Reviews

Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins, Published online: 17 January 2019; doi:10.1038/s41580-018-0089-8 BCL-2 family proteins are the mediators of apoptotic cell death. The balance between pro-apoptotic and pro-survival BCL-2 family members is differently
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Brain metastases Brain metastases, Published online: 17 January 2019; doi:10.1038/s41572-018-0055-y An estimated 20% of all patients with cancer will develop brain metastases, with the majority of brain metastases occurring in those with lung and breast cancer and melanoma. This Primer describes the mechanisms by which cancer cells migrate to the brain and the key advances
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Sodium in the microenvironment regulates immune responses and tissue homeostasis Sodium in the microenvironment regulates immune responses and tissue homeostasis, Published online: 15 January 2019; doi:10.1038/s41577-018-0113-4 Dietary salt can have direct effects on immune cell subsets as well as indirect effects through intestinal dysbiosis. We are beginning to appreciate that high salt diets not only
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Genomic imprinting disorders: lessons on how genome, epigenome and environment interact Genomic imprinting disorders: lessons on how genome, epigenome and environment interact, Published online: 15 January 2019; doi:10.1038/s41576-018-0092-0 Disruption of genomic imprinting can lead to disease. Recent studies suggest that interactions between the genome, the epigenome and the environment in germ cells and early embryos
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The control of release probability at nerve terminals The control of release probability at nerve terminals, Published online: 15 January 2019; doi:10.1038/s41583-018-0111-3 Neurosecretion is controlled by SNAREs and SNARE-binding proteins and is initiated by the influx of Ca2+ ions through voltage-gated calcium channels (VGCCs). In this Review, Dittman and Ryan discuss progress in our understanding
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Modelling cancer in microfluidic human organs-on-chips Modelling cancer in microfluidic human organs-on-chips, Published online: 15 January 2019; doi:10.1038/s41568-018-0104-6 In vitro cancer models often fail to faithfully recapitulate the local tissue and organ microenvironment. Organs-on-chips can overcome this limitation and better mimic in vivo cancer phenotypes. This Review outlines the advances that have been made with
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Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis, Published online: 14 January 2019; doi:10.1038/s41583-018-0113-1 Understanding the complex interplay of cells that protect neurons early in Alzheimer disease but later contribute to neurodegeneration is important for developing effective therapeutics. In this Review, Henstridge and colleagues discuss
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Organismal immunometabolism: advances in both directions Organismal immunometabolism: advances in both directions, Published online: 11 January 2019; doi:10.1038/s41577-018-0118-z The field of immunometabolism (both on the cellular as well as on the organismal level) is advancing rapidly. This article highlights several studies from 2018 that examine how immune cells can regulate systemic metabolism, as well as
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Mitochondrial proteins: from biogenesis to functional networks Mitochondrial proteins: from biogenesis to functional networks, Published online: 09 January 2019; doi:10.1038/s41580-018-0092-0 Recent functional and proteomic studies have revealed the remarkable complexity of mitochondrial protein organization and interactions. This Review discusses how the mitochondrial protein import machinery functions as a key organizer of these protein networks, its
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A great-ape view of the gut microbiome A great-ape view of the gut microbiome, Published online: 08 January 2019; doi:10.1038/s41576-018-0085-z Comparing the microbiomes of great apes enables an evolutionary perspective on microbial communities. This approach is revealing not only new insights about humans and what differentiates us from our closest relatives but also the factors that influence
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Expanding the search Expanding the search, Published online: 07 January 2019; doi:10.1038/s41568-018-0101-9 Laumont, Vincent et al. have developed a proteogenomic strategy for high-throughput mass spectrometry-based discovery of aberrantly expressed tumour-specific antigens from non-coding sequences as well as mutated tumour-specific antigens encoded by all genomic regions, thereby expanding the number of targetable antigens that can be
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Challenges in unsupervised clustering of single-cell RNA-seq data Challenges in unsupervised clustering of single-cell RNA-seq data, Published online: 07 January 2019; doi:10.1038/s41576-018-0088-9 Single-cell RNA sequencing (scRNA-seq) enables transcriptome-based characterization of the constituent cell types within a heterogeneous sample. However, reliable analysis and biological interpretation typically require optimal use of clustering algorithms. This Review discusses the
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Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases, Published online: 04 January 2019; doi:10.1038/s41573-018-0008-x The transcription factor NRF2 and its repressor KEAP1 have been implicated in the development and progression of chronic diseases. Here, Dinkova-Kostova and colleagues provide an overview of
