Regulation of Cajal bodies: Unexpected connection to 60S ribosomes.

Cajal bodies are essential sites for the biogenesis of small nuclear and nucleolar ribonucleoproteins. In this issue, Courvan and Parker discuss new work from Neugebauer and colleagues (https://doi.org/10.

Clinical and Diagnostic Value of ABCDE Stress Echocardiography With Exercise in Patients With Myocardial Infarction.

Aim: Evaluation of the clinical and diagnostic role of stepwise stress echocardiography (Stress Echo) with exercise using the ABCDE protocol in patients with myocardial infarction (MI).

Material And Methods: This single-site study included 75 patients (mean age 61.6±9.

Drug Development.

Background: Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC fragments tau fibrils from AD brains (AD-tau) into benign segments, whereas its six-residue analog D-TLKIVW cannot. However, the underlying fragmentation mechanism remains unknown, preventing the further development of this type of drug candidate for AD.

Deciphering risk elements: exploring precursors to recoarctation in individuals with aortic coarctation.

Introduction: Coarctation of the aorta (CoA) patients often experience recoarctation, the reoccurrence of aortic narrowing, presenting a considerable clinical challenge.

Aim: This study aims to investigate the triggers or contributing factors associated with the development of recoarctation (reCoA) following the initial repair of CoA.

Material And Methods: The retrospective cohort study includes information about 120 patients, who underwent 4 different types of surgical repairs of coarctation of the aorta through left thoracotomy in the period 2012-2022.

Enhanced diagnosis of pes planus and pes cavus using deep learning-based segmentation of weight-bearing lateral foot radiographs: a comparative observer study.

Unlabelled: A weight-bearing lateral radiograph (WBLR) of the foot is a gold standard for diagnosing adult-acquired flatfoot deformity. However, it is difficult to measure the major axis of bones in WBLR without using auxiliary lines. Herein, we develop semantic segmentation with a deep learning model (DLm) on the WBLR of the foot for enhanced diagnosis of pes planus and pes cavus.

Pancreatic organogenesis mapped through space and time.

The spatial organization of cells within a tissue is dictated throughout dynamic developmental processes. We sought to understand whether cells geometrically coordinate with one another throughout development to achieve their organization. The pancreas is a complex cellular organ with a particular spatial organization.

Structural polymorphism and diversity of human segmental duplications.

Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.

Triacylglycerol mobilization underpins mitochondrial stress recovery.

Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response.

A rare PRIMER cell state in plant immunity.

Plants lack specialized and mobile immune cells. Consequently, any cell type that encounters pathogens must mount immune responses and communicate with surrounding cells for successful defence. However, the diversity, spatial organization and function of cellular immune states in pathogen-infected plants are poorly understood.

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.

Autonomous ribosome biogenesis in vitro.

Ribosome biogenesis is pivotal in the self-replication of life. In Escherichia coli, three ribosomal RNAs and 54 ribosomal proteins are synthesized and subjected to cooperative hierarchical assembly facilitated by numerous accessory factors. Realizing ribosome biogenesis in vitro is a critical milestone for understanding the self-replication of life and creating artificial cells.

Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2.

Multidrug resistance-associated protein 2 (MRP2) is an ATP-powered exporter important for maintaining liver homeostasis and a potential contributor to chemotherapeutic resistance. Using cryogenic electron microscopy (cryo-EM), we determine the structures of human MRP2 in three conformational states: an autoinhibited state, a substrate-bound pre-translocation state, and an ATP-bound post-translocation state. In the autoinhibited state, the cytosolic regulatory (R) domain plugs into the transmembrane substrate-binding site and extends into the cytosol to form a composite ATP-binding site at the surface of nucleotide-binding domain 2.

A Small-Molecule Inhibitor of Gut Bacterial Urease Protects the Host from Liver Injury.

Hyperammonemia is characterized by the accumulation of ammonia within the bloodstream upon liver injury. Left untreated, hyperammonemia contributes to conditions such as hepatic encephalopathy that have high rates of patient morbidity and mortality. Previous studies have identified gut bacterial urease, an enzyme that converts urea into ammonia, as a major contributor to systemic ammonia levels.

Chromosome-level echidna genome illuminates evolution of multiple sex chromosome system in monotremes.

