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На сайте издательства Nature в свободном доступе статьи Нобелевских лауреатов по медицине 2019 г.

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25 октября 2019

Nobel Prize in Physiology or Medicine 2019

This collection of research, review and comment from Nature Research celebrates the 2019 Nobel Prize in Physiology or Medicine awarded to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza “for their discoveries of how cells sense and adapt to oxygen availability”. The ability of organisms to respond to changes in oxygen availability is of fundamental importance to life on earth. Work by the prize-winning scientists has shown that in animal cells, oxygen availability affects gene expression through oxygen-sensitive post-translational modification and the subsequent proteasomal degradation of Hypoxia Inducible Factors. This research laid the foundation for understanding the mechanistic basis for the cellular response to hypoxia and paved the way for the therapeutic targeting of the response pathway to treat conditions including cancer and anaemia.

All research papers under ‘From the winners’ are free to access until April 2020.

From the winners

The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis

  • Patrick H. Maxwell,
  • Michael S. Wiesener ⋯
  • Peter J. Ratcliffe

LETTER20 MAY 1999Nature

On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models

The small-molecule HIF-2α antagonist PT2399 causes tumour regression in animal models of clear cell renal cell carcinoma, but cell lines of this tumour type show unexpectedly variable responses to PT2399.

  • Hyejin Cho,
  • Xinlin Du ⋯
  • William G. Kaelin

LETTER5 SEP 2016Nature

Hypoxia and the extracellular matrix: drivers of tumour metastasis

Emerging data indicate that hypoxia and the extracellular matrix (ECM) together might have a crucial role in metastasis. In this Opinion article the authors suggest a model in which multiple microenvironmental signals might converge to synergistically influence metastatic outcome.

  • Daniele M. Gilkes,
  • Gregg L. Semenza &
  • Denis Wirtz

OPINION15 MAY 2014Nature Reviews Cancer

Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL

  • Wai-Ching Hon,
  • Michael I. Wilson ⋯
  • E. Yvonne Jones

LETTER5 JUN 2002Nature

Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases

The response to hypoxia involves multiple genes regulated by the hypoxia inducible transcription factors (HIFs), whose stability is regulated by prolyl hydroxylation. Here the authors provide a molecular basis for the substrate selectivity of the HIF prolyl…

  • Rasheduzzaman Chowdhury,
  • Ivanhoe K. H. Leung ⋯
  • Christopher J. Schofield

ARTICLEOPEN ACCESS26 AUG 2016Nature Communications


The structure of the CH1 domain of p300 in complex with the transactivation domain of CITED2 brings us one step closer toward understanding the molecular basis of the regulation of hypoxia response.

  • Shoumo Bhattacharya &
  • Peter J Ratcliffe

NEWS & VIEWS1 JUL 2003Nature Structural & Molecular Biology

Mechanisms of hypoxia signalling: new implications for nephrology

Therapeutic modulation of hypoxia-inducible factors, which transduce adaptive transcriptional responses to hypoxia, is an emerging theme in kidney disease. This Review summarizes the hypoxia signalling mechanisms underpinning these novel treatments and…

  • Johannes Schödel &
  • Peter J. Ratcliffe

REVIEW ARTICLE5 SEP 2019Nature Reviews Nephrology

Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans

The identification of Escherichia coli ycfD and human MINA53 and NO66 as ribosomal amino acid hydroxylases defines a role for 2-oxoglutarate/iron-dependent oxygenases in translational regulation.

  • Wei Ge,
  • Alexander Wolf ⋯
  • Christopher J Schofield

BRIEF COMMUNICATION28 OCT 2012Nature Chemical Biology

Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel–Lindau protein

  • Michael Ohh,
  • Cheol Won Park ⋯
  • William G. Kaelin

ARTICLE9 JUN 2000Nature Cell Biology

VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400

  • Arthur P. Young,
  • Susanne Schlisio ⋯
  • William G. Kaelin Jr

LETTER24 FEB 2008Nature Cell Biology

Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression

Johannes Schödel and colleagues report the identification of a distant transcriptional enhancer of CCND1 at the recently identified renal cell carcinoma susceptibility locus at 11q13.3. The protective haplotype shows reduced binding of HIF-2α, reduced…

  • Johannes Schödel,
  • Chiara Bardella ⋯
  • David R Mole

LETTER11 MAR 2012Nature Genetics

Genetic variation at the 8q24.21 renal cancer susceptibility locus affects HIF binding to a MYC enhancer

Genome-wide association studies have identified multiple loci associated with the risk of developing renal cancer. Here, the authors show that one of these loci generates open chromatin, which enhances the binding of HIF and HIF-mediated transactivation ofMYC.

