Mohandas N et al. (2015) Biotechnol Adv "The complement of family M1 aminopeptidases of haemonchus contortus - biotechnological implications."

Korhonen PK, Hall RS, Koehler AV, Hu M, Gasser RB, Mohandas N, Jabbar A, Hofmann A, Young ND

[Biotechnol Adv, 2015]

Although substantial research has been focused on the 'hidden antigen' H11 of Haemonchus contortus as a vaccine against haemonchosis in small ruminants, little is know about this and related aminopeptidases. In the present article, we reviewed genomic and transcriptomic data sets to define, for the first time, the complement of aminopeptidases (designated Hc-AP-1 to Hc-AP-13) of the family M1 with homologs in C. elegans, characterised by zinc-binding (HEXXH) and exo-peptidase (GAMEN) motifs. The three previously published H11 isoforms (accession nos. X94187, FJ481146 and AJ249941) had most sequence similarity to Hc-AP-2 and Hc-AP-8, whereas unpublished isoforms (accession nos. AJ249942 and AJ311316) were both most similar to Hc-AP-3. The aminopeptidases characterised here had homologs in C. elegans. Hc-AP-1 to Hc-AP-8 were most similar in amino acid sequence (28-41%) to C. elegans T07F10.1; Hc-AP-9 and Hc-AP-10 to C. elegans PAM-1 (isoform b) (53-54% similar); Hc-AP-11 and Hc-AP-12 to C. elegans AC3.5 and Y67D8C.9 (26% and 50% similar, respectively); and Hc-AP-13 to C. elegans C42C1.11 and ZC416.6 (50-58% similar). Comparative analysis suggested that Hc-AP-1 to Hc-AP-8 play roles in digestion, metabolite excretion, neuropeptide processing and/or osmotic regulation, with Hc-AP-4 and Hc-AP-7 having male-specific functional roles. The analysis also indicated that Hc-AP-9 and Hc-AP-10 might be involved in the degradation of cyclin (B3) and required to complete meiosis. Hc-AP-11 represents a leucyl/cystinyl aminopeptidase, predicted to have metallopeptidase and zinc ion binding activity, whereas Hc-AP-12 likely encodes an aminopeptidase Q homolog also with these activities and a possible role in gonad function. Finally, Hc-AP-13 is predicted to encode an aminopeptidase AP-1 homolog of C. elegans with hydrolase activity, suggested to operate, possibly synergistically with a PEPT-1 ortholog, as an oligopeptide transporter in the gut for protein uptake and normal development and/or reproduction of the worm. Appraisal of structure-based amino acid sequence alignments revealed that all conceptually translated Hc-AP proteins, with the exception of Hc-AP-12, adopt a topology similar to those observed with the two subgroups of mammalian M1 aminopeptidases which possess either three (I, II and IV) or four (I-IV) domains. In contrast, Hc-AP-12 lacks the N-terminal domain (I), but possesses a substantially expanded domain III. Although further work needs to be done to assess amino acid sequence conservation of the different aminopeptidases among individual worms within and among H. contortus populations, we hope that these insights will support future localisation, structural and functional studies of these molecules in H. contortus as well as facilitate future assessments of a recombinant subunit or cocktail vaccine against haemonchosis.

Lin PY et al. (2022) Int J Mol Sci "Redox and Metabolic Regulation of Intestinal Barrier Function and Associated Disorders."

Chen JH, Peng HH, Lin PY, Yang HC, Stern A

[Int J Mol Sci, 2022]

The intestinal epithelium forms a physical barrier assembled by intercellular junctions, preventing luminal pathogens and toxins from crossing it. The integrity of tight junctions is critical for maintaining intestinal health as the breakdown of tight junction proteins leads to various disorders. Redox reactions are closely associated with energy metabolism. Understanding the regulation of tight junctions by cellular metabolism and redox status in cells may lead to the identification of potential targets for therapeutic interventions. In vitro and in vivo models have been utilized in investigating intestinal barrier dysfunction and in particular the free-living soil nematode, Caenorhabditis elegans, may be an important alternative to mammalian models because of its convenience of culture, transparent body for microscopy, short generation time, invariant cell lineage and tractable genetics.

