Hansen EL et al. (1971) Experientia "Effect of insect hormones on nematodes in axenic culture."

Hansen EL, Buecher EJ

[Experientia, 1971]

Insect juvenile hormones (JH) or JH mimetics have been shown to affect development of nematodes: Trichinella spiralis larvae and fourth stage Phocanema decipiens were inhibited, and abnormal morphology was seen in Heterodera schactii. The effects of insect hormones and analogues on development of several free-living and parasitic nematodes cultured axenically are described in the present paper.

Po MD et al. (2012) Neuron "Releasing the inner inhibition for axon regeneration."

Po MD, Calarco JA, Zhen M

[Neuron, 2012]

The adult mammalian central nervous system exhibits restricted regenerative potential. Chen etal. (2011) and El Bejjani and Hammarlund (2012) used Caenorhabditis elegans to uncover intrinsic factors that inhibit regeneration of axotomized mature neurons, opening avenues for potential therapeutics.

Silverstein NJ et al. (2017) Immunity "Interleukin-17: Why the Worms Squirm."

Huh JR, Silverstein NJ

[Immunity, 2017]

IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen etal. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.

Artan M et al. (2016) Dev Cell "Heat FLiPs a Hormonal Switch for Longevity."

Lee SV, An SW, Artan M

[Dev Cell, 2016]

Temperature-sensing neurons in C.elegans reduce the life-shortening effects of high temperatures via steroid signaling. In this issue of Developmental Cell, Chen etal. (2016) elucidate the underlying mechanisms by which the transcription factor CREB induces the neuropeptide FLP-6 in the temperature-sensing neurons to counteract the life-shortening effects of high temperature.

Sim C et al. (2013) Front Physiol "Insulin signaling and the regulation of insect diapause."

Denlinger DL, Sim C

[Front Physiol, 2013]

A rich chapter in the history of insect endocrinology has focused on hormonal control of diapause, especially the major roles played by juvenile hormones (JHs), ecdysteroids, and the neuropeptides that govern JH and ecdysteroid synthesis. More recently, experiments with adult diapause in Drosophila melanogaster and the mosquito Culex pipiens, and pupal diapause in the flesh fly Sarcophaga crassipalpis provide strong evidence that insulin signaling is also an important component of the regulatory pathway leading to the diapause phenotype. Insects produce many different insulin-like peptides (ILPs), and not all are involved in the diapause response; ILP-1 appears to be the one most closely linked to diapause in C. pipiens. Many steps in the pathway leading from perception of daylength (the primary environmental cue used to program diapause) to generation of the diapause phenotype remain unknown, but the role for insulin signaling in mosquito diapause appears to be upstream of JH, as evidenced by the fact that application of exogenous JH can rescue the effects of knocking down expression of ILP-1 or the Insulin Receptor. Fat accumulation, enhancement of stress tolerance, and other features of the diapause phenotype are likely linked to the insulin pathway through the action of a key transcription factor, FOXO. This review highlights many parallels for the role of insulin signaling as a regulator in insect diapause and dauer formation in the nematode Caenorhabditis elegans.

Akin O et al. (2014) Cell "The shape of things to come."

Akin O, Zipursky SL

[Cell, 2014]

Surface receptors can link binding of ligands to changes in the actin-based cell cytoskeleton. Chia etal. and Chen etal. provide evidence for direct binding between the cytoplasmic tails ofreceptorsand the WAVE complex, a regulator of the actin nucleator Arp2/3 complex, which mighthelp to explain how environmental signals are translated into changes in morphology andmotility.

Fodor A et al. (1989) General & Comparative Endocrinology "Effects of precocene analogs on the nematode Caenorhabditis remanei (var. Bangaloreiensis). 2. Competitions with a juvenile hormone analog (methoprene)."

Timar T, Fodor A

[General & Comparative Endocrinology, 1989]

