Spiral galaxies have distinct internal structures, including a stellar bulge, a disk, and spiral arms. It is unknown when in cosmic history these structures formed. In this study, we analyzed observations of BRI 1335–0417, an intensely star-forming galaxy in the distant Universe, at a redshift of 4.41. The [C ii] gas kinematics shows a steep velocity rise near the galaxy center and has a two-armed spiral morphology, which extends from about 2 to 5 kiloparsecs in radius. We interpret these features as due to a central compact structure such as a bulge, a rotating gas disk, and either spiral arms or tidal tails. These features had formed within 1.4 billion years after the Big Bang, long before the peak of cosmic star formation.
Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRβ) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia. Selective deletion of PDGFRβ in adult V-SVZ NSCs leads to their release from quiescence, uncovering gliogenic domains for different glial cell types. These domains are also recruited upon injury. We identify an intraventricular oligodendrocyte progenitor derived from NSCs inside the brain ventricles that contacts supraependymal axons. Together, our findings reveal that the adult V-SVZ contains spatial domains for gliogenesis, in addition to those for neurogenesis. These gliogenic NSC domains tend to be quiescent under homeostasis and may contribute to brain plasticity.
Predicting and understanding how people make decisions has been a long-standing goal in many fields, with quantitative models of human decision-making informing research in both the social sciences and engineering. We show how progress toward this goal can be accelerated by using large datasets to power machine-learning algorithms that are constrained to produce interpretable psychological theories. Conducting the largest experiment on risky choice to date and analyzing the results using gradient-based optimization of differentiable decision theories implemented through artificial neural networks, we were able to recapitulate historical discoveries, establish that there is room to improve on existing theories, and discover a new, more accurate model of human decision-making in a form that preserves the insights from centuries of research.
Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo–electron microscopy structures of human HHAT in complex with its palmitoyl–coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures reveal how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis. These principles are relevant to related enzymes that catalyze the acylation of Wnt and of the appetite-stimulating hormone ghrelin. The structural and mechanistic insights may advance the development of inhibitors for cancer.
Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity. In addition to evincing a plausible evolutionary pathway for primordial viruses, these findings highlight practical strategies for developing nonviral carriers for diverse vaccine and delivery applications.
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT 03151239).
A decade after the first report, the family of two-dimensional (2D) carbides and nitrides (MXenes) includes structures with three, five, seven, or nine layers of atoms in an ordered or solid solution form. Dozens of MXene compositions have been produced, resulting in MXenes with mixed surface terminations. MXenes have shown useful and tunable electronic, optical, mechanical, and electrochemical properties, leading to applications ranging from optoelectronics, electromagnetic interference shielding, and wireless antennas to energy storage, catalysis, sensing, and medicine. Here we present a forward-looking review of the field of MXenes. We discuss the challenges to be addressed and outline research directions that will deepen the fundamental understanding of the properties of MXenes and enable their hybridization with other 2D materials in various emerging technologies.
Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this "AstroPath" whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti–programmed cell death-1 (PD-1)–based therapy, including CD163+PD-L1– myeloid cells and CD8+FoxP3+PD-1low/mid T cells. These features were combined to stratify long-term survival after anti–PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.
Ecological resilience is the magnitude of the largest perturbation from which a system can still recover to its original state. However, a transition into another state may often be invoked by a series of minor synergistic perturbations rather than a single big one. We show how resilience can be estimated in terms of average life expectancy, accounting for this natural regime of variability. We use time series to fit a model that captures the stochastic as well as the deterministic components. The model is then used to estimate the mean exit time from the basin of attraction. This approach offers a fresh angle to anticipating the chance of a critical transition at a time when high-resolution time series are becoming increasingly available.
X-inactive specific transcript (Xist) RNA directs the process of X chromosome inactivation in mammals by spreading in cis along the chromosome from which it is transcribed and recruiting chromatin modifiers to silence gene transcription. To elucidate mechanisms of Xist RNA cis-confinement, we established a sequential dual-color labeling, super-resolution imaging approach to trace individual Xist RNA molecules over time, which enabled us to define fundamental parameters of spreading. We demonstrate a feedback mechanism linking Xist RNA synthesis and degradation and an unexpected physical coupling between preceding and newly synthesized Xist RNA molecules. Additionally, we find that the protein SPEN, a key factor for Xist-mediated gene silencing, has a distinct function in Xist RNA localization, stability, and coupling behaviors. Our results provide insights toward understanding the distinct dynamic properties of Xist RNA.
Nature, Published online: 10 June 2021; doi:10.1038/d41586-021-01589-5Cases of dengue fever plummeted in a trial of modified virus-resistant mosquitoes. Plus, four urgent questions about long COVID and clues to the mysterious origins of fast radio bursts.
Nature, Published online: 10 June 2021; doi:10.1038/d41586-021-01563-1Food bags, drink bottles and similar items account for the biggest share of plastic waste near the shore.
Nature, Published online: 10 June 2021; doi:10.1038/s41586-021-03693-yBNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants
Nature, Published online: 10 June 2021; doi:10.1038/d41586-021-01579-7Gemma Derrick revisits calls for a better research culture.
Nature, Published online: 10 June 2021; doi:10.1038/d41586-021-01560-4A trove of new detections suggests that the bursts could be the result of at least two separate astrophysical phenomena.
Nature, Published online: 10 June 2021; doi:10.1038/d41586-021-01302-6The month’s sharpest science shots, selected by Nature’s photo team.
Nature, Published online: 10 June 2021; doi:10.1038/d41586-021-01549-zMass vaccination drives in several countries are providing new data on the extent to which adult vaccination protects children — but the conclusions are mixed.
Nature, Published online: 09 June 2021; doi:10.1038/d41586-021-01564-0The first new close-up images of Jupiter’s moon Ganymede in more than 20 years. Plus, how to get real about decarbonizing the global economy and we explain the COVID lab-leak hypothesis.