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Clinical Characteristics And Treatment Patterns Of Pregnant Women With Hypertension In Primary Care In The Federal Capital Territory Of Nigeria: Cross-Sectional Results From The Hypertension Treatment In Nigeria Program, Zainab Mahmoud, Ikechukwu A Orji, Gabriel L Shedul, Kasarachi Aluka-Omitiran, Nanna Ripiye, Blessing Akor, Helen Eze, Tunde Ojo, Guhan Iyer, Abigail S Baldridge, Lisa R Hirschhorn, Mark D Huffman, Dike B Ojji Jun 2023

Clinical Characteristics And Treatment Patterns Of Pregnant Women With Hypertension In Primary Care In The Federal Capital Territory Of Nigeria: Cross-Sectional Results From The Hypertension Treatment In Nigeria Program, Zainab Mahmoud, Ikechukwu A Orji, Gabriel L Shedul, Kasarachi Aluka-Omitiran, Nanna Ripiye, Blessing Akor, Helen Eze, Tunde Ojo, Guhan Iyer, Abigail S Baldridge, Lisa R Hirschhorn, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

BACKGROUND: Hypertensive disorders of pregnancy, including hypertension, are a leading cause of maternal mortality in Nigeria. However, there is a paucity of data on pregnant women with hypertension who receive care in primary health care facilities. This study presents the results from a cross-sectional analysis of pregnant women enrolled in the Hypertension Treatment in Nigeria Program which is aimed at integrating and strengthening hypertension care in primary health care centres.

METHODS: A descriptive analysis of the baseline results from the Hypertension Treatment in Nigeria Program was performed. Baseline blood pressures, treatment and control rates of pregnant women were analysed and …


Intrinsic Tgf-Β Signaling Attenuates Proximal Tubule Mitochondrial Injury And Inflammation In Chronic Kidney Disease, Merve Kayhan, Judith Vouillamoz, Daymé Gonzalez Rodriguez, Milica Bugarski, Yasutaka Mitamura, Julia Gschwend, Christoph Schneider, Andrew Hall, David Legouis, Cezmi A Akdis, Leary Peter, Hubert Rehrauer, Leslie Gewin, Roland H Wenger, Stellor Nlandu Khodo Jun 2023

Intrinsic Tgf-Β Signaling Attenuates Proximal Tubule Mitochondrial Injury And Inflammation In Chronic Kidney Disease, Merve Kayhan, Judith Vouillamoz, Daymé Gonzalez Rodriguez, Milica Bugarski, Yasutaka Mitamura, Julia Gschwend, Christoph Schneider, Andrew Hall, David Legouis, Cezmi A Akdis, Leary Peter, Hubert Rehrauer, Leslie Gewin, Roland H Wenger, Stellor Nlandu Khodo

2020-Current year OA Pubs

Excessive TGF-β signaling and mitochondrial dysfunction fuel chronic kidney disease (CKD) progression. However, inhibiting TGF-β failed to impede CKD in humans. The proximal tubule (PT), the most vulnerable renal segment, is packed with giant mitochondria and injured PT is pivotal in CKD progression. How TGF-β signaling affects PT mitochondria in CKD remained unknown. Here, we combine spatial transcriptomics and bulk RNAseq with biochemical analyses to depict the role of TGF-β signaling on PT mitochondrial homeostasis and tubulo-interstitial interactions in CKD. Male mice carrying specific deletion of Tgfbr2 in the PT have increased mitochondrial injury and exacerbated Th1 immune response in …


Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al. Jun 2023

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, C Charles Gu, Et Al.

2020-Current year OA Pubs

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …


Combinatorial Bcl2 Family Expression In Acute Myeloid Leukemia Stem Cells Predicts Clinical Response To Azacitidine/Venetoclax, Alexander Waclawiczek, Darja Karpova, Et Al. Jun 2023

Combinatorial Bcl2 Family Expression In Acute Myeloid Leukemia Stem Cells Predicts Clinical Response To Azacitidine/Venetoclax, Alexander Waclawiczek, Darja Karpova, Et Al.

