Search

The authors discover a homeostatic process termed interstasis, in which an increased concentration of proteins within RNA–protein condensates induces the sequestration of their own mRNAs.

EXO1 performs multiple roles in DNA replication and DNA damage repair (DDR), but its role in DDR-deficient cancers remains unclear. Here, the authors find EXO1 loss as synthetic lethal with many DDR genes involved in various cancers, including genes from Fanconi Anaemia pathway, BRCA1-A complex, and spliceosome factor ZRSR2; such interactions represent potential clinical targets.

Using globally consistent measurements and high-resolution modelling, this study finds that black carbon emissions are generally underestimated in the Global South.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

Cryptosporidium is an important threat to public health, yet it lacks a robust genetic toolkit. Here, Watson et al. introduce a targeted CRISPR-based screening method to identify parasite genes that are essential for its survival within the intestine.

An optical detection and analysis platform quantifies aggregate density, distribution and size in fluorescently labelled post-mortem human brain tissue.

The early events preceding the development of morphological abnormalities represent a key gap in the understanding of cancer. Here, the authors employ an oncogenic tagging strategy to define the contributions of HIF1A and HIF2A to the cell-type specific early events in VHL-associated oncogenesis and support therapeutic targeting of HIF2A early in VHL-associated cancers.

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.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Multiple freezing–melting pathways of ice VI are found at room temperature, occurring via the ice XXI and ice VII phases. Supercompressed water structurally evolves from high-density water to very-high-density water.

Lu et al. perform systematic functional analyses using data from the TRACERx cohort of patients with non-small-cell lung cancer and delineate how FAT1 regulates homologous recombination repair, chromosomal instability and whole-genome doubling with distinct mechanisms.

Francis et al. used cryo-electron microscopy to show how a SPIN90 dimer activates the metazoan Arp2/3 complex to nucleate linear actin filaments for unidirectional and bidirectional growth, forming potential scaffolds for rapid assembly of dynamic actin networks.

In Myeloiddysplastic syndromes, CEBPA mutations are linked to disease progression and AML. Here, the authors use somatic reprogramming and genome editing to generate isogenic cell lines from an MDS patient, identifying CEBPA bZIP domain disruption as causative for disease progression.

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.

Liu et al. show that SPIN90 dimerizes and binds two Arp2/3 complexes to nucleate two bidirectional actin filaments and the dimerization domain is conserved in multicellular animals, suggesting that the mechanism of bidirectional actin filament nucleation is conserved.

Authors measure plasma proteins in a cohort of hospitalised patients presenting to the emergency department with suspected infection, revealing six discrete host response clusters that were driven by pathogen exposure and organ dysfunction, and had distinct clinical characteristics, hospital courses, and responses to treatment.

FIKK effector kinases underwent rapid evolutionary expansion and are a druggable target in Plasmodium falciparum.

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.

The authors show human embryo lineage specification in the blastocyst is driven by differential FGF/ERK signaling, which segregates yolk sac-fated hypoblast and embryonic epiblast. They establish naïve embryonic stem cells based on these insights.

Lowering the levels of coagulation factor XII may prevent thrombosis without increasing the risk of bleeding. Here, Haj et al. use a large human dataset to show that this is the case for people carrying mutations that lower the levels of factor XII.

A study reports on the DNA methylation dynamics during embryogenesis in marsupials, showing that these differ from those occurring during embryogenesis in eutherian mammals.

Plasmacytoid dendritic cells produce type I interferons in response to viral sensing. Here the authors show that amines inhibit these plasmacytoid dendritic cell responses through CXCR4 engagement.

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.

The Perseverance rover detected polycyclic aromatic hydrocarbons preserved within sulfates in the fan and floor of Jezero crater on Mars, offering new insights into past habitability and the preservation of organic matter on Mars.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

In 2022, mpox predominantly spread through sexual contact, necessitating updated prevention strategies. Here, the authors show that rectal challenge in male cynomolgus macaques with a 2022 clade IIb MPXV isolate mimics sexual transmission, and that vaccination with modified-vaccinia Ankara protects pre- but not post-exposure.

National modeling estimates reported that three million children experience orphanhood and caregiver loss in the United States, with drug overdose surpassing COVID-19 as the leading cause of parental death by 2021.

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.

Walport & coworkers report cell-active, potent and selective cyclic peptide modulators for the enzyme peptidylarginine deiminase PADI4/PAD4, including an inhibitor, an activator and an affinity molecule, revealing insights into PADI4 regulation.

The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

Whole-genome sequencing of an ancient male Egyptian revealed a mixture of North African Neolithic and eastern Fertile Crescent ancestry, suggesting human migration between Egypt and Mesopotamia by the Old Kingdom period.

CRISPR screens reveal Toxoplasma’s GRA12 as a strain- and mouse species-transcendent virulence factor. GRA12 protects parasites from IFNγ-activated macrophage clearance and parasitophorous vacuole collapse.

Here, the authors show that Intracortical recordings in human motor cortex during attempted multi-finger movements reveal a largely linear code with two violations: magnitude normalization and greater shifts in tuning direction for weakly represented fingers.

The authors describe a sensory circuit involving the medial septum (MS), where MS glutamatergic neurons integrate food odours to prime satiety and regulate nutrient intake.

Experiments in fission yeast show that cyclin-dependent kinase is first activated in the nucleus, from which the mitotic signal is propagated from CDK at the centrosome to the cytoplasm.

The biological roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma (PDAC) are not fully explored. Here the authors perform activity based proteomics with a loss of function genetic screen and identify that USP25 promotes PDAC growth and survival through HIF-1 protein stability and transcriptional activity.

PBK is a mitotic kinase implicated in cancer. This study reveals how PBK evicts key C2H2-zinc finger transcription factors such as Ikaros, Aiolos and CTCF from DNA as cells divide, regulating mitotic chromatin accessibility and chromosome compaction.

Betaglycan is a co-receptor for selective TGF-β family ligands. Here, the authors solve its structure in complex with TGF-β and the signaling receptors, which explains its ligand selectivity and reveals its mechanism in potentiating TGF-β signaling.

A cell-penetrating fluorescent marker is used to label cells in the metastatic tumour microenvironment, revealing a variety of cell types including parenchymal cells with lung stem-cell characteristics.

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

A post-translational backbone extension acyl rearrangement (BEAR) reaction has now been developed that converts a ribosomal protein product into a new product containing a β-peptide, γ-peptide or δ-peptide backbone. BEAR reactions represent a general strategy to install extended backbones into genetically encoded proteins and peptides expressed in cells.

The Q-cycle is thought to be an essential energetic component of the photosynthetic electron-transfer chain. Here, Chlamydomonas mutants with an inactive Q-cycle but normal levels ofb₆fcomplexes are shown to display photosynthetic growth, demonstrating the dispensability of the Q-cycle in the oxygenic photosynthetic chain.

Inversion of the mouse α-globin super-enhancer reverses expression and interaction profiles of flanking genes. Contrary to the orientation-independent paradigm of enhancers, this super-enhancer acts in an orientation-dependent manner.

The role of the transcriptional effector SMAD4 in vertebrate embryo development remains unresolved. Here the authors show that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling, while Nodal signaling is maintained, but insufficient for optimal endoderm specification.