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[
Worm Breeder's Gazette,
1994]
mab-3 YAC rescue David Zarkower, Mario de Bono, and Jonathan Hodgkin MRC Laboratory of Molecular Biology, Cambridge, England
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[
European Worm Neurobiology Meeting,
2009]
Authors acknowledge support from MRC. Numerous studies support a role for aggregated Ab as a mediator of the toxicity that underlies Alzheimer.s disease (AD) and other diseases such as Inclusion Body myositis (IBM), an acquired muscle disease affecting people over 50 years old. In this pathology, muscle weakness and degeneration is accompanied by chronic muscle inflammation. Remarkably, despite the inflammation component of the disease, IBM patients are only poorly responsive to anti-inflammatory drugs suggesting that inflammation per se may not be the primary cause of the pathology. We have used a C. elegans transgenic line over-expressing human amyloid 1-42 peptide in the muscles as a model with which to test the efficiency of new compounds on in vivo amyloid toxicity. This C. elegans line becomes paralyzed shortly after the induction of amyloid expression in the muscles, which makes it an easily-recordable phenotype useful for exploring candidate treatments to alleviate the paralysis. We report on the actions of two novel chemicals, which inhibit amyloid aggregation and partially rescue the amyloid-induced phenotype. References: Wu Y, W.Z., Butko P, Christen Y, Lambert MP, Klein WL, Link CD, Luo Y. (2006) J. Neurosci., 26, 13102-13. Link CD, T.A., Kapulkin V, Duke K, Kim S, Fei Q, Wood DE, Sahagan BG. (2003) Neurobiol Aging., 24, 397-413. Jones, A.K., Buckingham, S.D. and Sattelle, D.B. (2005). Nat Rev Drug Discov, 4, 321-30.
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[
Ecotoxicol Environ Saf,
2019]
Wood ash is a beneficial fertilizer and liming agent in nutrient depleted soils, but it also contains considerable amounts of cadmium (Cd), which can be toxic to organisms in the environment. Therefore, risk assessments regarding utilization of wood ash is required. Here, we studied how wood ash (applied in doses equivalent to 0, 3 and 6t ha<sup>-1</sup>) and Cd (applied in doses of 0, 10, 150, 300, 600, 1200 and 2000mgkg<sup>-1</sup>) affected growth of the soil nematode Caenorhabditis elegans. The treatments were combined in a full factorial design. Wood ash alone greatly stimulated both soil respiration and growth of C. elegans, whereas Cd alone had a toxic effect. However, unrealistically high Cd levels were needed to severely affect growth of C. elegans and soil respiration, especially soil respiration was very resilient to Cd amendment. Ash addition decreased Cd toxicity to C. elegans, with an EC<sub>50</sub> value of 390mgCdkg<sup>-1</sup> in the 3t ash ha<sup>-1</sup> treatment, and an increase of EC<sub>50</sub> to 1894mgCdkg<sup>-1</sup> in the 6t ash ha<sup>-1</sup> treatment. This is probably because ash increases the Cd sorption capacity of the soil, and thereby decreases the bio-availability of Cd. The results suggest that there is no acute toxic effect of Cd to nematodes associated with wood ash recycling; in fact, our results suggest that ash actually decrease Cd toxicity.
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[
Z Naturforsch C,
2010]
A nematicide, beauvericin (1), was isolated from cultures of the fungus Fusarium bulbicola, and its structure was identified by spectroscopic analysis. Compound 1 showed nematicidal activities against the pine wood nematode Bursaphelenchus xylophilus and the free-living nematode Caenorhabditis elegans.
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[
Vet Parasitol,
2008]
Strongyloides sp. (Nematoda) are very wide spread small intestinal parasites of vertebrates that can form a facultative free-living generation. Most authors considered all Strongyloides of farm ruminants to belong to the same species, namely Strongyloides papillosus (Wedl, 1856). Here we show that, at least in southern Germany, the predominant Strongyloides found in cattle and the Strongyloides found in sheep belong to separate, genetically isolated populations. While we did find mixed infections in cattle, one form clearly dominated. This variety, in turn, was never found in sheep, indicating that the two forms have different host preferences. We also present molecular tools for distinguishing the two varieties, and an analysis of their phylogenetic relationship with the human parasite Strongyloides stercoralis and the major laboratory model species Strongyloides ratti. Based on our findings we propose that Strongyloides from sheep and the predominant Strongyloides from cattle should be considered separate species as it had already been proposed by [Brumpt, E., 1921. Recherches sur le determinisme des sexes et de l''evolution des Anguillules parasites (Strongyloides). Comptes rendu hebdomadaires des seances et memoires de la Societe de Biologie et de ses filiales 85, 149-152], but was largely ignored by later authors. For nomenclature, we follow [Brumpt, E., 1921. Recherches sur le determinisme des sexes et de l''evolution des Anguillules parasites (Strongyloides). Comptes rendu hebdomadaires des seances et memoires de la Societe de Biologie et de ses filiales 85, 149-152] and use the name S. papillosus for the Strongyloides of sheep and the name Strongyloides vituli for the predominant Strongyloides of cattle.
