-1alpha; and IL-1beta; de novo and transcribe many proinflammatory genes. During pulmonary infection, alveolar macrophages and neutrophils are targeted by the T4SS for translocation and contain viable L. pneumophila. These cells provide a niche for bacterial replication during infection, but also secrete IL-1 in response to virulent bacteria. Uninfected alveolar macrophages, neutrophils, as well as inflammatory monocytes and dendritic cells produce TNF during L. pneumophila infection in vivo. Inflammatory monocytes and dendritic cells also increase CD86 expression during infection. Importantly, this bystander TNF production and CD86 expression requires IL-1 signaling, as mice deficient for the IL-1R have diminished levels of TNF and CD86 expression during infection. These data suggest that infected cells have mechanisms to overcome protein synthesis inhibition to produce IL-1 and that uninfected bystander cells are important contributors to the immune response during infection with L. pneumophila. This mechanism of immune activation has broad significance as many other bacterial pathogens manipulate host cell processes, including immune cell signaling

Infiltration and short-term movement of nitrogen in a silt-loam soil typical of rice cultivation in Arkansas

Rice production in Arkansas is one of the top three crop commodities in terms of cash receipts. Researchers and farmers report that nitrogen (N) needs to be managed according to a variety of factors with two important ones being soil and fertilizer type. The objectives of this experiment were to determine: 1) the degree to which floodwater-incorporated N applied as urea or as ammonium sulfate infiltrates intact cores (7.2-cm dia., 10-cm depth) containing DeWitt siltloam soil, and 2) the distribution of N during 12 h of ponding. Inorganic-N concentrations were analyzed at 2-cm depth intervals in cores following removal of the flood. Nitrogen from applied fertilizer was recovered as ammonium. Ammonium sulfate-N remained in the top 4 cm of soil with concentrations of 375 µg N g-1 in the surface 2 cm and 300 µg N g-1 at the 2 - 4 cm depth after 12 hr of ponding. At all depth intervals below 4 cm, ammonium sulfate-N remained below 30 µg N g-1. In contrast, after 12 h of ponding, N in soil receiving urea was 105 µg N g-1 in the top 2 cm and 173 µg N g-1 at 2-4 cm. At 4-6, 6-8, and 8-10 cm, N was 109, 108, and 35 µg N g-1, respectively, after 12 h of ponding. These results demonstrate immediate and deeper movement of ammonium into silt loam soil receiving urea as compared to ammonium sulfate, demonstrating how the form of N in fertilizer affects its movement into the soil profile

Species Interactions Weakly Modify Climate-Induced Tree Co-Occurrence Patterns

Aims: Species distributions are hypothesized to be underlain by a complex association of processes that span multiple spatial scales including biotic interactions, dispersal limitation, fine-scale resource gradients and climate. Species disequilibrium with climate may reflect the effects of non-climatic processes on species distributions, yet distribution models have rarely directly considered non-climatic processes. Here, we use a Joint Species Distribution Model (JSDM) to investigate the influence of non-climatic factors on species co-occurrence patterns and to directly quantify the relative influences of climate and alternative processes that may generate correlated responses in species distributions, such as species interactions, on tree co-occurrence patterns. Location: US Rocky Mountains. Methods: We apply a Bayesian JSDM to simultaneously model the co-occurrence patterns of ten dominant tree species across the Rocky Mountains, and evaluate climatic and residual correlations from the fitted model to determine the relative contribution of each component to observed co-occurrence patterns. We also evaluate predictions generated from the fitted model relative to a single-species modelling approach. Results: For most species, correlation due to climate covariates exceeded residual correlation, indicating an overriding influence of broad-scale climate on co-occurrence patterns. Accounting for covariance among species did not significantly improve predictions relative to a single-species approach, providing limited evidence for a strong independent influence of species interactions on distribution patterns. Conclusions: Overall, our findings indicate that climate is an important driver of regional biodiversity patterns and that interactions between dominant tree species contribute little to explain species co-occurrence patterns among Rocky Mountain trees

Method and system for environmentally adaptive fault tolerant computing

A method and system for adapting fault tolerant computing. The method includes the steps of measuring an environmental condition representative of an environment. An on-board processing system's sensitivity to the measured environmental condition is measured. It is determined whether to reconfigure a fault tolerance of the on-board processing system based in part on the measured environmental condition. The fault tolerance of the on-board processing system may be reconfigured based in part on the measured environmental condition