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The signposts and winding roads to immunity and inflammation The signposts and winding roads to immunity and inflammation, Published online: 02 January 2019; doi:10.1038/s41577-018-0108-1 The field of innate immunity has been rapidly evolving and expanding its horizons during the past few years. 2018 was no exception, with the publication of several ground-breaking studies that bring
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Genomic evolution of cancer models: perils and opportunities Genomic evolution of cancer models: perils and opportunities, Published online: 21 December 2018; doi:10.1038/s41568-018-0095-3 Genomic instability in cancer models presents a major challenge in the design and reproducibility of research and its clinical translation. This Opinion article discusses the causes and consequences of intra-tumour genomic heterogeneity and
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Therapeutically exploiting STAT3 activity in cancer — using tissue repair as a road map Therapeutically exploiting STAT3 activity in cancer — using tissue repair as a road map, Published online: 21 December 2018; doi:10.1038/s41568-018-0090-8 This Review discusses how excessive signal transducer and activator of transcription 3 (STAT3) activation within cancer cells and cells of the
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Portraits of communication in neuronal networks Portraits of communication in neuronal networks, Published online: 14 December 2018; doi:10.1038/s41583-018-0094-0 In this Opinion article, Hahn, Kumar and colleagues propose that synchrony- and oscillation-based communication between brain networks can be described by a common theoretical framework. They also suggest a mechanism for control of the flow of information
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Hippo–YAP/TAZ signalling in organ regeneration and regenerative medicine Hippo–YAP/TAZ signalling in organ regeneration and regenerative medicine, Published online: 13 December 2018; doi:10.1038/s41580-018-0086-y The Hippo pathway effectors YAP and TAZ regulate normal and tumorigenic organ growth. Recent studies in vitro and in mouse models have shown that these two transcription co-activators can also promote tissue regeneration.
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Deciphering bacterial epigenomes using modern sequencing technologies Deciphering bacterial epigenomes using modern sequencing technologies, Published online: 13 December 2018; doi:10.1038/s41576-018-0081-3 DNA methylation is the primary epigenetic modification in bacteria, but a lack of suitable methods has hampered its study. Now, new sequencing technologies, including single-molecule, real-time sequencing and nanopore sequencing, are providing new opportunities for
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Polymer–drug conjugate therapeutics: advances, insights and prospects Polymer–drug conjugate therapeutics: advances, insights and prospects, Published online: 12 December 2018; doi:10.1038/s41573-018-0005-0 The conjugation of therapeutic agents to polymer carriers, such as polyethylene glycol (PEG), can control drug delivery, enhance solubilization, increase efficacy and improve pharmacokinetics. Here, Grinstaff, Colson and Ekladious discuss recent advances in the preclinical
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Post-GWAS in prostate cancer: from genetic association to biological contribution Post-GWAS in prostate cancer: from genetic association to biological contribution, Published online: 11 December 2018; doi:10.1038/s41568-018-0087-3 This Review discusses causal germline variants in prostate cancer identified through genome-wide association studies (GWAS) and post-GWAS analyses. The latter are vital to identify causal variants and molecular mechanisms
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The lung microenvironment: an important regulator of tumour growth and metastasis The lung microenvironment: an important regulator of tumour growth and metastasis, Published online: 10 December 2018; doi:10.1038/s41568-018-0081-9 In this Review, Altorki et al. discuss how the tumour-reprogrammed lung microenvironment can contribute to primary lung tumour progression as well as lung metastasis from extrapulmonary neoplasms
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Dynamics and functions of lipid droplets Dynamics and functions of lipid droplets, Published online: 06 December 2018; doi:10.1038/s41580-018-0085-z Lipid droplets are storage organelles that are important for the regulation of lipid and energy homeostasis, and that serve as buffers against lipotoxicity. Recent studies on the biology of lipid droplets have led to new discoveries about
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Non-nociceptive roles of opioids in the CNS: opioids’ effects on neurogenesis, learning, memory and affect Non-nociceptive roles of opioids in the CNS: opioids’ effects on neurogenesis, learning, memory and affect, Published online: 05 December 2018; doi:10.1038/s41583-018-0092-2 Maladaptive modulation of learning, memory and affect by opioids is linked to dysfunctional neurogenesis. In this Review, Kibaly and
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Prisoners of war — host adaptation and its constraints on virus evolution Prisoners of war — host adaptation and its constraints on virus evolution, Published online: 05 December 2018; doi:10.1038/s41579-018-0120-2 Studies of ancient DNA and endogenous viral elements have revealed extraordinary conservation of virus genome sequences over thousands or millions of years. In this Opinion
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Therapeutic strategies for sickle cell disease: towards a multi-agent approach Therapeutic strategies for sickle cell disease: towards a multi-agent approach, Published online: 04 December 2018; doi:10.1038/s41573-018-0003-2 Although the molecular basis for sickle cell disease (SCD) has been known for decades, progress in developing therapies that ameliorate the complex systemic manifestations of SCD has been slow.
