Expression, purification and characterization of phosphatidylserine-targeting antibodies for biochemical and therapeutic applications.

The externalization of Phosphatidylserine (PS) from the inner surface of the plasma membrane to the outer surface of the plasma membrane is an emblematic event during apoptosis and serves as a potent "eat-me" signal for the efferocytosis of apoptotic cells. Although less well understood, PS is also externalized on live cells in the tumor microenvironment and on live virus-infected cells whereby it serves as an immune modulatory signal that drives tolerance and immune escape. Given the importance of PS in cancer immunology and immune escape, PS-targeting monoclonal antibodies have been characterized with promising immunotherapeutic potential.

A biophysical basis for the spreading behavior and limited diffusion of Xist.

Xist RNA initiates X inactivation as it spreads in cis across the chromosome. Here, we reveal a biophysical basis for its cis-limited diffusion. Xist RNA and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the chromosome.

Microscopic evidence for nanoparticle-mediated growth of native gold in sulfide deposits at the Higashi-Aogashima Knoll Caldera hydrothermal field.

Gold (or electrum) in hydrothermal fluid precipitates directly from gold sulfide complex and/or partly via suspended nanoparticles. The hydrothermal fluid contains "invisible gold" that is atomically dispersed in sulfide minerals or as nanoparticles with a size of less than 10 nm. However, the contribution of these gold nanoparticles to the formation of native gold and its alloy with silver (electrum) remains unclear.

Predictive genetic circuit design for phenotype reprogramming in plants.

Plants, with intricate molecular networks for environmental adaptation, offer groundbreaking potential for reprogramming with predictive genetic circuits. However, realizing this goal is challenging due to the long cultivation cycle of plants, as well as the lack of reproducible, quantitative methods and well-characterized genetic parts. Here, we establish a rapid (~10 days), quantitative, and predictive framework in plants.

GZMK-expressing CD8 T cells promote recurrent airway inflammatory diseases.

Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers. T cells participate in a wide range of inflammatory diseases such as psoriasis, Crohn's disease, oesophagitis and multiple sclerosis, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities.

Methylglyoxal compromises callus mineralization and impairs fracture healing through suppression of osteoblast terminal differentiation.

Impaired fracture healing in diabetic patients leads to prolonged morbidity and increased healthcare costs. Methylglyoxal (MG), a reactive metabolite elevated in diabetes, is implicated in various complications, but its direct impact on bone healing remains unclear. Here, using a non-diabetic murine tibial fracture model, we demonstrate that MG directly impairs fracture healing.

Deficiency of histamine H receptors in parvalbumin-positive neurons leads to hyperactivity, impulsivity, and impaired attention.

Attention deficit hyperactivity disorder (ADHD), affecting 4% of the population, is characterized by inattention, hyperactivity, and impulsivity; however, its neurophysiological mechanisms remain unclear. Here, we discovered that deficiency of histamine H receptor (HR) in parvalbumin-positive neurons in substantia nigra pars recticulata (PV) attenuates PV neuronal activity and induces hyperactivity, impulsivity, and inattention in mice. Moreover, decreased HR expression was observed in PV in patients with ADHD symptoms and dopamine-transporter-deficient mice, whose behavioral phenotypes were alleviated by HR agonist treatment.

A foundation model of transcription across human cell types.

Transcriptional regulation, which involves a complex interplay between regulatory sequences and proteins, directs all biological processes. Computational models of transcription lack generalizability to accurately extrapolate to unseen cell types and conditions. Here we introduce GET (general expression transformer), an interpretable foundation model designed to uncover regulatory grammars across 213 human fetal and adult cell types.

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity.

Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles in permissive gene expression. We previously demonstrated that serotonylation and dopaminylation of Gln5 of histone H3 (H3Q5ser and H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), and alter both local and global chromatin states. Here we found that TG2 additionally functions as an eraser and exchanger of H3 monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic expression in brain and contributes to circadian gene expression and behaviour.

