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Serialized on-grid lift-in sectioning for tomography (SOLIST) improves the throughput of the serial lift-out technique for creating lamellas, addressing a major bottleneck in the use of cryo-electron tomography for in situ structural biology.

In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

Here, the authors combined and synchronized single-cell nanoindentation, electrophysiology and functional fluorescence imaging to evaluate the responses of neuronal networks to mechanical stimuli with piconewton force sensitivity and nanometre precision, enabling the exploration of nanomechanobiology and manipulation of neuronal systems.

Two products of the anal microbiome improve the specificity and sensitivity of diagnosing high-grade precursor lesions to anal cancer over cytology.

This study leverages existing fiber-optic networks for urban sensing. By mapping Seismic Source Power, it reveals urban activities, land use patterns, and demographic trends, enabling scalable urban monitoring without additional sensor deployment.

Pier Paolo Pandolfi and colleagues report that compound loss of Pten with Zbtb7a or Trp53 leads to de novo resistance to androgen deprivation therapy in prostate cancer. Integrative analysis of mouse and human data in a co-clinical approach identified XIAP and SRD5A1 inhibitors as potential therapies for castration-resistant prostate cancer.

This study shows that inactivation of Pml in the mouse prostate turns indolent Pten-null tumors into lethal metastatic disease. The authors identify an aberrant SREBP prometastatic lipogenic program and show that a high-fat diet induces lipid accumulation in prostate tumors and is sufficient to drive metastasis.

Experimental observations and theoretical analysis provide evidence that the spin polarization of the spin-spiral type II multiferroic NiI₂ exhibits p-wave magnetism and its spin chirality is related to ferroelectric polarization, which can be electrically controlled. 

The transcription factor Zbtb7a was previously described as an oncogene in non-Hodgkin lymphoma. Now, Pier Paolo Pandolfi and colleagues report that loss of Zbtb7a accelerates the progression of invasive prostate tumorigenesis in Pten-null mice and shows evidence of monoallelic loss in 18% of individuals with advanced prostate cancer.

NK cells play an important role in anti-tumour immunity, however, the immune-hostile microenvironment often impairs their function. Here authors show that cancers disable autophagy in NK cells, and by restoring this process, intra-tumour NK cells could be re-invigorated.

PTEN is a lipid phosphatase that functions as a dose-dependent tumor suppressor through the PI3K/AKT pathway. Here the authors describe a signaling feedback mechanism where PTEN stability is regulated through transcriptional upregulation of X-linked ubiquitin-specific protease 11 (USP11) via the PI3K/FOXO pathway.

The central amygdala inhibitory microcircuits mediate fear extinction by reversible, stimulus- and context-specific changes in neuronal responses. These alterations are absent when extinction is deficient and selective silencing of PKCδ neurons impairs fear extinction.

Polyketide natural products often contain common repeat motifs that are synthesized using iterative processes. Now a masked 1,3-diol motif, generated by a two-step process based on boronic ester homologation, has enabled the efficient iterative synthesis of polyacetates, including bahamaolide A. In addition to oxidation, the 1,3-polyboronic esters were shown to undergo various stereospecific transformations.

Pier Paolo Pandolfi and colleagues report that prostate-specific overexpression of ERG in transgenic mice results in no overt phenotype on its own but promotes progression of intraepithelial neoplasia to adenocarcinoma in a PTEN heterozygous background. They also find that human TMPRSS2-ERG–positive tumors are enriched for PTEN loss, suggesting that these two events cooperate in human prostate tumorigenesis.

Cellular senescence — an irreversible cell-cycle arrest — has been implicated in suppressing tumour formation or growth. A new cellular signalling pathway that drives senescence has now been identified. This pathway does not involve most known mediators of senescence, and instead signals via the proteins Atf4, p27 and p21. Inactivating the proto-oncogene Skp2 in the context of oncogenic signalling can induce senescence through this new pathway, indicating that drugs that target Skp2 might be useful in cancer treatment.

The metal-organic framework TAMOF-1 offers high performance for CO₂ capture and purification from model biogas streams, thanks to its high CO₂ adsorption potential, good stability in humid conditions, and energy-efficient regeneration.

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.

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.

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.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Accelerator mass spectrometry radiocarbon dating is used to construct a chronology of Neanderthal disappearance, showing that Neanderthals overlapped with anatomically modern humans for between about 2,000 and 5,000 years.

Since their initial operation, free-electron lasers are regularly upgraded in their performance and parameter control. Here the authors present the first lasing results of the soft X-ray free-electron laser beamline of the Paul Scherrer Institute, demonstrating different modes of operation and polarisation control of the tailored soft X-ray pulses.

The role of successional state in determining ecosystem sensitivity to climate change is largely unknown. Here, the authors subject seven European shrublands to moderate warming and drought conditions over 14 years and show that responsiveness is associated with the dynamic state of the ecosystem.

Two-colour X-ray free electron laser is a powerful tool for pump–probe measurements, but currently constrained by limited tunability. Here, Ferrari et al. develop a configuration that allows tuning both the pump and the probe to specific electronic excitations, providing element selectivity.

High-resolution molecular spectroscopy with cryogenic setups is hampered by the lack of a skilled interrogation tool. Here, the authors demonstrate absolute metrology of cold rovibrational spectra at 1 kHz accuracy level, by coupling a Lamb-dip saturated-absorption cavity ring-down spectrometer to a buffer-gas cooling source.

All-trans retinoic acid binds to, inhibits and induces degradation of the active form of the prolyl isomerase Pin1, thereby turning off and on a variety of Pin1 substrate oncogenes and tumor suppressors, respectively.

Skp2 is a known component of the SCF ubiquitin ligase that ubiquitylates the cell-cycle regulator p27. Akt kinase directly phosphorylates Skp2 and regulates SCF complex assembly and ligase activity, Skp2 cytoplasmic localization and Skp2-dependent regulation of cell proliferation and migration.

Although the valence and conduction electrons of a solid exist in states that extend throughout the solid, those of the innermost shells of its constituent atoms are usually considered to be strongly localized. A study of the photoelectron emission spectrum from graphene suggests that this isn’t always the case.