| | Neurodegeneration: Problems at the nuclear pore
Expansion of a repetitive DNA sequence is associated with neurodegeneration. Three studies identify genes involved in nuclear import and export that can mediate the toxicity this expansion causes.
| Molecular biology: Unequal opportunity during class switching
The DNA breakage-and-repair mechanism that generates antibodies of different classes has, in theory, a 50% chance of occurring correctly. But this recombination turns out to be heavily biased towards productive events.
| Cancer: A moving target
An in silico, three-dimensional model of tumour evolution suggests that cell motility is a key factor in the initial growth of a tumour mass. The model also reveals the dynamics of mutation spread.
| 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.
| The most incompressible metal osmium at static pressures above 750 gigapascals
Subtle anomalies in how the structure of metallic osmium evolves with pressure are detected using powder X-ray diffraction measurements at ultra-high static pressures; the anomaly at 440 gigapascals is attributed to an electronic transition caused by pressure-induced interactions between core electrons.
| 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.
| Allosteric receptor activation by the plant peptide hormone phytosulfokine
Insights derived from the crystal structures of the extracellular domain of PSKR, the receptor for the plant hormone phytosulfokine (PSK) that affects plant growth and development, reveal that PSK interacts with PSKR and enhances PSKR interaction with its co-receptor SERK allosterically.
| Crystal structure of the dynamin tetramer
The crystal structure of the large GTPase dynamin tetramer is presented, suggesting a mechanism by which oligomerization of dynamin is regulated, and revealing how mutations that interfere with tetramer formation and autoinhibition are of relevance to understanding the congenital muscle disorders Charcot–Marie–Tooth neuropathy and centronuclear myopathy.
| 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.
| Integrator mediates the biogenesis of enhancer RNAs
This study demonstrates a role for the Integrator complex in the stimulus-dependent induction of eRNAs and their 3′ processing; together with previously known roles of Integrator in transcription elongation and RNA processing, these results indicate that Integrator has broad functions in the regulation of eukaryotic gene expression.
| 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.
| A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity
A new model of tumour evolution is presented to explain how short-range migration and cell turnover within the tumour can provide the basic environment of rapid cell mixing, allowing even a small selective advantage to dominate the mass within relevant time frames.
| 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.
| Erratum: Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone
| Corrigendum: Lanosterol reverses protein aggregation in cataracts
| | | Brief Communications Arising | | | | Endosymbiotic origin and differential loss of eukaryotic genes
Eukaryotes acquired their prokaryotic genes in two episodes of evolutionary influx corresponding to the origin of mitochondria and plastids, respectively, followed by extensive differential gene loss, uncovering a massive imprint of endosymbiosis in the nuclear genomes of complex cells.
Chuan Ku, Shijulal Nelson-Sathi, Mayo Roettger et al. | 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.
Camilo Perez, Sabina Gerber, Jérémy Boilevin et al. | | 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.
Mohsan Saeed, Ursula Andreo, Hyo-Young Chung et al. | The disruption of multiplanet systems through resonance with a binary orbit
In a multiplanet system, when orbital precession is fast enough to resonate with the orbital motion of a distant binary companion, the results range from excitation of large planetary eccentricities and mutual inclinations to total disruption.
Jihad R. Touma, S. Sridhar | A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death
A new pathway of mitochondria-mediated cell death termed mitochondrial precursor over-accumulation stress (mPOS) is identified that could explain the link between mitochondrial dysfunction and misfolding of cytosolic proteins during ageing and disease; the pathway is triggered not only by mutations affecting the core protein import machineries, but also by conditions that interfere with mitochondrial inner membrane integrity and function, and a large network of genes that suppress mPOS in favour of cell survival is also identified.
Xiaowen Wang, Xin Jie Chen | Multi-gigaelectronvolt acceleration of positrons in a self-loaded plasma wakefield
A particle accelerator that is two orders of magnitude more efficient than conventional radio-frequency accelerators is described in which positrons (rather than electrons) at the front of a bunch transfer their energy to a substantial number of positrons at the rear of the same bunch by exciting a wakefield in the plasma.
