Featured
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Research Highlights |
Culprits in diabetic heart risk
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Review Article |
Inflammasomes in health and disease
- Till Strowig
- , Jorge Henao-Mejia
- & Richard Flavell
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Article |
DNA breaks and chromosome pulverization from errors in mitosis
Chromosomes within micronuclei are shown to be damaged during S phase and become highly fragmented, and the damaged pieces can be reincorporated into the genome.
- Karen Crasta
- , Neil J. Ganem
- & David Pellman
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Research Highlights |
Culprit in deafness
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Outlook |
Aetiology: The path to disease
Multiple myeloma begins with a benign condition before progression to full-blown cancer, and work is underway to uncover the origins of both.
- Cynthia Graber
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Letter |
DCC constrains tumour progression via its dependence receptor activity
A mouse model is developed in which the pro-apoptotic activity of DCC is silenced and the mice are more prone to intestinal tumour progression, giving insight into the role of DCC in human colorectal cancer.
- Marie Castets
- , Laura Broutier
- & Patrick Mehlen
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Letter |
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation
- Weiwei Yang
- , Yan Xia
- & Zhimin Lu
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Outlook |
Atopy: Marching with allergies
They come not single spies, but in battalions. The latest research helps explain why an individual may experience the 'atopic march' from one allergic disorder to another.
- Paige Brown
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Outlook |
Treatment: In search of a booster shot
A plethora of therapies can keep the symptoms of allergy under control, but they can't cure. New research aims to prevent allergies from developing in the first place.
- Lauren Gravitz
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Letter |
Reductive carboxylation supports growth in tumour cells with defective mitochondria
Tumour cells with defective mitochondria are found to use glutamine-dependent reductive carboxylation, rather than oxidative metabolism, as the major pathway of citrate and lipid formation.
- Andrew R. Mullen
- , William W. Wheaton
- & Ralph J. DeBerardinis
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Correspondence |
Nobels: Toll pioneers deserve recognition
- James P. Allison
- , Christophe Benoist
- & Alexander V. Chervonsky
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Research Highlights |
Breathing easier with stem cells
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News & Views |
A heavyweight knocked out
Caspase-1 is one of the main culprits behind sepsis, a form of systemic inflammation. The related enzyme caspase-11 is also involved, but the relative roles of the two proteins have been confusing, until now. See Letter p.117
- Douglas R. Green
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Letter |
Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model
- Yimin Hua
- , Kentaro Sahashi
- & Adrian R. Krainer
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Article |
Complement factor H binds malondialdehyde epitopes and protects from oxidative stress
- David Weismann
- , Karsten Hartvigsen
- & Christoph J. Binder
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News & Views |
Recognition of a unique partner
The mammalian immune system can fight a myriad of pathogens. In part, this involves a superfamily of cytoplasmic receptors that dictate assembly of specific pro-inflammatory inflammasome complexes. See Letters p.592 & p.596
- Denise M. Monack
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Letter |
Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
- Claudia Günther
- , Eva Martini
- & Christoph Becker
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Article |
Frequent pathway mutations of splicing machinery in myelodysplasia
- Kenichi Yoshida
- , Masashi Sanada
- & Seishi Ogawa
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Letter |
Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus
- Sébastien Jacquemont
- , Alexandre Reymond
- & Philippe Froguel
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Letter |
Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity
- Eric M. Kofoed
- & Russell E. Vance
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Letter |
Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia
- Han-Xiang Deng
- , Wenjie Chen
- & Teepu Siddique
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Letter |
TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation
- Mark C. Siracusa
- , Steven A. Saenz
- & David Artis
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Review Article |
A continuum model for tumour suppression
- Alice H. Berger
- , Alfred G. Knudson
- & Pier Paolo Pandolfi
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News |
Lessons about Alzheimer's disease
Psychologist Margaret Gatz explains what 25 years of research have taught her about reducing the risk of dementia.
- Gwyneth Dickey Zakaib
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News |
Antibodies linked to long-term Lyme symptoms
Researchers find molecules that might mark elusive syndrome.
- Amy Maxmen
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Letter |
FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
- Patrick-Simon Welz
- , Andy Wullaert
- & Manolis Pasparakis
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Letter |
Control of TH17 cells occurs in the small intestine
- Enric Esplugues
- , Samuel Huber
- & Richard A. Flavell
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News Explainer |
Review adds salt to a familiar concern
Link between salt consumption and heart disease challenged.
- Ewen Callaway
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Letter |
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
- Gina M. DeNicola
- , Florian A. Karreth
- & David A. Tuveson
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Review Article |
Genetics and pathogenesis of inflammatory bowel disease
- Bernard Khor
- , Agnès Gardet
- & Ramnik J. Xavier
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Review Article |
Intestinal homeostasis and its breakdown in inflammatory bowel disease
- Kevin J. Maloy
- & Fiona Powrie
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Letter |
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
- Bin-Zhi Qian
- , Jiufeng Li
- & Jeffrey W. Pollard
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Letter |
Transcriptomic analysis of autistic brain reveals convergent molecular pathology
- Irina Voineagu
- , Xinchen Wang
- & Daniel H. Geschwind
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Review Article |
Progress and challenges in translating the biology of atherosclerosis
- Peter Libby
- , Paul M Ridker
- & Göran K. Hansson
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News |
Stress can shorten telomeres in childhood
Children in orphanages have chromosome changes that could affect future health.