Background: A thorough analysis of genome evolution is fundamental for biodiversity understanding. The iconic monotremes (platypus and echidna) feature extraordinary biology. However, they also exhibit rearrangements in several chromosomes, especially in the sex chromosome chain.

Targeting N-Myc in neuroblastoma with selective Aurora kinase A degraders.

The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.

Efficacy of radiosurgery with and without angioembolization: A subgroup analysis of effectiveness in ruptured versus unruptured arteriovenous malformations - An updated systematic review and meta-analysis.

Background: Congenital arterial defects such as cerebral arteriovenous malformations (AVMs) increase brain bleeding risk. Conservative therapy, microsurgical removal, percutaneous embolization, stereotactic radiosurgery (SRS), or a combination may treat this serious disease. This study compares angioembolization with SRS to SRS alone in ruptured or unruptured brain ateriovenous malformations (BAVM) patients.

enhancement of CD8+ T cell activity using functionalized hydrogel encapsulating tonsil-derived lymphatic endothelial cells.

This study investigates a method for programming immune cells using a biomaterial-based system, providing an alternative to traditional cell manipulation techniques. It addresses the limitations of engineered adoptive T cell therapies, such as T cell exhaustion, by introducing a gelatin-hyaluronic acid (GH-GMA) hydrogel system. We characterized tonsil mesenchymal stem cells (TMSCs), lymphatic endothelial cells (T-LECs), stimulated T-CD8 T cells (STCs), and GH-GMA biomaterials.

Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications.

Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is regulated by protein cofactors and their crosstalk with histone modifications. Trimethylated histone H3 on K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription and inhibit PRC2 activity through unknown mechanisms.

Technological innovation and revolution with single-use digital flexible ureteroscopes: a review from section of EAU Endourology.

Purpose Of Review: Numerous scope-related innovations have taken place in the field of endourology. The presented analytical review is aimed at studying the technical innovations of the single-use digital flexible ureteroscopes. In November 2024, a comprehensive search was done for information on latest disposable flexible digital ureteroscopes, as well as their various unique characteristics.

Prevalence of piriformis syndrome and its associated risk factors among university students in Pakistan: a cross-sectional study.

Objective: To determine the prevalence of piriformis syndrome (PS) among undergraduate university health sciences students aged 18 to 25 and assess the significant predictors of PS regardless of its type and severe PS in particular.

Design: A cross-sectional study.

Setting: The study was conducted at a tertiary care hospital of a public university in Pakistan from December 2023 to May 2024.

Genetic and biochemical characterization of a radical SAM enzyme required for post-translational glutamine methylation of methyl-coenzyme M reductase.

Methyl-coenzyme M reductase (MCR), the key catalyst in the anoxic production and consumption of methane, contains an unusual 2-methylglutamine residue within its active site. data show that a B12-dependent radical SAM (rSAM) enzyme, designated MgmA, is responsible for this post-translational modification (PTM). Here, we show that two different MgmA homologs are able to methylate MCR when expressed in , an organism that does not normally possess this PTM.

Heterotropic Activation of Cytochrome P450 3A4 by Perillyl Alcohol.

: Perillyl alcohol (POH), a monoterpene natural product derived from the essential oils of plants such as perilla (), is currently in phase I and II clinical trials as a chemotherapeutic agent. In this study, we investigated the effect of POH on cytochrome P450 (CYP) activity for evaluating POH-drug interaction potential. : The investigation was conducted using pooled human liver microsomes (HLMs), recombinant CYP3A4 (rCYP3A4) enzymes, and human pluripotent stem cell-derived hepatic organoids (hHOs) employing liquid chromatography-tandem mass spectrometry.

Effects of Zinc-Biofortified Wheat Intake on Plasma Markers of Fatty Acid Metabolism and Oxidative Stress Among Adolescents.

Background/objective: Zinc deficiency is common worldwide and has been linked to reduced growth and immune function, increased risk of and slower recovery from infections, and increased risk of non-communicable diseases. To address the issue, zinc biofortification of wheat has been proposed as a sustainable approach to increase dietary zinc intake in countries like Pakistan, where zinc deficiency rates are high and wheat is the primary staple crop. Since plasma zinc concentration (PZC) does not reliably respond to small changes in zinc intake, biomarkers sensitive to small changes in zinc intake achievable though biofortification are needed.