2020-Current year OA Pubs

UNLABELLED: The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based "Mediators of …


Altered Signaling And Desensitization Responses In Pth1r Mutants Associated With Eiken Syndrome, Ignacio Portales-Castillo, Thomas Dean, Ross W Cheloha, Brendan A Creemer, Jean-Pierre Vilardaga, Sofya Savransky, Ashok Khatri, Harald Jüppner, Thomas J Gardella Jun 2023

Altered Signaling And Desensitization Responses In Pth1r Mutants Associated With Eiken Syndrome, Ignacio Portales-Castillo, Thomas Dean, Ross W Cheloha, Brendan A Creemer, Jean-Pierre Vilardaga, Sofya Savransky, Ashok Khatri, Harald Jüppner, Thomas J Gardella

2020-Current year OA Pubs

The parathyroid hormone receptor type 1 (PTH1R) is a G protein-coupled receptor that plays key roles in regulating calcium homeostasis and skeletal development via binding the ligands, PTH and PTH-related protein (PTHrP), respectively. Eiken syndrome is a rare disease of delayed bone mineralization caused by homozygous PTH1R mutations. Of the three mutations identified so far, R485X, truncates the PTH1R C-terminal tail, while E35K and Y134S alter residues in the receptor's amino-terminal extracellular domain. Here, using a variety of cell-based assays, we show that R485X increases the receptor's basal rate of cAMP signaling and decreases its capacity to recruit β-arrestin2 upon …


Uridine-Derived Ribose Fuels Glucose-Restricted Pancreatic Cancer, Zeribe C Nwosu, Matthew H Ward, Leah P Shriver, Gary J Patti, Et Al. Jun 2023

Uridine-Derived Ribose Fuels Glucose-Restricted Pancreatic Cancer, Zeribe C Nwosu, Matthew H Ward, Leah P Shriver, Gary J Patti, Et Al.

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy


Cochlear Implantation And Audiological Findings In A Child With Zellweger Spectrum Disorder, Amit Walia, Amy Lynn Birath, Craig A. Buchman Jun 2023

Cochlear Implantation And Audiological Findings In A Child With Zellweger Spectrum Disorder, Amit Walia, Amy Lynn Birath, Craig A. Buchman

2020-Current year OA Pubs

No abstract provided.


Comparison Between Gradients And Parcellations For Functional Connectivity Prediction Of Behavior, Ru Kong, Yan Rui Tan, Naren Wulan, Leon Qi Rong Ooi, Seyedeh-Rezvan Farahibozorg, Samuel Harrison, Janine D Bijsterbosch, Boris C Bernhardt, Simon Eickhoff, B T Thomas Yeo Jun 2023

Comparison Between Gradients And Parcellations For Functional Connectivity Prediction Of Behavior, Ru Kong, Yan Rui Tan, Naren Wulan, Leon Qi Rong Ooi, Seyedeh-Rezvan Farahibozorg, Samuel Harrison, Janine D Bijsterbosch, Boris C Bernhardt, Simon Eickhoff, B T Thomas Yeo

2020-Current year OA Pubs

Resting-state functional connectivity (RSFC) is widely used to predict behavioral measures. To predict behavioral measures, representing RSFC with parcellations and gradients are the two most popular approaches. Here, we compare parcellation and gradient approaches for RSFC-based prediction of a broad range of behavioral measures in the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) datasets. Among the parcellation approaches, we consider group-average "hard" parcellations (Schaefer et al., 2018), individual-specific "hard" parcellations (Kong et al., 2021a), and an individual-specific "soft" parcellation (spatial independent component analysis with dual regression; Beckmann et al., 2009). For gradient approaches, we consider the well-known …


A Pentasaccharide For Monitoring Pharmacodynamic Response To Gene Therapy In Gm1 Gangliosidosis, Pamela Kell, Rohini Sidhu, Mingxing Qian, Sonali Mishra, Dennis J Dietzen, Jingqin Luo, Jean E Schaffer, Daniel S Ory, Xuntian Jiang, Et Al. Jun 2023

A Pentasaccharide For Monitoring Pharmacodynamic Response To Gene Therapy In Gm1 Gangliosidosis, Pamela Kell, Rohini Sidhu, Mingxing Qian, Sonali Mishra, Dennis J Dietzen, Jingqin Luo, Jean E Schaffer, Daniel S Ory, Xuntian Jiang, Et Al.

