| | Cell fate: Transition loses its invasive edge
Two studies provide evidence that epithelial tumour cells do not need to transition to a mesenchymal-cell state to form metastases, but that this process does contribute to drug resistance.
| Ecology: Ecosystem vulnerability to ocean warming
Analysis of the temperature ranges occupied by marine species finds that the vulnerability of ecological communities to global warming may depend more on organismal physiology than on the magnitude of change.
| Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65
Yeast-based screening identifies the benzodiazepine drug lorazepam as a non-selective positive allosteric modulator of the G-protein-coupled receptor (GPCR) GPR68; homology modelling and molecular docking of 3.1 million molecules found a new compound, 'ogerin', as a potent GPR68 modulator, which suppressed recall in fear conditioning in wild-type mice, and the general method of combining physical and structure-based screening may lead to the discovery of selective ligands for other GPCRs.
| Dpp spreading is required for medial but not for lateral wing disc growth
The morphogen Decapentaplegic (Dpp) has been implicated in both wing patterning and growth in fruitflies; here, a nanobody-based morphotrap approach has been developed that rules out a role for the Dpp gradient in regulating lateral wing growth.
| Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance
An epithelial-to-mesenchymal transition (EMT) lineage-tracing system in a mouse model of breast-to-lung metastasis reveals that although some cells undergo EMT in a primary epithelial tumour, the lung metastases mainly arise from cells that have not undergone EMT; in addition, cells that have undergone EMT appear more resistant to chemotherapy.
| Thermal biases and vulnerability to warming in the world's marine fauna
How marine communities will respond to climate change depends on the thermal sensitivities of existing communities; existing reef communities do not show a perfect fit between current temperatures and the thermal niches of the species within them and this thermal bias is a major contributor to projected local species loss.
| DNA-dependent formation of transcription factor pairs alters their binding specificity
A high-throughput analysis of DNA binding in over 9,000 interacting transcription factor pairs reveals that the interactions are often actively mediated by the DNA itself and the composite DNA sites recognized are different from the individual motifs of each transcription factor.
| Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis
ASS1, a urea cycle enzyme, promotes cancer cell proliferation by facilitating pyrimidine synthesis via CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, and dihydroorotase complex) activation.
| Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism
A causal variant is identified at the LMO1 oncogene locus that drives the genetic association of LMO1 with neuroblastoma susceptibility; the causal SNP disrupts a GATA transcription factor binding site within a tissue-specific super-enhancer element in the first intron of LMO1, thereby affecting LMO1 expression.
| Transcriptional regulators form diverse groups with context-dependent regulatory functions
A large-scale enhancer complementation assay assessing the activating or repressing contributions of over 800 Drosophila transcription factors and cofactors to combinatorial enhancer control reveals a more complex picture than expected, with many factors having diverse regulatory functions that depend on the enhancer context.
| Single-molecule sequencing of the desiccation-tolerant grass Oropetium thomaeum. OPEN
Oropetium thomaeum is a resurrection plant that can survive extreme water stress through desiccation to complete dryness, providing a model for drought tolerance; here, whole-genome sequencing and assembly of the Oropetium genome using single-molecule real-time sequencing is reported.
| Force generation by skeletal muscle is controlled by mechanosensing in myosin filaments
It is widely accepted that contraction of skeletal muscle and the heart involves structural changes in actin-containing thin filaments to allow binding of myosin motors from neighbouring thick filaments, thus driving filament sliding; here, X-ray diffraction of single skeletal muscle cells reveals that this thin-filament mechanism can regulate muscle contraction against low load, but high-load contraction requires a second permissive step involving a structural change in the thick filament.
| Decapentaplegic and growth control in the developing Drosophila wing
The morphogen Decapentaplegic (Dpp) has been implicated in both wing patterning and growth in fruitflies; here, a CRISPR–Cas9 approach is used to rule out the Dpp gradient driving wing growth.
| Extra adsorption and adsorbate superlattice formation in metal-organic frameworks
Metal-organic frameworks have a porous structure that has useful applications in gas adsorption; here, small-angle X-ray scattering is used to visualize the process of adsorption as gas pressure increases, revealing that adsorbate molecules interact across pore walls in a way that allows extra adsorbate domains to be created in the framework and to form superlattices, before the adsorbate settles down into a more uniform distribution.
| Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way
The first stars and their immediate successors should be found today in the central regions (bulges) of galaxies; old, metal-poor stars have now been found in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than that of the Sun without noticeable carbon enhancement, making it possibly the oldest known star in the Galaxy.
| Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer
Deletion of Twist or Snail, two key transcription factors that induce epithelial-to-mesenchymal transition in a mouse model of pancreatic ductal adenocarcinoma leads to an increase in cell proliferation, and a greater sensitivity to the chemotherapeutic agent gemcitabine, with no effect on invasion or metastasis.
| Corrigendum: Regulatory analysis of the C. elegans genome with spatiotemporal resolution
| | | | | Nature Energy: Call for Papers
Launching in January 2016, Nature Energy is now open for submissions and inviting high-quality research from across the natural and social sciences. The journal will be dedicated to exploring all aspects of the on-going discussion of energy provision; from the generation and storage of energy, to its distribution and management, the needs and demands of the different actors, and the impacts that energy technologies and policies have on societies.
Submit your next research paper to the journal. | | | | | | | | | | | | | | | | | Basomedial amygdala mediates top-down control of anxiety and fear
Activation of the ventral medial prefrontal cortex–basomedial amygdala pathway is shown to suppress anxiety and fear-related freezing in mice, thus identifying the basomedial amygdala (and not intercalated cells, as posited by earlier models) as a novel target of top-down control.
Avishek Adhikari, Talia N. Lerner, Joel Finkelstein et al. | 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.
