The neuromolecular mechanisms that coordinate food availability with C. elegans male sexual behavior

Organisms must coordinate behavioral and physiological responses to changingenvironmental conditions. In the nematode C. elegans, the presence or absence of foodin the environment affects many metabolic and behavioral responses, including fathomeostasis, lifespan, and male mating. Specifically, male mating behavior normallyoccurs when a well-nourished male encounters a hermaphrodite, and is repressed if themale is under-nourished. To understand how environmental changes influence the driveto carry out specific behavioral tasks, I used C. elegans male mating as a model.Previously, mutants were isolated that display male mating behavior at inappropriatetimes, i.e. in the absence of mating cues. Loss of function mutations in the ERG K+channel, UNC-103, results in spontaneous seizures of the male sex muscles.Interestingly, I found that food deprivation can suppress unc-103(lf)-induced seizures,suggesting that pathways activated under this environmental condition can suppress theexcitability of the mating circuit.Using molecular, genetic, and behavioral assays, I identified sensory andmolecular mechanisms that reduce sex-muscle excitability under food-deprived conditions. I found that mutations that affect the muscular feeding organ, the pharynx,phenocopy the effects of food deprivation, and reduce sex-muscle excitability. Idemonstrated that mutations in the pharyngeal muscle protein, tropomyosin, cause thepharyngeal neurosecretory motor neurons (NSMs) to increase pharyngeal excitabilityand reduce sex-muscle excitability. Additionally, I found that olfactory neurons (AWCs)with sensory cilia exposed to the environment are up-regulated in the absence of foodstimuli, and also send inhibitory signals to the sex muscles. To determine howchemosensory and pharyngeal neurons in the head can signal to the genitalia, Ihypothesized that one mechanism could be via secretion of metabolic hormones. To testthis, I examined loss-of-function mutations in the insulin-like receptor, DAF-2, which isknown to regulate many behavioral and physiological responses to food. I demonstratedthat DAF-2 activity in the sex muscles is required for food-deprivation suppression ofunc-103(0)-induced seizures. I then identified components of a novel-insulin-like/DAF-2signaling pathway that reduces excitability. Specifically, I propose that ligand binding toDAF-2 activates PLC- and leads to increased cystolic Ca2+. This Ca2+ influx activatesCaMKII, which can phosphorylate/activate EAG-like K+ channels, thereby reducing cellexcitability

Food Deprivation Attenuates Seizures through CaMKII and EAG K+ Channels

Accumulated research has demonstrated the beneficial effects of dietary restriction on extending lifespan and increasing cellular stress resistance. However, reducing nutrient intake has also been shown to direct animal behaviors toward food acquisition. Under food-limiting conditions, behavioral changes suggest that neuronal and muscle activities in circuits that are not involved in nutrient acquisition are down-regulated. These dietary-regulated mechanisms, if understood better, might provide an approach to compensate for defects in molecules that regulate cell excitability. We previously reported that a neuromuscular circuit used in Caenorhabditis elegans male mating behavior is attenuated under food-limiting conditions. During periods between matings, sex-specific muscles that control movements of the male's copulatory spicules are kept inactive by UNC-103 ether-a-go-go–related gene (ERG)–like K+ channels. Deletion of unc-103 causes ∼30%–40% of virgin males to display sex-muscle seizures; however, when food is deprived from males, the incidence of spontaneous muscle contractions drops to 9%–11%. In this work, we used genetics and pharmacology to address the mechanisms that act parallel with UNC-103 to suppress muscle seizures in males that lack ERG-like K+ channel function. We identify calcium/calmodulin-dependent protein kinase II as a regulator that uses different mechanisms in food and nonfood conditions to compensate for reduced ERG-like K+ channel activity. We found that in food-deprived conditions, calcium/calmodulin-dependent protein kinase II acts cell-autonomously with ether-a-go-go K+ channels to inhibit spontaneous muscle contractions. Our work suggests that upregulating mechanisms used by food deprivation can suppress muscle seizures

Sensory Perception of Food and Insulin-Like Signals Influence Seizure Susceptibility

