Ji K et al. (2015) Food Funct "Inhibition effects of tanshinone on the aggregation of -synuclein."

Liu Y, Ji K, Zhao Y, Yang X, Gong H, Huang K, Wang Z, Yu T

[Food Funct, 2015]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Lewy bodies that are formed by the aggregated -synuclein are a major pathological feature of PD. Salvia miltiorrhiza has been used as food and as a traditional medicine for centuries in China, with tanshinone I (TAN I) and tanshinone IIA (TAN IIA) as its major bioactive ingredients. Here, we investigated the effects of TAN I and TAN IIA on -synuclein aggregation both in vitro and in a transgenic Caenorhabditis elegans PD model (NL5901). We demonstrated that TAN I and TAN IIA inhibited the aggregation of -synuclein as demonstrated by the prolonged lag time and the reduced thioflavin-T fluorescence intensity; TAN I and TAN IIA also disaggregated preformed mature fibrils in vitro. Moreover, the presence of TAN I or TAN IIA affected the secondary structural transformation of -synuclein from unstructured coils to -sheets, and alleviated the membrane disruption caused by aggregated -synuclein in vitro. Besides, the immuno-dot-blot assay indicated that TAN I and TAN IIA reduce the formation of oligomers and fibrils. We further found that TAN I and TAN IIA extended the life span of NL5901, a strain of transgenic C. elegans that expresses human -synuclein, possibly by attenuating the aggregation of -synuclein. Taken together, our results suggested that TAN I and TAN IIA may be explored further as potential candidates for the prevention and treatment of PD.

Zhang X et al. (2022) Free Radic Biol Med "Tanshinone IIA loaded chitosan nanoparticles decrease toxicity of β-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease"

Zhang X, Chang Y, Du L, Wang J, Zhang L, Wang S, Kang X, Liu Y, Zhao Y, Huang Y

[Free Radic Biol Med, 2022]

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases that characterized by the accumulation of β-amyloid peptide (Aβ). Overexpressions of Aβ could induce oxidative stress that might be a key insult to initiate the cascades of Aβ accumulation. As a result, anti-oxidative stress and attenuating Aβ accumulation might be one promising intervention for AD treatment. Tanshinone IIA (Tan IIA), a major component of lipophilic tanshinones in Danshen, is proven to be effective in several diseases, including AD. Due to the poor solubility in water, the clinical application of Tan IIA was limited. Therefore, a great number of nanoparticles were designed to overcome this issue. In the current study, we choose chitson as delivery carrier to load Tanshinone IIA (CS@Tan IIA) and explore the protective effects of CS@Tan IIA on the CL2006 strain, a transgenic C. elegans of AD model organism. Compared with Tan IIA monomer, CS@Tan IIA could significantly prolong the lifespan and attenuate the AD-like symptoms, including reducing paralysis and the Aβ deposition by inhibiting the oxidative stress. The mechanism study showed that the protection of CS@Tan IIA was attenuated by knockdown of daf-16 gene, but not skn-1. The results indicated that DAF-16/SOD-3 pathway was required in the protective effects of CS@Tan IIA. Besides DAF-16/SOD-3 pathway, the Tan IIA-loaded CS nanoparticles might protect the C. elegans against the AD insults via promoting autophagy. All the results consistently suggested that coating by chitosan could improve the solubility of Tan IIA and effectively enhance the protective effects of Tan IIA on AD, which might provide a potential drug loading approach for the hydrophobic drugs as Tan IIA.

Dahl JL et al. (2011) J Bacteriol "Role of phase variation in the resistance of Myxococcus xanthus fruiting bodies to Caenorhabditis elegans predation."

Ulrich CH, Kroft TL, Dahl JL

[J Bacteriol, 2011]

The phenomenon of phase variation between yellow and tan forms of Myxococcus xanthus has been recognized for several decades, but it is not known what role this variation may play in the ecology of myxobacteria. We confirm an earlier report that tan variants are disproportionately more numerous in the resulting spore population of a M. xanthus fruiting body than the tan vegetative cells that contributed to fruiting body formation. However, we found that tan cells may not require yellow cells for fruiting body formation or starvation-induced sporulation of tan cells. Here we report three differences between the yellow and tan variants that may play important roles in the soil ecology of M. xanthus. Specifically, the yellow variant is more capable of forming biofilms, is more sensitive to lysozyme, and is more resistant to ingestion by bacteriophagous nematodes. We also show that the myxobacterial fruiting body is more resistant to predation by worms than are dispersed M. xanthus cells.

Muir RE et al. (2008) Appl Environ Microbiol "Virulence of Leucobacter chromiireducens subsp. solipictus to Caenorhabditis elegans: characterization of a novel host-pathogen interaction."

