Investigation of canine extracellular vesicles in diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas (DLBCLs) are the most common lymphoproliferative diseases in dogs. DLBCL diagnosis to date has relied on histopathological analysis; however liquid biopsies have gained attention in recent years as a source of diagnostic and prognostic information. Liquid biopsies can be a source of circulating DNA, miRNA, circulating tumour cells or extracellular vesicles (EVs).

Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma.

Patients diagnosed with metastatic uveal melanoma (MUM) have a poor survival prognosis. Unfortunately for this rare disease, there is no known cure and suitable therapeutic options are limited. HDAC6 inhibitors (HDAC6i) are currently in clinical trials for other cancers and show potential beneficial effects against tumor cell survival in vitro and in vivo.

A companion to the preclinical common data elements for genomics, transcriptomics, and epigenomics data in rodent epilepsy models. A report of the TASK3-WG4 omics working group of the ILAE/AES joint translational TASK force.

The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force established the TASK3 working groups to create common data elements (CDEs) for various preclinical epilepsy research disciplines. The aim of the CDEs is to improve the standardization of experimental designs across a range of epilepsy research-related methods. Here, we have generated CDE tables with key parameters and case report forms (CRFs) containing the essential contents of the study protocols for genomics, transcriptomics, and epigenomics in rodent models of epilepsy, with a specific focus on adult rats and mice.

Priorities for rheumatic and musculoskeletal disease research in Ireland.

Background: Research priority setting is a useful approach to decide which unanswered questions are most worth trying to solve through research. The aim is to reduce bias in the research agenda. Traditionally, research was decided by funders, policymakers, and academics with limited influence from other stakeholders like people living with health conditions, caregivers, or the community.

Cytochrome P450 5208A3 is a promiscuous xenobiotic biotransforming enzyme in Cunninghamella elegans.

Cunninghamella elegans is a long-established microbial model of mammalian drug and xenobiotic metabolism enabled by the actions of cytochrome P450 enzymes that are poorly characterised. In this paper we describe the identification of a new cytochrome P450 (CYP) monooxygenase in the fungus that catalyses the biotransformation of a range of structurally distinct xenobiotic substrates. The fungal enzyme was heterologously expressed in the yeast Pichia pastoris X-33 alone and in combination with previously identified C.

Spatial and temporal assessment of crack cocaine use in 13 European cities through wastewater-based epidemiology.

Already in early 2000s, concerns have been growing in the EU about increasing use of cocaine and it is estimated that below 1 % of the population administer the drug by smoking crack cocaine. New available data suggests an increase in the use of crack cocaine and an increase in the number of crack cocaine users entering treatment has been reported in several European countries. Robust estimations of crack cocaine use are however not available yet.

Mapping the Immune Landscape in Metastatic Melanoma Reveals Localized Cell-Cell Interactions That Predict Immunotherapy Response.

Unlabelled: While immune checkpoint-based immunotherapy (ICI) shows promising clinical results in patients with cancer, only a subset of patients responds favorably. Response to ICI is dictated by complex networks of cellular interactions between malignant and nonmalignant cells. Although insights into the mechanisms that modulate the pivotal antitumoral activity of cytotoxic T cells (Tcy) have recently been gained, much of what has been learned is based on single-cell analyses of dissociated tumor samples, resulting in a lack of critical information about the spatial distribution of relevant cell types.

Improving the specificity of E. coli acetate/propionate exclusion biosensors via iterative engineering.

Real-time monitoring of key performance indicator analytes such as acetate and propionate within anaerobic digestors (AD) is required for optimum biogas production. In this paper the further refinement of acetate and propionate whole cell (E. coli) exclusion biosensors is reported following an iterative process in which key metabolites that might interfere with O-uptake measurements are identified and genes required for their catabolism are knocked out (exclusion).

SARS-CoV-2 variant trends in Ireland: Wastewater-based epidemiology and clinical surveillance.

SARS-CoV-2 RNA quantification in wastewater is an important tool for monitoring the prevalence of COVID-19 disease on a community scale which complements case-based surveillance systems. As novel variants of concern (VOCs) emerge there is also a need to identify the primary circulating variants in a community, accomplished to date by sequencing clinical samples. Quantifying variants in wastewater offers a cost-effective means to augment these sequencing efforts.

Dawn and dusk peaks of outer segment phagocytosis, and visual cycle function require Rab28.

RAB28 is a farnesylated, ciliary G-protein. Patient variants in RAB28 are causative of autosomal recessive cone-rod dystrophy (CRD), an inherited human blindness. In rodent and zebrafish models, the absence of Rab28 results in diminished dawn, photoreceptor, outer segment phagocytosis (OSP).

Evidence for local and international spread of Mycobacterium avium subspecies paratuberculosis through whole genome sequencing of isolates from the island of Ireland.

We describe application of whole genome sequencing (WGS) to a collection of 197 Mycobacterium avium subsp paratuberculosis (MAP) isolates gathered from 122 cattle herds across 27 counties of the island of Ireland. We compare WGS to MAP diversity quantified using mycobacterial interspersed random unit - variable number tandem repeats (MIRU-VNTR). While MIRU-VNTR showed only two major types, WGS could split the 197 isolates into eight major groups.

Analytical Validation of a Novel 6-Gene Signature for Prediction of Distant Recurrence in Estrogen Receptor-Positive, HER2-Negative, Early-Stage Breast Cancer.

Background: OncoMasTR is a recently developed multigene prognostic test for early-stage breast cancer. The test has been developed in a kit-based format for decentralized deployment in molecular pathology laboratories. The analytical performance characteristics of the OncoMasTR test are described in this study.