  • Steffen Grampp,
  • James L. Platt ⋯
  • Johannes Schödel

ARTICLEOPEN ACCESS24 OCT 2016Nature Communications

A genetic mechanism for Tibetan high-altitude adaptation

Josef Prchal and colleagues identify a mutation in EGLN1 associated with adaptation to high altitude in Tibetan individuals. Their functional studies suggest a mechanism acting to reduce the erythropoietic response to hypoxia.

  • Felipe R Lorenzo,
  • Chad Huff ⋯
  • Josef T Prchal

ARTICLE17 AUG 2014Nature Genetics

New insights into an enigmatic tumour suppressor

Dynamic regulation of the microtubule apparatus is central to cell division, cell migration, polarity and transport. New data demonstrating functional association of the von Hippel-Lindau (VHL) tumour suppressor with microtubules provide a new lead in unravelling VHL tumour suppressor mechanisms.

  • Peter J. Ratcliffe

NEWS & VIEWS1 JAN 2003Nature Cell Biology

Common pitfalls in preclinical cancer target validation

This Perspective discusses some of the causes of the robustness and reproducibility problem in preclinical cancer research and suggests solutions.

  • William G. Kaelin Jr

OPINION19 MAY 2017Nature Reviews Cancer

Targeting HIF-1 for cancer therapy

  • Gregg L. Semenza

REVIEW ARTICLE1 DEC 2003Nature Reviews Cancer

The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity

Oxygen levels regulate the stability of the transcription factor HIF-1 through the action of prolyl hydroxylases and the VHL ubiquitin ligase. Sharp and colleagues now identify a protein complex in which the Ajuba LIM-domain protein LIMD1 brings together prolyl…

  • Daniel E. Foxler,
  • Katherine S. Bridge ⋯
  • Tyson V. Sharp

LETTER29 JAN 2012Nature Cell Biology

The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases

Structural, biochemical and cellular studies reveal JMJD7 to be a Jumonji-C oxygenase that catalyzes (3S)-lysyl hydroxylation of the translation factor family of GTPases, DRG1 and DRG2.

  • Suzana Markolovic,
  • Qinqin Zhuang ⋯
  • Christopher J. Schofield

ARTICLE18 JUN 2018Nature Chemical Biology

Suppression of tumor growth through disruption of hypoxia-inducible transcription

  • Andrew L. Kung,
  • Stream Wang ⋯
  • David M. Livingston

ARTICLE1 DEC 2000Nature Medicine

Oxygen sensing by HIF hydroxylases

  • Christopher J. Schofield &
  • Peter J. Ratcliffe

REVIEW ARTICLE1 MAY 2004Nature Reviews Molecular Cell Biology

Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation

Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 have been identified in gliomas, the most common form of brain tumour, and in other cancers including leukaemias. The mutated enzymes produce 2-hydroxyglutarate (2HG), which is a potential…

  • Peppi Koivunen,
  • Sungwoo Lee ⋯
  • William G. Kaelin Jr

LETTER15 FEB 2012Nature

Clues from cell metabolism

Interest in the abnormal metabolism exhibited by cancer cells has been reawakened by the discovery of oncogenic mutations in metabolic enzymes, and by tools that monitor metabolism in living cells. Existing and emerging therapies aim to target this abnormal metabolism in various ways.

