Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions, such as inflammation and cancer1. Although ample efforts have been invested into the structural investigation of the chemokine receptors and receptor–chemokine recognition2–4, less is known about endogenous chemokine-induced receptor activation and G protein coupling

When waves propagate through a weak disordered potential with correlation length larger than the wavelength, they form channels (branches) of enhanced intensity that keep dividing as the waves propagate1. This fundamental wave phenomenon is known as branched flow. It was first observed for electrons1,2,3,4,5,6 and for microwave cavities7,8, and it is generally expected for waves with vastly different

Mutations in proteolipid protein 1 (PLP1) result in failure of myelination and neurological dysfunction in the X-linked leukodystrophy Pelizaeus-Merzbacher disease (PMD)1,2. Most PLP1 mutations, including point mutations and supernumerary copy variants, lead to severe and fatal disease. PLP1-null patients and mice, however, can display comparatively mild phenotypes, suggesting that PLP1-suppression

Dental enamel is a principal component of teeth1, and has evolved to bear large chewing forces, resist mechanical fatigue and withstand wear over decades2. Functional impairment and loss of dental enamel, caused by developmental defects or tooth decay (caries), affect health and quality of life, with associated costs to society3. Although the past decade has seen progress in our understanding of enamel

Forests provide a series of ecosystem services that are crucial to our society. In the European Union (EU), forests account for approximately 38% of the total land surface1. These forests are important carbon sinks, and their conservation efforts are vital for the EU’s vision of achieving climate neutrality by 20502. However, the increasing demand for forest services and products, driven by the bioeconomy

The interiors of giant planets remain poorly understood. Even for the planets in the Solar System, difficulties in observation lead to large uncertainties in the properties of planetary cores. Exoplanets that have undergone rare evolutionary processes provide a route to understanding planetary interiors. Planets found in and near the typically barren hot-Neptune ‘desert’1,2 (a region in mass–radius

The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens1. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity2. However, immune functions are not unique to haematopoietic cells, and many other cell types display basic mechanisms of pathogen defence3

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1,2,3,4,5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome

Valence electrons contribute a small fraction of the total electron density of materials, but they determine their essential chemical, electronic and optical properties. Strong laser fields can probe electrons in valence orbitals1,2,3 and their dynamics4,5,6 in the gas phase. Previous laser studies of solids have associated high-harmonic emission7,8,9,10,11,12 with the spatial arrangement of atoms

Plant hormones coordinate responses to environmental cues with developmental programs1, and are fundamental for stress resilience and agronomic yield2. The core signalling pathways underlying the effects of phytohormones have been elucidated by genetic screens and hypothesis-driven approaches, and extended by interactome studies of select pathways3. However, fundamental questions remain about how information

Mammalian cells reorganize their proteomes in response to nutrient stress through translational suppression and degradative mechanisms using the proteasome and autophagy systems1,2. Ribosomes are central targets of this response, as they are responsible for translation and subject to lysosomal turnover during nutrient stress3,4,5. The abundance of ribosomal (r)-proteins (around 6% of the proteome;

The vascular interface of the brain, known as the blood–brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1,2,3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers—as is standard in BBB studies—fully represents blood-to-brain

The mechanistic target of rapamycin complex 1 (mTORC1) is a key metabolic hub that controls the cellular response to environmental cues by exerting its kinase activity on multiple substrates1,2,3. However, whether mTORC1 responds to diverse stimuli by differentially phosphorylating specific substrates is poorly understood. Here we show that transcription factor EB (TFEB), a master regulator of lysosomal

The cortex organizes sensory information to enable discrimination and generalization1,2,3,4. As systematic representations of chemical odour space have not yet been described in the olfactory cortex, it remains unclear how odour relationships are encoded to place chemically distinct but similar odours, such as lemon and orange, into perceptual categories, such as citrus5,6,7. Here, by combining chemoinformatics

The measurement of minuscule forces and displacements with ever greater precision is inhibited by the Heisenberg uncertainty principle, which imposes a limit to the precision with which the position of an object can be measured continuously, known as the standard quantum limit1,2,3,4. When light is used as the probe, the standard quantum limit arises from the balance between the uncertainties of the

Ribosomes accurately decode mRNA by proofreading each aminoacyl-tRNA that is delivered by the elongation factor EF-Tu1. To understand the molecular mechanism of this proofreading step it is necessary to visualize GTP-catalysed elongation, which has remained a challenge2,3,4. Here we use time-resolved cryogenic electron microscopy to reveal 33 ribosomal states after the delivery of aminoacyl-tRNA by

