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Cell,
2004]
In this issue of Cell, Inoue et al. (2004) reports that LIN-18, an atypical receptor tyrosine kinase related to mammalian Ryk and Drosophila Derailed, mediates Wnt signaling in parallel to LIN-17/Frizzled (Fz) during worm vulval development. LIN-18/Ryk and LIN-17/Fz appear to exhibit distinct Wnt specificity, and surprisingly, the LIN-18 intracellular domain may be dispensable.
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Dev Dyn,
2005]
Fibroblast growth factors (FGFs) regulate many important developmental and homeostatic physiological events. The FGF superfamily contains several families. In this review, we present recent findings on the two FGFs of the nematode Caenorhabditis elegans from both functional and phylogenic points of view. C. elegans has a single FGFR (EGL-15) with two functionally exclusive isoforms, and two FGFs (LET-756 and EGL-17), which play distinct roles: an essential function for the former, and guidance of the migrating sex myoblasts for the latter. Regulation of homeostasis by control of the fluid balance could be the basis for the essential function of LET-756. Phylogenetic and functional studies suggest that LET-756, like vertebrate FGF9, -16, and -20, belongs to the FGF9 family, whereas EGL-17, like vertebrate FGF8, -17, and -18, could be included in the FGF8 family.
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Matrix Biol,
2015]
The members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of secreted proteins, MIG-17 and GON-1, play essential roles in Caenorhabditis elegans gonadogenesis. The genetic and molecular analyses of these proteinases uncovered novel molecular interactions regulating the basement membrane (BM) during the migration of the gonadal leader cells. MIG-17, which is localized to the gonadal BM recruits or activates fibulin-1 and type IV collagen, which then recruits nidogen, thereby inducing the remodeling of the BM that is required for directional control of leader cell migration. GON-1 acts antagonistically with fibulin-1 to regulate the levels of type IV collagen accumulation in the gonadal BM, which facilitates active migration of the leader cells. The cooperative action of MIG-17 and GON-1 represents an excellent model for understanding the mechanisms of organogenesis mediated by ADAMTS proteinases.
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Int J Parasitol,
2001]
The future direction of post-genomic nematode parasitology should focus on the function of the genes that are defined by large-scale expressed sequence tag sequencing and on broader questions about the genetic basis of parasitism. Functional characterisation will require the application of high throughput technologies that have been developed in other fields, including genome mapping strategies and DNA microarray analysis. These will be greatly aided by the development and application of appropriate model organisms. It is: crucial that the field make the transition from a narrow focus on one or a few genes at a time to a focus on whole genomes in order to fully realise the potential of the expressed sequence tag and other genomic projects currently under way.
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Methods,
2016]
The localization of a protein is intrinsically linked to its role in the structural and functional organization of the cell. Advances in transgenic technology have streamlined the use of protein localization as a function discovery tool. Here we review the use of large genomic DNA constructs such as bacterial artificial chromosomes as a transgenic platform for systematic tag-based protein function exploration.
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Parasitol Today,
1991]
The free-living nematode Caenorhabditis elegans offers many advantages as an experimental system and extensive similarities in overall structure and development exist between it and parasitic nematodes. The purpose of the meeting held at Broadway, 17-20 February 1991, with the financial support of the Wellcome Trust, was to stimulate interaction between schools of nematologists.
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Curr Opin Cell Biol,
1999]
In Caenorhabditis elegans, cell migration is guided by localized cues, including molecules such as EGL-17/FGF and UNC-6/netrin. These external cues are linked to an intracellular response to migrate, at least in part, by CED-5, a homolog of DOCK180/MBC, and MIG-2, a Rac-like GTPase. In addition, metalloproteases are required for a cell migration that controls organ shape.
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Trends Mol Med,
2007]
Transforming growth factor beta1 (TGFbeta1), an important pleiotropic, immunoregulatory cytokine, uses distinct signaling mechanisms in lymphocytes to affect T-cell homeostasis, regulatory T (T(reg))-cell and effector-cell function and tumorigenesis. Defects in TGFbeta1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases. TGFbeta1 prevents abnormal T-cell activation through the modulation of Ca(2+)-calcineurin signaling in a Caenorhabditis elegans Sma and Drosophila Mad proteins (SMAD)3 and SMAD4-independent manner; however, in T(reg) cells, its effects are mediated, at least in part, through SMAD signaling. TGFbeta1 also acts as a pro-inflammatory cytokine and induces interleukin (IL)-17-producing pathogenic T-helper cells (T(h) IL-17 cells) synergistically during an inflammatory response in which IL-6 is produced. Here, we will review TGFbeta1 and its signaling in T cells with an emphasis on the regulatory arm of immune tolerance.
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Trends in Parasitology,
2005]
Expressed sequence tag projects have currently produced over 400 000 partial gene sequences from more than 30 nematode species and the full genomic sequences of selected nematodes are being determined. In addition, functional analyses in the model nematode Caenorhabditis elegans have addressed the role of almost all genes predicted by the genome sequence. This recent explosion in the amount of available nematode DNA sequences, coupled with new gene function data, provides an unprecedented opportunity to identify pre-validated drug targets through efficient mining of nematode genomic databases. This article describes the various information sources available and strategies that can expedite this process.
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Rev Infect Dis
]
This report summarizes the findings of the 17 published studies involving humans who have been experimentally infected with filarial parasites. Over the past 60 years, 45 individuals have been deliberately infected with Wuchereria bancrofti, Brugia malayi, Brugia pahangi, Loa loa, Mansonella perstans, Mansonella ozzardi, and/or Onchocerca volvulus. The findings from these experimental infections of humans have helped define microfilarial survival and periodicity within human hosts, the prepatent period for the causative agents of lymphatic filariasis, etiologic agents for particular clinical syndromes, immunologic and hematologic consequences of filarial infection, and the role of chemotherapeutic agents in the prevention and treatment of filarial infections.