Al-Abd NM et al. (2013) Evid Based Complement Alternat Med "Recent advances on the use of biochemical extracts as filaricidal agents."

Al-Abd NM, Suhaimi A, Al-Adhroey AH, Nor ZM, Sivanandam S

[Evid Based Complement Alternat Med, 2013]

Lymphatic filariasis is a parasitic infection that causes a devastating public health and socioeconomic burden with an estimated infection of over 120 million individuals worldwide. The infection is caused by three closely related nematode parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera. The species have many ecological variants and are diversified in terms of their genetic fingerprint. The rapid spread of the disease and the genetic diversification cause the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. This in turn prompts the current challenge encountered in its management. Furthermore, most of the chemical medications used are characterized by adverse side effects. These complications urgently warrant intense prospecting on bio-chemicals that have potent efficacy against either the filarial worms or thier vector. In lieu of this, we presented a review on recent literature that reported the efficacy of filaricidal biochemicals and those employed as vector control agents. In addition, methods used for biochemical extraction, screening procedures, and structure of the bioactive compounds were also presented.

Al-Abd NM et al. (2017) Pathog Glob Health "Antifilarial activity of caffeic acid phenethyl ester on Brugia pahangi in vitro and in vivo."

Junaid QO, Nor ZM, Hasan MS, Mansor M, Kassim M, Al-Abd NM

[Pathog Glob Health, 2017]

Lymphatic filariasis (LF) is a vector borne disease caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi and B. timori, which are transmitted by mosquitoes. Current therapeutics to treat LF are mainly microfilarcidal, and lack activity against adult worms. This set back, poses a challenge for the control and elimination of filariasis. Thus, in this study the activities of caffeic acid phenethyl ester (CAPE) against the filarial worm B. pahangi and its bacterial endosymbiont, Wolbachia were evaluated. Different concentrations (2, 5, 10, 15, 20g/ml) of CAPE were used to assess its effects on motility, viability and microfilarial (mf) production of B. pahangi in vitro. Anti-Wolbachial activity of CAPE was measured in worms by quantification of Wolbachial wsp gene copy number using real-time polymerase chain reaction. Our findings show that CAPE was found to significantly reduce adult worm motility, viability, and mf release both in vitro and in vivo. 20g/ml of CAPE halts the release of mf in vitro by day 6 of post treatment. Also, the number of adult worms recovered in vivo were reduced significantly during and after treatment with 50mg/kg of CAPE relative to control drugs, diethylcarbamazine and doxycycline. Real time PCR based on the Wolbachia ftsZ gene revealed a significant reduction in Wolbachia copy number upon treatment. Anti-Wolbachia and antifilarial properties of CAPE require further investigation as an alternative strategy to treat LF.

Gupta S et al. (2015) Nanoscale Res Lett "Optimization of ZnO-NPs to Investigate Their Safe Application by Assessing Their Effect on Soil Nematode Caenorhabditis elegans."

Kushwah T, Yadav S, Vishwakarma A, Gupta S

[Nanoscale Res Lett, 2015]

Zinc oxide nanoparticles (ZnO-NPs) are increasingly receiving attention due to their widespread application in cosmetics, pigments and coatings. This has raised concerns in the public and scientific communities regarding their unexpected health effects. Toxicity effect of ZnO-NPs on the environment was assessed in the present study using Caenorhabditis elegans. Multiple toxicity end points including their mortality, behaviour, reproduction, in vitro distribution and expression of stress response mtl-1 and sod-1 genes were observed to evaluate safe application of ZnO-NPs. C. elegans were exposed to 10, 50, and 100 nm ZnO-NPs (0.1 to 2.0 g/l). Application of 10 nm 0.7g/l adversely affects the survivability of worms and was significantly not affected with exposure of 50 and 100 nm 1.0 g/l. However, reproduction was affected at much low concentration as compared to their survivability. LC50 was recorded 1.0 +/- 0.06 (g/l) for 100 nm, 0.90 +/- 0.60 for 50 nm and 0.620 +/- 0.08 for 10 nm. Expression of mtl-1 and sod-1 was significantly increased with application of 10 nm 0.7g/l and significantly unaffected with exposure of 50 and 100 nm at the same concentration. ZnO-NPs (10 nm) had shown even distribution extended nearly the entire length of the body. The distribution pattern of ZnO-NPs indicates that the intestine is the major target tissues for NP toxicity. Study demonstrates that small-sized (10 nm) ZnO-NPs 0.7g/l is more toxic than larger-sized particles. This may be suggested on the basis of available data; application of 50 and 100 nm 1.0 g/l ZnO-NPs may be used to the environment as this shows no significant toxicity. However, further calibration is warranted to explore safe dose on soil compartments prior to their field application.

Liu H et al. (2021) Sci Total Environ "Size-dependent transgenerational toxicity induced by nanoplastics in nematode Caenorhabditis elegans."

