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J Exp Biol,
2011]
When crawling on a solid surface, the nematode Caenorhabditis elegans (C. elegans) moves forward by propagating sinusoidal dorso-ventral retrograde contraction waves. A uniform propagating wave leads to motion that undulates about a straight line. When C. elegans turns as it forages or navigates its environment, it uses several different strategies of reorientation. These modes include the well-known omega turn, in which the worm makes a sharp angle turn forming an -shape, and the reversal, in which the worm draws itself backwards. In these two modes of reorientation, C. elegans strongly disrupts its propagating sinusoidal wave, either in form or in direction, leading to abrupt directional change. However, a third mode of reorientation, the shallow turn, involves a gentler disruption of the locomotory gait. Analyzing the statistics of locomotion suggests that the shallow turn is by far the most frequent reorienting maneuver in navigation in the absence of food. We show that the worm executes a shallow turn by modulating the amplitude and wavelength of its curvature during forward movement, and provide a minimal description of the process using a three-parameter mathematical model. The results of our study augment the understanding of how these parameters are controlled at the neuromotor circuit level.
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Dis Model Mech,
2008]
The genetic analysis of mechanisms of pathogen resistance in the nematode Caenorhabditis elegans has revealed a role for evolutionarily conserved signaling pathways that are required for innate immunity in a wide range of organisms, from worms to mammals. C. elegans represents one of the more simple host organisms in which mechanisms of host defense can be dissected, and the use of C. elegans presents the researcher with a wide array of genetic and genomic tools to probe the host-pathogen interface. The study of host defense mechanisms in C. elegans continues to provide an ancient evolutionary perspective on innate immunity, which may generate insights into the conserved processes in phylogenetically diverse host organisms, including humans.
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Front Neuroanat,
2022]
Studies on sexual dimorphism in the structure and function of the nervous system have been pivotal to understanding sex differences in behavior. Such studies, especially on invertebrates, have shown the importance of neurons specific to one sex (sex-specific neurons) in shaping sexually dimorphic neural circuits. Nevertheless, recent studies using the nematode C. elegans have revealed that the common neurons that exist in both sexes (sex-shared neurons) also play significant roles in generating sex differences in the structure and function of neural circuits. Here, we review the anatomical and functional differences in the sex-shared neurons of C. elegans. These sexually dimorphic characteristics include morphological differences in neurite projection or branching patterns with substantial changes in synaptic connectivity, differences in synaptic connections without obvious structural changes, and functional modulation in neural circuits with no or minimal synaptic connectivity changes. We also cover underlying molecular mechanisms whereby these sex-shared neurons contribute to the establishment of sexually dimorphic circuits during development and function differently between the sexes.
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Nucleic Acids Res,
2017]
Myrf is a key transcription factor for oligodendrocyte differentiation and central nervous system myelination. We and others have previously shown that Myrf is generated as a membrane protein in the endoplasmic reticulum (ER), and that it undergoes auto-processing to release its N-terminal fragment from the ER, which enters the nucleus to work as a transcription factor. These previous studies allow a glimpse into the unusual complexity behind the biogenesis and function of the transcription factor domain of Myrf. Here, we report that Myrf N-terminal fragments assemble into stable homo-trimers before ER release. Consequently, Myrf N-terminal fragments are released from the ER only as homo-trimers. Our re-analysis of a previous genetic screening result in Caenorhabditis elegans shows that homo-trimerization is essential for the biological functions of Myrf N-terminal fragment, and that the region adjacent to the DNA-binding domain is pivotal to its homo-trimerization. Further, our computational analysis uncovered a novel homo-trimeric DNA motif that mediates the homo-trimeric DNA binding of Myrf N-terminal fragments. Importantly, we found that homo-trimerization defines the DNA binding specificity of Myrf N-terminal fragments. In sum, our study elucidates the molecular mechanism governing the biogenesis and function of Myrf N-terminal fragments and its physiological significance.
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Neuronal Development, Synaptic Function and Behavior, Madison, WI,
2010]
Reversals and omega turns are two well-known reorientation modes observed in C. elegans crawling on an agar plate. In off food navigation, the worm utilizes another distinct type of small angle reorientation mode much more frequently than two previously described modes, confirmed by the occurrence frequencies of three reorientation modes in exploratory behavior in off food environment. We named this reorientation mode the "shallow turn". The shallow turn is defined as a turn with a shallow angle (< 90°) with the sustained sinusoidal wave throughout the turn. In addition, we propose a simple mathematical model for the shallow turn to elucidate its mechanism of turning motion. Based on our results, the neural mechanism of the shallow turn could be accomplished. For further studies, we plan to do shallow turn assay for a few selected mutants. This work was supported by the National Research Foundation (NRF) grant 2009-0073354 and KAIST KI for Design of Complex Systems.
