Search

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

A GRK-isoform immunoassay was used to quantify GPCR phosphorylation and evaluate the potency of GRK inhibitors in a controlled cellular system.

The impact of ACKR3 constitutive activity is unknown. Here, the authors suppress basal ACKR3 activity using inverse agonistic nanobodies to stabilize an inactive conformation and revealing a role for ACKR3 in basal cell motility.

Organisms vary in their nitrogen and phosphorus content, shaping ecological and evolutionary processes. This study shows that nitrogen deposition is a consistent global factor associated with plant and animal stoichiometry.

The internalization of GPCRs is a key process that regulates their intracellular signaling. Here, the authors reveal the importance of β-arrestins in the internalization of 60 GPCRs and identify the β-arrestin-independent and -dependent mechanisms for GLP-1R internalization.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Aberrant redox homeostasis links lipid metabolism and cell death programs. Here, authors reveal how cell stress reduces growth factor signaling, enriching polyunsaturated fatty acids in phospholipids and sensitizing membranes to oxidative damage.

Benoit, Ganea et al. show that changes in axon initial segment (AIS) length in the prefrontal cortex of mice accompany fear learning and extinction, revealing AIS plasticity as a key feature of neuronal adaptation and memory formation.

Despite being a virulence factor, candidalysin toxin is essential for Candida albicans to penetrate the oral epithelium to establish and maintain non-infectious colonization

Identification of cancer genes altered by non-genetic mechanisms in B-cell lymphoma is challenging. Here, the authors report the development of transposon tools to perform genome-wide recessive screens in vivo and validate identified putative tumor suppressor genes using a CRISPR/Cas9 validation platform.

The accuracy of melanoma diagnosis can vary considerably among clinicians, impacting both patient outcomes and the performance of related AI tools. Here, the authors systematically assess interrater variability among expert pathologists reviewing histopathological images and clinical metadata of melanoma-suspicious lesions collected at eight German hospitals.

Multicellular tissues behave akin to nematic liquid crystals, which are fluid as well as ordered. Here, the authors develop an image analysis method to capture the nematic ordering of tissues with the complex geometries typical of morphogenesis.

Some brain lesions recover in multiple sclerosis, while others do not; however, the underlying mechanisms are unclear. Here, the authors show that microglia-derived TGFα orchestrates immune control and tissue repair, and that intranasal delivery of TGFα in the autoimmune encephalomyelitis model promotes lesion resolution.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Rustrela virus (RusV) was detected in the brains of 27 out of 29 domestic cats with ‘staggering disease’, but not of 29 control cats. This suggests RusV as the long-sought causative agent of ‘staggering disease’, which had been obscure for 50 years.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.

Flavivirus infection or vaccination can induce cross-reactive immune responses. Here, the authors show how previous immunization with the tick-borne encephalitis virus vaccine affects the immune response to the yellow fever vaccine, suggesting that the yellow fever vaccine virus conceals epitopes shared with other flaviviruses in flavivirus-naive but not flavivirus-pre-exposed individuals.

Vanishing Chern numbers usually mean that a system is topologically trivial, but this rule may be violated for periodically driven systems. Here, Maczewskyet al.report topologically protected edge modes in a periodically driven photonic lattice with all bands of zero Chern number.

The mechanical properties of central nervous system (CNS) scar tissue are considered to contribute to axon regeneration failure. Here, the authors identify members of the small leucine-rich proteoglycan family as modulators of the inhibitory viscoelastic response of CNS lesions.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

Schwab, Rao et al. report that Zeb1 mediates enhanced ferroptosis sensitivity in cancer cells after EMT activation, associated with altered expression of selected lipogenic enzymes and an subsequent increase in the PUFA:MUFA ratio.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.

Artificial intelligence has become popular as a cancer classification tool, but there is distrust of such systems due to their lack of transparency. Here, the authors develop an explainable AI system which produces text- and region-based explanations alongside its classifications which was assessed using clinicians’ diagnostic accuracy, diagnostic confidence, and their trust in the system.

The propagation of light in photonic crystals with a honeycomb structure mirrors the behaviour of charges in graphene, therefore allowing for the investigation of electronic properties that cannot otherwise be accessed in graphene itself. This approach is now used to predict unexpected edge states that localize in the bearded edges of hexagonal lattices.

Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.

Magnetic effects are fundamentally weak at optical frequencies. Now, by applying inhomogeneous strain in photonic band structures of a honeycomb lattice of waveguides, scientists show experimentally and theoretically that it is possible to induce a pseudomagnetic field at optical frequencies. The field yields 'photonic Landau levels', which suggests the possibility of achieving greater field enhancements and slow-light effects in aperiodic photonic crystal structures than those available in periodic structures.

Class A and B GPCR show differential downstream regulation and functions. Here, the authors show how their C-termini largely mediate GRK-specific β-arrestin N-domain conformational changes and co-internalization, while GPCR helix-bundles govern pERK.

A neural epigenetic signature detectable via plasma analyses is prognostic in patients with glioblastoma, resembling an oligodendrocyte-progenitor- and neuronal-progenitor-cell-like state and showing increased neuro-to-glioma synapse formation.

Looking at genes that are differentially responsive to pathogens depending on the genetic background may help in the identification of therapeutic targets in personalized medicine. Here, using challenge of monocytes with three pathogens the authors identified eQTL that are shared between pathogens and loci that are pathogen specific.

Karpf et al. showed that distinct layers of the adult human and mouse DG are populated by astrocytes, which exhibit a subtype-specific molecular profile and morphology, leading to subtype-specific physiological characteristics.

Fatty acid unsaturation by stearoyl-CoA desaturase 1 (SCD1) protects against cellular stress through unclear mechanisms. Here the authors show 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) is an SCD1-derived signaling lipid that regulates stress-adaption, protects against cell death and promotes proliferation.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.