Tan MW, Muir RE

[Appl Environ Microbiol, 2008]

We describe the pathogenic interaction between a newly described Gram-positive bacterium Leucobacter chromiireducens subsp. solipictus strain TAN 31504 and the nematode Caenorhabditis elegans. TAN 31504 pathogenesis on C. elegans is exerted primarily through infection of the adult nematode uterus. TAN 31504 enters the uterus through the external vulval opening and the ensuing uterine infection is strongly correlated with a significant reduction in host life span. Young worms can fed and develop on TAN 31504, but not preferably over the standard food source. C. elegans reared on TAN 31504 as the sole food source develop into thin adults with little intestinal fat stores, produce few progeny, and subsequently can not persist on the pathogenic food source. Within 12 h of exposure, adult worms challenged with TAN 31504 alter the expression of a number of C. elegans innate immunity-related genes, including nlp-29, which encodes a neuropeptide-like protein. C. elegans exposed briefly to TAN 31504 develop lethal uterine infections analogous to worms exposed continuously to pathogen, suggesting that mere contact with the pathogen is sufficient for the host to become infected. TAN 31504 produces a robust biofilm and this behavior is speculated to play a role in the virulence exerted on the nematode host. The interaction between TAN 31504 and C. elegans provides a convenient opportunity to study bacterial virulence on nematode tissues other than the intestine and may allow for the discovery of host innate immunity elicited specifically in response to vulval-uterine infection.

Muir RE et al. (2007) Int J Syst Evol Microbiol "Leucobacter chromiireducens subsp. solipictus subsp. nov., a pigmented bacterium isolated from the nematode Caenorhabditis elegans, and emended description of L. chromiireducens."

Muir RE, Tan MW

[Int J Syst Evol Microbiol, 2007]

A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming, irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell-wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number of shared biochemical characteristics, strain TAN 31504(T) was placed in the genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG 22506(T) indicating that these two strains belong to the same species, when the recommended threshold value of 70 % DNA-DNA relatedness for the definition of a bacterial species by the ad hoc committee on reconciliation of approaches to bacterial systematics is considered. Based on distinct differences in morphology, physiology, chemotaxonomic markers and various biochemical characteristics, it is proposed to split the species L. chromiireducens into two novel subspecies, Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L-1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp. solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).

Bennett JL et al. (1988) Parasitol Today "Pharmacology of ivermectin."

Williams JF, Bennett JL, Dave V

[Parasitol Today, 1988]

Ivermectin is a semi-synthetic macrocyclic lactone (Fig. I) active in single low doses against many parasites - particularly nematodes and arthropods. It has been registered for animal health use since early 1985, and was earlier this year approved for human use by the French Directorate o f Pharmacy and Drugs. Of particular interest is ivermectin's potential as a micro filaricide for treatment o f onchocerciasis. Clinical trials leave little doubt about the potential o f ivermectin as a therapeutic tool for symptomatic relief from the effects o f infection with Onchocerca volvulus, and the drug is also recognized to have potential in reducing transmission o f the parasite. The manufacturers (Merck, Sharp and Dohme) recently arranged to provide the drug free o f charge to the WHO for mass trials against onchocerciasis in 12 African and Central American countries. In this article we focus on the pharmacological properties o f ivermectin, with a brief consideration of its absorption, fate, excretion and side-effects, and a discussion o f its micro filaricidal action.

Fire A et al. (2006) Genetics "Unusual DNA structures associated with germline genetic activity in Caenorhabditis elegans."

Fire A, Tan F, Alcazar R

[Genetics, 2006]

We describe a surprising long-range periodicity which underlies a substantial fraction of C. elegans genomic sequence. Extended segments (up to several hundred nucleotides) of the C. elegans genome show a strong bias toward occurrence of AA/TT dinucleotides along one face of the helix while little or no such constraint is evident on the opposite helical face. Segments with this characteristic periodicity are highly overrepresented in intron sequences and are associated with a large fraction of genes with known germline expression in C. elegans. In addition to altering the path and flexibility of DNA in vitro, sequences of this character have been shown by others to constrain DNA::nucleosome interactions, potentially producing a structure which could resist the assembly of highly ordered (phased) nucleosome arrays that have been proposed as a precursor to heterochromatin. We propose a number of ways that the periodic occurrence of An/Tn clusters could reflect evolution and function of genes which express in the germ cell lineage of C. elegans.

Kwiatkowski AV et al. (2010) Proc Natl Acad Sci U S A "In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans."