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Worm Breeder's Gazette,
1994]
Specification of vulval cell fates by sequential signaling pathways Jeffrey S. Simske and Stuart K. Kim, Dept. of Developmental Biology, Stanford University Medical Center, Stanford CA 94305
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Biosci Biotechnol Biochem,
2016]
We compared the growth inhibitory effects of all aldohexose stereoisomers against the model animal Caenorhabditis elegans. Among the tested compounds, the rare sugars d-allose (d-All), d-talose (d-Tal), and l-idose (l-Ido) showed considerable growth inhibition under both monoxenic and axenic culture conditions. 6-Deoxy-d-All had no effect on growth, which suggests that C6-phosphorylation by hexokinase is essential for inhibition by d-All.
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Bioorg Med Chem Lett,
2016]
Biological activities of unusual monosaccharides (rare sugars) have largely remained unstudied until recently. We compared the growth inhibitory effects of aldohexose stereoisomers against the animal model Caenorhabditis elegans cultured in monoxenic conditions with Escherichia coli as food. Among these stereoisomers, the rare sugar d-arabinose (d-Ara) showed particularly strong growth inhibition. The IC50 value for d-Ara was estimated to be 7.5mM, which surpassed that of the potent glycolytic inhibitor 2-deoxy-d-glucose (19.5mM) used as a positive control. The inhibitory effect of d-Ara was also observed in animals cultured in axenic conditions using a chemically defined medium; this excluded the possible influence of E. coli. To our knowledge, this is the first report of biological activity of d-Ara. The d-Ara-induced inhibition was recovered by adding either d-ribose or d-fructose, but not d-glucose. These findings suggest that the inhibition could be induced by multiple mechanisms, for example, disturbance of d-ribose and d-fructose metabolism.
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Bioorg Med Chem Lett,
2019]
The biological activities of deoxy sugars (deoxy monosaccharides) have remained largely unstudied until recently. We compared the growth inhibition by all 1-deoxyketohexoses using the animal model Caenorhabditis elegans. Among the eight stereoisomers, 1-deoxy-d-allulose (1d-d-Alu) showed particularly strong growth inhibition. The 50% inhibition of growth (GI<sub>50</sub>) concentration by 1d-d-Alu was estimated to be 5.4mM, which is approximately 10 times lower than that of d-allulose (52.7mM), and even lower than that of the potent glycolytic inhibitor, 2-deoxy-d-glucose (19.5mM), implying that 1d-d-Alu has a strong growth inhibition. In contrast, 5-deoxy- and 6-deoxy-d-allulose showed no growth inhibition of C. elegans. The inhibition by 1d-d-Alu was alleviated by the addition of d-ribose or d-fructose. Our findings suggest that 1d-d-Alu-mediated growth inhibition could be induced by the imbalance in d-ribose metabolism. To our knowledge, this is the first report of biological activity of 1d-d-Alu which may be considered as an antimetabolite drug candidate.
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Biochim Biophys Acta Proteins Proteom,
2020]
d-Aspartate oxidase (DDO) is a flavin adenine dinucleotide (FAD)-containing flavoprotein that stereospecifically acts on acidic D-amino acids (i.e., free d-aspartate and D-glutamate). Mammalian DDO, which exhibits higher activity toward d-aspartate than D-glutamate, is presumed to regulate levels of d-aspartate in the body and is not thought to degrade D-glutamate in vivo. By contrast, three DDO isoforms are present in the nematode Caenorhabditis elegans, DDO-1, DDO-2, and DDO-3, all of which exhibit substantial activity toward D-glutamate as well as d-aspartate. In this study, we optimized the Escherichia coli culture conditions for production of recombinant C. elegans DDO-1, purified the protein, and showed that it is a flavoprotein with a noncovalently but tightly attached FAD. Furthermore, C. elegans DDO-1, but not mammalian (rat) DDO, efficiently and selectively degraded D-glutamate in addition to d-aspartate, even in the presence of various other amino acids. Thus, C. elegans DDO-1 might be a useful tool for determining these acidic D-amino acids in biological samples.