Medicine and Health Sciences Commons^™

Machine Learning Reveals Distinct Neuroanatomical Signatures Of Cardiovascular And Metabolic Diseases In Cognitively Unimpaired Individuals, Sindhuja Tirumalai Govindarajan, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, Tammie L S Benzinger, John C Morris, Et Al.

2020-Current year OA Pubs

Comorbid cardiovascular and metabolic risk factors (CVM) differentially impact brain structure and increase dementia risk, but their specific magnetic resonance imaging signatures (MRI) remain poorly characterized. To address this, we developed and validated machine learning models to quantify the distinct spatial patterns of atrophy and white matter hyperintensities related to hypertension, hyperlipidemia, smoking, obesity, and type-2 diabetes mellitus at the patient level. Using harmonized MRI data from 37,096 participants (45-85 years) in a large multinational dataset of 10 cohort studies, we generated five in silico severity markers that: i) outperformed conventional structural MRI markers with a ten-fold increase in effect …

Dried Blood Spots To Assess Cardiovascular-Kidney-Metabolic Health, Tyler A Jacobson, Mark D Huffman, Et Al.

2020-Current year OA Pubs

Dried blood spot sampling offers a scalable strategy to close diagnostic gaps and improve global surveillance for cardiovascular-kidney-metabolic syndrome. However, assay performance and the extent of validity vary widely between biomarkers used in cardiovascular-kidney-metabolic health assessment under different settings and have not been well described. To fill this gap, we conducted a systematic search of the literature and a narrative synthesis through April 2024 and included reports with laboratory or field validation measuring biomarkers that can be used in cardiovascular-kidney-metabolic health assessment. We categorized assays into categories based on laboratory validation: excellent performance (r>0.95 with gold standard methods and …

Impact Of Vascular Geometry On Thrombosis In Pediatric Patients With Modified Blalock-Taussig-Thomas Shunt: A Pilot Study, Ethan Penn, Yi Qiao, Kimsey Platten, Scott M Bugenhagen, Ram Rohatgi, Jacob R Miller, Jiaxiao Fang, Kelsey Mercer, Blaire Kulp, Jinli Wang, Guy M Genin, David Bark, Edon J Rabinowitz

2020-Current year OA Pubs

BACKGROUND: Thrombosis in modified Blalock-Taussig-Thomas shunts (mBTTS) poses a life-threatening risk for infants with shunt-dependent congenital heart disease. Although hemodynamics influence thrombosis, the specific geometric contributors remain unclear. This study aimed to identify key variables to inform future hemodynamic analysis, hypothesizing that brachiocephalic, subclavian artery, mBTTS, and/or pulmonary artery (PA) geometry play a critical role in clot formation.

METHODS AND RESULTS: We retrospectively analyzed 11 infants with hypoplastic left heart syndrome who underwent mBTTS placement. Using computed tomography and magnetic resonance imaging, we generated 3-dimensional models of the shunt and surrounding vasculature. Geometric variables related to shunt positioning and vascular …

Predictors And Drivers Of End-Of-Life Medicare Spending Among Older Adults With Solid Tumors: A Population-Based Study, Courtney E Baird, Elizabeth Wulff-Burchfield, Pamela C Egan, Lee A Hugar, Ami Vyas, Nikolaos A Trikalinos, Michael A Liu, Adam J Olszewski, Leonidas E Bantis, Orestis A Panagiotou, Emmanuelle Bélanger

2020-Current year OA Pubs

High-intensity end-of-life (EoL) care for patients with cancer often includes multiple transitions to the hospital and intensive care unit (ICU) and is associated with adverse outcomes, such as declines in patient functional abilities [...].

Accelerating Implementation Of Visual Key Information To Improve Informed Consent In Research: A Single-Institution Feasibility Study And Implementation Testing, Angela Hill, Ashley J Housten, Krista Cooksey, Eliana Goldstein, Jessica Mozersky, Mary C Politi

2020-Current year OA Pubs

OBJECTIVE: Current consent processes often fail to communicate study information effectively and may lead to disparities in study participation. The 2018 Common Rule introduced a mandatory key information (KI) section as a means of improving consents; however, it frequently remains lengthy and prohibitively complex. We conducted a feasibility study of an accessible visual KI template for use in routine studies.

DESIGN: Parallel feasibility study and implementation testing.

SETTING: Single Midwestern US academic centre, between July 2023 and July 2024.

