| | DNA repair: Familiar ends with alternative endings
The faithful propagation of species requires a complex balance of DNA-repair pathways to maintain genome integrity. New work sheds light on one such poorly understood pathway and its role in certain cancers. | Neuroscience: The cortical connection
Neurons in the brain's visual cortex receive inputs from thousands of other neurons. But it now emerges that each is strongly connected to only a few others: those most similar to itself. | Molecular biology: Signals across domains of life
Signal sequences on messenger RNA that initiate protein synthesis are not thought to be interchangeable between life's domains. The finding that a signal from an arthropod virus can function in bacteria questions this idea. | Architecture of the RNA polymerase II–Mediator core initiation complex
Mediator is the key transcription co-activator complex that enables basal and regulated transcription initiation by RNA polymerase (Pol) II; here a 15-subunit yeast core Mediator bound to a core Pol II initiation complex is reconstituted and its structure determined by cryo-electron microscopy at subnanometre resolution. | The octahaem MccA is a haem c–copper sulfite reductase
Sulfite-reducing microbes couple the reduction of sulfite to the generation of a proton motive force that sustains organismic growth; here, two X-ray crystal structures are solved of MccA, a c-type cytochrome enzyme with eight haem groups that catalyses the six-electron reduction of sulfite to sulfide at a novel haem–copper active site. | Seismic evidence of effects of water on melt transport in the Lau back-arc mantle
Tomographically derived seismic velocities are used to infer the distribution of partial melt below the Lau Basin, revealing an unexpected relationship between the amount of in situ melt and the water content of the magma, indicating that subducted water enhances melt extraction. | Eocene primates of South America and the African origins of New World monkeys
The discovery of new primates from the ?Late Eocene epoch of Amazonian Peru extends the fossil record of primates in South America back approximately 10 million years. | Agrochemical control of plant water use using engineered abscisic acid receptors
In response to water shortage, plants produce abscisic acid (ABA), which improves water consumption and stress tolerance; now, a strategy for controlling water use by activating engineered ABA receptors using an existing agrochemical, mandipropamid, is described. | Mitochondrial DNA stress primes the antiviral innate immune response
Mitochondrial DNA stress potentiates type I interferon responses via activation of the cGAS–STING–IRF3 pathway. | Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination
Next-generation sequencing technology is used to show that the error-prone polymerase θ (Polθ) is needed to promote alternative non-homologous end joining at telomeres, and during chromosomal translocations, while counteracting homologous recombination; inhibition of Polθ represents a potential therapeutic strategy for tumours that have mutations in homology-directed repair genes. | Functional organization of excitatory synaptic strength in primary visual cortex
In complex networks of the cerebral cortex, the majority of connections are weak and only a minority strong, but it is not known why; here the authors show that excitatory neurons in primary visual cortex follow a rule by which strong connections are sparse and occur between neurons with correlated responses to visual stimuli, whereas only weak connections link neurons with uncorrelated responses. | Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair
In studies in mammalian cells, polymerase theta (Polθ, also known as POLQ) is identified as the polymerase responsible for non-homologous end joining DNA repair; this DNA repair pathway acts in many tumours when homologous recombination is inactivated and the identification of the polymerase responsible may aid the development of new therapeutic approaches. | Initiation of translation in bacteria by a structured eukaryotic IRES RNA
A eukaryotic viral internal ribosome entry site (IRES) element is described that binds both bacterial and eukaryotic ribosomes and initiates translation in both, demonstrating that RNA structure-based initiation can occur in both these domains of life, although in bacteria the element uses a mechanism that differs from that in eukaryotes. | | Plio-Pleistocene climate sensitivity evaluated using high-resolution CO2 records
A new record of Pliocene carbon dioxide variations derived from boron isotopes shows that climate sensitivity (the change in global mean temperature in response to radiative forcing) during the Plio-Pleistocene does not vary when cycles in continental ice are taken into account; this suggests that current estimates can be used to predict future climate.
M. A. Martínez-Botí, G. L. Foster, T. B. Chalk et al. | Biocontainment of genetically modified organisms by synthetic protein design
Essential enzymes in genetically modified organisms are computationally redesigned to functionally depend on non-standard amino acids, thereby achieving biocontainment with unprecedented resistance to escape by evolution or by supplementation with environmental metabolites.
Daniel J. Mandell, Marc J. Lajoie, Michael T. Mee et al. | Mechanistic insights into the recycling machine of the SNARE complex
Using single-particle electron cryomicroscopy, several structures are reported which illuminate the mechanisms of action of the ATPase NSF that disassembles the SNARE complex into individual protein components.
Minglei Zhao, Shenping Wu, Qiangjun Zhou et al. | Transport domain unlocking sets the uptake rate of an aspartate transporter
An analysis of a bacterial homologue of the human glutamate transporter using single-molecule FRET and X-ray crystallography reveals that opening of the interface between its distinct transport and scaffold domains is rate determining for the transport cycle.
