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Dunn, R., Chang, E., Farah , F., Nordquist, S., Coto Villa, D., L'Etoile, N., Baradwaj, A., Varshney, A., Bruggmann, C., Munoz, F., Siman-Tov, I., Benedetti, K., Bokka , A., Andersen, K., Li, J., Echeverria , C., VanHoven, M., Kato, S.
[
International Worm Meeting,
2019]
Sleep is a paradox: sleeping animals are less responsive to environmental dangers. vulnerable to predation, and not engaged in the pursuit of other, more immediately useful activities like finding food or a suitable mate. Nevertheless, all animals spend some portion of their lives asleep. Further, sleep deprivation has consequences for diverse organ systems, including-and especially-the brain. Experiments in flies, mice, and humans have shown that sleep is required for memory consolidation (Dudai et al., Neuron 2015). However, relatively little progress has been made toward providing satisfying molecular and cellular mechanisms of how the sleep state affects specific cellular substrates for memory (Kandel et al., Cell 2014). Our study provides a lens with which to examine one specific and well-accepted function of sleep - memory consolidation. Here we are the first to show that the soil nematode C. elegans requires sleep to consolidate long-term memory after a spaced, olfactory training paradigm. Animals that do not sleep after this training fail to consolidate the memory. Leveraging the compact, optically accessible olfactory circuit of C. elegans, we identified two specific cells and their synapses that store that olfactory memory. When we examined the dynamics of synaptic remodeling, we found that it occurs during the wakeful period after conditioning and sleep. After conditioning, sleep initiates specific downscaling of activity-marked synapses. Our research indicates that sleep initiates a cascade of cellular events that extend beyond the period of sleep. We propose that sleep triggers ongoing physical rearrangements of cells and synapses that extend into the awake state.
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Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO
[
Sci Rep,
2021]
The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).
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[
Worm Breeder's Gazette,
2003]
Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.
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Farah, F., Echeverria, C., Andersen, K., Benedetti, K., Chang, E., Varshney, A., Siman-Tov, I., Coto Villa, D., Nordquist, S., L'Etoile, N., Alladin, S., Bokka, A., Baradwaj, A., VanHoven, M., Munoz-Lobato, F.
[
International Worm Meeting,
2019]
Sleep is critical for the consolidation of memory. However, little is known about the effects of sleep on specific neuronal connections, though the modulation of these connections is thought to underlie learning and memory. We have focused our studies on the AWC olfactory circuit in C. elegans, which mediates attraction to several odorants, including butanone. Using the fluorescent split GFP-based trans-synaptic marker Neuroligin 1 GFP Reconstitution Across Synaptic Partners (NLG-1 GRASP), we have identified specific synaptic connections in the AWC olfactory circuit that are altered in a sleep-dependent manner after training with butanone. Specifically, we find that in animals that are trained three times with butanone and without food, then allowed to sleep on food for two hours, and recover on food for 14 more hours, synapses between AWC olfactory neurons and AIY interneurons are reduced in comparison with animals trained with a control buffer, but otherwise treated identically. The reduction in AWC-AIY synapses is not observed in animals that are deprived of sleep for the two hours immediately following butanone or buffer training by placing them on a plate without food, and then allowed to recover on food for 14 hours. We are currently focusing on determining the timeline of the synaptic changes using time course experiments. By discovering how memory is consolidated at the level of specific neuronal connections, we will set the stage to understand the basic cellular and molecular mechanisms of sleep, and develop more effective treatments for diseases in which memory consolidation is altered, such as Alzheimer's disease and dementia.
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[
Front Pharmacol,
2020]
Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.
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[
International Journal of Developmental Biology,
1998]
Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.
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[
Curr Biol,
2011]
Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.
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[
Naturwissenschaften,
2004]
Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.
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[
J Antibiot (Tokyo),
1990]
Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor.
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[
J Lab Autom,
2016]
Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology. In this paper, we demonstrate a microfluidic system in polydimethylsiloxane (PDMS) for dispensing of a single C. elegans worm into a 96-well plate. It consists of two PDMS layers, a flow and a control layer. Using five microfluidic pneumatic valves in the control layer, a single worm is trapped upon optical detection with a pair of optical fibers integrated perpendicular to the constriction channel and then dispensed into a microplate well with a dispensing tip attached to a robotic handling system. Due to its simple design and facile fabrication, we expect that our microfluidic chip can be expanded to a multiplexed dispensation system of C. elegans worms for high-throughput drug screening.