Fourteen 7-alkoxy-2,2-dimethylchromenes were synthetized and studied in JH competition experiments: prococenes (Ps) PI and PII, and synthetic analogs (PAs) including (i) three with both antiallatal and P-like activities: 7-ethoxy-PII (7-EPII); 7-(prop-2-ynyloxy)-2,2-dimethylchromene (PPI); and 6-methoxy-7-(prop-2-yynyloxy)-2,2-dimethylchromene (PPIII); (ii) six without antiallatal activity, exerting P-like activity in nematodes; and (iii) three without either antiallatal or P-like activity, but with a strong nematocidal effect. Within the dose range 8-1000 ug/ml, different concentrations of each PA were applied to nematode growth medium which did or did not contain 1000 ug methoprene (a juvenile hormone analog JHA)/ml. Plates inoculated with Caenorhabditis embryos were incubated and scored for developmentally affected survivors. The JHA did not compete with any PA mentioned as (iii). It competed moderately with some nonantiallatal PAs (8-Me-PPI, 8-MeO-PPI, and 3,4-diCl-PPI) with strong P-like and nematocidal activities. The JHA competed most efficiently with all Ps, antiallatal PAs, and two nonantiallatal PAs (PPII and thio-PI) which exerted severe P-like activities in nematodes. Parameters assumed to be indicators of the P-like (rather than nematocidal) activity of the PAs proved more sensitive to the JHA than those of nematocidal activity. Whether the JH-compensable P-like activity of some PAs can be regarded as a real anti-JH action needs further clarification.

Landis GN et al. (2020) J Gerontol A Biol Sci Med Sci "Metabolic Signatures of Life Span Regulated by Mating, Sex Peptide and Mifepristone/RU486 in Female Drosophila melanogaster."

Abdelmesieh M, Patel P, Wang T, Tower J, Wang L, Fan Y, Promislow DEL, Doherty DV, Lee S, Vroegop J, Wu J, Shen J, Landis GN, Yen CA, Wang I, Curran SP

[J Gerontol A Biol Sci Med Sci, 2020]

Mating and transfer of male Sex Peptide (SP), or transgenic expression of SP, causes inflammation and decreased life span in female Drosophila. Mifepristone rescues these effects, yielding dramatic increases in life span. Here targeted metabolomics data were integrated with further analysis of extant transcriptomic data. Each of seven genes positively correlated with life span were expressed in the brain or eye, and involved regulation of gene expression and signaling. Genes negatively correlated with life span were preferentially expressed in midgut and involved protein degradation, amino acid metabolism, and immune response. Across all conditions, life span was positively correlated with muscle breakdown product 1/3-methylhistadine and purine breakdown product urate, and negatively correlated with tryptophan breakdown product kynurenic acid, suggesting a SP-induced shift from somatic maintenance/turnover pathways to the costly production of energy and lipids from dietary amino acids. Some limited overlap was observed between genes regulated by mifepristone and genes known to be regulated by ecdysone, however, mifepristone was unable to compete with ecdysone for activation of an ecdysone-responsive transgenic reporter. In contrast, genes regulated by mifepristone were highly enriched for genes regulated by Juvenile Hormone (JH), and mifepristone rescued the negative effect of JH analog methoprene on life span in adult virgin females. The data indicate that mifepristone increases life span and decreases inflammation in mated females by antagonizing JH signaling downstream of male SP. Finally, mifepristone increased life span of mated, but not unmated, C. elegans, in two of three trials, suggesting possible evolutionary conservation of mifepristone mechanisms.

Le SY et al. (2003) Proc IEEE Comput Soc Bioinform Conf "Statistical inference for well-ordered structures in nucleotide sequences."

Maize JV, Le SY, Chen JH

[Proc IEEE Comput Soc Bioinform Conf, 2003]

Distinct, local structures are frequently correlated with functional RNA elements involved in post-transcriptional regulation of gene expression. Discovery of microRNAs (miRNAs) suggests that there are a large class of small non-coding RNAs in eukaryotic genomes. These miRNAs have the potential to form distinct fold-back stem-loop structures. The prediction of those well-ordered folding sequences (WFS) in genomic sequences is very helpful for our understanding of RNA-based gene regulation and the determination of local RNA elements with structure-dependent functions. In this study, we describe a novel method for discovering the local WFS in a nucleotide sequence by Monte Carlo simulation and RNA folding. In the approach the quality of a local WFS is assessed by the energy difference (E(diff)) between the optimal structure folded in the local segment and its corresponding optimal, restrained structure where all the previous base pairings formed in the optimal structure are prohibited. Distinct WFS can be discovered by scanning successive segments along a sequence for evaluating the difference between E(diff) of the natural sequence and those computed from randomly shuffled sequences. Our results indicate that the statistically significant WFS detected in the genomic sequences of Caenorhabditis elegans (C.elegans) F49E12, T07C5, T07D1, T10H9, Y56A3A and Y71G12B are coincident with known fold-back stem-loops found in miRNA precursors. The potential and implications of our method in searching for miRNAs in genomes is discussed.

Fodor A et al. (1987) Worm Breeder's Gazette "competition of exogenous methoprene and precocenes in nematodes: the end of the story."

