Xu T et al. (2022) Food Funct "Longevity-promoting properties of ginger extract in Caenorhabditis elegans via the insulin/IGF-1 signaling pathway."

Tao M, Pan S, Xu T, Wu T, Li R, Xu X

[Food Funct, 2022]

Ginger is a traditional medicinal and edible plant with multiple health-promoting properties. Nevertheless, the effects and potential mechanism of ginger on antiaging remain unknown. The aim of this study was to comprehend the antiaging effects and potential mechanism of ginger in Caenorhabditis elegans (C. elegans). The current findings showed that the lifespan of C. elegans was prolonged by 23.16% with the supplementation of 60 μg mL-1 ginger extract (GE), and the extension of lifespan was mainly attributed to the major bioactive compounds in GE, 6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol. Subsequently, GE promoted healthy aging by improving nematode movement and attenuating lipofuscin accumulation, and enhanced stress tolerance by up-regulating the expression of stress-related genes and activating DAF-16 and SKN-1. Moreover, lifespan assays of relative mutants revealed that GE mediated extension of lifespan via the insulin/IGF-1 signaling (IIS) pathway. In summary, GE endowed nematodes (C. elegans) with longevity and stress resistance in an IIS pathway dependent manner.

Aranaz P et al. (2021) Nutrients "Grifola frondosa (Maitake) Extract Reduces Fat Accumulation and Improves Health Span in C. elegans through the DAF-16/FOXO and SKN-1/NRF2 Signalling Pathways."

Vettorazzi A, Fabra MJ, Aranaz P, Pena A, Castellari M, Parlade J, Gonzalez-Navarro CJ, Pera J, Martinez-Abad A, Milagro FI, Lopez-Rubio A

[Nutrients, 2021]

In recent years, food ingredients rich in bioactive compounds have emerged as candidates to prevent excess adiposity and other metabolic complications characteristic of obesity, such as low-grade inflammation and oxidative status. Among them, fungi have gained popularity for their high polysaccharide content and other bioactive components with beneficial activities. Here, we use the <i>C. elegans</i> model to investigate the potential activities of a <i>Grifola frondosa</i> extract (GE), together with the underlying mechanisms of action. Our study revealed that GE represents an important source of polysaccharides and phenolic compounds with in vitro antioxidant activity. Treatment with our GE extract, which was found to be nongenotoxic through a <i>SOS/umu</i> test, significantly reduced the fat content of <i>C. elegans</i>, decreased the production of intracellular ROS and aging-lipofuscin pigment, and increased the lifespan of nematodes. Gene expression and mutant analyses demonstrated that the in vivo anti-obesity and antioxidant activities of GE were mediated through the <i>daf-2/daf-16</i> and <i>skn-1/nrf-2</i> signalling pathways, respectively. Taken together, our results suggest that our GE extract could be considered a potential functional ingredient for the prevention of obesity-related disturbances.

Huang CH et al. (2015) J Nutr Biochem "Analysis of lifespan-promoting effect of garlic extract by an integrated metabolo-proteomics approach."

Hsu FY, Wu YH, Liang SS, Kuo CJ, Hsu AL, Chiou SH, Huang CH, Zhong L, Tseng MY

[J Nutr Biochem, 2015]

The beneficial effects of garlic (Allium sativum) consumption in treating human diseases have been reported worldwide over a long period of human history. The strong antioxidant effect of garlic extract (GE) has also recently been claimed to prevent cancer, thrombus formation, cardiovascular disease and some age-related maladies. Using Caenorhabditis elegans as a model organism, aqueous GE was herein shown to increase the expression of longevity-related FOXO transcription factor daf-16 and extend lifespan by 20%. By employing microarray and proteomics analysis on C. elegans treated with aqueous GE, we have systematically mapped 229 genes and 46 proteins with differential expression profiles, which included many metabolic enzymes and yolky egg vitellogenins. To investigate the garlic components functionally involved in longevity, an integrated metabolo-proteomics approach was employed to identify metabolites and protein components associated with treatment of aqueous GE. Among potential lifespan-promoting substances, mannose-binding lectin and N-acetylcysteine were found to increase daf-16 expression. Our study points to the fact that the lifespan-promoting effect of aqueous GE may entail the DAF-16-mediated signaling pathway. The result also highlights the utility of metabolo-proteomics for unraveling the complexity and intricacy involved in the metabolism of natural products in vivo.

Monoson HL et al. (1973) Mycopathologia et Mycologia Applicata "Endoparasitic nematode-trapping fungi of Mason State Forest."

Monoson HL, Williams SA

[Mycopathologia et Mycologia Applicata, 1973]

An initial survey involving the endoparasitic nematode-trapping fungi of Mason State Forest in Illinois was conducted from 15 May to 26 July 1971. Three endoparasitic forms were isolated from the soil samples collected; one non-endoparasitic form was also isolated. Soil pH's and soil nutrient levels were determined for the investigation period.