Wilson DL (1998) Journal of Gerontology "Commentary - Survival of C. elegans in axenic culture."

Wilson DL

[Journal of Gerontology, 1998]

Vanfleteren and colleagues present an interesting example of environmental conditions altering the kinetics of survival. Most previous studies of survival in C. elegans have used abundant bacteria as a food source. Such studies have found that the Gompertz function (exponential growth in mortality rate with age) gives a relatively good fit to survival curves, but that there is some deceleration in the rate of growth of mortality later in the life span. Yulong Yang and I have completed dozens of studies of small populations of the wild-type strain, N2, as well as strains TJ401, TJ411, TJ412,and BA713 in the presence of abundant bacteria in liquid or on agar. Survival curves were better fit by Gompertz more often than by Weibull or logistic functions (unpublished observations).

Martel J et al. (2020) Microb Cell "Plant and fungal products that extend lifespan in Caenorhabditis elegans."

Wu CY, Peng HH, Martel J, Ojcius DM, Yang HC, Young JD, Ko YF

[Microb Cell, 2020]

The nematode <i>Caenorhabditis elegans</i> is a useful model to study aging due to its short lifespan, ease of manipulation, and available genetic tools. Several molecules and extracts derived from plants and fungi extend the lifespan of <i>C. elegans</i> by modulating aging-related pathways that are conserved in more complex organisms. Modulation of aging pathways leads to activation of autophagy, mitochondrial biogenesis and expression of antioxidant and detoxifying enzymes in a manner similar to caloric restriction. Low and moderate concentrations of plant and fungal molecules usually extend lifespan, while high concentrations are detrimental, consistent with a lifespan-modulating mechanism involving hormesis. We review here molecules and extracts derived from plants and fungi that extend the lifespan of <i>C. elegans</i>, and explore the possibility that these natural substances may produce health benefits in humans.

Guo D et al. (2014) RNA Biol "RNAa in action: from the exception to the norm."

Lin SS, Guo D, Barry L, Li LC, Huang V

[RNA Biol, 2014]

Small RNA programmed Argonautes are sophisticated cellular effector platforms known to be involved in a diverse array of functions ranging from mRNA cleavage, translational inhibition, DNA elimination, epigenetic silencing, alternative splicing and even gene activation. First observed in human cells, small RNA-induced gene activation, also known as RNAa, involves the targeted recruitment of Argonaute proteins to specific promoter sequences followed by induction of stable epigenetic changes which promote transcription. The existence of RNAa remains contentious due to its elusive mechanism. A string of recent studies in C. elegans provides unequivocal evidence for RNAa's fundamental role in sculpting the epigenetic landscape and maintaining active transcription of endogenous genes and supports the presence of a functionally sophisticated network of small RNA-Argonaute pathways consisting of opposite yet complementary &quot;yin and yang&quot; regulatory elements. In this review, we summarize key findings from recent studies of endogenous RNAa in C. elegans, with an emphasis on the Argonaute protein CSR-1.

Wu CY et al. (2024) Int J Mol Sci "Caenorhabditis elegans as a Convenient Animal Model for Microbiome Studies."

Yang HC, Davis S, Zhao W, Martel J, Ojcius D, Stern A, Shah S, Saudagar N, Wu CY

[Int J Mol Sci, 2024]

Microbes constitute the most prevalent life form on Earth, yet their remarkable diversity remains mostly unrecognized. Microbial diversity in vertebrate models presents a significant challenge for investigating host-microbiome interactions. The model organism <i>Caenorhabditis elegans</i> has many advantages for delineating the effects of host genetics on microbial composition. In the wild, the <i>C. elegans</i> gut contains various microbial species, while in the laboratory it is usually a host for a single bacterial species. There is a potential host-microbe interaction between microbial metabolites, drugs, and <i>C. elegans</i> phenotypes. This mini-review aims to summarize the current understanding regarding the microbiome in <i>C. elegans</i>. Examples using <i>C. elegans</i> to study host-microbe-metabolite interactions are discussed.