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Cardiac biology: A protein for healing infarcted hearts
Human heart tissue has minimal ability to regenerate following injury. But the protein Fstl1, which is normally expressed in the heart's epicardial region, has now been shown to induce regeneration following heart attack.
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Nanotechnology: Platelet mimicry
Cloaking drug-loaded nanoparticles with platelet membranes enhances the drugs' abilities to target desired cells and tissues. This technology might improve treatments for cardiovascular and infectious diseases.
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Immunology: Caspase target drives pyroptosis
Inflammatory caspase proteins help to control pathogen replication by triggering pyroptotic cell death. It now emerges that cleavage of the caspase substrate gasdermin D is sufficient to induce pyroptosis.
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The UK10K project identifies rare variants in health and disease OPEN
Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.
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Epicardial FSTL1 reconstitution regenerates the adult mammalian heart
The secreted factor follistatin-like 1 (FSTL1) becomes undetectable in the epicardium of infarcted hearts; when reconstituted using a collagen patch sutured onto an infarcted heart, FSTL1 can induce cell cycle entry and division of pre-existing cardiomyocytes, thus boosting heart function and survival in mouse and pig models of myocardial infarction.
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Single cell activity reveals direct electron transfer in methanotrophic consortia
The anaerobic oxidation of methane in marine sediments is performed by consortia of methane-oxidizing archaea and sulfate-reducing bacteria; an examination of the role of interspecies spatial positioning on single cell activity reveals that interspecies electron transfer may overcome the requirement for close spatial proximity, a proposition supported by large multi-haem cytochromes in ANME-2 genomes as well as redox-active electron microscopy staining.
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Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
CRISPR-Cas9 genome-editing screens identify gasdermin D as a substrate for inflammatory caspases, and its N-terminal cleavage fragment, as well as the equivalent regions in other gasdermins, is shown to be capable of inducing pyroptosis.
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BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
A CRISPR-Cas9 approach is used to perform saturating mutagenesis of the human and mouse BCL11A enhancers, producing a map that reveals critical regions and specific vulnerabilities; BCL11A enhancer disruption is validated by CRISPR-Cas9 as a therapeutic strategy for inducing fetal haemoglobin by applying it in both mice and primary human erythroblast cells.
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The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015
In this study, the authors present an analysis of the malaria burden in sub-Saharan Africa between 2000 and 2015, and quantify the effects of the interventions that have been implemented to combat the disease; they find that the prevalence of Plasmodium falciparum infection has been reduced by 50% since 2000 and the incidence of clinical disease by 40%, and that interventions have averted approximately 663 million clinical cases since 2000, with insecticide-treated bed nets being the largest contributor.
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Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture
Human population genomic studies, including whole‐genome sequencing, were undertaken to identify determinants of bone mineral density (BMD), a major predictor of osteoporotic fractures. Non‐coding variants with large effects on BMD and fractures were identified near the EN1 locus and mouse studies confirmed this gene has an important role in skeletal biology.
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BET inhibitor resistance emerges from leukaemia stem cells
BET inhibitors that target bromodomain chromatin readers such as BRD4 are being explored as potential therapeutics in cancer; here, in a MLL–AF9 mouse leukaemia model, resistance to BET inhibitors is shown to emerge from leukaemia stem cells, and be partly due to increased Wnt/β-catenin signalling.
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Transcriptional plasticity promotes primary and acquired resistance to BET inhibition
BET bromodomain inhibitors are being explored as potential therapeutics in cancer; here, AML cells are shown to evade sensitivity to BET inhibition through rewiring the transcriptional regulation of BRD4 target genes such as MYC in a process that is facilitated by suppression of PRC2 and WNT signalling activation.
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A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials
The complex anti-HIV alkaloid (+)-batzelladine B is efficiently synthesized by using aromatic heterocycles as synthetic precursors.
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Lithospheric controls on magma composition along Earth’s longest continental hotspot track
A 2,000-kilometre-long volcanic hotspot track is identified in eastern Australia, along which magma composition and volcanic outcrop show a strong correlation with lithospheric thickness, providing an observational constraint on the sub-continental melting depth of mantle plumes.
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Novel competitors shape species’ responses to climate change
Species’ range dynamics depend not only on their ability to track climate, but also on the migration of their competitors, and the extent to which novel and current competitors exert differing competitive effects.
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Neutrophil ageing is regulated by the microbiome
Neutrophil ageing, which encourages inflammation and vaso-occlusion in a mouse model of sickle-cell disease, is shown to depend on the intestinal microbiota and activation of the TLR/Myd88 signalling pathways.
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Nanoparticle biointerfacing by platelet membrane cloaking
The authors report a new biomimetic nanodelivery platform in which polymeric nanoparticles enclosed in the plasma membrane of human platelets are used for disease-relevant targeting, and the therapeutic potential of the concept is demonstrated in animal models of coronary restenosis and systemic bacterial infection.
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A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion
Sexual dimorphism in neuronal circuits is proposed to underlie sex differences in behaviour, such as virgin female mice acting maternally toward alien pups, while males ignore or attack them; here the authors show that specific tyrosine hydroxylase-expressing neurons in the hypothalamus are more numerous in mothers than in virgin females and males, and that they control parental behaviour in a sex-specific manner.
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Erratum: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
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Corrigendum: Selective killing of cancer cells by a small molecule targeting the stress response to ROS
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Labelling and optical erasure of synaptic memory traces in the motor cortex
A new light-activated probe that targets recently active neuronal spines for manipulation induces shrinkage of recently potentiated spines following a motor learning task; spine shrinkage disrupted learning, suggesting a causal relationship between the specific subset of targeted spines and the learned behaviour.
