Marquardt T et al. (2003) Eur J Pediatr "Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies."

Denecke J, Marquardt T

[Eur J Pediatr, 2003]

Congenital disorders of glycosylation (CDG, formerly named carbohydrate-deficient glycoprotein syndromes) are a rapidly growing family of inherited disorders affecting the assembly or processing of glycans on glycoconjugates. The clinical spectrum of the different types of CDG discovered so far is variable, ranging from severe multisystemic disorders to disorders restricted to specific organs. This review deals with clinical, diagnostic, and biochemical aspects of all characterized CDGs, including a disorder affecting the N-glycosylation of erythrocytes, congenital dyserythropoietic anemia type II (CDA II/HEMPAS), and the first disorders affecting O-glycosylation. Since the clinical spectrum of symptoms in CDG is variable and may be unspecific, a generous selective screening for the presence of CDG is recommended.

Stohr H et al. (2000) Cytogenet Cell Genet "cDNA cloning and genomic structure of a novel gene (C11orf9) localized to chromosome 11q12-->q13.1 which encodes a highly conserved, potential membrane-associated protein."

Stohr H, Marquardt A, White K, Weber BH

[Cytogenet Cell Genet, 2000]

We have cloned and characterized a novel gene (C11orf9) mapping to chromosome 11q12-->q13.1. The transcript was initially identified as a partial cDNA sequence in the course of constructing a transcript map of the region between markers D11S1765 and uteroglobin known to encompass the gene causing Best disease. Using a combination of EST mapping, computational exon prediction, RT-PCR, and 5'-RACE its 5. 7-kb full-length cDNA sequence was subsequently obtained. The C11orf9 gene consists of 26 exons spanning 33.1 kb of genomic DNA and is located about 4.3 kb centromeric to FEN1. Biocomputational analysis predicts that its conceptual translation product of 1,111 amino acids contains two transmembrane helices as well as two proline-rich regions. Alignment reveals significant homology to hypothetical peptides from several other species including C. elegans and D. melanogaster, indicating a high degree of conservation throughout evolution. Northern Blot and RT-PCR analyses demonstrate widespread expression of a single transcript but varying degrees of abundance among the individual tissues tested. Mutation analysis of the entire coding sequence excluded C11orf9 as the Best disease gene.

Kim, Jimin et al. (2021) International Worm Meeting "Identify the function of calcium-activated chloride channel Bestrophin in C. elegans"

Kim, Kyuhyung, Kim, Seoyeong, Kim, Jimin

[International Worm Meeting, 2021]

Bestrophin is a calcium-activated chloride channel of which gene family is identified in many organisms. In humans, bestrophins are encoded by the four genes; BEST1-4. BEST channels are expressed in multiple tissues and appear to mediate diverse functions, including cell volume regulation (Fischmeister & Hartzell, 2005; Milenkovic et al., 2015). For example, BEST-1 gene is expressed in the retinal pigment epithelium (RPE), and BEST-1 mutation is associated with a variety of eye diseases, including best vitelliform macular dystrophy (BVMD) (Marquardt et al., 1998; Petrukhin et al., 1998). However, the exact functions of the bestrophins have not been identified. C. elegans has 26 genes of bestrophin (best-1 to 26), of which expression patterns and functions remain largely unknown. To investigate the expression patterns of best genes in C. elegans, we expressed a green fluorescent protein (GFP) under the control of the promoter of each best gene. We found that these genes are expressed in most, but not all, cell types, including intestine, muscle, hypodermal and neuronal cells. For example, best-3 and best-4 genes are expressed in an excretory cell, which has been implicated in osmoregulation. We are also characterizing nine mutants, including best-3 and best-4. Furthermore, we plan to perform electrophysiology using the best cDNAs to examine physiological characteristics of the C. elegans BEST channels.

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.