Reviews

PIWI-interacting RNAs: small RNAs with big functions PIWI-interacting RNAs: small RNAs with big functions, Published online: 16 November 2018; doi:10.1038/s41576-018-0073-3 PIWI-interacting RNAs (piRNAs) have numerous crucial biological roles, particularly transposon silencing in the germ line. In this Review, the authors describe our latest understanding of piRNA biogenesis and functions across diverse species, highlighting how, despite
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Functions and mechanisms of epigenetic inheritance in animals Functions and mechanisms of epigenetic inheritance in animals, Published online: 13 November 2018; doi:10.1038/s41580-018-0074-2 Epigenetic profiling of germline and zygotic genomes has revealed that a fraction of mammalian genomes do not undergo epigenetic reprogramming during early development, highlighting the importance of epigenetic inheritance in animals. Inheritance of
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mTOR signalling and cellular metabolism are mutual determinants in cancer mTOR signalling and cellular metabolism are mutual determinants in cancer, Published online: 13 November 2018; doi:10.1038/s41568-018-0074-8 This Review discusses the interdependencies of mTOR signalling and metabolism pathways in cancer and how metabolic reprogramming in response to changes in mTOR signalling and vice versa can sustain
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A changing paradigm of transcriptional memory propagation through mitosis A changing paradigm of transcriptional memory propagation through mitosis, Published online: 12 November 2018; doi:10.1038/s41580-018-0077-z Recent data indicate that various transcription factors and RNA polymerase II bind to mitotic chromatin and that thousands of genes remain transcriptionally active in mitosis, contradicting the view that mitotic cells
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Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation Central CD4<sup>+</sup> T cell tolerance: deletion versus regulatory T cell differentiation, Published online: 12 November 2018; doi:10.1038/s41577-018-0083-6 Self-antigen recognition in the thymus can result in both clonal deletion of developing thymocytes and their diversion into the regulatory T cell lineage. How do thymocyte-intrinsic and
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GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures GPCR drug discovery: integrating solution NMR data with crystal and cryo-EM structures, Published online: 09 November 2018; doi:10.1038/nrd.2018.180 Determination of the crystal structures of more than 50 human G protein-coupled receptors (GPCRs) during the past decade has provided a platform for structure-based drug
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Nonsense-mediated RNA decay in the brain: emerging modulator of neural development and disease Nonsense-mediated RNA decay in the brain: emerging modulator of neural development and disease, Published online: 08 November 2018; doi:10.1038/s41583-018-0079-z Nonsense-mediated RNA decay — a highly selective and conserved RNA turnover pathway — is shown to have roles in both brain development and
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Diverse light responses of cyanobacteria mediated by phytochrome superfamily photoreceptors Diverse light responses of cyanobacteria mediated by phytochrome superfamily photoreceptors, Published online: 08 November 2018; doi:10.1038/s41579-018-0110-4 Cyanobacteria have evolved a number of photoreceptor-controlled mechanisms that enable them to sense and respond to environmental light conditions. In this Review, Kehoe and Wiltbank examine physiological responses that
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Current and future perspectives of liquid biopsies in genomics-driven oncology Current and future perspectives of liquid biopsies in genomics-driven oncology, Published online: 08 November 2018; doi:10.1038/s41576-018-0071-5 Liquid biopsies enable non-invasive, longitudinal analysis of tumour components (including circulating tumour cells and circulating tumour DNA) in bodily fluids such as blood. However, their analytical and clinical validity must be
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Tumour-targeting bacteria engineered to fight cancer Tumour-targeting bacteria engineered to fight cancer, Published online: 07 November 2018; doi:10.1038/s41568-018-0070-z Therapy with live tumour-targeting bacteria represents a unique opportunity to address the limitations associated with molecularly targeted therapies and immunotherapies. In this Review, Zhou et al. discuss the benefits and challenges of this approach and outline advances
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Versatile control of synaptic circuits by astrocytes: where, when and how? Versatile control of synaptic circuits by astrocytes: where, when and how?, Published online: 06 November 2018; doi:10.1038/s41583-018-0080-6 Astrocytes display widespread functional diversity that translates into distinct regulation of synaptic circuits. In this Review, Dallérac and colleagues discuss the determinants of these divergent regulations throughout
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The many lives of KATs — detectors, integrators and modulators of the cellular environment The many lives of KATs — detectors, integrators and modulators of the cellular environment, Published online: 02 November 2018; doi:10.1038/s41576-018-0072-4 Lysine acetyltransferases (KATs) act at the interface of the cellular environment and transcription to modify levels of acetylation on target proteins.
