Donfack J et al. (1999) Bull Soc Pathol Exot "[Variations under genetic control of onchocerca infection as a function of clinical profile in the endemic center of Cameroon]."

Same-Ekobo A, Zimmerman PA, Nutman J, Ngu JL, Lando G, Donfack J

[Bull Soc Pathol Exot, 1999]

Onchocerciasis, also known as "river blindness", presents a plenum of clinical manifestations which vary from one individual to another, and from one area to another. This large spectrum of clinical manifestations of the disease is an indication of the complexity of the pathogenesis of onchocerciasis and suggests that many interacting factors might influence the clinical features of the disease. The present study has focused on the heterogenicity of the host immune response as a plausible explanation for differences in clinical manifestations of the infection. Host genetic factors, namely HLA genes, might play an important role in determining the nature of the immune response mounted against the parasite Onchocerca volvulus, and thus the development of different manifestations of the infection. Genetic diversity of onchocerciasis was assessed in different endemic foci in Cameroon. In order to investigate the possibility that the Major Histocompatibility Complex (MHC) genes might be associated with the different clinical types of onchocerciasis, 146 subjects living in three endemic areas of Cameroon were studied. They were classified in four groups: A (asymptomatic subjects), P (putatively immune subjects) L (patients with localised disease) and G (patients with generalised disease). The four groups differed in the distribution of HLA class II alleles as determined by Direct Heteroduplex Analysis. On the one hand, allele HLA-DQA1*0501 appeared to be associated with protection against severe onchocerciasis; on the other, allele HLA-DQB1*0201 might play an important role in the severe form of the disease.

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.

Ding, Wei et al. (2015) International Worm Meeting "s-adenosylmethione levels govern innate immunity through distinct methylation-dependent pathways ."

Ding, Wei, Walker, Amy, Hou, Nicole, Smulan, Lorissa, Bozonnet, Noemie, Taubert, Stefan, Watts, Jennifer

[International Worm Meeting, 2015]

s-adenosylmethionine (SAMe) modulates cellular functions as the sole methyl donor modifying histones, nucleic acids and phospholipids. Fluctuation in SAMe impacts phosphatidylcholine (PC) synthesis in the liver and several mammalian studies correlate SAMe levels with variations in DNA or histone methylation. In addition, low SAMe is associated with with lipid accumulation, increased tissue injury and immune responses in mammalian metabolic diseases, such as fatty liver disease. However, molecular connections between SAMe limitation, individual methyltransferases and these phenotypes are unclear. We had previously found that knockdown or mutation in the C. elegans SAMe synthase sams-1 exhibited lipid accumulation and now we find that the low SAMe can also associated with activation or attenuation Caenorhabditis elegans immune responses depending on bacterial food source. On non-pathogenic Eschericia coli diets, innate immune pathways are stimulated with increased expression of genes associated with defense against bacterial pathogens and constituative phosphorylation of PMK-1, a p38 MAP kinase essential for innate immune responses. Dietary rescue experiments show that this activation of innate immunity is downstream of methylation-dependent PC production.However, when challenged with pathogenic Pseudomonas aeruginosa, sams-1(lof) animals die rapidly, despite activation of protective MAPK pathways. We find that distinct SAMe-dependent mechanisms are linked to Pseudomonas-specific responses in sams-1 animals. C. elegans undertakes a broad transcriptional response to pathogenic bacteria and we find that low SAMe restricts an activating histone methylation mark, H3K4me3, on promoters of Pseudomonas-responsive genes and limits induction of these pathogen responsive genes. Furthermore, we find the H3K4 methyltransferase set-16/MLL is critical for transcriptional responses to bacterial stress. Thus, our studies provide molecular links between SAMe levels and innate immune functions and suggest that a primary effect of SAMe depletion is limitation of stress-induced gene expression.

Banerjee N et al. (2023) Proc Natl Acad Sci U S A "Differential processing of a chemosensory cue across life stages sharing the same valence state in Caenorhabditis elegans."

