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| Open AccessFaecal bile acids are natural ligands of the mouse accessory olfactory system
The accessory olfactory system (AOS) processes social chemosensory information and guides behaviors that are important for survival and reproduction in mammals. Here the authors report that mouse feces are a source of AOS neuronal activity and identify unconjugated bile acids in feces as a class of natural AOS ligands.
- Wayne I. Doyle
- , Jordan A. Dinser
- & Julian P. Meeks
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| Open AccessGut environment-induced intraepithelial autoreactive CD4+ T cells suppress central nervous system autoimmunity via LAG-3
Experimental autoimmune encephalomyelitis (EAE) involves inflammatory cell infiltration into the central nervous system (CNS) and models the human disease multiple sclerosis. Here the authors show that transferred CD4+ gut intraepithelial lymphocytes can migrate into the CNS and inhibit inflammation in recipient mice with EAE.
- Atsushi Kadowaki
- , Sachiko Miyake
- & Takashi Yamamura
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| Open AccessA single gene of a commensal microbe affects host susceptibility to enteric infection
The interactions between gut bacteria and enteric pathogens are poorly understood. Here, Yoon et al. show that subinhibitory antibiotic treatment in a mouse model leads to overgrowth of an E. coli strain carrying a catalase-encoding gene that enhances infection with the human pathogen Vibrio cholerae.
- Mi Young Yoon
- , Kyung Bae Min
- & Sang Sun Yoon
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Article
| Open AccessThe molecular basis of the genesis of basal tone in internal anal sphincter
The molecular basis of the basal tone generated by internal anal sphincters (IAS) is largely unknown. Here, the authors show that the tone arises from a global rise in intracellular Ca2+ in smooth muscle cells via a Ryanodine receptor-TMEM16A-L-type Ca2+channel-MLC kinase pathway, suggesting a potential therapy for IAS motility disorders.
- Cheng-Hai Zhang
- , Pei Wang
- & Min-Sheng Zhu
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Article
| Open AccessMicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression
Liver fibrosis is a pathogenic driver of many liver diseases, so understanding its regulation might open the door to new therapies. Here the authors perform a screen for miRNA candidates and identify that miR-378 inhibits liver fibrosis in mice by interfering with Hedgehog signalling in hepatic stellate cells.
- Jeongeun Hyun
- , Sihyung Wang
- & Youngmi Jung
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Article
| Open AccessMICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration
Mitochondrial calcium uptake is a highly regulated process, and calcium overload can lead to cell death. Here, using knockout mouse model, the authors show that the mitochondrial calcium uniporter (MCU) regulator MICU1 is needed to prevent calcium overload and promotes survival under liver regeneration and postnatal adaptation-associated stress.
- Anil Noronha Antony
- , Melanie Paillard
- & György Hajnóczky
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| Open AccessHepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling
TRAF family proteins regulate immune signalling cascades. Here, the authors show that TRAF3 is upregulated in the liver in non-alcoholic fatty liver disease, promoting insulin resistance, inflammation and hepatic steatosis via its interaction with the kinase TAK1.
- Pi-Xiao Wang
- , Xiao-Jing Zhang
- & Hongliang Li
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Article
| Open AccessBone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells
Tissue-resident macrophages are mostly derived from embryonic progenitors. Scott et al. develop a mouse model to specifically deplete Kupffer cells (KC) in vivoand show that monocyte-derived cells can repopulate KC niche and behave similar to their embryonically-derived counterparts.
- Charlotte L. Scott
- , Fang Zheng
- & Martin Guilliams
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Article
| Open AccessGenetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
There has been limited success in generating tissues from human induced pluripotent stem cells (hiPSCs). Here, the authors genetically engineer expression of the transcription factor Gata6 in a single isogenic hiPSC population resulting in complex tissue structures that exhibit liver bud-like properties.
- Patrick Guye
- , Mohammad R. Ebrahimkhani
- & Ron Weiss
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Article
| Open AccessESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation
Alternative RNA splicing is important during organismal development. Here, the authors perform RNA-Seq on mouse and human liver samples to provide a comprehensive view of splicing events during liver development and growth, and identify Espr2 as a main regulator of these splicing processes.
