Digital Commons Network^™

Hiv-Associated Gut Microbial Alterations Are Dependent On Host And Geographic Context, Muntsa Rocafort, Guoyan Zhao, Scott A Handley, Et Al.

2020-Current year OA Pubs

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men …

Brain Injury Drives Optic Glioma Formation Through Neuron-Glia Signaling, Jit Chatterjee, Joshua P Koleske, Astoria Chao, Andrew D Sauerbeck, Ji-Kang Chen, Xuanhe Qi, Megan Ouyang, Lucy G Boggs, Rujuta Idate, Lara Isabel Marco Y Marquez, Terrence T Kummer, David H Gutmann

2020-Current year OA Pubs

Tissue injury and tumorigenesis share many cellular and molecular features, including immune cell (T cells, monocytes) infiltration and inflammatory factor (cytokines, chemokines) elaboration. Their common pathobiology raises the intriguing possibility that brain injury could create a tissue microenvironment permissive for tumor formation. Leveraging several murine models of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome and two experimental methods of brain injury, we demonstrate that both optic nerve crush and diffuse traumatic brain injury induce optic glioma (OPG) formation in mice harboring Nf1-deficient preneoplastic progenitors. We further elucidate the underlying molecular and cellular mechanisms, whereby glutamate released from damaged neurons …

Action Planning For Building Public Health Program Sustainability: Results From A Group-Randomized Trial, Sarah Moreland-Russell, Todd Combs, Jessica Gannon, Eliot Jost, Louise Farah Saliba, Kimberly Prewitt, Douglas Luke, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Public health programs are charged with implementing evidence-based interventions to support public health improvement; however, to achieve long-term population-based benefits, these interventions must be sustained. Empirical evidence suggests that program sustainability can be improved through training and technical assistance, but few resources are available to support public health programs in building capacity for sustainability.

METHODS: This study sought to build capacity for sustainability among state tobacco control programs through a multiyear, group-randomized trial that developed, tested, and evaluated a novel Program Sustainability Action Planning Model and Training Curricula. Using Kolb's experiential learning theory, we developed this action-oriented training model …

A Comparative Biochemical And Pathological Evaluation Of Brain Samples From Knock-In Murine Models Of Gaucher Disease, Makaila L Furderer, Bahafta Berhe, Tiffany C Chen, Stephen Wincovitch, Xuntian Jiang, Nahid Tayebi, Ellen Sidransky, Tae-Un Han

2020-Current year OA Pubs

Gaucher disease (GD) is a lysosomal storage disorder stemming from biallelic mutations in

Circulating Tumor Cells Prediction In Hormone Receptor Positive Her2-Negative Advanced Breast Cancer: A Retrospective Analysis Of The Monarch 2 Trial, Lorenzo Gerratana, Masha Kocherginsky, Andrew A Davis, Paolo D'Amico, Carolina Reduzzi, Fabio Puglisi, Massimo Cristofanilli

2020-Current year OA Pubs

BACKGROUND: The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials.

PATIENTS AND METHODS: Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage …

Rapid And Accurate Remethylation Of Dna In Dnmt3a- Deficient Hematopoietic Cells With Restoration Of Dnmt3a Activity, Yang Li, Haley J Abel, Michelle Cai, Taylor A Lavalle, Tiankai Yin, Nichole M Helton, Amanda M Smith, Christopher A Miller, Timothy J Ley

2020-Current year OA Pubs

Here, we characterize the DNA methylation phenotypes of bone marrow cells from mice with hematopoietic deficiency of

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …

Mechanical Circulatory Support In Pediatric Myocarditis: Support Strategies And Outcomes In A Nationally Representative Cohort, Alicia M Kamsheh, Jonathan B Edelson, Jennifer Faerber, Antara Mondal, William Quarshie, Jonathan J Edwards, Kimberly Y Lin, Matthew J O'Connor, Carol Wittlieb-Weber, Katsuhide Maeda, Michael P Goldsmith, Joseph W Rossano

2020-Current year OA Pubs

BACKGROUND: Myocarditis is a common cause of pediatric heart failure which may require mechanical circulatory support (MCS). The purpose of this study is to describe MCS strategies used in a nationwide cohort of pediatric patients with myocarditis, identify trends over time, and compare outcomes between MCS strategies.

METHODS: This study utilized the Kids' Inpatient Database (KID), a national sample of administrative discharge data. KID admissions from 2003-2016 were queried using ICD-9/10 codes to identify those with a diagnosis of myocarditis. MCS outcomes were compared using logistic regression.

RESULTS: Of 5,661 admissions for myocarditis, MCS was used in 424 (7.5%), comprised …

Epidemiology And Preventability Of Hospital-Onset Bacteremia And Fungemia In 2 Hospitals In India, Sumanth Gandra, Dorothy Sinclair, Dustin Stwalley, Jacaranda Van Rheenen, David K Warren, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs).

DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to …

Children's Neural Reactivity To Maternal Praise And Criticism: Associations With Early Depressive Symptoms And Maternal Depression, Matthew R J Vandermeer, Pan Liu, Ola Mohamed Ali, Andrew R Daoust, Marc F Joanisse, Deanna M Barch, Elizabeth P Hayden

2020-Current year OA Pubs

Caregiving experiences are implicated in children's depression risk; however, children's neural reactivity to positive and negative feedback from mothers, a potential mediator of depression risk, is poorly understood. In a sample of 81 children (

A 3'Utr Insertion Is A Candidate Causal Variant At The Tmem106b Locus Associated With Increased Risk For Ftld-Tdp, Augustine Chemparathy, Chengran Yang, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Single-nucleotide variants near

METHODS: An exploratory analysis identified structural variants on neurodegeneration-related genes. Subsequent analyses focused on an

RESULTS: The primary analysis included 432 participants (52.5% female, age range 45-92 years). We identified a 316 bp

DISCUSSION: We identified a novel

"We Need A Little Strength As Well": Examining The Social Context Of Informal Caregivers For Black Women With Breast Cancer, Tess Thompson, Jacquelyn Coats, Merriah Croston, Robert O Motley Jr, Vetta Sanders Thompson, Aimee S James, Lashaune P Johnson

2020-Current year OA Pubs

BACKGROUND: Informal caregivers (e.g., partners, other family members, friends) often provide social support to Black women with breast cancer, and caregivers find both benefits and challenges in their caregiving role.

METHODS: In this qualitative study, twenty-four caregivers for Black women with breast cancer participated in focus groups and interviews. Participants responded to a brief close-ended questionnaire as well as semi-structured questions about their experiences as cancer caregivers. Demographic information was collected, and relationship satisfaction was measured by the Relationship Assessment Scale-General scale (RAS-G). Focus groups and interviews were recorded, transcribed verbatim, and coded by two independent coders. Using an iterative, …

Bullous Pemphigoid With Prominent Mucosal Involvement In The Setting Of Renal Allograft Rejection, Wesley T Hodges, Ahmed H Badawi, Ilana S Rosman, Amy C Musiek, Leonid Shmuylovich

2020-Current year OA Pubs

No abstract provided.

Top 50 Most-Cited Studies About Osteochondritis Dissecans, Nicholas D Thomas, Raegan Mahler, Kylie Krombholz, Brendan Williams, Ted Ganley, Jeffrey J Nepple, Kevin Shea

2020-Current year OA Pubs

PURPOSE: To determine the 50 most frequently cited studies on osteochondritis dissecans (OCD) and to conduct a bibliometric analysis of these studies.

METHODS: We performed a search within the Clarivate Web of Science database, identifying articles published before December 2022 that encompass topics related to OCD. The search was conducted using the keywords "Osteochondritis Dissecans OR Osteochondritis OR Dissecans."Search results were then filtered using predetermined guidelines and criteria, and the 50 most-cited articles were selected for analysis. Extracted data included title, journal, design, main topic, joint, citations, year, country of origin, and level of evidence.

RESULTS: The search yielded 3,865 …

Screening For Problematic Opioid Use In The Emergency Department: Comparison Of Two Screening Measures, Brittany E Punches, Caroline E Freiermuth, Jon E Sprague, Jennifer L Brown, Elizabeth Hutzel-Dunham, Joshua Lambert, Robert Braun, Andrew Littlefield, Jennifer A Frey, Daniel J Bachmann, Jason J Bischof, Michael V Pantalon, Rachel M Ancona, David F Kisor, Michael S Lyons

2020-Current year OA Pubs

STUDY OBJECTIVE: Earlier intervention for opioid use disorder (OUD) may reduce long-term health implications. Emergency departments (EDs) in the United States treat millions with OUD annually who may not seek care elsewhere. Our objectives were (1) to compare two screening measures for OUD characterization in the ED and (2) to determine the proportion of ED patients screening positive for OUD and those who endorse other substance use to guide future screening programs.

METHODS: A cross-sectional study of randomly selected adult patients presenting to three Midwestern US EDs were enrolled, with duplicate patients excluded. Surveys were administered via research assistant and …

Optimal Approaches To Analyzing Functional Mri Data In Glioma Patients, Ki Yun Park, Joshua S Shimony, Satrajit Chakrabarty, Aaron B Tanenbaum, Carl D Hacker, Kara M Donovan, Patrick H Luckett, Mikhail Milchenko, Aristeidis Sotiras, Daniel S Marcus, Eric C Leuthardt, Abraham Z Snyder

2020-Current year OA Pubs

BACKGROUND: Resting-state fMRI is increasingly used to study the effects of gliomas on the functional organization of the brain. A variety of preprocessing techniques and functional connectivity analyses are represented in the literature. However, there so far has been no systematic comparison of how alternative methods impact observed results.

