Alternative patterns of neural activity drive different rhythmic locomotory patterns in both invertebrates and mammals. The neuro-molecular mechanisms responsible for the expression of rhythmic behavioral patterns are poorly understood. Here we show that Caenorhabditis elegans switches between distinct forms of locomotion, or crawling versus swimming, when transitioning between solid and liquid environments. These forms of locomotion are distinguished by distinct kinematics and different underlying patterns of neuromuscular activity, as determined by in vivo calcium imaging. The expression of swimming versus crawling rhythms is regulated by sensory input. In a screen for mutants that are defective in transitioning between crawl and swim behavior, we identified unc-79 and unc-80, two mutants known to be defective in NCA ion channel stabilization. Genetic and behavioral analyses suggest that the NCA channels enable the transition to rapid rhythmic behaviors in C. elegans. unc-79, unc-80, and the NCA channels represent a conserved set of genes critical for behavioral pattern generation.neural rhythms ͉ neurogenetics ͉ sodium leak channel D ifferent forms of rhythmic neural output are ubiquitously observed in motor behaviors such as locomotion, respiration, and feeding (1-4). Extensive research has revealed that a neural network can switch among alternate rhythms by altering the properties of specific intrinsic membrane currents and synapses (5). Consistent with this framework, some proteins appear to contribute more to the generation of one rhythm than other rhythms. For instance, channels that carry the persistent sodium current appear to be important for gasping but not the normal respiratory rhythm when studied in vitro (6). Physiological approaches are sometimes limited when trying to identify specific proteins involved in certain rhythms, however, because of the availability and selectivity of compounds that act on the relevant molecules. With the advent of reverse genetics, these limitations are beginning to be overcome by knocking out or modifying specific genes (7, 8), but both pharmacological and gene manipulation approaches are still limited by the a priori hypotheses on which molecules to target. In contrast, because forward genetic studies are unbiased, they can lead to the identification of novel or uncharacterized proteins that contribute to rhythmic neural output. We have therefore pursued a forward genetic approach to identify neural proteins that contribute more to the generation of one form of rhythmic locomotion (i.e., swimming) than another (i.e., crawling) in the nematode Caenorhabditis elegans.C. elegans moves by generating waves of dorsal-ventral (DV) bends along its body. Prior genetic studies have focused on the molecular mechanisms responsible for crawling over a solid agar substrate (9, 10), whereas the motion C. elegans displays in liquid has only begun to be characterized (11). Although C. elegans encounters water in its natural environment (12), it has been unclear whether its motion i...

Epithelial cells express antimicrobial proteins in response to invading pathogens, although little is known regarding epithelial defense mechanisms during healthy conditions. Here we report that epithelial cytokeratins have innate defense properties because they constitutively produce cytoprotective antimicrobial peptides. Glycine-rich C-terminal fragments derived from human cytokeratin 6A were identified in bactericidal lysate fractions of human corneal epithelial cells. Structural analysis revealed that these keratin-derived antimicrobial peptides (KDAMPs) exhibited coil structures with low α-helical content. Synthetic analogs of these KDAMPS showed rapid bactericidal activity against multiple pathogens and protected epithelial cells against bacterial virulence mechanisms, while a scrambled peptide showed no bactericidal activity. However, the bactericidal activity of a specific KDAMP was somewhat reduced by glycine-alanine substitutions. KDAMP activity involved bacterial binding and permeabilization, but the activity was unaffected by peptide charge or physiological salt concentration. Knockdown of cytokeratin 6A markedly reduced the bactericidal activity of epithelial cell lysates in vitro and increased the susceptibility of murine corneas to bacterial adherence in vivo. These data suggest that epithelial cytokeratins function as endogenous antimicrobial peptides in the host defense against infection and that keratin-derived antimicrobials may serve as effective therapeutic agents.

Neither fluorescein staining nor bacterial adhesion necessarily predict or enable corneal susceptibility to bacterial penetration or disease. Corneal epithelial defenses limiting traversal by adherent bacteria include EGTA-sensitive factors and SP-D. Understanding mechanisms modulating epithelial traversal by microbes could improve our understanding of susceptibility to infection and may indicate new strategies for preventing disease.

Many species of insects associated with cultivated rice do not over-winter in Korea and Japan, but migrate into these areas each year. To understand better the origins of these immigrations as well as the geographic structure of rice pests in Asian rice growing regions, intraspecific variation in two species of delphacid planthoppers, Nilaparvata lugens (Stål) and Sogatella furcifera Horvath, was examined. An 850 base pair region of mitochondrial DNA cytochrome oxidase-I (CO-I) was sequenced from a total of 71 individuals collected from 11 localities in seven countries: Korea, Philippines, China, Bangladesh, Malaysia, Vietnam and Thailand. In N. lugens, three haplotypes were found and all populations sampled shared a dominant haplotype. Localities in Korea contained two haplotypes and localities in China and the Philippines contained three. However, in samples from the Indochina peninsula no variation was detected either within or between populations, consistent with a hypothesis of regular migration and gene flow. These populations did not contain some haplotypes found in Korea, suggesting they were not the source of yearly immigration into Korea and, by extension, Japan. Populations from China did share haplotypes with Korea, which was consistent with the hypothesis that China was the source for yearly immigration into Korea. There was insufficient resolution to distinguish among populations in China. For N. lugens, the data suggested that populations south of the Red River Valley in Vietnam experienced regular mixing and were distinct from populations to the north which contributed to yearly immigrations. In S. furcifera, there was less differentiation among populations. Two haplotypes were found in all populations except Malaysia. The results for both species were consistent with seasonal weather data and indicated that more detailed analysis of DNA sequence data will be fruitful.