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Retinoic acid- and TGF-β1-preconditioned hBM-MSCs show distinct reparative profiles after transplantation in Busulfan-induced testicular injury
Allelopathic potential and allelochemical tolerance of bean (Phaseolus vulgaris L.) cultivars in interaction with Datura stramonium L
Neuronal expression of retinoid-related orphan receptor gamma (RORγ) and revisiting its role in the central nervous system
Line waves at the interface of magneto–electric boundaries
Correction: Insights into Sudbury’s deep architecture: a revised geodynamic model for Earth’s largest ore-bearing impact structure
Remaining useful life prediction of mechanical equipment based on attention kernel dynamic time warping
Public thresholds for antidepressant effectiveness and adverse drug reaction rates: a cross-sectional study
Abstract The effectiveness of antidepressants (ADs) in the treatment of depression is continuously discussed regarding its clinical relevance. The objective of this study was to explore thresholds of members of the public for effectiveness of ADs relative to the frequency of adverse drug reactions (ADRs) deemed acceptable. We conducted a cross-sectional online survey in Germany that included individuals with and without experiences of depression and ADs. Participants were presented a case scenario describing a moderate depressive episode, operationalized with the Montgomery Åsberg Depression Rating Scale (MADRS). Participants were asked to rate the effectiveness of different treatment options, estimate the frequency of 15 ADRs, and indicate the minimal level of treatment effectiveness they would require to accept certain ADRs. The survey was completed by 208 participants (144 female, 64 male), 44 were taking ADs. The effectiveness of ADs was significantly overestimated ( t (204) = 8.96, p < 0.001, d = 0.63). For 13 ADRs, participants selected package-insert frequency categories that were significantly lower than the corresponding reference categories. For example, to accept the potential ADR of seizures, participants required a symptom improvement of M = 23.51 ( SD = 8.82) points on the MADRS. We propose that patient-physician communication about risks and benefits of AD treatment should explicitly address individual expectations.
Butyrate epigenetically licenses sustained epithelial-T cell crosstalk for intestinal immune tolerance
Mechanical properties and failure characteristics of granite with non-through cracks under thermal cycling
Induced ubiquitination of the partially disordered estrogen receptor alpha via a 14-3-3 directed molecular glue-PROTAC
Abstract Proteins lacking defined ligandable pockets remain challenging drug targets. Here, we develop a molecular glue-based PROTAC ( MG PROTAC) approach that chemically conjugates a molecular glue stabilizer to a VHL-recruiting ligand to capture and ubiquitinate the 14-3-3/Estrogen receptor α (ERα) complex. Our designed MG PROTACs engage a composite interface between 14-3-3 and the disordered F-domain of ERα, promoting cooperative complex formation and targeted ubiquitination. Biophysical characterization revealed distinct linker-dependent cooperativities across the MG PROTAC series, which influenced both cellular permeability and ubiquitination efficiency. Cryo-EM of the most cooperative MG PROTAC uncovered de novo VHL–14-3-3ζ contacts, while molecular dynamics simulations rationalize the stabilizing interactions underlying cooperativity. Strikingly, fine-tuning linker design enables selective ubiquitination of distinct complex subunits. These findings establish a structural and mechanistic framework for integrating molecular glue and PROTAC principles, expanding the scope of drug discovery to previously intractable protein complexes.
Variant-specific and cross-reactive antibody responses following COVID-19 booster vaccinations and SARS-CoV-2 breakthrough infections
Abstract SARS-CoV-2 has evolved into several genetic variants, all bearing mutations that reduce antibody binding and affect vaccine and treatment effectiveness. Updated COVID-19 vaccines, including bivalent formulations (wild type [WT]/BA.1 or WT/BA.5) and more recent monovalent versions targeting emerging variants such as XBB.1.5, JN.1, KP.2 or LP.8.1, were developed to broaden protection. However, immune imprinting may limit the induction of neutralizing antibodies against strains that differ significantly, even after receiving several variant-specific boosters. A deeper understanding of how booster vaccination reshapes antibody specificity remains essential for rational vaccine design. We examined the antibody response to a bivalent WT/BA.5 booster, focusing on antibody levels and neutralization. Serum samples collected before and after a fourth dose of monovalent WT or bivalent (WT/BA.5) mRNA vaccines were compared with sera from individuals after primary WT infections and Omicron BA.1, BA.2, or BA.5 breakthrough infections. We found that both monovalent and bivalent boosters significantly increased IgG and neutralizing antibodies, but breakthrough infections induced broader cross-reactive responses. Depletion experiments revealed that booster-induced immunity was predominantly mediated by cross-reactive antibodies, with the highest levels after breakthrough infections and the lowest after a primary WT infection. These findings provide functional insights into the antibody specificities associated with imprinting effects following variant-adapted booster vaccination.
