Chemosensation of Bacterial Secondary Metabolites Modulates Neuroendocrine Signaling and Behavior of C. elegans

Discrimination between pathogenic and beneficial microbes is essential for host organism immunity and homeostasis. Here, we show that chemosensory detection of two secondary metabolites produced by Pseudomonas aeruginosa modulates a neuroendocrine signaling pathway that promotes avoidance behavior in the simple animal host Caenorhabditis elegans. Secondary metabolites phenazine-1-carboxamide and pyochelin activate a G-protein-signaling pathway in the ASJ chemosensory neuron pair that induces expression of the neuromodulator DAF-7/TGF-β. DAF-7, in turn, activates a canonical TGF-β signaling pathway in adjacent interneurons to modulate aerotaxis behavior and promote avoidance of pathogenic P. aeruginosa. Our data provide a chemical, genetic, and neuronal basis for how the behavior and physiology of a simple animal host can be modified by the microbial environment and suggest that secondary metabolites produced by microbes may provide environmental cues that contribute to pathogen recognition and host survival.National Science Foundation (U.S.). Graduate Research Fellowship ProgramEllison Medical Foundation (New Scholar Award

Molecular Determinants of the Regulation of Development and Metabolism by Neuronal eIF2α Phosphorylation in

Cell-nonautonomous effects of signaling in the nervous system of animals can influence diverse aspects of organismal physiology. We previously showed that phosphorylation of Ser49 of the α-subunit of eukaryotic translation initiation factor 2 (eIF2α) in two chemosensory neurons by PEK-1/PERK promotes entry of Caenorhabditis elegans into dauer diapause. Here, we identified and characterized the molecular determinants that confer sensitivity to effects of neuronal eIF2α phosphorylation on development and physiology of C. elegans. Isolation and characterization of mutations in eif-2Ba encoding the α-subunit of eIF2B support a conserved role, previously established by studies in yeast, for eIF2Bα in providing a binding site for phosphorylated eIF2α to inhibit the exchange factor eIF2B catalytic activity that is required for translation initiation. We also identified a mutation in eif-2c, encoding the γ-subunit of eIF2, which confers insensitivity to the effects of phosphorylated eIF2α while also altering the requirement for eIF2Bγ. In addition, we show that constitutive expression of eIF2α carrying a phosphomimetic S49D mutation in the ASI pair of sensory neurons confers dramatic effects on growth, metabolism, and reproduction in adult transgenic animals, phenocopying systemic responses to starvation. Furthermore, we show that constitutive expression of eIF2α carrying a phosphomimetic S49D mutation in the ASI neurons enhances dauer entry through bypassing the requirement for nutritionally deficient conditions. Our data suggest that the state of eIF2α phosphorylation in the ASI sensory neuron pair may modulate internal nutrient sensing and signaling pathways, with corresponding organismal effects on development and metabolism. Keywords: Caenorhabditis elegans; Dauer; EIF2α; phosphorylation; sensory neurons; translational contro

What's in your next-generation sequence data? An exploration of unmapped DNA and RNA sequence reads from the bovine reference individual.

BackgroundNext-generation sequencing projects commonly commence by aligning reads to a reference genome assembly. While improvements in alignment algorithms and computational hardware have greatly enhanced the efficiency and accuracy of alignments, a significant percentage of reads often remain unmapped.ResultsWe generated de novo assemblies of unmapped reads from the DNA and RNA sequencing of the Bos taurus reference individual and identified the closest matching sequence to each contig by alignment to the NCBI non-redundant nucleotide database using BLAST. As expected, many of these contigs represent vertebrate sequence that is absent, incomplete, or misassembled in the UMD3.1 reference assembly. However, numerous additional contigs represent invertebrate species. Most prominent were several species of Spirurid nematodes and a blood-borne parasite, Babesia bigemina. These species are either not present in the US or are not known to infect taurine cattle and the reference animal appears to have been host to unsequenced sister species.ConclusionsWe demonstrate the importance of exploring unmapped reads to ascertain sequences that are either absent or misassembled in the reference assembly and for detecting sequences indicative of parasitic or commensal organisms

Boundary manifolds of projective hypersurfaces

We study the topology of the boundary manifold of a regular neighborhood of a complex projective hypersurface. We show that, under certain Hodge theoretic conditions, the cohomology ring of the complement of the hypersurface functorially determines that of the boundary. When the hypersurface defines a hyperplane arrangement, the cohomology of the boundary is completely determined by the combinatorics of the underlying arrangement and the ambient dimension. We also study the LS category and topological complexity of the boundary manifold, as well as the resonance varieties of its cohomology ring.Comment: 31 pages; accepted for publication in Advances in Mathematic

What is the fate of the heavy electron at a quantum critical point?

