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Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, compared to the HK2 isoform, explains the conditional essentiality of HK2 in cancer cells cultured in physiologic media.

Replication-dependent histone mRNA decay involves the RNA helicase UPF1, the histone stem-loop binding protein SLBP and the exoribonuclease 3’hExo. Here, the authors present evidence for assembly of a degradosome-like complex involving the three proteins and delineate the mechanism that drives their concerted action to achieve histone mRNA decay.

Caspase 8 protein expression is largely absent in small cell lung cancer (SCLC) patients. Here, the authors generate a caspase 8 deletion SCLC mouse model and show that it promotes a neuronal progenitor-like cell state and pre-tumoral immunosuppression triggered by necroptosis that promotes metastasis.

An EU-wide analysis shows that drained peatlands are major, underreported sources of greenhouse gases. By mapping emission hotspots, the study provides guidance for targeted rewetting and strengthens the basis for climate policy and reporting.

While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.

Polarons are hybrid particles comprising a charged particle coupled to lattice vibrations. Here, the authors identify a hole-based polaron of intermediate coupling strength in zinc oxide using infrared reflection–absorption spectroscopy and first-principles-based electronic structure theory calculations.

Accumulation of advanced glycation end products such as carboxymethyllysine (CML) has been associated with aging but their molecular roles are largely unclear. Here, the authors use proteomics to identify CML sites and show that CML formation affects protein homeostasis and cell proliferation.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

X-ray free-electron lasers offer a wealth of possibilities for future diffraction studies, but variations in successive pulses mean the wavefront is not well defined. Rutishauseret al. use grating interferometry to characterize the wavefronts shot to shot, both in situand under operating conditions.

The grain boundaries between two coexisting phases in organic semiconductor pentacene are expected to obstruct charge transport in its thin-film devices. Westermeier et al. use infrared-spectroscopic nano-imaging to show an interlocking morphology, which is uncorrelated with its grain structures.

The notion that catalysts are static entities that barely change under operation is still prevalent although it is often not true. Here, a range of operando and in situ techniques reveals the dynamic nature of Co₃O₄ during the oxidation of 2-propanol to acetone, unveiling a network of interconnected solid-state processes, such as exsolution, diffusion or void formation, that govern the catalytic performance.

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.

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.

The selective formation of C–C bonds using carbynes or carbyne equivalents is difficult due to their highly reactive nature. Now, a three-component formal cycloaddition reaction between phosphorus ylides, electron-rich olefins and electron-deficient olefins is reported, using the photocatalytic carbyne reactivity of phosphorus ylides.

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.

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 selective hydrogenation of trace acetylene to ethylene is a well-established process for purifying fossil-derived ethylene streams. Here, the authors present a self-repairing Pd-C laterally condensed catalyst that improves selectivity, prevents sub-surface hydride formation, and achieves high ethylene productivity, effectively bridging the gap between powder catalysts and single-crystal model catalysts.

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.

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.

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.

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.

Here the authors demonstrate how protein translation, controlled by Ire1α, regulates neuronal diversification in the developing neocortex.

Ataxia Telangiectasia and Rad3-related (ATR) is a key regulator of replication stress response; yet, mutations within the ATR gene cause human ATR-Seckel Syndrome associated with microcephaly and intellectual disability. Here, the authors show neuron-specific ATR deletion increases intrinsic neuronal and epileptiform activity, revealing a function of ATR beyond its role in DNA damage response.

The impact of ultrasound-controlled microbubble dynamics on the blood-brain barrier remains largely unexplored. Through theoretical and experimental research, the authors show that microbubble resonant effects in brain vessels can control the enrichment of inflammatory pathways and modulate cytotoxic T-cell infiltration in tumours.

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

Spectroscopic measurements confirm that when water is adsorbed on drops of an alkali alloy at low pressure a gold-coloured metallic layer forms as electrons rapidly move from the drop into the water.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

A vesicle trafficking Rab11 effector switch is important for ciliogenesis. Here, the authors report a ciliopathy-related disorder caused by variants in WDR44, a Rab11 effector. WDR44 variants show higher affinity for Rab11 and can impair ciliogenesis.

MethyLYZR, an epigenetic classifier of brain tumors, provides clinically relevant cancer classification results within 15 min of sequencing, with potential applications for neurosurgical intraoperative use.

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.

The lysosomal transmembrane protein CLN3 is required for the lysosomal clearance of glycerophosphodiesters in mice and in human cells, suggesting that the loss of CLN3 causes Batten disease in children due to defects in glycerophospholipid metabolism.