Wood WB et al. (1994) Worm Breeder's Gazette "Low Temperature Affects Embryonic Handedness Reversal."

Bergmann DC, Florance A, Wood WB

[Worm Breeder's Gazette, 1994]

LOW TEMPERATURE AFFECTS EMBRYONIC HANDEDNESS REVERSAL Bill Wood, Arny Florance and Dominique Bergmann Department of MCD Biology, University of Colorado, Boulder C. elegans embryos become left-right asymmetric at the 6-cell stage witlf a handedness which is essentially invariant among N2 animals reared at 20, and which persists into adulthood, determining the asymmetric placement of the gonad, intestine, the coelomocytes, and several other cells. Reversal of embryonic handedness at the 6-cell stage by micromanipulation results in development of healthy adults with all left-right asymmetries reversed. l Spontaneous reversal occurs at a frequency of a few percent among animals developing embryos treated with chitinase at the 2-cell stage to remove the egg shell.2 We have now found that when N2 are reared at 10, the frequency of animals with reversed gonad handedness as adults increases to above 0.5%. Those examined by Nomarski microscopy exhibited handedness reversal of the ventral nerve cord (cell bodies on the left) and reversed placement of the coelomocytes as well as the intestine and gonad, suggesting that these animals developed from reversed embryos. To determine the cold-sensitive period for handedness reversal, young gravid adults reared at 20 were placed at 10 for 2 hours, then transferred to new 20 plates and subsequently transferred to fresh 20 plates at 2-hr intervals. Eggs laid during the cold pulse (interval l; exposed to 10 after fertilization), the first 2 hr after return to 20 (interval 2; exposed to 10 either just before or just after fertilization), and each of the four subsequent 2-hr intervals at 20 (3-6, exposed to 10 before fertilization) were allowed to hatch and develop at 20 into adults, which were then scored for gonad handedness. Among animals developing from embryos exposed to 10 after fertilization (interval 1), no reversals were' observed (N=1,956), whereas among animals developing from oocytes and sperm exposed to 10 before fertilization (intervals 3-6), the frequency of reversal was 0.21% + 0.09% (N=9,223). Surprisingly, although left-right asymmetry first appears at the 6-cell stage, and the embryo's left and right are highly unlikely to be specified until the 4-cell stage, I the cold-sensitive period for reversal is before fertilization. This result suggests that the effect is on the gametes. We can imagine two possible explanations: 1) Production of some eggshell precursor component, synthesized during oogenesis, could be cold sensitive, such that embryos with "soft" eggshells are produced at 10, leading to a low frequency of reversal as seen in chitinased embryos.2 2) Some handed structure in a gamete, such as the sperm centriole for example, may normally dictate the skewing of the ABa and ABp spindles that leads to handed asymmetry in the embryo;l when this structure is exposed to 10 its subsequent ability to dictate handedness could be impaired, leading to a low frequency of reversal. We are currently carrying out experiments with chilled males to determine whether egg or sperm is the cold-sensitive gamete, as well as examining effects of other treatments on handedness reversal. Finally, we are continuing small scale screens for maternal-effect mutations that result in a high frequency of embryonic reversal. None have been found, but so far we have screened only about 1000 EMS-mutagenized genomes. I Wood, W. B. (1991) Nature 349: 536-538. 2 Wood, W. B. and Kershaw, D. (1991) In Biological Asymmetry and Handedness, CIBA Foundation Symposium 162: 143-164.

Wood WB et al. (1996) Dev Genet "Maternal effect of low temperature on handedness determination in C. elegans embryos."

Florance A, Wood WB, Bergmann DC

[Dev Genet, 1996]

C. elegans embryos, larvae, and adults exhibit several left-right asymmetries with an invariant dextral handedness, which first becomes evident in the embryo at the 6-cell stage. Reversed (sinistral) handedness was not observed among > 10,000 N2 adults reared at 16 degrees C or 20 degrees C under standard conditions. However, among the progeny of adults reproducing at 10 degrees C, the frequency of animals with sinistral handedness was increased to approximately 0.5%. Cold pulse experiments indicated that the critical period for this increase was in early oogenesis, several hours before the first appearance of left-right asymmetry in the embryo. Hermaphrodites reared at 10 degrees C and mated with males reared at 20 degrees C produced sinistral outcross as well as sinistral self-progeny, indicating that the low temperature effect on oocytes was sufficient to cause reversals. Increased frequency of reversal was also observed among animals developed from embryos lacking the egg shell. Possible mechanisms for the control of embryonic handedness are discussed in the context of these results, including the hypothesis that handedness could be dictated by the chirality of a gametic component.

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

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).

Danielle Thierry-Mieg et al. (2003) Worm Breeder's Gazette "www.wormgenes.org , a new gene centered database"

Vahan Simonyan, Michel Potdevin, Mark Sienkiewicz, Yuji KOHARA, Jean Thierry-Mieg, Danielle Thierry-Mieg, Tadasu SHIN-I

[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.

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[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.

Hodgkin JA (1998) International Journal of Developmental Biology "Seven types of pleiotropy."

Hodgkin JA

[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.

Tuck S (2011) Curr Biol "Extracellular vesicles: budding regulated by a phosphatidylethanolamine translocase."

Tuck S

[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.

Viney ME et al. (2004) Naturwissenschaften "Is dauer pheromone of Caenorhabditis elegans really a pheromone?"

Viney ME, Franks NR

[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.

Schaeffer JM et al. (1990) J Antibiot (Tokyo) "Cochlioquinone A, a nematocidal agent which competes for specific [3H]ivermectin binding sites."

Williamson JM, Schaeffer JM, Bergstrom AR, Liesch JM, Goetz MA, Frazier EG

[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.

Desta IT et al. (2016) J Lab Autom "Detecting and Trapping of a Single C. elegans Worm in a Microfluidic Chip for Automated Microplate Dispensing."

Giakoumidis N, Mustafa N, AlGharibeh N, Orozaliev A, Al-Sharif A, Song YA, Desta IT, Gunsalus KC

[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.