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[
Nat Rev Genet,
2003]
Many crucial decisions, such as the location and timing of cell division, cell-fate determination, and embryonic axes establishment, are made in the early embryo, a time in development when there is often little or no transcription. For this reason, the control of variation in gene expression in the early embryo often relies on post-transcriptional control of maternal genes. Although the early embryo is rife with translational control, controlling mRNA activity is also important in other developmental processes, such as stem-cell proliferation, sex determination, neurogenesis and erythropoiesis.
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Prog Mol Biol Transl Sci,
2009]
Translational control of specific messenger RNAs, which themselves are often asymmetrically localized within the cytoplasm of a cell, underlies many events in germline development, and in embryonic axis specification. This comprehensive, but by no means exhaustive, review attempts to present a picture of the present state of knowledge about mechanisms underlying mRNA localization and translational control of specific mRNAs that are mediated by trans-acting protein factors. While RNA localization and translational control are widespread in evolution and have been studied in many experimental systems, this article will focus mainly on three particularly well-characterized systems: Drosophila, Caenorhabditis elegans, and Xenopus. In keeping with the overall theme of this volume, instances in which translational control factors have been linked to human disease states will also be discussed.
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Neurosci Biobehav Rev,
1996]
The early embryo orients to the antero-posterior axis and differentiates along this, and the dorso-ventral and lateral axes. From Drosophila melanogaster, detailed knowledge has accrued of how segmentation and dorso-ventral differentiation proceed, and of their genic control, mostly by selector and homeobox (Hox) genes. The study of the control of lateral differentiation, instead, has been largely neglected. Yet handed asymmetry (the "obvious" asymmetries of, for example, heart, lung, anatomical features of the nervous system, etc.) is basic and, possibly, universal. In the mouse, two genes control this: the iv gene which, when mutated, leads to random, in the place of biased, asymmetry and so to random situs inversus viscerum: and the inv mutation which, by contrast, results in 100% situs inversus. Both mutants act as autosomal recessives. Human situs inversus is heterogeneous and may be akin to that produced by the murine iv gene. In spite of situs inversus, there is no shift of hand preference; but there is no information on other lateralization, e.g. of language or of dermatoglyphic patterns. Handed asymmetry is known in Drosophila, but there is no information on its control. In the experimental nematode, Caenorhabditis elegans, asymmetry arises when differently programmed cells arrange themselves to the two body sides, and is present already at the six-cell stage; and even the major sensory neurons chains along the body axis are distributed unequally on the two sides of the worm. Experimentally, by embryonic micro-manipulation or the use of chemical mutagens, the normal and invariate direction of handed asymmetry can be reversed.
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[
Curr Biol,
1994]
Two genes that control dauer formation in the soil nematode Caenorhabditis elegans have direct effects on senescence.
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Med Trop (Mars),
1998]
Two methods are being used to control onchocerciasis. The first has a delayed effect and consists in reducing or interrupting transmission of Onchocerca volvulus by eradication of the vector at its most vulnerable developmental stage, i.e. the larval stage. The second method has more immediate effects and consists in mass treatment using ivermectin, the only widely available drug, to reduce the density of microfilariae (the pathogenic stage of the parasite) in the population. Both strategies have been implemented within the framework of two international programs: the Onchocerciasis Control Program (OCP) in West Africa, which started in 1974 and will continue until the end of 2002, and the African Program for Onchocerciasis Control (APOC), which was launched in 1995 and will last for 12 years. This article presents an overview of the efficacy of available control tools, as well as the objectives, strategies, organization, and results of the two ongoing control programs. Also dealt with are future perspectives of onchocerciasis control including monitoring techniques to maintain OCP gains, and research to develop new control tools and optimize the program efficacy.
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Sci Robot,
2021]
Analysis of <i>Caenorhabditis elegans</i> natural movement and optogenetic control of its muscle cells enable controlled locomotion.
