Zhao, W. et al. (2019) International Worm Meeting "A transcriptional response leads to inherited immunity to microsporidia."

Zhao, W., Willis, A., Wadi, L., Reinke, A.

[International Worm Meeting, 2019]

In the wild, C. elegans will encounter a variety of pathogenic species, including eukaryotic intracellular parasites of the microsporidia phylum. Nematocida parisii is a microsporidian species that naturally infects C. elegans and drastically reduces the fertility and life span of its host. One advantage C. elegans have to defend itself against this parasite is the ability to for parental infection by N. parisii to cause enhanced progeny resistance to infection, a phenomenon termed "inherited immunity". We hypothesize that the transcriptional response which occurs in the host upon infection by this parasite contains factors involved in transferring protection to the next generation. Host animals carrying loss of function mutant alleles in either of two genes, pals-22 and lin-35, have an overlapping transcriptional response to wild-type animals infected with N. parisii. These mutants are also both resistant to infection by N. parisii. Thus, these two strains represent a constitutively activated response to infection. Using pals-22 and lin-35 mutant strains, as well as transgenic rescue lines, we show that cross-progeny offspring are more resistant to the pathogen and to the effects of infection. Further, we show that this resistance to N. parisii is maternal dependent, and the mechanisms of this inherited immunity can originate cell non-autonomously. Interestingly, our data suggests that multiple somatic tissues can signal for offspring resistance. We are currently using the auxin-inducible degradation system to deplete PALS-22 and LIN-35 in a tissue-specific and time-dependent manner to test the kinetics of this transgenerational phenotype and further uncover the mechanisms behind it. This work suggests that the initial response to infection is not only potentially able to provide defense against the pathogen for the infected parents, but also to provide immunity for their progeny.

Zhao W et al. (2024) Sci Rep "Inhibiting HSD17B8 suppresses the cell proliferation caused by PTEN failure."

Qu Z, Zhao W, Zhang Y, Huang R, Zheng S, Ran D

[Sci Rep, 2024]

Loss of the tumor suppressor PTEN homolog daf-18 in Caenorhabditis elegans (C. elegans) triggers diapause cell division during L1 arrest. While prior studies have delved into established pathways, our investigation takes an innovative route. Through forward genetic screening in C. elegans, we pinpoint a new player, F12E12.11, regulated by daf-18, impacting cell proliferation independently of PTEN's typical phosphatase activity. F12E12.11 is an ortholog of human estradiol 17-beta-dehydrogenase 8 (HSD17B8), which converts estradiol to estrone through its NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. We found that PTEN engages in a physical interplay with HSD17B8, introducing a distinctive suppression mechanism. The reduction in estrone levels and accumulation of estradiol may arrest tumor cells in the G2/M phase of the cell cycle through MAPK/ERK. Our study illuminates an unconventional protein interplay, providing insights into how PTEN modulates tumor suppression by restraining cell division through intricate molecular interactions.

Zhao W et al. (2020) Zhejiang Da Xue Xue Bao Yi Xue Ban "[Intrinsic and extrinsic mechanisms regulating neuronal dendrite morphogenesis]."

Zou W, Zhao W

[Zhejiang Da Xue Xue Bao Yi Xue Ban, 2020]

Neurons are the structural and functional unit of the nervous system. Precisely regulated dendrite morphogenesis is the basis of neural circuit assembly. Numerous studies have been conducted to explore the regulatory mechanisms of dendritic morphogenesis. According to their action regions, we divide them into two categories: the intrinsic and extrinsic regulators of neuronal dendritic morphogenesis. Intrinsic factors are cell type-specific transcription factors, actin polymerization or depolymerization regulators and regulators of the secretion or endocytic pathways. These intrinsic factors are produced by neuron itself and play an important role in regulating the development of dendrites. The extrinsic regulators are either secreted proteins or transmembrane domain containing cell adhesion molecules. They often form receptor-ligand pairs to mediate attractive or repulsive dendritic guidance. In this review, we summarize recent findings on the intrinsic and external molecular mechanisms of dendrite morphogenesis from multiple model organisms, including <i>Caenorhabditis elegans</i>, <i>Drosophila</i> and mice. These studies will provide a better understanding on how defective dendrite development and maintenance are associated with neurological diseases.

