| | Lagging-strand replication shapes the mutational landscape of the genome
The emRiboSeq sequencing method is used to track polymerase activity genome-wide in vivo; despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-α (Pol-α) is retained in vivo and comprises ∼1.5% of the genome, establishing Pol-α as an important source of genomic variability and providing a mechanism for site-specific variation in nucleotide substitution rates.
| Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation
Parasites of the Theileria genus infect cattle and transform their host cells, a transformation that can be reversed by treatment with the drug buparvaquone; here, a Theileria homologue of the peptidyl-prolyl isomerase PIN1 is shown to be secreted into the host cell, where it promotes transformation and can be directly inhibited by buparvaquone.
| β-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis
The monocyclic β-lactam rings of the nocardicin family of antibiotics are biosynthesized by an unprecedented activity of non-ribosomal peptide synthetases, a mechanism that is distinct from the pathways to the other classes of β-lactam antibiotics.
| Thirst driving and suppressing signals encoded by distinct neural populations in the brain
Two genetically distinct populations of neurons in the subfornical organ of mice can either induce thirst and water-seeking behaviour or suppress thirst, regardless of the hydration status of the animal.
| Hydrogens detected by subatomic resolution protein crystallography in a [NiFe] hydrogenase
A sub-ångström-resolution X-ray crystal structure of [NiFe] hydrogenase, with direct detection of the products of the heterolytic splitting of dihydrogen into a hydride bridging the Ni and Fe and a proton attached to the sulphur of a cysteine ligand.
| EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors
A subset of lung cancer cells with EGFR or BRG1 mutations shows selective sensitivity to a combination of EZH2 inhibitors with topoisomerase II inhibitors such as the commonly used chemotherapeutic drug etoposide.
| Levantine cranium from Manot Cave (Israel) foreshadows the first European modern humans
A partial skull from northern Israel dated to be from around 55,000 years ago sheds light on a crucial but little-known period of prehistory: the spread of anatomically modern humans from Africa.
| 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.
| | Erratum: Antarctic glaciation caused ocean circulation changes at the Eocene–Oligocene transition | | | | | | Chronic Lymphocytic Leukemia: Recent advances in biology and therapy
Access this new Collection from Leukemia available free online for six months.
Produced with support from: Janssen Pharmaceuticals Companies of Johnson & Johnson | | | | | | | | | | | | | Forcing, feedback and internal variability in global temperature trends
A study of the effect of radiative forcing, climate feedback and ocean heat uptake on global-mean surface temperature indicates that overestimation of the response of climate models to radiative forcing from increasing greenhouse gas concentrations is not responsible for the post-1998 discrepancy between model simulations and observations.
Jochem Marotzke, Piers M. Forster | Comprehensive genomic characterization of head and neck squamous cell carcinomas OPEN
The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.
The Cancer Genome Atlas Network | Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
The CRISPR-Cas9 system, a powerful tool for genome editing, has been engineered to activate endogenous gene transcription specifically and potently on a genome-wide scale and applied to a large-scale gain-of-function screen for studying melanoma drug resistance.
Silvana Konermann, Mark D. Brigham, Alexandro E. Trevino et al. | An Arabidopsis gene regulatory network for secondary cell wall synthesis
The full complement of transcriptional regulators that affect synthesis of the plant secondary cell wall remains largely undetermined; here, the network of protein–DNA interactions controlling secondary cell wall synthesis of Arabidopsis thaliana is determined, showing that gene expression is regulated by a series of feed-forward loops to ensure that the secondary cell wall is deposited at the right time and in the right place.
M. Taylor-Teeples, L. Lin, M. de Lucas et al. | | A spin-down clock for cool stars from observations of a 2.5-billion-year-old cluster
The measurement of the rotational periods of 30 cool stars in the 2.5-billion-year-old cluster NGC 6819 allows the calibration of gyrochronology — the determination of a star's age on the basis of its rotation period — over a much broader age range than hitherto, meaning that it might be possible to determine the ages of many cool stars in the Galactic field with a precision of roughly 10 per cent.
Søren Meibom, Sydney A. Barnes, Imants Platais et al. | Michelson–Morley analogue for electrons using trapped ions to test Lorentz symmetry
An electronic analogue of a Michelson–Morley experiment, in which an electron wave packet bound inside a calcium ion is split into two parts and subsequently recombined, demonstrates that the relative change in orientation of the two parts that results from the Earth's rotation reveals no anisotropy in the electron dispersion; this verification of Lorentz symmetry improves on the precision of previous tests by a factor of 100.
