Browse Articles

Alzheimer’s trial results lend momentum to drugs targeting tau

First drug to lower the protein and slow cognitive decline created buzz despite puzzling data

Entanglement-enhanced learning of quantum processes at scale

Unmasking adversarial attacks using a robust XAI-driven approach for secure medical image classification

Contagious fish cancer overruns New England lake

Genetic studies reveal rare example of identical transmissible tumors

Elucidation of the intrinsic electronic mechanism governing interfacial chemical bonding in metal-polymer hybrids

Deep learning-based classification of benign anorectal lesions on endoanal ultrasound: a proof-of-concept study

Publisher Correction: A 98-qubit trapped-ion quantum computer with all-to-all connectivity

Prominent Salk Institute biologist to resign following sexual misconduct investigation

Staffers complain that Salk allowed circadian rhythms researcher Satchidananda Panda to depart quietly, while the allegations and findings remain under wraps

SYCP2 recruits HORMAD2 to chromosome axes for unsynapsed chromatin silencing and synapsis surveillance in meiosis

Abstract Faithful chromosome segregation during meiosis requires accurate recombination and synapsis of homologous chromosomes. These processes are monitored in mammals by checkpoints involving the meiotic HORMA-domain proteins HORMAD1 and HORMAD2, which bind unsynapsed chromosome axes and promote activation of the DNA damage–response kinase ATR independently of DNA double-strand breaks (DSBs). However, the in vivo mechanism for axial HORMAD1 and HORMAD2 recruitment and its relevance to checkpoint signaling remain unclear, although the chromosome-axis component SYCP2 has been proposed to contain a candidate HORMAD-binding closure motif (CM). We show that deletion of the SYCP2 CM disrupts SYCP2–HORMAD2 complexes and selectively prevents HORMAD2 axis binding without affecting axis assembly, recombination, or axial HORMAD1 recruitment. Consequently, ATR accumulation and signaling on unsynapsed axes are reduced, and the prophase checkpoint malfunctions, manifesting in aberrant elimination of synapsis-proficient spermatocytes and persistence of asynaptic oocytes, which reflect sex-specific characteristics of checkpoint mechanisms. The phenotypes of SYCP2-CM–deficient and HORMAD2-null mice are indistinguishable, establishing the requirement for HORMAD2 axis recruitment in synapsis surveillance. We propose that axial recruitment generates a HORMAD2 scaffold that drives clustering-mediated ATR network activation independently of DSBs, thereby linking chromosome-axis architecture to synapsis quality control in mammalian meiosis.

Efficacy of different irrigation activation techniques in removing biofilm-mimicking hydrogel from internal root resorption and lateral canals

A 3D genome atlas of human tonsil and the role of loop extrusion in B cell somatic hypermutation

B cell maturation within the germinal center tissue microenvironment involves immunoglobulin gene diversification by somatic hypermutation (SHM). How three-dimensional (3D) genome architecture influences SHM is not fully understood. We leveraged sequencing-based and image-based 3D genomics and transcriptomics to map single-cell 3D genome organization and gene expression across cell types and states in human tonsils and in B cell lymphoma cell lines. These analyses revealed trajectories of compartment, looping, and nuclear position changes during the B cell immune response and activation of SHM. Targeted protein degradation of cohesin component RAD21 revealed its contribution to enabling SHM. Our results provide a single-cell 3D genome atlas of human tonsil cells and outline the links between the chromatin loop extrusion machinery and SHM.

Spatial transcriptomics reveals distinct cell type dynamics following opioid dependence in female mice with the common human μ-opioid receptor variant Oprm1 A118G

Marine heatwaves in the Northeast Pacific intensify landfalling atmospheric rivers on the west coast of North America

Abstract Extreme precipitation along the west coast of North America is often associated with atmospheric rivers (ARs), fueled by evaporation from the ocean. When ARs interact with marine heatwaves (MHWs), they can form compound extreme events with amplified hydrological impacts. Here, we quantify how MHWs influence the intensity and precipitation of landfalling ARs through thermodynamic air–sea interaction processes. We use high-resolution regional coupled ocean–atmosphere ensemble simulations to isolate the influence of large-scale MHW-related sea surface temperature (SST) anomalies while constraining the synoptic-scale atmospheric circulation. Focusing on well-documented AR events during the 2013–16 Northeast Pacific MHW, we show that anomalously warm SSTs enhance evaporation and lower-tropospheric moisture availability, leading to a robust increase in integrated vapor transport and intensified landfalling ARs. The enhanced moisture transport results in earlier onset and substantially increased coastal precipitation, particularly over drought-vulnerable regions of California. Moisture-budget diagnostics demonstrate that this amplification arises from a direct thermodynamic response to SST anomalies, rather than indirect modulation through changes in large-scale atmospheric circulation. Insights gained from this case study identify a thermodynamic pathway linking MHWs and ARs, highlighting the role of persistent oceanic thermal anomalies in shaping compound hydrological extremes under continued climate warming.

What lies beyond the Fields Medal?

Tunable yielding and emergent rheology in amorphous solids with active particle doping

Daraxonrasib in Advanced <i>RAS</i> -Mutated Pancreatic Cancer

Diagnostic validity of ELISA-IgM, DPP® rapid test, and MAT for leptospirosis diagnosis in Brazilian reference laboratories: a latent class analysis

HELZ is a RNA-DNA helicase that resolves R loops to facilitate homologous recombination repair

Abstract R loop homeostasis is critical for DNA double-strand break (DSB) repair; however, how R loops are resolved in this context is poorly understood. Here, we define HELZ as a unique RNA-DNA helicase that resolves R loops to facilitate homologous recombination (HR) repair. From a synthetic lethal etoposide resistance siRNA screen, we found that HELZ depletion causes R loop-mediated hypersensitivity to DSB-inducing agents, and HELZ localizes and binds to DSBs. HELZ preferentially binds to and unwinds RNA-DNA hybrids with 5’ssRNA overhangs to promote R loop resolution genome-wide and at DSBs. Interestingly, HELZ facilitates BRCA1 recruitment to DSBs by preventing R loop accumulation, thereby promoting DNA end resection and HR to prevent R loop mediated genomic instability. In summary, we show that HELZ resolves R loops critical for HR, thereby promoting genome stability and resistance to DSB-inducing agents.

Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer

Effects of pulse-type near-fault ground motions on the nonlinear seismic response of steel frames with inverted-V CBF and EBF systems