| | Cancer: Mutant p53 and chromatin regulation
The finding that genes encoding enzymes that modify histone proteins are among the targets of certain mutant forms of the p53 protein sheds light on how these mutations cause cancer beyond p53 inactivation.
| Cancer: Repositioned to kill stem cells
Chemotherapy-resistant cancer stem cells make it hard to cure many forms of the disease. Repositioning an existing drug to tackle this problem could significantly improve treatment for one form of leukaemia.
| Evolutionary biology: Perplexing effects of phenotypic plasticity
Research on guppies provides evidence that phenotypic plasticity — an organism's ability to alter its characteristics in response to changes in the environment — can both constrain and facilitate adaptive evolution.
| Economics: Simple market models fail the test
An analysis of energy markets with prices that vary according to demand finds that this market design unexpectedly serves to amplify, rather than dampen, fluctuations in power use.
| 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.
| Mapping tree density at a global scale
Ground-sourced tree density data is assembled to provide a global map of tree density, which reveals that there are three trillion trees (tenfold more than previous estimates); tree numbers have declined by nearly half since the start of human civilization and over 15 billion trees are lost on an annual basis.
| Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth
A ChIP-seq analysis of the DNA-binding properties of mutant gain-of-function p53 protein compared to wild-type p53 reveals the gain-of-function proteins bind to and activate a distinct set of genes including chromatin modifying enzymes such as the histone methyltransferase MLL; small molecular inhibitors of MLL function may represent a new target for cancers with mutant p53.
| Arithmetic and local circuitry underlying dopamine prediction errors
Dopamine neurons in the ventral tegmental area calculate reward prediction error by subtracting input from neighbouring GABA neurons.
| η-Secretase processing of APP inhibits neuronal activity in the hippocampus
A new pathway for the processing of β-amyloid precursor protein (APP) is described in which η-secretase activity, in part mediated by the MT5-MMP metalloproteinase, cleaves APP, and further processing by ADAM10 and BACE1 generates proteolytic fragments capable of inhibiting long-term potentiation in the hippocampus.
| 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.
| Quadrature squeezed photons from a two-level system
Measurements of a steady emission of single photons from a quantum dot demonstrate that the fluctuations of the electric field can periodically be 3% below the fundamental quantum limit and confirm the long-standing prediction that the quantum state of single photons can be squeezed.
| Computational design of co-assembling protein–DNA nanowires
Computational protein design is used to create a protein–DNA co-assembling nanomaterial; by varying the arrangement of protein-binding sites on the double-stranded DNA, a 'nanowire' with single-molecule width can be spontaneously formed by mixing the protein and double-stranded DNA building blocks.
| Real-time observation of the initiation of RNA polymerase II transcription
A single-molecule optical tweezer assay is developed to monitor transcription initiation in eukaryotic RNA polymerase II in real-time, making use of a highly purified preinitiation complex (PIC) from yeast; observations show that a large bubble is opened up in the DNA template during initiation, driven by the TFIIH helicase that forms part of the PIC, along with synthesis of an extended transcript before the transition from transcription initiation into elongation.
| Distinct EMT programs control normal mammary stem cells and tumour-initiating cells
This study finds that the epithelial-to-mesenchymal (EMT) transition program, which is common to both mammary gland reconstituting stem cells and mammary tumour-initiating cells, is differentially regulated by two distinct EMT factors, Slug and Snail; the findings illustrate that although they appear similar, normal tissue stem cells and tumour-initiating cells are controlled by distinct regulatory processes.
| Evolutionary origin of the turtle skull
Computed tomography and phylogenetic analysis of the Eunotosaurus africanus skull suggests that not only is Eunotosaurus an early relative of the group that eventually evolved into turtles, but that it is also a diapsid caught in the act of evolving towards a secondarily anapsid state.
| 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.
| 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.
| 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.
| | The quiet revolution of numerical weather prediction
The cumulative progress of numerical weather prediction represents one of the most remarkable successes of modern science; here the many technological and scientific advances that have brought NWP to its present level are reviewed, as are the considerable challenges for the future.
Peter Bauer, Alan Thorpe, Gilbert Brunet | | The C9orf72 repeat expansion disrupts nucleocytoplasmic transport
A candidate-based genetic screen in Drosophila expressing 30 G4C2-repeat-containing RNAs finds that RanGAP, a key regulator of nucleocytoplasmic transport, is a potent suppressor of neurodegeneration; the defects caused by the G4C2 repeat expansions can be rescued with antisense oligonucleotides or small molecules targeting the G-quadruplexes.
Ke Zhang, Christopher J. Donnelly, Aaron R. Haeusler et al. | Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis
The first crystal structures of complexes between synaptotagmin-1 and neuronal SNARE, bound to either Ca2+ or Mg2+, are described, and show that Ca2+-triggered neurotransmitter release relies on a large, Ca2+-independent interface.
Qiangjun Zhou, Ying Lai, Taulant Bacaj et al. | Structural insights into the bacterial carbon–phosphorus lyase machinery
The crystal structure of the 240-kilodalton C–P lyase core complex from the bacterium E. coli offers insights into the relatively unknown mechanisms of the enzymatic machinery that allows some microbes to extract phosphate from phosphonate compounds.
