| Cell biology: Ubiquitination without E1 and E2 enzymes A protein in the pathogenic bacterium Legionella pneumophila has been found to attach the modifying molecule ubiquitin to human proteins, using a mechanism that, surprisingly, does not involve cellular E1 and E2 enzymes. | Materials science: Clockwork at the atomic scale Design rules for exotic materials known as polar metals have been put into practice in thin films. The findings will motivate studies of how a phenomenon called screening can be manipulated to generate new phases in metals. | Parkinson's disease: Guilt by genetic association Certain sequence variants of the α-synuclein gene are linked to the risk of Parkinson's disease. An analysis of these variants using gene-editing technology provides a possible explanation for this increased risk. | Ocean science: The rise of Rhizaria Large amoeba-like organisms known as Rhizaria have often been overlooked in studies of ocean biology and biogeochemistry. Underwater imaging and ecological network analyses are revealing their roles. | The Atlantic salmon genome provides insights into rediploidization OPEN The genome sequence is presented for the Atlantic salmon (Salmo salar), providing information about a rediploidization following a salmonid-specific whole-genome duplication event that resulted in an autotetraploidization. | First North American fossil monkey and early Miocene tropical biotic interchange Here, 21-million-year-old fossils of a New World monkey from Panama are described, constituting the earliest known evidence for mammalian interchange between North and South America. | The pentadehydro-Diels–Alder reaction A modification to the classic Diels–Alder [4 + 2] cycloaddition reaction, termed the pentadehydro-Diels–Alder reaction, is reported; this reaction generates a highly reactive intermediate, an α,3-dehydrotoluene, that can be captured using various trapping agents to produce structurally diverse products. | Scalable and sustainable electrochemical allylic C–H oxidation An electrochemical C–H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity is described; it uses inexpensive and readily available materials and represents a scalable allylic C–H oxidation that could be adopted in large-scale industrial settings without substantial environmental impact. | Polar metals by geometric design Ab initio calculations are used to identify the structural conditions under which a polar state in metals might be stabilized; this information is used to guide the experimental realization of new room-temperature polar metals. | Structural insights into inhibition of lipid I production in bacterial cell wall synthesis The crystal structure of the MraY enzyme from Aquifex aeolicus in complex with the naturally occurring nucleoside inhibitor muraymycin D2 (MD2) reveals that MraY undergoes a large conformational rearrangement near the active site after the binding of MD2, leading to the generation of a nucleoside-binding pocket and a peptide-binding site. | In situ imaging reveals the biomass of giant protists in the global ocean An in situ imaging technique has been used to show that large rhizarian plankton represent a much larger biomass than previously thought, meaning that they are likely to make an important contribution to ocean ecosystems. | Normalizing the environment recapitulates adult human immune traits in laboratory mice The immune system of laboratory mice raised in an ultra-hygienic environment resembles that of newborn humans, but can be induced to resemble the immune system of adult humans or 'dirty' mice by co-housing with pet store-bought mice. | Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression A CRISPR/Cas9 system is used to dissect the role of allelic risk variants on the expression of the α-synuclein gene SNCA, which has been linked to Parkinson’s disease development. | The crystal structure of Cpf1 in complex with CRISPR RNA The crystal structure of monomeric Lachnospiraceae bacterium Cpf1 protein bound to CRISPR RNA is presented, establishing a framework for engineering LbCpf1 to improve its efficiency and specificity for genome editing. | The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA The CRISPR-associated protein Cpf1 from Francisella novicida is a novel enzyme with specific, dual-endoribonuclease–endonuclease activities in precursor crRNA processing and crRNA-programmable cleavage of target DNA. | Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage CRISPR/Cas9 DNA editing creates a double-stranded break in the target DNA, which can frequently generate random insertion or deletion of bases (indels); a new genome editing approach combining Cas9 with a cytidine deaminase is described here, which corrects point mutations more efficiently than canonical Cas9, while avoiding double-stranded breaks and indel formation. | Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells Defects in LC3-associated phagocytosis in mice are shown to result in systemic lupus erythematosus-like disease; dying cells are engulfed but not degraded in LAP-deficient mice, resulting in increased serum levels of autoantibodies and inflammatory cytokines, and evidence of kidney disease. | Structure of the thermally stable Zika virus The 3.7 Å cryo-electron microscopy structure of Zika virus is presented, revealing a typical flavivirus architecture; in contrast to the related flavivirus dengue virus, Zika virus is thermally stable at 40 °C, and this structural stability may be a feature that helps it to survive in semen, saliva and urine. | Corrigendum: Structure of promoter-bound TFIID and model of human pre-initiation complex assembly | | Distinct bone marrow blood vessels differentially regulate haematopoiesis Bone marrow endothelial cells have dual roles in the regulation of haematopoietic stem cell maintenance and in the trafficking of blood cells between the bone marrow and the blood circulatory system; this study shows that these different functions are regulated by distinct types of endothelial blood vessels with different permeability properties, affecting the metabolic state of their neighbouring stem cells. Tomer Itkin, Shiri Gur-Cohen, Joel A. Spencer et al. | DNA methylation on N6-adenine in mammalian embryonic stem cells The prevalence of N6-adenine DNA methylation in mammals was previously unknown; this study reveals that N6-methyladenine can be found in mouse