Search

The choroid plexus is a crucial but understudied brain tissue. Here, the authors use stem cells and tissue samples to trace its origins and lineage during pregnancy and to create new models for its support of the developing human brain.

Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

PAPD5 is responsible for adenylation of microRNAs. Here, the authors show that elevated level of PAPD5 enhances the adenylation and reduced expression of miR-7-5p. As a result, expression of TAB2, a target of miR-7-5p, is induced triggering neuronal apoptosis in Huntington’s disease.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Serological profiles from two observational cohort studies in The Gambia characterize surrogates of protection against Streptococcus pyogenes and reveal an antibody response against antigens that are currently in vaccine development.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

CryoEM snapshots of the nitrogenase-like DPOR protein complex captured during turnover reveal that asymmetric conformational changes, substrate recognition, and an interplay between copper and iron sulfur metalloclusters is required for electron transfer.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

Intronic GGGGCC repeat expansion in the C9orf72 gene causes ALS/FTD. Here the authors show that mutant GGGGCC RNA triggers YY1-Fuzzy transcriptional dysregulation which subsequently induces Wnt/β-catenin pathway and activates cell death in C9ALS/FTD.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Mass cytometry can be used to scale up multiplexed serology testing, as shown for the simultaneous detection of antibody levels against multiple SARS-CoV-2 proteins in hundreds of serum samples.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

Truncation of exon 18 of FGFR2 (FGFR2^ΔE18) is a potent driver mutation in mice and humans, and FGFR-targeted therapy should be considered for patients with cancer expressing stable FGFR2^ΔE18 variants.

Glutaminase is a mitochondrial complex that deaminates glutamine to form glutamate. Here the authors investigate inorganic-phosphate-induced enzyme filamentation, revealing an allosteric mechanism and roles of filamentous glutaminase in mitochondrial morphology and recycling.

Jacobsen and colleagues elucidate the nonhierarchical relationship between two types of stem cells: Vwf⁻ hematopoietic stem cells that stably replenish all blood cell lineages without a platelet bias, and Vwf⁺ stem cells that replenish almost exclusively platelets, and demonstrate that the two types utilize cellularly and molecularly distinct progenitor trajectories for replenishment of platelets.

Remote tumours cause liver dysfunction by releasing extracellular vesicles and particles containing palmitic acid, which induces TNF signalling in Kupffer cells, resulting in inflammation, fatty deposits and metabolic dysregulation, thus both reducing the efficacy and increasing the toxicity of chemotherapies.

Whole-genome sequencing of metastatic biopsies longitudinally sampled during the course of anticancer treatment reveals that the actionable metastatic cancer genome remains relatively stable over time.

Analysis of rare protein-truncating, damaging missense and copy number variants from exome sequencing of 63,237 individuals identifies 72 genes associated with autism spectrum disorder.

Synaptotagmin (syt) 1 is a calcium sensor for neuronal exocytosis. Here, the authors show that the juxtamembrane linker of this integral membrane protein negatively regulates its calcium sensing activity by mediating self-association via liquid-liquid phase separation.

Molecular landscapes of metastatic colorectal cancers (mCRC) have often been restricted to coding regions or low numbers of patients. Here the authors present a whole-genome landscape of 429 mCRC patients, revealing the mutational impact of prior therapies and potential actionable targets.

RPA is a master coordinator of DNA metabolism. Here, authors uncover that RPA is regulated by an Aurora B-signaling circuit that is critical for chromosome segregation in mitosis. Distinct phosphorylation of RPA70 modulates accessibility of RPA domains.

Bloodstream infections with Candida parapsilosis in allogeneic hematopoietic cell transplantation recipients are associated with heteroresistance to the antifungal micafungin, which can be predicted from genomic features using machine learning.