Hallem EA, Shih PY, Banerjee N, Sternberg PW, Rojas Palato EJ

[Proc Natl Acad Sci U S A, 2023]

Many chemosensory cues evoke responses of the same valence under widely varying physiological conditions. It remains unclear whether similar or distinct neural mechanisms are involved in the detection and processing of such chemosensory cues across contexts. We show that in Caenorhabditis elegans, a chemosensory cue is processed by distinct neural mechanisms at two different life stages that share the same valence state. Both starved adults and dauer larvae are attracted to carbon dioxide (CO2), but CO2 evokes different patterns of neural activity and different motor outputs at the two life stages. Moreover, the same interneuron within the CO2 microcircuit plays a different role in driving CO2-evoked motor output at the two life stages. The dauer-specific patterns of CO2-evoked activity in this interneuron require a dauer-specific gap junction complex and insulin signaling. Our results demonstrate that functionally distinct microcircuits are engaged in response to a chemosensory cue that triggers the same valence state at different life stages, revealing an unexpected complexity to chemosensory processing.

Marie-Anne Felix (2006) WormBook "Oscheius tipulae."

Marie-Anne FELIX

[WormBook, 2006]

Oscheius tipulae is a common soil nematode of the same family as C. elegans (Rhabditidae), which presents the same hermaphroditic mode of reproduction and is easily cultured in the same conditions. Oscheius tipulae has been used as a developmental genetic model system to study vulva formation. Compared to C. elegans, it has a simpler vulval cell lineage, a reduced competence group and a different mechanism of vulval cell fate patterning. The spectrum of vulval phenotypes obtained in genetic screens differs from that found in C. elegans. Its easy isolation from soil and the availability of numerous wild isolates of O. tipulae from all over the world facilitate population genetic and microevolutionary studies, especially of the evolution of cell lineage. The Oscheius genus also presents many species with interesting evolutionary changes in mode of reproduction, gonad development, body size, etc.

Ding, Wei et al. (2013) International Worm Meeting "Genome wide responses to methyl donor availability reveal effects on metabolic, stress response and germline function genes."

Ding, Wei, Irwin, Michael, Hansen, Malene, Walker, Amy K.

[International Worm Meeting, 2013]

Animals must coordinate nutritional input and metabolism with growth and reproduction. Small molecules, such as s-adenosylmethionine (SAMe) produced by the 1-carbon/folate cycle (1CC) and used as the major methyl donor, can modify protein activity and contribute to phospholipid biosynthesis. In C. elegans, reducing function of sams-1, a SAMe synthase, increases lifespan and lipid droplet accumulation while reducing fertility. We hypothesize that SAMe levels provide signals reseting physiology to compensate for altered nutritional inputs. SAMe is used for methylation of proteins, such as histones in epigenetic modification, but is also critical for production of phosphatidylcholine (PC), a major membrane phospholipid. Indeed sams-1(RNAi) animals have low levels of PC and lipid accumulation, fertility and lifespan return to wild-type levels when methylation-independent pathways of PC production are supported through dietary addition of choline. However, links between SAMe levels and direct changes of gene expression are unknown. To separate SAMe-specific effects from combined SAMe/PC functions, we compared global gene expression levels in sams-1(RNAi) animals with sams-1(RNAi) rescued by choline. Major functional groups of genes increasing with sams-1(RNAi) included metabolism (1CC, lipid biosynthesis, carbohydrate modification) and stress responses. However, decreased genes grouped in distinct subsets of metabolic pathways (carbohydrate catabolism, amino sugar metabolism and lipid binding), as well as genes important for germline function and RNA processing. We found that more than 90% of sams-1(RNAi) up- or downregulated genes returned to wild-type levels with choline supplementation. Interestingly, genes not returning to wild-type levels clustered in metabolic pathways such as the 1CC, suggesting potential for PC-independent SAMe effects. However, essentially all germline function genes were rescued. This correlates with the near complete rescue of fertility by choline, and suggests coordination of brood size with metabolic function acts through SAMe/PC pathways in these animals.

Wade N (1997) New York Times "Dainty worm tells secrets of the human genetic code."

