Punishing and rewarding experiences can change the valence of sensory stimuli and guide animal behavior in opposite directions, resulting in avoidance or approach. Often, however, a stimulus is encountered with both positive and negative experiences. How is such conflicting information represented in the brain and resolved into a behavioral decision? We address this question by dissecting a circuit for sexual conditioning in C.
View Article and Find Full Text PDFNew findings in the nematode Caenorhabditis elegans identify neuromodulation of behavioural responses to pheromones as a mechanism for regulating dispersal and foraging strategies.
View Article and Find Full Text PDFSexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in through the direct transdifferentiation of sex-shared glial cells.
View Article and Find Full Text PDFBacteria are the simplest cellular model in which amyloidosis has been addressed. It is well documented that bacterial consortia (biofilms) assemble their extracellular matrix on an amyloid scaffold, yet very few intracellular amyloids are known in bacteria. Here, we describe the methods we have resorted to characterize in Escherichia coli cells the amyloidogenesis, propagation, and dynamics of the RepA-WH1 prionoid.
View Article and Find Full Text PDFAmyloid aggregation of the eukaryotic translation terminator eRF3/Sup35p, the [PSI ] prion, empowers yeast ribosomes to read-through UGA stop codons. No similar functional prion, skipping a stop codon, has been found in Escherichia coli, a fact possibly due to the efficient back-up systems found in bacteria to rescue non-stop complexes. Here we report that engineering hydrophobic amyloidogenic repeats from a synthetic bacterial prion-like protein (RepA-WH1) into the E.
View Article and Find Full Text PDFPlasmid stability can be measured using antibiotic-resistance plasmid derivatives by positive selection. However, highly stable plasmids are below the sensitivity range of these assays. To solve this problem we describe a novel, highly sensitive method to measure plasmid stability based on the selection of plasmid-free cells following elimination of plasmid-containing cells.
View Article and Find Full Text PDFThe synthetic bacterial prionoid RepA-WH1 causes a vertically transmissible amyloid proteinopathy in that inhibits growth and eventually kills the cells. Recent studies show that RepA-WH1 builds pores through model lipid membranes, suggesting a possible mechanism for bacterial cell death. By comparing acutely (A31V) and mildly (ΔN37) cytotoxic mutant variants of the protein, we report here that RepA-WH1(A31V) expression decreases the intracellular osmotic pressure and compromise bacterial viability under either aerobic or anaerobic conditions.
View Article and Find Full Text PDFCertain serovars belonging to subspecies I carry low-copy-number virulence plasmids of variable size (50-90 kb). All of these plasmids share the operon, which is important for systemic infection. Virulence plasmids are present at low copy numbers.
View Article and Find Full Text PDFDNA replication is tightly regulated to constrain the genetic material within strict spatiotemporal boundaries and copy numbers. Bacterial plasmids are autonomously replicating DNA molecules of much clinical, environmental and biotechnological interest. A mechanism used by plasmids to prevent over-replication is 'handcuffing', i.
View Article and Find Full Text PDFIn bacterial plasmids, Rep proteins initiate DNA replication by undergoing a structural transformation coupled to dimer dissociation. Amyloidogenesis of the 'winged-helix' N-terminal domain of RepA (WH1) is triggered in vitro upon binding to plasmid-specific DNA sequences, and occurs at the bacterial nucleoid in vivo. Amyloid fibers are made of distorted RepA-WH1 monomers that assemble as single or double intertwined tubular protofilaments.
View Article and Find Full Text PDFThe N-terminal domain (winged-helix domain, or WH1) of the Pseudomonas pPS10 plasmid DNA replication protein RepA can assemble into amyloid fibers in vitro and, when expressed in Escherichia coli, leads to a unique intracellular amyloid proteinopathy by hampering bacterial proliferation. RepA-WH1 amyloidosis propagates along generations through the transmission of aggregated particles across the progeny, but it is unable to propagate horizontally as an infectious agent and is thus the first synthetic bacterial prionoid. RepA-WH1 amyloidosis is promoted by binding to double-stranded DNA (dsDNA) in vitro, and it is modulated by the Hsp70 chaperone DnaK in vivo.
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