- Amruta Bhate
- , Darren J. Parker
- & Auinash Kalsotra
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Article
| Open AccessAntibiotics in neonatal life increase murine susceptibility to experimental psoriasis
Commensal microbes are necessary for proper development of the immune system. Here Zanvit et al. show that neonatal antibiotics treatment causes long-term changes in the gut and skin microbiomes, and exacerbates immune-mediated skin pathology at adult age in mouse experimental models of psoriasis.
- Peter Zanvit
- , Joanne E. Konkel
- & WanJun Chen
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Article
| Open AccessThe outer mucus layer hosts a distinct intestinal microbial niche
The inner layer of the mucus that covers our intestine is nearly sterile. Here, the authors show in mice that the outer mucus layer constitutes a unique microbial niche hosting bacterial communities with distinct proliferation rates and resource utilization activities.
- Hai Li
- , Julien P. Limenitakis
- & Andrew J. Macpherson
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Article
| Open AccessBile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery
Gastric bypass surgery is one of the most effective interventions to achieve durable weight loss. Here, Flynnet al. show that, in mice, bile diversion to the small intestine results in beneficial and sustained metabolic improvements similar to Roux-en-Y gastric bypass surgery.
- Charles Robb Flynn
- , Vance L. Albaugh
- & Naji N. Abumrad
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| Open AccessMetabolic and metagenomic outcomes from early-life pulsed antibiotic treatment
The potential recovery of the human gut microbiota after an antibiotic treatment, and its effects on our health, are poorly understood. Here, the authors use a mouse model mimicking paediatric antibiotic use to shed new light into these processes.
- Yael R. Nobel
- , Laura M. Cox
- & Martin J. Blaser
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| Open AccessGlycan complexity dictates microbial resource allocation in the large intestine
The human gut microbiota helps us to degrade complex dietary carbohydrates such as xylan and, in turn, the carbohydrate breakdown products control the structure of the microbiota. Here the authors characterize the xylan-degrading apparatus of a key member of the gut microbiota, Bacteroides ovatus.
- Artur Rogowski
- , Jonathon A. Briggs
- & David N. Bolam
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| Open AccessCircadian control of bile acid synthesis by a KLF15-Fgf15 axis
Bile acids are important for the absorption of nutrients. Here the authors provide a molecular explanation for the oscillatory release of bile acids, showing that diurnal expression of the transcription factor KLF15 regulates FGF15 secretion from enterocytes, which then inhibits bile acid synthesis in the liver.
- Shuxin Han
- , Rongli Zhang
- & Mukesh K. Jain
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Article |
Dietary methionine can sustain cytosolic redox homeostasis in the mouse liver
NADPH acts as a reducing currency in mammalian cells and is thought to be required to maintain redox homeostasis. Here the authors discover an alternative NADPH-independent pathway, based on the conversion of methionine into cysteine, which is capable of sustaining redox homeostasis in the mouse liver.
- Sofi Eriksson
- , Justin R. Prigge
- & Edward E. Schmidt
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| Open AccessTransformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2
The adult gastro-intestinal tract harbours stem cells that differ in their differentiation programme and in the gene repertoire that they express. Here the authors show that single adult Lgr5-positive stem cells require Cdx2 to maintain their intestinal identity and are converted into pyloric stem cells in the absence of this transcription factor.
- Salvatore Simmini
- , Monika Bialecka
- & Jacqueline Deschamps
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| Open AccessIntestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status
Gut microbes are known to influence whole-body metabolism. Here Everard et al.show the adaptor protein MyD88 in intestinal epithelial cells is sensitive to changes in the diet and affects composition of the gut microbiota, which influences the development of obesity and associated diseases.
- Amandine Everard
- , Lucie Geurts
- & Patrice D. Cani
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Prediction and quantification of bioactive microbiota metabolites in the mouse gut
Metabolites produced by the gut microbiota can potentially affect our physiology. Here, the authors present a metabolomics strategy that models microbiota metabolism as a reaction network and uses pathway analysis to facilitate identification and characterization of microbial metabolites.
- Gautham V. Sridharan
- , Kyungoh Choi
- & Arul Jayaraman
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Integrated control of hepatic lipogenesis versus glucose production requires FoxO transcription factors
The transcription factors FoxoO1 and Srebp-1 control hepatic glucose and lipid production, respectively. Here, Haeusler et al.propose a model that integrates glucose and lipid regulation in the normal and diabetic liver under the unifying control of FoxO transcription factors.
- Rebecca A. Haeusler
- , Kirsten Hartil
- & Domenico Accili