T. Pruttivarasin, M. Ramm, S. G. Porsev et al. | Anomalous dispersions of 'hedgehog' particles
Micrometre-sized particles covered with stiff, nanoscale spikes are shown to exhibit long-term colloidal stability in both hydrophilic and hydrophobic media, without the need for chemical coating, owing to the effect of the spikes on the contact area and, consequently, the force between the particles.
Joong Hwan Bahng, Bongjun Yeom, Yichun Wang et al. | Metal-catalysed azidation of tertiary C–H bonds suitable for late-stage functionalization
Most currently used catalysts for the amination of C–H bonds are ill suited to the functionalization of complex molecules; here it is shown that a mild, selective, iron-catalysed azidation of tertiary C–H bonds is suitable for the amination of complex molecules containing a range of functional groups.
Ankit Sharma, John F. Hartwig | p63+Krt5+ distal airway stem cells are essential for lung regeneration
Many patients experiencing sudden loss of lung tissue somehow undergo full recovery; here this recovery is traced to a discrete population of lung stem cells that are not only essential for lung regeneration but can be cloned and then transplanted to other mice to contribute new lung tissue.
Wei Zuo, Ting Zhang, Daniel Zheng'An Wu et al. | IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo
p53 is often mutated or lost in cancer; here inactivation of ΔNp63 and ΔNp73 in the absence of p53 is shown to result in metabolic reprogramming and tumour regression via activation of IAPP (islet amyloid polypeptide or amylin), and IAPP-based anti-diabetes therapeutic strategies show potential for the treatment of p53-deficient and mutant tumours.
Avinashnarayan Venkatanarayan, Payal Raulji, William Norton et al. | Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide
Time--β bound to substrate DNA as it inserts 8-oxo-dGTP opposite either cytosine or adenine.
Bret D. Freudenthal, William A. Beard, Lalith Perera et al. | Interception of host angiogenic signalling limits mycobacterial growth
Using a model of tuberculosis in zebrafish, granuloma formation is shown to coincide with hypoxia and angiogenesis; furthermore, the pharmacological inhibition of the pro-angiogenic VEGF pathway reduces infection burden, suggesting a possible treatment strategy in patients with the disease.
Stefan H. Oehlers, Mark R. Cronan, Ninecia R. Scott et al. | Structural insight into autoinhibition and histone H3-induced activation of DNMT3A
A working model for histone H3-induced dynamic regulation of the de novo DNA methyltransferase.
Xue Guo, Ling Wang, Jie Li et al. | Resolving the complexity of the human genome using single-molecule sequencing
Single-molecule, real-time DNA sequencing is used to analyse a haploid human genome (CHM1), thus closing or extending more than half of the remaining 164 euchromatic gaps in the human genome; the complete sequences of euchromatic structural variants (including inversions, complex insertions and tandem repeats) are resolved at the base-pair level, suggesting that a greater complexity of the human genome can now be accessed.
Mark J. P. Chaisson, John Huddleston, Megan Y. Dennis et al. | The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C
By binding and inhibiting a second CDC20 molecule, the mitotic checkpoint complex can convert a local 'wait' signal from unattached kinetochores to inhibit the anaphase promoting complex/cyclosome throughout the cell and avoid premature cell division.
Daisuke Izawa, Jonathon Pines | Effects of electron correlations on transport properties of iron at Earth's core conditions
Based on first-principles resistivity calculations, it was recently concluded that the thermal conductivity of iron in Earth's core was too high to sustain thermal convection, thus invalidating such geodynamo models; new calculations including electron correlations find that electron–electron scattering is comparable to the electron–phonon scattering at high temperatures in iron, doubling the expected resistivity, and reviving conventional geodynamo models.
Peng Zhang, R. E. Cohen, K. Haule | Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury
Lineage-tracing experiments identify a rare, undifferentiated population of quiescent cells in the mouse distal lung that are activated through a Notch signalling pathway to repair the epithelium after bleomycin- or influenza-mediated injury; inappropriate Notch signalling may be a major contributor to failed regeneration within the lungs of patients with chronic lung disease.
Andrew E. Vaughan, Alexis N. Brumwell, Ying Xi et al. | | | | |
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