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| Open AccessASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail
Serine/threonine phosphatases such as PP1 associate with a large array of subunit proteins, such as ASPP (apoptosis-stimulating protein of p53) to achieve selective targeting. Here authors solved the crystal structure of the human ASPP2/PP1 complex and explain how ASPP2 can distinguish between PP1 isoforms.
- M. Teresa Bertran
- , Stéphane Mouilleron
- & Nicolas Tapon
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Article
| Open Accesstmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.
- Aaron M. Savage
- , Sathishkumar Kurusamy
- & Robert N. Wilkinson
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Article
| Open AccessBMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis
BMP ligands act as retrograde signalling molecules to regulate presynaptic development, and regulation of BMP receptors by endocytosis may be an important component of this signalling pathway. Here, the authors show that Abi-mediated macropinocytosis of BMP receptors in Drosophila larva and contributes to neuromuscular development.
- Najin Kim
- , Sungdae Kim
- & Seungbok Lee
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Article
| Open AccessDifferentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche
Human embryonic stem cells can be differentiated in vitro into primordial germ cell-like cells (PGCLCs) that resemble early primordial germ cells (PGCs). Here the authors transplant PGCLCs generated from rhesus macaque iPSCs into mouse and rhesus macaque seminiferous tubules, which matures these into late PGCs and spermatogonia-like cells.
- Enrique Sosa
- , Di Chen
- & Amander T. Clark
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Article
| Open AccessQuantifying post-transcriptional regulation in the development of Drosophila melanogaster
Proteome and transcriptome often show poor correlation, hindering the system-wide analysis of post-transcriptional regulation. Here, the authors study proteome and transcriptome dynamics during Drosophila embryogenesis and present basic mathematical models describing the temporal regulation of most protein-RNA pairs.
- Kolja Becker
- , Alina Bluhm
- & Stefan Legewie
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| Open AccessHeart enhancers with deeply conserved regulatory activity are established early in zebrafish development
During early embryogenesis, critical cardiac specification events occur. Here the authors isolate cardiac progenitor cells from early zebrafish embryos and characterize accessible chromatin regions specific to this cell population, finding that many of these regions overlap with conserved non-coding elements that are ortholgous to accessible chromatin regions in human.
- Xuefei Yuan
- , Mengyi Song
- & Michael D. Wilson
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Article
| Open AccessWnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling
Wnt signaling is known to regulate the formation of the blood-brain barrier. Here Hübner et al. dissect the underlying mechanisms using high resolution live imaging in zebrafish, and find that Wnt regulates anastomosis of angiogenic sprouts in the brain by counteracting sphingosine-1-phosphate receptor signaling.
- Kathleen Hübner
- , Pauline Cabochette
- & Wiebke Herzog
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Article
| 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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Article
| Open AccessSystems glycomics of adult zebrafish identifies organ-specific sialylation and glycosylation patterns
Zebrafish is a popular system for studying the molecular basis of glycan-related human diseases. Here, the authors present glycomic profiles of eight zebrafish organs and establish the organ-specific expression patterns of related biosynthetic enzymes.
- Nao Yamakawa
- , Jorick Vanbeselaere
- & Yann Guerardel
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Article
| Open AccessDifferential lateral and basal tension drive folding of Drosophila wing discs through two distinct mechanisms
Epithelial folding has mainly been linked to forces acting in the apical actomyosin network of cells. Here, the authors show using live imaging that two distinct mechanisms, changes in basal surface tension and changes in lateral surface tension, drive the formation of two folds in the Drosophila wing disc.
- Liyuan Sui
- , Silvanus Alt
- & Christian Dahmann
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Article
| Open AccessEngineered bidirectional promoters enable rapid multi-gene co-expression optimization
Classic monodirectional promoters are of limited use for multiple gene co-expression. Here the authors generate a library of 168 bidirectional promoters for the yeast K. phaffii (syn. P. pastoris) with diverse expression profiles to optimize metabolic pathway design.
- Thomas Vogl
- , Thomas Kickenweiz
- & Anton Glieder
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Article
| Open AccessIridophores as a source of robustness in zebrafish stripes and variability in Danio patterns
Iridophores interact with other cells to give zebrafish their stripes, but what drives their form shifts is unknown. Here, modelling allows the authors to identify robust cues that may specify iridophore form and to find changes to these cues that likely account for altered patterns on related fish.
- Alexandria Volkening
- & Björn Sandstede
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Article
| Open AccessLipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply
Lipoprotein lipase (LPL) hydrolyzes triglycerides to supply free fatty acids (FFAs) to muscle for energy and adipocytes for storage. Here, the authors demonstrate that Lpl and its product, the FFA docosahexaenoic acid (DHA) are required for haematopoietic stem progenitor cell expansion during zebrafish embryogenesis.