- Marian Turner
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Letter |
COP1 is a tumour suppressor that causes degradation of ETS transcription factors
- Alberto C. Vitari
- , Kevin G. Leong
- & Vishva M. Dixit
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Letter |
Non-apoptotic role of BID in inflammation and innate immunity
- Garabet Yeretssian
- , Ricardo G. Correa
- & Maya Saleh
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Article |
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease
This paper shows that gut flora can influence cardiovascular disease, by metabolizing a dietary phospholipid. Using a metabolomics approach it is found that plasma levels of three metabolites of dietary phosphatidylcholine—choline, betaine and TMAO—are associated with increased risk of cardiovascular disease in humans. The gut flora is known to have a role in TMAO formation from choline, and this paper shows that dietary choline supplementation enhances macrophage foam cell formation and lesion formation in atherosclerosis-prone mice, but not if the gut flora are depleted with antibiotics.
- Zeneng Wang
- , Elizabeth Klipfell
- & Stanley L. Hazen
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Letter |
Suppression of lung adenocarcinoma progression by Nkx2-1
- Monte M. Winslow
- , Talya L. Dayton
- & Tyler Jacks
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Article |
Mapping and analysis of chromatin state dynamics in nine human cell types
- Jason Ernst
- , Pouya Kheradpour
- & Bradley E. Bernstein
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Article
| Open Access
Initial genome sequencing and analysis of multiple myeloma
Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Using next-generation sequencing of several multiple myeloma genomes reveals that this disease involves mutations of genes involved in protein translation, histone methylation and blood coagulation. The study suggests that BRAF inhibitors should be evaluated in multiple myeloma clinical trials.
- Michael A. Chapman
- , Michael S. Lawrence
- & Todd R. Golub
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Letter |
The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset
Using a zebrafish model of melanoma, this study has searched for genes that can cooperate with mutated BRAF, a frequent oncogenic event in human melanomas. It is found that SETDB1 can accelerate melanoma formation in fish and resides in a region frequently amplified in human melanomas. SETDB1, a histone methylating enzyme, is also frequently overexpressed in human melanomas and functions at least in part by regulating the expression of HOX genes.
- Craig J. Ceol
- , Yariv Houvras
- & Leonard I. Zon
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Letter |
Aberrant chromosome morphology in human cells defective for Holliday junction resolution
Exchange of sister chromatids to form four-stranded Holliday junctions occurs naturally during meiosis, to hold sister chromatids together, and during various repair events. In eukaryotes, double Holliday junctions that escape dissolution by a helicase/topoisomerase (BTR) complex are instead processed by one of several nucleases known as resolvases. This study defines the activities of the GEN1, MUS81-EME1 and SLX1-SLX4 resolvases in the absence of BLM, the helicase component of BTR that is mutated in Bloom's syndrome.
- Thomas Wechsler
- , Scott Newman
- & Stephen C. West
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Letter |
Tumour evolution inferred by single-cell sequencing
Although it is known that tumours are genetically heterogeneous it has so far been difficult to dissect this heterogeneity at a single cell level. This paper combines whole-genome amplification and next-generation sequencing of flow-sorted nuclei from breast tumours to investigate their population structure and evolution. In contrast to gradual models of tumour progression, the results indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
- Nicholas Navin
- , Jude Kendall
- & Michael Wigler
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Letter |
CREBBP mutations in relapsed acute lymphoblastic leukaemia
In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.
- Charles G. Mullighan
- , Jinghui Zhang
- & James R. Downing
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Article |
Caspase signalling controls microglia activation and neurotoxicity
- Miguel A. Burguillos
- , Tomas Deierborg
- & Bertrand Joseph
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Article |
Inactivating mutations of acetyltransferase genes in B-cell lymphoma
In three different subtypes of B-cell lymphomas, two papers now report frequent somatic mutations in CREBBP and EP300, present in primary tumours or acquired at relapse. These genes encode related acetyltransferases that mainly function to regulate gene expression by acetylating histones and other transcriptional regulators. The mutations found inactivate these activities and thus alter chromatin regulation of gene expression, as well as proliferation and potentially the response to therapeutic drugs.
- Laura Pasqualucci
- , David Dominguez-Sola
- & Riccardo Dalla-Favera
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Letter |
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers
Using whole-transcriptome sequencing, this paper identifies recurrent gene translocations in B-cell lymphomas that involve the MHC class II transactivator CIITA. These translocations lead to downregulation of cell surface HLA class II expression and, in the case of some fusion partners, overexpression of CD274/CD273 ligands, which have the potential to reduce the antitumour response against these lymphomas.
- Christian Steidl
- , Sohrab P. Shah
- & Randy D. Gascoyne
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Letter |
The RAG2 C terminus suppresses genomic instability and lymphomagenesis
Misrepair of DNA double strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin and T-cell receptor loci has been implicated in the pathogenesis of lymphoid malignancies. Here, the RAG2 carboxy terminus is shown to be critical for maintaining genomic stability. Rag2c/c p53−/− mice, unlike Rag1c/c p53−/− and p53−/− mice, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcrα/δ and Igh loci. These results reveal a new 'genome guardian' role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2c/c p53−/− and Atm−/− mice.
- Ludovic Deriano
- , Julie Chaumeil
- & David B. Roth
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity