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[
Clin Dermatol
]
Onchocerciasis results from infestation by the nematode Onchocerca volvulus and is characterized by troublesome itching, skin lesions, and eye manifestations. Although partially controlled by international mass prevention programs, onchocerciasis remains a major health hazard and is endemic in Africa, Arabia, and the Americas. Onchocerciasis is spread by bites from infested black flies, which transmit larvae that subsequently develop into adult filariae. Skin symptoms are commonly nonspecific and include severe pruritus, acute and chronic dermatitis, vitiligo-like hypopigmentation, and atrophy. Onchocercal ocular disease covers a large spectrum of manifestations, which in severe cases, may lead to blindness. Diagnosis is usually made by direct visualization of the larvae emerging from superficial skin biopsies, "skin snips." In some cases, the microfilariae can also be directly observed at the slit lamp when migrating into the anterior chamber of the eye. Ivermectin is, at present, the drug of choice for skin and ocular manifestations. Recent research using a chemotherapeutic approach that targets filarial Wolbachia symbionts in the treatment and control of onchocerciasis, however, suggests that 100 mg/d of doxycycline for 6 weeks might be effective in reducing the filarial load and preventing ocular symptoms.
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Genes, Brain, & Behavior,
2005]
The intensely studied model organisms Caenorhabditis elegans and Drosophila melanogaster have been employed to study a number of neurodegenerative diseases, including Alzheimer''''s disease (AD). Although worms and flies are phylogenetically distant from humans, results of both classic genetic analyses and transgenic manipulation of these invertebrates suggest they are valid models for at least some aspects of AD. This review describes the rationale for AD-relevant studies in worms and flies and discusses both what has been learned from these studies and what may be discovered in the future.
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[
1980]
Locomotory behavior has been investigated in a wide variety of animals, including nematodes. Many studies have concluded that locomotory behavior is under neurogenic control, i.e., during locomotion the coordinated contractions of relevant muscles results from a coordinated firing of motoneurons. Nematodes have long been known to have only a small number of neurons (about 250 in the adult female), an attribute which should make them an attractive simple system in which to examine the control of locomotion. It should be possible, for example, to examine the role of individual neurons in the control of locomotion and also to determine which interactions between neurons are responsible for locomotory behavior. These studies have not been previously attempted primarily because the anatomy of nematode motoneurons had not been determined (a situation recently remedied, see Section IV, B). In the absence of this knowledge, the analysis of nematode locomotion has concentrated on the role of interconnections between muscle cells, and has been dominated by the suggestion that the coordinated contraction of muscle cells results from these interconnections (i.e., myogenic control of locomotion). In these models, the nervous system is relegated to switching the musculature between different patterns of contraction (i.e., directions of wave propagation). This type of organization has been called neurocratic. It is not yet clear whether the control of locomotion in nematodes in neurogenic or myogenic. Our bias (which will be clear) is that it is the nervous system which plays the major role, but the crucial experiments
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Mech Ageing Dev,
2001]
Transgenic Drosophila melanogaster and Caenorhabditis elegans strains have been engineered to express human proteins associated with neurodegenerative diseases. These model systems include transgenic animals expressing beta-amyloid peptide (Alzheimer's disease), polyglutamine repeat proteins (Huntington's disease, Spinocerebellar ataxia), and alpha-synuclein (Parkinson's disease). In most of these invertebrate models, some aspects of the human diseases are reproduced, Although expression of all these proteins in transgenic mice has been instructive, the invertebrate models offer experimental advantages (e.g. forward genetic screens) that can potentially address some of the outstanding questions regarding the cellular processes underlying these diseases. This review considers what has been learned from these invertebrate models, and speculates what further insight may be gained from them.