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Non-invasive delivery strategies for biologics Non-invasive delivery strategies for biologics, Published online: 30 November 2018; doi:10.1038/nrd.2018.183 The requirement for delivery by injection is currently a limitation for the use of biologic drugs such as antibodies. In this Review, Mitragotri and colleagues discuss advances made in non-invasive drug delivery for biologics, including the transdermal, oral and
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Therapeutic potential of ectopic olfactory and taste receptors Therapeutic potential of ectopic olfactory and taste receptors, Published online: 30 November 2018; doi:10.1038/s41573-018-0002-3 Olfactory and taste receptors are ectopically expressed in multiple extra-nasal and extra-oral tissues, exhibiting potential functions in a diverse range of biological processes. Here, Lee et al. discuss the physiological roles of these
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The value of genetic testing for family health history of adopted persons The value of genetic testing for family health history of adopted persons, Published online: 29 November 2018; doi:10.1038/s41576-018-0080-4 The lack of family health history experienced by most adopted persons can represent a marked disadvantage for these individuals. Genetic testing has the potential to
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Host and viral determinants of influenza A virus species specificity Host and viral determinants of influenza A virus species specificity, Published online: 28 November 2018; doi:10.1038/s41579-018-0115-z Influenza A viruses cause pandemics when they cross between species. In this Review, Barclay and colleagues examine the host barriers that influenza A viruses must overcome to initiate a
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Clinical epigenetics: seizing opportunities for translation Clinical epigenetics: seizing opportunities for translation, Published online: 27 November 2018; doi:10.1038/s41576-018-0074-2 Disruptions to the epigenome occur during the pathogenesis of various human diseases. In this Review, Berdasco and Esteller describe the challenges and progress of harnessing epigenetic changes for clinical application, including for diagnostics, disease classification and therapeutics.
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Cooperation among cancer cells: applying game theory to cancer Cooperation among cancer cells: applying game theory to cancer, Published online: 23 November 2018; doi:10.1038/s41568-018-0083-7 This Opinion argues that understanding the interactions between cells that occur in tumours requires concepts from evolutionary game theory. Game theory can provide insights into the stability of cooperation among cells
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Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases, Published online: 22 November 2018; doi:10.1038/s41583-018-0093-1 Necroptosis is a form of cell death mediated by receptor-interacting protein kinase 1 (RIPK1), and is observed in several CNS disorders. Here, Yuan, Amin and Ofengeim give an overview of necroptosis in the CNS and
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Mitochondria as central regulators of neural stem cell fate and cognitive function Mitochondria as central regulators of neural stem cell fate and cognitive function, Published online: 21 November 2018; doi:10.1038/s41583-018-0091-3 Neural stem and progenitor cells can be regulated through mitochondrial signalling mechanisms and this has major implications in physiological and pathological conditions. In this Review,
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Rhythms of life: circadian disruption and brain disorders across the lifespan Rhythms of life: circadian disruption and brain disorders across the lifespan, Published online: 20 November 2018; doi:10.1038/s41583-018-0088-y Many neurobiological processes are regulated on a circadian basis. Circadian rhythms change during development, into adulthood and with ageing, when certain disorders typically emerge. Here, Logan and
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New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer, Published online: 20 November 2018; doi:10.1038/s41580-018-0080-4 Epithelial–mesenchymal transition (EMT) is crucial for embryogenesis, wound healing and cancer development, and confers greater resistance to cancer therapies. This Review discusses the mechanisms of
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N6-mA marks the spot <i>N</i><sup>6</sup>-mA marks the spot, Published online: 19 November 2018; doi:10.1038/s41568-018-0085-5 Xie et al. have shown that a recently reported DNA modification in mammals, repressive N6-methyladenine, is enriched in human glioblastoma and targeting this modification can reduce cancer cell growth by restricting chromatin accessibility at oncogenic loci.
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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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