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Cross-linkable co-SAMs improve hole-selective SAM stability, preventing defects and thermal degredation in perovskite solar cells, enabling 26.92% efficiency with high heat durability, and guiding the design of more efficient and durable solar cells.

The conserved SAM motif of Polycomb Repressive Complex 1 subunit Ph has been shown to play an important role in chromatin organization. Here, the authors study the effect of Ph SAM on chromatin in vitro, showing that it induces the formation of concentrated, phase-separated condensates, which enhance the ubiquitin ligase activity of PRC1.

The realization of efficient perovskite/organic tandem solar cells has been challenging due to large voltage deficits and severe non-radiative recombination. Here, the authors introduce sandwiched hole transport configuration for more balanced carrier transport, achieving efficiency of 26.05%.

In molecular junctions, where a molecule is placed between two electrodes, the current passed decays exponentially as a function of length. Here, Chen et al. show that this exponentially attenuation can be controlled by changing a single atom at the end of the molecular wire.

Polycomb Group (PcG) proteins regulate gene expression and genome architecture. Using super-resolution microscopy and molecular simulations, Waniet al. describe the organization of PcG proteins into hundreds of nano-scale protein clusters and suggest these clusters shape genome architecture.

The tumor suppressor FBW7 is a substrate adaptor for the E3 ubiquitin ligase complex SKP1-CUL1-F-box (SCF) and itself a target for ubiquitylation. Here, the authors show that TRIP12 mediates branched K11-linked ubiquitylation of FBW7, to regulate its stability and thus abundance of a subset of SCF^FBW7 substrates.

Whether and how anatomically distinct regions of the superior colliculus (SC) exhibit specialisation in multisensory temporal integration to facilitate different behavioural responses are not fully understood. This study shows that nonlinear integration in the SC enhances temporal encoding of multisensory signals, varies across the sensory field, and is supported by specialized intracollicular subnetworks.

A temperature-controlled vacuum quenching method enables the fabrication of perovskite solar modules with a power conversion efficiency of 22.69% and an area of 11.7 cm², while the corresponding cells maintain over 93% of their initial efficiency after 3,500 h of operation.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

The lysine methyltransferase SMYD5 and its newly identified substrate ribosomal protein L40 are implicated in the progression of gastric adenocarcinoma, and ablation of SMYD5 prevents metastatic disease in mouse models of this cancer.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

S-adenosylmethionine (SAM) is a widely available dietary supplement. Exogenous SAM is catabolized to adenine, an inhibitor of adenosylhomocysteinase, leading to widespread methylation inhibition and disruption of circadian rhythms in vitro and in mice.

SAMHD1 is a regulator of dNTP homeostasis and an HIV restriction factor. The authors use time-resolved cryo-EM to visualise dynamic conformational changes that drive the catalytic cycle and allosteric regulation of this multi-subunit enzyme.

In this study, Vande Voorde et al. investigate the potential of untargeted metabolomics as a stratification tool for colorectal cancer (CRC). They present a comprehensive pipeline to uncover metabolic vulnerabilities in CRC based on its genetic origin. With this approach, they show perturbations in methionine metabolism linked to APC deficiency, and identify adenosylhomocysteinase as an actionable therapeutic target.

The transcription factor p63 mediates different cellular responses affecting epithelial and oocyte biology. Here, the authors generate a mouse model (HET Δ13p63 mice) expressing the p63β isoform and show this affects ovary development, phenocopying a human syndrome, primary ovary insufficiency.

Polycomb repressive complex 2 (PRC2) silences gene expression through trimethylation of K27 of histone H3 (H3K27Me). Here, the authors report the structure of the human PRC2 complex bound to the oncogenic H3K27M mutant, and suggest a mechanism for its potency in childhood brain cancers.

The functional relevance of epigenetic modifications on transcription regulation has been an important question since their discovery. Here, the authors investigate the effect of DNA methylation on Pioneer Transcription Factor (PF) binding and distinguish between PFs that protect their binding sites from methylation and those that bind to methylated DNA and induce DNA demethylation.

A regulated stress response is essential for healthy child growth and development. Here, the authors show that a nutrition, water, sanitation, and hygiene intervention enhanced adaptive responses of the physiological stress system in early childhood.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Post-translational modifications are critical for regulating the DNA damage response. Here, the authors identify a methylation-deubiquitination crosstalk between methyltransferase PRMT1 and deubiquitinase USP11, showing that the enzymes regulate each other’s functions in DNA repair.

The Structured Operational Research Training Initiative has increased operational research capacities in Sierra Leone, and provides a model for Global North–Global South and Global South–Global South regional partnerships for health system planning and performance.

Dietary serine and glycine starvation has emerged as a potential therapy for cancer. Here, the authors show that inhibition of PHGDH, which mediates the first step in the serine synthesis pathway, improves the therapeutic efficacy of serine depletion diet in mouse xenograft models.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

SAMHD1 catalyses the hydrolysis of dNTPs into 2′-deoxynucleosides and triphosphate and is an important regulator of cellular dNTP homeostasis. Here, the authors provide insights into the catalytic mechanism of SAMHD1 by performing kinetic measurements and determining crystal structures of α-β-imido-dNTP inhibitor complexes, which reveal a bi-metallic iron-magnesium centre and catalytic hydroxyl molecule in the active site of the enzyme.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Protein kinase NEK8 is important for cilliary function, but the mechanism by which it acts is unknown. Czarnecki et al. identify the cilliary protein ANKS6 as a target and crucial activator of NEK8 and describe the importance of this protein interaction in embryonic development and organogenesis.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

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.

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.

Responses to diet composition may be linked to susceptibility to metabolic diseases such as type 2 diabetes. Here the authors report that Drosophila melanogaster displays genetic variation in survival on different diets and describe the importance for JNK-pathway and a conserved orphan nuclear hormone receptor tailless in regulating sugar tolerance.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Methylthio-alkane reductases are recently discovered enzymes that can produce methanethiol and small hydrocarbons from methylated sulfur compounds. Now the cryo-EM structure of a methylthio-alkane reductase complex is solved, revealing large metalloclusters previously observed only within nitrogenases.

Diamondoids are building blocks for nanostructured materials that can be used in molecular devices. Here, Randel et al.demonstrate an all-hydrocarbon single-molecule rectifier composed of a buckyball cage fused to a diamondoid, which outperforms either of its separate molecular constituents.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

The suboptimal performance of perovskite solar cells based on non-fullerene acceptor as the electron-transporting layer underscores the need for their molecular engineering. Here, authors substitute the core of Y6 with phenanthroline and crown ether, achieving a certified efficiency of 25.59%.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Regulation of tissue growth is crucial for development, but the underlying mechanisms remain unclear. Here, the authors identify a role for deubiquitylating enzymes in the regulation of the function of the atypical cadherin Fat and Hippo signalling.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

If left unrepaired, meiotic DSBs are toxic to mammalian cells, thus oocytes in which DSBs persist are eliminated by the DNA-damage checkpoint. Here the authors provide insights into the roles of PUMA, NOXA and BAX during DNA damage checkpoint that eliminates Dmc1^−/− and Msh5^−/− oocytes.