Physicists can better study the quantum behaviour of objects on the atomic scale.
The European Union has set a worrying trend by ignoring scientific advice on overfishing. It must put long-term sustainability plans ahead of short-term political gains.
Nature digs into the rumours about the effect of festive illuminations on wireless fidelity.
Monkey King is first in a line of Chinese space missions focused on scientific discovery.
Researchers have big hopes for Kirsty Duncan, the country’s newly appointed scientist-turned-science minister.
String theory is at the heart of a debate over the integrity of the scientific method itself.
Late spending bill gives the NIH and several other research agencies healthy increases.
Gene-editing, climate change and Pluto are among the year’s top stories.
From Pluto to viral structures, this year produced an array of dazzling pictures.
Ten people who mattered this year.
News & Views
The cellular process of autophagy has been proposed to help kill Mycobacterium tuberculosis. But although the autophagy gene Atg5 is key to host immunity, other autophagy genes do not affect the outcome of tuberculosis. See Letter p.565
Microprocessor communications have received a boost from the integration of electronics and photonics in silicon — a first step towards low power consumption and efficient computing systems. See Letter p.534
Machine learning, applied to complex multidimensional data, is shown to provide personalized dietary recommendations to control blood glucose levels. This is a step towards integrating the gut microbiome into personalized medicine.
Nanoscale particles have been uniformly dispersed in a magnesium alloy, yielding composites with record-breaking strengths — and raising the prospect of using magnesium as a lightweight metal for structural applications. See Letter p.539
The discovery of microorganisms that can oxidize ammonia all the way to nitrate refutes the century-old paradigm that this nitrification process requires the activity of two types of microbe. See Article p.504 & Letter p.555
It emerges that innate immune cells called group 3 innate lymphoid cells signal directly to intestinal stem cells to promote the replacement of damaged epithelial cells lining the gut. See Letter p.560
Network analysis to determine the maximally bridged ring (or rings) of molecules is used as part of a strategy for the syntheses of architecturally complex natural chemicals; this strategy is demonstrated via the synthesis of the diterpenoid alkaloids weisaconitine D and liljestrandinine.
The first genome-wide scan for selection using ancient DNA, based on data from 230 West Eurasians dating between to 6500 and 300 BC and including new data from 163 individuals among which are 26 Neolithic Anatolians, provides a direct view of selection on loci associated with diet, pigmentation and immunity.
Until now, the oxidation steps necessary for complete nitrification have always been observed to occur in two separate microorganisms in a cross-feeding interaction; here, together with the study by van Kessel et al., Daims et al. report the enrichment and characterization of Nitrospira species that encode all of the enzymes necessary to catalyse complete nitrification, a phenotype referred to as 'comammox' (for complete ammonia oxidation).
A new deep proteomic analysis method is used to identify proteins that interact with wild-type cystic fibrosis transmembrane conductance regulator (CFTR) and its mutant version that is the major cause of cystic fibrosis.
The ability of the DEAD-box RNA helicase DDX5 to interact with master transcription factor RORγt is dependent on binding of the long noncoding RNA Rmrp; the DDX5–RORγt complex coordinates transcription of selective TH17 genes and is required for the pathogenicity of TH17 cells.
Fast radio burst FRB 110523, discovered in archival data, reveals Faraday rotation and scattering that suggests dense magnetized plasma near the source; this means that to infer the source of the burst, models should involve young stellar populations such as magnetars.
Coronal mass ejections are driven by a sudden release of magnetic energy stored in flux ropes in the Sun’s corona, but when the ambient magnetic field that runs toroidally along an unstable flux rope is strong enough to prevent the flux rope from kinking, a dynamic magnetic tension force halts the eruption.
Matter-wave interferometers provide an opportunity to measure whether quantum superpositions exist at macroscopic length scales or only at microscopically small scales; now such instruments have demonstrated quantum interference of wave packets separated by 54 cm.
An electronic–photonic microprocessor chip manufactured using a conventional microelectronics foundry process is demonstrated; the chip contains 70 million transistors and 850 photonic components and directly uses light to communicate to other chips.
Magnesium is light but not very strong; here the addition of silicon carbide nanoparticles uniformly dispersed to 14 per cent by volume, achieved through a nanoparticle self-stabilization mechanism in a molten metal alloy, yields improved strength, stiffness, plasticity and high-temperature stability.
A textural examination of volcanic ash erupted from Santiaguito volcano in Guatemala coupled with an analysis of the geophysical signals indicates that rapid heating during fault friction can cause melting and vesiculation (development of bubbles) of hydrated silicic magma, thus strongly affecting magma strength and eruptive behaviour.
