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Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

Using inbred medaka strains, the authors mapped 59 genetic loci linked to heart rate. Gene editing validated conserved genes affecting heart rate and morphology, highlighting the power of isogenic strains in uncovering mechanisms of cardiac traits and disease.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

The West Antarctic Ice Sheet responded to different natural forcing mechanisms than the East Antarctic Ice Sheet through the mid-Pliocene due to a greater sensitivity to oceanic feedbacks, according to iceberg-rafted debris records and ice-sheet modelling experiments.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

The Antarctic ice sheet during the late Oligocene (26.2–25.2 million years ago) was highly dynamic, alternating between near-modern size during glacial periods and smaller volumes during interglacials, driven by orbitally-paced climate variations, according to a high-resolution multi-proxy record.

Methods for generating macroscopic chiral matter struggle with limited scalability. Here, the authors show two vacuum filtration methods - twist stacking and mechanical rotation - to align carbon nanotubes into chiral structures at wafer scale with tunable circular dichroism.

Optimizations of X-ray nanotomography including the choice of resin allows high-resolution imaging of mouse brain tissue, approaching the resolution of volume electron microscopy. Since it does not require slicing the tissue, this technology may become an attractive alternative to current standard methods for connectomics.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

Integration of transplanted photoreceptors into the host retina has been assumed as the underlying mechanism for vision improvement in pre-clinical studies. Here, the authors show that the majority of transplanted photoreceptors do not structurally integrate but exchange intercellular material with host cells.

In this work, Beyer and colleagues have utilized display screening technologies to comprehensively chart RAS proteins “druggability” and in doing so unravel a targetable ligand-induced pocket in RAS opening unprecedented anti-RAS targeted opportunities.

Resting CD4⁺ T cells are resistant to HIV-1 infection, but the underlying reasons for this lack of permissiveness have not been clear. Oliver Fackler and colleagues now report that SAMHD1, the deoxynucleoside triphosphate triphosphohydrolase responsible for restriction of HIV-1 infection in myeloid cells, also restricts infection of resting CD4⁺ T cells. The findings shed new light on the mechanisms of cellular and molecular regulation of HIV-1 infection.

The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome IV has been determined. Apart from chromosome XII, which contains the 1–2 Mb rDNA cluster, chromosome IV is the longest S. cerevisiae chromosome. It was split into three parts, which were sequenced by a consortium from the European Community, the Sanger Centre, and groups from St Louis and Stanford in the United States. The sequence of 1,531,974 base pairs contains 796 predicted or known genes, 318 (39.9%) of which have been previously identified. Of the 478 new genes, 225 (28.3%) are homologous to previously identified genes and 253 (32%) have unknown functions or correspond to spurious open reading frames (ORFs). On average there is one gene approximately every two kilobases. Superimposed on alternating regional variations in G+C composition, there is a large central domain with a lower G+C content that contains all the yeast transposon (Ty) elements and most of the tRNA genes. Chromosome IV shares with chromosomes II, V, XII, XIII and XV some long clustered duplications which partly explain its origin.

Terrestrially derived dissolved organic carbon is pervasive in the Arctic Ocean, especially within the Transpolar Drift current, and changing inputs could impact future marine carbon cycling, according to a dissolved organic carbon inventory.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

This directory was made possible by a unique international collaboration between the 633 scientists whose names appear below. It represents both the first published description of the complete sequence of most chromsomes from Saccharomyces cerevisiae, and the first published overview of the entire sequence. As such, the authors would like future papers referring to the entire sequence and/or its contents to cite this directory; future papers referring to the sequence of individual chromosomes should refer to the papers listed at the head of page 9. The authors’ affiliations appear in the papers describing the individual chromosomes.

Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.

The study reveals strikingly different nonlinear Rabi splitting dynamics in MoSe₂ monolayers and (Ga,In)As quantum wells, highlighting the pivotal role of Coulomb interactions in shaping light–matter coupling in two-dimensional semiconductors.

The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome VII has 572 predicted open reading frames (ORFs), of which 341 are new. No correlation was found between G+C content and gene density along the chromosome, and their variations are random. Of the ORFs, 17% show high similarity to human proteins. Almost half of the ORFs could be classified in functional categories, and there is a slight increase in the number of transcription (7.0 %) and translation (5.2 %) factors when compared with the complete S. cerevisiae genome. Accurate verification procedures demonstrate that there are less than two errors per 10,000 base pairs in the published sequence.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Accurate segmentation of ischemic stroke lesions from brain MRI is crucial for timely diagnosis and treatment planning. Here, the authors present DeepISLES, an AI ensemble for stroke MRI analysis that outperforms previous methods and matches expert radiologist performance in identifying stroke lesions.

Conodonts, early vertebrates, are thought to have evolved complex tooth tissue as an adaptation for feeding. Here, the authors use Electron Backscatter Diffraction to show increasing dental crystallographic order through conodont evolution, in parallel with dietary adaptations.

Causal and mechanistic modelling strategies, which aim to infer cause–effect relationships, provide insights into cellular responses to perturbations. The authors review computational approaches that harness machine learning and single-cell data to advance our understanding of cellular heterogeneity and causal mechanisms in biological systems.

A product of the soluble epoxide hydrolase enzyme, 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP), is implicated in the pathogenesis of diabetic retinopathy; levels of 19,20-DHDP increase in the retinas of mice and humans with diabetes, and inhibition of its production can rescue vascular abnormalities in a mouse model of the disease.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

The first-in-human trial of AAV2i8-I1c (AB-1002) — an adeno-associated virus vector that targets a protein phosphatase inhibitor to cardiac muscle — suggests a cautious return of cardiac gene therapy after earlier setbacks, with a new target, dose optimization and improved vector design shaping future directions.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

This study shows that photosynthesis in the Arctic Ocean can occur at lower light levels than previously thought. This finding is based on unique measurements made on microalgae underneath sea ice in the high Arctic at the end of the polar night.

R-loops formed by RNA hybridization to DNA template strand during transcription influence HIV-1 integration into the CD4⁺ T cell genome. The unwinding of R-loops by splicing helicase Aquarius facilitates integration into speckle-associated domains.

Wood density is a key control on tree biomass, and understanding its spatial variation improves estimates of forest carbon stock. Sullivan et al. measure >900 forest plots to quantify wood density and produce high resolution maps of its variation across South American tropical forests.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Although patients with rheumatoid arthritis (RA) usually exhibit symmetrical joint involvement, some can develop alternative patterns of arthritis, often translating into differences in responsiveness to treatment. In this study, the authors propose that the long-noncoding RNA, HOTAIR, might contribute to these differences.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

This work compares the preclinical lung biodistribution and efficacy profile of inhaled anti-CCN2 (cellular communication network factor 2) Anticalin® protein PRS-220 for the treatment for idiopathic pulmonary fibrosis (IPF) compared to systemic delivery of a CCN2 inhibitor.

Magnetic cooling could be a radically different energy solution that could replace conventional vapour compression refrigeration in the future. It is now shown that a Heusler-type magnetocaloric alloy exhibits a remarkable cooling capability due to the effect of a sharp structural transformation at a specific temperature. The finding may be of relevance beyond Heusler alloys and represents an important step towards the implementation of cooling systems based on magnetocaloric materials.