2020-Current year OA Pubs

BACKGROUND: GM1 gangliosidosis is a rare, fatal, neurodegenerative disease caused by mutations in the GLB1 gene and deficiency in β-galactosidase. Delay of symptom onset and increase in lifespan in a GM1 gangliosidosis cat model after adeno-associated viral (AAV) gene therapy treatment provide the basis for AAV gene therapy trials. The availability of validated biomarkers would greatly improve assessment of therapeutic efficacy.

METHODS: The liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to screen oligosaccharides as potential biomarkers for GM1 gangliosidosis. The structures of pentasaccharide biomarkers were determined with mass spectrometry, as well as chemical and enzymatic degradations. Comparison of LC-MS/MS data …


Ex Vivo Nonbiomaterial Gel-Based Model For Endoscopic Training, Ameya Deshmukh, Juan Reyes Genere, Ahmad Najdat Bazarbashi Jun 2023

Ex Vivo Nonbiomaterial Gel-Based Model For Endoscopic Training, Ameya Deshmukh, Juan Reyes Genere, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

Video 1Use of artificial model for endoscopic training.


Defects In Lysosomal Function And Lipid Metabolism In Human Microglia Harboring A Trem2 Loss Of Function Mutation, Fabia Filipello, Shih-Feng You, Farzaneh S Mirfakhar, Sidhartha Mahali, Bryan Bollman, Mariana Acquarone, Jacob A Marsh, Anirudh Sivaraman, Rita Martinez, Claudia Cantoni, Luca De Feo, Laura Ghezzi, Miguel A Minaya, Arun Renganathan, Anil G Cashikar, Wandy Beatty, Abhirami K Iyer, Marina Cella, Laura Piccio, Celeste M Karch, Et Al. Jun 2023

Defects In Lysosomal Function And Lipid Metabolism In Human Microglia Harboring A Trem2 Loss Of Function Mutation, Fabia Filipello, Shih-Feng You, Farzaneh S Mirfakhar, Sidhartha Mahali, Bryan Bollman, Mariana Acquarone, Jacob A Marsh, Anirudh Sivaraman, Rita Martinez, Claudia Cantoni, Luca De Feo, Laura Ghezzi, Miguel A Minaya, Arun Renganathan, Anil G Cashikar, Wandy Beatty, Abhirami K Iyer, Marina Cella, Laura Piccio, Celeste M Karch, Et Al.

2020-Current year OA Pubs

TREM2 is an innate immune receptor expressed by microglia in the adult brain. Genetic variation in the TREM2 gene has been implicated in risk for Alzheimer's disease and frontotemporal dementia, while homozygous TREM2 mutations cause a rare leukodystrophy, Nasu-Hakola disease (NHD). Despite extensive investigation, the role of TREM2 in NHD pathogenesis remains poorly understood. Here, we investigate the mechanisms by which a homozygous stop-gain TREM2 mutation (p.Q33X) contributes to NHD. Induced pluripotent stem cell (iPSC)-derived microglia (iMGLs) were generated from two NHD families: three homozygous TREM2 p.Q33X mutation carriers (termed NHD), two heterozygous mutation carriers, one related non-carrier, and two …


Acinetobacter Baumannii Atcc 17978 Encodes A Microcin System With Antimicrobial Properties For Contact-Independent Competition, Fabiana Bisaro, Howard A Shuman, Mario F Feldman, Michael J Gebhardt, Stefan Pukatzki Jun 2023

Acinetobacter Baumannii Atcc 17978 Encodes A Microcin System With Antimicrobial Properties For Contact-Independent Competition, Fabiana Bisaro, Howard A Shuman, Mario F Feldman, Michael J Gebhardt, Stefan Pukatzki

2020-Current year OA Pubs

No abstract provided.