Nuclear processes, such as V(D)J recombination, are orchestrated by the three-dimensional organization of chromosomes at multiple levels, including compartments1 and topologically associated domains (TADs)2,3 consisting of chromatin loops4. TADs are formed by chromatin-loop extrusion5,6,7, which depends on the loop-extrusion function of the ring-shaped cohesin complex8,9,10,11,12. Conversely, the cohesin-release

On the 21st of February 2020 a resident of the municipality of Vo’, a small town near Padua, died of pneumonia due to SARS-CoV-2 infection1. This was the first COVID-19 death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. We collected information on

GABA (γ-aminobutyric acid) stimulation of the metabotropic GABAB receptor results in prolonged inhibition of neurotransmission that is central to brain physiology1. GABAB belongs to the Family C of G protein-coupled receptors (GPCRs), which operate as dimers to relay synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins2,3. GABAB

The human GABAB receptor—a member of the class C family of G-protein-coupled receptors (GPCRs)—mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction1. A unique GPCR that is known to require heterodimerization for function2,3,4,5,6, the GABAB receptor has two subunits, GABAB1 and GABAB2, that are structurally homologous but perform distinct and complementary functions

Fundamental studies of chemical reactions often consider the molecular dynamics along a reaction coordinate using a calculated or suggested potential energy surface1,2,3,4,5. But fully mapping such dynamics experimentally, by following all nuclear motions in a time-resolved manner—that is, the motions of wavepackets—is challenging and has not yet been realized even for the simple stereotypical bimolecular

Autoimmune thyroid disease is the most common autoimmune disease and is highly heritable1. Here, by using a genome-wide association study of 30,234 cases and 725,172 controls from Iceland and the UK Biobank, we find 99 sequence variants at 93 loci, of which 84 variants are previously unreported2,3,4,5,6,7. A low-frequency (1.36%) intronic variant in FLT3 (rs76428106-C) has the largest effect on risk

Parkinson’s disease is characterized by loss of dopamine neurons in the substantia nigra1. Similar to other major neurodegenerative disorders, there are no disease-modifying treatments for Parkinson’s disease. While most treatment strategies aim to prevent neuronal loss or protect vulnerable neuronal circuits, a potential alternative is to replace lost neurons to reconstruct disrupted circuits2. Here

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13

Cytokines were the first modern immunotherapies to produce durable responses in patients with advanced cancer, but they have only modest efficacy and limited tolerability1,2. In an effort to identify alternative cytokine pathways for immunotherapy, we found that components of the interleukin-18 (IL-18) pathway are upregulated on tumour-infiltrating lymphocytes, suggesting that IL-18 therapy could enhance

Many proteins that bind specific DNA sequences search the genome by combining three-dimensional diffusion with one-dimensional sliding on nonspecific DNA1,2,3,4,5. Here we combine resonance energy transfer and fluorescence correlation measurements to characterize how individual lac repressor (LacI) molecules explore the DNA surface during the one-dimensional phase of target search. To track the rotation

Molecular noise is a natural phenomenon that is inherent to all biological systems1,2. How stochastic processes give rise to the robust outcomes that support tissue homeostasis remains unclear. Here we use single-molecule RNA fluorescent in situ hybridization (smFISH) on mouse stem cells derived from haematopoietic tissue to measure the transcription dynamics of three key genes that encode transcription

Laser additive manufacturing is attractive for the production of complex, three-dimensional parts from metallic powder using a computer-aided design model1,2,3. The approach enables the digital control of the processing parameters and thus the resulting alloy’s microstructure, for example, by using high cooling rates and cyclic re-heating4,5,6,7,8,9,10. We recently showed that this cyclic re-heating

AU Microscopii (AU Mic) is the second closest pre-main-sequence star, at a distance of 9.79 parsecs and with an age of 22 million years1. AU Mic possesses a relatively rare2 and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star4, and with clumps exhibiting non-Keplerian motion5,6,7. Detection of newly formed planets around such a star is challenged

Formation of the body of vertebrate embryos proceeds sequentially by posterior addition of tissues from the tail bud. Cells of the tail bud and the posterior presomitic mesoderm, which control posterior elongation1, exhibit a high level of aerobic glycolysis that is reminiscent of the metabolic status of cancer cells experiencing the Warburg effect2,3. Glycolytic activity downstream of fibroblast growth

Cancers arise through the acquisition of oncogenic mutations and grow by clonal expansion1,2. Here we reveal that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterize this process