  • William G. Kaelin Jr &
  • Craig B. Thompson


Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution

Papillary renal cell carcinoma (pRCC) is a subtype of kidney cancer characterized by highly variable clinical behaviour. Here the authors sequence either the genomes or exomes of 31 pRCCs and identify several genes in sub-clones and large copy number variants in…

  • Michal Kovac,
  • Carolina Navas ⋯
  • Ian Tomlinson

ARTICLEOPEN ACCESS19 MAR 2015Nature Communications

A RASSF1A-HIF1α loop drives Warburg effect in cancer and pulmonary hypertension

Pulmonary hypertension is characterized by a metabolic switch similar to the Warburg effect in cancer. Here Dabral et al. describe a RASSF1a-HIF-1α feedforward loop driving the Warburg effect both in a mouse model of hypoxia-induced pulmonary hypertension and a subset of human cancer cells.

  • Swati Dabral,
  • Christian Muecke ⋯
  • Soni S. Pullamsetti

ARTICLEOPEN ACCESS13 MAY 2019Nature Communications

Publish houses of brick, not mansions of straw

Papers need to include fewer claims and more proof to make the scientific literature more reliable, warns William G. Kaelin Jr.

Sam Ogden

  • William G. Kaelin Jr

WORLD VIEW25 MAY 2017Nature

Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit

  • Ulrich K. Binné,
  • Marie K. Classon ⋯
  • Nicholas J. Dyson

LETTER24 DEC 2006Nature Cell Biology


Structural basis for negative regulation of hypoxia-inducible factor-1α by CITED2

  • Steven J Freedman,
  • Zhen-Yu J Sun ⋯
  • Michael J Eck

ARTICLE1 JUN 2003Nature Structural & Molecular Biology

Hypoxia-specific ultrasensitive detection of tumours and cancer cells in vivo

As hypoxia is a hallmark of tumour microenvironment, hypoxia-sensing probes are used for tumour imaging. Here, the authors report a hypoxia probe with increased sensitivity, water solubility and functional pH range, allowing in vivodetection of early metastases as small as a few thousand cells.

  • Xianchuang Zheng,
  • Xin Wang ⋯
  • Xiqun Jiang

ARTICLE5 JAN 2015Nature Communications

Human 3D cellular model of hypoxic brain injury of prematurity

Brain organoids derived from human iPSCs are used to study the effects of hypoxia on early cortical neurodevelopment and identify defects in specific human progenitor populations that likely contribute to encephalopathy of prematurity.

  • Anca M. Pașca,
  • Jin-Young Park ⋯
  • Sergiu P. Pașca

LETTER6 MAY 2019Nature Medicine

Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy

The conventional view holds that hypoxia confers drug resistance. In contrast, here the authors use a multilayer ‘omics data approach to characterize the molecular features associated with tumour hypoxia and identify molecular alterations that correlate with…

  • Youqiong Ye,
  • Qingsong Hu ⋯
  • Leng Han

ARTICLE18 MAR 2019Nature Metabolism

miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS

Wu et al. find that tumour hypoxic conditions increase miR25/93 levels, which via targeting Ncoa3 downregulate the expression of the innate immune regulator cGAS, thus allowing escape of the anti-tumour immune response.

  • Min-Zu Wu,
  • Wei-Chung Cheng ⋯
  • Juan Carlos Izpisua Belmonte

ARTICLE18 SEP 2017Nature Cell Biology

Plant cysteine oxidases control the oxygen-dependent branch of the N-end-rule pathway

Oxygen sensing in plants is mediated by the N-end rule pathway, in which the N-terminal cysteine residue of ERF-VII transcription factors is selectively oxidised. Weits et al.identify cysteine oxidases responsible for this modification, and show that their expression is itself regulated by ERF-VII.

  • Daan A. Weits,
  • Beatrice Giuntoli ⋯
  • Francesco Licausi

ARTICLEOPEN ACCESS6 MAR 2014Nature Communications

A three-dimensional engineered heterogeneous tumor model for assessing cellular environment and response

This protocol describes TRACER, a 3D cell culture system that enables the assembly of heterogeneous model tumors or tissues that easily disassemble for rapid analysis of different cell populations from particular microenvironments.

  • Darren Rodenhizer,
  • Teresa Dean ⋯
  • Alison P. McGuigan

PROTOCOL6 SEP 2018Nature Protocols

Refined control of cell stemness allowed animal evolution in the oxic realm

The earliest animal diversification has been associated with increased oxygenation. Here an alternative model is proposed: hypoxia-inducible transcription factors gave animals unprecedented control of cell stemness that allowed them to cope with fluctuating oxygen concentrations.

