| Biodiversity: Multiple origins of mountain life A study of DNA sequences from more than 1,800 organisms on Mount Kinabalu in Borneo reveals the evolutionary mechanisms that led to the mountain's high and unique biodiversity. | Cell biology: Tagged tags engage disposal Damaged organelles called mitochondria were once thought to be disposed of by a simple signalling cascade. Cell-based analyses now reveal that a network of complicated molecular interactions initiates disposal. | Organic chemistry: Light opens pathways for nickel catalysis The report of a light-activated catalyst that generates usually inaccessible nickel intermediates provides a general strategy that might allow elusive catalytic reactions to be realized. | Structural biology: Lipid gymnastics Crystal structures of the bacterial protein PglK uncover structural features that suggest how the protein 'flips' lipid-bound oligosaccharide molecules from one side of the cell membrane to the other. | The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy The PINK1 ubiquitin kinase is shown to recruit the two autophagy receptors NDP52 and OPTN to mitochondria to activate mitophagy directly, independently of the ubiquitin ligase parkin; once recruited to mitochondria, NDP52 and OPTN recruit autophagy initiation components, and parkin may amplify the phospho-ubiquitin signal generated by PINK1, resulting in robust autophagy induction. | Structure and mechanism of an active lipid-linked oligosaccharide flippase The X-ray crystal structure of the ABC transporter PglK, which facilitates the flipping of lipid-linked oligosaccharides (LLOs) in C. jejuni, in inward- and outward-facing states is solved; the structures and follow-up biochemical experiments support an unprecedented mechanism in which the polyprenyl tail of LLO remains partially embedded in the lipid bilayer, and the pyrophosphate-oligosaccharide head group is flipped into the outward-facing cavity after ATP is hydrolysed. | The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia Zinc transporter ZIP12 expression is increased in many cell types in remodelled mammalian pulmonary arterioles in hypoxia-induced pulmonary hypertension. | The pre-vertebrate origins of neurogenic placodes A study showing that tunicates possess a proto-placodal ectoderm that produces neurons with dual neurosecretory and chemosensory function, which may represent the ancestral origin of placode-derived neurons in vertebrates. | Structural basis of JAZ repression of MYC transcription factors in jasmonate signalling Structural view of a dynamic molecular switch mechanism that governs repression and activation of the jasmonate plant hormone pathway. | 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. | 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. | 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. | Measurement-based control of a mechanical oscillator at its thermal decoherence rate A position sensor is demonstrated that is capable of resolving the zero-point motion of a nanomechanical oscillator in the timescale of its thermal decoherence; it achieves an imprecision that is four orders of magnitude below that at the standard quantum limit and is used to feedback-cool the oscillator to a mean photon number of five. | Conformational dynamics of a class C G-protein-coupled receptor smFRET is used to probe the activation mechanism of two full-length mammalian glutamate receptors, revealing that the extracellular ligand-binding domains of these G-protein-coupled receptors interconvert between three confirmations (resting, activated and a short-lived intermediate state), and that the efficacy of an orthosteric agonist correlates with the degree of occupancy of the active state. | Switching on elusive organometallic mechanisms with photoredox catalysis Despite advances in carbon–carbon fragment couplings, the ability to forge carbon–oxygen bonds in a general fashion via nickel catalysis has been largely unsuccessful; here, visible-light-excited photoredox catalysts are shown to provide transient access to Ni(iii) species that readily participate in reductive elimination, leading to carbon–oxygen coupling. | SEC14L2 enables pan-genotype HCV replication in cell culture Hepatitis C virus cannot replicate in cell culture unless it possesses adaptive mutations; here, expression of cellular factor SEC14L2 is shown to allow replication of diverse hepatitis C virus genotypes in several hepatoma cell lines by enhancing vitamin E-mediated protection against lipid peroxidation. | Evolution of endemism on a young tropical mountain Investigating the evolutionary origins of montane biodiversity by sampling the entire biota from a single mountain, Mount Kinabalu in Borneo, allows for a better understanding not only of the origins of endemism, but also of this biota's forecasted response to environmental change. | Corrigendum: Bipolar seesaw control on last interglacial sea level | | | | Nature Genetics in association with the Wellcome Trust present: THE GENOMICS OF COMMON DISEASES 2015 September 2-5, 2015 | Cambridge, UK REGISTER NOW! | | | | | | | | | | | Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver In the uninjured liver, a population of self-renewing, diploid hepatocytes is identified near the central vein; these cells respond to Wnt signals that are provided by the adjacent central vein endothelial cells, and can give rise to all other hepatocytes to maintain liver homeostasis. Bruce Wang, Ludan Zhao, Matt Fish et al. | Structure of the eukaryotic MCM complex at 3.8 Å Cryo-electron microscopy is used to visualize the double hexamer of the eukaryotic minichromosome maintenance complex (MCM), which is assembled during the G1 phase of DNA replication; two interdigitated hexamers have a central channel that tightly fits a DNA duplex, and the orientation of the tilted single hexamers sheds light on many functional aspects, particularly in the initial origin DNA melting. Ningning Li, Yuanliang Zhai, Yixiao Zhang et al. | | A giant protogalactic disk linked to the cosmic web A two-dimensional spectroscopic investigation of a large, luminous filament of the cosmic web near QSO UM287 reveals that the brightest emission region is an extended rotating hydrogen disk with a velocity profile that is characteristic of gas in a 1013-solar-mass dark-matter halo, with a geometry that is strongly suggestive of cold flow accretion. D. Christopher