Ryder EF et al. (1997) International C. elegans Meeting "SENSORY MAP FORMATION IN THE C. ELEGANS NERVOUS SYSTEM."

Kaplan JM, Ryder EF, Mason GE, Burket CT

[International C. elegans Meeting, 1997]

Many sensory systems convey spatial information from the external world to the brain by forming an ordered set of neuronal connections known as a topographic map. We are studying the development of topographic maps formed by two sets of head sensory neurons in C. elegans, the IL1!s (visualized by an unc-5::GFP construct kindly provided by J. Culotti) and the IL2!s (visualized by DiO staining; C. Bargmann, pers. comm.). We conducted genetic screens for mutations affecting the formation of these sensory maps, and isolated several alleles of dig-1 (WBG 14:1; ECWM 1996). Sensory processes of dig-1 animals follow aberrant pathways. Mapping data (Michael Basson, Jim Thomas) indicated that dig-1 maps close to sma-3 on III. The genome consortium identified a large gene (>40 kb) in this region with homology to cell adhesion molecules of the Ig superfamily. Probes to this gene show polymorphisms in two dig-1 alleles. We plan to analyze the dig-1 expression pattern. To isolate more genes involved in the adhesion pathway, we are conducting a dig-1 suppresser screen. In vertebrates, sensory maps are formed through axons following a sequence of partially redundant guidance cues; neuronal activity is also involved. If a similar scheme is followed in C. elegans, then mutations in other genes important in map formation may greatly enhance the dig-1 phenotype, even if they have only weak map phenotypes by themselves. We are investigating this possibility by constructing double mutants with a number of candidate genes involved in guidance or activity. We also plan to perform a dig-1 enhancer screen. In addition, we are constructing animals with the unc-5::GFP construct in the background of cilia mutants that affect activity of IL1 neurons.

Morita S et al. (2001) Physica A "Geometrical structure of the neuronal network of Caenorhabditis elegans."

Funabashi Y, Morita S, Oka K, Oshio K, Osana Y, Kawamura K

[Physica A, 2001]

The neuronal network of the soil nematode Caenorhabditis elegans (C. elegans), which is a good prototype for biological studies, is investigated. Here, the neuronal network is simplified as a graph. We use three indicators to characterize the graph; vertex degree, generalized eccentricity (GE), and complete subgraphs. The graph has the central part and the strong clustering structure. We present a simple model, which shows that the neuronal network has a high-dimensional geometrical structure.

Pooranachithra M et al. (2021) J Proteomics "Proteomic analysis of Caenorhabditis elegans wound model reveals novel molecular players involved in repair."

Pooranachithra M, Bhaskar JP, Balamurugan K, Kumar CS, Venkateswaran K, Ravichandiran V

[J Proteomics, 2021]

Wound repair is a multistep process which involves coordination of multiple molecular players from different cell types and pathways. Though the cellular processes that are taking place in order to repair damage is already known, molecular players involved in crucial pathways are still scarce. In this regard, the present study intends to uncover crucial players that are involved in the central repair events through proteomics approach which included 2-D GE and LC-MS/MS using Caenorhabditis elegans wound model. Initial gel-based 2-D GE and following protein-protein interaction (PPI) network analyses revealed active role of calcium signaling, acetylcholine transport and serotonergic neurotransmitter pathways. Further, gel-free LC-MS/MS and following PPI network analyses revealed the incidence of actin nucleation at the initial hours immediately after injury. Further by visualizing the PPI network and the interacting players, pink-1, a mitochondrial Serine/threonine-protein kinase which is known to regulate mitochondrial dynamics, was found to be the central player in facilitating the mitochondrial fission and its role was further verified using qPCR analysis and pink-1 transgenic worms. Overall, the study delivers new insights from crucial regulatory pathways and central players involved in wound repair using high throughput proteomic approaches and the mass spectrometry Data (PXD024629/px-submission #487081) are available via ProteomeXchange. SIGNIFICANCE.

Littleford, H. et al. (2013) International Worm Meeting "Identification of DMD-3 targets in the C. elegans male tail tip."

Ercan, S., Fitch, D., Yang, J-S., Kiontke, K., Mason, A., Herrera, R. A., Littleford, H.

