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Activation of caged fluorophores has mostly relied on the absorption of either a single ultraviolet photon or two NIR photons. Here, the authors show that two green photons (515 nm) can substitute for a single photon ( ~ 260 nm) to activate rhodamine-based dyes, thus enabling STED imaging in thick samples.

The authors devised a new behavioral task to study cooling perception in head-fixed mice. Using whole-cell recordings from layer 2/3 neurons in the somatosensory cortex, they reveal that the same neurons that respond to mechanical stimulation of the skin also respond to its cooling. In addition, they find that both the perception of cooling and the cooling responses in S1 are eliminated in TRPM8 knockout mice.

Monkeypox virus is a pathogen with pandemic potential, encoding for its own RNA capping machinery. Here, the authors present crystal structures of its 2′-O-RNA methyltransferase VP39 in complex with sub-micromolar inhibitors and reveal similarities to SARS-CoV−2 nsp14 methyltransferase.

Optical interference filters are multilayer structures for controlling the propagation of electromagnetic waves. Jin et al. have developed a method of via inkjet printing to fabricate optical interference filters with commercially relevant quality with remarkable A4 paper size (29.7 × 21.0 cm²) in ambient conditions.

Currently many of the time resolved serial femtosecond (SFX) crystallography experiments are done with light driven protein systems, whereas the reaction initiation for non-light triggered enzymes remains a major bottle neck. Here, the authors present an expanded Drop-on-Tape system, where picoliter-sized droplets of a substrate or inhibitor are turbulently mixed with nanoliter sized droplets of microcrystal slurries, and they use it for time-resolved SFX measurements of inhibitor binding to lysozyme and secondly, binding of a β-lactam antibiotic to a bacterial serine β-lactamase.

Multisystem inflammatory syndrome following SARS-CoV-2 infection results from increased serum levels of TGFβ, which impairs the reactivation of virus-specific T cells.

We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Mutations in the RRAGD gene are causative of an autosomal dominant disorder characterized by kidney tubulopathy and cardiomyopathy. Here, the authors identify a new RRAGD P88L mutation, demonstrating that all the identified RRAGD mutations inhibit the nuclear translocation of MiT/TFE transcription factors, resulting in defective responses to lysosomal or mitochondrial damage.

Angle-resolved photoemission spectroscopy (ARPES) is ideal to measure the electronic structure of materials, but its interpretation can be delicate. Here, by using a combination of density functional theory, one-step model of photoemission and soft x-ray ARPES, the authors reveal of the presence of electronic correlations in YNi₂B₂C.

Structural variants (SV) can accumulate in repeat-rich parts of the genome and transform them in unexpected ways. Here, with their new assembly-based genotyper (NAHRwhals), the authors verify multi-step SVs in 37 human loci and identify alleles at risk for copy-number variation.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Complex tissue flows in epithelia arise from the coordination of mechanical forces, where cell shape anisotropy and nematic order play a significant role. By introducing internal viscous dissipation in an active nematic vertex model, this study explains the emergence of organised, long-range flows in epithelial sheets, linking cellular dynamics to continuum active nematic and collective cell migration.

Sub-nanometer localization precision is achieved with all-optical microscopy.

The study of HIV proteolysis during maturation and replication can be difficult since different steps in these processes occur simultaneously. Here, the authors present a photolabile HIV protease inhibitor which can be deactivated by light irradiation, allowing synchronized induction of viral maturation.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Large oil spills have negative effects on marine ecosystems, but the effects of chronic smallscale spills are less well understood. Here, Brussaard et al. detect high bioavailability and toxicity of small-scale crude oil spills within 24 hours after release, which are associated with localised declines in marine plankton.

The authors show that neuronal populations in the human prefrontal-motor network interact via two discernible communication modes – ramping dynamics and neural oscillations. These modes operate in concert to facilitate rule-guided behavior.

Chromothripsis (CT) is a type of genome instability which is prevalent in medulloblastoma with germline TP53 mutations (Li-Fraumeni syndrome, LFS). Here the authors combine single-cell genomic and transcriptomic analyses to reveal the clonal heterogeneity and functional consequences of CT in LFS medulloblastoma.

Few aerobic hyperthermophilic microorganisms are known to degrade polysaccharides. Here, Nou et al. use genomic information to enrich and optical tweezers to isolate an aerobic hyperthermophilic bacterium that can grow at 65–87.5 °C using polysaccharides as sole carbon sources.

AMPK integrates information about a cell’s energy status to inform decisions about cellular processes, including autophagy. Here the authors identify cyclin Y as an AMPK substrate, which phosphorylates cyclin Y and promotes its interaction with CDK16 to stimulate autophagy.

Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia.

The endocardium lines the interior of the heart chambers and has been debated as a source of hematopoietic lineages. Here they show that the endocardium may act as a source of, and resident tissue for, hematopoietic stem and progenitor cells in zebrafish, providing evidence for diversity in origins and residences of hematopoietic cells.

DEAD-box ATPases are important regulators of RNA metabolism and are involved in all stages of RNA biogenesis. Here, the authors identify Dbp2 as a key ribonucleoprotein remodelling enzyme required for transcript release after 3’-end formation by the cleavage and polyadenylation complex.

David Page and colleagues report the sequence of the chicken W sex chromosome and compare ancestral W-linked genes across bird species. They find that the W chromosome did not acquire genes expressed exclusively in reproductive tissue, but retained genes through selection to maintain appropriate dosage levels of broadly expressed genes.

Nociceptin is an opioid peptide regulating important brain functions, including motivation and 2stress responses. Here, the authors develop and validate a genetically encoded sensor as a tool for high-resolution detection of endogenous nociceptin in living animals.

Characterizing surfaces by Raman spectroscopy is limited by the competition of surface and bulk Raman responses. Here the authors use nanoporous plasmonic membranes to enhance surface Raman signals while suppressing bulk contributions.

Antiviral nanoparticle-formulated mimics of heparan sulfate proteoglycans were developed and shown to permit strong viral association as well as inhibition of a range of viruses on in vitro and in vivo models of infection.

Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups.

Focusing on two ill-characterized subtypes of medulloblastoma (group 3 and group 4), this study identifies prevalent genomic structural variants that are restricted to these two subtypes and independently bring together coding regions of GFI1 family proto-oncogenes with active enhancer elements, leading to their mutually exclusive oncogenic activation.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

ALS is somewhat heritable, but the genetic basis is not completely understood. Here, the authors identify alterations in splicing in neurons associated with amyotrophic lateral sclerosis and uncover several associated genetic loci, with a potential link to nuclear pore defects.

A photoelectrochemical cell made from combining a dye sensitized solar cell with a semiconductor-oxide photoanode is demonstrated to perform water splitting with an efficiency of up to 3.1%. As the scheme uses relatively inexpensive materials and fabrication techniques it could provide a cost effective approach to hydrogen production.

In this prospective cohort study, authors follow 328 households in Germany with at least one confirmed SARS-CoV-2 infection and find that children are more likely to seroconvert without symptoms and have higher specific antibody levels that persist longer than in adults.

Individuals seeking post-exposure prophylaxis (PEP) for HIV may represent an important risk group for future HIV infection. Here the authors find HIV infections at long-term follow-up in 22 of 348 men who have sex with men, and 0 of 623 other PEP seekers.

Large genes require dual adeno-associated viral (AAV) vectors for in vivo delivery/expression, but current methods have limitations. Here the authors develop and functionally evaluate REVeRT, an efficient and flexible dual AAV vector technology based on reconstitution via mRNA trans-splicing.

Staphylococcus epidermidis IVK83, a nasal commensal, produces an extremely short-lived, broad-spectrum antimicrobial peptide–polyene called epifadin, which eliminates Staphylococcus aureus in vitro and in vivo.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Brain functions require a constant supply of glucose. However, the brain energy stores are unclear. Here, the authors show that oligodendroglial fatty acid metabolism can be an energy reserve for white matter axons, supporting their function.

NPM1 gene mutation is a founding event in acute myeloid leukaemia. Here, the authors find that at relapse, some patients lose the NPM1 mutation and show distinct mutational and gene expression patterns, highlighting a potential route for relapse.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

miR-132 was shown to drive pathological cardiac remodeling, a hallmark of heart failure. Here, the authors show that an antisense inhibitor of miR-132 has favourable pharmacokinetics, safety-tolerability and preclinical efficacy in mouse and porcine models of heart failure.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

Red and green genetically encoded indicators for norepinephrine have been developed and employed to monitor norepinephrine during locomotion and reward behavior in mice. The strategy used for generating these indicators also produced indicators for other neuromodulators.