Argonaute proteins use nucleic acid guides to find and bind specific DNA or RNA target sequences. Argonaute proteins can be found in all kingdoms of life, and play diverse biological functions including genome defense, gene regulation, and chromosome partitioning. Many Argonautes retain their ancestral endoribonuclease activity, cleaving the phosphodiester bond between target nucleotides t10 and t11

The January 2022 Hunga Tonga–Hunga Haʻapai eruption was one of the most explosive volcanic events of the modern era1,2, producing a vertical plume which peaked > 50km above the Earth3. The initial explosion and subsequent plume triggered atmospheric waves which propagated around the world multiple times4. A global-scale wave response of this magnitude from a single source has not previously been observed

Single-aperture cavities are a key component of lasers, instrumental for the amplification and emission of a single light mode. However, the appearance of high-order transverse modes as cavities size increases has frustrated efforts to scale up cavities whilst preserving single-mode operation since the invention of the laser six decades ago1-8. A suitable physical mechanism that allows single-mode

The heart, the first organ to develop, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of CHD patients survive into adulthood but often suffer premature death from heart failure (HF) and non-cardiac causes 1. To gain insight into poorly understood disease progression, we performed single nuclear RNA sequencing (snRNA-seq)

There is a well-documented gap in the observed number of scientific works produced by women and men in science, with clear consequences for the retention and promotion of women in science1. The gap might be a result of productivity differences2-5, or it might be due to women’s contributions not being acknowledged6,7. This paper finds that at least part of this gap is due to the latter: women in research

In mice, only the zygotes and blastomeres from 2-cell embryos are authentic totipotent stem cells (TotiSCs), capable of producing all the differentiated cells in both embryonic and extraembryonic tissues and forming an entire organism1. However, it remains challenging whether and how TotiSCs, representing the very beginning of a life, can be established in vitro in the absence of germline cells. Here

SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants’ receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization

The identification of general and efficient methods for the construction of oligosaccharides stands as one of the great challenges for the field of synthetic chemistry1,2. Selective glycosylation of unprotected sugars and other polyhydroxylated nucleophiles is a particularly significant goal, requiring not only control over the stereochemistry of the forming bond but also differentiation between similarly

Gastrulation controls the emergence of cellular diversity and axis patterning in the early embryo. In mammals, this transformation is orchestrated by dynamic signalling centres at the interface of embryonic and extraembryonic tissues1–3. Elucidating the molecular framework of axis formation in vivo is fundamental for our understanding of human development4–6 and to advance stem-cell-based regenerative

Magic-angle twisted trilayer graphene (MATTG) has emerged as a moiré material that exhibits strong electronic correlations and unconventional superconductivity1,2. However, local spectroscopic studies of this system are still lacking. Here we perform high-resolution scanning tunnelling microscopy and spectroscopy of MATTG that reveal extensive regions of atomic reconstruction favouring mirror-symmetric

The origin of the medieval Black Death pandemic (ad 1346–1353) has been a topic of continuous investigation because of the pandemic’s extensive demographic impact and long-lasting consequences1,2. Until now, the most debated archaeological evidence potentially associated with the pandemic’s initiation derives from cemeteries located near Lake Issyk-Kul of modern-day Kyrgyzstan1,3,4,5,6,7,8,9. These

Entangling microwave-frequency superconducting quantum processors through optical light at ambient temperature would enable means of secure communication and distributed quantum information processing1. However, transducing quantum signals between these disparate regimes of the electro-magnetic spectrum remains an outstanding goal2,3,4,5,6,7,8,9, and interfacing superconducting qubits, which are constrained

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n = 51) and observed significantly higher rates of major pathological response

The activation of eukaryotic origins of replication occurs in temporally separated steps to ensure that chromosomes are copied only once per cell cycle. First, the MCM helicase is loaded onto duplex DNA as an inactive double hexamer. Activation occurs after the recruitment of a set of firing factors that assemble two Cdc45–MCM–GINS (CMG) holo-helicases. CMG formation leads to the underwinding of DNA

