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Int J Hyperthermia,
2013]
Heat shock proteins (HSP) are molecular chaperones and have been implicated in longevity and aging in many species. Their major functions include chaperoning misfolded or newly synthesised polypeptides, protecting cells from proteotoxic stress, and processing of immunogenic agents. These proteins are expressed constitutively and can be induced by stresses such as heat, oxidative stress and many more. The induction of HSP in aging could potentially maintain protein homeostasis and longevity by refolding the damaged proteins which accumulate during aging and are toxic to cells. HSP are shown to increase life span in model organisms such as Caenorhabditis elegans and decrease aging-related proteotoxicity. Thus, decrease in HSP in aging is associated with disruption of cellular homeostasis which causes diseases such as cancer, cell senescence and neurodegeneration. HSP levels are decreased with aging in most organs including neurons. Aging also causes attenuation or alteration of many signalling pathways as well as the expression of transcription factors such as heat shock factor (HSF). The alteration in regulation and synthesis of Forkhead box O3a (FoxO3a) family of transcription factors as well as major antioxidant enzymes (manganese superoxide dismutase, catalase) are also seen in aging. Among many signalling mechanisms involved in altering longevity and aging, the insulin/IGF-1 pathway and the Sir2 deacetylase are highly significant. This review enquires into the role of some of these pathways in longevity/aging along with HSP.
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WormBook,
2012]
The pharynx is a neuromuscular pump at the anterior end of the alimentary tract. It is made up of 20 muscle cells, 20 neurons, and 20 other cells. Pharyngeal activity correlates with food intake. The proper feeding rate, as well as the precise timing of pharyngeal movements, is required for efficient feeding and likely for survival in nature. For most purposes, pharyngeal behavioral analysis requires no more than a routine stereomicroscope and a pair of eyes, but accuracy can be increased by video recording followed by off-line analysis in slow motion. Like other C. elegans behaviors, pharyngeal behavior is sensitive to both the immediate environmental conditions as well as to the history of such conditions.
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Biochim Biophys Acta,
2010]
The enzymes of O-GlcNAc cycling couple the nutrient-dependent synthesis of UDP-GlcNAc to O-GlcNAc modification of Ser/Thr residues of key nuclear and cytoplasmic targets. This series of reactions culminating in O-GlcNAcylation of targets has been termed the hexosamine signaling pathway (HSP). The evolutionarily ancient enzymes of O-GlcNAc cycling have co-evolved with other signaling effecter molecules; they are recruited to their targets by many of the same mechanisms used to organize canonic kinase-dependent signaling pathways. This co-recruitment of the enzymes of O-GlcNAc cycling drives a binary switch impacting pathways of anabolism and growth (nutrient uptake) and catabolic pathways (nutrient sparing and salvage). The hexosamine signaling pathway (HSP) has thus emerged as a versatile cellular regulator modulating numerous cellular signaling cascades influencing growth, metabolism, cellular stress, circadian rhythm, and host-pathogen interactions. In mammals, the nutrient-sensing HSP has been harnessed to regulate such cell-specific functions as neutrophil migration, and activation of B-cells and T-cells. This review summarizes the diverse approaches being used to examine O-GlcNAc cycling. It will emphasize the impact O-GlcNAcylation has upon signaling pathways that may be become deregulated in diseases of the immune system, diabetes mellitus, cancer, cardiovascular disease, and neurodegenerative diseases.
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Physiol Genomics,
2003]
Life developed in a stressful environment. Stressors at the cellular level include heat, hypoxia, oxidative or reductive substances, mechanical or osmotic pressure, and toxic compounds like heavy metals. Various molecular pathways, more or less specific for the different stressors, developed during evolution to combat the molecular consequences of cell stress. Thermal stress induces the induction of a highly conserved protein family, the heat shock proteins (HSP).
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Dev Dyn,
2008]
The 20 neurons that innervate the Caenorhabditis elegans pharynx form a simple nervous system that develops and operates in near complete isolation from the rest of the worm body and, therefore, offers a manageable degree of complexity for developmental genetics studies. This review discusses the progress that has been made in determining the mechanisms by which 4 of the 20 pharyngeal neurons develop, and emphasizes surprising processes that add to the classic growth cone guidance model which is usually thought to explain how most axons establish their trajectories. Developmental Dynamics 237:2073-2080, 2008. (c) 2008 Wiley-Liss, Inc.
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Semin Cell Dev Biol,
2017]
The midgut (intestine) of the nematode, C. elegans, is a tube consisting of 20 cells that arises from a single embryonic precursor. Owing to its comparatively simple anatomy and the advantages inherent to the C. elegans system, the gut has been used as a model for organogenesis for more than 25 years. In this review, the salient features of C. elegans gut development are described from the E progenitor through to the 20-cell intestine. The core gene regulatory network that drives specification of the gut, and other genes with roles in organogenesis, lumen morphogenesis and the cell cycle, are also described. Questions for future work are posed.
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Parasitol Today,
1991]
The free-living nematode Caenorhabditis elegans offers many advantages as an experimental system and extensive similarities in overall structure and development exist between it and parasitic nematodes. The purpose of the meeting held at Broadway, 17-20 February 1991, with the financial support of the Wellcome Trust, was to stimulate interaction between schools of nematologists.
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Science,
1998]
About 800 biologists gathered at Stanford University from 20 to 25 June for the 57th annual meeting of the Society for Developmental Biology. Study organisms ranged from flies to mice to plants, but there was plenty of common ground, including a new pathway by which signaling molecules can shape the early embryo and a new gene that helps specify right from left.
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Biogerontology,
2002]
This is a personal account of the early days in the genetic analysis of aging when it was difficult to persuade the world that there were genes that specified life prolongation. I describe the situation in 1980 and briefly describe the background of early work on the nematode Caenorhabditis elegans and my role in the revolution in aging research that has occurred in the last 20 years.
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Parasitology,
2000]
This detailed review of the published studies underlying ivermectin's recent registration for use in lymphatic filariasis (LF) demonstrates the drug's single-dose efficacy (over the range of 20-400 microg/kg) in clearing microfilaraemia associated with both Wuchereria bancrofti and Brugia malayi infections of humans. While doses as low as 20 microg/kg could effect transient microfilarial (mf) clearance, higher dosages induced greater and more sustained mf reduction. The single dose of 400 microg/kg yielded maximal responses, but a number of practical considerations suggest that either 400 microg/kg or 200 microg/kg doses would be acceptable for use in LF control programmes. Associated safety assessments indicate that adverse events, which occur commonly following treatment of microfilaraemic individuals, develop not because of drug toxicity but because of host inflammatory responses to dying microfilariae killed by the ivermectin treatment. Ivermectin is, therefore, a highly effective and generally well tolerated microfilaricide that may soon become an essential component of many public health initiatives to interrupt transmission of lymphatic filarial infection in an effort to eliminate LF globally.