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| Open AccessPheromone-based communication influences the production of somatic extracellular vesicles in C. elegans
Extracellular vesicles are fundamental in cellular communication. Here, authors show how C. elegans pheromones regulate vesicle production, showcasing the impact of social behaviors on cellular mechanisms.
- Agata Szczepańska
- , Katarzyna Olek
- & Michał Turek
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| Open AccessEvolutionarily related host and microbial pathways regulate fat desaturation in C. elegans
Fatty acid desaturation is central to metazoan lipid metabolism. Here, using C. elegans as a model, the authors show that both endogenous and microbiota-dependent small molecule signals converge to promote lipid desaturation via the nuclear receptor NHR-49/PPARα.
- Bennett W. Fox
- , Maximilian J. Helf
- & Frank C. Schroeder
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| Open AccessAncient diversity in host-parasite interaction genes in a model parasitic nematode
Host-parasite interactions can lead to negative frequency-dependent selection. Here, the authors sequence the genomes of H. bakeri and H. polygyrus, parasites of house and wood mice, respectively, and find that proteins that interact with the host immune response are often highly diverse.
- Lewis Stevens
- , Isaac Martínez-Ugalde
- & Mark Blaxter
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| Open AccessProlonging somatic cell proliferation through constitutive hox gene expression in C. elegans
Somatic cells in C. elegans stop dividing after completing their normal lineage at the end of development. Here, Heinze et al. show that constitutive expression of a hox gene prolongs proliferation beyond the restriction imposed by the cell lineage.
- Svenia D. Heinze
- , Simon Berger
- & Alex Hajnal
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| Open AccessCisplatin toxicity is counteracted by the activation of the p38/ATF-7 signaling pathway in post-mitotic C. elegans
In contrast to mammalian cells, C. elegans models can be useful because of cells being post-mitotic in adults. Here the authors show activation of the p38 pathway in cisplatin resistant adult animals and characterise the proteins upstream and downstream of the p38 MAPK signalling pathway that are involved in the cisplatin response.
- Dorota Raj
- , Bashar Kraish
- & Peter Naredi
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| Open AccessThe dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation
In this work, the authors report that heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1 by inducing hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation.
- Markus Meier
- , Monika Gupta
- & Jörg Stetefeld
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| Open AccessSex-specificity of the C. elegans metabolome
Biological sex affects all aspects of animal physiology. Using the model C. elegans, the authors show that metabolomes are highly sex-specific and include a vast space of yet unidentified metabolites that may control development and lifespan.
- Russell N. Burkhardt
- , Alexander B. Artyukhin
- & Frank C. Schroeder
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| Open AccessThermosensation in Caenorhabditis elegans is linked to ubiquitin-dependent protein turnover via insulin and calcineurin signalling
Sensation of environmental changes is vital for organismal homeostasis. Here, the authors report that protein degradation in the gut of Caenorhabditis elegans is regulated through insulin and calcineurin signalling upon neuronal sensation of temperature changes.
- Alexandra Segref
- , Kavya L. Vakkayil
- & Thorsten Hoppe
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| Open AccessMapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan
The only known animal polyketide-nonribosomal peptides, the nemamides, are biosynthesized by two megasynthetases in the canal-associated neurons (CANs) of C. elegans. Here, the authors map the biosynthetic roles of individual megasynthetase domains and identify additional enzymes in the CANs required for nemamide biosynthesis.
- Likui Feng
- , Matthew T. Gordon
- & Rebecca A. Butcher
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| Open AccessSubcellular three-dimensional imaging deep through multicellular thick samples by structured illumination microscopy and adaptive optics
Optical aberrations in Structured Illumination Microscopy (SIM) can lead to loss of resolution and artifacts making it unsuitable for thick samples. Here the authors combine Adaptive Optics and SIM (AO-3DSIM) to improve the 3D resolution and reduce artifacts, performing 3D-SIM in C.elegans.
- Ruizhe Lin
- , Edward T. Kipreos
- & Peter Kner
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| Open AccessCell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading
C. elegans miRNAs associate with AGO proteins ALG-1 and ALG-2. Here the authors provide a map of miRNAs loaded into ALG-1 and ALG-2 from intestine, body wall muscles and nervous system in C. elegans providing insights into spatial and temporal AGO loading flexibility.
