Plasticity of the Electrical Connectome of C. elegans

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Multiple Molecular Mechanisms Rescue mtDNA Disease in C. elegans

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Entosis Controls a Developmental Cell Clearance in C. elegans

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Natural Genetic Variation in a Multigenerational Phenotype in C. elegans

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Assessment and Maintenance of Unigametic Germline Inheritance for C. elegans

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Loss of intestinal nuclei and intestinal integrity in aging C. elegans

The roundworm C. elegans is widely used as an aging model, with hundreds of genes identified that modulate aging (Kaeberlein et al., 2002. Mech. Ageing Dev. 123 , 1115–1119). The development and bodyplan of the 959 cells comprising the adult have been well described and established for more than 25 years ( Sulston & Horvitz, 1977 . Dev. Biol. 56 , 110–156; Sulston et al., 1983. Dev. Biol. 100 , 64–119.). However, morphological changes with age in this optically transparent animal are less well understood, with only a handful of studies investigating the pathobiology of aging. Age‐related changes in muscle ( Herndon et al., 2002 . Nature 419 , 808–814), neurons ( Herndon et al., 2002 ), intestine and yolk granules ( Garigan et al., 2002 . Genetics 161 , 1101–1112; Herndon et al., 2002 ), nuclear architecture ( Haithcock et al., 2005 . Proc. Natl Acad. Sci. USA 102 , 16690–16695), tail nuclei ( Golden et al., 2007 . Aging Cell 6 , 179–188), and the germline ( Golden et al., 2007 ) have been observed via a variety of traditional relatively low‐throughput methods. We report here a number of novel approaches to study the pathobiology of aging C. elegans. We combined histological staining of serial‐sectioned tissues, transmission electron microscopy, and confocal microscopy with 3D volumetric reconstructions and characterized age‐related morphological changes in multiple wild‐type individuals at different ages. This enabled us to identify several novel pathologies with age in the C. elegans intestine, including the loss of critical nuclei, the degradation of intestinal microvilli, changes in the size, shape, and cytoplasmic contents of the intestine, and altered morphologies caused by ingested bacteria. The three‐dimensional models we have created of tissues and cellular components from multiple individuals of different ages represent a unique resource to demonstrate global heterogeneity of a multicellular organism.     

Natural C. elegans Microbiota Protects against Infection via Production of a Cyclic Lipopeptide of the Viscosin Group

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Glia Modulate a Neuronal Circuit for Locomotion Suppression during Sleep in C. elegans

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Coupling of Rigor Mortis and Intestinal Necrosis during C. elegans Organismal Death

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A Switch in Microtubule Orientation during C. elegans Meiosis

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Carbonylated proteins are eliminated during reproduction in C. elegans

Oxidatively damaged proteins accumulate with age in many species (Stadtman (1992) Science 257 , 1220–1224). This means that damage must be reset at the time of reproduction. To visualize this resetting in the roundworm Caenorhabditis elegans, a novel immunofluorescence technique that allows the detection of carbonylated proteins in situ was developed. The application of this technique revealed that carbonylated proteins are eliminated during C. elegans reproduction. This purging occurs abruptly within the germline at the time of oocyte maturation. Surprisingly, the germline was markedly more oxidized than the surrounding somatic tissues. Because distinct mechanisms have been proposed to explain damage elimination in yeast and mice (Aguilaniu et al. (2003) Science 299 , 1751–1753; Hernebring et al. (2006) Proc Natl Acad Sci USA 103 , 7700–7705), possible common mechanisms between worms and one of these systems were tested. The results show that, unlike in yeast (Aguilaniu et al. (2003) Science 299 , 1751–1753; Erjavec et al. (2008) Proc Natl Acad Sci USA 105 , 18764–18769), the elimination of carbonylated proteins in worms does not require the presence of the longevity‐ensuring gene, SIR‐2.1. However, similar to findings in mice (Hernebring et al. (2006) Proc Natl Acad Sci USA 103 , 7700–7705), proteasome activity in the germline is required for the resetting of carbonylated proteins during reproduction in C. elegans. Thus, oxidatively damaged proteins are eliminated during reproduction in worms through the proteasome. This finding suggests that the resetting of damaged proteins during reproduction is conserved, therefore validating the use of C. elegans as a model to study the molecular basis of damage elimination.     

Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline

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Energy Scarcity Promotes a Brain-wide Sleep State Modulated by Insulin Signaling in C. elegans

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The DNA damage-inducible C. elegans tankyrase is a nuclear protein closely linked to chromosomes

Liver-specific ZP domain-containing protein (LZP) was recently identified as a secreted protein that is specifically expressed in liver. However, the physiological effects of LZP are largely unknown. In this study, we found that LZP was detectable in mouse kidneys, testes, ovaries and heart, in addition to liver. LZP was localized in the spermatid cells of testes, corpus luteum cells of ovaries, and cardiac muscle cells of heart. But the protein mainly anchored on the apical membrane of the thick ascending limb of the loop of Henle (TAL) cell in mouse kidney. In rat kidney LZP and Tamm-Horsfall protein (THP) were co-localized in TAL. The in vivo interaction between LZP and THP was confirmed in kidney and urine by co-immunoprecipitation assay, and the in vitro interaction was detected by GST pull-down assay, implying that the interaction could be independent on N-linked glycosylated modification of LZP. Surprisingly, LZPs with intramolecular disulfide bridges could self-interact, and then self-aggregate into spheres of varying sizes, but not polymerize into filaments. The finding that LZP might act as a new partner of THP would provide novel insights into renal functions related to THP and LZP, such as the urothelial permeability barrier and the host defense against the adhesion of pathogens.     

The Coding Regions of Germline mRNAs Confer Sensitivity to Argonaute Regulation in C. elegans

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Increased Levels of Hydrogen Peroxide Induce a HIF-1-dependent Modification of Lipid Metabolism in AMPK Compromised C. elegans Dauer Larvae

Cells have evolved numerous mechanisms to circumvent stresses caused by the environment, and many of them are regulated by the AMP-activated kinase (AMPK). Unlike most organisms, C.?elegans AMPK-null mutants are viable, but they die prematurely in the "long-lived" dauer stage due?to exhaustion of triglyceride stores. Using?a genome-wide RNAi approach, we demonstrate that the disruption of genes that increase hydrogen peroxide levels enhance the survival of AMPK mutant dauers by altering both the abundance and the nature of the fatty-acid content in the animal by?increasing the HIF-1-dependent expression of several key enzymes involved in fatty-acid biosynthesis. Our data provide a mechanistic foundation to explain how an optimal level of an often vilified ROS-generating compound such as hydrogen peroxide can provide cellular benefit, a phenomenon described as hormesis, by instructing cells to readjust their lipid biosynthetic capacity through downstream HIF-1 activation to correct cellular energy deficiencies.     

Sensory regulation of the C. elegans germline through TGF-β-dependent signaling in the niche

The proliferation/differentiation balance of stem and progenitor cell populations must respond to the physiological needs of the organism [1, 2]. Mechanisms underlying this plasticity are not well understood. The C. elegans germline provides a tractable system to study the influence of the environment on progenitor cells (stem cells and their proliferative progeny). Germline progenitors accumulate during larval stages to form an adult pool from which gametes are produced. Notch pathway signaling from the distal tip cell (DTC) niche to the germline maintains the progenitor pool [3-5], and the larval germline cell cycle is boosted by insulin/IGF-like receptor signaling [6]. Here we show that, independent of its role in the dauer decision, TGF-β regulates the balance of proliferation versus differentiation in the C. elegans germline in response to sensory cues that report population density and food abundance. Ciliated ASI sensory neurons are required for TGF-β-mediated expansion of the larval germline progenitor pool, and the TGF-β receptor pathway acts in the germline stem cell niche. TGF-β signaling thereby couples germline development to the quality of the environment, providing a novel cellular and molecular mechanism linking sensory experience of the environment to reproduction.