Akiko Hayashi-Takagi, Sho Yagishita, Mayumi Nakamura et al. |
Panorama of ancient metazoan macromolecular complexes
Using biochemical fractionation and mass spectrometry, animal protein complexes are identified from nine species in parallel, and, along with genome sequence information, complex conservation is investigated and over one million protein–protein interactions are predicted in 122 eukaryotes.
Cuihong Wan, Blake Borgeson, Sadhna Phanse et al. |
The mechanism of DNA replication termination in vertebrates
This study describes a new model of eukaryotic replication termination in which converging leading strands pass each other unhindered and the replicative DNA helicase is unloaded late, after all strands have been ligated.
James M. Dewar, Magda Budzowska, Johannes C. Walter |
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Designing switchable polarization and magnetization at room temperature in an oxide
Ferroelectricity and ferromagnetism are combined in a bulk perovskite oxide at room temperature by constructing a percolating network of interacting magnetic ions within a complex polar solid.
P. Mandal, M. J. Pitcher, J. Alaria et al. |
Replisome speed determines the efficiency of the Tus−Ter replication termination barrier
The Tus–Ter termination site of Escherichia coli is not completely efficient in stopping DNA replication, with about half of replisomes bypassing this blockade; here the speed of the replication machinery is shown to determine the outcome of the encounter between the replisome and Tus–Ter.
Mohamed M. Elshenawy, Slobodan Jergic, Zhi-Qiang Xu et al. |
Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists
Although imatinib gives good clinical results in chronic myeloid leukaemia (CML), residual disease attributed to quiescent CML stem cells remains in many patients; here glitazones are shown to reduce the pool of CML stem cells and achieve lasting disease eradication in CML patients in combination with imatinib.
Stéphane Prost, Francis Relouzat, Marc Spentchian et al. |
Integrator mediates the biogenesis of enhancer RNAs
This study demonstrates a role for the Integrator complex in the stimulus-dependent induction of eRNAs and their 3′ processing; together with previously known roles of Integrator in transcription elongation and RNA processing, these results indicate that Integrator has broad functions in the regulation of eukaryotic gene expression.
Fan Lai, Alessandro Gardini, Anda Zhang et al. |
Relativistic boost as the cause of periodicity in a massive black-hole binary candidate
The amplitude and sinusoid-like shape of the optical variability of the light curve of PG 1302-102 is best fitted by relativistic Doppler boosting of emission from a compact, steadily accreting, unequal-mass binary, which is consistent with archival ultraviolet data, and suggests the existence of a binary black hole in the relativistic regime.
Daniel J. D'Orazio, Zoltán Haiman, David Schiminovich |
Spawning rings of exceptional points out of Dirac cones
Exceptional points are singularities in non-Hermitian systems that can produce unusual effects, and it is shown that a Dirac cone in a photonic crystal can generate a continuous ring of exceptional points through flattening the tip of the cone.
Bo Zhen, Chia Wei Hsu, Yuichi Igarashi et al. |
Inhomogeneity of charge-density-wave order and quenched disorder in a high-Tc superconductor
Micro X-ray diffraction imaging of the spatial distribution of charge-density-wave puddles and quenched disorder in HgBa2CuO4 + y reveals a complex, inhomogeneous spatial landscape due to the interplay between charge and dopant order.
G. Campi, A. Bianconi, N. Poccia et al. |
The contribution of outdoor air pollution sources to premature mortality on a global scale
Investigation of premature mortality by seven emission sources of atmospheric pollutants shows that outdoor air pollution, mostly by fine particulate matter, leads to more than three million premature deaths per year worldwide, which could double by 2050.
J. Lelieveld, J. S. Evans, M. Fnais et al. |
Non-adaptive plasticity potentiates rapid adaptive evolution of gene expression in nature
Experimentally transplanting guppies to evolve in a novel, predator-free environment reveals that the direction of plasticity in gene expression is usually opposite to the direction of adaptive evolution; that is, those genes whose expression changes are disadvantageous are more strongly selected upon than those whose changes are advantageous.
Cameron K. Ghalambor, Kim L. Hoke, Emily W. Ruell et al. |
A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence
Untargeted metabolomics and coexpression analysis uncovers the complete biosynthetic pathway of a previously unknown Arabidopsis metabolite, 4-hydroxyindole-3-carbonyl nitrile (4-OH-ICN), which harbours cyanogenic functionality.
Jakub Rajniak, Brenden Barco, Nicole K. Clay et al. |
The spliceosome is a therapeutic vulnerability in MYC-driven cancer
Splicing factors such as BUD31 are identified in a synthetic-lethal screen with cells overexpressing the transcription factor MYC; oncogenic MYC leads to an increase in pre-mRNA synthesis, and spliceosome inhibition impairs the growth and tumorigenicity of MYC-dependent breast cancers, suggesting that spliceosome components may be potential therapeutic targets for MYC-driven cancers.
Tiffany Y.-T. Hsu, Lukas M. Simon, Nicholas J. Neill et al. |
Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6
The Tet2 enzyme, which catalyses de novo hydroxymethylation of DNA, is shown here to act as a transcriptional repressor by recruiting the histone deacetylase Hdac2 to the Il6 promoter in the course of resolution of the LPS-induced inflammatory response.
Qian Zhang, Kai Zhao, Qicong Shen et al. |
Crystal structure of the dynamin tetramer
The crystal structure of the large GTPase dynamin tetramer is presented, suggesting a mechanism by which oligomerization of dynamin is regulated, and revealing how mutations that interfere with tetramer formation and autoinhibition are of relevance to understanding the congenital muscle disorders Charcot–Marie–Tooth neuropathy and centronuclear myopathy.
Thomas F. Reubold, Katja Faelber, Nuria Plattner et al. |
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