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Trends in Ecology & Evolution,
1999]
In a recent TREE news & comment, Gadagkar made some useful comments on LaMunyon and Ward's interesting study on sexual reproduction in nematodes. I think, however, that he - and LaMunyon and Ward - have confused the benefits of sex for species or demes with those for individuals or genes.
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Aging (Albany NY),
2010]
A major goal of aging research is to identify interventions that prolong lifespan in distantly related organisms. In recent years, genetic studies in both nematodes and rodents have reported that moderate inactivation of genes important for mitochondrial electron transport chain (ETC) function can promote longevity. We performed an RNAi screen to probe the role of ETC components in modulating lifespan in the fruit fly Drosophila melanogaster. In this Research Perspective, we discuss our findings and how they may relate to similar studies in worms and mice.
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FEBS J,
2021]
Electron transport chain (ETC) dysfunction is a common feature of mitochondrial diseases and induces severe cellular stresses, including mitochondrial membrane potential (<sub>m</sub> ) reduction, mitochondrial matrix acidification, metabolic derangements and proteostatic stresses. Extensive studies of ETC dysfunction in yeast, C. elegans, cultured cells and mouse models have revealed multiple mitochondrial stress response pathways. Here, we summarize the current understanding of the triggers, sensors, signaling mechanisms, and the functional outcomes of mitochondrial stress responses in different species. We highlight <sub>m</sub> reduction as a major trigger of stress responses in different species, but the responses are species-specific and the outcomes are context-dependent. ETC dysfunction elicits a mitochondrial unfolded protein response (UPR<sup>mt</sup> ) to repair damaged mitochondria in C. elegans, and activates a global adaptive program to maintain <sub>m</sub> in yeast. Yeast and C. elegans responses are remarkably similar at the downstream responses, although they are activated by different signaling mechanisms. UPR<sup>mt</sup> generally protects ETC-defective worms, but its constitutive activation is toxic for wildtype worms and worms carrying mutant mtDNA. In contrast to lower organisms, ETC dysfunction in mammals mainly activates a mitochondrial integrated stress response (ISR<sup>mt</sup> ) to reprogram metabolism and a PINK1-Parkin mitophagy pathway to degrade damaged mitochondria. Accumulating in vivo results suggest that the ATF4 branch of ISR<sup>mt</sup> exacerbates metabolic derangements to accelerate mitochondrial disease progression. The in vivo roles of mitophagy in mitochondrial diseases are also context-dependent. These results thus reveal the common and unique aspects of mitochondrial stress responses in different species and highlight their multifaceted roles in mitochondrial diseases.
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WormBook,
2014]
C. elegans detect and respond to diverse mechanical stimuli using neuronal circuitry that has been defined by decades of work by C. elegans researchers. In this WormMethods chapter, we review and comment on the techniques currently used to assess mechanosensory response. This methods review is intended both as an introduction for those new to the field and a convenient compendium for the expert. A brief discussion of commonly used mechanosensory assays is provided, along with a discussion of the neural circuits involved, consideration of critical protocol details, and references to the primary literature.
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Trends in Ecology & Evolution,
1999]
In a recent TREE news & comment, Gadagkar made some useful comments on LaMunyon and Ward's interesting study on sexual reproduction in nematodes. I think, however, that he - and LaMunyon and Ward - have confused the benefits of sex for species or demes with those for individuals or genes. For females and hermaphrodites (but not for species or demes), the twofold cost of sexual reproduction or producing males' in Maynard Smith's sense implies the cost of producing offspring that have only half of the hermaphrodite parent's genome set - not directly that of producing males. An offspring of a hermaphrodite Caenorhabditis briggsae inherits half, not more, of each parental genome set. The hermaphrodite parent still pays the two fold cost of sexual reproduction in the same way as
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Cold Spring Harb Perspect Med,
2015]
The mechanisms underlying biological aging have been extensively studied in the past 20 years with the avail of mainly four model organisms: the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster, and the domestic mouse Mus musculus. Extensive research in these four model organisms has identified a few conserved genetic pathways that affect longevity as well as metabolism and development. Here, we review how the mechanistic target of rapamycin (mTOR), sirtuins, adenosine monophosphate-activated protein kinase (AMPK), growth hormone/insulin-like growth factor 1 (IGF-1), and mitochondrial stress-signaling pathways influence aging and life span in the aforementioned models and their possible implications for delaying aging in humans. We also draw some connections between these biochemical pathways and comment on what new developments aging research will likely bring in the near future.
