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[
FEBS J,
2013]
Pumilio/fem-3 mRNA binding factor proteins are characterized by a sequence-specific RNA-binding domain. This unique single-stranded RNA recognition module, whose sequence specificity can be reprogrammed, has been fused with functional modules to engineer protein factors with various functions. We summarize the advances made with respect to developing RNA regulatory tools, as well as opportunities for the future.
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[
Acta Leiden,
1990]
Ivermectin, a recently developed macrocyclic lactone with broad antiparasitic activity, has been shown by a series of clinical trials to be safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/Kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement, although ivermectin has no known long-lasting effects on the adult worms. With treatment there is no significant exacerbation of either anterior or posterior segment eye disease even in those with severe ocular disease. Treatment leads to a marked and prolonged improvement in ocular status. Because of its safety and efficacy, ivermectin can be used on a mass scale and promises to revolutionize the treatment of onchocerciasis.
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[
Chembiochem,
2003]
I never expected to spend most of my life studying worms. However, when the time came for me to choose an area for my postdoctoral research, I was intrigued both with the problems of neurobiology and with the approaches of genetics. Having heard that a new "genetic organism" with a remarkably simple nervous system was being explored by Sydney Brenner - the microscopic soil nematode Caenorhabditis elegans - I decided to join Sydney in his efforts.
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[
Curr Biol,
1996]
Proteins associated with epithelial cell junctions regulate receptor tyrosine kinase activity by maintaining the basolateral localization of the receptor molecules.
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[
Bioessays,
2017]
Chromatin composition differs across the genome, with distinct compositions characterizing regions associated with different properties and functions. Whereas many histone modifications show local enrichment over genes or regulatory elements, marking can also span large genomic intervals defining broad chromatin domains. Here we highlight structural and functional features of chromatin domains marked by histone modifications, with a particular emphasis on the potential roles of H3K27 methylation domains in the organization and regulation of genome activity in metazoans.
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[
1980]
In addition to the extensively studied class of mutants with alterations of muscle organization (this volume, Chapter 2), mutants with enzymatic defect are being investigated in Caenorhabditis elegans. This chapter reviews mutants affecting kynurenine hydrolylase, kynureninase, acetylcholinesterase, choline acetyltransferase, and endodeoxyribonuclease. Also included are mutants altered in the metabolism of
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[
Clin Microbiol Infect,
2011]
Lymphatic filariasis (LF) and onchocerciasis are parasitic nematode infections that are responsible for a major disease burden in the African continent. Disease symptoms are induced by the immune reactions of the host, with lymphoedema and hydrocoele in LF, and dermatitis and ocular inflammation in onchocerciasis. Wuchereria bancrofti and Onchocerca volvulus, the species causing LF and onchocerciasis in Africa, live in mutual symbiosis with Wolbachia endobacteria, which cause a major part of the inflammation leading to symptoms and are antibiotic targets for treatment. The standard microfilaricidal drugs ivermectin and albendazole are used in mass drug administration programmes, with the aim of interrupting transmission, with a consequent reduction in the burden of infection and, in some situations, leading to regional elimination of LF and onchocerciasis. Co-endemicity of Loa loa with W. bancrofti or O. volvulus is an impediment to mass drug administration with ivermectin and albendazole, owing to the risk of encephalopathy being encountered upon administration of ivermectin. Research into new treatment options is exploring several improved delivery strategies for the classic drugs or new antibiotic treatment regimens for anti-wolbachial chemotherapy.
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[
Front Genet,
2017]
Parkinson's disease (PD) is a neurodegenerative disorder with symptoms that progressively worsen with age. Pathologically, PD is characterized by the aggregation of -synuclein in cells of the substantia nigra in the brain and loss of dopaminergic neurons. This pathology is associated with impaired movement and reduced cognitive function. The etiology of PD can be attributed to a combination of environmental and genetic factors. A popular animal model, the nematode roundworm Caenorhabditis elegans, has been frequently used to study the role of genetic and environmental factors in the molecular pathology and behavioral phenotypes associated with PD. The current review summarizes cellular markers and behavioral phenotypes in transgenic and toxin-induced PD models of C. elegans.
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[
Curr Opin Struct Biol,
2018]
The cysteine protease separase opens the cohesin ring by cleaving its kleisin subunit and is a pivotal cell cycle factor for the transition from metaphase to anaphase. It is inhibited by forming a complex with the chaperone securin, and in vertebrates, also by the Cdk1-cyclin B1 complex. Separase is activated upon the destruction of securin or cyclin B1 by the proteasome, after ubiquitination by the anaphase-promoting complex/cyclosome (APC/C). Here we review recent structures of the active protease segment of Chaetomium thermophilum separase in complex with a substrate-mimic inhibitor and full-length Saccharomyces cerevisiae and Caenorhabditis elegans separase in complex with securin. These structures define the mechanism for substrate recognition and catalysis by separase, and show that securin has extensive contacts with separase, consistent with its chaperone function. They confirm that securin inhibits separase by binding as a pseudo substrate.
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[
RNA,
2009]
GW182 family proteins interact directly with Argonaute proteins and are required for miRNA-mediated gene silencing in animal cells. The domains of the GW182 proteins have recently been studied to determine their role in silencing. These studies revealed that the middle and C-terminal regions function as an autonomous domain with a repressive function that is independent of both the interaction with Argonaute proteins and of P-body localization. Such findings reinforce the idea that GW182 proteins are key components of miRNA repressor complexes in metazoa.