PARTICIPANTS: To develop and implement the visual KI template, we used rapid implementation science methods and recruited decision-making and clinical experts, …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

2020-Current year OA Pubs

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

Identification Of Lysosomal Lipolysis As An Essential Noncanonical Mediator Of Adipocyte Fasting And Cold-Induced Lipolysis, Yu-Sheng Yeh, Trent D. Evans, Mari Iwase, Se-Jin Jeong, Arick Park, Ali Ghasemian, Borna Dianati, Ali Javaheri, Et Al.

2020-Current year OA Pubs

Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. …

The Gain-Of-Function Ube3aq588e Variant Causes Angelman-Like Neurodevelopmental Phenotypes In Mice, Kellan P Weston, Anna M Gunelson, Susan E Maloney, Xia Ge, Jalin A Stelzer, Kwang-Soo Kim, Shylyn Collier, Marissa M Mindt, Megan J Agajanian, Michael B Major, Dennis Goldfarb, Kevin K Noguchi, Jason J Yi

2020-Current year OA Pubs

Mutations in the E3 ubiquitin ligase UBE3A that cause enzymatic gain-of-function result in disease phenotypes which differ from classic Angelman syndrome. However, these phenotypes are highly heterogeneous raising questions about the mechanistic basis of such phenotypic diversity. Here, we characterize a mouse model harboring a Ube3a

Reprogramming Aerobic Metabolism Mitigates Streptococcus Pyogenes Tissue Damage In A Mouse Necrotizing Skin Infection Model, Wei Xu, Tara R Bradstreet, Zongsen Zou, Suzanne Hickerson, Yuan Zhou, Hongwu He, Brian T Edelson, Michael G Caparon

2020-Current year OA Pubs

Disease tolerance is a host response to infection that limits collateral damage to host tissues while having a neutral effect on pathogen fitness. Previously, we found that the pathogenic lactic acid bacterium Streptococcus pyogenes manipulates disease tolerance using its aerobic mixed-acid fermentation pathway via the enzyme pyruvate dehydrogenase, but the microbe-derived molecules that mediate communication with the host's disease tolerance pathways remain elusive. Here we show in a murine model that aerobic mixed-acid fermentation inhibits the accumulation of inflammatory cells including neutrophils and macrophages, reduces the immunosuppressive cytokine interleukin-10, and delays bacterial clearance and wound healing. In infected macrophages, the …

Matrix Metalloproteinases Accelerate Pericellular Matrix Breakdown And Disrupt Mechanotransduction In Osteoarthritis, Jule Nieuwstraten, Rosa Riester, Ulf Krister Hofmann, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

The pericellular matrix (PCM) is a specialized, narrow matrix surrounding each chondrocyte in articular cartilage, together constituting the chondron - the fundamental metabolic and functional unit of cartilage. The PCM plays a vital role in mediating biomechanical and biochemical signals essential for chondrocyte function. In osteoarthritis (OA), a chronic joint disorder characterized by progressive cartilage degradation, the PCM is one of the earliest sites of catabolic degradation, primarily driven by matrix metalloproteinases (MMPs). This study aims to investigate the functional relationship between PCM degradation and chondrocyte mechanosignaling, with an emphasis on MMP-driven changes in mechanotransduction in osteoarthritic cartilage. Human chondrons …

C10-Benzoate Esters Of Anhydrotetracycline Inhibit Tetracycline Destructases And Recover Tetracycline Antibacterial Activity, Emily E Williford, Yao-Peng Xue, Wai Kwan Tang, Ruihao Li, Katherine V Jones, Kevin S Blake, Helen C Blaine, Xiang Lian, Christina L Stallings, Niraj H Tolia, Gautam Dantas, Timothy A Wencewicz

2020-Current year OA Pubs

Tetracyclines (TCs) are an important class of antibiotics threatened by enzymatic inactivation. These tetracycline-inactivating enzymes, also known as tetracycline destructases (TDases), are a subfamily of class A flavin monooxygenases (FMOs) that catalyze hydroxyl group transfer and oxygen insertion (Baeyer-Villiger type) reactions on TC substrate scaffolds. Semisynthetic modification of TCs (e.g., tigecycline, omadacycline, eravacycline, and sarecycline) has proven effective in evading certain resistance mechanisms, such as ribosomal protection and efflux, but does not protect against TDase-mediated resistance. Here, we report the design, synthesis, and evaluation of a new series of 22 semisynthetic TDase inhibitors that explore D-ring substitution of anhydrotetracycline (aTC) …

