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Journal of Applied Toxicology : JAT Jan 2017Caenorhabditis elegans is a small nematode that can be maintained at low cost and handled using standard in vitro techniques. Unlike toxicity testing using cell... (Review)
Review
Caenorhabditis elegans is a small nematode that can be maintained at low cost and handled using standard in vitro techniques. Unlike toxicity testing using cell cultures, C. elegans toxicity assays provide data from a whole animal with intact and metabolically active digestive, reproductive, endocrine, sensory and neuromuscular systems. Toxicity ranking screens in C. elegans have repeatedly been shown to be as predictive of rat LD ranking as mouse LD ranking. Additionally, many instances of conservation of mode of toxic action have been noted between C. elegans and mammals. These consistent correlations make the case for inclusion of C. elegans assays in early safety testing and as one component in tiered or integrated toxicity testing strategies, but do not indicate that nematodes alone can replace data from mammals for hazard evaluation. As with cell cultures, good C. elegans culture practice (GCeCP) is essential for reliable results. This article reviews C. elegans use in various toxicity assays, the C. elegans model's strengths and limitations for use in predictive toxicology, and GCeCP. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons Ltd.
Topics: Animal Use Alternatives; Animals; Caenorhabditis elegans; Lethal Dose 50; Toxicity Tests
PubMed: 27443595
DOI: 10.1002/jat.3357 -
WormBook : the Online Review of C.... May 2017Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome... (Review)
Review
Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome content in the next generation. This reduction in genetic content is accomplished during a specialized cell division called meiosis, in which two rounds of chromosome segregation follow a single round of DNA replication. In preparation for the first meiotic division, homologous chromosomes pair and synapse, creating a context that promotes formation of crossover recombination events. These crossovers, in conjunction with sister chromatid cohesion, serve to connect the two homologs and facilitate their segregation to opposite poles during the first meiotic division. During the second meiotic division, which is similar to mitosis, sister chromatids separate; the resultant products are haploid cells that become gametes. In Caenorhabditis elegans (and most other eukaryotes) homologous pairing and recombination are required for proper chromosome inheritance during meiosis; accordingly, the events of meiosis are tightly coordinated to ensure the proper execution of these events. In this chapter, we review the seminal events of meiosis: pairing of homologous chromosomes, the changes in chromosome structure that chromosomes undergo during meiosis, the events of meiotic recombination, the differentiation of homologous chromosome pairs into structures optimized for proper chromosome segregation at Meiosis I, and the ultimate segregation of chromosomes during the meiotic divisions. We also review the regulatory processes that ensure the coordinated execution of these meiotic events during prophase I.
Topics: Animals; Caenorhabditis elegans; Cell Division; Chromosome Segregation; Chromosomes; Meiosis; Meiotic Prophase I; Recombination, Genetic
PubMed: 26694509
DOI: 10.1895/wormbook.1.178.1 -
Cells Jan 2020DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in , integrates signals from upstream pathways to elicit transcriptional changes in many genes... (Review)
Review
DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in , integrates signals from upstream pathways to elicit transcriptional changes in many genes involved in aging, development, stress, metabolism, and immunity. The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood. This program includes elevated antioxidant defense and a metabolic shift toward accumulation of carbohydrates (i.e., trehalose and glycogen) and triglycerides, and activation of the glyoxylate shunt, which could allow fat-to-carbohydrate conversion. The longevity of mutants seems to be partially supported by endogenous trehalose, a nonreducing disaccharide that mammals cannot synthesize, which points toward considerable differences in downstream mechanisms by which IIS regulates aging in distinct groups.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Forkhead Transcription Factors; Models, Biological; Mutation; Signal Transduction; Stress, Physiological
PubMed: 31906434
DOI: 10.3390/cells9010109 -
Molecules and Cells Feb 2017is an important model organism with many useful features, including rapid development and aging, easy cultivation, and genetic tractability. Survival assays using are... (Review)
Review
is an important model organism with many useful features, including rapid development and aging, easy cultivation, and genetic tractability. Survival assays using are powerful methods for studying physiological processes. In this review, we describe diverse types of survival assays and discuss the aims, uses, and advantages of specific assays. survival assays have played key roles in identifying novel genetic factors that regulate many aspects of animal physiology, such as aging and lifespan, stress response, and immunity against pathogens. Because many genetic factors discovered using are evolutionarily conserved, survival assays can provide insights into mechanisms underlying physiological processes in mammals, including humans.