Gratings1 and holograms2 use patterned surfaces to tailor optical signals by diffraction. Despite their long history, variants with remarkable functionalities continue to be developed3,4. Further advances could exploit Fourier optics5, which specifies the surface pattern that generates a desired diffracted output through its Fourier transform. To shape the optical wavefront, the ideal surface profile

Clonally expanded blood cells that contain somatic mutations (clonal haematopoiesis) are commonly acquired with age and increase the risk of blood cancer1,2,3,4,5,6,7,8,9. The blood clones identified so far contain diverse large-scale mosaic chromosomal alterations (deletions, duplications and copy-neutral loss of heterozygosity (CN-LOH)) on all chromosomes1,2,5,6,9, but the sources of selective advantage

Oceanic lithosphere carries volatiles, notably water, into the mantle through subduction at convergent plate boundaries. This subducted water exercises control on the production of magma, earthquakes, formation of continental crust and mineral resources. Identifying different potential fluid sources (sediments, crust and mantle lithosphere) and tracing fluids from their release to the surface has proved

The extent to which the biology of oncogenesis and ageing are shaped by factors that distinguish human populations is unknown. Haematopoietic clones with acquired mutations become common with advancing age and can lead to blood cancers1,2,3,4,5,6,7,8,9,10. Here we describe shared and population-specific patterns of genomic mutations and clonal selection in haematopoietic cells on the basis of 33,250 autosomal

Decrease in processing speed due to increased resistance and capacitance delay is a major obstacle for the down-scaling of electronics1,2,3. Minimizing the dimensions of interconnects (metal wires that connect different electronic components on a chip) is crucial for the miniaturization of devices. Interconnects are isolated from each other by non-conducting (dielectric) layers. So far, research has

Observation of the neutrinoless double β decay is the only practical way to establish that neutrinos are their own antiparticles1. Because of the small masses of neutrinos, the lifetime of neutrinoless double β decay is expected to be at least ten orders of magnitude greater than the typical lifetimes of natural radioactive chains, which can mimic the experimental signature of neutrinoless double β

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report

Optical frequency combs have a wide range of applications in science and technology1. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators2,3,4,5,6,7,8,9. Such soliton microcombs10 have been applied to spectroscopy11,12,13, the search for exoplanets14,15, optical frequency synthesis16

Calcified eggshells protect developing embryos against environmental stress and contribute to reproductive success1. As modern crocodilians and birds lay hard-shelled eggs, this eggshell type has been inferred for non-avian dinosaurs. Known dinosaur eggshells are characterized by an innermost membrane, an overlying protein matrix containing calcite, and an outermost waxy cuticle2,3,4,5,6,7. The calcitic

Imaging of biomolecules guides our understanding of their diverse structures and functions1,2. Real-space imaging at sub-nanometre resolution using cryo-electron microscopy has provided key insights into proteins and their assemblies3,4. Direct molecular imaging of glycans—the predominant biopolymers on Earth, with a plethora of structural and biological functions5—has not been possible so far6. The

The nature and distribution of political power in Europe during the Neolithic era remains poorly understood1. During this period, many societies began to invest heavily in building monuments, which suggests an increase in social organization. The scale and sophistication of megalithic architecture along the Atlantic seaboard, culminating in the great passage tomb complexes, is particularly impressive2

The ongoing uptake of anthropogenic carbon by the ocean leads to ocean acidification, a process that results in a reduction in pH and in the saturation state of biogenic calcium carbonate minerals aragonite (Ωarag) and calcite (Ωcalc)1,2. Because of its naturally low Ωarag and Ωcalc (refs. 2,3), the Arctic Ocean is considered the region most susceptible to future acidification and associated ecosystem

Coordinated skills such as speech or dance involve sequences of actions that follow syntactic rules in which transitions between elements depend on the identities and order of past actions. Canary songs consist of repeated syllables called phrases, and the ordering of these phrases follows long-range rules1 in which the choice of what to sing depends on the song structure many seconds prior. The neural

Many corals harbour symbiotic dinoflagellate algae. The algae live inside coral cells in a specialized membrane compartment known as the symbiosome, which shares the photosynthetically fixed carbon with coral host cells while host cells provide inorganic carbon to the algae for photosynthesis1. This endosymbiosis—which is critical for the maintenance of coral reef ecosystems—is increasingly threatened

Metabotropic γ-aminobutyric acid receptors (GABAB) are involved in the modulation of synaptic responses in the central nervous system and have been implicated in neuropsychological conditions that range from addiction to psychosis1. GABAB belongs to class C of the G-protein-coupled receptors, and its functional entity comprises an obligate heterodimer that is composed of the GB1 and GB2 subunits2.