Food deprivation is known to affect physiology and behavior. Changes that occur could be the result of the organism's monitoring of internal and external nutrient availability. In C. elegans, male mating is dependent on food availability; food-deprived males mate with lower efficiency compared to their well-fed counterparts, suggesting that the mating circuit is repressed in low-food environments. This behavioral response could be mediated by sensory neurons exposed to the environment or by internal metabolic cues. We demonstrated that food-deprivation negatively regulates sex-muscle excitability through the activity of chemosensory neurons and insulin-like signaling. Specifically, we found that the repressive effects of food deprivation on the mating circuit can be partially blocked by placing males on inedible food, E. coli that can be sensed but not eaten. We determined that the olfactory AWC neurons actively suppress sex-muscle excitability in response to food deprivation. In addition, we demonstrated that loss of insulin-like receptor (DAF-2) signaling in the sex muscles blocks the ability of food deprivation to suppress the mating circuit. During low-food conditions, we propose that increased activity by specific olfactory neurons (AWCs) leads to the release of neuroendocrine signals, including insulin-like ligands. Insulin-like receptor signaling in the sex muscles then reduces cell excitability via activation of downstream molecules, including PLC-γ and CaMKII

Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection

Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions. A total of 336 organisms were present in available rumen metagenomic data sets, and 134 were present in human gut microbiome data sets. Comparison with the human microbiome revealed rumen-specific enrichment for genes encoding de novo synthesis of vitamin B12, ongoing evolution by gene loss and potential vertical inheritance of the rumen microbiome based on underrepresentation of markers of environmental stress. We estimate that our Hungate genome resource represents ?75% of the genus-level bacterial and archaeal taxa present in the rumen.publishersversionPeer reviewe

Semantic Web and Big Data meets Applied Ontology

The role that ontologies play or can play in designing and employing semantic technologies has been widely acknowledged by the Semantic Web and Linked Data communities. But the level of collaboration between these communities and the Applied Ontology community has been much less than expected. And ontologies and ontological techniques appear to be of marginal use in Big Data and its applications. To understand this situation and foster greater collaboration, Ontology Summit 2014 brought together representatives from the Semantic Web, Linked Data, Big Data and Applied Ontology communities, to address three basic problems involving applied ontology and these communities: (1) The role of ontologies [in these communities], (2) Current uses of ontologies in these communities, and (3) Engineering of ontologies and semantic integration. The intent was to identify and understand: (a) causes and challenges (e.g. scalability) that hinder reuse of ontologies in SW and LD, (b) solutions that can reduce the differences between ontologies on and off line, and (c) solutions to overcome engineering bottlenecks in current Semantic Web and Big Data applications. Over the past four months, presentations from, and discussions with, representatives of the Semantic Web, Linked Data, and Applied Ontology communities have taken place across four tracks. Each Track focused on different aspects of this year?s Summit topic: (Track A) Investigation of sharable and reusable ontologies; (Track B) Tools, services and techniques for a comprehensive and effective use of ontologies; (Track C) Investigation of the engineering bottlenecks and the ways to prevent and overcome them; (Track D) Enquiry on the variety problem in Big Data. In addition to the four Tracks? activities there was a Hackathon. Six different Hackathon projects took place, all available at their individual project public repositories. An online Community Library and an online Ontology Repository have been created as freely accessible Community resources. This Ontology Summit 2014 Communique presents a summary of the results, original in its attempt both to merge different communities? discourses and to achieve consensus across the Summit participants with respect to open problems and recommendations to address them.Fil: Obrst, Leo. The MITRE Corporation; Estados UnidosFil: Gruninger, Michael. University Of Toronto; CanadáFil: Baclawski, Ken. Northeastern University; Estados UnidosFil: Bennett, Mike. Hypercube Ltd.; Reino UnidoFil: Brickley, Dan. Google; Reino UnidoFil: Berg Cross, Gary. Knowledge Strategies; Estados UnidosFil: Hitzler, Pascal. Wright State University; Estados UnidosFil: Janowicz, Krzysztof. University of California; Estados UnidosFil: Kapp, Christine. Hypercube Ltd; Estados UnidosFil: Kutz, Oliver. Otto von Guericke University Magdeburg; AlemaniaFil: Lange, Christoph. University of Bonn; AlemaniaFil: Levenchuk, Anatoly. TechInvestLab.ru; RusiaFil: Quattri, Francesca. The Hong Kong Polytechnic University; Hong KongFil: Rector, Alan. University Of Manchester; Reino UnidoFil: Schneider, Todd. PDS, Inc.; Estados UnidosFil: Spero, Simon. University Of North Carolina; Estados UnidosFil: Thessen, Anne. Arizona State University; Estados UnidosFil: Vegetti, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo y Diseño (i); ArgentinaFil: Vizedom, Amanda. Criticollab; Estados UnidosFil: Westerinen, Andrea. Nine Points Solutions; Estados UnidosFil: West, Matthew. Information Junction; Reino UnidoFil: Yim, Peter. CIM Engineering, Inc.; Estados Unido