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Articles 1741 - 1770 of 11035
Full-Text Articles in Entire DC Network
Zoledronic Acid Blocks Overactive Kir6.1/Sur2-Dependent Katp Channels In Skeletal Muscle And Osteoblasts In A Murine Model Of Cantú Syndrome, Rosa Scala, Fatima Maqoud, Conor Mcclenaghan, Theresa M Harter, Maria Grazia Perrone, Antonio Scilimati, Colin G Nichols, Domenico Tricarico
Zoledronic Acid Blocks Overactive Kir6.1/Sur2-Dependent Katp Channels In Skeletal Muscle And Osteoblasts In A Murine Model Of Cantú Syndrome, Rosa Scala, Fatima Maqoud, Conor Mcclenaghan, Theresa M Harter, Maria Grazia Perrone, Antonio Scilimati, Colin G Nichols, Domenico Tricarico
2020-Current year OA Pubs
Cantú syndrome (CS) is caused by the gain of function mutations in the
Ide-Cel Or Standard Regimens In Relapsed And Refractory Multiple Myeloma, Paula Rodriguez-Otero, Ravi Vij, Et Al.
Ide-Cel Or Standard Regimens In Relapsed And Refractory Multiple Myeloma, Paula Rodriguez-Otero, Ravi Vij, Et Al.
2020-Current year OA Pubs
BACKGROUND: Survival is poor among patients with triple-class-exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma.
METHODS: In this international, open-label, phase 3 trial involving adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen, we randomly assigned patients in a 2:1 ratio to receive either ide-cel (dose range, 150×10
RESULTS: A total …
Animal Models And Their Role In Imaging-Assisted Co-Clinical Trials, Donna M Peehl, Li Ding, Kooresh I Shoghi, Et Al.
Animal Models And Their Role In Imaging-Assisted Co-Clinical Trials, Donna M Peehl, Li Ding, Kooresh I Shoghi, Et Al.
2020-Current year OA Pubs
The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients' tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant …
An Essential Endoplasmic Reticulum-Resident N-Acetyltransferase Ortholog In Plasmodium Falciparum, Alexander J Polino, Muhammad M Hasan, Katherine Floyd, Yolotzin Avila-Cruz, Yujuan Yang, Daniel E Goldberg
An Essential Endoplasmic Reticulum-Resident N-Acetyltransferase Ortholog In Plasmodium Falciparum, Alexander J Polino, Muhammad M Hasan, Katherine Floyd, Yolotzin Avila-Cruz, Yujuan Yang, Daniel E Goldberg
2020-Current year OA Pubs
N-terminal acetylation is a common eukaryotic protein modification that involves the addition of an acetyl group to the N-terminus of a polypeptide. This modification is largely performed by cytosolic N-terminal acetyltransferases (NATs). Most associate with the ribosome, acetylating nascent polypeptides co-translationally. In the malaria parasite Plasmodium falciparum, exported effectors are thought to be translated into the endoplasmic reticulum (ER), processed by the aspartic protease plasmepsin V and then N-acetylated, despite having no clear access to cytosolic NATs. Here, we used inducible gene deletion and post-transcriptional knockdown to investigate the primary ER-resident NAT candidate, Pf3D7_1437000. We found that it localizes to …
Kdm6a Loss Triggers An Epigenetic Switch That Disrupts Urothelial Differentiation And Drives Cell Proliferation In Bladder Cancer, Hong Qiu, Jennifer K Bolzenius, Angela Halstead, Vivek Arora, Et Al.
Kdm6a Loss Triggers An Epigenetic Switch That Disrupts Urothelial Differentiation And Drives Cell Proliferation In Bladder Cancer, Hong Qiu, Jennifer K Bolzenius, Angela Halstead, Vivek Arora, Et Al.