MPicker: visualizing and picking membrane proteins for cryo-electron tomography.

Advancements in cryo-electron tomography (cryoET) allow the structure of macromolecules to be determined in situ, which is crucial for studying membrane protein structures and their interactions in the cellular environment. However, membranes are often highly curved and have a strong contrast in cryoET tomograms, which masks the signals from membrane proteins. These factors pose difficulties in observing and revealing the structures of membrane proteins in situ.

Regulation of cGAS-STING signalling and its diversity of cellular outcomes.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway, which recognizes both pathogen DNA and host-derived DNA, has emerged as a crucial component of the innate immune system, having important roles in antimicrobial defence, inflammatory disease, ageing, autoimmunity and cancer. Recent work suggests that the regulation of cGAS-STING signalling is complex and sophisticated. In this Review, we describe recent insights from structural studies that have helped to elucidate the molecular mechanisms of the cGAS-STING signalling cascade and we discuss how the cGAS-STING pathway is regulated by both activating and inhibitory factors.

Intestinal Foxl1+ cell-derived CXCL12 maintains epithelial homeostasis by modulating cellular metabolism.

Several mesenchymal cell populations are known to regulate intestinal stem cell (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host and microbial metabolites, such as taurine and GABA, act on PDGFRαhigh Foxl1high sub-epithelial mesenchymal cells to regulate their transcription.

Enhanced Structure Stability of Au Nanobipyramids by an Customized Silver Armor.

Revealing the structure stability and evolution of gold nanocrystals at the atomic scale is crucial to their versatile applications; however, the fundamental mechanism remains elusive due to the lack of characterizations. In this work, the structural evolution of two types of Au nanobipyramids (Au NBPs) at elevated temperatures is monitored through electron microscopy analysis, and there is a sharp distinction between their structure stability despite that they possess the same crystalline structure. Detailed material characterization reveals that the surface alloying of residual Ag with Au (customized Ag armor) can greatly inhibit the Au atom diffusion and contribute remarkably to the stability and surface-enhanced Raman scattering improvement.

Automatic Single-Cell Harvesting for Fetal Nucleated Red Blood Cell Isolation on a Self-Assemble Cell Array (SACA) Chip.

(1) Background: Fetal chromosomal examination is a critical component of modern prenatal testing. Traditionally, maternal serum biomarkers such as free β-human chorionic gonadotropin (Free β-HCG) and pregnancy-associated plasma protein A (PAPPA) have been employed for screening, achieving a detection rate of approximately 90% for fetuses with Down syndrome, albeit with a false positive rate of 5%. While amniocentesis remains the gold standard for the prenatal diagnosis of chromosomal abnormalities, including Down syndrome and Edwards syndrome, its invasive nature carries a significant risk of complications, such as infection, preterm labor, or miscarriage, occurring at a rate of 7 per 1000 procedures.

Nonenzymatic lysine D-lactylation induced by glyoxalase II substrate SLG dampens inflammatory immune responses.

Immunometabolism is critical in the regulation of immunity and inflammation; however, the mechanism of preventing aberrant activation-induced immunopathology remains largely unclear. Here, we report that glyoxalase II (GLO2) in the glycolysis branching pathway is specifically downregulated by NF-κB signaling during innate immune activation via tristetraprolin (TTP)-mediated mRNA decay. As a result, its substrate S-D-lactoylglutathione (SLG) accumulates in the cytosol and directly induces D-lactyllysine modification of proteins.

Spatial transcriptome analysis of lung squamous cell carcinoma arising from interstitial pneumonia provides insights into tumor heterogeneity.

Interstitial pneumonia (IP) is a refractory disease that causes severe inflammation and fibrosis in the interstitium of the lungs, often resulting in the development of lung cancer (LC) during treatment. Previous studies have demonstrated that the prognosis of LC complicated by IP is inferior to that of LC without IP. It is therefore of the utmost importance to gain a deeper understanding of the heterogeneity of such tumors.