NEW METHOD: We first surveyed current literature and identified alternative analytical approaches commonly used in the field. Following, we systematically compared alternative approaches to atlas registration, parcellation scheme, and choice of graph-theoretical measure as regards differentiating glioma patients (N = 59) from age-matched reference subjects (N = 163).

RESULTS: Our results …

Semaglutide Improves Metabolic Dysfunction-Associated Steatohepatitis: A 10-Year Retrospective Study, Parth Shah, Megan White, Alex Sievert, Alexander Conway, Adam Kneepkens, Gregory Sayuk, Mauricio Lisker-Melman, Jill Elwing

2020-Current year OA Pubs

BACKGROUND AND AIMS: Semaglutide has been studied in patients with metabolic dysfunction-associated steatohepatitis (MASH) due to potential benefit from weight loss on liver inflammation. However, preclinical studies suggest that MASH improvement may be independent of weight loss. We aim to assess the impact of semaglutide on MASH in relation to weight loss.

METHODS: This retrospective study included 420 patients with diabetes on semaglutide for at least 12 months between 2011 and 2022. Exclusion criteria were liver disease other than MASH, decompensated cirrhosis, malignancy, and bariatric surgery. Primary endpoints were clinically significant improvements in AST or ALT (mean difference > 6.3 U/L …

Covid-19 Vaccine Perspective From Adolescents' Lens In The Us, Meher Garg, Arnav A. Nagrecha, Ruchi Gupta, Makeba Williams

2020-Current year OA Pubs

Introduction The COVID-19 pandemic has presented an unprecedented global health issue. The World Health Organization estimates 773 million confirmed cases and 7 million deaths. Vaccination continues to be the most effective way to prevent COVID-19 and has demonstrated safety and efficacy in all age groups. Though a lot of studies have looked at COVID-19 vaccination acceptance and hesitancy in adults, there is scarce research addressing adolescent vaccination readiness. COVID-19 infection in this age group may result in lost school days, school and community transmission, and loss of productivity for parents. Aim This study aims to determine COVID-19 vaccination rates and …

Structural Biases In Disordered Proteins Are Prevalent In The Cell, David Moses, Karina Guadalupe, Feng Yu, Eduardo Flores, Anthony R Perez, Ralph Mcanelly, Nora M Shamoon, Gagandeep Kaur, Estefania Cuevas-Zepeda, Andrea D Merg, Erik W Martin, Alex S Holehouse, Shahar Sukenik

2020-Current year OA Pubs

Intrinsically disordered proteins and protein regions (IDPs) are prevalent in all proteomes and are essential to cellular function. Unlike folded proteins, IDPs exist in an ensemble of dissimilar conformations. Despite this structural plasticity, intramolecular interactions create sequence-specific structural biases that determine an IDP ensemble's three-dimensional shape. Such structural biases can be key to IDP function and are often measured in vitro, but whether those biases are preserved inside the cell is unclear. Here we show that structural biases in IDP ensembles found in vitro are recapitulated inside human-derived cells. We further reveal that structural biases can change in a sequence-dependent …

Calorie Restriction Reduces Biomarkers Of Cellular Senescence In Humans, Zaira Aversa, Susan B Racette, Et Al.

2020-Current year OA Pubs

Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change …

Outcomes Of Ceftriaxone Compared With Cefazolin Or Nafcillin/Oxacillin For Outpatient Therapy For Methicillin-Sensitive Staphylococcus Aureus Bloodstream Infections: Results From A Large United States Claims Database, Yasir Hamad, Katelin B Nickel, Margaret A Olsen, Ige A George

2020-Current year OA Pubs

BACKGROUND: Ceftriaxone is a convenient option for methicillin-sensitive

METHODS: In this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models.

RESULTS: Of 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within …

Pycallingcards: An Integrated Environment For Visualizing, Analyzing, And Interpreting Calling Cards Data, Juanru Guo, Wenjin Zhang, Xuhua Chen, Allen Yen, Lucy Chen, Christian A Shively, Daofeng Li, Ting Wang, Joseph D Dougherty, Robi D Mitra

2020-Current year OA Pubs

MOTIVATION: Unraveling the transcriptional programs that control how cells divide, differentiate, and respond to their environments requires a precise understanding of transcription factors' (TFs) DNA-binding activities. Calling cards (CC) technology uses transposons to capture transient TF binding events at one instant in time and then read them out at a later time. This methodology can also be used to simultaneously measure TF binding and mRNA expression from single-cell CC and to record and integrate TF binding events across time in any cell type of interest without the need for purification. Despite these advantages, there has been a lack of dedicated …