Topics: Animals; Caenorhabditis elegans; Longevity; Models, Animal
PubMed: 28241407
DOI: 10.14348/molcells.2017.0017 -
WormBook : the Online Review of C.... Sep 2017The nematode Caenorhabditis elegans is now a major model organism in biology. The choice of Sydney Brenner to adopt this species in the mid-1960s and the success of his... (Review)
Review
The nematode Caenorhabditis elegans is now a major model organism in biology. The choice of Sydney Brenner to adopt this species in the mid-1960s and the success of his team in raising it to a model organism status have been told (http://www.wormbook.org/toc_wormhistory.html; Brenner, 2001; Ankeny, 2001). Here we review the pre-Brenner history of the use of free-living nematodes as models for general questions in biology. We focus on the period that started in 1899 with the first publication of Emile Maupas mentioning Rhabditis elegans and ended in 1974 with the first publications by Brenner. A common thread in this period, aided by the variety in modes of reproduction of different nematode species, is found in studies of meiosis, fertilization, heredity, and sex determination. Maupas in his 1900 opus on reproduction had already chosen C. elegans as the species of reference. Hikokura Honda determined its hermaphrodite chromosomal content in 1925. C. elegans was again isolated and chosen as a main subject by Victor Nigon in the 1940-50s. Nigon mastered crosses between C. elegans hermaphrodites and males, described the meiotic behavior of chromosomes in XX hermaphrodites and X0 males and, using tetraploids, correctly inferred that sex was determined by X chromosome to autosome dosage. With Ellsworth Dougherty, Nigon isolated and studied a C. briggsae body size mutant and a C. elegans slow growth mutant. Dougherty and his team devoted most of their work to finding a defined culture medium to screen for physiological mutants, focusing on C. briggsae. With Helene Fatt, Dougherty also performed the first genetic study of natural variation in C. elegans, concerning the difference in heat resistance of the Bergerac and Bristol strains. Jean Brun, a student of Nigon, performed a long and remarkable experiment in acclimatization of C. elegans Bergerac to higher temperatures, the significance of which remains to be clarified.
Topics: Adaptation, Physiological; Aging; Animals; Biomedical Research; Caenorhabditis elegans; Fertility; Hermaphroditic Organisms; History, 19th Century; History, 20th Century; Meiosis; Models, Animal; Parthenogenesis; Sex Determination Analysis; Temperature
PubMed: 28326696
DOI: 10.1895/wormbook.1.181.1 -
Genetics Oct 2017Lipid and carbohydrate metabolism are highly conserved processes that affect nearly all aspects of organismal biology. eat bacteria, which consist of lipids,... (Review)
Review
Lipid and carbohydrate metabolism are highly conserved processes that affect nearly all aspects of organismal biology. eat bacteria, which consist of lipids, carbohydrates, and proteins that are broken down during digestion into fatty acids, simple sugars, and amino acid precursors. With these nutrients, synthesizes a wide range of metabolites that are required for development and behavior. In this review, we outline lipid and carbohydrate structures as well as biosynthesis and breakdown pathways that have been characterized in We bring attention to functional studies using mutant strains that reveal physiological roles for specific lipids and carbohydrates during development, aging, and adaptation to changing environmental conditions.
Topics: Animals; Caenorhabditis elegans; Carbohydrate Metabolism; Lipid Metabolism
PubMed: 28978773
DOI: 10.1534/genetics.117.300106 -
WormBook : the Online Review of C.... Aug 2018The nematode Caenorhabditis elegans relies on its innate immune defenses to counter infection. In this review, we focus on its response to infection by bacterial and... (Review)
Review
The nematode Caenorhabditis elegans relies on its innate immune defenses to counter infection. In this review, we focus on its response to infection by bacterial and fungal pathogens. We describe the different families of effector proteins that contribute to host defense, as well as the signal transduction pathways that regulate their expression. We discuss what is known of the activation of innate immunity in C. elegans, via pathogen recognition or sensing the damage provoked by infection. Damage causes a stress response; we review the role of stress signaling in host defense to infection. We examine examples of inter-tissue communication in innate immunity and end with a survey of post-transcriptional regulation of innate immune responses.
