Genetic variants that modify neuroendocrine gene expression and foraging behavior of .

The molecular mechanisms underlying diversity in animal behavior are not well understood. A major experimental challenge is determining the contribution of genetic variants that affect neuronal gene expression to differences in behavioral traits. In , the neuroendocrine transforming growth factor-β ligand, DAF-7, regulates diverse behavioral responses to bacterial food and pathogens.

CMTR-1 RNA methyltransferase mutations activate widespread expression of a dopaminergic neuron-specific mitochondrial complex I gene.

The mitochondrial proteome is comprised of approximately 1,100 proteins, all but 12 of which are encoded by the nuclear genome in C. elegans. The expression of nuclear-encoded mitochondrial proteins varies widely across cell lineages and metabolic states, but the factors that specify these programs are not known.

Neuroendocrine gene expression coupling of interoceptive bacterial food cues to foraging behavior of .

Animal internal state is modulated by nutrient intake, resulting in behavioral responses to changing food conditions. The neural mechanisms by which internal states are generated and maintained are not well understood. Here, we show that in the nematode distinct cues from bacterial food - interoceptive signals from the ingestion of bacteria and gustatory molecules sensed from nearby bacteria - act antagonistically on the expression of the neuroendocrine TGF-beta ligand DAF-7 from the ASJ pair of sensory neurons to modulate foraging behavior.

Hypoxia and intra-complex genetic suppressors rescue complex I mutants by a shared mechanism.

The electron transport chain (ETC) of mitochondria, bacteria, and archaea couples electron flow to proton pumping and is adapted to diverse oxygen environments. Remarkably, in mice, neurological disease due to ETC complex I dysfunction is rescued by hypoxia through unknown mechanisms. Here, we show that hypoxia rescue and hyperoxia sensitivity of complex I deficiency are evolutionarily conserved to C.

Genetic Variants That Modify the Neuroendocrine Regulation of Foraging Behavior in .

The molecular mechanisms underlying diversity in animal behavior are not well understood. A major experimental challenge is determining the contribution of genetic variants that affect neuronal gene expression to differences in behavioral traits. The neuroendocrine TGF-beta ligand, DAF-7, regulates diverse behavioral responses of to bacterial food and pathogens.

Neuroendocrine Gene Expression Coupling of Interoceptive Bacterial Food Cues to Foraging Behavior of .

Animal internal state is modulated by nutrient intake, resulting in behavioral responses to changing food conditions. The neural mechanisms by which internal states are generated and maintained are not well understood. Here, we show that in the nematode , distinct cues from bacterial food - interoceptive signals from the ingestion of bacteria and gustatory molecules sensed from nearby bacteria - act antagonistically on the expression of the neuroendocrine TGF-beta ligand DAF-7 from the ASJ pair of sensory neurons to modulate foraging behavior.

Medical cannabis identity and public health paternalism.

Objectives: State-dependent and variable lists of medical conditions granting access to medical cannabis in the United States may be an example of public health paternalism. While purporting to ensure that medical use is clearly defined, the variability of approved conditions has created an atmosphere of ambiguity and medical precarity. The purpose of this study is to examine the relationship between "state" and "self" medical cannabis user identities and the ways non-medical users understand their cannabis consumption.

MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations.

The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from the mitochondrial DNA (mtDNA). We previously developed MitoCarta, a catalogue of over 1000 genes encoding the mammalian mitochondrial proteome. This catalogue was compiled using a Bayesian integration of multiple sequence features and experimental datasets, notably protein mass spectrometry of mitochondria isolated from fourteen murine tissues.

Immediate activation of chemosensory neuron gene expression by bacterial metabolites is selectively induced by distinct cyclic GMP-dependent pathways in Caenorhabditis elegans.

Dynamic gene expression in neurons shapes fundamental processes in the nervous systems of animals. However, how neuronal activation by different stimuli can lead to distinct transcriptional responses is not well understood. We have been studying how microbial metabolites modulate gene expression in chemosensory neurons of Caenorhabditis elegans.

Hypoxia Rescues Frataxin Loss by Restoring Iron Sulfur Cluster Biogenesis.

Friedreich's ataxia (FRDA) is a devastating, multisystemic disorder caused by recessive mutations in the mitochondrial protein frataxin (FXN). FXN participates in the biosynthesis of Fe-S clusters and is considered to be essential for viability. Here we report that when grown in 1% ambient O, FXN null yeast, human cells, and nematodes are fully viable.

MICU1 imparts the mitochondrial uniporter with the ability to discriminate between Ca and Mn.

The mitochondrial uniporter is a Ca-activated Ca channel complex that displays exceptionally high conductance and selectivity. Here, we report cellular metal toxicity screens highlighting the uniporter's role in Mn toxicity. Cells lacking the pore-forming uniporter subunit, MCU, are more resistant to Mn toxicity, while cells lacking the Ca-sensing inhibitory subunit, MICU1, are more sensitive than the wild type.

Inhibition of Lithium-Sensitive Phosphatase BPNT-1 Causes Selective Neuronal Dysfunction in C. elegans.

Lithium has been a mainstay for the treatment of bipolar disorder, yet the molecular mechanisms underlying its action remain enigmatic. Bisphosphate 3'-nucleotidase (BPNT-1) is a lithium-sensitive phosphatase that catalyzes the breakdown of cytosolic 3'-phosphoadenosine 5'-phosphate (PAP), a byproduct of sulfation reactions utilizing the universal sulfate group donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) [1-3]. Loss of BPNT-1 leads to the toxic accumulation of PAP in yeast and non-neuronal cell types in mice [4, 5].

Physiology and evolution of nitrate acquisition in Prochlorococcus.

Prochlorococcus is the numerically dominant phototroph in the oligotrophic subtropical ocean and carries out a significant fraction of marine primary productivity. Although field studies have provided evidence for nitrate uptake by Prochlorococcus, little is known about this trait because axenic cultures capable of growth on nitrate have not been available. Additionally, all previously sequenced genomes lacked the genes necessary for nitrate assimilation.

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.

Behavioral avoidance of pathogenic bacteria by Caenorhabditis elegans.

The simple animal host Caenorhabditis elegans utilizes its nervous system to respond to diverse microbial cues, and can engage in a protective behavioral avoidance response to environmental pathogens. This behavior bears hallmarks of an immune response, with sensors and recognition systems that trigger a protective response following a learning experience. Neuronal circuits required for aversive learning have been defined, revealing conserved signaling modules with dual roles in immunity and neuronal responses to pathogenic bacteria.

The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea.

Freshwater planarians are able to regenerate any missing part of their body and have extensive tissue turnover because of the action of dividing cells called neoblasts. Neoblasts provide an excellent system for in vivo study of adult stem cell biology. We identified the Smed-CHD4 gene, which is predicted to encode a chromatin-remodeling protein similar to CHD4/Mi-2 proteins, as required for planarian regeneration and tissue homeostasis.