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[
International C. elegans Meeting,
1999]
In order to characterize the neural circuit of C. elagans, we construct a simple model by making use of the data table completed recently by Oshio et al . [1]. We assume that the signal of a neuron is calculated by the product of the signals from the neighboring neurons, and we investigate the touch sensitivity to continuous stimuli described by sinusoidal functions as defined in the rage from 0.0 to 1.0. We calculate the responses of the motor neurons by changing the frequencies of the stimuli. In our calculations, we change only the frequency w PLM for the input signal to the sensory neuron PLM, while the frequency for the other sensory neurons ALM, AVM and PVM is fixed to be a same value w 0 . We show that the output signals from the motor neurons A and B oscillate in time. We measure the minima of the oscillation for each w PLM value. The plot of the minima versus w PLM shows different hehaviors for the case of the neuron A and B. As for the signals from the neuron A, the values of the minima are widely distributed between 0.0 and 1.0 for all w PLM . As for the signals from the neuron B, on the other hand, the features are different for different w PLM values. (a) In the high frequency region of w PLM / w 0 0.4, the oscillation is simple harmonic and there exists only one minimum value (I min = 0.0). (b) As w PLM / w 0 is decreased, another minimum appears at a certain frequency, and the bifurcation takes place discontinuously. This behavior is different from usual continuous bifurcation observed in nonlinear systems. After a few discontinuous branching occur, signals with five periods can be seen in the intermediate frequency region of 0.3 w PLM / w 0 w PLM / w 0 [1] K. Oshio et al. ; C. elegans synaptic connectivity data'', Technical Report, CCEP, Keio Future No.1 (1998).
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[
International C. elegans Meeting,
1999]
In order to study the habituation of C. elegans for the touch sensitivity, we carry out computer simulations, in which the neural circuit is formed by making use of the data table constructed recently by Oshio et al [1]. The i -th neuron is connected with the neighboring j -th neuron through the coupling strength K ij , which is varied dynamically by the Hebb rule. Note that K ij is not necessarily equal to K ji because there are one-way connections between the neurons by chemical synapses. As a reference state, we first deal with the neural circuit consisting only of the neurons ALM, AVM, PLM, PVM, AVA, AVB, PVC, AVD, A and B, that are related to the forward and backward movement directly. We give periodic stimuli to the sensory neurons PLM, PVM, and monitor the response of the motor neuron A. We find that the frequency of the response decreases with time, which indicates that the habituation to the touch sensitivity actually takes place. As one deviation from the reference state, we kill the inter-neuron AVD, and perform the same analysis described in the above. There is a tendency that the decay of the response curve becomes faster, and the habituation is enhanced. As the other deviations, there are several possibilities of killing the inter-neurons AVA, AVB, PVC and/or AVD. We discuss the enhancement of the habituation in relation with the recent experimental results by Hosono. [1.] K. Oshio, S. Morita, Y. Osana and K. Oka; C. elegans synaptic connectivity data'', Technical Report, CCEP, Keio Future No.1 (1998)
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[
Genome Biol,
2000]
SUMMARY: The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction. F-box proteins were first characterized as components of SCF ubiquitin-ligase complexes (named after their main components, Skp I, Cullin, and an F-box protein), in which they bind substrates for ubiquitin-mediated proteolysis. The F-box motif links the F-box protein to other components of the SCF complex by binding the core SCF component Skp I. F-box proteins have more recently been discovered to function in non-SCF protein complexes in a variety of cellular functions. There are 11 F-box proteins in budding yeast, 326 predicted in Caenorhabditis elegans, 22 in Drosophila, and at least 38 in humans. F-box proteins often include additional carboxy-terminal motifs capable of protein-protein interaction; the most common secondary motifs in yeast and human F-box proteins are WD repeats and leucine-rich repeats, both of which have been found to bind phosphorylated substrates to the SCF complex. The majority of F-box proteins have other associated motifs, and the functions of most of these proteins have not yet been defined.
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[
Worm Breeder's Gazette,
1995]
lin-49, an essential gene required for normal F and U cells
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[
Parasitol Today,
1988]
Ivermectin is a semi-synthetic macrocyclic lactone (Fig. I) active in single low doses against many parasites - particularly nematodes and arthropods. It has been registered for animal health use since early 1985, and was earlier this year approved for human use by the French Directorate o f Pharmacy and Drugs. Of particular interest is ivermectin's potential as a micro filaricide for treatment o f onchocerciasis. Clinical trials leave little doubt about the potential o f ivermectin as a therapeutic tool for symptomatic relief from the effects o f infection with Onchocerca volvulus, and the drug is also recognized to have potential in reducing transmission o f the parasite. The manufacturers (Merck, Sharp and Dohme) recently arranged to provide the drug free o f charge to the WHO for mass trials against onchocerciasis in 12 African and Central American countries. In this article we focus on the pharmacological properties o f ivermectin, with a brief consideration of its absorption, fate, excretion and side-effects, and a discussion o f its micro filaricidal action.
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[
Curr Biol,
2015]
Establishment of a neuronal system requires proper regulation of the F-actin-rich leading edges of migrating neurons and neurite growth cones. A new study shows that RhoG signals through the multi-domain protein anillin to stabilize F-actin in these structures.