Wade N

[New York Times, 1997]

Early this month, nearly a thousand biologists met here to discuss the affairs of a speck of protoplasm with a grandiloquent name, a barely visible, almost transparent worm called Caenorhabditis elegans. The worm holds the same secrets of life as other animals, but may be the first to yield them, an event that would deeply influence biology and medicine....

Green, James W.M. et al. (2013) International Worm Meeting "Comparative mapping of dauer larvae development in growing populations of C. elegans and C. briggsae."

Harvey, Simon C., Green, James W.M.

[International Worm Meeting, 2013]

Dauer larvae in Caenorhabditis elegans are long-lived and resistant to environmental stress. Outside of growing populations they are also the only life cycle stage that can be routinely isolated from the environment. The appropriate induction of dauer larvae development is therefore likely to be critical to genotype fitness in C. elegans. Given this, the extensive variation observed between wild isolates requires explanation. Does it represent adaptation to different environments or does it imply that there are multiple different ways to maximise fitness within the same environment? To investigate this question we have analysed dauer larvae formation and population growth in growing populations using different recombinant inbred lines (RILs) of C. elegans. These analyses allow direct comparisons between: (1) different RIL panels produced from distinct parental isolates analysed for the same dauer development same trait; (2) RILs and nearly isogenic lines (NILs) produced from the same parental isolates and analysed for the same dauer development same trait; and (3) different dauer development traits mapped using the same RIL panel. These results identify common QTL regions and both genotype and trait specific QTLs. Comparison with the results of analysis of variation in dauer larvae development within growing populations of C. briggsae RILs allows a more general picture of the control of variation of dauer larvae development in growing populations.

Ogg SC et al. (1990) Nucleic Acids Res "Splicing of a C. elegans myosin pre-mRNA in a human nuclear extract."

Wickens MP, Anderson P, Ogg SC

[Nucleic Acids Res, 1990]

Splicing of mammalian introns requires that the intron possess at least 80 nucleotides. This length requirement presumably reflects the constraints of accommodating multiple snRNPs simultaneously in the same intron. In the free-living nematode, C. elegans, introns typically are 45 to 55 nucleotides in length. In this report, we determine whether C. elegans introns can obviate the mammalian length requirement by virtue of their structure or sequence. We demonstrate that a 53 nucleotide intron from the unc-54 gene of C. elegans does not undergo splicing in a mammalian (HeLa) nuclear extract. However, insertion of 31 nucleotides of foreign, prokaryotic sequence into the same intron results in efficient splicing. The observed splicing proceeds by the same two-step mechanism observed with mammalian introns, and exploits the same 3' and 5' splice sites as are used in C. elegans. The branch point used lies in the inserted sequence. We conclude that C. elegans splicing components are either fewer in number or smaller than their mammalian counterparts.

Marck A et al. (2016) J Gerontol A Biol Sci Med Sci "Age-Related Changes in Locomotor Performance Reveal a Similar Pattern for Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus, and Homo sapiens."

Noirez P, Di Meglio JM, Garland T, Toussaint JF, Bronikowski AM, Hersen P, Foulonneau V, Marc A, Carter PA, Antero-Jacquemin J, Marck A, Berthelot G, Morgan TJ

[J Gerontol A Biol Sci Med Sci, 2016]

Locomotion is one of the major physiological functions for most animals. Previous studies have described aging mechanisms linked to locomotor performance among different species. However, the precise dynamics of these age-related changes, and their interactions with development and senescence, are largely unknown. Here, we use the same conceptual framework to describe locomotor performances in Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus, and Homo sapiens We show that locomotion is a consistent biomarker of age-related changes, with an asymmetrical pattern throughout life, regardless of the type of effort or its duration. However, there is variation (i) among species for the same mode of locomotion, (ii) within species for different modes of locomotion, and (iii) among individuals of the same species for the same mode of locomotion. Age-related patterns are modulated by genetic (such as selective breeding) as well as environmental conditions (such as temperature). However, in all cases, the intersection of the rising developmental phase and the declining senescent phase reveals neither a sharp transition nor a plateau, but a smooth transition, emphasizing a crucial moment: the age at peak performance. This transition may define a specific target for future investigations on the dynamics of such biological interactions.