Hyperexcitability and translational phenotypes in a preclinical mouse model of SYNGAP1-related intellectual disability.

Disruption of SYNGAP1 directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability (SRID). Without functional SynGAP1 protein, individuals are developmentally delayed and have prominent features of intellectual disability (ID), motor impairments, and epilepsy. Over the past two decades, there have been numerous discoveries indicating the critical role of Syngap1.

Estimation of sex assigned at birth using dental crown and cervical measurements in a modern global sample.

Despite developing prior to the appearance of secondary sexual characteristics of the skeleton, the permanent dentition exhibits sexual dimorphism. Therefore, teeth can serve as a means to estimate sex assigned at birth even in young individuals. This project takes a large global sample of maximum dimensions of the crown as well as measurements of the crown at the cervix to explore sexual dimorphism.

Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model.

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus.

Hyperexcitability and translational phenotypes in a preclinical mouse model of Related Intellectual Disability.

Disruption of directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability (SRID). Without functional SynGAP1 protein, individuals are developmentally delayed and have prominent features of intellectual disability, motor impairments, and epilepsy. Over the past two decades, there have been numerous discoveries indicting the critical role of Syngap1.

Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study.

Introduction: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.

The role of the minor colonization factor CS14 in adherence to intestinal cell models by geographically diverse ETEC isolates.

Enterotoxigenic (ETEC) is a primary causative agent of diarrhea in travelers and young children in low- to middle-income countries. ETEC adheres to small intestinal epithelia via colonization factors (CFs) and secretes heat-stable toxin and/or heat-labile toxin, causing dysregulated ion transport and water secretion. There are over 30 CFs identified, including major CFs associated with moderate-to-severe diarrhea (MSD) and minor CFs for which a role in pathogenesis is less clear.

Hyperexcitability and translational phenotypes in a preclinical model of mutations.

is a critical gene for neuronal development, synaptic structure, and function. Although rare, the disruption of directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability. Without functional SynGAP1 protein, patients present with intellectual disability, motor impairments, and epilepsy.

The role of CFA/I in adherence and toxin delivery by ETEC expressing multiple colonization factors in the human enteroid model.

Enterotoxigenic Escherichia coli (ETEC) is a primary causative agent of diarrhea in travelers and young children in low-to-middle-income countries (LMICs). ETEC adhere to intestinal epithelia via colonization factors (CFs) and secrete heat-stable toxin (ST) and/or heat-labile toxin (LT), causing dysregulated cellular ion transport and water secretion. ETEC isolates often harbor genes encoding more than one CF that are targets as vaccine antigens.

Research in a time of enteroids and organoids: how the human gut model has transformed the study of enteric bacterial pathogens.

Enteric bacterial pathogens cause significant morbidity and mortality globally. Studies in tissue culture and animal models shaped our initial understanding of these host-pathogen interactions. However, intrinsic shortcomings in these models limit their application, especially in translational applications like drug screening and vaccine development.

Effectiveness of Auditory Measures for Detecting Hidden Hearing Loss and/or Cochlear Synaptopathy: A Systematic Review.

Standard audiometric evaluations are not sensitive enough to identify hidden hearing loss (HHL) and/or cochlear synaptopathy (CS). Patients with either of these conditions frequently present with difficulty understanding speech in noise or other complaints such as tinnitus. The purpose of this systematic review is to identify articles in peer-reviewed journals that assessed the sensitivity of audiologic measures for detecting HHL and/or CS, and which showed potential for use in a clinical test battery for these disorders.

Host Factors Alter Effects of Angiopoietin-Like Protein 8 on Glucose Homeostasis in Diabetic Mice.

Recovery of functional beta cell mass offers a biological cure for type 1 diabetes. However, beta cell mass is difficult to regain once lost since the proliferation rate of beta cells after youth is very low. Angiopoietin like-protein 8 (ANGPTL8), a peptide that has a role in the regulation of lipoprotein lipase activity, was reported to increase beta cell proliferation in mice in 2013.

Complement Component C1q Programs a Pro-Efferocytic Phenotype while Limiting TNFα Production in Primary Mouse and Human Macrophages.

Deficiency in complement component C1q is associated with an inability to clear apoptotic cells (efferocytosis) and aberrant inflammation in lupus, and identification of the pathways involved in these processes should reveal important regulatory mechanisms in lupus and other autoimmune or inflammatory diseases. In this study, C1q-dependent regulation of TNFα/IL-6 expression and efferocytosis was investigated using primary mouse bone marrow-derived macrophages and human monocyte-derived macrophages. C1q downregulated LPS-dependent TNFα production in mouse and human macrophages.