The oligosaccharyltransferase TaOST1B promotes viral infection by enhancement of RNA silencing suppression in wheat
Abstract Viral suppressors of RNA silencing (VSRs) are crucial for viral infection. Here, we show that a wheat ( Triticum aestivum ) oligosaccharyltransferase ( TaOST1B ) is associated with resistance to Wheat yellow mosaic virus (WYMV). TaOST1B interacts with WYMV-encoded P1 and enhances the VSR function of P1 by N-glycosylating its asparagine residue at position 116. This increases intranuclear accumulation of P1 through interaction with the nuclear transport protein TaIMP-α2 and blocks the interaction between calmodulin (CaM3) and CaM-binding transcriptional activator (CaMTA3) to suppress RNA interference. Nevertheless, nonglycosylated P1 loses its VSR function and forms aggregates triggering endoplasmic reticulum (ER) stress and is subsequently degraded by the 26S proteasome. A natural variant of TaOST1B fails to bind P1 and regulate its N-glycosylation, which induces ER stress and proteasome-mediated degradation to attenuate WYMV infection. Our study identifies an oligosaccharyltransferases as being utilized by VSR to promote viral infection, offering insights into the arms race between plants and viruses.
Catalytic Dehydrogenation Enhanced by Controlling Platinum Nanoparticle Density
Development and validation of an in-house one-step RT-qPCR method for the quantification of the BCR::ABL1 p210 transcripts
ADAPT-M: a workflow for rapid, quantitative in vitro measurements of enriched protein libraries
Abstract Protein-protein interactions underpin most cellular processes, and engineered binders present powerful tools for probing biology and developing novel therapeutics. However, scalable, quantitative characterization of large numbers of candidates remains a major bottleneck. Here we show that ADAPT-M ( A ffinity D etermination by A daptation of P ro T ein binders for M icrofluidics) enables rapid, parallel measurement of binding affinities and dissociation behavior directly from enriched display libraries in under one week, without requiring gene synthesis or hands-on protein purification. Applied to a computationally designed library targeting the SARS-CoV-2 Omicron BA.1 receptor binding domain, ADAPT-M recovered most highly enriched variants and revealed that many display-enriched binders lacked measurable binding in vitro, highlighting limitations of screening alone. ADAPT-M enabled quantitative characterization of dozens of binders in parallel and selection of lead candidates for structural analysis. Unexpectedly, structural and mutational studies revealed that designed binding interfaces were preserved despite engaging alternative epitopes. By bridging screening and scalable in vitro validation, ADAPT-M accelerates protein binder discovery and supports data-driven protein engineering.
Upscaling MSWI fly ash into multifunctional foamed geopolymers: synergistic water filtration and intrinsic heavy metal immobilization via a dual-stabilization mechanism
Impact of crystal symmetry lowering on proton tunneling
Multiparametric analysis of sperm chromatin and ROS reveals the existence of subpopulations that are linked to embryo development after ICSI
Uncovering an alternate pathway of antibiotic resistance in spore-forming bacteria
Abstract Spore-forming bacteria produce two distinct cell types: vegetative cells and resilient spores. While antibiotic resistance is typically associated with vegetative cells, spores play a critical role in disseminating resistance genes due to their durability and transmissibility. We previously demonstrated that cephamycin antibiotics target the conserved spore-specific protein SpoVD, significantly reducing spore formation in pathogens including Clostridioides difficile . Here, we show that when C. difficile acquires CdmecA , a homologue of Staphylococcus aureus mecA , one of the most globally burdensome resistance genes, the anti-sporulation effect of cephamycins is bypassed. Cd MecA functionally replaces Cd SpoVD, restoring sporulation and producing phenotypically distinct spores. We further show that mecA is prevalent across C. difficile strains and other pathogenic, gut, and environmental spore-formers. Since SpoVD is conserved, MecA may broadly co-opt sporulation; we confirm this in Clostridium perfringens . This work reveals an unusual resistance mechanism with unexpected physiological consequences, reshaping our understanding of antibiotic resistance within the context of sporulation and microbial adaptation.