- Christopher A. Brosnan
- , Alexander J. Palmer
- & Steven Zuryn
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| Open AccessThe decrease of intraflagellar transport impairs sensory perception and metabolism in ageing
Sensory perception and metabolic homeostasis are known to deteriorate with ageing, while mechanisms underlying their deterioration remain poorly understood. Here, the authors demonstrate that decrease of intraflagellar transport in the cilia of sensory neurons impairs sensory perception and metabolism in ageing C. elegans.
- Yincong Zhang
- , Xiaona Zhang
- & Yidong Shen
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| Open AccessUPRmt scales mitochondrial network expansion with protein synthesis via mitochondrial import in Caenorhabditis elegans
The mitochondrial network expands to accommodate cell growth, but how scaling occurs is unclear. Here, the authors show in C. elegans that ATFS-1 mitochondrial import is reduced when mitochondrial proteins are highly expressed, activating the unfolded protein response and causing expansion.
- Tomer Shpilka
- , YunGuang Du
- & Cole M. Haynes
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| Open AccessSub-nanowatt resolution direct calorimetry for probing real-time metabolic activity of individual C. elegans worms
Calorimetry is widely used for metabolic studies, but measurements of single cells and small organisms are limited by the sensitivity of current techniques. Here the authors develop a sensitive platform for performing time-resolved metabolic measurements of single C. elegans worms from larval to adult stages.
- Sunghoon Hur
- , Rohith Mittapally
- & Edgar Meyhofer
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| Open AccessSymmetry group factorization reveals the structure-function relation in the neural connectome of Caenorhabditis elegans
The 302-neuron connectome of the nematode C. elegans has been completely mapped, yet the design principles that explain how the connectome structure determines its function are unknown. Here, the authors show that physical principles of symmetry and mathematical tools of symmetry groups can be used to understand C. elegans neural locomotion circuits.
- Flaviano Morone
- & Hernán A. Makse
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| Open AccessThe marginal cells of the Caenorhabditis elegans pharynx scavenge cholesterol and other hydrophobic small molecules
The C. elegans nematode worm is a filter-feeder and requires dietary sources of cholesterol. Here, the authors show that the C. elegans pharynx works as a filter to scavenge hydrophobic small molecules from its surrounding liquid environment.
- Muntasir Kamal
- , Houtan Moshiri
- & Peter J. Roy
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| Open AccessKLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants
Cytochrome P450 oxidases (CYPs) are enzymes that participate in the xenobiotic detoxification and their expression is enhanced in long-lived model organisms. Here the authors show that KLF-1 promotes cyp expression and ensures lifespan extension in C. elegans mitomutants by activating mitohormesis.
- Marija Herholz
- , Estela Cepeda
- & Aleksandra Trifunovic
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| Open AccessThe longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity
Resistance to stress is often associated with increased longevity. Using the model organism C. elegans the authors here show that TCER-1 enhances lifespan while at the same time increasing sensitivity to a number of biotic and abiotic stressors.
- Francis R. G. Amrit
- , Nikki Naim
- & Arjumand Ghazi
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| Open AccessDietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain
Lipid droplets (LDs) are fat storage organelles that are initiated and expanded by seipins at ER contact sites. Here the authors show that the C. elegans seipin ortholog SEIP-1 is recruited to these sites by certain dietary fatty acids to support the expansion of a subset of LDs.
- Zhe Cao
- , Yan Hao
- & Ho Yi Mak
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| Open AccessEngulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1
It is unclear how removal of axon debris and initiation of axon regeneration following nerve injury is co-regulated. In this study, the authors show that the extracellular domain (ECD) of the engulfment receptor, CED-1, functions as an adhesion molecule to promote axonal regeneration after injury, independent of its function in phagocytosis
- Hui Chiu
- , Yan Zou
- & Chieh Chang
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| Open AccessVisible light reduces C. elegans longevity
The nematode C. elegans is known to alter its behavior in response to UV light. Here, the authors show that visible light triggers photo-oxidative stress and a wider stress response in C. elegans, suggesting that light exposure during routine laboratory handling may influence the outcome of lifespan experiments.
- C. Daniel De Magalhaes Filho
- , Brian Henriquez
- & Andrew Dillin
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| Open AccessSpatiotemporal regulation of Aurora B recruitment ensures release of cohesion during C. elegans oocyte meiosis
During meiosis, step-wise release of sister chromatid cohesion mediated by REC-8 cohesin is required for the formation of haploid gametes. Here, the authors show that in C. elegans oocytes, regulated recruitment of Aurora B kinase ensures the correct distribution of REC-8 phosphorylation, which promotes cohesion release.
- Nuria Ferrandiz
- , Consuelo Barroso
- & Enrique Martinez-Perez
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| Open AccessA conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age-associated vascular dysfunction
KLF family transcription factors (KLFs) regulate many cellular processes, including proliferation, survival and stress responses. Here, the authors position KLFs as important regulators of autophagy and lifespan in C. elegans, a role that may extend to the modulation of age-associated vascular phenotypes in mammals.
- Paishiun N. Hsieh
- , Guangjin Zhou
- & Mukesh K. Jain
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| Open AccessSmall nucleoli are a cellular hallmark of longevity
Animal lifespan is plastic and is regulated by conserved signalling pathways. Here, Tikuet al.show that longevity-enhancing mutations or interventions are associated with reduced nucleolar size in worms, flies, mice and humans, and that nucleolar size can predict life-expectancy in individual worms.
- Varnesh Tiku
- , Chirag Jain
- & Adam Antebi
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| Open AccessIncreased mitochondrial fusion allows the survival of older animals in diverse C. elegans longevity pathways
Mitochondria can undergo shape changes as a result of fusion and fission events. Here the authors describe how insulin signalling regulates mitochondrial fusion in C. elegans, and show that mitochondrial fusion is necessary, but not sufficient, for longevity of worms with mutations that increase lifespan.
- Snehal N. Chaudhari
- & Edward T. Kipreos
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Article
| Open AccessGlycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress
Glycogen is a storage form of glucose in cells. Here, Gusarovet al. show that glycogen-derived glucose can be used to quickly regenerate the antioxidant glutathione and that inhibiting glycogen synthesis extends C. eleganslifespan, whereas glycogen accumulation drives organismal ageing in worms.
- Ivan Gusarov
- , Bibhusita Pani
- & Evgeny Nudler
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| Open AccessTwo forms of death in ageing Caenorhabditis elegans
Despite its wide use in ageing research, the contribution of specific age-associated pathologies toC. elegansmortality is not well understood. Here the authors identify two types of death in worms, with either a swollen or a shrunken pharynx, that are differentially affected by age and mutations that extend worm lifespan.
- Yuan Zhao
- , Ann F. Gilliat
- & David Gems
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| Open AccessRNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans
The decline of DNA and protein quality control contributes to organismal ageing. Here, Sonet al. report that nonsense-mediated mRNA decay, a RNA quality control mechanism, is enhanced in long-lived daf-2 mutant worms and contributes to their longevity by regulating expression of the yars-2/tyrosyl tRNA synthetase.
- Heehwa G. Son
- , Mihwa Seo
- & Seung-Jae V. Lee
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| Open AccessImpact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects
Irreproducibility of biological findings is a major challenge for drug development. Here the authors examine the lifespans of 22 worm strains in three different laboratories and the effects of ten known chemicals to assess reproducibility in the face of variations in genetic background, chemical treatment and lab environment.
- Mark Lucanic
- , W. Todd Plummer
- & Patrick C. Phillips
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| Open AccessHormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans
Mild heat stress has beneficial effects on organismal health and survival. Here, Kumstaet al. show that a mild heat shock and HSF-1 overexpression induce autophagy in multiple tissues of C. elegansand autophagy-related genes are essential for both heat shock-induced and HSF-1–mediated stress resistance and longevity.
- Caroline Kumsta
- , Jessica T. Chang
- & Malene Hansen
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| Open AccessBacillus subtilis biofilm extends Caenorhabditis elegans longevity through downregulation of the insulin-like signalling pathway
Probiotic bacteria can improve host health, but the mechanisms underlying such beneficial effects are often unclear. Here, the authors show that biofilm formation of the probiotic bacteriumB. subtilis extends the lifespan of its host, the nematode C. elegans, by reducing insulin-like signalling.
- Verónica Donato
- , Facundo Rodríguez Ayala
- & Roberto Grau
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| Open AccessA tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism
Serotonin is a potent stimulator of fat loss and energy expenditure in several species, includingC. elegans. Here, Palamiuc et al. identify the neuropeptide, FP-7, and its receptor in the intestine, NRP-22 as mediators of serotonergic body fat loss in worms.
- Lavinia Palamiuc
- , Tallie Noble
- & Supriya Srinivasan
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| Open AccessLong-term time-lapse microscopy of C. elegans post-embryonic development
Long-term time-lapse imaging of motile developing organisms at the single cell level is challenging. Here the authors culture free-moving C. eleganslarvae in hydrogel chambers containing a food source, and use fast image acquisition to follow developmental processes.
- Nicola Gritti
- , Simone Kienle
- & Jeroen Sebastiaan van Zon
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| Open AccessThe hydrolethalus syndrome protein HYLS-1 regulates formation of the ciliary gate
Transition fibres (TFs) and the transition zone (TZ) are basal ciliary structures thought to act as a gate to regulate protein transport. Here the authors show that the C. elegansorthologue of hydrolethalus protein 1, HYLS-1, disrupts both structures and compromises the trafficking of cargo through the ciliary gate.
- Qing Wei
- , Yingyi Zhang
- & Jinghua Hu
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| Open AccessOptogenetic mutagenesis in Caenorhabditis elegans
Inducing random mutation of C. elegansDNA is a widely used technique to investigate gene and protein function. Here the authors introduce a method of optogenetic mutagenesis, driving the generation of reactive oxygen species, which avoids the use of toxic chemicals.
- Kentaro Noma
- & Yishi Jin
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| Open AccessA redox signalling globin is essential for reproduction in Caenorhabditis elegans
Globins are best known for their role in respiration, but recent studies suggest they might contribute to redox signalling as well. Here, the authors present biochemical, structural and in vivoevidence that the roundworm globin Glb-12 acts as a superoxide generator necessary for germline development.
- Sasha De Henau
- , Lesley Tilleman
- & Bart P. Braeckman
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| Open AccessC. elegans maximum velocity correlates with healthspan and is maintained in worms with an insulin receptor mutation
Increases in lifespan do not necessarily translate into prolonged healthspan. Here, the authors devise a simple metric, maximum velocity, to study ageing in C. elegansand, using this metric, show that reduced insulin signalling improves physical healthspan as well as worm lifespan.
- Jeong-Hoon Hahm
- , Sunhee Kim
- & Hong Gil Nam
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| Open AccessSonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans
Common optogenetic approaches require surgical procedures to deliver light of specific wavelengths to the target cells. Here the authors demonstrate the use of low-pressure ultrasound as a non-invasive trigger to activate specific neurons in Caenorhabditis elegansand find that the mechanotransduction channel TRP-4 sensitizes cells to the ultrasound stimulus.
- Stuart Ibsen
- , Ada Tong
- & Sreekanth H. Chalasani
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| Open AccessCaenorhabditis elegans is a useful model for anthelmintic discovery
Screening for new anthelmintic compounds that are active against parasitic nematodes is costly and labour intensive. Here, the authors use the non-parasitic nematode Caenorhabditis elegansto identify 30 anthelmintic lead compounds in an effective and cost-efficient manner.
- Andrew R. Burns
- , Genna M. Luciani
- & Peter J. Roy
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Neurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neurons
Abnormal accumulation of TDP-43 and FUS proteins is found in a neurodegenerative disease amyotrophic lateral sclerosis. Here the authors show by modelling the disease in worms that these proteins activate local and distal immune responses, and blocking this pathway in neurons ameliorates the disease.
- Julie Vérièpe
- , Lucresse Fossouo
- & J Alex Parker
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Article
| Open AccessLigand regulation of a constitutively dimeric EGF receptor
Whereas epidermal growth factor-induced dimerization is considered essential for EGFR signalling, the structurally related insulin receptor is a disulfide-linked dimer. Here the authors show that C. elegansEGFR is constitutively dimeric and undergoes subtle structural changes upon ligand binding that likely underlie allosteric activation.
- Daniel M. Freed
- , Diego Alvarado
- & Mark A. Lemmon
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| Open AccessNon-autonomous DAF-16/FOXO activity antagonizes age-related loss of C. elegans germline stem/progenitor cells
The number of germline stem/progenitor cells in C. elegansdeclines with age. Here the authors show this cell loss is mediated by the transcription factor DAF-16/FOXO acting in specific somatic gonad cells, demonstrating that stem cell aging can be anatomically uncoupled from organismal aging.
- Zhao Qin
- & E. Jane Albert Hubbard