A growing body of evidence suggests that the quantum critical behavior at the onset of magnetism in heavy fermion systems can not be understood in terms of a simple quantum spin density wave. This talk will discuss the consequences of this conclusion, touching on its possible implications in the realm of two dimensional systems and outlining current theoretical and experimental efforts to characterize the nature of the critical point in heavy fermion materials.Comment: To appear in SCES 200

Precise Analysis of Polymer Rotational Dynamics

Through the analysis of individual chain dynamics alongside the corresponding molecular structures under shear via nonequilibrium molecular dynamics simulations of C178H358 linear and short-chain branched polyethylene melts under shear flow, we observed that the conventional method based on the chain end-to-end vector (and/or the gyration tensor of chain) is susceptible to quantitatively inaccurate measurements and often misleading information in describing the rotational dynamics of polymers. Identifying the flaw as attributed to strong irregular Brownian fluctuations inherent to the chain ends associated with their large free volume and strong molecular collisions, we propose a simple, robust way based on the chain center-to-center vector connecting the two centers of mass of the bisected chain, which is shown to adequately describe polymer rotational dynamics without such shortcomings. We present further consideration that the proposed method can be useful in accurately measuring the overall chain structure and dynamics of polymeric materials with various molecular architectures, including branched and ring polymers.open

Global Emergency Medicine: A Review of the Literature From 2012

Objectives The Global Emergency Medicine Literature Review ( GEMLR ) conducts an annual search of peer‐reviewed and grey literature relevant to global emergency medicine ( EM ) to identify, review, and disseminate the most important new research in this field to a worldwide audience of academics and clinical practitioners. Methods This year, our search identified 4,818 articles written in six languages. These articles were distributed among 20 reviewers for initial screening based on their relevance to the field of global EM . Two additional reviewers searched and screened the grey literature. A total of 224 articles were deemed appropriate by at least one reviewer and were approved by their editor for formal scoring of overall quality and importance. Results Of the 224 articles that met our predetermined inclusion criteria, 56% were categorized as Emergency Care in Resource‐limited Settings, 18% as EM development, and 26% as Disaster and Humanitarian Response. A total of 28 articles received scores of 16 or higher and were selected for formal summary and critique. Inter‐rater reliability for two reviewers using our scoring system was good, with an intraclass correlation coefficient of 0.625 (95% confidence interval = 0.512 to 0.711). Conclusions In 2012 there were more disaster and humanitarian response articles than in previous years. As in prior years, the majority of articles addressed the acute management of infectious diseases or the care of vulnerable populations such as children and pregnant women. Resumen Medicina de Urgencias y Emergencias Global: Una Revisión de la Literatura de 2012 Objetivos La revisión de la literatura publicada en Medicina de Urgencias y Emergencias ( MUE ) global comporta una búsqueda anual de los trabajos relevantes para la MUE global, tanto publicados tras revisión por pares como corresponedientes a literatura gris. La finalidad es identificar, revisar y diseminar las investigaciones novedosas más importantes en este campoa médicos clínicos y universitarios de todo el mundo. Metodología Este año, nuestra búsqueda identificó 4.818 artículos escritos en seis lenguas. Estos artículos se distribuyeron entre 20 revisores para el despistaje inicial basándose en su relevancia para el campo de la MUE global. Dos revisores adicionales buscaron y filtraron la literatura gris. Un total de 224 artículos se consideraron apropiados por al menos un revisor, y se aprobaron por su editor para la puntuación formal de la calidad e importancia totales. Resultados De los 224 artículos que cumplieron nuestros criterios de inclusión predeterminados, un 56% se clasificaron como atención de urgencias y emergencias en ámbitos de recursos limitados, un 18% como desarrollo de la MUE y un 26% como catástrofes y respuesta humanitaria. Un total de 28 artículos recibieron una puntuación de 16 o más y se seleccionaron para el resumen y la crítica formal. La fiabilidad interobservador para los 2 revisores usando nuestro sistema de puntuación fue buena, con un coeficiente de correlación intraclase de 0,625 ( IC 95% = 0,512 a 0,711). Conclusiones En 2012 hubo más artículos sobre catástrofes y respuesta humanitaria que en años anteriores. Como en los años previos, la mayoría de los artículos valoraron el manejo agudo de enfermedades infecciosas o la atención de poblaciones vulnerables como los niños y las mujeres embarazadas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99685/1/acem12173.pd

A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans

Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation. © 2016 Neal et al.1

Long-Term Column Leaching of Phase II Mercury Control Technology By-Products

An NETL research, development and demonstration program under DOE/Fossil Energy Innovations for Existing Plants is directed toward the improvement of the performance and economics of mercury control from coal-fired plants. The current Phase II of the RD&D program emphasizes the evaluation of performance and cost of control technologies through slip-stream and full scale field testing while continuing the development of novel concepts. One of the concerns of the NETL program is the fate of the captured flue gas mercury which is transferred to the condensed phase by-product stream. The stability of mercury and any co-captured elements in the by-products could have a large economic impact if it reduced by-product sales or increasing their disposal costs. As part of a greater characterization effort of Phase II facility baseline and control technology sample pairs, NETL in-house laboratories have performed continuous leaching of a select subset of the available sample pairs using four leachants: water (pH=5.7), dilute sulfuric acid (pH=1.2), dilute acetic acid (pH=2.9), and sodium carbonate (pH=11.1). This report describes results obtained for mercury, arsenic, and selenium during the 5-month leaching experiments