Chromosomal instability (CIN) results in the accumulation of large-scale losses, gains and rearrangements of DNA1. The broad genomic complexity caused by CIN is a hallmark of cancer2; however, there is no systematic framework to measure different types of CIN and their effect on clinical phenotypes pan-cancer. Here we evaluate the extent, diversity and origin of CIN across 7,880 tumours representing

Immunosurveillance of cancer requires the presentation of peptide antigens on major histocompatibility complex class I (MHC-I) molecules1,2,3,4,5. Current approaches to profiling of MHC-I-associated peptides, collectively known as the immunopeptidome, are limited to in vitro investigation or bulk tumour lysates, which limits our understanding of cancer-specific patterns of antigen presentation in vivo6

Linkages between the outer membrane of Gram-negative bacteria and the peptidoglycan layer are crucial for the maintenance of cellular integrity and enable survival in challenging environments1,2,3,4,5. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine6,7 (BAM). Growing Escherichia coli cells segregate

Galaxy protoclusters, which will eventually grow into the massive clusters we see in the local Universe, are usually traced by locating overdensities of galaxies1. Large spectroscopic surveys of distant galaxies now exist, but their sensitivity depends mainly on a galaxy’s star-formation activity and dust content rather than its mass. Tracers of massive protoclusters that do not rely on their galaxy

Gains and losses of DNA are prevalent in cancer and emerge as a consequence of inter-related processes of replication stress, mitotic errors, spindle multipolarity and breakage–fusion–bridge cycles, among others, which may lead to chromosomal instability and aneuploidy1,2. These copy number alterations contribute to cancer initiation, progression and therapeutic resistance3,4,5. Here we present a conceptual

Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically considered an inefficient back-up. Caspase-1 activates gasdermin D pores to lyse the cell; however, caspase-1 also activates caspase-7 for unknown reasons1. Caspases can also trigger cell-type-specific death responses; for example, caspase-1

Haematopoietic stem cells (HSCs) arise in the embryo from the arterial endothelium through a process known as the endothelial-to-haematopoietic transition (EHT)1,2,3,4. This process generates hundreds of blood progenitors, of which a fraction go on to become definitive HSCs. It is generally thought that most adult blood is derived from those HSCs, but to what extent other progenitors contribute to

Two-dimensional (2D) carbon materials, such as graphene, have attracted particular attention owing to the exceptional carrier transport characteristics that arise from the unique π-electron system in their conjugated carbon network structure1,2,3,4. To complement zero-bandgap graphene, material scientists have devoted considerable effort to identifying 2D carbon materials5,6,7,8. However, it is a challenge

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1,2,3,4,5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis

Chromosomal instability (CIN) drives cancer cell evolution, metastasis and therapy resistance, and is associated with poor prognosis1. CIN leads to micronuclei that release DNA into the cytoplasm after rupture, which triggers activation of inflammatory signalling mediated by cGAS and STING2,3. These two proteins are considered to be tumour suppressors as they promote apoptosis and immunosurveillance

Quantum electrodynamics (QED) is one of the most fundamental theories of physics and has been shown to be in excellent agreement with experimental results1,2,3,4,5. In particular, measurements of the electron’s magnetic moment (or g factor) of highly charged ions in Penning traps provide a stringent probe for QED, which allows testing of the standard model in the strongest electromagnetic fields6.

Volcanoes can produce tsunamis through earthquakes, caldera and flank collapses, pyroclastic flows, or underwater explosions1,2,3,4. These mechanisms rarely displace enough water to trigger transoceanic tsunamis. Violent volcanic explosions, however, can cause global tsunamis1,5 by triggering acoustic-gravity waves6,7,8 that excite the atmosphere-ocean interface. The colossal eruption of the Hunga

The observation of the Higgs boson solidified the standard model of particle physics. However, explanations of anomalies (for example, dark matter) rely on further symmetry breaking, calling for an undiscovered axial Higgs mode1. The Higgs mode was also seen in magnetic, superconducting and charge density wave (CDW) systems2,3. Uncovering the vector properties of a low-energy mode is challenging, and