Search

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Lenalidomide, a derivative of thalidomide, is an effective drug for myelodysplastic syndrome; lenalidomide binds the CRL4^CRBN E3 ubiquitin ligase and promotes degradation of casein kinase 1a, on which the malignant cells rely for survival.

Affinity-selection platforms are powerful tools in early drug discovery, but current technologies such as DNA-encoded libraries (DELs) are limited by synthesis complexity and incompatibility with nucleic acid binding targets. Here, the authors present a barcode-free self-encoded library (SEL) platform that enables direct screening of over half a million small molecules in a single experiment.

Fanconi Anemia (FA) is caused by deficiencies in DNA repair, making it hard to correct. Here the authors report a therapeutic base editing strategy to address two of the most prevalent FANCA mutations in patient hematopoietic stem and progenitor cells.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

Dendrobium is a genus of mostly epiphytic and lithophytic orchids. Here, the authors conduct comparative genome analysis for 24 chromosome-level genome assemblies and genome skimming sequencing data for 204 species in this genus, and reveal genomic variation, biosynthesis and evolutionary adaptation in Dendrobium orchids.

Formaldehyde (FA) is known to exert cytotoxicity through DNA damage. Here, the authors show that FA also triggers cellular redox imbalance by reacting with glutathione (GSH), and that FA cytotoxicity is prevented by GSH synthesis and by ADH5, an enzyme that metabolizes FA-GSH products.

Il futuro dell'istruzione superiore nelle regioni meridionali è a rischio, con gli studenti che migrano sempre più spesso al nord o rinunciano a iscriversi. Si può fermare l’esodo?

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

Defective DNA interstrand crosslink repair in Fanconi anaemia drives extensive genomic rearrangements, thereby substantially increasing the risk of cancer development.

Growing evidence suggests that immune dysregulation is involved in the pathogenesis of myelodysplastic syndromes (MDSs). Glimcher and colleagues report haplosufficiency of the serine–threonine kinase RIOK2 leads to increased IL-22 production that, in turn, suppresses erythropoiesis. Blocking IL-22 rescues this defect in mice, suggesting that IL-22 blockade might be of therapeutic value in treating MDSs.

The Tachykinin 2 (Tac2) pathway in the central amygdala is sufficient and necessary for modulating fear memory consolidation. The authors show that silencing Tac2 neurons in the amygdala of male mice reduces fear expression, while fear expression in female mice is increased when manipulations are made during proestrus.

Stability issues hinder the commercialization of perovskite solar cells. An evaporated, highly oriented wide-bandgap perovskite film is reported, enabled through an intermediate phase evolution, resulting in enhanced stability and efficiency.

Replication fork degradation can result in genome instability. Here authors reveal a role for Rif1 protein in protecting stalled replication forks from undergoing extensive, DNA2-dependent, degradation.

Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

Iron is shown to have a central role in senescence, both by triggering senescence and through its accumulation in senescent cells, which is driving the senescence-associated secretory phenotype and, in turn, promotes fibrogenesis.

This study demonstrates that ABHD10, a mitochondrial depalmitoylase, is indispensable for male fertility in mice. ABHD10 deficiency causes sperm motility defects by disrupting mitochondrial sheath formation and oxidative phosphorylation.

In an early-phase lentiviral gene therapy trial, gene-corrected autologous hematopoietic stem cells show sustained engraftment and phenotypic correction in non-conditioned patients with Fanconi anemia.

Single-cell analyses of immune cells from patients with pathogenic, single large-scale mitochondrial DNA (mtDNA) deletions including Pearson syndrome describe heteroplasmy dynamics consistent with purifying selection, as well as T-cell state-specific regulatory mechanisms and metabolic vulnerabilities.

LAMTOR2 is involved in mTOR and ERK signalling and plays a role in immunity, but its function in dendritic cells (DCs) is not clear. Here the authors show that deletion of LAMTOR2 in DCs results in increased mTOR signalling, accumulation of Flt3 on the cell surface and excessive DC proliferation in ageing mice.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Single-cell transcriptomics excel in cell subset classification and can be augmented by suitable genotype information. Here the authors devise a long-read sequencing workflow, termed nanoranger, for detection of molecular barcodes from single-cell cDNA and apply this to clonal tracking of acute myeloid leukemia and identification of complex immune phenotypes.