Paulina Seweryn, Lan Bich Van, Morten Kjeldgaard et al. | | Conventional superconductivity at 203 kelvin at high pressures in the sulfur hydride system
Conventional superconductivity is observed at 203 kelvin in the sulfur hydride system, well above the highest superconducting transition temperature obtained in the copper oxides, raising hopes that even higher transition temperatures will be discovered in other hydrogen-rich systems.
A. P. Drozdov, M. I. Eremets, I. A. Troyan et al. | Negative refractive index and acoustic superlens from multiple scattering in single negative metamaterials
A negative refractive index, a property that does not exist in natural materials, can be produced in so-called metamaterials by combining two building blocks; here it is shown that it is possible to design and fabricate a metamaterial with a negative refractive index that consists of only one type of building block by taking advantage of its crystalline structure, and this approach is demonstrated through an acoustic superlens.
Nadège Kaina, Fabrice Lemoult, Mathias Fink et al. | Guiding the folding pathway of DNA origami
Probing the assembly process that occurs when single-stranded DNA is folded into desired shapes by 'DNA origami' shows that it can be guided by controlling the strengths of local and long-range interactions, enabling more reproducible synthesis.
Katherine E. Dunn, Frits Dannenberg, Thomas E. Ouldridge et al. | Alcohols as alkylating agents in heteroarene C–H functionalization
The biochemical process of spin-centre shift is used to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors; this represents the first broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis.
Jian Jin, David W. C. MacMillan | Global separation of plant transpiration from groundwater and streamflow
Soil water is usually assumed to be equally available for all purposes, supplying plant transpiration as well as groundwater and streamflow; however, a study of hydrogen and oxygen isotopes from 47 globally distributed sites shows that in fact the water used by plants tends to be isotopically distinct from the water that feeds streamflow.
Jaivime Evaristo, Scott Jasechko, Jeffrey J. McDonnell | Broad plumes rooted at the base of the Earth's mantle beneath major hotspots
A whole-mantle seismic imaging technique, combining accurate wavefield computations with information contained in whole seismic waveforms, is used to reveal the presence of broad conduits beneath many of Earth's surface hotspots, supporting the idea that these conduits are the source of hotspot volcanoes.
Scott W. French, Barbara Romanowicz | Global exchange and accumulation of non-native plants
A global database of alien plants, showing that over 13,000 species, nearly 4% of the global flora, have become naturalized in a new location.
Mark van Kleunen, Wayne Dawson, Franz Essl et al. | Genetic evidence for two founding populations of the Americas
Previous genetic studies have suggested that the Americas were peopled by a single founding population of Eurasian origin, but a genome-wide study of 30 Native American groups shows that Amazonian Native Americans also have a second source of ancestry that is deeply related to indigenous Australians, New Guineans and Andaman Islanders.
Pontus Skoglund, Swapan Mallick, Maria Cátira Bortolini et al. | Mutations in DCHS1 cause mitral valve prolapse
Two mutations in the gene DCHS1 are shown to cause non-syndromic mitral valve prolapse (MVP), a common cardiac valve disease; understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds therapeutic potential.
Ronen Durst, Kimberly Sauls, David S. Peal et al. | PIK3CAH1047R induces multipotency and multi-lineage mammary tumours
PIK3CA mutations are associated with distinct types of human breast cancers but the cellular origin and mechanisms responsible for this heterogeneity were unclear; here, using a genetic approach in mice, the PIK3CAH1047R mutation is shown to induce multipotent stem-like cells and mammary tumours with different levels of malignancy depending on the cell of origin.
Shany Koren, Linsey Reavie, Joana Pinto Couto et al. | Reactivation of multipotency by oncogenic PIK3CA induces breast tumour heterogeneity
PIK3CA mutations are associated with distinct types of human breast cancers but the cellular origin and mechanisms responsible for this heterogeneity were unclear; here, using a genetic approach in mice, PIK3CA mutations are shown to activate a genetic program directing multiple cell fates in normally lineage-restricted cell types.
Alexandra Van Keymeulen, May Yin Lee, Marielle Ousset et al. | Regulation of mitochondrial morphology and function by stearoylation of TFR1
Mitochondria have essential functions within cells, and their dysfunction is linked to various disorders; here, the fatty acid stearic acid (C18:0), which is a dietary component, and the transferrin receptor (TFR1) are shown to regulate mitochondrial function.
Deniz Senyilmaz, Sam Virtue, Xiaojun Xu et al. | GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport
An unbiased genetic screen in Drosophila expressing G4C2-repeat-containing transcripts (repeats that in human cause pathogenesis in C9orf72-related neurological disease) finds genes that encode components of the nuclear pore and nucleocytoplasmic transport machinery, and reveals that G4C2 expanded-repeat-induced alterations in nucleocytoplasmic transport contribute to C9orf72 pathology and neurodegeneration.
Brian D. Freibaum, Yubing Lu, Rodrigo Lopez-Gonzalez et al. | Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching
High-throughput genome-wide sequencing reveals why class switch recombination in the IgH locus, an essential step in the process of antibody generation, has a directional joining bias towards deletion rather than inversion.
Junchao Dong, Rohit A. Panchakshari, Tingting Zhang et al. | A four-helix bundle stores copper for methane oxidation
Csp1, a novel copper-binding protein that is exported from the cytosol of the methanotroph Methylosinus trichosporium OB3b and stores copper ions for particulate methane monooxygenase, is identified and characterized.
Nicolas Vita, Semeli Platsaki, Arnaud Baslé et al. | | | | |
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