Nurunisa Akyuz, Elka R. Georgieva, Zhou Zhou et al. | | A possible close supermassive black-hole binary in a quasar with optical periodicity
A search of a data set of light curves for 247,000 known, spectroscopically confirmed quasars with a temporal baseline of about 9 years reveals a strong, smooth periodic signal in the optical variability of quasar PG 1302−102 with a mean observed period of 1,884 ± 88 days, indicating a possible supermassive black-hole binary.
Matthew J. Graham, S. G. Djorgovski, Daniel Stern et al. | Brittle intermetallic compound makes ultrastrong low-density steel with large ductility
Alloying steel with aluminium improves the material’s strength-to-weight ratio, but the resulting formation of brittle intermetallic compounds within the steel matrix reduces its ductility; here the morphology and distribution of the intermetallic precipitates are controlled to alleviate this problem.
Sang-Heon Kim, Hansoo Kim, Nack J. Kim | Silylation of C–H bonds in aromatic heterocycles by an Earth-abundant metal catalyst
Carbon–hydrogen (C–H) bond functionalization catalysed by potassium tert-butoxide, which is abundant and inexpensive, offers a direct route to the silylation of aromatic heterocycles that both obviates the need for precious metal catalysts and overcomes the limitations of previous methods.
Anton A. Toutov, Wen-Bo Liu, Kerry N. Betz et al. | A seismic reflection image for the base of a tectonic plate
A high-resolution image for the base of an oceanic plate that is subducting beneath North Island, New Zealand, reveals a channel, which is interpreted as a sheared zone of ponded partial melts or volatiles; this low-viscosity channel decouples the plate from mantle flow beneath, allowing plate tectonics to work.
T. A. Stern, S. A. Henrys, D. Okaya et al. | Recoded organisms engineered to depend on synthetic amino acids
Construction of a series of genomically recoded organisms whose growth is restricted by the expression of essential genes dependent on exogenously supplied synthetic amino acids introduces novel orthogonal barriers between these engineered organisms and the environment, thereby creating safer genetically modified organisms.
Alexis J. Rovner, Adrian D. Haimovich, Spencer R. Katz et al. | Predicting climate-driven regime shifts versus rebound potential in coral reefs
An analysis of 21 coral reefs in the Indian Ocean using data across 17 years that spanned a major climatic disturbance reveals factors that predispose a coral reef to recovery or regime shift from hard corals to macroalgae; these results could foreshadow the likely outcomes of tropical coral reefs to the effects of climate change, informing management and adaptation plans.
Nicholas A. J. Graham, Simon Jennings, M. Aaron MacNeil et al. | Transferred interbacterial antagonism genes augment eukaryotic innate immune function
Documented cases of horizontal gene transfer from bacteria to eukaryotes are rare, but now, not only is a new class of transferred genes identified, the function of one representative is also demonstrated in its new setting, where it controls bacterial growth.
Seemay Chou, Matthew D. Daugherty, S. Brook Peterson et al. | Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction
Exome sequence analysis of nearly 10,000 people was carried out to identify alleles associated with early-onset myocardial infarction; mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein A-V (APOA5) were associated with disease risk, identifying the key roles of low-density lipoprotein cholesterol and metabolism of triglyceride-rich lipoproteins.
Ron Do, Nathan O. Stitziel, Hong-Hee Won et al. | MicroRNA silencing for cancer therapy targeted to the tumour microenvironment
A novel anti-microRNA delivery platform that targets the acidic tumour microenvironment, in which a chosen anti-miRNA is coupled to a peptide that can transport the anti-miRNA across cell membranes specifically in an acidic environment.
Christopher J. Cheng, Raman Bahal, Imran A. Babar et al. | Optogenetic control of organelle transport and positioning
An optogenetic strategy allowing light-mediated recruitment of distinct cytoskeletal motor proteins to specific organelles is established; this technique enabled rapid and reversible activation or inhibition of the transport of organelles such as peroxisomes, recycling endosomes and mitochondria with high spatiotemporal accuracy, and the approach was also applied to primary neurons to demonstrate optical control of axonal growth by recycling endosome repositioning.
Petra van Bergeijk, Max Adrian, Casper C. Hoogenraad et al. | Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A
Mycothiol and ergothioneine are shown to have important roles in the biosynthesis of lincomycin A, a sulfur-containing antibiotic that is used to treat severe Gram-positive bacterial infections in people who cannot receive penicillin antibiotics.
Qunfei Zhao, Min Wang, Dongxiao Xu et al. | Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase
A novel biotin-dependent carboxylase with a preference for long-chain acyl-CoA substrates and a unique holoenzyme architecture is described.
Timothy H. Tran, Yu-Shan Hsiao, Jeanyoung Jo et al. | | | | |
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