Crypticproteindb: An Integrated Database Of Proteome And Immunopeptidome Derived Non-Canonical Cancer Proteins, Ghofran Othoum, Christopher A Maher Jun 2023

Crypticproteindb: An Integrated Database Of Proteome And Immunopeptidome Derived Non-Canonical Cancer Proteins, Ghofran Othoum, Christopher A Maher

2020-Current year OA Pubs

Translated non-canonical proteins derived from noncoding regions or alternative open reading frames (ORFs) can contribute to critical and diverse cellular processes. In the context of cancer, they also represent an under-appreciated source of targets for cancer immunotherapy through their tumor-enriched expression or by harboring somatic mutations that produce neoantigens. Here, we introduce the largest integration and proteogenomic analysis of novel peptides to assess the prevalence of non-canonical ORFs (ncORFs) in more than 900 patient proteomes and 26 immunopeptidome datasets across 14 cancer types. The integrative proteogenomic analysis of whole-cell proteomes and immunopeptidomes revealed peptide support for a nonredundant set of …


Temperament & Character Account For Brain Functional Connectivity At Rest: A Diathesis-Stress Model Of Functional Dysregulation In Psychosis, Igor Zwir, Javier Arnedo, Alberto Mesa, Coral Del Val, Gabriel A De Erausquin, C Robert Cloninger Jun 2023

Temperament & Character Account For Brain Functional Connectivity At Rest: A Diathesis-Stress Model Of Functional Dysregulation In Psychosis, Igor Zwir, Javier Arnedo, Alberto Mesa, Coral Del Val, Gabriel A De Erausquin, C Robert Cloninger

2020-Current year OA Pubs

The human brain's resting-state functional connectivity (rsFC) provides stable trait-like measures of differences in the perceptual, cognitive, emotional, and social functioning of individuals. The rsFC of the prefrontal cortex is hypothesized to mediate a person's rational self-government, as is also measured by personality, so we tested whether its connectivity networks account for vulnerability to psychosis and related personality configurations. Young adults were recruited as outpatients or controls from the same communities around psychiatric clinics. Healthy controls (n = 30) and clinically stable outpatients with bipolar disorder (n = 35) or schizophrenia (n = 27) were diagnosed by structured interviews, and …


Interleukin-18 Signaling Promotes Activation Of Hepatic Stellate Cells In Mouse Liver Fibrosis, Jana Knorr, Joel D. Schilling, Et Al. Jun 2023

Interleukin-18 Signaling Promotes Activation Of Hepatic Stellate Cells In Mouse Liver Fibrosis, Jana Knorr, Joel D. Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Nucleotide-binding oligomerization domain-like receptor-family pyrin domain-containing 3 (NLRP3) inflammasome activation has been shown to result in liver fibrosis. Mechanisms and downstream signaling remain incompletely understood. Here, we studied the role of IL-18 in hepatic stellate cells (HSCs), and its impact on liver fibrosis.

APPROACH AND RESULTS: We observed significantly increased serum levels of IL-18 (128.4 pg/ml vs. 74.9 pg/ml) and IL-18 binding protein (BP; 46.50 ng/ml vs. 15.35 ng/ml) in patients with liver cirrhosis compared with healthy controls. Single cell RNA sequencing data showed that an immunoregulatory subset of murine HSCs highly expresses Il18 and Il18r1 . …


Clinical Programs For Cardiometabolic Health For South Asian Patients In The United States: A Review Of Key Program Components, Reeti K Gulati, Mustafa Husaini, Rajesh Dash, Jaideep Patel, Nilay S Shah Jun 2023

Clinical Programs For Cardiometabolic Health For South Asian Patients In The United States: A Review Of Key Program Components, Reeti K Gulati, Mustafa Husaini, Rajesh Dash, Jaideep Patel, Nilay S Shah

