Editing specificity of ADAR isoforms.

Adenosine to inosine deaminases acting on RNA (ADARs) enzymes are found in all metazoa. Their sequence and protein organization is conserved but also shows distinct differences. Moreover, the number of ADAR genes differs between organisms, ranging from one in flies to three in mammals.

A probe-based capture enrichment method for detection of A-to-I editing in low abundance transcripts.

Exactly two decades ago, the ability to use high-throughput RNA sequencing technology to identify sites of editing by ADARs was employed for the first time. Since that time, RNA sequencing has become a standard tool for researchers studying RNA biology and led to the discovery of RNA editing sites present in a multitude of organisms, across tissue types, and in disease. However, transcriptome-wide sequencing is not without limitations.

Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.

Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.

MITIGATING OVER-SATURATED FLUORESCENCE IMAGES THROUGH A SEMI-SUPERVISED GENERATIVE ADVERSARIAL NETWORK.

Multiplex immunofluorescence (MxIF) imaging is a critical tool in biomedical research, offering detailed insights into cell composition and spatial context. As an example, DAPI staining identifies cell nuclei, while CD20 staining helps segment cell membranes in MxIF. However, a persistent challenge in MxIF is saturation artifacts, which hinder single-cell level analysis in areas with over-saturated pixels.

Stem cell-derived exosome delivery systems for treating atherosclerosis: The new frontier of stem cell therapy.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. As a chronic inflammatory disease with a complicated pathophysiology marked by abnormal lipid metabolism and arterial plaque formation, atherosclerosis is a major contributor to CVDs and can induce abrupt cardiac events. The discovery of exosomes' role in intercellular communication has sparked a great deal of interest in them recently.

Establishing a Pan-European, multi-disciplinary taphonomic research Infrastructure: The 'UK-Netherlands decomposition experimental research (UNDER) Group'.

This study unveils the establishment of the United Kingdom-Netherlands Decomposition Experimental Research (UNDER) working group, marking a pioneering initiative in practical Forensic Taphonomy within the UK. Our primary objective was to craft a cohesive multidisciplinary framework, designed to ethically orchestrate, execute, and assess human decomposition. Concurrently, we aimed to amass data through human burials, fostering collaboration among diverse forensic experts across Europe.

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

Optimized genetic tools for neuroanatomical and functional mapping of the Aedes aegypti olfactory system.

The mosquito Aedes aegypti is an emerging model insect for invertebrate neurobiology. We detail the application of a dual transgenesis marker system that reports the nature of transgene integration with circular donor template for CRISPR-Cas9-mediated homology-directed repair at target mosquito chemoreceptor genes. Employing this approach, we demonstrate the establishment of cell-type-specific T2A-QF2 driver lines for the A.

Discovery of three novel neutralizing antibody epitopes on the human astrovirus capsid spike and mechanistic insights into virus neutralization.

Human astroviruses (HAstVs) are a leading cause of viral childhood diarrhea that infects nearly every individual during their lifetime. Although human astroviruses are highly prevalent, no approved vaccine currently exists. Antibody responses appear to play an important role in protection from HAstV infection; however, knowledge about the neutralizing epitope landscape is lacking, as only three neutralizing antibody epitopes have previously been determined.

Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing.

Assembly of actin-based stereocilia is critical for cochlear hair cells to detect sound. To tune their mechanosensivity, stereocilia form bundles composed of graded rows of ascending height, necessitating the precise control of actin polymerization. Myosin 15 (MYO15A) drives hair bundle development by delivering critical proteins to growing stereocilia that regulate actin polymerization via an unknown mechanism.

Roles for the canonical polarity machinery in the establishment of polarity in budding yeast spores.

The yeast buds at sites pre-determined by cortical landmarks deposited during prior budding. During mating between haploid cells in the lab, external pheromone cues override the cortical landmarks to drive polarization and cell fusion. By contrast, in haploid gametes (called spores) produced by meiosis, a pre-determined polarity site drives initial polarized morphogenesis independent of mating partner location.

Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction.

Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage. We investigated this by generating Drosophila mutants lacking BCAA-catabolic activity, resulting in elevated BCAA levels and neurological dysfunction, mimicking disease-relevant symptoms. Our findings reveal a reduction in neuronal AMP-activated protein kinase (AMPK) activity, which disrupts autophagy in mutant brain tissues, linking BCAA imbalance to brain dysfunction.

Regionalized regulation of actomyosin organization influences cardiomyocyte cell shape changes during chamber curvature formation.

Cardiac chambers emerge from a heart tube that balloons and bends to create expanded ventricular and atrial structures, each containing a convex outer curvature (OC) and a recessed inner curvature (IC). A comprehensive understanding of the cellular and molecular mechanisms underlying the formation of these characteristic curvatures remains lacking. Here, we demonstrate in zebrafish that the initially similar populations of OC and IC ventricular cardiomyocytes diverge in the organization of their actomyosin cytoskeleton and subsequently acquire distinct OC and IC cell shapes.

The PEBP genes FLOWERING LOCUS T and TERMINAL FLOWER 1 modulate seed dormancy and size.

The phosphatidylethanolamine-binding protein (PEBP) family members FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) are major regulators of plant reproduction. In Arabidopsis, the FT/TFL1 balance defines the timing of floral transition and the determination of inflorescence meristem identity. However, emerging studies have elucidated a plethora of previously unknown functions for these genes in various physiological processes.

Ontogeny of adenohypophyseal cells, pituitary gland development, and structure in adults of Astyanax lacustris (Teleostei, Characiformes): an emerging Neotropical model fish species.

Pituitary gland morphogenesis and the ontogeny of the adenohypophyseal (AH) cells of Astyanax lacustris are presented herein. This Characiformes species shows great ecological and commercial importance, and it has been increasingly used as animal model. For this study, A.

Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM) infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic. The extent of GBM integration into the brain-wide neuronal circuitry remains unclear.

Functional test of a naturally occurred tumor modifier gene provides insights to melanoma development.

Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness in most animal systems. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus, is used to study hybrid dysfunction, and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids.

Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice.

Longitudinal single-cell profiles of lung regeneration after viral infection reveal persistent injury-associated cell states.

Functional regeneration of the lung's gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using single-cell transcriptomics combined with lineage tracing of proliferating progenitors, we examined mouse lung regeneration after influenza injury, demonstrating an asynchronously phased response across different cellular compartments. This longitudinal atlas of injury responses has produced a catalog of transient and persistent transcriptional alterations in cells as they transit across axes of differentiation.

The BEN domain protein LIN-14 coordinates neuromuscular positioning during epidermal maturation.

Development and function of an organism depend on coordinated inter-tissue interaction. How such interactions are maintained during tissue renewal and reorganization remains poorly understood. Here, we find that BEN domain transcription factor LIN-14 is required in epidermis for maintaining the position of motor neurons and muscles during developmental tissue reorganization.

Morphological change in an isolated population of red squirrels () in Britain.

The mechanical properties of dietary items are known to influence skull morphology, either through evolution or by phenotypic plasticity. Here, we investigated the impact of supplementary feeding of peanuts on the morphology of red squirrels () from five populations in Britain (North Scotland, Borders, Jersey and two temporally distinct populations from Formby (Merseyside)). Stable isotope analysis confirmed dietary ecology in 58 specimens.

Autoactive CNGC15 enhances root endosymbiosis in legume and wheat.

Nutrient acquisition is crucial for sustaining life. Plants develop beneficial intracellular partnerships with arbuscular mycorrhiza (AM) and nitrogen-fixing bacteria to surmount the scarcity of soil nutrients and tap into atmospheric dinitrogen, respectively. Initiation of these root endosymbioses requires symbiont-induced oscillations in nuclear calcium (Ca) concentrations in root cells.