Invariant TAD Boundaries Constrain Cell-Type-Specific Looping Interactions between Promoters and Distal Elements around the CFTR Locus.

Three-dimensional genome structure plays an important role in gene regulation. Globally, chromosomes are organized into active and inactive compartments while, at the gene level, looping interactions connect promoters to regulatory elements. Topologically associating domains (TADs), typically several hundred kilobases in size, form an intermediate level of organization.

Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation.

Epigenetic events that are essential drivers of lymphocyte transformation remain incompletely characterized. We used models of Epstein-Barr virus (EBV)-induced B-cell transformation to document the relevance of protein arginine methyltransferase 5 (PRMT5) to regulation of epigenetic-repressive marks during lymphomagenesis. EBV(+) lymphomas and transformed cell lines exhibited abundant expression of PRMT5, a type II PRMT enzyme that promotes transcriptional silencing of target genes by methylating arginine residues on histone tails.

Novel human butyrylcholinesterase variants: toward organophosphonate detoxication.

Human butyrylcholinesterase (hBChE) is currently being developed as a detoxication enzyme for stoichiometric binding and/or catalytic hydrolysis of organophosphates. Herein, we describe the use of a molecular evolution method to develop novel hBChE variants with increased resistance to stereochemically defined nerve agent model compounds of soman, sarin, and cyclosarin. Novel hBChE variants (Y332S, D340H, and Y332S/D340H) were identified with an increased resistance to nerve agent model compounds that retained robust intrinsic catalytic efficiency.

Supercritical fluid extraction provides an enhancement to the immune response for orally-delivered hepatitis B surface antigen.

The hepatitis B virus continues to be a major pathogen worldwide despite the availability of an effective parenteral vaccine for over 20 years. Orally-delivered subunit vaccines produced in maize may help to alleviate the disease burden by providing a low-cost, heat-stable alternative to the parenteral vaccine. Oral subunit vaccination has been an elusive goal due to the large amounts of antigen required to induce an immunologic response when administered through the digestive tract.

Characterization of multiple myeloma vesicles by label-free relative quantitation.

Multiple myeloma (MM) is a hematological malignancy caused by a microenviromentally aided persistence of plasma cells in the bone marrow. The role that extracellular vesicles (EVs), microvesicles and exosomes, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown. This paper describes the proteomic content of EVs derived from MM.

Analysis of long-range chromatin interactions using Chromosome Conformation Capture.

Chromosome Conformation Capture, or 3C, is a pioneering method for investigating the three-dimensional structure of chromatin. 3C is used to analyze long-range looping interactions between any pair of selected genomic loci. Most 3C studies focus on defined genomic regions of interest that can be up to several hundred Kb in size.

In vitro inhibition of cytochrome P450-mediated reactions by gemfibrozil, erythromycin, ciprofloxacin and fluoxetine in fish liver microsomes.

Inhibition of mammalian cytochrome P450 enzymes (CYPs) is well characterized; major hepatic CYPs can be inhibited by drugs and other environmental contaminants. CYP function and inhibition has not yet been well established in fish yet these studies are important for several reasons. First, such studies will provide functional information for non-mammalian CYPs.

Cell-type-specific long-range looping interactions identify distant regulatory elements of the CFTR gene.

Identification of regulatory elements and their target genes is complicated by the fact that regulatory elements can act over large genomic distances. Identification of long-range acting elements is particularly important in the case of disease genes as mutations in these elements can result in human disease. It is becoming increasingly clear that long-range control of gene expression is facilitated by chromatin looping interactions.

Cross-species comparison of fluoxetine metabolism with fish liver microsomes.

Pharmaceuticals discharged in municipal wastewater are of emerging concern because of their potential for inducing biological effects in aquatic organisms. Selective serotonin reuptake inhibitors (SSRIs), pharmaceuticals prescribed to treat chronic depression, have been detected in receiving and wastewaters. Fluoxetine is a highly prescribed model SSRI used to assess impacts of antidepressants on aquatic organisms.

Assessment of cytochrome P450 fluorometric substrates with rainbow trout and killifish exposed to dexamethasone, pregnenolone-16alpha-carbonitrile, rifampicin, and beta-naphthoflavone.

Cytochrome P450s (CYPs) are important xenobiotic metabolizing proteins. While their functions are well understood in mammals, CYP function in non-mammalian vertebrate systems is much less defined, with function often inferred from mammalian data, assuming similar function across vertebrate species. In this study, we investigate whether in vivo treatment with known mammalian CYP inducers can alter the in vitro catalytic activity of fish microsomes using eleven fluorescent CYP-mediated substrates.