Hardin J, Weis WI, Nelson WJ, Choi HJ, Lynch AM, Kwiatkowski AV, Benjamin JM, Pokutta S, Maiden SL

[Proc Natl Acad Sci U S A, 2010]

The ternary complex of cadherin, beta-catenin, and alpha-catenin regulates actin-dependent cell-cell adhesion. alpha-Catenin can bind beta-catenin and F-actin, but in mammals alpha-catenin either binds beta-catenin as a monomer or F-actin as a homodimer. It is not known if this conformational regulation of alpha-catenin is evolutionarily conserved. The Caenorhabditis elegans alpha-catenin homolog HMP-1 is essential for actin-dependent epidermal enclosure and embryo elongation. Here we show that HMP-1 is a monomer with a functional C-terminal F-actin binding domain. However, neither full-length HMP-1 nor a ternary complex of HMP-1-HMP-2(beta-catenin)-HMR-1(cadherin) bind F-actin in vitro, suggesting that HMP-1 is auto-inhibited. Truncation of either the F-actin or HMP-2 binding domain of HMP-1 disrupts C. elegans development, indicating that HMP-1 must be able to bind F-actin and HMP-2 to function in vivo. Our study defines evolutionarily conserved properties of alpha-catenin and suggests that multiple mechanisms regulate alpha-catenin binding to F-actin.

Wang A et al. (2021) BMC Genomics "Genome-wide characterization, evolution, structure, and expression analysis of the F-box genes in Caenorhabditis."

Chen W, Tao S, Wang A

[BMC Genomics, 2021]

Background: F-box proteins represent a diverse class of adaptor proteins of the ubiquitin-proteasome system (UPS) that play critical roles in the cell cycle, signal transduction, and immune response by removing or modifying cellular regulators. Among closely related organisms of the Caenorhabditis genus, remarkable divergence in F-box gene copy numbers was caused by sizeable species-specific expansion and contraction. Although F-box gene number expansion plays a vital role in shaping genomic diversity, little is known about molecular evolutionary mechanisms responsible for substantial differences in gene number of F-box genes and their functional diversification in Caenorhabditis. Here, we performed a comprehensive evolution and underlying mechanism analysis of F-box genes in five species of Caenorhabditis genus, including C. brenneri, C. briggsae, C. elegans, C. japonica, and C. remanei.Results: Herein, we identified and characterized 594, 192, 377, 39, 1426 F-box homologs encoding putative F-box proteins in the genome of C. brenneri, C. briggsae, C. elegans, C. japonica, and C. remanei, respectively. Our work suggested that extensive species-specific tandem duplication followed by a small amount of gene loss was the primary mechanism responsible for F-box gene number divergence in Caenorhabditis genus. After F-box gene duplication events occurred, multiple mechanisms have contributed to gene structure divergence, including exon/intron gain/loss, exonization/pseudoexonization, exon/intron boundaries alteration, exon splits, and intron elongation by tandem repeats. Based on high-throughput RNA sequencing data analysis, we proposed that F-box gene functions have diversified by sub-functionalization through highly divergent stage-specific expression patterns in Caenorhabditis species.Conclusions: Massive species-specific tandem duplications and occasional gene loss drove the rapid evolution of the F-box gene family in Caenorhabditis, leading to complex gene structural variation and diversified functions affecting growth and development within and among Caenorhabditis species. In summary, our findings outline the evolution of F-box genes in the Caenorhabditis genome and lay the foundation for future functional studies.

Ono S et al. (2001) J Biol Chem "The C-terminal tail of UNC-60B (actin depolymerizing factor/cofilin) is critical for maintaining its stable association with F-actin and is implicated in the second actin-binding site."

Gernert KM, Weeds AG, McGough A, Bui A, Pope BJ, Benian GM, Ono S, Tolbert VT, Pohl J

[J Biol Chem, 2001]

Actin depolymerizing factor (ADF)/cofilin changes the twist of actin filaments by binding two longitudinally associated actin subunits, In the absence of an atomic model of the ADF/cofilin-F-actin complex, we have identified residues in ADF/cofilin that are essential for filament binding. Here, we have characterized the C-terminal tail of UNC-60B (a nematode ADF/cofilin isoform) as a novel determinant for its association with F-actin, Removal of the C-terminal isoleucine (Ile(152)) by carboxypeptidase A or truncation by mutagenesis eliminated F-actin binding activity but strongly enhanced actin depolymerizing activity, Replacement of Ile(152) by Ala had a similar but less marked effect; F-actin binding was weakened and depolymerizing activity slightly enhanced. Truncation of both Arg(151) and Ile(152) or replacement of Arg(151) with Ala also abolished F-actin binding and enhanced depolymerizing activity. Loss of F-actin binding in these mutants was accompanied by loss or greatly decreased severing activity. All of the variants of UNC-60B interacted with G-actin in an indistinguishable manner from wild type. Cryoelectron microscopy showed that UNC-60B changed the twist of F-actin to a similar extent to vertebrate ADF/cofilins. Helical reconstruction and structural modeling of UNC-60B-F-actin complex reveal how the C terminus of UNC-60B might be involved in one of the two actin-binding sites.