2020-Current year OA Pubs
UNLABELLED: Disruption of KDM6A, a histone lysine demethylase, is one of the most common somatic alternations in bladder cancer. Insights into how KDM6A mutations affect the epigenetic landscape to promote carcinogenesis could help reveal potential new treatment approaches. Here, we demonstrated that KDM6A loss triggers an epigenetic switch that disrupts urothelial differentiation and induces a neoplastic state characterized by increased cell proliferation. In bladder cancer cells with intact KDM6A, FOXA1 interacted with KDM6A to activate genes instructing urothelial differentiation. KDM6A-deficient cells displayed simultaneous loss of FOXA1 target binding and genome-wide redistribution of the bZIP transcription factor ATF3, which in turn …
Generation Of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated By Mesenchymal Stem Cell Therapy, María García-Bonilla, Kirill Shumilov, James P Mcallister 2nd, David D Limbrick Jr., Et Al.
Generation Of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated By Mesenchymal Stem Cell Therapy, María García-Bonilla, Kirill Shumilov, James P Mcallister 2nd, David D Limbrick Jr., Et Al.
2020-Current year OA Pubs
Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh …
The Thin Line Between Conventional Dendritic Cells (Cdcs) And Group 3 Innate Lymphoid Cells (Ilc3s) In The Gut, Alina Ulezko Antonova, José Luís Fachi, Susan Gilfillan, Marco Colonna
The Thin Line Between Conventional Dendritic Cells (Cdcs) And Group 3 Innate Lymphoid Cells (Ilc3s) In The Gut, Alina Ulezko Antonova, José Luís Fachi, Susan Gilfillan, Marco Colonna
2020-Current year OA Pubs
Dendritic cells (DCs) express major histocompatibility complex class II (MHC-II) and are best known for proficiently presenting antigens to T cells, thereby eliciting specific adaptive T cell responses. Moreover, conventional DCs (cDCs) are specifically adept at handling intestinal antigens. Relatively recent discoveries and investigations have proven the existence of a new group of innate lymphocytes that reside in tissues like the intestine. They lack specific antigen receptors and can express MHC-II. These group 3 innate lymphoid cells (ILC3s) comprise a subset of heterogeneous innate lymphocytes that mirror the phenotype and functions of T-helper cells and act in the first line …
Molecular Mechanism Of Biased Signaling At The Kappa Opioid Receptor, Amal El Daibani, Joseph M Paggi, Kuglae Kim, Yianni D Laloudakis, Petr Popov, Sarah M Bernhard, Brian E Krumm, Reid H J Olsen, Jeffrey Diberto, F Ivy Carroll, Vsevolod Katritch, Bernhard Wünsch, Ron O Dror, Tao Che
Molecular Mechanism Of Biased Signaling At The Kappa Opioid Receptor, Amal El Daibani, Joseph M Paggi, Kuglae Kim, Yianni D Laloudakis, Petr Popov, Sarah M Bernhard, Brian E Krumm, Reid H J Olsen, Jeffrey Diberto, F Ivy Carroll, Vsevolod Katritch, Bernhard Wünsch, Ron O Dror, Tao Che
2020-Current year OA Pubs
The κ-opioid receptor (KOR) has emerged as an attractive drug target for pain management without addiction, and biased signaling through particular pathways of KOR may be key to maintaining this benefit while minimizing side-effect liabilities. As for most G protein-coupled receptors (GPCRs), however, the molecular mechanisms of ligand-specific signaling at KOR have remained unclear. To better understand the molecular determinants of KOR signaling bias, we apply structure determination, atomic-level molecular dynamics (MD) simulations, and functional assays. We determine a crystal structure of KOR bound to the G protein-biased agonist nalfurafine, the first approved KOR-targeting drug. We also identify an arrestin-biased …
Mechanism Of Kmt5b Haploinsufficiency In Neurodevelopment In Humans And Mice, Sarah E Sheppard, Marisa Andrews, Dustin Baldridge, John Constantino, Et Al.