GATD3A, a mitochondrial deglycase with evolutionary origins from gammaproteobacteria, restricts the formation of advanced glycation end products.

Background: Functional complexity of the eukaryotic mitochondrial proteome is augmented by independent gene acquisition from bacteria since its endosymbiotic origins. Mammalian homologs of many ancestral mitochondrial proteins have uncharacterized catalytic activities. Recent forward genetic approaches attributed functions to proteins in established metabolic pathways, thereby limiting the possibility of identifying novel biology relevant to human disease.

Plant-derived cannabinoids as anticancer agents.

Substantial preclinical evidence demonstrates the antiproliferative, cytotoxic, and antimetastatic properties of plant-derived cannabinoids (phytocannabinoids) such as cannabidiol and tetrahydrocannabinol. The cumulative body of research into the intracellular mechanisms and phenotypic effects of these compounds supports a logical, judicious progression to large-scale phase II/III clinical trials in certain cancer types to truly assess the efficacy of phytocannabinoids as anticancer agents.

Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor.

Metastatic uveal melanoma (MUM) is characterized by poor patient survival. Unfortunately, current treatment options demonstrate limited benefits. In this study, we evaluate the efficacy of ACY-1215, a histone deacetylase inhibitor (HDACi), to attenuate growth of primary ocular UM cell lines and, in particular, a liver MUM cell line in vitro and in vivo, and elucidate the underlying molecular mechanisms.

Emerging role for the Serum Response Factor (SRF) as a potential therapeutic target in cancer.

Introduction: The Serum Response Factor (SRF) is a transcription factor involved in three hallmarks of cancer: the promotion of cell proliferation, cell death resistance and invasion and metastasis induction. Many studies have demonstrated a leading role in the development and progression of multiple cancer types, thus highlighting the potential of SRF as a prognostic biomarker and therapeutic target, especially for cancers with poor prognosis.

Areas Covered: This review examines the role of SRF in several cancers in promoting cellular processes associated with cancer development and progression.

Nitroreduction of flutamide by NADPH: Cytochrome P450 reductase.

The microbial model of mammalian drug metabolism, , has three cytochrome P450 reductase genes in its genome: g1631 (CPR_A), g4301 (CPR_B), and g7609 (CPR_C). The nitroreductase activity of the encoded enzymes was investigated via expression of the genes in the yeast X33. Whole cell assays with the recombinant yeast demonstrated that the reductases converted the anticancer drug flutamide to the nitroreduced metabolite that was also produced from the same substrate when incubated with human NADPH: cytochrome P450 reductase.

Discovery and Development of the Quininib Series of Ocular Drugs.

The quininib series is a novel collection of small-molecule drugs with antiangiogenic, antivascular permeability, anti-inflammatory, and antiproliferative activity. Quininib was initially identified as a drug hit during a random chemical library screen for determinants of developmental ocular angiogenesis in zebrafish. To enhance drug efficacy, novel quininib analogs were designed by applying medicinal chemistry approaches.

Affordable and effective optokinetic response methods to assess visual acuity and contrast sensitivity in larval to juvenile zebrafish.

The optokinetic response (OKR) is an effective behavioural assay to investigate functional vision in zebrafish. The rapid and widespread use of gene editing, drug screening and environmental modulation technologies has resulted in a broader need for visual neuroscience researchers to access affordable and more sensitive OKR, contrast sensitivity (CS) and visual acuity (VA) assays. Here, we demonstrate how 2D- and 3D-printed, striped patterns or drums coupled with a motorised base and microscope provide a simple, cost-effective but efficient means to assay OKR, CS and VA in larval-juvenile zebrafish.

The Role of Mitochondria in Optic Atrophy With Autosomal Inheritance.

Optic atrophy (OA) with autosomal inheritance is a form of optic neuropathy characterized by the progressive and irreversible loss of vision. In some cases, this is accompanied by additional, typically neurological, extra-ocular symptoms. Underlying the loss of vision is the specific degeneration of the retinal ganglion cells (RGCs) which form the optic nerve.

Association of circulating short chain fatty acid levels with colorectal adenomas and colorectal cancer.

Background & Aims: Short chain fatty acid (SCFAs) are bacterially derived metabolites suggested to have protective roles against colorectal cancer (CRC) development. However, there is sparse evidence from epidemiological studies in this context. Here, we assessed whether circulating SCFA concentrations varied in patients with colorectal adenomas (CRA) and CRC.

Minimizing errors in RT-PCR detection and quantification of SARS-CoV-2 RNA for wastewater surveillance.

Wastewater surveillance for pathogens using reverse transcription-polymerase chain reaction (RT-PCR) is an effective and resource-efficient tool for gathering community-level public health information, including the incidence of coronavirus disease-19 (COVID-19). Surveillance of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in wastewater can potentially provide an early warning signal of COVID-19 infections in a community. The capacity of the world's environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is increasing rapidly.

Conformation and membrane interaction studies of the potent antimicrobial and anticancer peptide palustrin-Ca.

Palustrin-Ca (GFLDIIKDTGKEFAVKILNNLKCKLAGGCPP) is a host defence peptide with potent antimicrobial and anticancer activities, first isolated from the skin of the American bullfrog Lithobates catesbeianus. The peptide is 31 amino acid residues long, cationic and amphipathic. Two-dimensional NMR spectroscopy was employed to characterise its three-dimensional structure in a 50/50% water/2,2,2-trifluoroethanol-[Formula: see text] mixture.