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.

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.

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.

Ouazana R (1978) Experientia "A morphological temperature-sensitive mutant of the nematode C. elegans var. Bergerac."

Ouazana R

[Experientia, 1978]

A morphological temperature-sensitive mutant of Caenorhabditis elegans displays 2 overlapping temperature-sensitive periods, both occurring during the post-embryonic development. Data prove that these 2 phenotypes are controlled by the same locus and are not inherited as maternal factors.

Zarse K et al. (2008) PLoS One "Antidepressants of the serotonin-antagonist type increase body fat and decrease lifespan of adult Caenorhabditis elegans."

Zarse K, Ristow M

[PLoS One, 2008]

It was recently suggested that specific antidepressants of the serotonin-antagonist type, namely mianserin and methiothepin, may exert anti-aging properties and specifically extend lifespan of the nematode C.elegans by causing a state of perceived calorie restriction (Petrascheck M, Ye X, Buck LB: An antidepressant that extends lifespan in adult Caenorhabditis elegans; Nature, Nov 22, 2007;450(7169):553-6, PMID 18033297). Using the same model organism, we instead observe a reduction of life expectancy when employing the commonly used, standardized agar-based solid-phase assay while applying the same or lower concentrations of the same antidepressants. Consistent with a well-known side-effect of these compounds in humans, antidepressants not only reduced lifespan but also increased body fat accumulation in C. elegans reflecting the mammalian phenotype. Taken together and in conflict with previously published findings, we find that antidepressants of the serotonin-antagonist type not only promote obesity, but also decrease nematode lifespan.

Teichmann SA et al. (2002) Trends Biotechnol "Conservation of gene co-regulation in prokaryotes and eukaryotes."

Babu MM, Teichmann SA

[Trends Biotechnol, 2002]

Genes that are part of the same operon in prokaryotes, or have the same expression pattern in eukaryotes, are transcriptionally co-regulated. If genes are consistently co-regulated across distantly related organisms, the genes have closely associated functions. It has been shown previously that such genes have a strong tendency to belong to the same protein complex in prokaryotes, and we show by an analysis of the sequences and their expression in the yeast Saccharomyces cerevisiae and the worm Caenorhabditis elegans that this is also true for eukaryotes. Our analysis reveals that the number of conserved co-regulated genes is small in eukaryotes, as has been shown previously in prokaryotes, indicating that there are extensive variations in the gene regulatory network across organisms.

Walker AK et al. (2011) Cell "A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans."

Rottiers V, Watts JL, Walker AK, Hansen M, Niebergall LJ, Finnegan DM, Naar AM, Jacobs RL, Jiang K, Shioda T, Yang F, Vance DE, Tzoneva M, Hart AC

[Cell, 2011]

Sterol regulatory element-binding proteins (SREBPs) activate genes involved in the synthesis and trafficking of cholesterol and other lipids and are critical for maintaining lipid homeostasis. Aberrant SREBP activity, however, can contribute to obesity, fatty liver disease, and insulin resistance, hallmarks of metabolic syndrome. Our studies identify a conserved regulatory circuit in which SREBP-1 controls genes in the one-carbon cycle, which produces the methyl donor S-adenosylmethionine (SAMe). Methylation is critical for the synthesis of phosphatidylcholine (PC), a major membrane component, and we find that blocking SAMe or PC synthesis in C. elegans, mouse liver, and human cells causes elevated SREBP-1-dependent transcription and lipid droplet accumulation. Distinct from negative regulation of SREBP-2 by cholesterol, our data suggest a feedback mechanism whereby maturation of nuclear, transcriptionally active SREBP-1 is controlled by levels of PC. Thus, nutritional or genetic conditions limiting SAMe or PC production may activate SREBP-1, contributing to human metabolic disorders.

Schwartz HT et al. (2018) Trends Genet "A Toolkit of Engineered Recombinational Balancers in C. elegans."

Schwartz HT, Sternberg PW

[Trends Genet, 2018]

Dejima and colleagues report using CRISPR/Cas9 to generate a new collection of greatly improved balancer chromosomes in the standard laboratory nematode Caenorhabditis elegans, using methods previously reported by the same laboratory, expanding the set of C. elegans balancers to cover nearly 90% of coding genes.