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[
Worm Breeder's Gazette,
1994]
Mutagenesis of C. elegans using N-ethyl-N-nitrosourea Elizabeth De Stasio, Dinesh Stanislaus and Catherine Lephoto. Department of Biology, Lawrence University, Appleton, Wl 54911
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[
Nature,
2002]
Behavioral ecologists have shown that many animals form social groups in conditions. Neurobiological evidence for this behaviour has now been discovered in the nematode worm, Caenorhabditis elegans. On pages 899 and 925 of this issue, de Bono et al. and Coates and de Bono present striking results on the genetic, molecular and neural mechanisms underlying nematode social feeding. These discoveries provide tantalizing insights into the effects of stress in social groupings.
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[
International C. elegans Meeting,
1995]
mig-10 is required for the long range antero-posterior migration of embryonic neurons CAN, ALM and HSN and proper development of the excretory canals (Manser and Wood, Dev. Genet. 11: 49-64). Mosaic analysis suggests a cell non-autonomous role for
mig-10 in exc canal development.
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Stegmann APA, Bonati MT, Panis B, Smith-Hicks C, Lemke JR, Pepler A, Wilson C, Iascone M, McWalter K, Brasington C, Allen W, Di Donato N, Platzer K, Ramos L, Edwards SL, Jamra R, Gamble CN, Mandel H, Stobe P, Mahida S, Marquardt T, Demmer LA, Miller KG, Falik-Zaccai T, Pinz H, Hellenbroich Y, Sticht H, Kok F, Cho MT, Stumpel CTRM, Shinde DN, Angione KM
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Am J Hum Genet,
2018]
Using exome sequencing, we have identified de novo variants in MAPK8IP3 in 13 unrelated individuals presenting with an overlapping phenotype of mild to severe intellectual disability. The de novo variants comprise six missense variants, three of which are recurrent, and three truncating variants. Brain anomalies such as perisylvian polymicrogyria, cerebral or cerebellar atrophy, and hypoplasia of the corpus callosum were consistent among individuals harboring recurrent de novo missense variants. MAPK8IP3 has been shown to be involved in the retrograde axonal-transport machinery, but many of its specific functions are yet to be elucidated. Using the CRISPR-Cas9 system to target six conserved amino acid positions in Caenorhabditis elegans, we found that two of the six investigated human alterations led to a significantly elevated density of axonal lysosomes, and five variants were associated with adverse locomotion. Reverse-engineering normalized the observed adverse effects back to wild-type levels. Combining genetic, phenotypic, and functional findings, as well as the significant enrichment of de novo variants in MAPK8IP3 within our total cohort of 27,232 individuals who underwent exome sequencing, we implicate de novo variants in MAPK8IP3 as a cause of a neurodevelopmental disorder with intellectual disability and variable brain anomalies.
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[
J Am Soc Mass Spectrom,
2015]
De novo sequencing software has been widely used in proteomics to sequence new peptides from tandem mass spectrometry data. This study presents a new software tool, Novor, to greatly improve both the speed and accuracy of today's peptide de novo sequencing analyses. To improve the accuracy, Novor's scoring functions are based on two large decision trees built from a peptide spectral library with more than 300,000 spectra with machine learning. Important knowledge about peptide fragmentation is extracted automatically from the library and incorporated into the scoring functions. The decision tree model also enables efficient score calculation and contributes to the speed improvement. To further improve the speed, a two-stage algorithmic approach, namely dynamic programming and refinement, is used. The software program was also carefully optimized. On the testing datasets, Novor sequenced 7%-37% more correct residues than the state-of-the-art de novo sequencing tool, PEAKS, while being an order of magnitude faster. Novor can de novo sequence more than 300 MS/MS spectra per second on a laptop computer. The speed surpasses the acquisition speed of today's mass spectrometer and, therefore, opens a new possibility to de novo sequence in real time while the spectrometer is acquiring the spectral data. Graphical Abstract .