Expression Of A Single Inhibitory Member Of The Ly49 Receptor Family Is Sufficient To License Nk Cells For Effector Functions, Sytse J Piersma, Shasha Li, Pamela Wong, Michael D Bern, Jennifer Poursine-Laurent, Li-Ping Yang, Diana L Beckman, Bijal A Parikh, Wayne M Yokoyama

2020-Current year OA Pubs

Natural killer (NK) cells recognize target cells through germline-encoded activation and inhibitory receptors enabling effective immunity against viruses and cancer. The Ly49 receptor family in the mouse and killer immunoglobin-like receptor family in humans play a central role in NK cell immunity through recognition of major histocompatibility complex class I (MHC-I) and related molecules. Functionally, these receptor families are involved in the licensing and rejection of MHC-I-deficient cells through missing-self. The Ly49 family is highly polymorphic, making it challenging to detail the contributions of individual Ly49 receptors to NK cell function. Herein, we showed mice lacking expression of all Ly49s …

Altered Joint Forces Found In Symptomatic Dysplastic Hips In Women During Sport-Specific Activities, Molly C Shepherd, Rannon Huo, John C Clohisy, Jeffrey J Nepple, Michael Harris

2020-Current year OA Pubs

BACKGROUND: Many patients with developmental dysplasia of the hip (DDH) are young and highly active but often become limited by activity-induced pain. Characterizing how the abnormal bony geometry of DDH affects hip joint loading and multiplanar kinematics during sport-specific motions relevant to active patients may provide insight into injury mechanisms and inform optimal treatment options.

PURPOSE/HYPOTHESIS: The purpose of this study was to determine how hip joint loading and kinematics are altered in DDH during 2 common sport activities: running and multidirectional hop-cutting. It was hypothesized that superior and medial joint-reaction forces (JRFs) would be elevated during running and that …

High-Throughput Repurposing Screen Reveals Compounds With Activity Against Toxoplasma Gondii Bradyzoites, Taher Uddin, Jing Xia, Yong Fu, Case W Mcnamara, Arnab K Chatterjee, L David Sibley

2020-Current year OA Pubs

No abstract provided.

Antibodies To Recombinant Human Alpha-L-Iduronidase Prevent Disease Correction In Cortical Bone In Mps I Mice, Sarah C Hurt, Steven Q Le, Shih-Hsin Kan, Quang D Bui, Michael D Brodt, Patricia I Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder caused by deficiency of the enzyme α-l-iduronidase (IDUA). Failure of enzyme replacement therapy (ERT) to treat skeletal disease may be due to development of anti-IDUA antibodies, found previously to alter tissue distribution of ERT in animal models. To test this hypothesis, immunocompromised (non-obese diabetic [NOD]-severe combined immunodeficiency [SCID]) MPS I mice were treated with weekly ERT from birth (ERT alone). Some mice also received weekly injections of rabbit immunoglobulin G (IgG) against IDUA (immunized rabbit immune globulin [IRIG]) concomitant with ERT, imitating antibodies developed in patients (ERT+IRIG). Mice treated with ERT+IRIG …

Differences In Plasma Metabolome Between Non-Hispanic White And Non-Hispanic Black Women, Ghazaleh Pourali, Liang Li, Myung Sik Jeon, Jingqin Luo, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: To understand potential racial differences in disease susceptibility and develop targeted prevention strategies, it is essential to establish biological differences between racial groups in healthy individuals. However, knowledge about how race impacts metabolites is limited. We therefore performed a cross-sectional study using comprehensive metabolomics analysis to investigate racial differences in metabolites among 506 non-Hispanic White (NHW) women and 163 non-Hispanic Black (NHB) women.

METHODS: We performed untargeted plasma metabolomic profiling using Metabolon's platform (Durham, NC®) and identified 1074 metabolites in 9 super-pathways. We used multivariable linear regression models, adjusted for confounders, to identify associations between race and metabolites. We …

Late Adverse Event Reporting From Medical Device Manufacturers To The Us Food And Drug Administration: Cross Sectional Study, Alexander O Everhart, Pinar Karaca-Mandic, Rita F Redberg, Joseph S Ross, Sanket S Dhruva

2020-Current year OA Pubs

OBJECTIVE: To describe the extent of late adverse event reporting by manufacturers to the US Food and Drug Administration's (FDA) Manufacturer And User Facility Device Experience (MAUDE) database as well as the distribution of late reporting among manufacturers and associations with device characteristics.

DESIGN: Cross sectional study.

SETTING: The FDA MAUDE database, a central postmarket safety surveillance tool for US medical devices, from 1 September 2019 to 31 December 2022.

PARTICIPANTS: Medical device manufacturers that submitted initial adverse event reports to the FDA between 1 September 2019 and 31 December 2022.