  • Emma U. Hammarlund,
  • Kristoffer von Stedingk &
  • Sven Påhlman

PERSPECTIVE18 JAN 2018Nature Ecology & Evolution

Bidirectional modulation of HIF-2 activity through chemical ligands

Structural analysis of HIF-2α in complex with agonists and antagonists reveal that chemical ligands regulate the activity of HIF-2α by affecting the stability of the HIF-2α–ARNT heterodimer via redirecting residues in the PAS-B pocket.

  • Dalei Wu,
  • Xiaoyu Su ⋯
  • Fraydoon Rastinejad

ARTICLE25 FEB 2019Nature Chemical Biology

Allosteric inhibition of hypoxia inducible factor-2 with small molecules

A new small-molecule inhibitor that selectively binds an internal cavity in HIF-2α allosterically disrupts HIF-2α–ARNT interaction in vitro and in cells. This compound should allow scientists to interrogate HIF-2α's activity in hypoxia and cancer cells.

  • Thomas H Scheuermann,
  • Qiming Li ⋯
  • Richard K Bruick

ARTICLE24 FEB 2013Nature Chemical Biology

Osteocytic oxygen sensing controls bone mass through epigenetic regulation of sclerostin

Osteocytes reside in a low oxygen environment, but it is not clear if oxygen sensing regulates their function. Here, the authors show that deletion of the oxygen sensor prolyl hydroxylase 2 in osteocytes leads to increased bone mass via regulation of sclerostin,…

  • Steve Stegen,
  • Ingrid Stockmans ⋯
  • Geert Carmeliet

ARTICLEOPEN ACCESS2 JUL 2018Nature Communications

TRPA1 underlies a sensing mechanism for O2

The redox-sensitive TRP channel TRPA1 is activated in hyperoxic and hypoxic conditions directly through modification of cysteine residues by O2 and indirectly through prolyl hydroxylation by PHDs, enzymes related to the hypoxia-inducible factor HIF-1, thus…

  • Nobuaki Takahashi,
  • Tomoyuki Kuwaki ⋯
  • Yasuo Mori

ARTICLE28 AUG 2011Nature Chemical Biology

Mitochondrial protein E2F3d, a distinctive E2F3 product, mediates hypoxia-induced mitophagy in cancer cells

Keigo Araki and colleagues show that E2F3d, a previously unidentified isoform of transcription factor E2F3, mediates hypoxia-induced mitophagy in cancer cells. This study discovers another mitophagy receptor that regulates mitochondrial quality control.

  • Keigo Araki,
  • Keiko Kawauchi ⋯
  • Kiyoshi Ohtani

ARTICLEOPEN ACCESS3 JAN 2019Communications Biology

Activation of intestinal hypoxia-inducible factor 2α during obesity contributes to hepatic steatosis

Obesity induces hypoxia and upregulation of HIF-2α in the gastrointestinal tract, resulting in excess ceramide production and exacerbation of NAFLD.

  • Cen Xie,
  • Tomoki Yagai ⋯
  • Frank J Gonzalez

ARTICLE9 OCT 2017Nature Medicine

Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210

Hypoxia stabilizes the transcription factor HIF-1α, which promotes TH17 polarization. Weiss and colleagues show that miR-210 mediates a negative feedback regulatory loop that diminishes HIF-1α abundance under hypoxic conditions.

  • Haopeng Wang,
  • Henrik Flach ⋯
  • Arthur Weiss

ARTICLE9 MAR 2014Nature Immunology

TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia in Drosophila

The hypoxia response pathway couples oxygen availability to physiological adaptations. Using the model system Drosophila melanogaster, here the authors show that hypoxia inhibits TORC1 signalling and increases lipid levels in the larval fat body and that these…

  • Byoungchun Lee,
  • Elizabeth C. Barretto &
  • Savraj S. Grewal

ARTICLEOPEN ACCESS23 APR 2019Nature Communications

Hypoxia-inducible factor–dependent induction of netrin-1 dampens inflammation caused by hypoxia

Hypoxia incites inflammation, particularly at mucosal surfaces. Eltzschig and colleagues show that hypoxia also suppresses inflammation by inducing expression of the neuronal guidance molecule netrin-1, which inhibits the transepithelial migration of neutrophils.

