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Exp Gerontol,
2004]
Aging has been characterised in detail in relatively few animal species. Here we describe the aging process in free-living adults of the parasitic nematode Strongyloides ratti. We find that the phenomenology of aging in S. ratti free-living females, resembles that of the short-lived free-living nematode Caenorhabditis elegans, except that it unfolds far more rapidly. The mean (3.0+/-0.1 days) and maximum (4.5+/-0.8 days) lifespans of free-living S. ratti females are approximately one quarter of equivalent values for C. elegans. Demographic senescence (a hallmark of aging) was observed in free-living S. ratti, with a mortality rate doubling time of 0.8+/-0.1 days (females), compared with 2.0+/-0.3 in C. elegans. S. ratti lifetime fertility and lifespan were affected by temperature, and there is an age-related decline in feeding rate and movement, similar to C. elegans, but occurring more quickly. Gut autofluorescence (lipofuscin) also increased with age in S. ratti free-living females, as in aging C. elegans. These findings show that the extreme brevity of life in free-living S. ratti adults, the shortest-lived nematode described to date, is the consequence of rapid aging, rather than some other, more rapid and catastrophic life-shorteningpathology.
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Science,
2012]
Piwi-interacting RNAs (piRNAs) are small RNAs required to maintain germline integrity and fertility, but their mechanism of action is poorly understood. Here we demonstrate that Caenorhabditis elegans piRNAs silence transcripts in trans through imperfectly complementary sites. Target silencing is independent of Piwi endonuclease activity or "slicing." Instead, piRNAs initiate a localized secondary endogenous small interfering RNA (endo-siRNA) response. Endogenous protein-coding gene and transposon transcripts exhibit Piwi-dependent endo-siRNAs at sites complementary to piRNAs and are derepressed in Piwi mutants. Genomic loci of piRNA biogenesis are depleted of protein-coding genes and tend to overlap the start and end of transposons in sense and antisense, respectively. Our data suggest that nematode piRNA clusters are evolving to generate piRNAs against active mobile elements. Thus, piRNAs provide heritable, sequence-specific triggers for RNA interference in C. elegans.
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Methods Mol Biol,
2017]
Noncoding RNAs have essential biochemical functions in different areas of cellular metabolism, including protein synthesis, RNA splicing, protein secretion, and DNA replication. We have successfully used Morpholino antisense oligonucleotides for the functional inactivation of small noncoding RNAs required for DNA replication (Y RNAs in vertebrates and stem-bulge RNAs in nematodes). Here we discuss specific issues of targeting functional noncoding RNAs for inactivation by Morpholino antisense oligonucleotides. We present protocols for the design, preparation, and efficacy controls of Morpholino antisense oligonucleotides, as well as brief descriptions for their delivery into vertebrate and nematode embryos.
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Nature,
2018]
During development and adulthood, brain plasticity is evident at several levels, from synaptic structure and function to the outgrowth of dendrites and axons. Whether and how sex impinges on neuronal plasticity is poorly understood. Here we show that the sex-shared GABA (-aminobutyric acid)-releasing DVB neuron in Caenorhabditis elegans displays experience-dependent and sexually dimorphic morphological plasticity, characterized by the stochastic and dynamic addition of multiple neurites in adult males. These added neurites enable synaptic rewiring of the DVB neuron and instruct a functional switch of the neuron that directly modifies a step of male mating behaviour. Both DVB neuron function and male mating behaviour can be altered by experience and by manipulation of postsynaptic activity. The outgrowth of DVB neurites is promoted by presynaptic neurexin and antagonized by postsynaptic neuroligin, revealing a non-conventional activity and mode of interaction of these conserved, human-disease-relevant factors.
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Nature,
2020]
Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms<sup>1</sup>. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts<sup>2,3</sup>. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine -hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C.elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.
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Biophys J,
2007]
Formation of heteromeric complexes between voltage-gated K(+) (Kv) channels and accessory (beta) subunits, is a widespread means to generate heterogeneity of K(+) current in the nervous system. Here we investigate the principles that determine the interactions of Caenorhabditis elegans MPS-1--a bifunctional beta-subunit which possesses kinase activity--with Kv channels. MPS-1 belongs to the evolutionarily conserved family of KCNE beta-subunits that modulate the functional properties of a variety of Kv channels and when defective, can cause congenital and acquired disease in Homo sapiens. In Chinese Hamster ovary (CHO) cells, MPS-1 forms stable complexes with different alpha-subunits. The transmembrane domain (TMD) of MPS-1 is necessary and sufficient for MPS-1 complex formation. The hydropathicity of the TMD is an important factor controlling MPS-1 assembly. A highly hydropathic MPS-1 mutant fails to interact with its endogenous channel partners when transgenically expressed in living worms. The hydropathic mechanism does not require specific points of contact between interacting proteins. This may allow MPS-1 to assemble with various Kv channels presumably modifying the electrical properties of each.