2020-Current year OA Pubs

Medical literature shows that South Asians have approximately a 2-fold higher risk of atherosclerotic cardiovascular disease (CVD) compared with other populations. Given this high prevalence, clinical programs to promote cardiovascular health have emerged in the United States that are dedicated to clinical care for South Asian individuals. In this review, we have summarized the key characteristics of clinical programs in the U.S. dedicated to preventing and managing CVD in South Asian American patients. These clinical centers have many unique components in common that are catered to South Asian patient populations including ethnicity concordance of clinical providers, intensive cardiovascular screening protocols …


Neurosteroid Enantiomers As Potentially Novel Neurotherapeutics, Douglas F Covey, Alex S Evers, Yukitoshi Izumi, Jamie L Maguire, Steven J Mennerick, Charles F Zorumski Jun 2023

Neurosteroid Enantiomers As Potentially Novel Neurotherapeutics, Douglas F Covey, Alex S Evers, Yukitoshi Izumi, Jamie L Maguire, Steven J Mennerick, Charles F Zorumski

2020-Current year OA Pubs

Endogenous neurosteroids and synthetic neuroactive steroids (NAS) are important targets for therapeutic development in neuropsychiatric disorders. These steroids modulate major signaling systems in the brain and intracellular processes including inflammation, cellular stress and autophagy. In this review, we describe studies performed using unnatural enantiomers of key neurosteroids, which are physiochemically identical to their natural counterparts except for rotation of polarized light. These studies led to insights in how NAS interact with receptors, ion channels and intracellular sites of action. Certain effects of NAS show high enantioselectivity, consistent with actions in chiral environments and likely direct interactions with signaling proteins. Other …


The Sphingolipids Ceramide And Inositol Phosphorylceramide Protect The Leishmania Major Membrane From Sterol-Specific Toxins, Chaitanya S Haram, Samrat Moitra, Rilee Keane, F Matthew Kuhlmann, Cheryl Frankfater, Fong-Fu Hsu, Stephen M Beverley, Kai Zhang, Peter A Keyel Jun 2023

The Sphingolipids Ceramide And Inositol Phosphorylceramide Protect The Leishmania Major Membrane From Sterol-Specific Toxins, Chaitanya S Haram, Samrat Moitra, Rilee Keane, F Matthew Kuhlmann, Cheryl Frankfater, Fong-Fu Hsu, Stephen M Beverley, Kai Zhang, Peter A Keyel

2020-Current year OA Pubs

The accessibility of sterols in mammalian cells to exogenous sterol-binding agents has been well-described previously, but sterol accessibility in distantly related protozoa is unclear. The human pathogen Leishmania major uses sterols and sphingolipids distinct from those used in mammals. Sterols in mammalian cells can be sheltered from sterol-binding agents by membrane components, including sphingolipids, but the surface exposure of ergosterol in Leishmania remains unknown. Here, we used flow cytometry to test the ability of the L. major sphingolipids inositol phosphorylceramide (IPC) and ceramide to shelter ergosterol by preventing binding of the sterol-specific toxins streptolysin O and perfringolysin O and subsequent …


Peptidoglycan Recognition In Drosophila Is Mediated By Lysmd3/4, Mark Snee, Jason Wever, Jennifer Guyton, Ryan Beehler-Evans, Christine C Yokoyama, Craig A Micchelli Jun 2023

Peptidoglycan Recognition In Drosophila Is Mediated By Lysmd3/4, Mark Snee, Jason Wever, Jennifer Guyton, Ryan Beehler-Evans, Christine C Yokoyama, Craig A Micchelli

