Hydroquinine Enhances the Efficacy of Contact Lens Solutions for Inhibiting Adhesion and Biofilm Formation.

is one of the most common bacteria causing contact lens-related microbial keratitis (CLMK). Previous studies report that disinfecting solutions were ineffective in preventing biofilm formation. Solutions containing novel natural agents may be an excellent alternative for reducing the risk of CLMK.

Spatial transcriptomics reveals novel genes during the remodelling of the embryonic human arterial valves.

Abnormalities of the arterial valves, including bicuspid aortic valve (BAV) are amongst the most common congenital defects and are a significant cause of morbidity as well as predisposition to disease in later life. Despite this, and compounded by their small size and relative inaccessibility, there is still much to understand about how the arterial valves form and remodel during embryogenesis, both at the morphological and genetic level. Here we set out to address this in human embryos, using Spatial Transcriptomics (ST).

A Novel and Quantitative Detection Assay () for Identifying Efflux-Associated Resistance Genes Using Multiplex Digital PCR in Clinical Isolates of .

The rise of multidrug resistance of highlights an increased need for selective and precise antimicrobial treatment. Drug efflux pumps are one of the major mechanisms of antimicrobial resistance found in many bacteria, including . .

Hydroquinine Inhibits the Growth of Multidrug-Resistant via the Suppression of the Arginine Deiminase Pathway Genes.

Hydroquinine has antimicrobial potential with demonstrated activity against several bacteria, including multidrug-resistant (MDR) reference strains. Despite this, there is limited evidence confirming the antibacterial activity of hydroquinine against clinical isolates and the underlying mechanism of action. Here, we aimed to investigate the antibacterial effect of hydroquinine in clinical strains using phenotypic antimicrobial susceptibility testing and synergistic testing.

The Comparative Pathology Workbench: Interactive visual analytics for biomedical data.

Pathologists need to compare histopathological images of normal and diseased tissues between different samples, cases, and species. We have designed an interactive system, termed Comparative Pathology Workbench (CPW), which allows direct and dynamic comparison of images at a variety of magnifications, selected regions of interest, as well as the results of image analysis or other data analyses such as scRNA-seq. This allows pathologists to indicate key diagnostic features, with a mechanism to allow discussion threads amongst expert groups of pathologists and other disciplines.

The Promise of Single-Cell RNA Sequencing to Redefine the Understanding of Crohn's Disease Fibrosis Mechanisms.

Crohn's disease (CD) is a chronic inflammatory bowel disease with a high prevalence throughout the world. The development of Crohn's-related fibrosis, which leads to strictures in the gastrointestinal tract, presents a particular challenge and is associated with significant morbidity. There are currently no specific anti-fibrotic therapies available, and so treatment is aimed at managing the stricturing complications of fibrosis once it is established.

A Roadmap for the Human Gut Cell Atlas.

The number of studies investigating the human gastrointestinal tract using various single-cell profiling methods has increased substantially in the past few years. Although this increase provides a unique opportunity for the generation of the first comprehensive Human Gut Cell Atlas (HGCA), there remains a range of major challenges ahead. Above all, the ultimate success will largely depend on a structured and coordinated approach that aligns global efforts undertaken by a large number of research groups.

Towards a clinically-based common coordinate framework for the human gut cell atlas: the gut models.

Background: The Human Cell Atlas resource will deliver single cell transcriptome data spatially organised in terms of gross anatomy, tissue location and with images of cellular histology. This will enable the application of bioinformatics analysis, machine learning and data mining revealing an atlas of cell types, sub-types, varying states and ultimately cellular changes related to disease conditions. To further develop the understanding of specific pathological and histopathological phenotypes with their spatial relationships and dependencies, a more sophisticated spatial descriptive framework is required to enable integration and analysis in spatial terms.

Fluoroquinolones: old drugs, putative new toxicities.

Introduction: Fluoroquinolone (FQ) antibiotics were approved in 1986 for treatment of urinary tract infections, sinusitis, and bronchitis. Numerous putative FQ-associated adverse events have been recently reported.

Areas Covered: We review international regulatory agency experience with these FQ-associated toxicities.

High-Throughput Transcriptomic Profiling Reveals the Inhibitory Effect of Hydroquinine on Virulence Factors in .

Hydroquinine is an organic alkaloid compound that exhibits antimicrobial activity against several bacterial strains including strains of both drug-sensitive and multidrug-resistant P. aeruginosa. Despite this, the effects of hydroquinine on virulence factors in P.

Hydroquinine Possesses Antibacterial Activity, and at Half the MIC, Induces the Overexpression of RND-Type Efflux Pumps Using Multiplex Digital PCR in .

Hydroquinine is an organic compound that is closely related to quinine-derivative drugs and contains anti-malarial and anti-arrhythmia activities. It has been also found in abundance in some natural extracts that possess antibacterial properties. However, there is little evidence demonstrating the antibacterial effect of hydroquinine.