- Chao Liu
- , Tianxu Han
- & Yury I. Miller
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Article
| Open AccessFunctional architecture of reward learning in mushroom body extrinsic neurons of larval Drosophila
The mushroom body of Drosophila integrates sensory information with past experience to guide behaviour. Here, the authors provide an atlas of the input and output neurons of the stage 3 larval mushroom body at the single-cell level, and analyse their function in learned and innate behaviours.
- Timo Saumweber
- , Astrid Rohwedder
- & Bertram Gerber
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| Open AccessEarly-life exposure to low-dose oxidants can increase longevity via microbiome remodelling in Drosophila
Low doses of harmful chemicals such as oxidants can have beneficial effects, in some cases mediated by increased expression of stress response genes. In this study, the authors show that low-dose oxidants increase the longevity of Drosophila via a different mechanism, remodelling of the microbiome.
- Fumiaki Obata
- , Clara O. Fons
- & Alex P. Gould
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Article
| 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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Article
| Open AccessZebrafish and medaka offer insights into the neurobehavioral correlates of vertebrate magnetoreception
Advances in animal magnetoreception have been limited by a lack of tractable vertebrate laboratory models. Here, the authors demonstrate light-independent magnetoreception in mature zebrafish and medaka, as well as magnetosensitive locomotion in juvenile medaka associated with neuronal activation in the lateral hindbrain.
- Ahne Myklatun
- , Antonella Lauri
- & Gil G. Westmeyer
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| Open AccessTbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration
It is not clear if it is the embryonic origin or anatomical location of cardiomyocytes that restrict their contribution to zebrafish heart regeneration. Here, the authors show a plasticity of embryonic precursors following tbx5a fate mapping and that trabecular cardiomyocytes help to rebuild the cortical myocardium.
- Héctor Sánchez-Iranzo
- , María Galardi-Castilla
- & Nadia Mercader
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| Open AccessGeneric wound signals initiate regeneration in missing-tissue contexts
Some wounds trigger regeneration, while others simply heal but how this is regulated is unclear. Here, by manipulating ERK and Wnt signalling pathways, the authors create headless planarians and finless zebrafish and show that wounds that normally only trigger wound healing can activate regeneration of heads and bones.
- Suthira Owlarn
- , Felix Klenner
- & Kerstin Bartscherer
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Article
| Open AccessSmall molecule screen in embryonic zebrafish using modular variations to target segmentation
Chemical screens can identify small molecules that affect biological development, with potential therapeutic value. Here, the authors use a modular approach in a screen in zebrafish embryos, varying concentration, genotype and timing to target segmentation disorders, birth defects that affect the spinal column.
- Sandra Richter
- , Ulrike Schulze
- & Andrew C. Oates
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Article
| Open AccessPlasma cell survival in the absence of B cell memory
The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.
- Erika Hammarlund
- , Archana Thomas
- & Mark K. Slifka
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Article
| Open AccessA multiplexable TALE-based binary expression system for in vivo cellular interaction studies
Binary expression systems enable researchers to deliver loss-of-function or gain-of-function transgenes with spatial-temporal resolution in vivo. Here, the authors present a programmable TALE-based system for multiplexed orthogonal activation of transgenes in Drosophila.
- Markus Toegel
- , Ghows Azzam
- & Tudor A. Fulga
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| Open AccessSpatial regulation of contractility by Neuralized and Bearded during furrow invagination in Drosophila
In the Drosophila embryo, increased cortical contractility in ventral cells causes furrow formation and gastrulation. Here, the authors show that contractility is regulated by Neuralized (an E3 ubiquitin ligase) in ventral cells, and that inhibiting this process with Bearded in the ectoderm causes furrow invagination.
- Gantas Perez-Mockus
- , Khalil Mazouni
- & François Schweisguth
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Article
| Open AccessDevelopmental diet regulates Drosophila lifespan via lipid autotoxins
The diet consumed during development can have long-lasting effects on adult physiology. Here, the authors show that developmental undernutrition in Drosophila extends lifespan by inhibiting the production of toxic lipids, called autotoxins, on the adult body surface.
- M. Irina Stefana
- , Paul C. Driscoll
- & Alex P. Gould
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Article
| Open AccessQuantitative microscopy of the Drosophila ovary shows multiple niche signals specify progenitor cell fate
In the Drosophila ovary, it is unclear how signalling from the stem cell niche regulates follicle precursor cell fate/differentiation. Here, the authors use quantitative microscopy to define the role of Wnt, Hedgehog and Notch signalling in progenitor cells, showing regulation of cell fate and differentiation.
- Wei Dai
- , Amy Peterson
- & Denise J. Montell
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Article
| 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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Article
| Open AccessDifferent developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth
Βeta-cells have recently been shown to be heterogeneous with regard to morphology and function. Here, the authors show that β-cells in zebrafish switch from proliferative to functional states with increasing time since β-cell birth, leading to functional and proliferative heterogeneity.