S. Corde, E. Adli, J. M. Allen et al. | Atomic inner-shell laser at 1.5-ångström wavelength pumped by an X-ray free-electron laser
A copper target is used to achieve an atomic laser in the hard-X-ray regime with strong amplified spontaneous coherent emission at a wavelength ten times shorter than previous lasers have achieved.
Hitoki Yoneda, Yuichi Inubushi, Kazunori Nagamine et al. | Substitutional doping in nanocrystal superlattices
Substitutional atomic doping is a process by which atomic defects are introduced into a host material, altering its properties; substitutional doping of cadmium selenide or lead selenide nanocrystal lattices with gold nanocrystals has now been achieved, the key being to ensure that the dopant nanocrystals are similar in size to the host nanocrystals.
Matteo Cargnello, Aaron C. Johnston-Peck, Benjamin T. Diroll et al. | Multimetallic catalysed cross-coupling of aryl bromides with aryl triflates
A new method for catalysing the cross-coupling of two different aryl electrophiles is described; the principle of this method, which involves cooperation between two metal catalysts that are selective towards different substrates, should be generally useful in catalysis.
Laura K. G. Ackerman, Matthew M. Lovell, Daniel J. Weix | 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.
Philip Barron Abitua, T. Blair Gainous, Angela N. Kaczmarczyk et al. | Sidekick 2 directs formation of a retinal circuit that detects differential motion
The mouse retinal ganglion cell type known as the W3B-RGC, which detects motion of objects against a moving background, is shown to receive strong specific and excitatory input from amacrine cells expressing vesicular glutamine transporter 3; this selective connection is mediated by homophilic interactions of the recognition molecule sidekick 2 (Sdk2), which is expressed on both cells, and disruption of this connection affects object motion detection in W3B-RGCs.
Arjun Krishnaswamy, Masahito Yamagata, Xin Duan et al. | Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol
Mitochondrial dysfunction and cellular protein homeostasis failure are hallmarks of many diseases and age-associated pathologies; this study shows that the mitochondrial import defect of nuclear-encoded proteins triggers a cellular pathway, termed unfolded protein response activated by mistargeting of proteins (UPRam), that acts to minimize the stress caused by non-imported mitochondrial precursor proteins in order to sustain cellular protein homeostasis and organismal fitness.
Lidia Wrobel, Ulrike Topf, Piotr Bragoszewski et al. | Structural basis for stop codon recognition in eukaryotes
All eukaryotes utilize a single termination factor, eRF1, to halt translation when the ribosome encounters one of three possible stop codons; here electron cryo-microscopy structures of ribosome–eRF1 complexes in the process of recognizing each stop codon reveal how stop codons are discriminated from sense codons.
Alan Brown, Sichen Shao, Jason Murray et al. | Western US intermountain seismicity caused by changes in upper mantle flow
Results from mantle flow models reveal a relationship between seismicity away from the plate boundary in the western United States and the rate change of the vertical normal stress from mantle flow, showing that mantle flow plays an important part in shaping topography, tectonics and seismic hazard within such intraplate settings.
Thorsten W. Becker, Anthony R. Lowry, Claudio Faccenna et al. | Cell mixing induced by myc is required for competitive tissue invasion and destruction
Live imaging of myc-driven competition in healthy Drosophila tissues shows that cells expressing higher levels of myc actively mix with the neighbouring cells, which increases the probability of eliminating neighbouring cells.
Romain Levayer, Barbara Hauert, Eduardo Moreno | Kinetochore-localized PP1–Sds22 couples chromosome segregation to polar relaxation
A study of division in proliferating animal cells points to the existence of a kinetochore-based signalling pathway, independent of furrow formation, centrosomes and microtubules, that couples chromosome segregation to cell division.
Nelio T. L. Rodrigues, Sergey Lekomtsev, Silvana Jananji et al. | 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.
Reza Vafabakhsh, Joshua Levitz, Ehud Y. Isacoff | | | | |
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