Topics: Animals; Bacteria; Caenorhabditis elegans; Fungi; Immunity, Innate; Signal Transduction
PubMed: 26694508
DOI: 10.1895/wormbook.1.83.2 -
Molecules (Basel, Switzerland) Dec 2021In the forms of either herbs or functional foods, plants and their products have attracted medicinal, culinary, and nutraceutical applications due to their abundance in... (Review)
Review
In the forms of either herbs or functional foods, plants and their products have attracted medicinal, culinary, and nutraceutical applications due to their abundance in bioactive phytochemicals. Human beings and other animals have employed those bioactive phytochemicals to improve health quality based on their broad potentials as antioxidant, anti-microbial, anti-carcinogenic, anti-inflammatory, neuroprotective, and anti-aging effects, amongst others. For the past decade and half, efforts to discover bioactive phytochemicals both in pure and crude forms have been intensified using the aging model, in which various metabolic pathways in humans are highly conserved. In this review, we summarized the aging and longevity pathways that are common to and humans and collated some of the bioactive phytochemicals with health benefits and lifespan extending effects that have been studied in . This simple animal model is not only a perfect system for discovering bioactive compounds but is also a research shortcut for elucidating the amelioration mechanisms of aging risk factors and associated diseases.
Topics: Aging; Animals; Caenorhabditis elegans; Humans; Longevity; Metabolic Networks and Pathways; Phytochemicals
PubMed: 34885907
DOI: 10.3390/molecules26237323 -
Genetics Oct 2020' behavioral states, like those of other animals, are shaped by its immediate environment, its past experiences, and by internal factors. We here review the literature... (Review)
Review
' behavioral states, like those of other animals, are shaped by its immediate environment, its past experiences, and by internal factors. We here review the literature on behavioral states and their regulation. We discuss dwelling and roaming, local and global search, mate finding, sleep, and the interaction between internal metabolic states and behavior.
Topics: Animals; Behavior, Animal; Caenorhabditis elegans; Energy Metabolism; Genetics, Behavioral; Sleep
PubMed: 33023930
DOI: 10.1534/genetics.120.303539 -
Nature Nov 2023Establishing how neural function emerges from network properties is a fundamental problem in neuroscience. Here, to better understand the relationship between the...
Establishing how neural function emerges from network properties is a fundamental problem in neuroscience. Here, to better understand the relationship between the structure and the function of a nervous system, we systematically measure signal propagation in 23,433 pairs of neurons across the head of the nematode Caenorhabditis elegans by direct optogenetic activation and simultaneous whole-brain calcium imaging. We measure the sign (excitatory or inhibitory), strength, temporal properties and causal direction of signal propagation between these neurons to create a functional atlas. We find that signal propagation differs from model predictions that are based on anatomy. Using mutants, we show that extrasynaptic signalling not visible from anatomy contributes to this difference. We identify many instances of dense-core-vesicle-dependent signalling, including on timescales of less than a second, that evoke acute calcium transients-often where no direct wired connection exists but where relevant neuropeptides and receptors are expressed. We propose that, in such cases, extrasynaptically released neuropeptides serve a similar function to that of classical neurotransmitters. Finally, our measured signal propagation atlas better predicts the neural dynamics of spontaneous activity than do models based on anatomy. We conclude that both synaptic and extrasynaptic signalling drive neural dynamics on short timescales, and that measurements of evoked signal propagation are crucial for interpreting neural function.
Topics: Animals; Caenorhabditis elegans; Calcium; Models, Neurological; Mutation; Neural Pathways; Neurons; Neuropeptides; Synapses; Signal Transduction
PubMed: 37914938
DOI: 10.1038/s41586-023-06683-4