Long L et al. (2023) Elife "A toxin-antidote selfish element increases fitness of its host."

McGrath PT, Paaby AB, Long L, Xu W, Valencia F

[Elife, 2023]

Selfish genetic elements can promote their transmission at the expense of individual survival, creating conflict between the element and the rest of the genome. Recently, a large number of toxin-antidote (TA) post-segregation distorters have been identified in non-obligate outcrossing nematodes. Their origin and the evolutionary forces that keep them at intermediate population frequencies are poorly understood. Here, we study a TA element in C. elegans called zeel-1;peel-1. Two major haplotypes of this locus, with and without the selfish element, segregate in C. elegans. We evaluate the fitness consequences of the zeel-1;peel-1 element outside of its role in gene drive in non-outcrossing animals, and demonstrate that loss of the toxin peel-1 decreased fitness of hermaphrodites and resulted in reductions in fecundity and body size. These findings suggest a biological role for peel-1 beyond toxin lethality. This work demonstrates that a TA element can provide a fitness benefit to its hosts, either during their initial evolution or by being co-opted by the animals following their selfish spread. These findings guide our understanding on how TA elements can remain in a population where gene drive is minimized, helping resolve the mystery of prevalent TA elements in selfing animals.

Clynen E et al. (2009) Ann N Y Acad Sci "Identification of new members of the (short) neuropeptide F family in locusts and Caenorhabditis elegans."

Schoofs L, Clynen E, Husson SJ

[Ann N Y Acad Sci, 2009]

Both the long and short neuropeptides F (NPF) represent important families of invertebrate neuropeptides that have been implicated in the regulation of reproduction and feeding behavior. In the present study, two short NPFs (SNRSPS(L/I)R(L/I)RFamide and SPS(L/I)R(L/I)RFamide) were de novo sequenced by mass spectrometry in two major pest insects, the desert locust Schistocerca gregaria and the African migratory locust Locusta migratoria. They are two of the most widespread peptides in the locust neuroendocrine system. A peptide that was previously reported to accelerate egg development in S. gregaria is shown to represent a truncated form of long NPF. This peptide is most likely derived by a novel processing mechanism involving cleavage at RY. In addition, an NPF peptide from the nematode Caenorhabditis elegans was isolated and sequenced by tandem mass spectrometry.

Liu D et al. (2020) Aging (Albany NY) "Carnitine promotes recovery from oxidative stress and extends lifespan in C. elegans."

Liu D, Li L, Ou ZL, Zeng X

[Aging (Albany NY), 2020]

Carnitine is required for transporting fatty acids into the mitochondria for -oxidation. Carnitine has been used as an energy supplement but the roles in improving health and delaying aging remain unclear. Here we show in <i>C. elegans</i> that L-carnitine improves recovery from oxidative stress and extends lifespan. L-carnitine promotes recovery from oxidative stress induced by paraquat or juglone and improves mobility and survival in response to H₂O₂ and human amyloid (A) toxicity. L-carnitine also alleviates the oxidative stress during aging, resulting in moderate but significant lifespan extension, which was dependent on SKN-1 and DAF-16. Long-lived worms with germline loss (<i>glp-1</i>) or reduced insulin receptor activity (<i>daf-2)</i> recover from aging-associated oxidative stress faster than wild-type controls and their long lifespans were not further increased by L-carnitine. A new gene, T08B1.1, aligned to a known carnitine transporter OCTN1 in humans, is required for L-carnitine uptake in <i>C. elegans</i>. T08B1.1 expression is elevated in <i>daf-2</i> and <i>glp-1</i> mutants and its knockdown prevents L-carnitine from improving oxidative stress recovery and prolonging lifespan. Together, our study suggests an important role of L-carnitine in oxidative stress recovery that might be important for healthy aging in humans.

Forrester S et al. (2007) Foodborne Pathog Dis "Evaluation of the pathogenicity of Listeria spp. in Caenorhabditis elegans."