Mousevuer: Video Based Open-Source System For Laboratory Mouse Home-Cage Monitoring, Ghadi Salem, Niall Cope, Marcial Garmendia, Alex Pu, Abhishek Somenhalli, Jonathan Krynitsky, Noah Cubert, Thomas Jones, George Dold, Anthony Fletcher, Alexxai Kravitz, Thomas Pohida, John Dennis

2020-Current year OA Pubs

Video monitoring of mice in the home-cage reveals behavior profiles without the disruptions caused by specialized test setups and makes it possible to quantify changes in behavior patterns continually over long time frames. Several commercial home-cage monitoring systems are available with varying costs and capabilities; however there are currently no open-source systems for home-cage monitoring. We present an open-source system for top-down video monitoring of research mice in a slightly modified home-cage. The system is designed for integration with Allentown NexGen ventilated racks and allows unobstructed view of up to three mice, but can also be operated outside the rack. …

Functional Network Disorganization And Cognitive Decline Following Fractionated Whole-Brain Radiation In Mice, Benjamin A. Seitzman, Francisco J. Reynoso, Timothy J. Mitchell, Annie R. Bice, Anmol Jarang, Xiaodan Wang, Cedric Mpoy, Lori Strong, Buck E. Rogers, Carla M. Yuede, Joshua B. Rubin, Stephanie M. Perkins, Adam Q. Bauer

2020-Current year OA Pubs

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of …

Clinicopathologic Features Of Antibrush Border Antibody Disease, Joel D Murphy, Nidia Messias, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Antibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management.

METHODS: We identified 67 patients with ABBA who underwent kidney biopsy, including 65 native and 2 transplants. Demographics, clinical findings, and laboratory data were obtained. Histopathologic data included light microscopy, immunofluorescence, electron microscopy and immunostaining for LRP2, CUBN, and AMN. Follow-up data, including treatment(s), laboratory values, and outcomes, were available …

Quantification Of Enteric Dysfunction In Cystic Fibrosis: Inter- And Intraindividual Variability, Laura A Duckworth, Kimberly A Sutton, Nurmohammad Shaikh, Jinli Wang, Carla Hall-Moore, Lori R Holtz, Phillip I Tarr, Ronald C Rubenstein

2020-Current year OA Pubs

OBJECTIVES: To test the utility of various biomarkers as indicators of gut dysfunction in cystic fibrosis (CF) and determine whether intraindividual variations in these measures are repeatable over short intervals and whether interindividual variations correlate with clinical outcomes.

STUDY DESIGN: We performed a cross-sectional, limited longitudinal study of children with CF aged 1-21 years who provided blood and stool samples at 2 or 3 visits, 2 weeks and 3 months apart, which were assayed for markers of intestinal inflammation (fecal calprotectin [fCal], lipocalin-2 [fLcn2], neopterin), and permeability (plasma lipopolysaccharide [LPS] antibodies, LPS-binding protein) by enzyme immunoassays. Control specimens were obtained …

Assessment Of Bovine Cortical Bone Fracture Behavior Using Impact Microindentation As A Surrogate Of Fracture Toughness, Babak Jahani, Rachana Vaidya, James M Jin, Donald A Aboytes, Kaitlyn S Broz, Siva Krothapalli, Bhanuteja Pujari, Walee M Baig, Simon Y Tang

2020-Current year OA Pubs

The fracture behavior of bone is critically important for evaluating its mechanical competence and ability to resist fractures. Fracture toughness is an intrinsic material property that quantifies a material's ability to withstand crack propagation under controlled conditions. However, properly conducting fracture toughness testing requires the access to calibrated mechanical load frames and the destructive testing of bone samples, and therefore fracture toughness tests are clinically impractical. Impact microindentation mimicks certain aspects of fracture toughness measurements, but its relationship with fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh …

Bintrafusp Alfa With Ccrt Followed By Bintrafusp Alfa Versus Placebo With Ccrt Followed By Durvalumab In Patients With Unresectable Stage Iii Nsclc: A Phase 2 Randomized Study, Everett E Vokes, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment.

METHODS: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 …

Control Intervention Design For Preclinical And Clinical Trials: Consensus-Based Core Recommendations From The Third Stroke Recovery And Rehabilitation Roundtable, Kathryn S Hayward, Emily J Dalton, Jessica Barth, Marian Brady, Leora R Cherney, Leonid Churilov, Andrew N Clarkson, Jesse Dawson, Sean P Dukelow, Peter Feys, Maree Hackett, Steve R Zeiler, Catherine E Lang

2020-Current year OA Pubs

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was …

Integrative Analysis Of Pathogenic Variants In Glucose-6-Phosphatase Based On An Alphafold2 Model, Matt Sinclair, Richard A Stein, Jonathan H Sheehan, Emily M Hawes, Richard M O'Brien, Emad Tajkhorshid, Derek P Claxton

2020-Current year OA Pubs

Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. In this study, we determine the atomic interactions …