Matthew C. Canver, Elenoe C. Smith, Falak Sher et al. | Oxidative stress inhibits distant metastasis by human melanoma cells
Human melanoma cells grown in mice experience high levels of oxidative stress in the bloodstream such that few metastasizing cells survive to form tumours; the rare melanoma cells that successfully metastasize undergo metabolic changes that increase their capacity to withstand this stress, and antioxidant treatments increase metastasis formation by human melanoma cells, while inhibiting antioxidant pathways had the reverse effect.
Elena Piskounova, Michalis Agathocleous, Malea M. Murphy et al. | Cryo-electron microscopy structure of the Slo2.2 Na+-activated K+ channel
The structure of the full-length Slo2.2 Na+-activated K+ channel is determined by cryo-electron microscopy, revealing features that explain the high conductance and gating mechanism of the Slo K+ channel family.
Richard K. Hite, Peng Yuan, Zongli Li et al. | | Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A
The drug daclatasvir (DCV), which inhibits the hepatitis C virus (HCV) non-structural protein 5A (NS5A), can successfully reduce viral load in patients; here, a combination of DCV and an NS5A analogue is shown to enhance DCV potency on multiple genotypes and overcome resistance in vitro and in a mouse model.
Jin-Hua Sun, Donald R. O'Boyle II, Robert A. Fridell et al. | Global non-linear effect of temperature on economic production
Economic productivity is shown to peak at an annual average temperature of 13 °C and decline at high temperatures, indicating that climate change is expected to lower global incomes more than 20% by 2100.
Marshall Burke, Solomon M. Hsiang, Edward Miguel | A rocky planet transiting a nearby low-mass star
A low-mass star that is just 12 parsecs away from Earth is shown to be transited by an Earth-sized planet, GJ 1132b, which probably has a rock/iron composition and might support a substantial atmosphere.
Zachory K. Berta-Thompson, Jonathan Irwin, David Charbonneau et al. | Entangling two transportable neutral atoms via local spin exchange
Spin-entangled states between two neutral atoms in different optical tweezers are prepared by combining them in the same optical tweezer and allowing for controlled interactions, after which the particles are dynamically separated in space and their entanglement is maintained.
A. M. Kaufman, B. J. Lester, M. Foss-Feig et al. | Large anomalous Hall effect in a non-collinear antiferromagnet at room temperature
The Hall effect is sometimes encountered in ferromagnetic materials in the absence of an external magnetic field; this so-called anomalous Hall effect is now reported in the antiferromagnetic material Mn3Sn, where it occurs as a consequence of the unusual and complex arrangement of the constituent magnetic moments.
Satoru Nakatsuji, Naoki Kiyohara, Tomoya Higo | Liquids with permanent porosity
Porous materials find use in applications such as gas separation, drug delivery and energy storage, but have hitherto been solid rather than liquid; now a combination of cage molecules and a crown-ether solvent that cannot enter the cage molecules is used to create a porous liquid that can solubilize methane gas better than non-porous liquids.
Nicola Giri, Mario G. Del Pópolo, Gavin Melaugh et al. | Plate tectonics on the Earth triggered by plume-induced subduction initiation
High-resolution three-dimensional thermomechanical simulations of Earth's lithosphere indicate that mantle plumes could have initiated the first subduction zones, but only in the hotter early Earth for old oceanic plates.
T. V. Gerya, R. J. Stern, M. Baes et al. | Widespread exploitation of the honeybee by early Neolithic farmers
Detection of molecular biomarkers characteristic of beeswax in pottery vessels at archaeological sites reveals that humans have exploited bee products (such as beeswax and honey) at least 9,000 years ago since the beginnings of agriculture.
Mélanie Roffet-Salque, Martine Regert, Richard P. Evershed et al. | Deep-time evolution of regeneration and preaxial polarity in tetrapod limb development
Salamanders are the only tetrapod that can fully regenerate their limbs and tail, a capacity that might be linked to their unique preaxial mode of limb development; here, data from fossils reveal the existence of preaxial polarity in various amphibians from the Carboniferous and Permian periods, suggesting that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes.
Nadia B. Fröbisch, Constanze Bickelmann, Jennifer C. Olori et al. | Oxygen regulation of breathing through an olfactory receptor activated by lactate
In addition to its role in olfaction, Olfr78 is involved in sensing hypoxia.
Andy J. Chang, Fabian E. Ortega, Johannes Riegler et al. | Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy
Treating ovarian cancer in mouse models with inhibitors for the epigenetic regulators EZH2 and DNMT1 increases the expression of the inflammatory chemokines CXCL9 and CXCL10, resulting in enhanced tumour infiltration by effector T cells, and slowed tumour progression.
Dongjun Peng, Ilona Kryczek, Nisha Nagarsheth et al. | The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions
Crystal structures of the DNA glycosylase AlkD with DNA containing various modified bases show that neither substrate recognition nor catalysis use a base-flipping mechanism; instead, AlkD scans the phosphodeoxyribose backbone for increased cationic charge imparted by the alkylated base, and then uses the positive charge to facilitate cleavage of the glycosidic bond, thus explaining the specificity of AlkD for cationic lesions.
Elwood A. Mullins, Rongxin Shi, Zachary D. Parsons et al. | Structure of a eukaryotic SWEET transporter in a homotrimeric complex
The X-ray crystal structure is presented of a seven-transmembrane eukaryotic SWEET glucose transporter, revealing the link between seven-transmembrane eukaryotic SWEETs and their three-transmembrane bacterial homologues and providing insight into eukaryotic sugar transport mechanisms.
Yuyong Tao, Lily S. Cheung, Shuo Li et al. | | | | |
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