Schwab U, Wiedmann M, Hoose WA, Milillo SR, Forrester S

[Foodborne Pathog Dis, 2007]

Caenorhabditis has proven to be a useful model for studying host-pathogen interactions as well as the ability of nematodes to serve as vectors for the dispersal of foodborne pathogens. In this study, we evaluated whether C. elegans can serve as a host for Listeria spp. While there was an effect of growth media on C. elegans killing, C. elegans exposed to L. monocytogenes and L. innocua pregrown in Luria-Bertani medium showed reduced survival when compared to nonpathogenic E. coli OP50, while L. seeligeri showed survival similar to E. coli OP50. In a preference assay, C. elegans preferred E. coli over L. monocytogenes and L. innocua, but showed no preference between L. monocytogenes and L. innocua. A gentamicin assay indicated that L. monocytogenes did not persist within the C. elegans intestinal tract. Our findings that L. monocytogenes and L. innocua strains tested have equally deleterious effects on C. elegans and that L. monocytogenes did not establish intestinal infection conflict with other recently published results, which found intestinal infection and killing of C. elegans by L. monocytogenes. Further studies are thus needed to clarify the interactions between L. monocytogenes and C. elegans, including effects of environmental conditions and strain differences on killing and intestinal infection.

Rose JK et al. (2002) Learn Mem "A new group-training procedure for habituation demonstrates that presynaptic glutamate release contributes to long-term memory in Caenorhabditis elegans."

Rankin CH, Kaun KR, Rose JK

[Learn Mem, 2002]

In the experiments reported here we have developed a new group-training protocol for assessing long-term memory for habituation in Caenorhabditis elegans. We have replicated all of the major findings of the original single-worm protocol using the new protocol: (1) distributed training produced long-term retention of training, massed training did not; (2) distributed training at long interstimulus intervals (ISIs) produced long-term retention, short ISIs did not; and (3) long-term memory for distributed training is protein synthesis-dependent as it could be blocked by heat shock during the inter-block interval. In addition, we have shown that long-term memory for habituation is graded, depending on the number of blocks of stimuli in training. The inter-block interval must be >40 min for long-term retention of training to occur. Finally, we have tested long-term memory for habituation training in a strain of worms with a mutation in a vesicular glutamate transporter in the sensory neurons that transduce tap (eat-4). The results from these eat-4 worms indicate that glutamate release from the sensory neurons has an important role in the formation of long-term memory ror habituation.

Zhang J et al. (2013) Bull Environ Contam Toxicol "Toxic effects of acetochlor on mortality, reproduction and growth of Caenorhabditis elegans and Pristionchus pacificus."

Li Q, Wu X, Jiang S, Zhang J, Liang W

[Bull Environ Contam Toxicol, 2013]

The effects of acetochlor on the mortality, growth and reproduction of two nematode species were assessed. The LC50 values for Caenorhabditis elegans and Pristionchus pacificus were 1,296 and 210.7mg/L at 24h, and 540.0 and 126.4mg/L at 48h exposure, respectively. In three succession generations, reproductive capacity was more sensitive in P. pacificus than in C. elegans. Moreover, the sublethal test endpoint of final length was more sensitive with P. pacificus. This study suggested that acetochlor had no long-term effects on C. elegans at lower concentrations. The higher concentrations of acetochlor (from 40 to 160mg/L) revealed sublethal toxicity to the two tested species, with P. pacificus being more sensitive than C. elegans.

Ludewig AH et al. (2004) Genes Dev "A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging."

Kober-Eisermann C, Neubert K, Bethke A, Hutter H, Antebi A, Weitzel C, Ludewig AH, Gerisch B

[Genes Dev, 2004]

Environmental cues transduced by an endocrine network converge on Caenorhabditis elegans nuclear receptor DAF-12 to mediate arrest at dauer diapause or continuous larval development. In adults, DAF-12 selects long-lived or short-lived modes. How these organismal choices are molecularly specified is unknown. Here we show that coregulator DIN-1 and DAF-12 physically and genetically interact to instruct organismal fates. Homologous to human corepressor SHARP, DIN-1 comes in long (L) and short (S) isoforms, which are nuclear localized but have distinct functions. DIN-1L has embryonic and larval developmental roles. DIN-1S, along with DAF-12, regulates lipid metabolism, larval stage-specific programs, diapause, and longevity. Epistasis experiments reveal that din-1S acts in the dauer pathways downstream of lipophilic hormone, insulin/IGF, and TGFbeta signaling, the same point as daf-12. We propose that the DIN-1S/DAF-12 complex serves as a molecular switch that implements slow life history alternatives in response to diminished hormonal signals.