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Integrative regulation of physiology by histone deacetylase 3 Integrative regulation of physiology by histone deacetylase 3, Published online: 02 November 2018; doi:10.1038/s41580-018-0076-0 The activity of many cell type-specific enhancers is regulated by histone deacetylase 3 (HDAC3), which acts in complex with various nuclear receptor co-repressors. HDAC3 is required for many aspects of mammalian development and
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Autism spectrum disorder: insights into convergent mechanisms from transcriptomics Autism spectrum disorder: insights into convergent mechanisms from transcriptomics, Published online: 02 November 2018; doi:10.1038/s41576-018-0066-2 Transcriptome profiling in different brain regions has revealed distinct patterns of gene and non-coding RNA expression, as well as alternative splicing, in autism spectrum disorder (ASD). The authors review these ASD-associated
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The causes of evolvability and their evolution The causes of evolvability and their evolution, Published online: 01 November 2018; doi:10.1038/s41576-018-0069-z In this article, Payne and Wagner discuss how recent experimental studies are complementing theoretical work to enhance our understanding of the evolvability of diverse biological systems. They highlight phenotypic heterogeneity, robustness and adaptive landscape topography
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Organizational principles of 3D genome architecture Organizational principles of 3D genome architecture, Published online: 26 October 2018; doi:10.1038/s41576-018-0060-8 High-resolution studies of chromosome conformation are revealing that the 3D genome is organized into smaller structural features than was previously supposed and is primarily composed of compartmental domains and CTCF loops. In this Perspectives article Rowley and
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Systemic immunoglobulin light chain amyloidosis Systemic immunoglobulin light chain amyloidosis, Published online: 25 October 2018; doi:10.1038/s41572-018-0034-3 Systemic immunoglobulin light chain amyloidosis is a disease characterized by the tissue accumulation of amyloid fibrillar aggregates, which leads to organ dysfunction. This Primer discusses the molecular mechanisms of this form of amyloidosis and highlights management strategies that have
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The hippocampal sharp wave–ripple in memory retrieval for immediate use and consolidation The hippocampal sharp wave–ripple in memory retrieval for immediate use and consolidation, Published online: 24 October 2018; doi:10.1038/s41583-018-0077-1 Sharp wave–ripples (SWRs) are specific neural activity patterns in the hippocampus that are thought to support memory. In this Review, Hannah Joo and Loren Frank
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Coaching from the sidelines: the nuclear periphery in genome regulation Coaching from the sidelines: the nuclear periphery in genome regulation, Published online: 24 October 2018; doi:10.1038/s41576-018-0063-5 Recent technological advances are enabling new views of the 3D genome within the space of the nucleus. These studies are beginning to reveal the ways cells co-opt the structures
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Going to the negative: genomics for optimized medical prescription Going to the negative: genomics for optimized medical prescription, Published online: 22 October 2018; doi:10.1038/s41576-018-0061-7 In personalized medicine, a major aim is to provide the right treatment to the right patient. In this Comment article, Gibson discusses how a more overt and genomics-informed focus on those
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Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes, Published online: 18 October 2018; doi:10.1038/s41580-018-0071-5 The distribution of lipids largely depends on their non-vesicular transport by lipid transfer proteins (LTPs). Recent progress in understanding the mechanisms of LTPs, including the appreciation of
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Fasting and cancer: molecular mechanisms and clinical application Fasting and cancer: molecular mechanisms and clinical application, Published online: 16 October 2018; doi:10.1038/s41568-018-0061-0 This Opinion discusses the potential of fasting and fasting-mimicking diets to help overcome toxicities induced by anticancer therapy. The differential response of normal and cancer cells undergoing starvation is argued to make normal
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Actin–microtubule crosstalk in cell biology Actin–microtubule crosstalk in cell biology, Published online: 15 October 2018; doi:10.1038/s41580-018-0067-1 Actin and microtubules are essential for key cellular processes, including cell polarization, migration and division. Although their cellular roles are distinct, actin and microtubules also extensively influence each other’s dynamics and organization. This crosstalk encompasses multiple mechanisms and involves
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Back to the beginning to understand metastasis Back to the beginning to understand metastasis, Published online: 15 October 2018; doi:10.1038/s41568-018-0069-5 Yang et al. have used genetically engineered mouse models of small cell lung cancer to show that the same genomic alterations in different cells of origin lead to the formation of tumours that follow distinct
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Base editing: precision chemistry on the genome and transcriptome of living cells Base editing: precision chemistry on the genome and transcriptome of living cells, Published online: 15 October 2018; doi:10.1038/s41576-018-0059-1 Genome editing through direct editing of bases holds promise for achieving precise genomic changes at single-nucleotide resolution while minimizing the occurrence of potentially mutagenic double-strand DNA breaks.