2020-Current year OA Pubs

Microbial recognition is a key step in regulating the immune signaling pathways of multicellular organisms. Peptidoglycan, a component of the bacterial cell wall, exhibits immune stimulating activity in both plants and animals. Lysin motif domain (LysMD) family proteins are ancient peptidoglycan receptors that function in bacteriophage and plants. This report focuses on defining the role of LysMD-containing proteins in animals. Here, we characterize a novel transmembrane LysMD family protein. Loss-of-function mutations at the lysMD3/4 locus in Drosophila are associated with systemic innate immune activation following challenge, so we refer to this gene as immune active (ima). We show that Ima …


Pet-Determined Prevalence Of Coronary Microvascular Dysfunction And Different Types In A Cardio-Metabolic Risk Population, Anita R Bhandiwad, Ines Valenta, Sudhir Jain, Thomas H Schindler Jun 2023

Pet-Determined Prevalence Of Coronary Microvascular Dysfunction And Different Types In A Cardio-Metabolic Risk Population, Anita R Bhandiwad, Ines Valenta, Sudhir Jain, Thomas H Schindler

2020-Current year OA Pubs

BACKGROUND:

METHODS: We prospectively enrolled 239 symptomatic patients with normal pharmacologically-stress and rest myocardial perfusion on

RESULTS: In the whole study population, CMD was present in 54% (130/239). The classical type was more prevalent than the endogen type of CMD (65% vs 35%, p ≤ 0.008). The classical type of CMD was paralleled by a high prevalence of diabetes mellitus, metabolic syndrome, and obesity, while the endogen type of CMD was accompanied by a higher prevalence of arterial hypertension, obesity, and/or morbid obesity. Further, the classical type of nCMF was more frequently observed that the endogen type (74% vs. 26%, …


"Brain Age" Predicts Disability Accumulation In Multiple Sclerosis, Matthew R Brier, Zhuocheng Li, Maria Ly, Helmet T Karim, Leda Liang, Weixin Du, John E Mccarthy, Anne H Cross, Tammie L S Benzinger, Robert T Naismith, Salim Chahin Jun 2023

"Brain Age" Predicts Disability Accumulation In Multiple Sclerosis, Matthew R Brier, Zhuocheng Li, Maria Ly, Helmet T Karim, Leda Liang, Weixin Du, John E Mccarthy, Anne H Cross, Tammie L S Benzinger, Robert T Naismith, Salim Chahin

2020-Current year OA Pubs

OBJECTIVE: Neurodegenerative conditions often manifest radiologically with the appearance of premature aging. Multiple sclerosis (MS) biomarkers related to lesion burden are well developed, but measures of neurodegeneration are less well-developed. The appearance of premature aging quantified by machine learning applied to structural MRI assesses neurodegenerative pathology. We assess the explanatory and predictive power of "brain age" analysis on disability in MS using a large, real-world dataset.

METHODS: Brain age analysis is predicated on the over-estimation of predicted brain age in patients with more advanced pathology. We compared the performance of three brain age algorithms in a large, longitudinal dataset ( …


Protein Kinetics Of Superoxide Dismutase-1 In Familial And Sporadic Amyotrophic Lateral Sclerosis, Cindy V Ly, Margaret D Ireland, Wade K Self, James Bollinger, Jennifer Jockel-Balsarotti, Hillary Herzog, Peggy Allred, Leah Miller, Michael Doyle, Isabel Anez-Bruzual, Bhavesh Trikamji, Ted Hyman, Tyler Kung, Katherine Nicholson, Robert C Bucelli, Bruce W Patterson, Randall J Bateman, Timothy M Miller Jun 2023

Protein Kinetics Of Superoxide Dismutase-1 In Familial And Sporadic Amyotrophic Lateral Sclerosis, Cindy V Ly, Margaret D Ireland, Wade K Self, James Bollinger, Jennifer Jockel-Balsarotti, Hillary Herzog, Peggy Allred, Leah Miller, Michael Doyle, Isabel Anez-Bruzual, Bhavesh Trikamji, Ted Hyman, Tyler Kung, Katherine Nicholson, Robert C Bucelli, Bruce W Patterson, Randall J Bateman, Timothy M Miller

2020-Current year OA Pubs

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts.

METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured.

RESULTS: In …


Cat Lca-Crx Model, Homozygous For An Antimorphic Mutation Has A Unique Phenotype, Laurence M Occelli, Nicholas M Tran, Shiming Chen, Simon M Petersen-Jones Jun 2023

Cat Lca-Crx Model, Homozygous For An Antimorphic Mutation Has A Unique Phenotype, Laurence M Occelli, Nicholas M Tran, Shiming Chen, Simon M Petersen-Jones

2020-Current year OA Pubs

PURPOSE: Mutations in the CRX transcription factor are associated with dominant retinopathies often with more severe macular changes. The CRX-mutant cat (Rdy-A182d2) is the only animal model with the equivalent of the critical retinal region for high-acuity vision, the macula. Heterozygous cats (CRXRdy/+) have a severe phenotype modeling Leber congenital amaurosis. This study reports the distinct ocular phenotype of homozygous cats (CRXRdy/Rdy).

METHODS: Gene expression changes were assessed at both mRNA and protein levels. Changes in globe morphology and retinal structure were analyzed.

RESULTS: CRXRdy/Rdy cats had high levels of mutant CRX mRNA and protein. The expression of photoreceptor target …


A Functional Genomics Pipeline To Identify High-Value Asthma And Allergy Cpgs In The Human Methylome, Andréanne Morin, Katherine Rivera-Spoljaric, Et Al. Jun 2023

A Functional Genomics Pipeline To Identify High-Value Asthma And Allergy Cpgs In The Human Methylome, Andréanne Morin, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: DNA methylation of cytosines at cytosine-phosphate-guanine (CpG) dinucleotides (CpGs) is a widespread epigenetic mark, but genome-wide variation has been relatively unexplored due to the limited representation of variable CpGs on commercial high-throughput arrays.

OBJECTIVES: To explore this hidden portion of the epigenome, this study combined whole-genome bisulfite sequencing with in silico evidence of gene regulatory regions to design a custom array of high-value CpGs. This study focused on airway epithelial cells from children with and without allergic asthma because these cells mediate the effects of inhaled microbes, pollution, and allergens on asthma and allergic disease risk.

METHODS: This study …


Molecular Imaging Of Bone Metastasis, Eliana Khojasteh, Farrokh Dehdashti, Monica Shokeen Jun 2023

Molecular Imaging Of Bone Metastasis, Eliana Khojasteh, Farrokh Dehdashti, Monica Shokeen

2020-Current year OA Pubs

Recent advances in molecularly targeted modular designs for in vivo imaging applications has thrusted open possibilities of investigating deep molecular interactions non-invasively and dynamically. The shifting landscape of biomarker concentration and cellular interactions throughout pathological progression requires quick adaptation of imaging agents and detection modalities for accurate readouts. The synergy of state of art instrumentation with molecularly targeted molecules is resulting in more precise, accurate and reproducible data sets, which is facilitating investigation of several novel questions. Small molecules, peptides, antibodies and nanoparticles are some of the commonly used molecular targeting vectors that can be applied for imaging as well …


Deficiency In Galectin-3, -8, And -9 Impairs Immunity To Chronic Mycobacterium Tuberculosis Infection But Not Acute Infection With Multiple Intracellular Pathogens, Huntly M. Morrison, Wandy L. Beatty, Et Al. Jun 2023

Deficiency In Galectin-3, -8, And -9 Impairs Immunity To Chronic Mycobacterium Tuberculosis Infection But Not Acute Infection With Multiple Intracellular Pathogens, Huntly M. Morrison, Wandy L. Beatty, Et Al.

2020-Current year OA Pubs

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis (Mtb) and Salmonella enterica serovar Typhimurium (Stm) and localizes to Mtb in macrophages. To determine the combined contribution of membrane damage-sensing galectins to immunity, we generated …


Assessment Of Brain Magnetic Resonance And Spectroscopy Imaging Findings And Outcomes After Pediatric Cardiac Arrest, Ericka L Fink, Stuart Friess, Et Al. Jun 2023

Assessment Of Brain Magnetic Resonance And Spectroscopy Imaging Findings And Outcomes After Pediatric Cardiac Arrest, Ericka L Fink, Stuart Friess, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Morbidity and mortality after pediatric cardiac arrest are chiefly due to hypoxic-ischemic brain injury. Brain features seen on magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) after arrest may identify injury and aid in outcome assessments.