How repair of DNA interstrand crosslinks contributes to mutagenesis is not understood. Here, the authors identify two mutagenic repair pathways in C. elegans: FAN1-mediated translesion synthesis causing SNVs, and POLQ-mediated end joining leading to deletions. They also uncover a role for TRAIP.

Intermediate-coverage long-read sequencing in 1,019 diverse humans from the 1000 Genomes Project, representing 26 populations, enables the generation of comprehensive population-scale structural variant catalogues comprising common and rare alleles.

Coordinated gene segment rearrangement across a long genomic distance is essential for antibody gene production, but how this is regulated at the chromatin level is still unclear. Here the authors show that an architectural protein, CTCF, modulates both chromatin loop extrusion and diffusion to enforce diverse Vκ gene segment utilization for a diverse Igκ repertoire.

Here the authors introduce VACmap, a nonlinear long-read aligner that improves detection of complex structural variations like duplications, inversions, and gene conversions. It enhances SV callers’ performance on benchmarks and resolves clinically relevant loci in LPA, GBA1, and STRC genes.

Da ormai tre anni, istituzioni scientifiche e governative non trovano l’accordo su uno strumento cruciale per la prevenzione del rischio sismico.

Thalidomide and its derivatives lenalidomide and pomalidomide, which are used to treat multiple myeloma and del(5q) myelodysplastic syndrome, have antitumor and teratogenic effects through a mechanism involving destabilization of the CD147 and MCT1 proteins.

Tree peony (Paeonia ostii) has the largest chromosome of any sequenced plants to date. Here, the authors assemble its genome and reveal the association of a list of candidate genes with fatty acid biosynthesis and the possible contribution of transposon and histone expansion to maintain the giga-chromosomes.

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.

Here, the authors show that the soybean GmSNAP02 gene confers a unique mode of resistance to the soybean cyst nematode Heterodera glycines through loss-of-function mutations that implicate GmSNAP02 as a nematode virulence target.

Proximity-ligation-based sequencing from 111 samples and 5 environments reveals that a substantial proportion of phages infect multiple species.

Here, the authors present 74 radiocarbon and 31 luminescence age determinations from four sites in southern Italy. They use these data to suggest that Neanderthal disappearance in the region predated the appearance of early modern humans, a previously unclear chronology

This work introduces a pedigree-derived benchmark for single-nucleotide variants, indels, structural variants and tandem repeats, offering a variant map to validate sequencing workflows or to support the development and evaluation of new variant callers.

Here, the authors investigate gene dosage compensation in mouse pluripotent stem cells to better understand the process of X-chromosome upregulation. They report that mammalian cells can sense when segments of one of the two X chromosomes are genetically deleted in cis and compensate gene expression by upregulation in trans.

Most of the iron-binding ligands are from freshly biologically produced organic matter which likely controls iron biogeochemistry across the Southern Ocean. Our findings have consequences for iron cycling, productivity, and ocean-climate feedbacks.

A phase 1/2 trial of dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis, administered by bilateral intrathalamic, cisterna magna and intrathecal delivery found a dose-dependent biochemical correction of the disease.

Analysis of whole-genome sequencing data from 3,023 human genomes from mainland Southeast Asia identifies high genetic heterogeneity among populations in the region and many unique small and structural variants.

Grazie a 320 milioni di euro stanziati dall'UE, prende forma un'infrastruttura distribuita per la scienza dei dati. La sfida sarà quella di renderla sostenibile a lungo termine.

The use of of CDK4/6 inhibitors to treat patients with TNBC is limited by loss of Rb. Here, the authors show that a combination of CDK4/6 inhibitor and EGFR inhibitor is effective against DEDD-overexpressing TNBC, independent of Rb status.