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Regulatory T cells in the treatment of disease Regulatory T cells in the treatment of disease, Published online: 12 October 2018; doi:10.1038/nrd.2018.148 Regulatory T cells are important in controlling immune reactions and thus are implicated in autoimmune diseases, transplantation and cancer. In this Review, Tsokos and colleagues discuss how these cells can be harnessed or
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Drug repurposing: progress, challenges and recommendations Drug repurposing: progress, challenges and recommendations, Published online: 12 October 2018; doi:10.1038/nrd.2018.168 Drug repurposing — a strategy for identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication — has the potential for greater success rates and reduced costs compared with
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Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing, Published online: 10 October 2018; doi:10.1038/s41583-018-0068-2 Age-related changes in cognitive ability are the focus of a growing field of research. Cabeza, Rajah and colleagues aim to promote clarity in the field by agreeing upon consensual
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The phylogenomics of evolving virus virulence The phylogenomics of evolving virus virulence, Published online: 10 October 2018; doi:10.1038/s41576-018-0055-5 The virulence of viruses is a major determinant of the health burden of viral infections in humans and other species. In this article, Geoghegan and Holmes discuss how largely disparate research fields — theoretical modelling of virulence
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The oral microbiota: dynamic communities and host interactions The oral microbiota: dynamic communities and host interactions, Published online: 09 October 2018; doi:10.1038/s41579-018-0089-x The dynamic and polymicrobial oral microbiota is a direct precursor of diseases such as dental caries and periodontitis. In this Review, Lamont, Koo and Hajishengallis discuss the mechanisms by which oral microbial communities
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The neural mechanisms and circuitry of the pair bond The neural mechanisms and circuitry of the pair bond, Published online: 09 October 2018; doi:10.1038/s41583-018-0072-6 Recent research advances have yielded fresh insights into the fundamental neural processes underlying pair bonding. In this Review, Walum and Young discuss how neural representations of a partner become inherently rewarding,
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Imaging-based parcellations of the human brain Imaging-based parcellations of the human brain, Published online: 09 October 2018; doi:10.1038/s41583-018-0071-7 The brain can be parcellated into areas or networks with different structural or functional properties. Eickhoff, Yeo and Genon describe various imaging-based strategies to parcellate the human brain, including those based on local properties, such as cytoarchitecture,
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The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers, Published online: 06 October 2018; doi:10.1038/s41568-018-0060-1 This Review discusses the 2018 Catalogue of Somatic Mutations in Cancer (COSMIC) Cancer Gene Census (CGC), an expert-curated description of human cancer genes, which has
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Lysosomal storage diseases Lysosomal storage diseases, Published online: 01 October 2018; doi:10.1038/s41572-018-0025-4 Lysosomal storage diseases (LSDs) are a diverse group of disorders that can manifest at any stage of life. This Primer by Platt and colleagues provides an overview of the LSDs, including how lysosomal dysfunction gives rise to disease and how these disorders are
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Targeting G protein-coupled receptor signalling by blocking G proteins Targeting G protein-coupled receptor signalling by blocking G proteins, Published online: 28 September 2018; doi:10.1038/nrd.2018.135 Identifying ligands of G protein-coupled receptors (GPCRs) that elicit biased downstream signalling is an established strategy for separating the desired and unwanted effects of these receptors. Campbell and Smrcka describe how
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Imaging the evolution and pathophysiology of Alzheimer disease Imaging the evolution and pathophysiology of Alzheimer disease, Published online: 28 September 2018; doi:10.1038/s41583-018-0067-3 Various techniques can be used to image aspects of the pathophysiology of Alzheimer disease in humans, notably protein deposition and neurodegeneration. In this Review, William Jagust discusses how human neuroimaging studies have shaped
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Are tolerance and training required to end TB? Are tolerance and training required to end TB?, Published online: 28 September 2018; doi:10.1038/s41577-018-0070-y Host defence strategies against Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), include host resistance and disease tolerance. To date, most studies have focused on resistance mechanisms, but developing new strategies to
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Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs, Published online: 28 September 2018; doi:10.1038/nrd.2018.136 Existing dopaminergic-based therapies for Parkinson disease (PD) are limited by side effects and lack of long-term efficacy. Here, Charvin et al. discuss the challenges facing the development of novel treatments for PD, assess
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Towards quantitative and multiplexed in vivo functional cancer genomics Towards quantitative and multiplexed in vivo functional cancer genomics, Published online: 28 September 2018; doi:10.1038/s41576-018-0053-7 CRISPR–Cas genome editing and next-generation sequencing are driving advances in cancer modelling and functional cancer genomics. Their application to autochthonous mouse models of human cancer to generate and analyse multiplexed and/or
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Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer, Published online: 25 September 2018; doi:10.1038/s41577-018-0066-7 This Review considers the key roles of the IL-6 cytokine family in regulating innate and adaptive immunity, as well as other physiological responses.
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Therapeutic approaches to Huntington disease: from the bench to the clinic Therapeutic approaches to Huntington disease: from the bench to the clinic, Published online: 21 September 2018; doi:10.1038/nrd.2018.133 New therapies, including RNA-based and gene therapies, are poised to change the therapeutic landscape for Huntington disease. In this article, Hayden and colleagues review the progress that
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mRNA alterations mimic genetic mutations mRNA alterations mimic genetic mutations, Published online: 21 September 2018; doi:10.1038/s41568-018-0059-7 Lee, Singh et al. find that cancer-specific intronic polyadenylation events occur frequently in tumour suppressor genes in chronic lymphocytic leukaemia (CLL) and generate truncated proteins that could act as CLL drivers.
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The emerging role of ADAM metalloproteinases in immunity The emerging role of ADAM metalloproteinases in immunity, Published online: 21 September 2018; doi:10.1038/s41577-018-0068-5 A-DAM good Review discussing the role of ADAM protein-mediated cleavage of a wide range of substrates in the development and regulation of the immune system, with a focus on ADAM10 and ADAM17.
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