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Int J Mol Sci,
2019]
Aging is an unstoppable process coupled to the loss of physiological function and increased susceptibility to diseases. Epigenetic alteration is one of the hallmarks of aging, which involves changes in DNA methylation patterns, post-translational modification of histones, chromatin remodeling and non-coding RNA interference. Invertebrate model organisms, such as <i>Drosophila melanogaster</i> and <i>Caenorhabditis elegans</i>, have been used to investigate the biological mechanisms of aging because they show, evolutionarily, the conservation of many aspects of aging. In this review, we focus on recent advances in the epigenetic changes of aging with invertebrate models, providing insight into the relationship between epigenetic dynamics and aging.
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Nature Neuroscience,
2001]
To reach their proper targets, axons rely upon the actions of highly conserved families of attractive and repulsive guidance molecules, including the netrins, Slits, semaphorins and ephrins. These guidance systems are used to generate an astonishingly varied set of neuronal circuits. Here we consider the mechanisms by which a few guidance systems can be used to generate diverse outcomes. Recent studies have revealed extensive transcriptional and post-transcriptional regulation of guidance cues and their regulators, as well as combinatorial mechanisms that integrate information from different families of guidance cues.
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Brain Sci,
2022]
Multisensory integration refers to sensory inputs from different sensory modalities being processed simultaneously to produce a unitary output. Surrounded by stimuli from multiple modalities, animals utilize multisensory integration to form a coherent and robust representation of the complex environment. Even though multisensory integration is fundamentally essential for animal life, our understanding of the underlying mechanisms, especially at the molecular, synaptic and circuit levels, remains poorly understood. The study of sensory perception in Caenorhabditis elegans has begun to fill this gap. We have gained a considerable amount of insight into the general principles of sensory neurobiology owing to C. elegans' highly sensitive perceptions, relatively simple nervous system, ample genetic tools and completely mapped neural connectome. Many interesting paradigms of multisensory integration have been characterized in C. elegans, for which input convergence occurs at the sensory neuron or the interneuron level. In this narrative review, we describe some representative cases of multisensory integration in C. elegans, summarize the underlying mechanisms and compare them with those in mammalian systems. Despite the differences, we believe C. elegans is able to provide unique insights into how processing and integrating multisensory inputs can generate flexible and adaptive behaviors. With the emergence of whole brain imaging, the ability of C. elegans to monitor nearly the entire nervous system may be crucial for understanding the function of the brain as a whole.
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Exp Gerontol,
2010]
More than 400 genes have been noted to modulate Caenorhabditis elegans longevity. Recent studies testing the role of proposed secreted insulin-binding proteins unexpectedly revealed a potent role for the EGF signaling pathway in promoting healthy aging and longevity in C. elegans. Activation of EGF receptor LET-23 is associated with increased mean and maximum lifespan, maintained pharyngeal pumping, extended locomotory function, and low lipofuscin and advanced glycation end product accumulation. Conversely, reducing the activity of the EGF pathway is associated with system-wide evidence of progeria. The EGF pathway appears to work in a manner largely independent of the insulin/IGF-like pathway, in that effects are additive with reduction of DAF-2/InsR activity and are not affected by DAF-16/FOXO transcription factor deficiency. Two novel regulators of EGF signaling, called HPA-1 and HPA-2 (for the high performance in advanced age locomotory phenotypes that their disruption confers), negatively regulate EGF action, possibly by binding and sequestering EGF. Interestingly, whereas HPA-1 appears to control aging of the animal overall, HPA-2 exerts an effect primarily on locomotory aging. As such, HPA-2 is an example of a protein with an effect on healthspan but not lifespan, a gene class that may have been missed in screens focused on longevity endpoint. To date, roles for EGF signaling in adult maintenance (particularly in non-dividing tissues) have not been addressed in other organisms-should EGF signaling exert a conserved impact on healthy aging, testing this hypothesis could hold implications for anti-aging therapies.
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Semin Cell Dev Biol,
2016]
During meiotic prophase, chromosomes pair and synapse with their homologs and undergo programmed DNA double-strand break (DSB) formation to initiate meiotic recombination. These DSBs are processed to generate a limited number of crossover recombination products on each chromosome, which are essential to ensure faithful segregation of homologous chromosomes. The nematode Caenorhabditis elegans has served as an excellent model organism to investigate the mechanisms that drive and coordinate these chromosome dynamics during meiosis. Here we focus on our current understanding of the regulation of DSB induction in C. elegans. We also review evidence that feedback regulation of crossover formation prolongs the early stages of meiotic prophase, and discuss evidence that this can alter the recombination pattern, most likely by shifting the genome-wide distribution of DSBs.
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Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi,
2009]
Humans are negatively affected by parasitic infection. However, recent researches revealed that to some extent, parasitic infections are advantageous to humans. Parasitic infections are found to benefit patients of inflammatory bowel disease, diabetes mellitus, autoimmune disease and allergic disorder. Furthermore, they promoted studies on pathogenesis of these diseases, and therefore on safe and effective therapeutic strategy. In addition, by taking the Caenorhabditis elegans as model organism, researchers have made a breakthrough in the area of life science, including signal transduction, functional genomics and drug screening.
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Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi,
2012]
Macrophage migration inhibitory factor (MIF) is an important proinflammatory and immunoregulatory mediator, which locates at the apex of the cascade of innate immune response. It also plays an important role in regulating adaptive immune responses and counter-regulating the immunosuppressive effect of glucocorticoid. MIF is actively involved in a series of cell processes such as cell proliferation and differentiation as well as cell apoptosis. MIF is reported to regulate the host immune response to parasitic infection. Interestingly, the ortholog of mammalian MIF was identified in multiple parasites such as Plasmodium spp., Leishmania major, Brugia malayi and so on, which is actively involved in the regulation of host-pathogen interaction and therefore provides a novel immune evasion mechanism. Therefore, development of small molecular inhibitors and vaccines against MIF will pave a new avenue for the prevention and treatment of related parasitic diseases.
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International Journal of Developmental Biology,
1998]
Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.
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Curr Biol,
2003]
A novel protein in Caenorhabditis elegans, SAS-4, is a component of centrioles and is required for centriole duplication. Depletion of SAS-4 results in stunted centrioles and a smaller centrosome, suggesting a link to organelle size control.
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Curr Biol,
1997]
An increasing body of evidence indicates that
p53, the product of a tumour suppressor gene, has a role in development - could this developmental role have provided the primary driving force in the evolution of a protein best known as a stress-response integrator?