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Antioxidants (Basel),
2019]
The characterization of compounds with antioxidant activity is of great interest due to their ability to reduce reactive oxygen species production and, therefore, prevent some age-related diseases. Its antioxidant capacity can be analyzed by different methods both in vitro and in vivo. <i>Caenorhabditis elegans</i> is an in vivo model widely used in ageing research. Until now, available tests analyze functional effects in the worms, so the antioxidant activity of the compound is indirectly monitored. We have developed a simple and a reliable method to quantify internal antioxidant activity in vivo. To validate this method, we analyzed an aqueous green tea extract and two other compounds with a well-known antioxidant activity and without this activity. The results obtained (EC<sub>50</sub> green tea = 21.76 +/- 1.28 g/mL; EC<sub>50</sub> positive control = 8.50 +/- 0.33 g/mL; negative control EC<sub>50</sub> > 500 g/mL) can help in the design of further in vivo experiments. Thus, our method can be used as a previous screening capable of reducing the gap between in vitro and in vivo assays.
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Lancet,
2004]
BACKGROUND: Infection with the parasitic filarial nematode Onchocerca volvulus can lead to severe visual impairment and ultimately blindness. Excess mortality has been noted among people with onchocerciasis, but it is not clear whether this effect is entirely due to blindness, or mediated by some more direct effects of the infection. METHODS: We assessed the relations between infection with O volvulus, visual acuity, and host mortality with data obtained by the Onchocerciasis Control Programme in West Africa from 2315 villages in 11 countries. FINDINGS: 297,756 people were eligible for follow-up, and accumulated 2,579449 person-years of follow-up from 1971 through 2001. 24,517 people died during this period; 1283 (5.2%) of these deaths were due to onchocerciasis. Mortality of the human host was significantly and positively associated with increasing microfilarial burden (p<0.00001), but not with blindness after adjustment for microfilarial load and other variables. Overall, after adjustment for microfilarial load and other variables, female individuals had a risk of death about 7.5% lower than males (p<0.00001). Rates of mortality peaked in the mid 1980s but generally decreased thereafter. INTERPRETATION: We have shown a direct relation between O volvulus microfilarial load and host mortality in a comprehensive dataset and in both sexes.
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Bioinformatics,
2017]
Motivation: Genome-scale phenotypic data are available for many model organisms, yet existing tools to functionally interpret gene sets from these phenotypic data are largely based on mutagenesis-derived phenotypes observed in mouse or human. Results: Data from both mutagenesis and knockdown experiments are incorporated into mod PhEA to allow users to perform enrichment analyses based on phenotypes observed in budding yeast ( Saccharomyces cerevisiae ), roundworm ( Caenorhabditis elegans ), fruit fly ( Drosophila melanogaster ), zebrafish ( Danio rerio ), mouse ( Mus musculus ), and humans ( Homo sapiens ). The phenotypes analyzed can be customized to investigate complex traits and gene sets from any fully sequenced animal or fungal genome are also supported by mod PhEA. Availability: Freely available on the web at
http://evol.nhri.org.tw/modPhEA /. Contact: liaoby@nhri.org.tw. Supplementary information: Supplementary data are available at Bioinformatics online.
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J Biol Chem,
2005]
We have identified a family of ancillary subunits of K+ channels in C. elegans. MPS-1 and its related members MPS-2, MPS-3 and MPS-4 are detected in the nervous system of the nematode. Electrophysiological analysis in ASE neurons and mammalian cells and epigenetic inactivation by double-stranded RNA interference (RNAi) in vivo show that each MPS can associate with and functionally endow the voltage-gated K+ channel KVS-1. In the chemosensory neuron ADF, three different MPS subunits combine with KVS-1 to form both "homomeric" (MPS-1/KVS-1) and "heteromeric" (MPS-2/MPS-3/KVS-1) complexes. RNAi of MPS-2, MPS-3 or both, enhance the taste of the animal for sodium without altering the susceptibility to other attractants. When sodium is introduced in the test plate as background or as antagonist attractant, the nematode loses the ability to recognize a second attractant. Thus, it appears that the chemosensory apparatus of C. elegans uses sensory thresholds and that a voltage-gated K+ channel is specifically required for this mechanism.