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[
Acta Leiden,
1990]
Community trials were started to address questions concerning the safety of ivermectin during large scale treatment, its potential for transmission control, its effect in preventing ocular onchocercal disease, its acceptability and the organization of large scale treatment. A summary is presented of the major, latest results on the short-term epidemiological impact of large scale ivermectin treatment, as observed in eight community trials undertaken in the Onchocerciasis Control Programme in West Africa (OCP). Ivermectin treatment resulted in a 96%-99% reduction in the mean load of microfilariae (mf) in the skin in treated patients. The subsequent mf-repopulation of the skin was faster than in the clinical trials and after 12 months the mean loads had returned to more than 40% of the pre-treatment load. Ocular mf loads were also greatly reduced and a post-treatment regression of early lesions of the anterior segment of the eye was observed. The transmission of Onchocerca volvulus was reduced by some 60% during the first year after treatment in one trial but no additional reduction was observed after the second treatment round. These results, and other recent research findings, have been used to quantify an epidemiological model for the transmission and control of onchocerciasis. Preliminary results of computer simulations of the predicted long-term epidemiological impact of large scale ivermectin treatment indicate that ivermectin treatment may play a very important role in disease control but that it is unlikely to become a practical tool for transmission control in endemic foci. Ivermectin treatment appears to be the most appropriate method for control of recrudescence of infection in an area where the parasite reservoir has been virtually eliminated by vector control, such as in the core area of the OCP.
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WormBook,
2005]
Early development of many species depends on the temporal and spatial control of maternal gene products. This review discusses the control of maternal mRNAs that encode regulators of C. elegans embryogenesis. In the C. elegans embryo, maternal mRNA regulation is crucial to the patterning of early cell fates. Translational control of key mRNAs spatially organizes cell signaling pathways, localizes transcription factor activities, and controls germ cell precursor development. From the few mRNAs studied thus far, some themes are beginning to emerge. Control of maternal mRNA translation begins in the hermaphrodite germ line. Distinct regulatory systems keep mRNAs silent during different stages of oogenesis, and lead to precise temporal and spatial patterns of translation in the embryo. In the embryo, cell polarity factors control the localization of translational regulators. Each maternal mRNA contains multiple elements in its 3'' untranslated region (3'' UTR) that specify the timing and localization of translation. A relatively small number of RNA-binding proteins likely control many mRNAs through these 3'' UTR elements. Therefore, the combination of RNA elements and the regulatory complexes recruited to them specify unique patterns of translation for different mRNAs. The mechanisms of translational control are only beginning to be explored, but are likely to regulate diverse developmental and cellular events in metazoans.
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Philos Trans R Soc Lond B Biol Sci,
2018]
Control is essential to the functioning of any neural system. Indeed, under healthy conditions the brain must be able to continuously maintain a tight functional control between the system's inputs and outputs. One may therefore hypothesize that the brain's wiring is predetermined by the need to maintain control across multiple scales, maintaining the stability of key internal variables, and producing behaviour in response to environmental cues. Recent advances in network control have offered a powerful mathematical framework to explore the structure-function relationship in complex biological, social and technological networks, and are beginning to yield important and precise insights on neuronal systems. The network control paradigm promises a predictive, quantitative framework to unite the distinct datasets necessary to fully describe a nervous system, and provide mechanistic explanations for the observed structure and function relationships. Here, we provide a thorough review of the network control framework as applied to <i>Caenorhabditis elegans</i> (Yan <i>et al.</i> 2017 <i>Nature</i><b>550</b>, 519-523. (doi:10.1038/nature24056)), in the style of Frequently Asked Questions. We present the theoretical, computational and experimental aspects of network control, and discuss its current capabilities and limitations, together with the next likely advances and improvements. We further present the Python code to enable exploration of control principles in a manner specific to this prototypical organism.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling <i>C. elegans</i> at cellular resolution'.
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Exp Gerontol,
1997]
The nematode Caenorhabditis elegans has been used extensively as a model system for the study of basic biological processes. In this species, apoptosis and aging are both under genetic control. Molecular studies have shown that the death machinery that kills C. elegans cells has remained conserved through evolution and also functions to promote apoptotic death in mammalian cells. At least some of the genes that affect C. elegans life span are also evolutionarily conserved; whether the vertebrate homologs of these genes also influence life span remains to be determined. Although a large number of mutations have been isolated that affect either apoptosis or aging in C. elegans, there is so far no evidence that the genetic pathways that control these processes might overlap.