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[
Proc Natl Acad Sci U S A,
2010]
The ternary complex of cadherin, beta-catenin, and alpha-catenin regulates actin-dependent cell-cell adhesion. alpha-Catenin can bind beta-catenin and F-actin, but in mammals alpha-catenin either binds beta-catenin as a monomer or F-actin as a homodimer. It is not known if this conformational regulation of alpha-catenin is evolutionarily conserved. The Caenorhabditis elegans alpha-catenin homolog HMP-1 is essential for actin-dependent epidermal enclosure and embryo elongation. Here we show that HMP-1 is a monomer with a functional C-terminal F-actin binding domain. However, neither full-length HMP-1 nor a ternary complex of HMP-1-HMP-2(beta-catenin)-HMR-1(cadherin) bind F-actin in vitro, suggesting that HMP-1 is auto-inhibited. Truncation of either the F-actin or HMP-2 binding domain of HMP-1 disrupts C. elegans development, indicating that HMP-1 must be able to bind F-actin and HMP-2 to function in vivo. Our study defines evolutionarily conserved properties of alpha-catenin and suggests that multiple mechanisms regulate alpha-catenin binding to F-actin.
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[
BMC Genomics,
2021]
Background: F-box proteins represent a diverse class of adaptor proteins of the ubiquitin-proteasome system (UPS) that play critical roles in the cell cycle, signal transduction, and immune response by removing or modifying cellular regulators. Among closely related organisms of the Caenorhabditis genus, remarkable divergence in F-box gene copy numbers was caused by sizeable species-specific expansion and contraction. Although F-box gene number expansion plays a vital role in shaping genomic diversity, little is known about molecular evolutionary mechanisms responsible for substantial differences in gene number of F-box genes and their functional diversification in Caenorhabditis. Here, we performed a comprehensive evolution and underlying mechanism analysis of F-box genes in five species of Caenorhabditis genus, including C. brenneri, C. briggsae, C. elegans, C. japonica, and C. remanei.Results: Herein, we identified and characterized 594, 192, 377, 39, 1426 F-box homologs encoding putative F-box proteins in the genome of C. brenneri, C. briggsae, C. elegans, C. japonica, and C. remanei, respectively. Our work suggested that extensive species-specific tandem duplication followed by a small amount of gene loss was the primary mechanism responsible for F-box gene number divergence in Caenorhabditis genus. After F-box gene duplication events occurred, multiple mechanisms have contributed to gene structure divergence, including exon/intron gain/loss, exonization/pseudoexonization, exon/intron boundaries alteration, exon splits, and intron elongation by tandem repeats. Based on high-throughput RNA sequencing data analysis, we proposed that F-box gene functions have diversified by sub-functionalization through highly divergent stage-specific expression patterns in Caenorhabditis species.Conclusions: Massive species-specific tandem duplications and occasional gene loss drove the rapid evolution of the F-box gene family in Caenorhabditis, leading to complex gene structural variation and diversified functions affecting growth and development within and among Caenorhabditis species. In summary, our findings outline the evolution of F-box genes in the Caenorhabditis genome and lay the foundation for future functional studies.
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[
West Coast Worm Meeting,
2004]
In C. elegans epidermal intermediate filaments (IFs) and their associated structures, the trans-epidermal attachments, are essential for embryonic epidermal elongation (Woo et al 2004). The formation of muscle contractile units and trans-epidermal attachments are mutually dependent during epidermal elongation. To understand how the connection between epidermis and muscle is established and how the two tissues communicate during organogenesis, we performed a screen for epidermal elongation-defective mutants. One locus identified in this screen was defined by three lethal alleles and mapped to the cluster of LG II. Subsequent analysis showed that these mutations were allelic to
vab-13 and
ven-3 . By genetic mapping and allele sequencing we showed that all these mutations affect F10E7.4, which encodes the C. elegans member of the F-spondin family of secreted proteins. F-spondin has been shown to play roles in axon guidance, cell migration, and angiogenesis. Our genetic analysis shows that in C. elegans F-spondin is required for epidermal elongation and muscle attachment, as well as for proper positioning of neuronal processes. Using GFP reporters, we found that F-spondin is expressed in body muscle cells and is a secreted protein. Thus, F-spondin may function in embryogenesis in communication between muscle and epidermis. Immunostaining of F-spondin mutants suggest that F-spondin may indirectly affect the organization of epidermal actin microfilaments and trans-epidermal attachments . We are examining the expression patterns of muscle and basement membrane components in F-spondin mutants. To study the signaling pathways regulated by F-spondin, we are testing mutations in candidate receptor genes for genetic interactions with F-spondin mutations.
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[
J Biol Chem,
2001]
Actin depolymerizing factor (ADF)/cofilin changes the twist of actin filaments by binding two longitudinally associated actin subunits, In the absence of an atomic model of the ADF/cofilin-F-actin complex, we have identified residues in ADF/cofilin that are essential for filament binding. Here, we have characterized the C-terminal tail of UNC-60B (a nematode ADF/cofilin isoform) as a novel determinant for its association with F-actin, Removal of the C-terminal isoleucine (Ile(152)) by carboxypeptidase A or truncation by mutagenesis eliminated F-actin binding activity but strongly enhanced actin depolymerizing activity, Replacement of Ile(152) by Ala had a similar but less marked effect; F-actin binding was weakened and depolymerizing activity slightly enhanced. Truncation of both Arg(151) and Ile(152) or replacement of Arg(151) with Ala also abolished F-actin binding and enhanced depolymerizing activity. Loss of F-actin binding in these mutants was accompanied by loss or greatly decreased severing activity. All of the variants of UNC-60B interacted with G-actin in an indistinguishable manner from wild type. Cryoelectron microscopy showed that UNC-60B changed the twist of F-actin to a similar extent to vertebrate ADF/cofilins. Helical reconstruction and structural modeling of UNC-60B-F-actin complex reveal how the C terminus of UNC-60B might be involved in one of the two actin-binding sites.