Meneely PM et al. (1997) Worm Breeder's Gazette "him-8, spontaneous males, and interference"

Meneely PM, Ganta A, Kean B, Wong J

[Worm Breeder's Gazette, 1997]

Mutations in the autosomal gene cause a very high frequency X-chromosome nondisjunction without apparently affecting meiotic segregation of the autosomes. As one approach to understanding X-chromosome meiosis, we cloned him-8 by transformation rescue several years ago (S. Broverman, Meneely, and others). The putative gene as identified by transformation consists of 3 exons and is predicted to encode a novel and somewhat unremarkable protein of 195 amino acids. This structure differs from the prediction by Genefinder for this region; the first two exons are the same, but Genefinder predicts a much larger gene that does not include the third exon and whose downstream exons have homology to phosphatases. No cDNAs of this part of the gene have been found. Using RT-PCR, we have confirmed that our predicted third exon is transcribed and is spliced to the predicted second exon; in addition, the transcript is trans-spliced to SL1. We are now attempting to clarify the relationship (if any) of exons of the him-8 gene with the exons of the larger phosphatase gene downstream. Two possibilities are being explored: alternative splicing of one gene to give the smaller three exon him-8 product and the larger twelve exon phosphatase; or two genes compressed into one by Genefinder. On a related project, a simple experiment was done to explore if spontaneous males arise from X-chromosome loss during hermaphrodite oogenesis or hermaphrodite spermatogenesis. Wild-type males were mated with hermaphrodites marked with a recessive X-linked marker and the progeny scored for the presence (or absence) of patroclinous males-- that is, wild-type males arising from a nullisomic ovum and the paternal X chromosome. No patroclinous males have been found yet, suggesting that most if not all spontaneous males arise from X chromosome loss during hermaphrodite spermatogenesis. This result, in combination with previous data from others, suggests a simple idea. There is probably only one exchange per chromosome during oogenesis, based on observed interference on the X chromosome and inferences from the genetic map (Barnes et al, 1995). Zetka and Rose (1990) showed that there is less recombination on the autosomes during spermatogenesis than during oogenesis, implying that there may be slightly less than one exchange per chromosome during spermatogenesis. In addition, Hodgkin et al. (1979) showed that, in one case examined, double crossovers on the autosomes do arise during spermatogenesis, which we have confirmed. The combination of less interference and less crossing-over on the autosomes is expected to lead to a non-exchange chromosome during spermatogenesis occasionally. Perhaps there is some (unknown) mechanism by which the X chromosome is preferentially the non-exchange chromosome, accounting for its rate of loss during hermaphrodite spermatogenesis.

Meneely PM et al. (1998) East Coast Worm Meeting "Genetic and Molecular Analysis of Meiosis"

Wong J, Ganta A, Miller Z, Meneely PM, Heilig E, Lehnhoff L, Kean B, Cross E

[East Coast Worm Meeting, 1998]

Mutations in the autosomal gene him-8 cause a very high frequency X-chromosome nondisjunction without apparently affecting meiotic segregation of the autosomes. As one approach to understanding X-chromosome meiosis, we cloned him-8 by transformation rescue several years ago (S. Broverman, Meneely, and others). The putative gene as identified by transformation consists of 3 exons and is predicted to encode a novel and somewhat unremarkable protein of 195 amino acids. This structure differs from the prediction by Genefinder for this region; the first two exons are the same, but Genefinder predicts a much larger gene that does not include the third exon and whose downstream exons have homology to phosphatases. These putative downstream exons were not presented on the plasmids needed to rescue him-8 mutants. No cDNAs of the upstream part of the gene have been found. Using RT-PCR, we have confirmed that our predicted third exon is transcribed and is spliced to the two upstream exons; in addition, the transcript is trans-spliced. We have also found a transcript lacking this third exon and corresponding (in size and general structure) to the larger gene predicted by Genefinder. Most of this portion of the locus is not needed for transformation rescue of the him-8 mutant phenotype. These results suggest that the expression and splicing pattern at this locus may be complex, with only one of the transcripts corresponding to him-8. We are also using STS and morphological markers to examine the distribution and regulation of crossing-over during meiosis, that is, interference. We find that, for most of the X chromosome, there is exactly one crossover per meiosis. This confirms and extends previous suggestions by numerous others, and shows that most of the X chromosome exhibits complete interference. There appear to be important exceptions, however, since crossovers in one region near the left end of the X do not cause interference. This result is being confirmed, and the region is being mapped more precisely. The "left end of the X chromosome" has been shown to have several unusual functions in meiosis, including a proposed role in homolog recognition and/or pairing, but the unusual meiotic functions have not been localized in detail. Preliminary results suggest that there is also exactly one crossover per autosome during oogenesis. Work by others (and us) has shown that double crossovers do occur on the autosomes during spermatogenesis and that there is less crossing over in general during spermatogenesis than during oogenesis. We suggest that this combination of reduced interference and fewer crossovers is what leads to preferential nondisjunction of the X chromosome during hermaphrodites spermatogenesis-- that is, this accounts for the origin of spontaneous males.

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.