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms1. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts2,3. However, the mechanistic basis of this microbiota–brain signalling and its physiological relevance are

The nearby radio galaxy Centaurus A belongs to a class of active galaxies that are luminous at radio wavelengths. Most show collimated relativistic outflows known as jets, which extend over hundreds of thousands of parsecs for the most powerful sources. Accretion of matter onto the central supermassive black hole is believed to fuel these jets and power their emission1. Synchrotron radiation from relativistic

Cellular senescence is characterized by stable cell-cycle arrest and a secretory program that modulates the tissue microenvironment1,2. Physiologically, senescence serves as a tumour-suppressive mechanism that prevents the expansion of premalignant cells3,4 and has a beneficial role in wound-healing responses5,6. Pathologically, the aberrant accumulation of senescent cells generates an inflammatory

Proteins carry out the vast majority of functions in all biological domains, but for technological reasons their large-scale investigation has lagged behind the study of genomes. Since the first essentially complete eukaryotic proteome was reported1, advances in mass-spectrometry-based proteomics2 have enabled increasingly comprehensive identification and quantification of the human proteome3,4,5,6

The well known trade-off between hardness and toughness (resistance to fracture) makes simultaneous improvement of both properties challenging, especially in diamond. The hardness of diamond can be increased through nanostructuring strategies1,2, among which the formation of high-density nanoscale twins — crystalline regions related by symmetry — also toughens diamond2. In materials other than diamond

Fast radio bursts (FRBs) are bright, millisecond-duration radio transients originating from sources at extragalactic distances1, the origin of which is unknown. Some FRB sources emit repeat bursts, ruling out cataclysmic origins for those events2,3,4. Despite searches for periodicity in repeat burst arrival times on timescales from milliseconds to many days2,5,6,7, these bursts have hitherto been observed

N4-acetylcytidine (ac4C) is an ancient and highly conserved RNA modification that is present on tRNA and rRNA and has recently been investigated in eukaryotic mRNA1,2,3. However, the distribution, dynamics and functions of cytidine acetylation have yet to be fully elucidated. Here we report ac4C-seq, a chemical genomic method for the transcriptome-wide quantitative mapping of ac4C at single-nucleotide

Wave instability—the process that gives rise to turbulence in hydrodynamics1—represents the mechanism by which a small disturbance in a wave grows in amplitude owing to nonlinear interactions. In photonics, wave instabilities result in modulated light waveforms that can become periodic in the presence of coherent locking mechanisms. These periodic optical waveforms are known as optical frequency combs2

Egg size and structure reflect important constraints on the reproductive and life-history characteristics of vertebrates1. More than two-thirds of all extant amniotes lay eggs2. During the Mesozoic era (around 250 million to 65 million years ago), body sizes reached extremes; nevertheless, the largest known egg belongs to the only recently extinct elephant bird3, which was roughly 66 million years

The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 μM and are known to block the growth of Clostridium difficile1, promote hepatocellular carcinoma2 and modulate host metabolism via the G-protein-coupled

The β1-adrenoceptor (β1AR) is a G-protein-coupled receptor (GPCR) that couples1 to the heterotrimeric G protein Gs. G-protein-mediated signalling is terminated by phosphorylation of the C terminus of the receptor by GPCR kinases (GRKs) and by coupling of β-arrestin 1 (βarr1, also known as arrestin 2), which displaces Gs and induces signalling through the MAP kinase pathway2. The ability of synthetic

Quantum key distribution (QKD)1,2,3 is a theoretically secure way of sharing secret keys between remote users. It has been demonstrated in a laboratory over a coiled optical fibre up to 404 kilometres long4,5,6,7. In the field, point-to-point QKD has been achieved from a satellite to a ground station up to 1,200 kilometres away8,9,10. However, real-world QKD-based cryptography targets physically separated

Design-specific control over excited-state dynamics is necessary for any application seeking to convert light into chemical potential. Such control is especially desirable in iron(ii)-based chromophores, which are an Earth-abundant option for a wide range of photo-induced electron-transfer applications including solar energy conversion1 and catalysis2. However, the sub-200-femtosecond lifetimes of

The gut–brain axis, a reciprocal interaction between the central nervous system (CNS) and peripheral intestinal functions, is conceptually feasible from recent clinical and experimental evidence showing mutual interactions between the CNS and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel diseases (IBDs) and CNS disorders1–4. Despite recent advances