Ding X et al. (2017) Sci Total Environ "Long-term exposure to thiolated graphene oxide in the range of g/L induces toxicity in nematode Caenorhabditis elegans."

Wang J, Rui Q, Ding X, Wang D

[Sci Total Environ, 2017]

The in vivo toxicity and translocation of thiolated graphene oxide (GO-SH) are still largely unclear. We hypothesized that long-term exposure to GO-SH may cause the adverse effects on environmental organisms. We here employed in vivo assay system of Caenorhabditis elegans to investigate the possible toxicity and translocation of GO-SH after long-term exposure. In wild-type nematodes, we observed that prolonged exposure to GO-SH at concentrations&gt;100g/L resulted in the toxicity on functions of both primary targeted organs such as the intestine and secondary targeted organs such as the neurons and the reproductive organs. The severe accumulation of GO-SH was further detected in the body of wild-type nematodes. The translocation of GO-SH into secondary targeted organs such as reproductive organs through intestinal barrier might be associated with the enhancement in intestinal permeability in GO-SH exposed wild-type nematodes. Prolonged exposure to GO-SH (100g/L) decreased the expression of gas-1 encoding a subunit of mitochondrial complex I, and mutation of gas-1 caused the formation of GO-SH toxicity at concentration&gt;10g/L and more severe accumulation of GO-SH in the body of animals. Therefore, our results confirm the possibility for prolonged exposure to GO-SH in inducing adverse effects on nematodes. Our data highlight the potential adverse effects of GO-SH in the range of g/L on environmental organisms after long-term exposure.

Abraham D et al. (1989) Am J Trop Med Hyg "Immunity to larval Brugia malayi in BALB/c mice: protective immunity and inhibition of larval development."

Grieve RB, Christensen BM, Abraham D, Holy JM

[Am J Trop Med Hyg, 1989]

The objective of this study was to analyze the immune response of mice to the larval stages of Brugia malayi. Male BALB/c mice were inoculated with 3 doses of irradiated third-stage larvae (L-3) of B. malayi and were subsequently challenged with L-3 implanted ip within diffusion chambers. After 3 weeks, larvae were recovered to determine their viability, length, and stage of development. A significant reduction in parasite survival was observed in immunized mice. Furthermore, larvae recovered from immunized mice were significantly shorter than larvae recovered from control mice. All larvae recovered from immunized mice were L-3, whereas 96% of larvae recovered from controls were fourth-stage larvae (L-4). Sera collected from control and immunized mice were tested for the presence of antibodies reactive with L-3 and L-4 antigens using an indirect fluorescent antibody assay employing frozen larval cross-sections as antigen. Sera recovered after challenge of control mice reacted with internal, but not surface, antigens of L-3 and L-4. Alternatively, sera from immunized mice reacted with both internal and external antigens of both L-3 and L-4.

Tauffenberger A et al. (2019) Cell Death Dis "Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling."

Magistretti PJ, Almustafa S, Fiumelli H, Tauffenberger A

[Cell Death Dis, 2019]

L-lactate was long considered a glycolytic by-product but is now being recognized as a signaling molecule involved in cell survival. In this manuscript, we report the role of L-lactate in stress resistance and cell survival mechanisms using neuroblastoma cells (SH-SY5Y) as well as the C. elegans model. We observed that L-lactate promotes cellular defense mechanisms, including Unfolded Protein Response (UPR) and activation of nuclear factor erythroid 2-related factor 2 (NRF2), by promoting a mild Reactive Oxygen Species (ROS) burst. This increase in ROS triggers antioxidant defenses and pro-survival pathways, such as PI3K/AKT and Endoplasmic Reticulum (ER) chaperones. These results contribute to the understanding of the molecular mechanisms involved in beneficial effects of L-lactate, involving mild ROS burst, leading to activation of unfolded protein responses and detoxification mechanisms. We present evidence that this hormetic mechanism induced by L-lactate protects against oxidative stress in vitro and in vivo. This work contributes to the identification of molecular mechanisms, which could serve as targets for future therapeutic approaches for cell protection and aging-related disorders.