| | Stem cells: Chasing blood
Many experiments have probed the mechanisms by which transplanted stem cells give rise to all the cell types of the blood, but it emerges that the process is different in unperturbed conditions. | Evolution of Darwin’s finches and their beaks revealed by genome sequencing
Comprehensive genome sequencing of 120 individuals representing all of the Darwin’s finch species and two close relatives reveals important discrepancies with morphology-based taxonomy, widespread hybridization, and a gene, ALX1, underlying variation in beak shape. | Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation
A large ex vivo screen of approved and investigational anti-cancer drugs in primary cells derived from CML and ALL patients identifies axitinib, a VEGFR inhibitor approved for the treatment of kidney cancer, as a potent inhibitor of BCR–ABL1(T315I) with unique binding interactions that overcome the gatekeeper resistance mutation, highlighting the potential of repurposing existing drugs for additional cancer types. | The double-degenerate, super-Chandrasekhar nucleus of the planetary nebula Henize 2-428
The probable evolution of the planetary nebula Henize 2-428 is examined, from a close binary system in which both stars ejected their envelopes to the white dwarf stage with a short orbital period and combined mass above the Chandrasekhar limit, suggesting that the system should merge in about 700 million years and trigger a type Ia supernova. | Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9
Crystal structures of three forms of Toll-like receptor (TLR) 9 — unliganded or bound either to immune stimulatory CpG-containing DNA or inhibitory DNA — together reveal the molecular basis of TLR9 activation. | X-domain of peptide synthetases recruits oxygenases crucial for glycopeptide biosynthesis
Glycopeptide antibiotics are biosynthesized by non-ribosomal peptide synthetases, which contain a previously uncharacterized ‘X-domain’ now shown to recruit three cytochrome P450 oxygenases that are necessary for the antibiotics to achieve their final, active conformation. | ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes
The essential autophagy mediator ATG14 promotes vesicle fusion by forming homo-oligomers, which bind to a component of the SNARE membrane fusion complex and stabilize this complex on autophagosomes. | Fundamental properties of unperturbed haematopoiesis from stem cells in vivo
Inducible genetic labelling of haematopoietic stem cells (HSCs) and linked mathematical modelling show that at least 30% of all HSCs are productive, and that adult haematopoiesis is largely sustained by ‘short-term’ downstream stem cells that operate near self-renewal in the steady state; HSC fate mapping provides a quantitative model for better understanding of HSC functions in health and disease. | | Erratum: Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation | | New genetic loci link adipose and insulin biology to body fat distribution
Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.
A list of authors and their affiliations appears at the end of the paper, Dmitry Shungin, Thomas W. Winkler et al. | Genetic studies of body mass index yield new insights for obesity biology
A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.
A list of authors and their affiliations appears at the end of the paper, Adam E. Locke, Bratati Kahali et al. | Shearing-induced asymmetry in entorhinal grid cells
Grid cells are cells of the brain’s internal map of space that fire when an animal is in a location corresponding to the vertices of a hexagonal grid pattern tiling the entire environment; how the pattern is mapped onto the external environment has remained a mystery, however, new studies in rat reveal that the axes of the grid are determined by the boundaries of the external environment and provide insight into the rotation of the grid axis in relation to these boundaries.
Tor Stensola, Hanne Stensola, May-Britt Moser et al. | | RNA helicase DDX21 coordinates transcription and ribosomal RNA processing
DEAD-box RNA helicase DDX21 is involved in both the transcription and RNA processing of ribosomal genes in human cells, sensing the transcriptional status of both RNA polymerase I and RNA polymerase II and associating with non-coding RNAs involved in ribonucleoprotein formation, possibly allowing for coordinated regulation of protein synthesis.
Eliezer Calo, Ryan A. Flynn, Lance Martin et al. | Comet 67P/Churyumov-Gerasimenko sheds dust coat accumulated over the past four years
Grains collected from comet 67P/Churyumov-Gerasimenko by the Rosetta mission come from a dusty crust that is predicted to be imminently shed as the comet nears the Sun; the grains are high in sodium and fluffy, not icy, suggesting that they are the precursors of interplanetary dust particles.