Wang S, Wang D, Tian L, Liu H

[Sci Total Environ, 2021]

Nanoplastic exposure can potentially cause the severe transgenerational toxicity in organisms. However, the transgenerational nanoplastic toxicity and the underlying mechanisms are still largely unclear. Using Caenorhabditis elegans as an animal model, we here compared the transgenerational toxicity of two sizes of polystyrene nanoparticles (PS-NPs, 20 and 100 nm). The nematodes were exposed to PS-NPs at the P0 generation, and from the F1 generation the nematodes were grown under the normal condition. Exposure to 20 nm PS-NPs resulted in more severe transgenerational toxicity than exposure to 100 nm PS-NPs. At the concentration of 100 g/L, the toxicity of 20 nm PS-NPs on locomotion and reproduction was detected at the F1-F6 generations, whereas the toxicity of 100 nm PS-NPs could only be observed at the F1-F3 generations. The difference in transgeneration toxicity between PS-NPs (20 nm) and PS-NPs (100 nm) was associated with the difference in transgenerational activation of oxidative stress. Based on observations on SOD-3::GFP, HSP-6::GFP, and HSP-4::GFP expressions, PS-NPs (20 nm) and PS-NPs (100 nm) further induced different transgenerational responses of anti-oxidation, mt UPR, and ER UPR. Our data suggested that the induction of transgenerational toxicity of PS-NPs was size dependent in nematodes. The results are helpful for our understanding the cellular mechanisms for the induction of transgenerational nanoplastic toxicity in organisms.

Scheibel T et al. (2001) Nat Struct Biol "The role of conformational flexibility in prion propagation and maintenance for Sup35p."

Scheibel T, Lindquist SL

[Nat Struct Biol, 2001]

The [PSI(+)] factor of Saccharomyces cerevisiae is a protein-based genetic element (prion) comprised of a heritable altered conformation of the cytosolic translation termination factor Sup35p. In vitro, the prion-determining region (NM) of Sup35p undergoes conformational conversion from a highly flexible soluble state to structured amyloid fibers, with a rate that is greatly accelerated by preformed NM fiber nuclei. Nucleated conformational conversion is the molecular basis of the genetic inheritance of [PSI(+)] and provides a new model for studying amyloidogenesis. Here we investigate the importance of structure and structural flexibility in soluble NM. Elevated temperatures, chemical chaperones and certain mutations in NM increase or change its structural content and inhibit or enhance nucleated conformational conversion. We propose that the structural flexibility of NM is particularly suited to allowing heritable protein-based changes in cellular behavior.

Keller CI et al. (1987) Photochem Photobiol "UV photobiology of the nematode Caenorhabditis elegans: action spectra, absence of photoreactivation and effects of caffeine."

Rupert CS, Keller CI, Calkins J, Hartman PS

[Photochem Photobiol, 1987]

Action spectra for UV inactivation of reproduction in Caenorhabditis elegans have been obtained for strains N2 (wild-type) and rad-3 (radiation-sensitive). Use of a dye laser radiation source, providing high intensity in a narrow wavelength band, has permitted more detail (14 wavelenghts between 260 and 320 nm) than available in the spectra for other multicellular organisms. Overall sensitivity of N2 is similar to that of wild-type Escherichia coli; that of rad-3 is 30-fold higher between 265 and 310 nm; relative sensitivity decreases above 310 nm but also seems to increase for irradiation below 265 nm. Tests for photoreactivation and for modification of survival by post-irradiation treatment with caffeine were

Leitz G et al. (2002) Biophys J "Stress response in Caenorhabditis elegans caused by optical tweezers: wavelength, power, and time dependence."

Leitz G, Tuck S, Fallman E, Axner O

[Biophys J, 2002]

Optical tweezers have emerged as a powerful technique for micromanipulation of living cells. Although the technique often has been claimed to be nonintrusive, evidence has appeared that this is not always the case. This work presents evidence that near-infrared continuous-wave laser light from optical tweezers can produce stress in Caenorhabditis elegans. A transgenic strain of C. elegans, carrying an integrated heat-shock-responsive reporter gene, has been exposed to laser light under a variety of illumination conditions. It was found that gene expression was most often induced by light of 760 nm, and least by 810 nm. The stress response increased with laser power and irradiation time. At 810 nm, significant gene expression could be observed at 360 mW of illumination, which is more than one order of magnitude above that normally used in optical tweezers. In the 700-760-nm range, the results show that the stress response is caused by photochemical processes, whereas at 810 nm, it mainly has a photothermal origin. These results give further evidence that the 700-760-nm wavelength region is unsuitable for optical tweezers and suggest that work at 810 nm at normal laser powers does not cause stress at the cellular level.

Alam, Tanimul et al. (2015) International Worm Meeting "A tensin3 homolog SVH-6 regulates axon regeneration by stabilization of a MET-like receptor tyrosine kinase SVH-2."