- Sumeet Pal Singh
- , Sharan Janjuha
- & Nikolay Ninov
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| Open AccessApplication of bio-orthogonal proteome labeling to cell transplantation and heterochronic parabiosis
Clarifying the source of proteins in mixed biological environments, such as after transplantation or parabiosis, remains a challenge. Here, the authors address this need with a mouse strain that incorporates a methionine derivate into proteins, allowing for their detection using click chemistry and antibody arrays.
- Yan Liu
- , Michael J. Conboy
- & Irina M. Conboy
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Article
| Open Accessinterleukin-11 induces and maintains progenitors of different cell lineages during Xenopus tadpole tail regeneration
Xenopus laevis tadpoles have maintained their ability to regenerate various organs. Here, the authors show that interleukin-11 is necessary for organ regeneration, by inducing and maintaining undifferentiated progenitors across cell lineages during Xenopus tail regeneration.
- Hiroshi Tsujioka
- , Takekazu Kunieda
- & Takeo Kubo
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Article
| Open AccessThe Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan
The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.
- Nitish Mittal
- , Joao C. Guimaraes
- & Mihaela Zavolan
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Article
| Open AccessPromoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster
Mitochondrial fission and fusion are important mechanisms to maintain mitochondrial function. Here, the authors report that middle-aged flies have more elongated, or ‘hyper-fused’ mitochondria, and show that induction of mitochondrial fission in midlife, but not in early life, extends the health and life of flies.
- Anil Rana
- , Matheus P. Oliveira
- & David W. Walker
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Article
| Open AccessCre/lox-assisted non-invasive in vivo tracking of specific cell populations by positron emission tomography
Non-invasive cell tracking is a powerful method to visualize cells in vivo under physiological and pathophysiological conditions. Here Thunemann et al. generate a mouse model for in vivo tracking and quantification of specific cell types by combining a PET reporter gene with Cre-dependent activation that can be exploited for any cell population for which a Cre mouse line is available.
- Martin Thunemann
- , Barbara F. Schörg
- & Robert Feil
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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 AccessRegulation of Drosophila hematopoietic sites by Activin-β from active sensory neurons
Hematopoietic sites in theDrosophilalarva require the local peripheral nervous system for blood cells (hemocytes) to survive and proliferate, but how this is mediated is unclear. Here, the authors identify Activin-β from sensory neurons as signalling to hemocytes, affecting proliferation and adhesion.
- Kalpana Makhijani
- , Brandy Alexander
- & Katja Brückner
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Article
| Open AccessProgrammable base editing of zebrafish genome using a modified CRISPR-Cas9 system
The use of base editing enables precise genetic modifications in model animals. Here the authors show high efficient single-base editing in zebrafish using modified Cas9 and its VQR variant with an altered PAM specificity.
- Yihan Zhang
- , Wei Qin
- & Shuo Lin
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Article
| Open AccessPrevalence of sexual dimorphism in mammalian phenotypic traits
Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.
- Natasha A. Karp
- , Jeremy Mason
- & Jacqueline K. White
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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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Article
| Open AccessSara phosphorylation state controls the dispatch of endosomes from the central spindle during asymmetric division
Asymmetric segregation of cell fate determinants during cell division governs daughter cell fate. Here the authors show that Sara endosomes, known to regulate Notch signalling, are targeted to the mitotic spindle and once phosphorylated are asymmetrically dispatched into a daughter cell to determine cell fate.
- Sylvain Loubéry
- , Alicia Daeden
- & Marcos Gonzalez-Gaitan
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Article
| Open AccessCentral and peripheral clocks are coupled by a neuropeptide pathway in Drosophila
The emergence of the adult fruit flies from the pupae is jointly regulated by the central and peripheral clocks. Selchoet al. show that synchronization of the two clocks is mediated by the master clock brain neurons producing sNPF, and non-clock PTTH neurons that regulate the peripheral clock producing the steroid moulting hormone, ecdysone.
- Mareike Selcho
- , Carola Millán
- & John Ewer
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Article
| 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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Article
| 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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Article
| Open AccessATF3 acts as a rheostat to control JNK signalling during intestinal regeneration
Stress response JNK signalling is important for cell death-induced regeneration. Here the authors show in adultDrosophilaenterocytes that ATF3 regulates the expression of Raw, a JNK antagonist, to control intestinal regeneration and barrier function in response to infection.
- Jun Zhou
- , Bruce A. Edgar
- & Michael Boutros
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Article
| 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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Article
| 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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Article
| 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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Article
| 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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Article
| Open AccessCaloric restriction improves health and survival of rhesus monkeys
Caloric restriction (CR) delays ageing of model organisms, but whether it works in nonhuman primates has been controversial. Here, the authors pool and reanalyse data from two long-running CR primate studies, concluding that moderate CR indeed improves health and survival of rhesus monkeys.
- Julie A. Mattison
- , Ricki J. Colman
- & Rozalyn M. Anderson