Timar T, Hosztafi S, Dinya Z, Fodor A, Kiss I

[Worm Breeder's Gazette, 1987]

We have accomplished a ten year long project aimed to learn whether competition between the juvenile hormone (JH) analogue methoprene (JHA) and precocenes (P's) (chromene derivatives capable to destruct the JH producing organ (CA) in sensitive insect species tissue specifically) in C. elegans (Fodor, et. al., Gen. Comp. Endcr. 46: p. 99 (1982)) can or cannot be explained by a comparable 'anti-JH' action of P's in nematodes. Neither JH or CA like organ has been discovered in nematodes so far. There are only a few indirect data showing that insect juvenile hormones may influence certain nematodes pathogenizing insects. We adopted a 'structure/activity' approach including design, synthesis and test P analogues on nematodes in the presence and absence of JHA. If (at least part of) those analogues which capable to destruct the CA of a sensitive insect (Locusta migratoria) were also effective in nematodes and their effect could be compensated by JHA exogenously, then this hormone (analogue) should play a physiological role in the P-poisoned nematodes. If those P's could be competed by JHA, which proved effective (as 'anti-JH' compounds) in insects, but those which exerted only aspecific toxicity could not be, then it would be logical to suggest, that P's are the same kind of 'suicide compounds' for nematodes as for insects. More than 200 P derivatives were synthesized (Tim r, Hosztafi) and tested on C. elegans (Fodor) and L. migratoria (Kiss). After a detailed quantitative structure/activity relation (QSAR) analysis ( Dinya, et. al., QSAR Strat. Des. Bioact. Compd. Proc. Eur. Symp. Struct.-Act. Relat. 5th (1984) Publ. 1985) several new P analogue were designed, synthesized and tested on L. migratoria and on C. remanei var. Bangaloriensis. (We choose this nematode strain because half of its population consists of males, therefore it is easy to distinguish male adultoids from other type of retarded worms.) Altogether, 121 molecules were retested C. remanei and 17 of them was found to exert some significant biological effect. These compounds were retested again several times both in the absence and in the presence of 1 mg/ml NGM dose of JHA: altogether, more that 144,000 C. remanei embryos were counted, treated and scored afterwards. The tests on nematodes were carried out as described in our attached paper. The most characteristic data concerning precocene activity in nematodes were the following: (1) LC50: the half lethal dose (in g/ml) at which half of the embryos develops to worms (calculated by probit analysis); (2) AD50: the dose ( g/ml) at which half of the embryos develops to normal adults; (3) EC50: the dose ( g/ml) at which half of the nematodes on the plates found as 'normal' fertile adults; (4) The maximum frequency of 'adultoid mini worms' during the experiments. [See Figures 1- 2] The main conclusions are the following: About structure/activity relations: (1) All the three (P1-P3) precocene is effective in nematodes and their effects can be compensated by exogenous JHA. (2) The longer the chain of the R7 substituent the less the effect of the compounds in nematodes. (3) The 7-proparglyoxy analogues are much more effective in nematodes than any other C7 substituted compound. (compare P1 to TT51; P2 to K460; P3 to TT80; TT56 to TT58 or 3,4-diCl-P1 (inactive) to FI121.) (4) The asymmetrically disubstituted analogues are much more effective than the symmetrically disubstituted ones (compare TT80 to K460). It is true, if R7 is longer than R6. (5) Me substitution at C5 position inactivates the originally potent P's (compare TT58 to TT51) but restore the activity of originally inactive (for instance, 7-sBuO-P1) analogues (compare it to TT56). 8-MeO substitution eliminate specific P activity (compare TT51 to K464). (6) Both 8-Me and 8-MeO substitution increase toxic rather than JH compatible biological activity of P's. 8-MeO analogues are more toxic than 8-Me ones, but the consequences of the action of 8-MeO compounds in nematodes can be cured more efficiently by JHA than those concerning 8-Me compounds (compare TT100 to K475). About JHA competition experiments: JHA competed the effects of all precocenes which effected both insects and nematodes. However, the data concerning K354 and FI121 show, that there are analogues which effective only in nematodes and their effects can also be cured by exogenous JHA. Although there are aspecifically toxic analogues (like K454 or 2,3,5-triMe-7 propargO-P1) which cannot be compensated by methoprene, we cannot conclude, that our data unambiguously support the idea of existence JH-like hormones in nematodes. It seems very probable, however, that JH-like compounds can interfere with the lethal metabolism of P's.