Zhao C et al. (1993) Worm Breeder's Gazette "Cloning of the lin-32 Gene"

Emmons SW, Zhao C

[Worm Breeder's Gazette, 1993]

Cloning of the lin-32 gene Connie Zhao and Scott W. Emmons, Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461

K Omata et al. (1999) International C. elegans Meeting "Characterization of the neural circuit of C. elegans: model analysis of the touch response"

F Yonezawa, K Omata, K Kawamura

[International C. elegans Meeting, 1999]

In order to characterize the neural circuit of C. elagans, we construct a simple model by making use of the data table completed recently by Oshio et al . [1]. We assume that the signal of a neuron is calculated by the product of the signals from the neighboring neurons, and we investigate the touch sensitivity to continuous stimuli described by sinusoidal functions as defined in the rage from 0.0 to 1.0. We calculate the responses of the motor neurons by changing the frequencies of the stimuli. In our calculations, we change only the frequency w PLM for the input signal to the sensory neuron PLM, while the frequency for the other sensory neurons ALM, AVM and PVM is fixed to be a same value w 0 . We show that the output signals from the motor neurons A and B oscillate in time. We measure the minima of the oscillation for each w PLM value. The plot of the minima versus w PLM shows different hehaviors for the case of the neuron A and B. As for the signals from the neuron A, the values of the minima are widely distributed between 0.0 and 1.0 for all w PLM . As for the signals from the neuron B, on the other hand, the features are different for different w PLM values. (a) In the high frequency region of w PLM / w 0 0.4, the oscillation is simple harmonic and there exists only one minimum value (I min = 0.0). (b) As w PLM / w 0 is decreased, another minimum appears at a certain frequency, and the bifurcation takes place discontinuously. This behavior is different from usual continuous bifurcation observed in nonlinear systems. After a few discontinuous branching occur, signals with five periods can be seen in the intermediate frequency region of 0.3 w PLM / w 0 w PLM / w 0 [1] K. Oshio et al. ; C. elegans synaptic connectivity data'', Technical Report, CCEP, Keio Future No.1 (1998).

Wang C et al. (2018) Nat Commun "Author Correction: Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan."

Zhao T, Oswald NW, Li Y, Lin R, Wang C, Jaramillo J, Zhou A, McMillan EA, Douglas PM, MacMillan JB, Huang G, Luo M, Gao J, Mendiratta S, Lin Z, Wang Z, Niederstrasser H, Posner BA, Brekken RA, White MA

[Nat Commun, 2018]

The originally published version of this Article contained an error in the spelling of the author Nathaniel W. Oswald, which was incorrectly given as Nathaniel W. Olswald. This has now been corrected inboth the PDF and HTML versions of the Article.

Nawa Y et al. (1985) Parasite Immunol "Defective protective capacity of W/Wv mice against Strongyloides ratti infection and its reconstitution with bone marrow cells."

Kotani M, Nawa Y, Kiyota M, Korenaga M

[Parasite Immunol, 1985]

The susceptibility of congenitally anemic, and mast cell deficient W/Wv mice to infection with Strongyloides ratti was examined. After a primary infection, W/Wv mice showed greater and more persistent peak larval counts than did normal littermates. Worm expulsion was also slower in W/Wv mice than in +/+ mice. Furthermore, difference in susceptibility was expressed as early as 24 h after infection, suggesting not only that protective mechanisms of the gut but also of the connective tissue were defective in W/Wv mice. Reconstitution with bone marrow or spleen cells from +/+ mice was effective in restoring the protective response in W/Wv mice, whereas thymocytes or mesenteric lymph nodes had no effect. Both connective tissue and mucosal mast cells were repaired in W/Wv mice after marrow reconstitution and infection. Since relatively long incubation period was required for the expression of such reconstituting activities, bone marrow cells seem to contain precursor cells of the effector and/or regulator cells.

Casiraghi M et al. (2004) Int J Parasitol "Mapping the presence of Wolbachia pipientis on the phylogeny of filarial nematodes: evidence for symbiont loss during evolution."