Integrated analysis of Wnt signalling system component gene expression.

Wnt signalling controls patterning and differentiation across many tissues and organs of the developing embryo through temporally and spatially restricted expression of multi-gene families encoding ligands, receptors, pathway modulators and intracellular components. Here, we report an integrated analysis of key genes in the 3D space of the mouse embryo across multiple stages of development. We applied a method for 3D/3D image transformation to map all gene expression patterns to a single reference embryo for each stage, providing both visual analysis and volumetric mapping allowing computational methods to interrogate the combined expression patterns.

Beyond base excision repair: an evolving picture of mitochondrial DNA repair.

Mitochondria are highly specialised organelles required for key cellular processes including ATP production through cellular respiration and controlling cell death via apoptosis. Unlike other organelles, mitochondria contain their own DNA genome which encodes both protein and RNA required for cellular respiration. Each cell may contain hundreds to thousands of copies of the mitochondrial genome, which is essential for normal cellular function - deviation of mitochondrial DNA (mtDNA) copy number is associated with cellular ageing and disease.

RAD51 paralog function in replicative DNA damage and tolerance.

RAD51 paralog gene mutations are observed in both hereditary breast and ovarian cancers. Classically, defects in RAD51 paralog function are associated with homologous recombination (HR) deficiency and increased genomic instability. Several recent investigative advances have enabled characterization of non-canonical RAD51 paralog function during DNA replication.

Evolution-based screening enables genome-wide prioritization and discovery of DNA repair genes.

DNA repair is critical for genome stability and is maintained through conserved pathways. Traditional genome-wide mammalian screens are both expensive and laborious. However, computational approaches circumvent these limitations and are a powerful tool to identify new DNA repair factors.

A 3D molecular atlas of the chick embryonic heart.

We present a detailed analysis of gene expression in the 2-day (HH12) embryonic chick heart. RNA-seq of 13 micro-dissected regions reveals regionalised expression of 15,570 genes. Of these, 132 were studied by in situ hybridisation and a subset (38 genes) was mapped by Optical Projection Tomography or serial sectioning to build a detailed 3-dimensional atlas of expression.

Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.

Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ubiquitylation on other proteins, and are themselves carriers of such regulatory signals. Here we show that the DNA damage checkpoint regulating S-phase entry is controlled by a phosphorylation-dependent interaction of 53BP1 and TOPBP1. BRCT domains of TOPBP1 selectively bind conserved phosphorylation sites in the N-terminus of 53BP1.

RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination.

The proficiency of cancer cells to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) is a key determinant in predicting response to targeted therapies such as PARP inhibitors. The RAD51 paralogs work as multimeric complexes and act downstream of BRCA1 to facilitate HR. Numerous epidemiological studies have linked RAD51 paralog mutations with hereditary cancer predisposition.

Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair.

The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage.

Constant-pressure nested sampling with atomistic dynamics.

The nested sampling algorithm has been shown to be a general method for calculating the pressure-temperature-composition phase diagrams of materials. While the previous implementation used single-particle Monte Carlo moves, these are inefficient for condensed systems with general interactions where single-particle moves cannot be evaluated faster than the energy of the whole system. Here we enhance the method by using all-particle moves: either Galilean Monte Carlo or the total enthalpy Hamiltonian Monte Carlo algorithm, introduced in this paper.

eHistology image and annotation data from the Kaufman Atlas of Mouse Development.

"The Atlas of Mouse Development" by Kaufman is a classic paper atlas that is the de facto standard for the definition of mouse embryo anatomy in the context of standard histological images. We have redigitized the original haematoxylin and eosin-stained tissue sections used for the book at high resolution and transferred the hand-drawn annotations to digital form. We have augmented the annotations with standard ontological assignments (EMAPA anatomy) and made the data freely available via an online viewer (eHistology) and from the University of Edinburgh DataShare archive.

The 'straight mouse': defining anatomical axes in 3D embryo models.

Unlabelled: A primary objective of the eMouseAtlas Project is to enable 3D spatial mapping of whole embryo gene expression data to capture complex 3D patterns for indexing, visualization, cross-comparison and analysis. For this we have developed a spatio-temporal framework based on 3D models of embryos at different stages of development coupled with an anatomical ontology. Here we introduce a method of defining coordinate axes that correspond to the anatomical or biologically relevant anterior-posterior (A-P), dorsal-ventral (D-V) and left-right (L-R) directions.

eMouseAtlas: An atlas-based resource for understanding mammalian embryogenesis.

The eMouseAtlas resource is an online database of 3D digital models of mouse development, an ontology of mouse embryo anatomy and a gene-expression database with about 30K spatially mapped gene-expression patterns. It is closely linked with the MGI/GXD database at the Jackson Laboratory and holds links to almost all available image-based gene-expression data for the mouse embryo. In this resource article we describe the novel web-based tools we have developed for 3D visualisation of embryo anatomy and gene expression.

A strategy to discover new organizers identifies a putative heart organizer.

Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments.