Dessauges C et al. (2017) Dev Cell "Developmental ERK Signaling Goes Digital."

Pertz O, Dessauges C

[Dev Cell, 2017]

Reporting in Developmental Cell, de la Cova etal. (2017) present a biosensor to measure ERK activity dynamics in C.elegans larvae. They find that fate decision signaling involves frequency-modulated, digital ERK activity pulses. These findings may explain how graded morphogen signals are converted into precise and robust cell fate patterns.

Chen TC et al. (2023) Prostaglandins Leukot Essent Fatty Acids "Effect of omega-6 linoleic acid on neurobehavioral development in Caenorhabditis elegans."

Chao HR, Lai YR, Chen TC, Tsai MH, Wu CY, Hsu WL, Chen CH

[Prostaglandins Leukot Essent Fatty Acids, 2023]

Linoleic acid (LA, omega-6), an essential polyunsaturated fatty acid, is supplied by vegetable oils such as corn, sunflower and soybean. Supplementary LA in infants and children is required for normal growth and brain development, but has also been reported to induce brain inflammation and neurodegenerative diseases. This controversial role of LA development requires further investigation. Our study utilized Caenorhabditis elegans (C. elegans) as a model to clarify the role of LA in regulating neurobehavioral development. A mere supplementary quantity of LA in C. elegans larval stage affected the worm's locomotive ability, intracellular ROS accumulation and lifespan. We found that more serotonergic neurons were activated by supplementing LA above 10 μM thereby promoting locomotive ability with upregulation of serotonin-related genes. Supplementation with LA above 10 μM also inhibited the expression of mtl-1, mtl-2 and ctl-3 to accelerate oxidative stress and attenuate lifespan in nematodes; however, enhancement of stress-related genes such as sod-1, sod-3, mtl-1, mtl-2 and cyp-35A2 by supplementary LA under 1 μM decreased oxidative stress and increased the worm's lifespan. In conclusion, our study reveals that supplementary LA possesses both pros and cons in worm physiology and provides new suggestions for LA intake administration in childhood.

Eberhardt AG et al. (2008) Vet Parasitol "The Strongyloides (Nematoda) of sheep and the predominant Strongyloides of cattle form at least two different, genetically isolated populations."

Mayer WE, Eberhardt AG, Streit A, Bonfoh B

[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.

Lavatelli A et al. (2020) J Biol Chem "Defining Caenorhabditis elegans as a model system to investigate lipoic acid metabolism."

de Mendoza D, Lavatelli A, Mansilla MC

[J Biol Chem, 2020]

Lipoic acid (LA) is a sulfur-containing cofactor that covalently binds to a variety of cognate enzymes that are essential for redox reactions in all three domains of life. Inherited mutations in the enzymes that make LA, namely lipoyl synthase, octanoyltransferase and amidotransferase, result in devastating human metabolic disorders. Unfortunately, because many aspects of this essential pathway are still obscure, available treatments only serve to alleviate symptoms. We envisioned that the development of an organismal model system might provide new opportunities to interrogate LA biochemistry, biology, and physiology. Here we report our investigations on three <i>Caenorhabditis elegans</i> orthologous proteins involved in this post-translational modification. We established that M01F1.3 encodes a lipoyl synthase, ZC410.7 an octanoyltransferase and C45G3.3 an amidotransferase. Worms subjected to RNAi against <i>M01F1.3</i> and <i>ZC410.7</i> manifest larval arrest in the second generation. The arrest was not rescued by LA supplementation, indicating that endogenous synthesis of LA is essential for <i>C. elegans</i> development. Expression of the enzymes M01F1.3, ZC410.7 and C45G3.3 completely rescue bacterial or yeast mutants affected in different steps of the lipoylation pathway, indicating functional overlap. Thus, we demonstrate that, similarly to humans, <i>C. elegans</i> is able to synthesize LA de novo via a lipoyl-relay pathway, and suggest this nematode could be a valuable model to dissect the role of protein mislipoylation and to develop new therapies.

Zhang J et al. (2019) J Food Biochem "An aqueous polyphenol extract from Rosa rugosa tea has antiaging effects on Caenorhabditis elegans."

Guan Y, Zhang J, Rui X, Dong M, Ma W, Zhang Y, Xiao Y

[J Food Biochem, 2019]

Rosa rugosa aqueous polyphenol (RAP) is a kind of polyphenol from Rosa rugosa flower tea. In this study, the antiaging activities of RAP were studied in the model organism Caenorhabditis elegans. UHPLC-HESI-MS/MS was employed to identify the specific phenolic profile, revealing that there were 23 types of phenolic compounds in RAP and that quercetin glycoside was the principal component. RAP increased the mean lifespan of C. elegans and enhanced the thermotolerance and resistance to oxidative stress of C. elegans in a concentration-dependent manner. Furthermore, RAP showed powerful antioxidant effects in vitro and strong protection against oxidative DNA damage. RAP significantly improved the levels of total superoxide dismutase and total antioxidant capacity of C. elegans. In conclusion, RAP has antiaging effects on C. elegans, which might be related to its powerful antioxidant effects both in vitro and in vivo. PRACTICAL APPLICATIONS: In recent years, chronic diseases associated with aging have had a profound impact on quality of life. Many healthy foods have antiaging properties, especially flower teas, such as those made from Rosa rugosa. Our results indicated that Rosa rugosa tea is good for health and that RAP could potentially be developed as a bioactive product that could be used to combat aging.

Vrbanac A et al. (2017) Cell Host Microbe "An Elegan(t) Screen for Drug-Microbe Interactions."

Morton JT, Debelius JW, Knight R, Jiang L, Dorrestein P, Vrbanac A

[Cell Host Microbe, 2017]

Microbes affect drug responses, but mechanisms remain elusive. Two papers in Cell exploit C.elegans to infer anticancer drug mechanisms. Through high-throughput screens of drug-microbe-host interactions, Garcia-Gonzalez etal. (2017) and Scott etal. (2017) determine that bacterial metabolism underpins fluoropyrimidine cytotoxicity, providing a paradigm for unraveling bacterial mechanisms in drug metabolism.

Lindblade KA et al. (2007) Am J Trop Med Hyg "Elimination of Onchocercia volvulus transmission in the Santa Rosa focus of Guatemala."

Richards FO, Unnasch TR, Catu E, Lindblade KA, Zea-Flores G, Castro J, Richards J, Punkosdy GA, Porter CH, Cruz-Ortiz N, Arana B, Dominguez A, Rizzo N, Oliva O, Sauerbrey M

[Am J Trop Med Hyg, 2007]

To eliminate transmission of Onchocerca volvulus, semiannual mass treatment with ivermectin (Mectizan; donated by Merck &amp; Co) has been underway in Guatemala since 2000. We applied the 2001 World Health Organization (WHO) elimination criteria in the Santa Rosa focus of onchocerciasis transmission in Guatemala (10,923 persons at risk). No evidence of parasite DNA was found in 2,221 Simulium ochraceum vectors (one-sided 95% confidence interval [CI], 0-0.086%), and no IgG4 antibody positives to recombinant antigen OV16 were found in a sample of 3,232 school children (95% CI, 0-0.009%). We also found no evidence of microfilariae in the anterior segment of the eye in 363 area residents (95% CI, 0-0.08%). Our interpretation of these data, together with historical information, suggest that transmission of O. volvulus is permanently interrupted in Santa Rosa and that ivermectin treatments there can be halted.

GroBe Brinkhaus S et al. (2014) Metallomics "Elemental bioimaging of manganese uptake in C. elegans."

Niehaus R, Reifschneider O, Wehe CA, Aschner M, Bornhorst J, Karst U, Chakraborty S, GroBe Brinkhaus S

[Metallomics, 2014]

A new method for elemental bioimaging with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to study the uptake of manganese (Mn) in Caenorhabditis elegans (C. elegans). C. elegans is a well-established model organism in neuroscience, genetics and genomics, which has been extensively studied to decipher mechanisms of heavy metal induced toxicity. Knowledge about the distribution of manganese (Mn) and other metals in this organism will be helpful in elucidating pathways and mechanisms of transport, distribution and excretion. The LA-ICP-MS method requires limited sample preparation and can be used rapidly and easily to visualize the Mn distribution in C. elegans. Due to thorough optimization of the analytical parameters, intense Mn signals in C. elegans wild-type (WT) and mutants were obtained at a spatial resolution as small as 4 m, thus proving the suitability of LA-ICP-MS to study the uptake of metals in C. elegans.

Platzer K et al. (2018) Am J Hum Genet "De Novo Variants in MAPK8IP3 Cause Intellectual Disability with Variable Brain Anomalies."

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

[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.

Han GC et al. (2021) Toxicology "Effects of lanthanum nitrate on behavioral disorder, neuronal damage and gene expression in different developmental stages of Caenorhabditis elegans."

Li ZN, Gao S, Han GC, Jing HM, Zhang WJ, Zhang GY, Zhang N, Ning JY, Li GJ

[Toxicology, 2021]

Rare earth elements (REEs) are widely used in the industry, agriculture, biomedicine, aerospace, etc, and have been shown to pose toxic effects on animals, as such, studies focusing on their biomedical properties are gaining wide attention. However, environmental and population health risks of REEs are still not very clear. Also, the REEs damage to the nervous system and related molecular mechanisms needs further research. In this study, the L1 and L4 stages of the model organism Caenorhabditis elegans were used to evaluate the effects and possible neurotoxic mechanism of lanthanum(III) nitrate hexahydrate (La(NO3)3-6H2O). For the L1 and L4 stage worms, the 48-h median lethal concentrations (LC50s) of La(NO3)3-6H2O were 93.163 and 648.0 mg/L respectively. Our results show that La(NO3)3-6H2O induces growth inhibition and defects in behavior such as body length, body width, body bending frequency, head thrashing frequency and pharyngeal pumping frequency at the L1 and L4 stages in C. elegans. The L1 stage is more sensitive to the toxicity of lanthanum than the L4 stage worms. Using transgenic strains (BZ555, EG1285 and NL5901), we found that La(NO3)3-6H2O caused the loss or break of soma and dendrite neurons in L1 and L4 stages; and &#945;-synuclein aggregation in L1 stage, indicating that Lanthanum can cause toxic damage to dopaminergic and GABAergic neurons. Mechanistically, La(NO3)3-6H2O exposure inhibited or activated the neurotransmitter transporters and receptors (glutamate, serotonin and dopamine) in C. elegans, which regulate behavior and movement functions. Furthermore, significant increase in the production of reactive oxygen species (ROS) was found in the L4 stage C. elegans exposed to La(NO3)3-6H2O. Altogether, our data show that exposure to lanthanum can cause neuronal toxic damage and behavioral defects in C. elegans, and provide basic information for understanding the neurotoxic effect mechanism and environmental health risks of rare earth elements.