Guerrero R, Bandi C, Franceschi A, Pocacqua V, Gardner SL, Casiraghi M, Martin C, Bain O

[Int J Parasitol, 2004]

Wolbachia pipientis is a bacterial endosymbiont associated with arthropods and filarial nematodes. In filarial nematodes, W. pipientis has been shown to play an important role in the biology of the host and in the immuno-pathology of filariasis. Several species of filariae, including the most important parasites of humans and animals (e.g. Onchocerca volvulus, Wuchereria bancrofti and Dirofilaria immitis) have been shown to harbour these bacteria. Other filarial species, including an important rodent species (Acanthocheilonema viteae), which has been used as a model for the study of filariasis, do not appear to harbour these symbionts. There are still several open questions about the distribution of W. pipientis in filarial nematodes. Firstly the number of species examined is still limited. Secondly, it is not clear whether the absence of W. pipientis in negative species could represent an ancestral characteristic or the result of a secondary loss. Thirdly, several aspects of the phylogeny of filarial nematodes are still unclear and it is thus difficult to overlay the presence/absence of W. pipientis on a tree representing filarial evolution. Here we present the results of a PCR screening for W. pipientis in 16 species of filariae and related nematodes, representing different families/subfamilies. Evidence for the presence of W. pipientis is reported for five species examined for the first time (representing the genera Litomosoides, Litomosa and Dipetalonema); original results on the absence of this bacterium are reported for nine species; for the remaining two species, we have confirmed the absence of W. pipientis recently reported by other authors. In the positive species, the infecting W. pipientis bacteria have been identified through 16S rDNA gene sequence analysis. In addition to the screening for W. pipientis in 16 species, we have generated phylogenetic reconstructions based on mitochondrial gene sequences (12S rDNA; COI), including a total of 28 filarial species and related spirurid nematodes. The mapping of the presence/absence of W. pipientis on the trees generated indicates that these bacteria have possibly been lost during evolution along some lineages of filarial nematodes.

Lewis JA (1981) Worm Breeder's Gazette "Modified Ficoll Method for Cleaning Worms"

Lewis JA

[Worm Breeder's Gazette, 1981]

I have made two modifications in the Ficoll method I originally described in WBG, vol. 3, #2. First, all Ficoll solutions are made 0. 1 M in NaCl to avoid shocking osmoticalIy sensitive worms like unc-29( e1072). Second, after sedimenting worms through 15% w/w Ficoll 400 ( 15', 300 x g), the worms are diluted with an equal volume of 0.1 M NaCl and floated on 35% w/w Ficoll (15', 300 x g) before washing 2x with 0.1 M NaCl. The Ficoll sedimentation removes dead or degenerated worms, cuticles, bacteria. The flotation removes crystalline debris sometimes occurring in worm cultures. We also find that special care to pipette out the last residue of bacterial medium (e.g. 3XD) before resuspending bacteria for worm growth is most conducive to obtaining uncontaminated worms.

Li Z et al. (2018) Pak J Pharm Sci "Cellulase-assisted extraction and anti-ultraviolet activity of polysaccharides from the root of Flammulina velutipes on Caenorhabditis elegans."

Chen M, Lin L, Zhang Y, Wang T, Cui H, Wang C, Li Z

[Pak J Pharm Sci, 2018]

We investigated the cellulase-assisted extraction and anti-ultraviolet activity of water-soluble polysaccharides from the root of Flammulina velutipes on Caenorhabditis elegans. A Box-Behnken design experiment with three factors and three levels, including enzymolysis temperature, microwave time, and microwave power, was designed on the basis of the results of single-factor experiments. For improving the polysaccharide yield of F. velutipes root, the following optimal extraction conditions were used: 52.67C enzymolysis temperature, 80s microwave time, and 144 W microwave power. Under optimal conditions, the actual measured value of the yield was 2.01% (w/w) and the predicted value was 2.06% (w/w). One fraction (FRP-2) was isolated and purified, and its characteristics were analyzed. The average mean molecular weight of FRP-2 was measured to be 2.60x10⁵ Da, and its monosaccharide composition is mainly glucose. The sugar units are present both in the -configuration and -configuration. Moreover, FRP-2 exhibited certain anti-ultraviolet activity to C. elegans when the polysaccharide concentration ranged between 0.05mg/mL and 0.20mg/mL.