Martin, Mateusz Matuszewski, Patrick Morrissey et al. | High-precision comparison of the antiproton-to-proton charge-to-mass ratio OPEN The CPT theorem (the assumption that physical laws are invariant under simultaneous charge conjugation, parity transformation and time reversal) is central to the standard model of particle physics; here the charge-to-mass ratio of the antiproton is compared to that of the proton, with a precision of 69 parts per trillion, and the result supports the CPT theorem at the atto-electronvolt scale. S. Ulmer, C. Smorra, A. Mooser et al. | Rejuvenation of metallic glasses by non-affine thermal strain This study shows that metallic glasses can be rejuvenated (taken to higher energy states with more plasticity) by thermally cycling them at relatively low temperatures (well below the glass transition temperature); this is attributed to the effect of intrinsic structural inhomogeneities in the glassy state, which translate into localized internal strains as the temperature is cycled and the different regions expand and contract by different amounts. S. V. Ketov, Y. H. Sun, S. Nachum et al. | Graphene kirigami The ratio of in-plane stiffness to out-of-plane bending stiffness of graphene is shown to be similar to that of a piece of paper, which allows ideas from kirigami (a variation of origami that allows cutting) to be applied to micrometre-scale graphene sheets to build mechanically stretchable yet robust electrodes, springs and hinges. Melina K. Blees, Arthur W. Barnard, Peter A. Rose et al. | Dosage delivery of sensitive reagents enables glove-box-free synthesis A method of supplying exactly the amounts of air- and moisture-sensitive catalysts and ligands needed for three commonly used syntheses in a stable, storable form in a sealed capsule is described; it should reduce the unnecessary waste of chemicals, money and time. Aaron C. Sather, Hong Geun Lee, James R. Colombe et al. | The role of ridges in the formation and longevity of flat slabs Flat-slab subduction is often proposed to cause deformation of continental crust far from plate boundaries as well as unusual patterns of volcanism; a study of the largest-known flat slab, located in Peru, now shows that the ridge is necessary for the formation and longevity of the flat slab, whereas other contributing factors such as trench retreat and suction alone will not suffice. Sanja Knezevic Antonijevic, Lara S. Wagner, Abhash Kumar et al. | An early modern human from Romania with a recent Neanderthal ancestor Analysis of DNA from a 37,000–42,000-year-old modern human from Romania reveals that 6–9% of the genome is derived from Neanderthals, with the individual having a Neanderthal ancestor as recently as four to six generations back. Qiaomei Fu, Mateja Hajdinjak, Oana Teodora Moldovan et al. | The octopus genome and the evolution of cephalopod neural and morphological novelties OPEN Octopus bimaculoides genome and transcriptome sequencing demonstrated that a core gene repertoire broadly similar to that of other invertebrate bilaterians is accompanied by expansions in the protocadherin and C2H2 zinc-finger transcription factor families and large-scale genome rearrangements closely associated with octopus-specific transposable elements. Caroline B. Albertin, Oleg Simakov, Therese Mitros et al. | Identification of cis-suppression of human disease mutations by comparative genomics Patterns of amino acid conservation have been used to guide the interpretation of the disease-causing potential of genetic variants in patients; now, an appreciable fraction of pathogenic alleles are shown to be fixed in the genomes of other species, suggesting that the genomic context has an important role in allele pathogenicity. Daniel M. Jordan, Stephan G. Frangakis, Christelle Golzio et al. | Genetic compensation induced by deleterious mutations but not gene knockdowns Zebrafish embryos injected with egfl7 morpholino exhibit severe vascular defects but egfl7 mutants do not show any obvious phenotypes, illustrating the power of comparing mutants and morphants to identify modifier genes. Andrea Rossi, Zacharias Kontarakis, Claudia Gerri et al. | Metabolic rescue in pluripotent cells from patients with mtDNA disease Mutations in mitochondrial (mt)DNA are associated with severe disorders for which treatment is currently limited; this study shows that mtDNA mutations can be genetically corrected and normal metabolic function restored in cells derived from patients with mtDNA disease and reprogrammed to pluripotency through factor-mediated reprogramming or via a somatic cell nuclear transfer approach. Hong Ma, Clifford D. L. Folmes, Jun Wu et al. | Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes A high-content phenotypic screening method has been developed allowing the first systematic RNA interference screen for nearly 800 genes mediating mammalian meiosis. Sybille Pfender, Vitaliy Kuznetsov, Michał Pasternak et al. | The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1 Studies in mice reveal that CREB regulated transcription coactivator 2 (CRTC2) acts as a mediator of mTOR signalling in the liver to regulate SREBP1-controlled lipid homeostasis during feeding and diabetes; overexpression of a CRTC2 mutant defective for mTOR regulation improves the lipogenic program and insulin sensitivity in obese mice. Jinbo Han, Erwei Li, Liqun Chen et al. | Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation An efficient protein disaggregation system uncovered in metazoan cells requires transient interactions between J-protein co-chaperones of classes A and B, which synergistically boost HSP70-dependent disaggregation activity, providing a flexible further level of regulation for metazoan protein quality control, with direct relevance to human diseases such as age-related neurodegeneration. Nadinath B. Nillegoda, Janine Kirstein, Anna Szlachcic et al. | X-ray structure of a mammalian stearoyl-CoA desaturase The crystal structure of mouse SCD1 bound to fatty acid stearoyl-CoA is solved at 2.6 Å resolution; the structure reveals a novel geometry for the dimetal centre, and the acyl chain of the bound fatty acid is shown to be shielded and shaped to a particular conformation by the enzyme, providing a structural basis for the selectivity of fatty acid metabolism. Yonghong Bai, Jason G. McCoy, Elena J. Levin et al. | | | | |
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