MAIN OUTCOME MEASURES: Time in days between date manufacturer …

Structural Mapping Of Polyclonal Igg Responses To Ha After Influenza Virus Vaccination Or Infection, André Nicolás León, Alesandra J Rodriguez, Sara T Richey, Alba Torrents De La Pena, Rachael M Wolters, Abigail M Jackson, Katherine Webb, C Buddy Creech, Sandra Yoder, Philip A Mudd, James E Crowe, Julianna Han, Andrew B Ward

2020-Current year OA Pubs

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses …

Comprehensive Cross-Sectional And Longitudinal Comparisons Of Plasma Glial Fibrillary Acidic Protein And Neurofilament Light Across Ftd Spectrum Disorders, Udit Sheth, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker.

METHODS: We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and …

Innate Immune Sensing Of Rotavirus By Intestinal Epithelial Cells Leads To Diarrhea, Gaopeng Hou, Juhee Son, Maria Florencia Gomez Castro, Takahiro Kawagishi, Avan Antia, Qiru Zeng, Anna L Deveaux, Hinissan P Kohio, Megan T Baldridge, Siyuan Ding, Et Al.

2020-Current year OA Pubs

Diarrhea is the predominant symptom of acute gastroenteritis resulting from enteric infections and a leading cause of death in infants and young children. However, the role of the host response in diarrhea pathogenesis is unclear. Using rotavirus and neonatal mice as a model, we found that oral inoculation of UV-inactivated replication-defective rotavirus consistently induced watery diarrhea by robust activation of cytosolic double-stranded RNA sensing pathways and type III interferon (IFN-λ) secretion. Diarrhea was significantly diminished in mice lacking the IFN-λ receptor. Mechanistically, IFN-λ signaling downregulates the expression of Dra, a chloride and bicarbonate exchanger, which contributes to reduced water absorption. …

Recessive Genetic Contribution To Congenital Heart Disease In 5,424 Probands, Weilai Dong, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and …

Autism- And Intellectual Disability-Associated Myt1l Mutation Alters Human Cortical Interneuron Differentiation, Maturation, And Physiology, Ramachandran Prakasam, Julianna Determan, Gareth Chapman, Mishka Narasimhan, Renata Shen, Maamoon Saleh, Komal Kaushik, Paul Gontarz, Kesavan Meganathan, Bilal Hakim, Bo Zhang, James E Huettner, Kristen L Kroll

2020-Current year OA Pubs

Myelin transcription factor 1 like (MYT1L) is a neuronal transcription factor highly expressed in the developing and adult brain, and, while pathogenic MYT1L mutations cause neurodevelopmental disorders, these have not been characterized in human models of neurodevelopment. Here, we modeled the consequences of pathogenic MYT1L mutation using human stem cell-derived cortical neurons, demonstrating that MYT1L mutation alters the differentiation trajectory, increasing neuronal gene expression, morphological complexity, and synapse production. We also examined consequences of MYT1L mutation in mature cortical interneurons, identifying hallmarks of impaired neuronal identity and maturation and correspondingly altered channel expression and electrophysiological properties. Finally, by defining MYT1L …

Ibrutinib For Therapy Of Steroid-Refractory Chronic Graft-Versus-Host Disease: A Multicenter Real-World Analysis, Joseph Pidala, Iskra Pusic, Et Al.

2020-Current year OA Pubs

To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a …

Resilience And Its Association With Hopelessness, Depression, Loneliness, Post-Traumatic Stress Disorder (Ptsd) And Suicidal Ideations And Behavior In A Cohort In The Nairobi Metropolitan, David M Ndetei, Victoria Mutiso, Christine Musyimi, Eric Jeremiah, Pascalyne Nyamai, Samuel Walusaka, Veronica Onyango, Kamaldeep Bhui, Daniel Mamah

2020-Current year OA Pubs

Comprehending resilience in the face of mental health issues is important, especially for young people who deal with a variety of psychological pressures. This study aims to investigate the co-occurrence of several mental health conditions and the role of resilience as a potential intervention in youth 14-25 years in the Nairobi metropolitan area. We recruited 1,972 youths. The following self-administered instruments were used: resilience (ARM-R), hopelessness (BHS), depression (BDI, PHQ-9), PTSD (HTQ), loneliness (UCLA Loneliness Scale) and suicidality (C-SSRS). Descriptive statistics, Pearson correlation and hierarchical multiple regression analyses were conducted on the data. The key findings are that depression and …