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Semin Cell Dev Biol,
2014]
In the natural environment it is vital that organisms are capable of locating mates to reproduce and, consequently, increase the diversity of their gene pool. Many species make use of audio and visual communication for mate location. However, the more ancient form of chemical communication is used by all forms of life, from bacteria to mammals. In the past decade, much information has been discovered regarding pheromones in the nematode Caenorhabditis elegans. In this review, chemical signals that govern mating behavior in C. elegans will be discussed, from the existence and identification of mating cues, to the neurons involved in the behavioral response. Specifically, mate attraction is dictated by specific glycosides and side chains of the dideoxysugar ascarylose, a class of molecules known as ascarosides. Intriguingly, modifications of the ascarosides can dictate different behaviors such as male attraction, hermaphrodite attraction, and dauer formation. In general, interactions between core sensory neurons such as ASK and sex-specific neurons like CEM are critical for detecting these small molecules. These data reveal the existence of a complex, synergistic, chemical mating cue system between males and hermaphrodites in C. elegans, thereby highlighting the importance of mate attraction in a primarily hermaphroditic population.
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Choudhury M, Bansal A, Audouze K, Langouet S, Touma C, Howard S, Kassotis CD, Shree N, Munic Kos V, Lagadic-Gossmann D, Legrand A, Barouki R, Babin PJ, Le Mentec H, Ji Kim M, Martin-Chouly C, Vom Saal FS, Podechard N, Mohajer N, Heindel JJ, Blumberg B
[
Biochem Pharmacol,
2022]
There is increasing evidence of a role for environmental contaminants in disrupting metabolic health in both humans and animals. Despite a growing need for well-understood models for evaluating adipogenic and potential obesogenic contaminants, there has been a reliance on decades-old in vitro models that have not been appropriately managed by cell line providers. There has been a quick rise in available in vitro models in the last ten years, including commercial availability of human mesenchymal stem cell and preadipocyte models; these models require more comprehensive validation but demonstrate real promise in improved translation to human metabolic health. There is also progress in developing three-dimensional and co-culture techniques that allow for the interrogation of a more physiologically relevant state. While diverse rodent models exist for evaluating putative obesogenic and/or adipogenic chemicals in a physiologically relevant context, increasing capabilities have been identified for alternative model organisms such as Drosophila, C. elegans, zebrafish, and medaka in metabolic health testing. These models have several appreciable advantages, including most notably their size, rapid development, large brood sizes, and ease of high-resolution lipid accumulation imaging throughout the organisms. They are anticipated to expand the capabilities of metabolic health research, particularly when coupled with emerging obesogen evaluation techniques as described herein.
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Trends Microbiol,
2005]
The nematode Caenorhabditis elegans is emerging as a facile and economical model host for the study of evolutionarily conserved mechanisms of microbial pathogenesis and innate immunity. A rapidly growing number of human and animal microbial pathogens have been shown to injure and kill nematodes. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. C. elegans has been used in mutation-based screening systems to identify novel virulence-related microbial genes and immune-related host genes, many of which have been validated in mammalian models of disease. C. elegans-based pathogenesis systems hold the potential to simultaneously explore the molecular genetic determinants of both pathogen virulence and host defense.
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[
Ciba Found Symp,
1987]
Onchocerciasis can cause severe dermal and ocular disease due, it is thought, to the events surrounding the destruction of the microfilarial stage. The evolution of papular pruritic dermatitis and punctate keratitis is clearly related to the killing of microfilariae. Other more chronic changes such as dermal and epidermal atrophy are probably due to repeated episodes of microfilarial killing. It is common to find that not all patients are, at any one time, mounting clinically obvious destructive host responses against the microfilariae, and such individuals can carry very high loads of parasites without any apparent adverse effects. The immunological basis of the differences between these types of patients forms one of the most important questions in the pathogenesis of onchocerciasis today. Various explanations are now emerging. These include immunosuppressive factors and variation in the form of Onchocerca volvulus antigens presented to the host. Clinical presentations of this disease appear to reflect variations in host responses and can be used to provide information concerning the protective immune responses an individual can mount against this parasite.
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Exp Gerontol,
2006]
Caenorhabditis elegans has been used to model aspects of a number of age-associated neurodegenerative diseases, including Alzheimer''s, Parkinson''s and Huntington''s diseases. These models have typically involved the transgenic expression of disease-associated human proteins. Here I describe my laboratory''s specific experience engineering C. elegans models of Alzheimer''s disease, and give a general consideration of the advantages and disadvantages of these C. elegans models. The type of insights that might be gained from using these (relatively) simple models are highlighted. In particular, I consider the potential these models have for uncovering common and unique fundamental toxic mechanisms underlying human neurodegenerative diseases.