OBJECTIVE: To analyze the association of brain lesions seen on T2-weighted MRI and diffusion-weighted imaging and N-acetylaspartate (NAA) and lactate concentrations seen on MRS with 1-year outcomes after pediatric cardiac arrest.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study took place in pediatric intensive care units at 14 US hospitals between May 16, 2017, and August 19, 2020. Children aged 48 hours …


Language Exposure During Infancy Is Negatively Associated With White Matter Microstructure In The Arcuate Fasciculus, Katiana A Estrada, Sharnya Govindaraj, Hervé Abdi, Luke E Moraglia, Jason J Wolff, Shoba Sreenath Meera, Stephen R Dager, Robert C Mckinstry, Martin A Styner, Lonnie Zwaigenbaum, Joseph Piven, Meghan R Swanson, Ibis Network Jun 2023

Language Exposure During Infancy Is Negatively Associated With White Matter Microstructure In The Arcuate Fasciculus, Katiana A Estrada, Sharnya Govindaraj, Hervé Abdi, Luke E Moraglia, Jason J Wolff, Shoba Sreenath Meera, Stephen R Dager, Robert C Mckinstry, Martin A Styner, Lonnie Zwaigenbaum, Joseph Piven, Meghan R Swanson, Ibis Network

2020-Current year OA Pubs

Decades of research have established that the home language environment, especially quality of caregiver speech, supports language acquisition during infancy. However, the neural mechanisms behind this phenomenon remain under studied. In the current study, we examined associations between the home language environment and structural coherence of white matter tracts in 52 typically developing infants from English speaking homes in a western society. Infants participated in at least one MRI brain scan when they were 3, 6, 12, and/or 24 months old. Home language recordings were collected when infants were 9 and/or 15 months old. General linear regression models indicated that …


Patients With Stricturing Or Penetrating Crohn's Disease Phenotypes Report High Disease Burden And Treatment Needs, Yanni Fan, Ling Zhang, Negar Omidakhsh, Rhonda L Bohn, Jennifer S Thompson, Kimberly G Brodovicz, Parakkal Deepak Jun 2023

Patients With Stricturing Or Penetrating Crohn's Disease Phenotypes Report High Disease Burden And Treatment Needs, Yanni Fan, Ling Zhang, Negar Omidakhsh, Rhonda L Bohn, Jennifer S Thompson, Kimberly G Brodovicz, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Crohn's disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited.

METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference.

RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), …


Mri Findings Associated With Anterior Cruciate Ligament Tears In National Football League Athletes, Robert H. Brophy, Jon C. Baker, Jana M. Crain, Mackenzie M. Herzog, Ben Stollberg, Edward M. Wojtys, Christina D. Mack Jun 2023

Mri Findings Associated With Anterior Cruciate Ligament Tears In National Football League Athletes, Robert H. Brophy, Jon C. Baker, Jana M. Crain, Mackenzie M. Herzog, Ben Stollberg, Edward M. Wojtys, Christina D. Mack

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament (ACL) tears are a high-frequency injury requiring a lengthy recovery in professional American football players. Concomitant pathology associated with ACL tears as identified on magnetic resonance imaging (MRI) is not well understood in these athletes.

PURPOSE: To describe the MRI findings of concomitant injuries associated with ACL tears among athletes in the National Football League (NFL).

STUDY DESIGN: Cross-sectional study; Level of evidence, 3.

METHODS: Of 314 ACL injuries in NFL athletes from 2015 through 2019, 191 complete MRI scans from the time of primary ACL injury were identified and reviewed by 2 fellowship-trained musculoskeletal radiologists. …