The Role of Chromatid Interference in Determining Meiotic Crossover Patterns

Plants, like all sexually reproducing organisms, create genetic variability by reshuffling parental alleles during meiosis. Patterns of genetic variation in the resulting gametes are determined by the independent assortment of chromosomes in meiosis I and by the number and positioning of crossover (CO) events during meiotic recombination. On the chromosome level, spatial distribution of CO events is biased by multiple regulatory mechanisms, such as CO assurance, interference and homeostasis. However, little is known about how multiple COs are distributed among the four chromatids of a bivalent. Chromatid interference (CI) has been proposed as a regulatory mechanism that biases distribution of multiple COs toward specific chromatid partners, however, its existence has not been well-studied and its putative mechanistic basis remains undescribed. Here, we introduce a novel method to quantitatively express CI, and take advantage of available tetrad-based genotyping data from Arabidopsis and maize male meiosis to quantify CI effects on a genome-wide and chromosomal scale. Overall, our analyses reveal random involvement of sister chromatids in double CO events across paired chromosomes, indicating an absence of CI. However, on a genome-wide level, CI was found to vary with physical distance between COs, albeit with different effects in Arabidopsis and maize. While effects of CI are minor in Arabidopsis and maize, the novel methodology introduced here enables quantitative interpretation of CI both on a local and genome-wide scale, and thus provides a key tool to study CI with relevance for both plant genetics and crop breeding

Amyloid Precursor Proteins Are Dynamically Trafficked and Processed during Neuronal Development

Proteolytic processing of the Amyloid Precursor Protein (APP) produces beta-amyloid (Aβ) peptide fragments that accumulate in Alzheimer’s Disease (AD), but APP may also regulate multiple aspects of neuronal development, albeit via mechanisms that are not well understood. APP is a member of a family of transmembrane glycoproteins expressed by all higher organisms, including two mammalian orthologs (APLP1 and APLP2) that have complicated investigations into the specific activities of APP. By comparison, insects express only a single APP-related protein (APP-Like, or APPL) that contains the same protein interaction domains identified in APP. However, unlike its mammalian orthologs, APPL is only expressed by neurons, greatly simplifying an analysis of its functions in vivo. Like APP, APPL is processed by secretases to generate a similar array of extracellular and intracellular cleavage fragments, as well as an Aβ-like fragment that can induce neurotoxic responses in the brain. Exploiting the complementary advantages of two insect models (Drosophila melanogaster and Manduca sexta), we have investigated the regulation of APPL trafficking and processing with respect to different aspects of neuronal development. By comparing the behavior of endogenously expressed APPL with fluorescently tagged versions of APPL and APP, we have shown that some full-length protein is consistently trafficked into the most motile regions of developing neurons both in vitro and in vivo. Concurrently, much of the holoprotein is rapidly processed into N- and C-terminal fragments that undergo bi-directional transport within distinct vesicle populations. Unexpectedly, we also discovered that APPL can be transiently sequestered into an amphisome-like compartment in developing neurons, while manipulations targeting APPL cleavage altered their motile behavior in cultured embryos. These data suggest that multiple mechanisms restrict the bioavailability of the holoprotein to regulate APPL-dependent responses within the nervous system. Lastly, targeted expression of our double-tagged constructs (combined with time-lapse imaging) revealed that APP family proteins are subject to complex patterns of trafficking and processing that vary dramatically between different neuronal subtypes. In combination, our results provide a new perspective on how the regulation of APP family proteins can be modulated to accommodate a variety of cell type-specific responses within the embryonic and adult nervous system

Adapting an Evidence-Based Intervention Targeting HIV-Infected Prisoners in Malaysia

HIV-infected prisoners in Malaysia represent a critical target population for secondary HIV risk reduction interventions and care. We report on the process and outcome of our formative research aimed at systematically selecting and adapting an EBI designed to reduce secondary HIV risk and improve adherence to antiretroviral therapy among soon-to-be-released HIV-infected prisoners. Our formative work involved a critical examination of established EBIs and associated published reports complemented by data elicited through structured interviews and focus groups with key stakeholders, members of the target population, and their family members. Based on all information, we adapted the Holistic Health Recovery Program targeting people living with HIV (HHRP+), an EBI, to consist of eight 2-hour sessions that cover a range of specified topics so that participants may individually apply intervention content as needed to accommodate their particular substance abuse, HIV risk, and antiretroviral adherence issues. This study provides a complete example of the process of selecting and adapting an EBI—taking into account both empirical evidence and input from target organization stakeholders and target population members and their families—for use in real world prison settings where high-risk populations are concentrated