Rita Schulz, Martin Hilchenbach, Yves Langevin et al. | Apico-basal forces exerted by apoptotic cells drive epithelium folding
Apoptotic cell death is required for morphogenesis of the developing leg joint of fruitflies; using this model system, the authors show here that within apoptotic cells a transient pulling force exerted through a highly dynamic apico-basal myosin II cable-like structure acts as a mechanical signal to increase tissue tension and modify tissue shape.
Bruno Monier, Melanie Gettings, Guillaume Gay et al. | RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration
Structural synaptic plasticity and remodelling are features of the healthy adult brain and are seen during hibernation; a hibernation-inspired model of mouse cooling used to study synaptic regeneration has identified the ‘cold-shock’ RNA-binding protein, RBM3, as a regulator of synaptic assembly, deficiency of which contributes to synapse loss in neurodegenerative disease.
Diego Peretti, Amandine Bastide, Helois Radford et al. | The formation of a quadruple star system with wide separation
Observations of a wide-separation quadruple system in the Perseus star-forming region reveal a young protostar and three gravitationally bound dense gas condensations; each condensation is expected to form a star and the closest pair will form a bound binary, while the quadruple stellar system itself is bound but unstable on timescales of 500,000 years.
Jaime E. Pineda, Stella S. R. Offner, Richard J. Parker et al. | Grid cell symmetry is shaped by environmental geometry
Neuronal grid cells fire in a spatial grid pattern laid out across the surface of a familiar environment, however the role of environmental boundaries in the construction of this pattern is not well understood; this study shows that the grid pattern orients to the walls of polarized environments such as squares but not circles and that the hexagonal grid symmetry is permanently broken in highly polarized environments such as trapezoids.
Julija Krupic, Marius Bauza, Stephen Burton et al. | Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair
In studies in mammalian cells, polymerase theta (Polθ, also known as POLQ) is identified as the polymerase responsible for non-homologous end joining DNA repair; this DNA repair pathway acts in many tumours when homologous recombination is inactivated and the identification of the polymerase responsible may aid the development of new therapeutic approaches.
Raphael Ceccaldi, Jessica C. Liu, Ravindra Amunugama et al. | Homo erectus at Trinil on Java used shells for tool production and engraving
Argon and luminescence dating of fossil shell infills from Trinil in Java, where Homo erectus lived, reveals that the hominin-bearing deposits are younger than previously thought; perforated shells, a shell tool and an engraved shell indicate that Homo erectus ate freshwater mussels, used their shells as tools and was able to create abstract engravings.
Josephine C. A. Joordens, Francesco d’Errico, Frank P. Wesselingh et al. | Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor
A study of genome evolution in a metastatic breast cancer bearing an activating PIK3CA mutation, following treatment with the PI(3)Kα inhibitor BYL719, shows that all metastatic lesions, when compared to the pre-treatment tumour, had lost a copy of PTEN; parallel genetic evolution of separate sites with different PTEN genomic alterations had led to a convergent PTEN-null phenotype resistant to PI(3)Kα inhibition.
Dejan Juric, Pau Castel, Malachi Griffith et al. | Recharge of a subglacial lake by surface meltwater in northeast Greenland
Observations of rapid, persistent elevation gains that occur on the ice surface above a subglacial lake as the lake is refilled with surface meltwater during the summer melt period in Greenland show that surface meltwater may be trapped and stored at the bed of an ice sheet, affecting ice dynamics downstream.
Michael J. Willis, Bradley G. Herried, Michael G. Bevis et al. | Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination
Next-generation sequencing technology is used to show that the error-prone polymerase θ (Polθ) is needed to promote alternative non-homologous end joining at telomeres, and during chromosomal translocations, while counteracting homologous recombination; inhibition of Polθ represents a potential therapeutic strategy for tumours that have mutations in homology-directed repair genes.
Pedro A. Mateos-Gomez, Fade Gong, Nidhi Nair et al. | Boron isotope evidence for oceanic carbon dioxide leakage during the last deglaciation
The boron isotope pH proxy in sediment-core planktic foraminifera is used as a tracer of oceanic CO2 outgassing to show that surface waters which derive partly from deep water upwelled in the Southern Ocean became a significant source of carbon to the atmosphere during the last deglaciation.
M. A. Martínez-Botí, G. Marino, G. L. Foster et al. | | | | |
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