  • Peter Rosenberger,
  • Jan M Schwab ⋯
  • Holger K Eltzschig

ARTICLE4 JAN 2009Nature Immunology

Plant cysteine oxidases are dioxygenases that directly enable arginyl transferase-catalysed arginylation of N-end rule targets

The N-end rule pathway targets substrate proteins for proteasomal degradation. Here, Whiteet al. show that ArabidopsisPLANT CYSTEINE OXIDASEs show dioxygenase activity producing Cys-sulfinic acid at the N-terminus of target proteins, which then act as direct substrates for arginyl transferase.

  • Mark D. White,
  • Maria Klecker ⋯
  • Emily Flashman

ARTICLEOPEN ACCESS23 MAR 2017Nature Communications

A hypoxia-responsive TRAF6–ATM–H2AX signalling axis promotes HIF1α activation, tumorigenesis and metastasis

Lin and colleagues report that hypoxia induces TRAF6-dependent mono-ubiquitylation of histone H2AX, which promotes binding and stabilization of HIF1α. Activated HIF1α signalling in turn promotes tumorigenesis and metastasis.

  • Abdol-Hossein Rezaeian,
  • Chien-Feng Li ⋯
  • Hui-Kuan Lin

ARTICLE5 DEC 2016Nature Cell Biology

A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion

The mechanisms by which organisms adapt their growth according to the availability of oxygen are incompletely understood. Here the authors identify the Drosophila fat body as a tissue regulating growth in response to oxygen sensing via a mechanism involving Hph…

  • Michael J. Texada,
  • Anne F. Jørgensen ⋯
  • Kim F. Rewitz

ARTICLEOPEN ACCESS26 APR 2019Nature Communications

Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent

Humans that reach high altitude soon after the first ascent show faster adaptation to hypoxia. Songet al. show that this adaptive response relies on decreased red blood cell uptake of plasma adenosine due to reduced levels of nucleoside transporter ENT1…

  • Anren Song,
  • Yujin Zhang ⋯
  • Yang Xia

ARTICLEOPEN ACCESS7 FEB 2017Nature Communications

Hypoxia-inducible factors enhance the effector responses of CD8+ T cells to persistent antigen

The transcription factor HIF is induced in response to hypoxic stress, TCR activation and cytokines. Goldrath and colleagues show that HIF signaling enhances CTL effector responses and can render cells refractory to immune exhaustion.

  • Andrew L Doedens,
  • Anthony T Phan ⋯
  • Ananda W Goldrath

ARTICLE29 SEP 2013Nature Immunology

Local lung hypoxia determines epithelial fate decisions during alveolar regeneration

Xi et al. show that after influenza infection, hypoxia drives Notch signalling to expand Krt5+ basal-like cells in the lung. On HIF1α loss, epithelial progenitors directly differentiate into alveolar type II cells and promote functional regeneration.

  • Ying Xi,
  • Thomas Kim ⋯
  • Andrew E. Vaughan

ARTICLE24 JUL 2017Nature Cell Biology

HIF activation by pH-dependent nucleolar sequestration of VHL

  • Karim Mekhail,
  • Lakshman Gunaratnam ⋯
  • Stephen Lee

LETTER6 JUN 2004Nature Cell Biology

Reviews and Comment

VHL, the story of a tumour suppressor gene

The identification in 1993 of inherited mutations in the von Hippel–Lindau (VHL) gene in families with VHL disease was a seminal finding. This and subsequent discoveries have given the VHL tumour suppressor gene a central role in our understanding of the…

  • Lucy Gossage,
  • Tim Eisen &
  • Eamonn R. Maher

TIMELINE23 DEC 2014Nature Reviews Cancer

Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases

Hypoxia-inducible factors (HIFs) have important roles in ischaemic and inflammatory diseases and strategies aimed at therapeutically modulating hypoxia signalling pathways are gaining considerable attention. Here, Eltzschig and colleagues focus on a set of…