Migrasome formation is initiated preferentially in tubular junctions by membrane tension.

Migrasomes, the vesicle-like membrane micro-structures, arise on the retraction fibers (RFs), the branched nano-tubules pulled out of cell plasma membranes during cell migration and shaped by membrane tension. Migrasomes form in two steps: a local RF bulging is followed by a protein-dependent stabilization of the emerging spherical bulge. Here we addressed theoretically and experimentally the previously unexplored mechanism of bulging of membrane tubular systems.

Development of the membrane ceiling method for in vitro spermatogenesis.

Spermatogenesis is one of the most complex processes of cell differentiation and its failure is a major cause of male infertility. Therefore, a proper model that recapitulates spermatogenesis in vitro has been long sought out for basic and clinical research. Testis organ culture using the gas-liquid interphase method has been shown to support spermatogenesis in mice and rats.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

Transposon exonization generates new protein-coding sequences.

In a recent issue of Cell, Arribas et al. and Pasquesi et al. explore the phenomenon of transposable element (TE) exonization and its impact on proteomic and immune diversity, highlighting its potential role as a driver of evolutionary innovation.

Electro-chemo-mechanics of anode-free solid-state batteries.

Anode-free solid-state batteries contain no active material at the negative electrode in the as-manufactured state, yielding high energy densities for use in long-range electric vehicles. The mechanisms governing charge-discharge cycling of anode-free batteries are largely controlled by electro-chemo-mechanical phenomena at solid-solid interfaces, and there are important mechanistic differences when compared with conventional lithium-excess batteries. This Perspective provides an overview of the factors governing lithium nucleation, growth, stripping and cycling in anode-free solid-state batteries, including mechanical deformation of lithium, the chemical and mechanical properties of the current collector, microstructural effects, and stripping dynamics.

Single-molecule two- and three-colour FRET studies reveal a transition state in SNARE disassembly by NSF.

SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins are the minimal machinery required for vesicle fusion in eukaryotes. Formation of a highly stable four-helix bundle consisting of SNARE motif of these proteins, drives vesicle/membrane fusion involved in several physiological processes such as neurotransmission. Recycling/disassembly of the protein machinery involved in membrane fusion is essential and is facilitated by an AAA+ ATPase, N-ethylmaleimide sensitive factor (NSF) in the presence of an adapter protein, α-SNAP.

Supervised multi-frame dual-channel denoising enables long-term single-molecule FRET under extremely low photon budget.

Camera-based single-molecule techniques have emerged as crucial tools in revolutionizing the understanding of biochemical and cellular processes due to their ability to capture dynamic processes with high precision, high-throughput capabilities, and methodological maturity. However, the stringent requirement in photon number per frame and the limited number of photons emitted by each fluorophore before photobleaching pose a challenge to achieving both high temporal resolution and long observation times. In this work, we introduce MUFFLE, a supervised deep-learning denoising method that enables single-molecule FRET with up to 10-fold reduction in photon requirement per frame.

Commentary on: "Structural insights into a bacterial β-glucosidase capable of degrading sesaminol triglucoside to produce sesaminol: toward the understanding of the aglycone recognition mechanism by the C-terminal lid domain".

Sesaminol is an organic compound which shows the strong antioxidant, anti-inflammatory, and neuroprotective properties. Sesaminol triglucoside (STG) is glycosylated form of sesaminol and abundantly exists in sesame seeds. However, typical β-glucosidases could not deglycosylate STG probably due to its bulky aglycone.

In Vivo Clonal Analysis Using MADM with Spatiotemporal Specificity.

Mosaic analysis with double markers (MADM) is a powerful in vivo lineage tracing technique. It utilizes Cre recombinase-dependent interchromosomal recombination to restore the stable expression of two fluorescent proteins sparsely in individual dividing stem or progenitor cells and their progenies. Here, we describe the application of this technique for quantitative lineage analysis of radial glial progenitors in the developing mouse neocortex at the single-cell resolution.