Tracking And Mitigating Imprint Erasure During Induction Of Naive Human Pluripotency At Single-Cell Resolution, Laura A Fischer, Brittany Meyer, Monica Reyes, Joseph E Zemke, Jessica K Harrison, Kyoung-Mi Park, Ting Wang, Harald Jüppner, Sabine Dietmann, Thorold W Theunissen

2020-Current year OA Pubs

Naive human pluripotent stem cells (hPSCs) model the pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded in naive hPSCs, which represents an important deviation from the epiblast in vivo. To track the dynamics of imprint erasure during naive resetting in real time, we established a dual-colored fluorescent reporter at both alleles of the imprinted SNRPN locus. During primed-to-naive resetting, SNRPN expression becomes biallelic in most naive cells, and biallelic SNRPN expression is irreversible upon re-priming. We utilized this live-cell reporter to evaluate chemical and genetic strategies to minimize imprint erasure. Decreasing the level of MEK/ERK inhibition or overexpressing the …

Structural Basis For Dimerization And Activation Of Uvrd-Family Helicases, Ankita Chadda, Binh Nguyen, Timothy M Lohman, Eric A Galburt

2020-Current year OA Pubs

UvrD-family helicases are superfamily 1A motor proteins that function during DNA replication, recombination, repair, and transcription. UvrD family monomers translocate along single-stranded (ss) DNA but need to be activated by dimerization to unwind DNA in the absence of force or accessory factors. However, prior structural studies have only revealed monomeric complexes. Here, we report the first structures of a dimeric UvrD-family helicase,

Individualized Peep Can Improve Both Pulmonary Hemodynamics And Lung Function In Acute Lung Injury, Mayson L A Sousa, Luca S Menga, Annia Schreiber, Mattia Docci, Fernando Vieira, Bhushan H Katira, Mariangela Pellegrini, Sebastian Dubo, Ghislaine Douflé, Eduardo L V Costa, Martin Post, Marcelo B P Amato, Laurent Brochard

2020-Current year OA Pubs

RATIONALE: There are several approaches to select the optimal positive end-expiratory pressure (PEEP), resulting in different PEEP levels. The impact of different PEEP settings may extend beyond respiratory mechanics, affecting pulmonary hemodynamics.

OBJECTIVES: To compare PEEP levels obtained with three titration strategies-(i) highest respiratory system compliance (C

METHODS: Experimental studies in two porcine models of acute lung injury: (I) bilateral injury induced in both lungs, generating a highly recruitable model (n = 37); (II) asymmetrical injury, generating a poorly recruitable model (n = 13). In all experiments, a decremental PEEP titration was performed monitoring P

MEASUREMENTS AND MAIN RESULTS: PEEP …

Augmented Expression Of Superoxide Dismutase 2 Mitigates Progression And Rupture Of Experimental Abdominal Aortic Aneurysm, Huimin Yan, Ying Hu, Yang Lyu, Antonina Akk, Angela C Hirbe, Samuel A Wickline, Hua Pan, Elisha D O Roberson, Christine T N Pham

2020-Current year OA Pubs

No abstract provided.

Apobec3a Drives Ovarian Cancer Metastasis By Altering Epithelial-Mesenchymal Transition, Jessica M. Devenport, Thi Tran, Brooke R. Harris, Dylan Fingerman, Rachel A. Deweerd, Lojain H. Elkhidir, Danielle Lavigne, Katherine Fuh, Lulu Sun, Jeffrey J. Bednarski, Ronny Drapkin, Mary M. Mullen, Abby M. Green

2020-Current year OA Pubs

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive histological subtype of ovarian cancer and often presents with metastatic disease. The drivers of metastasis in HGSOC remain enigmatic. APOBEC3A (A3A), an enzyme that generates mutations across various cancers, has been proposed as a mediator of tumor heterogeneity and disease progression. However, the role of A3A in HGSOC has not been explored. We observed an association between high levels of APOBEC3-mediated mutagenesis and poor overall survival in primary HGSOC. We experimentally addressed this correlation by modeling A3A expression in HGSOC, and this resulted in increased metastatic behavior of HGSOC …

Nad+ Prevents Chronic Kidney Disease By Activating Renal Tubular Metabolism, Bryce A. Jones, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD+) is a small molecule that participates in hundreds of metabolism-related reactions. NAD+ levels are decreased in CKD, and NAD+ supplementation is protective. However, both the mechanism of how NAD+ supplementation protects from CKD, as well as the cell types involved, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD+ precursor, stimulated renal PPARα signaling and restored FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing showed …