  • Holger K. Eltzschig,
  • Donna L. Bratton &
  • Sean P. Colgan

REVIEW ARTICLE31 OCT 2014Nature Reviews Drug Discovery

Characterization of hypoxia-associated molecular features to aid hypoxia-targeted therapy

The conventional view holds that hypoxia confers drug resistance. In contrast, here the authors use a multilayer ‘omics data approach to characterize the molecular features associated with tumour hypoxia and identify molecular alterations that correlate with…

  • Youqiong Ye,
  • Qingsong Hu ⋯
  • Leng Han

ARTICLE18 MAR 2019Nature Metabolism

Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD

IBD is associated with markedly reduced intestinal mucosal oxygen levels. In this Review, the authors discuss the role of mucosal hypoxia and hypoxia-induced signalling in IBD and identify potential targets for therapies, focusing on the cell-specific functions…

  • Sophie Van Welden,
  • Andrew C. Selfridge &
  • Pieter Hindryckx

REVIEW ARTICLE30 AUG 2017Nature Reviews Gastroenterology & Hepatology

A new approach to treating renal anaemia

Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with kidney disease. A potential alternative approach is to increase erythropoietin production using small-molecule inhibitors of prolyl hydroxylase domain (PHD) enzymes.…

  • Patrick H. Maxwell

NEWS & VIEWS11 SEP 2019Nature Reviews Nephrology

Hypoxia—a key regulator of angiogenesis and inflammation in rheumatoid arthritis

The role of inflammation in rheumatoid arthritis (RA) is well characterized, but how hypoxia affects RA and the potential interplay between inflammation, angiogenesis and hypoxia in this disease is less defined. Here, the authors describe how hypoxia affects RA,…

  • Sofia Konisti,
  • Serafim Kiriakidis &
  • Ewa M. Paleolog

REVIEW ARTICLE31 JAN 2012Nature Reviews Rheumatology

Hypoxia-driven pathways in bone development, regeneration and disease

Oxygen is thought to be an indispensable regulatory signal in tissue development and homeostasis, via its controlling of specific genetic programs. Hypoxia-inducible transcription factors (HIFs), which are regulated by oxygen tension, are central mediators of…

  • Christa Maes,
  • Geert Carmeliet &
  • Ernestina Schipani

REVIEW ARTICLE27 MAR 2012Nature Reviews Rheumatology

Immunometabolism: Oxygen sensing and cell metabolism in inflammation

Hypoxia-inducible transcription factors (HIFs) are key mediators of several molecular and cellular responses that are activated under hypoxic conditions. New findings demonstrate an important role for the HIF system in mediating the activation and inflammatory…

  • Kai-Uwe Eckardt

NEWS & VIEWS24 OCT 2017Nature Reviews Nephrology

Hypoxia, mitochondrial dysfunction and synovial invasiveness in rheumatoid arthritis

In this article, the authors provide a comprehensive and timely review of the mechanisms and consequences of hypoxia in the biology of inflammatory arthritis, with a focus on mitochondrial function, hypoxia signalling pathways in rheumatoid arthritis, and therapeutic implications.

  • Ursula Fearon,
  • Mary Canavan ⋯
  • Douglas J. Veale

REVIEW ARTICLE26 MAY 2016Nature Reviews Rheumatology

Control and dysregulation of redox signalling in the gastrointestinal tract

Redox signalling in the gastrointestinal mucosa is held in an intricate balance. This Review addresses both the spectrum and intensity of redox activity pertaining to host–immune and host–microbiota crosstalk during homeostasis and disease processes in the gastrointestinal tract.

  • Eric L. Campbell &
  • Sean P. Colgan

REVIEW ARTICLE15 NOV 2018Nature Reviews Gastroenterology & Hepatology

Oxygen and mammalian cell culture: are we repeating the experiment of Dr. Ox?

Mammalian cell culture represents a cornerstone of modern biomedical research. There is growing appreciation that the media conditions in which cells are cultured can profoundly influence the observed biology and reproducibility. Here, we consider a key but…

  • Tslil Ast &
  • Vamsi K. Mootha

COMMENT5 AUG 2019Nature Metabolism

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