[International Worm Meeting, 2013]

Morphogenesis is a fundamental developmental process in which cells can change shape and identity, migrate, and fuse to form a variety of structures. Despite its importance in development, little is known about how transcriptional regulation is linked to cytoskeletal processes that facilitate morphogenesis. Morphogenesis occurs in 4 cells of the C. elegans male tail tip as it retracts and changes shape during L4. Previous work demonstrated that DMD-3, a conserved, DM-domain transcription factor related to the human male fate-determining gene DMRT1, is necessary and sufficient for male tail tip retraction (Mason et al. 2008). DMD-3 is at the center of a genetic network with a bow-tie structure, regulated by pathways including Wnt signaling and heterochronic regulation, and in turn regulating genes involved in cellular processes such as vesicle trafficking and cytoskeletal rearrangement (Nelson et al 2011). However, while some of the regulatory pathways involved in specifying DMD-3 expression are known, the structure of the network downstream of DMD-3 is uncharacterized. We are using two methods to investigate downstream targets of DMD-3. To identify tail tip-specific targets, we are performing transcriptome profiling of tail tip tissue from worms that undergo tail tip morphogenesis (wild-type males and hermaphrodites ectopically expressing dmd-3), and worms that do not (wild-type hermaphrodites and dmd-3 mutant males). To identify direct DMD-3 transcriptional targets, we are employing chromatin immunoprecipitation and next-generation sequencing (ChIP-Seq), using an epitope-tagged DMD-3::GFP::FLAG transgene. Preliminary microarray transcriptome analysis on tail tip-specific RNA identified 134 significantly differentially-expressed genes (alpha = 0.05) in the dmd-3 mutant relative to wild-type. Combining the results of both approaches will yield direct targets of DMD-3 that act in the male tail tip. References: Mason et al. 2008. Development 135:2373-2382. Nelson et al. 2011. PLoS Genetics 7(3):e1002010.

Jodie F Wren et al. (2005) International Worm Meeting "Environmental Genomics of Fluoranthene Exposure"

Stephen R Sturzenbaum, Jodie F Wren, A John Morgan, Peter K Hankard, Nick Redshaw, Suresh C Swain, Claus Svendsen, Martijs J Jonker, David J Spurgeon

[International Worm Meeting, 2005]

Benzo(j)Fluoranthene, is a 5-ring polycyclic aromatic hydrocarbon (PAH), known to occur as a product of plant biosynthesis, but also as a byproduct of incomplete combustion of organic material. Fluoranthene has been identified in cigarette smoke, char-broiled foods, drinking water, lake sediments and ambient air. It is thought to interact with DNA, cause heritable genetic disorders and has been associated with lung, intestinal and pharyngeal cancer. Information regarding the toxicity of fluoranthene in C.elegans still remains scarce, a shortfall we are aiming to redress. Using GE-31 (an embryonic lethal TS mutant) an elaborate toxicity test identified a dose dependant slippery pharynx phenotype and effects on specific demographic endpoints, such as brood size, volumetric growth and life span. Exploiting whole genome oligo array technology, we are currently exploring the stage-specific toxic effects of fluoranthene at a transcriptional level.

Yang, Ji-Sup et al. (2015) International Worm Meeting "Identification of DMD-3 targets in the C. elegans male tail tip."

Williams, Emily, Herrera, R Antonio, Ercan, Sevinc, Kiontke, Karin, Yang, Ji-Sup, Fitch, David, Mason, Adam, Littleford, Hana

[International Worm Meeting, 2015]

Cellular morphogenesis is a fundamental developmental mechanism that governs how cells migrate, change identity, change shape, and fuse. The C. elegans male tail tip undergoes a morphogenetic event in just four cells during late L4, making this a powerful model for elucidating linkage between regulators of timing, position, and epidermal fate and the cell-biological mechanisms required for morphogenesis. Male tail tip morphogenesis (TTM) is governed by DMD-3, a conserved DM-domain transcription factor that is homologous to DMRT1, which regulates male fate in humans. Expression of dmd-3 is necessary and sufficient for TTM to occur (Mason et al. 2008). Previous work done in the lab has shown that DMD-3 is at the center of a genetic network with a bow-tie structure, regulated by pathways including Wnt signaling and heterochronic regulation, and in turn regulating genes involved in cellular processes such as vesicle trafficking and cytoskeletal rearrangement (Nelson et al 2011). However, while some of the regulatory pathways involved in specifying DMD-3 expression are known, the structure of the network downstream of DMD-3 is uncharacterized. We are using two methods to investigate downstream targets of DMD-3: To identify tail tip-specific targets, we are performing transcriptome profiling of isolated tail tip tissue from worms that undergo tail tip morphogenesis (wild-type males and hermaphrodites ectopically expressing dmd-3), and worms that do not (wild-type hermaphrodites and dmd-3 mutant males). To identify direct DMD-3 transcriptional targets, we are employing chromatin immunoprecipitation and next-generation sequencing (ChIP-Seq), utilizing a CRISPR-generated dmd-3 allele tagged with GFP and 3xFLAG. Preliminary microarray transcriptome analysis on tail tip-specific RNA identified 134 significantly differentially expressed genes in the dmd-3 mutant relative to wild-type. Combining the results of both approaches will yield direct targets of DMD-3 that act in the male tail tip.References: Mason et al. 2008. Development 135:2373-2382. Nelson et al. 2011. PLoS Genetics 7(3):e1002010.