Browse Articles
Discover research articles across all indexed journals
Selective electrosynthesis of urea from nitrate and carbon dioxide with low overpotential
Anaesthetic management for combined cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and hyperthermic intrathoracic chemotherapy (HITHOC) in a patient with advanced ovarian carcinoma and pleural metastases: A case report
Tailoring polarization homogeneity in discontinuous-columnar Bi(Fe,Mn)O3 thin films via dislocation engineering with controlled self-assembly
Comparing the effectiveness of ultrasound guided transverse abdominis plane block and quadratus lumborum block for post operative pain management in lower segment caesarean section patients– A randomised controlled trial
OCT4 enhances the firing efficiency of late DNA replication origins in mouse embryonic stem cells
Abstract DNA replication initiates at specific genomic regions known as initiation zones (IZs), which follow a defined spatiotemporal program that is partially dependent on cell type. Here, we examine the replication-initiation patterns of pluripotent mouse embryonic stem cells (mESCs), which are characterized by a very short G1 phase and rapid entry into S phase. Using EdU-seq combined with cell-cycle synchronization and Repli-seq, we identify IZs that activate during S phase in mESCs and classify them as early, mid, or late according to the replication-timing (RT) domain to which they map. Remarkably, we find that some IZs mapping to mid or late RT domains activate within 1–2 hours of entry into S phase. Chromatin and nascent-transcriptome profiling reveal that these IZs associate with regions of open chromatin structure that are bound by the pluripotency factor OCT4. Transient OCT4 depletion reduces both chromatin accessibility and replication-initiation efficiency at these sites. These results provide an example of a pioneer factor, OCT4, facilitating DNA replication initiation by promoting local chromatin accessibility.
Comparison between blockbuster laryngeal mask airway and proseal laryngeal mask airway in paediatric patients under controlled ventilation
Cryo-EM structure of the human COP1-DET1 ubiquitin ligase complex
Abstract Ubiquitin modifications regulate fundamental cellular activities by modulating protein stability and function. The ubiquitin ligase COP1, which is present across species from plants to humans, plays a crucial role in the ubiquitination of developmental transcription factors. While COP1 can function independently, it can also be incorporated into CULLIN4-RING ubiquitin ligase (CRL4) complexes through the DET1 adaptor protein. Despite its biological significance, the structural and functional mechanisms of COP1 and DET1-containing complexes remains poorly understood. Here we present the cryo-electron microscopy structures of human COP1 in complex with DDB1-DDA1-DET1 and Ube2e2, revealing an inactive stacked assembly state. Co-expression with COP1 substrates including c-Jun or ETS2 disrupts this configuration, inducing a conformational rearrangement into a distinct dimeric state that allows substrate access. Structural modelling identifies the spatial organization of COP1 WD40 domains where substrate recruits. DET1 serves as a structural scaffold, bridging COP1 and Ube2e2 to initiate potential ubiquitin addition on substrates, while DDB1 recruits the CULLIN4-RBX1 complex to facilitate Ube2d3-mediated ubiquitin chain elongation. These results reveal the dynamic interplay between the structural states of the CRL4 DET1-COP1 E3 ligase complex and its substrate specific activation mechanism, offering mechanistic insights into ubiquitination regulation and a basis for future studies on E3 ligase dynamics.
A randomized double-blind comparison of dexmedetomidine versus dexamethasone as adjuvants to levobupivacaine for peritonsillar infiltration in pediatric tonsillectomy
Development of a split-toxin CRISPR screening platform to systematically identify regulators of human myoblast fusion
Anaesthetic management of endotracheal stent placement: A case series highlighting challenges in shared airway procedures
Oldest known poison arrows show Stone Age humans’ technological talents
Control of telomerase recruitment and end protection by independent shelterin components
Abstract Telomeres are proposed to alternate between “closed” states, in which chromosome ends are protected from DNA damage signaling and inaccessible to telomerase, and “open” states, where they become accessible for telomerase mediated elongation but less protected. Whether these states reflect distinct molecular mechanisms or mutually exclusive structural conformations remains unclear. Here, we develop a single-cell assay to monitor telomerase activity in mouse embryonic stem cells. Using this approach, we demonstrate that the shelterin component TPP1 is essential for telomerase recruitment via its interaction with TIN2, independently of POT1. In contrast, POT1 is dispensable for telomerase function but required for telomere end protection, acting independently of TPP1. These findings challenge the classical open-closed telomere model and reveal that telomerase recruitment and end protection are mediated by genetically and molecularly separable mechanisms.
Delayed recovery following general anaesthesia: A comprehensive review of causes, assessment, and treatment
Light-driven restructuring generates nanoisland NiIr alloy for efficient methane dry reforming
Emergency laparotomy in a patient with thyroid storm, sepsis, and anticoagulation: A hybrid guideline approach to perioperative management
A high-throughput, flow cytometry approach to measure phase behavior and exchange in biomolecular condensates
Abstract Biomolecular condensates are essential for cellular organization, yet their formation dynamics and molecular content exchange properties remain poorly understood. Here we show that flow cytometry provides a high-throughput, solution-based platform for analyzing condensate behavior at the single-droplet level. Using self-interacting NPM1 condensates as a model, we demonstrate that this approach quantifies phase behavior across protein and salt conditions, measures the partitioning of diverse macromolecules—including antibodies, lipids, small-molecule drugs, and RNA—and detects molecular colocalization with high statistical precision. Importantly, we establish a high-throughput assay to track real-time molecular exchange between preformed condensates and newly added, orthogonally tagged protein. These measurements reveal that condensate aging significantly reduces molecular dynamisms, likely due to altered biophysical properties with time. Compared to conventional imaging techniques that require surface immobilization or complex instrumentation, our method enables rapid, quantitative characterization of condensate dynamics and molecular content, providing a scalable framework for probing condensate function.