Alam, Tanimul, Asai, Kazuma, Hisamoto, Naoki, Matsumoto, Kunihiro

[International Worm Meeting, 2015]

The Jun N-terminal kinase (JNK) MAP kinase (MAPK) pathway, which is composed of MLK-1 (MAPKKK), MEK-1 (MAPKK) and KGB-1 (MAPK), plays a pivotal role in axon regeneration in C. elegans. Recently, we have identified an HGF-like growth factor SVH-1 and a Met-like receptor tyrosine kinase SVH-2 as positive regulators acting upstream of JNK MAPK pathway in axon regeneration. However, other molecular factors that regulate this pathway are not well understood. In this study, we identified the svh-6 gene, which encodes a homolog of mammalian tensin3, as a regulator of axon regeneration. In svh-6 mutants, frequency of axon regeneration was significantly reduced. This defect was rescued by the expression of the svh-6 gene under the D-type motor neuron specific promoter, suggesting that SVH-6 acts cell-autonomously. SVH-6 contains an Actin Binding Domain (ABD), a Src Homology 2 (SH2) domain, and a Phospho-Tyrosine Binding (PTB) domain. We found that both SH2 and PTB domains, but not ABD, are required for SVH-6 function in axon regeneration. Further genetic analysis revealed that SVH-6 acts upstream of SVH-2 in axon regeneration. Biochemical analysis using mammalian cultured cells showed that SVH-6 lacking ABD (SVH-6 delta-ABD) associates with Tpr-SVH-2C, an activated form of cytoplasmic domain of SVH-2. This interaction is dependent on both the kinase activity of Tpr-SVH-2C and the SH2 domain of SVH-6, indicating that the SH2 domain of SVH-6 can interact with the activated form of SVH-2 cytoplasmic domain. To evaluate the in vivo function of SVH-6, we overexpressed SVH-6 delta-ABD and determined the effect on the SVH-2 protein in severed axons. In wild-type animals, the SVH-2 protein fused to VENUS fluorescent protein (SVH-2::VENUS) is unstable and not visible by fluorescent microscope in both unsevered and severed neurons. However, SVH-6 delta-ABD overexpression enabled it to be visible at proximal retraction bulb in severed neurons. Thus, these results suggest that SVH-6 interacts with SVH-2 via SH2 domain and regulates axon regeneration by stabilizing the active SVH-2 protein at retraction bulb.

Khare P et al. (2011) J Biomed Nanotechnol "Adverse effects of TiO2 and ZnO nanoparticles in soil nematode, Caenorhabditis elegans."

Satish A, Ali S, Gupta KC, Sonane M, Pandey R, Khare P

[J Biomed Nanotechnol, 2011]

During the last decade, advancement of nanotechnology has revolutionized various fields such as electronics, optics, materials science as well as architecture, and medicine. However, their health and environmental impact is not fully understood. TiO2 and ZnO nanoparticles (NPs), which are abundantly used for commercial purposes, pose a great risk to environment. In this context, we examined the adverse effects of TiO2 and ZnO NPs of < 25 nm and < 100 nm sizes to nematode Caenorhabditis elegans. < 25 nm TiO2 and ZnO NPs showed LC50 of 77 mg/L and 0.32 mg/L respectively, while < 100 nm TiO2 NPs were non-toxic and LC50 of 2 mg/L was obtained for < 100 nm ZnO NPs. Our studies indicate that in both cases, smaller particle sizes are more toxic than larger NPs and ZnO NPs are more toxic than TiO2 NPs. Further, we observed low LC50 values for ZnO NPs, probably reflecting the sensitivity of C. elegans as a model for eco-toxicity studies of NPs.

Ben-Harush K et al. (2009) J Mol Biol "The supramolecular organization of the C. elegans nuclear lamin filament."

Aebi U, Soreq E, Medalia O, Herrmann H, Frenkiel-Krispin D, Wiesel N, Moeller D, Gruenbaum Y, Ben-Harush K

[J Mol Biol, 2009]

Nuclear lamins are involved in most nuclear activities and are essential for retaining the mechano-elastic properties of the nucleus. They are nuclear intermediate filament (IF) proteins forming a distinct meshwork-like layer adhering to the inner nuclear membrane, called the nuclear lamina. Here, we present for the first time, the three-dimensional supramolecular organization of lamin 10 nm filaments and paracrystalline fibres. We show that Caenorhabditis elegans nuclear lamin forms 10 nm IF-like filaments, which are distinct from their cytoplasmic counterparts. The IF-like lamin filaments are composed of three and four tetrameric protofilaments, each of which contains two partially staggered anti-parallel head-to-tail polymers. The beaded appearance of the lamin filaments stems from paired globular tail domains, which are spaced regularly, alternating between 21 nm and 27 nm. A mutation in an evolutionarily conserved residue that causes Hutchison-Gilford progeria syndrome in humans alters the supramolecular structure of the lamin filaments. On the basis of our structural analysis, we propose an assembly pathway that yields the observed 10 nm IF-like lamin filaments and paracrystalline fibres. These results serve also as a platform for understanding the effect of laminopathic mutations on lamin supramolecular organization.