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Integr Comp Biol,
2014]
Gamete cells pass on information to the next generation via DNA sequence and also through epigenetic mechanisms such as small RNAs, DNA methylation, or chromatin modifications. Caenorhabditis elegans is a genetic model system that an enormous number of talented researchers have used to understand biological phenomenon and develop molecular tools that have ultimately led to paradigm-shifting ideas in biology. Thus, this model is well poised to further investigate the molecular mechanisms involved with epigenetic modifications and transgenerational epigenetic inheritance. The strengths of this model system include a historical wealth of information regarding genetics, development, germline function, chromosome biology, and the regulation of gene expression. Using this system, one can investigate the mechanisms involved with how the germline passes on heritable epigenetic information to subsequent generations. Here, we highlight aspects about the biology of C. elegans that make it amenable to epigenetic studies, highlight some recent findings in the field of epigenetics, and comment on how this system would be beneficial for future biological studies involving epigenetic processes.
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Int J Mol Sci,
2013]
Oxidative stress is thought to play a significant role in the development and progression of neurodegenerative diseases. Although it is currently considered a hallmark of such processes, the interweaving of a multitude of signaling cascades hinders complete understanding of the direct role of oxidative stress in neurodegeneration. In addition to its extensive use as an aging model, some researchers have turned to the invertebrate model Caenorhabditis elegans (C. elegans) in order to further investigate molecular mediators that either exacerbate or protect against reactive oxygen species (ROS)-mediated neurodegeneration. Due to their fully characterized genome and short life cycle, rapid generation of C. elegans genetic models can be useful to study upstream markers of oxidative stress within interconnected signaling pathways. This report will focus on the roles of C. elegans homologs for the oxidative stress-associated transcription factor Nrf2, as well as the autosomal recessive, early-onset Parkinson's disease (PD)-associated proteins Parkin, DJ-1, and PINK1, in neurodegenerative processes.
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J Neuropathol Exp Neurol,
1994]
Morphological features of cerebral cortical dysplasias generally regarded under the umbrella term 'migration disorders' have been reviewed and critically analyzed against current knowledge of gene activity involved in neurogenesis. Although data are plentiful regarding the nature and role of these genes in lower forms, i.e. C. elegans and Drosophila, relatively few human homologs have been identified. Multiple genes are involved in various specific aspects of neurogenesis, i.e. neuroblast proliferation, PCD, migration, etc., and it is postulated that there are parallel gene actions in human neural development. A hypothetical construct of specific gene defects in human neurogenesis accounting for the morphological variations observed in the migration disorders is postulated.
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Oxid Med Cell Longev,
2012]
Many insights into the mechanisms and signaling pathways underlying aging have resulted from research on the nematode Caenorhabditis elegans. In this paper, we discuss the recent findings that emerged using this model organism concerning the role of reactive oxygen species (ROS) in the aging process. The accrual of oxidative stress and damage has been the predominant mechanistic explanation for the process of aging for many years, but reviewing the recent studies in C. elegans calls this theory into question. Thus, it becomes more and more evident that ROS are not merely toxic byproducts of the oxidative metabolism. Rather it seems more likely that tightly controlled concentrations of ROS and fluctuations in redox potential are important mediators of signaling processes. We therefore discuss some theories that explain how redox signaling may be involved in aging and provide some examples of ROS functions and signaling in C. elegans metabolism. To understand the role of ROS and the redox status in physiology, stress response, development, and aging, there is a rising need for accurate and reversible in vivo detection. Therefore, we comment on some methods of ROS and redox detection with emphasis on the implementation of genetically encoded biosensors in C. elegans.