Early life is a critical window for immune development, marked by shifts in cell composition and function. Age and sex influence this process and are associated with epigenetic differences in immune-related DNA methylation, based on analysis of whole blood samples collected at ages 1 vs. 5 from a Canadian longitudinal paediatric cohort

The HIV-1 entry inhibitor temsavir prevents the interaction of the envelope glycoprotein with its cellular receptor. Here, authors apply CryoEM to show that HIV-1 clade AE resistance to temsavir is a combination of the residue at position 375 (His) and mutations in the gp120 mobile layers. Mutation of His375 to Ser/Thr and reversion of the layer mutations are required to restore temsavir sensitivity.

Analyses of single epithelial cells from early-stage lung adenocarcinoma and normal lung identifies a population of intermediate cells that may have an increased likelihood of transforming to tumour cells after injury such as tobacco exposure.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Ependymoma is a tumor of the brain or spinal cord with the two most common and aggressive types mainly occurring in children. Here the authors employ 3D genomics and epigenomics to reveal targets for aggressive ependymoma tumors in children.

The stem cells in the Arabidopsis root meristem are maintained by the expression of the transcription factor WOX5 in the stem cell organizer. This study reveals that WOX5 functions in a coherent feed-forward loop, regulating auxin signalling.

Mediator proteins such as BRCA2 and Rad52 direct formation of Rad51 filaments in Homologous Recombination. Here, the authors present cryoEM structures of Saccharomyces cerevisiae Rad52 revealing a homodecamer and Rad51 binding to two regions in Rad52.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Cell-type-resolved spatial proteomics of the skin from patients with toxic epidermal necrolysis reveals that it is driven by JAK/STAT signaling, leading to successful treatment of this potentially fatal condition in patients using JAK inhibitors.

The autism spectrum disorders are complex genetic traits characterized by various neurodevelopmental deficits. Here, the authors analyse defective gene family interaction networks in autism cases and healthy controls and identify potential gene family interactions that may contribute to autism aetiology.

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.

Results from a comprehensive evaluation of the function of BRCA2 variants, particularly variants of uncertain significance, provide a useful resource to improve the clinical management of individuals who carry such genetic variants.

The genomic differences between primary and metastatic tumours are assessed across 23 cancer types using pan-cancer whole-genome analysis.

The prevalence and conservation of C-degrons across eukaryotes is unclear. Here, the authors perform an unbiased survey of C-degrons in budding yeast and identify a C-degron pathway of broad specificity operated by the SCF^Das1 ubiquitin ligase.

Identifying patients that will respond to a particular therapy remains a key challenge in precision oncology. Here, in gastric cancer, the authors show that circulating tumour DNA can predict recurrence, provided that the signal from white blood cells is filtered out.

Cancers deficient in homologous recombination can benefit from treatment with poly ADP-ribose polymerase (PARP) inhibitors. Here, the authors generated a classifier that can predict homologous recombination deficiency from genomic data and suggest several cancer types that may benefit from PARP inhibitor treatment.

Neoadjuvant treatment with nivolumab plus ipilimumab is well tolerated and demonstrates clinical efficacy in patients with early stage lung cancer.

Pre-clinical studies have shown that TP53 mutations can account for acquired resistance to HDM2 antagonists. This study provides clinical evidence for the emergence of TP53mutations in circulating cell-free DNA, seen in 5 out of 20 de-differentiated liposarcoma patients treated with an HDM2 antagonist.

Small liposomes of uniform sizes are valuable tools for studying membrane biology and developing drug-delivery vehicles. Now, a DNA-assisted sorting technique has been shown to produce multiple species of monodispersed liposomes with mean diameters below 150 nm in a scalable manner. This approach has enabled the high-resolution analyses of curvature-dependent membrane protein activities.

Chiuppesi et al. demonstrate the use of a synthetic poxvirus-based platform to rapidly generate multi-antigenic vaccine candidates expressing spike and nucleocapsid antigens of SARS-CoV-2. Immunization of mice stimulates potent antigen-specific humoral and cellular immune responses, including neutralizing antibodies.