| | Drug discovery: Designing the ideal opioid
The development of a drug that mimics the pain-relieving activity of opioid compounds, but has fewer side effects, points to an effective strategy for the discovery of many types of drug. | Cancer: Suffocation of gene expression
If a tumour outgrows its blood supply, oxygen levels in its cells decrease. It emerges that this change can alter gene expression by limiting the activity of TET enzymes, which remove methyl groups from DNA. | | Tumour hypoxia causes DNA hypermethylation by reducing TET activity | Uncovering Earth’s virome
An integrated computational approach that explores the viral content of more than 3,000 metagenomic samples collected globally highlights the existing global viral diversity, increases the known number of viral genes by an order of magnitude, and provides detailed insights into viral distribution across diverse ecosystems and into virus–host interactions. | SEDS proteins are a widespread family of bacterial cell wall polymerases
SEDS proteins are core peptidoglycan polymerases involved in bacterial cell wall elongation and division. | Structure-based discovery of opioid analgesics with reduced side effects
Computational docking to the the μ-opioid-receptor identifies PZM21, a novel selective biased agonist that generates substantial affective analgesia in mice without altering respiration or inducing drug reinforcement. | The awakening of a classical nova from hibernation
Long-term pre- and post-eruption observations of the classical nova V1213 Centauri reveal that its progenitor was a dwarf nova and that the mass-transfer rate increased considerably as a result of the nova explosion. | The TRPM2 ion channel is required for sensitivity to warmth
The neuronal mechanism for the detection of non-painful warm stimuli has remained unclear; mammalian TRPM2 ion channel is shown to be required for warmth detection in the non-noxious range of 33–38 °C, and surprisingly to mediate responses to warmth in the autonomic nervous system. | Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
Both a high number of species and abundance in multiple trophic levels are required for ecosystems to continue to provide the services humans require of them. | Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region
A highly conserved rearrangement of residue contacts functions as a common step in the activation pathways of diverse G-protein-coupled receptors. | Digits and fin rays share common developmental histories
Hoxa- and Hoxd-deficient zebrafish generated using Crispr/Cas with fate mapping have reduced fin rays and increased endochondral elements, establishing homology between the developmental programs that create fin rays and the wrists and digits of mammals. | | The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan | Evolutionary biology: Fin to limb within our grasp
There was thought to be little in common between fish fin bones and the finger bones of land-dwellers. But zebrafish studies reveal that hox genes have a surprisingly similar role in patterning the two structures. | | | | Nature Outlook Open Innovation
In the competitive world of drug discovery and development, secrecy is no longer as important as it was. As it has become more difficult and costly to produce therapies, competitors have begun to view greater collaboration and openness as a way to improve the efficiency of research.
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Produced with support from Boehringer Ingelheim | | | | | | | | | | | Defining the clonal dynamics leading to mouse skin tumour initiation
Skin stem cells, but not their progenitors, are able to form tumours owing to the ability of oncogene-targeted stem cells to increase symmetric self-renewing division and a higher p53-dependent resistance to apoptosis.
Adriana Sánchez-Danés, Edouard Hannezo, Jean-Christophe Larsimont et al. | Analysis of protein-coding genetic variation in 60,706 humans OPEN
Exome sequencing data from 60,706 people of diverse geographic ancestry is presented, providing insight into genetic variation across populations, and illuminating the relationship between DNA variants and human disease.
Monkol Lek, Konrad J. Karczewski, Eric V. Minikel et al. | Circadian neuron feedback controls the Drosophila sleep–activity profile
A subset of dorsal clock neurons are identified in Drosophila as sleep-promoting cells, which participate in a feedback loop with pacemaker neurons to drive both midday siesta and night-time sleep.
Fang Guo, Junwei Yu, Hyung Jae Jung et al. | Capturing a substrate in an activated RING E3/E2–SUMO complex
A new method based on protein engineering to trap an intact complex between Siz1, SUMO-bound E2, and PCNA for structure determination.
Frederick C. Streich Jr, Christopher D. Lima | | Operation of a homeostatic sleep switch
Sleep-promoting neurons in Drosophila are shown to switch between electrical activity and silence as a function of sleep need; the switch is operated by dopamine and involves the antagonistic regulation of two potassium channels.
Diogo Pimentel, Jeffrey M. Donlea, Clifford B. Talbot et al. | Dependence of the critical temperature in overdoped copper oxides on superfluid density
The scaling law for the critical temperature and zero-temperature stiffness in an overdoped copper oxide semiconductor does not conform to the standard Bardeen–Cooper–Schrieffer description.
I. Božović, X. He, J. Wu et al. | High-efficiency two-dimensional Ruddlesden–Popper perovskite solar cells
Thin-film solar cells were fabricated using layered two-dimensional perovskites with near-single-crystalline out-of-plane alignment, which facilitates efficient charge transport leading to greatly improved power conversion efficiency with technologically relevant stability to light exposure, humidity and heat stress.
Hsinhan Tsai, Wanyi Nie, Jean-Christophe Blancon et al. | The active site of low-temperature methane hydroxylation in iron-containing zeolites
Iron-containing zeolites have an exceptional ability to convert methane into methanol, but their active site have been hard to study; now, magnetic circular dichroism has been used to explore the reactive species, providing a technique that should be generally applicable, and revealing the value of constraining active sites within a lattice to improve catalyst functionality.
Benjamin E. R. Snyder, Pieter Vanelderen, Max L. Bols et al. | Metallaphotoredox-catalysed sp3–sp3 cross-coupling of carboxylic acids with alkyl halides
The long-sought direct formation of a bond between two sp3-hybridized carbon atoms is achieved by the merger of photoredox and nickel catalysis using only simple carboxylic acids and alkyl halides as starting materials.
Craig P. Johnston, Russell T. Smith, Simon Allmendinger et al. | An early geodynamo driven by exsolution of mantle components from Earth’s core
Experiments show that magnesium oxide can dissolve in core-forming metallic melts at very high temperatures; core formation models suggest that a giant impact during Earth’s accretion could have contributed large amounts of magnesium to the early core, the subsequent exsolution of which would have generated enough gravitational energy to power an early geodynamo and produce an ancient magnetic field.
James Badro, Julien Siebert, Francis Nimmo | Natural courtship song variation caused by an intronic retroelement in an ion channel gene
Natural variation in the courtship song of Drosophila is mapped to the intronic insertion of a retroelement at the slowpoke locus, which encodes an ion channel.
Yun Ding, Augusto Berrocal, Tomoko Morita et al. | A human neurodevelopmental model for Williams syndrome
A human neurodevelopmental model fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.
Thanathom Chailangkarn, Cleber A. Trujillo, Beatriz C. Freitas et al. | Asymmetric division of contractile domains couples cell positioning and fate specification
Here, a combination of biophysical measurement, modelling, and genetic and experimental manipulation of cell contractile components is used to analyse the formation of the inner cell mass in the early mouse embryo.
Jean-Léon Maître, Hervé Turlier, Rukshala Illukkumbura et al. | HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis
Size-selective pores in the HIV-1 capsid hexamer recruit nucleotides, thereby allowing reverse transcription to take place inside the capsid.
David A. Jacques, William A. McEwan, Laura Hilditch et al. | Structure of mammalian respiratory complex I
Electron cryomicroscopy structures are provided for all core and supernumerary protein subunits of mammalian complex I, a 45-subunit enzyme that powers eukaryotic respiration.
Jiapeng Zhu, Kutti R. Vinothkumar, Judy Hirst | | | | |