embryonic stem cells, especially at subfamilies of young (<1.5 million years old) LINE-1 transposons. Tao P. Wu, Tao Wang, Matthew G. Seetin et al. | X-ray structures and mechanism of the human serotonin transporter X-ray crystal structures of the human serotonin transporter (SERT) bound to the antidepressants (S)-citalopram or paroxetine show that the antidepressants lock the protein in an outward-open conformation, and directly block serotonin from entering its binding site; the structures define the mechanism of antidepressant action in SERT and pave the way for future drug design. Jonathan A. Coleman, Evan M. Green, Eric Gouaux | | A 17-billion-solar-mass black hole in a group galaxy with a diffuse core The galaxy NGC 1600 is found to contain an enormous black hole of 17 billion solar masses—the first black hole of such a size to be found in an environment outside the richest clusters of galaxies. Jens Thomas, Chung-Pei Ma, Nicholas J. McConnell et al. | Detection of a Cooper-pair density wave in Bi2Sr2CaCu2O8+x Scanned Josephson tunnelling microscopy is used to image Cooper pair tunnelling from a superconducting microscope tip to the quantum condensate of Bi2Sr2CaCu2O8+x, thus revealing the spatially modulated density of Cooper pairs predicted from several theories of the cuprate pseudogap phase. M. H. Hamidian, S. D. Edkins, Sang Hyun Joo et al. | A pressure-amplifying framework material with negative gas adsorption transitions For adsorption processes, gas uptake usually increases with increasing pressure; however, here the phenomenon of negative gas adsorption is demonstrated in a metal–organic framework, which undergoes a sudden hysteretic structural deformation and pore contraction, releasing guest molecules. Simon Krause, Volodymyr Bon, Irena Senkovska et al. | Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols Here, a method is described by which to generate all possible stereoisomers of certain amino alcohols—a protocol that should see use in drug discovery and development, where it is important to determine the differing effects of stereoisomeric drug candidates. Shi-Liang Shi, Zackary L. Wong, Stephen L. Buchwald | Recent improvement and projected worsening of weather in the United States Population-weighted analysis of US weather conditions shows that the nation’s weather has generally become more pleasant since 1974, possibly explaining the lack of broad public support for action on climate change; projections of future US weather indicate that conditions will probably worsen. Patrick J. Egan, Megan Mullin | The Parkfield tremors reveal slow and fast ruptures on the same asperity A tremor source on the San Andreas Fault produced an unusual sequence of low-frequency earthquakes until it was disrupted by the 2004 Parkfield earthquake; the peculiar recurrence pattern has now been modelled, showing that such slip behaviour occurs when the tremor asperity size is close to the critical nucleation size of earthquakes. Deepa Mele Veedu, Sylvain Barbot | Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia New excavations in Liang Bua, where the remains of the ‘Hobbit’ (Homo floresiensis) were discovered, show that this diminutive human species this cave between 190,000 and 50,000 years ago, and not until as recently as 12,000 years ago as previously interpreted; modern humans have been present in Australia since around 50,000 years ago, so whether Homo floresiensis survived long enough to witness the arrival of modern humans is still an open question. Thomas Sutikna, Matthew W. Tocheri, Michael J. Morwood et al. | Anatomy and function of an excitatory network in the visual cortex Two-photon calcium imaging and electron microscopy were used to explore the relationship between structure and function in mouse primary visual cortex, showing that layer 2/3 neurons are connected in subnetworks, that pyramidal neurons with similar orientation selectivity preferentially form synapses with each other, and that neurons with similar orientation tuning form larger synapses; this study exemplifies functional connectomics as a powerful method for studying the organizational logic of cortical networks. Wei-Chung Allen Lee, Vincent Bonin, Michael Reed et al. | Daily magnesium fluxes regulate cellular timekeeping and energy balance Circadian rhythms in the intracellular concentration of magnesium ions act as a cell-autonomous timekeeping component to determine key clock properties and tune cellular metabolism both in a human cell line and in a unicellular alga. Kevin A. Feeney, Louise L. Hansen, Marrit Putker et al. | Age-dependent modulation of vascular niches for haematopoietic stem cells Notch signalling in endothelial cells of the bone induces change in the capillaries and mesenchymal stem cells of the environment to support haematopoietic stem cell amplification. Anjali P. Kusumbe, Saravana K. Ramasamy, Tomer Itkin et al. | The diversity-generating benefits of a prokaryotic adaptive immune system Population-level spacer diversity is a key fitness determinant of CRISPR-Cas adaptive immune systems because it limits the emergence of escape virus. Stineke van Houte, Alice K. E. Ekroth, Jenny M. Broniewski et al. | Metabolic maintenance of cell asymmetry following division in activated T lymphocytes The asymmetric distribution of mTORC1 and c-Myc in the first division of daughter cells of activated CD8 T cells affects the proliferation, metabolism and differentiation potential of their progeny. Katherine C. Verbist, Cliff S. Guy, Sandra Milasta et al. | NOD1 and NOD2 signalling links ER stress with inflammation A novel link between the unfolded protein response and NOD1/2 innate immune signalling, showing that NOD1/2 are required for ER-stress-induced IL-6 production in response to infection with Brucella abortus. A. Marijke Keestra-Gounder, Mariana X. Byndloss, Núbia Seyffert et al. | USP14 deubiquitinates proteasome-bound substrates that are ubiquitinated at multiple sites The proteasome-associated enzyme USP14 regulates protein degradation by removing ubiquitin from proteins; here it is shown that USP14 removes ubiquitin chains from in vitro generated cyclin B conjugates en bloc and within milliseconds, before the proteasome has a chance to initiate degradation, and proceeds until a single chain remains. Byung-Hoon Lee, Ying Lu, Miguel A. Prado et al. | | | | |
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