Despite substantial evidence that neonicotinoid pesticides can have negative effects on bees, there have been no reports that this leads to problems with pollination; here bumblebee colonies exposed to a neonicotinoid are shown to provide reduced pollination services to apple trees, leading to a reduction in seed number.
The discovery of embryos and their associated nutrient storage tissues in exceptionally well-preserved angiosperm seeds from the Early Cretaceous period.
Until now, the oxidation steps necessary for complete nitrification had always been observed to occur in two separate microorganisms in a cross-feeding interaction; here, together with the study by Daims et al., van Kessel et al. report the enrichment and characterization of Nitrospira species that encode all of the enzymes necessary to catalyse complete nitrification, a phenotype referred to as ‘comammox’ (for complete ammonia oxidation).
Innate lymphoid cells increase the growth of mouse intestinal organoids via IL-22 production; recombinant IL-22 promotes growth of both mouse and human organoids, and promotes mouse intestinal stem cell (ISC) expansion and ISC-driven organoid growth via a STAT3-dependent pathway and independently of Paneth cells; IL-22 treatment in vivo enhances the recovery of ISCs from intestinal injury.
Genetic engineering in mice reveals that autophagy is not an essential mechanism in myeloid cells for controlling Mycobacterium tuberculosis infection, and that autophagy factor ATG5 protects organisms by regulating neutrophil influx and tissue damage.
Variant rs351855-G/A is a commonly occurring single-nucleotide polymorphism of coding regions in exon 9 of the fibroblast growth factor receptor FGFR4 (CD334) gene (c.1162G>A). It results in an amino-acid change at codon 388 from glycine to arginine (p.Gly388Arg) in the transmembrane domain of the receptor. Despite compelling genetic evidence for the association of this common variant with cancers of the bone, breast, colon, prostate, skin, lung, head and neck, as well as soft-tissue sarcomas and non-Hodgkin lymphoma, the underlying biological mechanism has remained elusive. Here we show that substitution of the conserved glycine 388 residue to a charged arginine residue alters the transmembrane spanning segment and exposes a membrane-proximal cytoplasmic signal transducer and activator of transcription 3 (STAT3) binding site Y390-(P)XXQ393. We demonstrate that such membrane-proximal STAT3 binding motifs in the germline of type I membrane receptors enhance STAT3 tyrosine phosphorylation by recruiting STAT3 proteins to the inner cell membrane. Remarkably, such germline variants frequently co-localize with somatic mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Using Fgfr4 single nucleotide polymorphism knock-in mice and transgenic mouse models for breast and lung cancers, we validate the enhanced STAT3 signalling induced by the FGFR4 Arg388-variant in vivo. Thus, our findings elucidate the molecular mechanism behind the genetic association of rs351855 with accelerated cancer progression and suggest that germline variants of cell-surface molecules that recruit STAT3 to the inner cell membrane are a significant risk for cancer prognosis and disease progression.
The relationship between DNA methylation and transcription factor binding was studied across the genome in mouse embryonic stem cells—the study reveals that the transcription factor NRF1 is methylation-sensitive and how physiological binding of NRF1 relies on local removal of DNA methylation.
In this study, 83 proteins containing helix–loop–helix–loop repeats were designed—with sequences unrelated to known repeat proteins—and experimentally characterized; 43 solution X-ray scattering spectra and 15 structures of the designed proteins show that these non-natural repeat proteins have a broad range of curvatures and that their overall structures are in close agreement with design models.
Tandem repeat proteins, which are formed by repetition of modular units of protein sequence and structure, play important biological roles as macromolecular binding and scaffolding domains, enzymes, and building blocks for the assembly of fibrous materials. The modular nature of repeat proteins enables the rapid construction and diversification of extended binding surfaces by duplication and recombination of simple building blocks. The overall architecture of tandem repeat protein structures—which is dictated by the internal geometry and local packing of the repeat building blocks—is highly diverse, ranging from extended, super-helical folds that bind peptide, DNA, and RNA partners, to closed and compact conformations with internal cavities suitable for small molecule binding and catalysis. Here we report the development and validation of computational methods for de novo design of tandem repeat protein architectures driven purely by geometric criteria defining the inter-repeat geometry, without reference to the sequences and structures of existing repeat protein families. We have applied these methods to design a series of closed α-solenoid repeat structures (α-toroids) in which the inter-repeat packing geometry is constrained so as to juxtapose the amino (N) and carboxy (C) termini; several of these designed structures have been validated by X-ray crystallography. Unlike previous approaches to tandem repeat protein engineering, our design procedure does not rely on template sequence or structural information taken from natural repeat proteins and hence can produce structures unlike those seen in nature. As an example, we have successfully designed and validated closed α-solenoid repeats with a left-handed helical architecture that—to our knowledge—is not yet present in the protein structure database.