Mechanism Of Kmt5b Haploinsufficiency In Neurodevelopment In Humans And Mice, Sarah E Sheppard, Marisa Andrews, Dustin Baldridge, John Constantino, Et Al.
2020-Current year OA Pubs
Pathogenic variants in
Synthesis And Characterization Of Pt(Ii) And Pd(Ii) Complexes With Planar Aromatic Oximes, Mikala Meadows, Lei Yang, Cody Turner, Mikhail Berezin, Sergiy Tyukhtenko, Nikolay Gerasimchuk
Synthesis And Characterization Of Pt(Ii) And Pd(Ii) Complexes With Planar Aromatic Oximes, Mikala Meadows, Lei Yang, Cody Turner, Mikhail Berezin, Sergiy Tyukhtenko, Nikolay Gerasimchuk
2020-Current year OA Pubs
No abstract provided.
Nirogacestat, A Γ-Secretase Inhibitor For Desmoid Tumors, Mrinal Gounder, Brian A Van Tine, Et Al.
Nirogacestat, A Γ-Secretase Inhibitor For Desmoid Tumors, Mrinal Gounder, Brian A Van Tine, Et Al.
2020-Current year OA Pubs
BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments.
METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival.
RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit …
Adipose-Targeted Swell1 Deletion Exacerbates Obesity- And Age-Related Nonalcoholic Fatty Liver Disease, Susheel K. Gunasekar, John Heebink, Danielle H Carpenter, Ashutosh Kumar, Litao Xie, Haixia Zhang, Joel D. Schilling, Rajan Sah
Adipose-Targeted Swell1 Deletion Exacerbates Obesity- And Age-Related Nonalcoholic Fatty Liver Disease, Susheel K. Gunasekar, John Heebink, Danielle H Carpenter, Ashutosh Kumar, Litao Xie, Haixia Zhang, Joel D. Schilling, Rajan Sah
2020-Current year OA Pubs
Healthy expansion of adipose tissue is critical for the maintenance of metabolic health, providing an optimized reservoir for energy storage in the form of triacylglycerol-rich lipoproteins. Dysfunctional adipocytes that are unable to efficiently store lipid can result in lipodystrophy and contribute to nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Leucine-rich repeat containing protein 8a/SWELL1 functionally encodes the volume-regulated anion channel complex in adipocytes, is induced in early obesity, and is required for normal adipocyte expansion during high-fat feeding. Adipose-specific SWELL1 ablation (Adipo KO) leads to insulin resistance and hyperglycemia during caloric excess, both of which are associated with NAFLD. …
Microbiology Clinical Culture Diagnostic Yields And Antimicrobial Resistance Proportions Before And During The Covid-19 Pandemic In An Indian Community Hospital And Two Us Community Hospitals, Sumanth Gandra, Gerardo Alvarez-Uria, Dustin Stwalley, Katelin B Nickel, Kimberly A Reske, Jennie H Kwon, Erik R Dubberke, Margaret A Olsen, Jason P Burnham
Microbiology Clinical Culture Diagnostic Yields And Antimicrobial Resistance Proportions Before And During The Covid-19 Pandemic In An Indian Community Hospital And Two Us Community Hospitals, Sumanth Gandra, Gerardo Alvarez-Uria, Dustin Stwalley, Katelin B Nickel, Kimberly A Reske, Jennie H Kwon, Erik R Dubberke, Margaret A Olsen, Jason P Burnham
2020-Current year OA Pubs
Studies comparing the impact of the COVID-19 pandemic on diagnostic microbiology culture yields and antimicrobial resistance proportions in low-to-middle-income and high-income countries are lacking. A retrospective study using blood, respiratory, and urine microbiology data from a community hospital in India and two community hospitals (Hospitals A and B) in St. Louis, MO, USA was performed. We compared the proportion of cultures positive for selected multi-drug-resistant organisms (MDROs) listed on the WHO's priority pathogen list both before the COVID-19 pandemic (January 2017-December 2019) and early in the COVID-19 pandemic (April 2020-October 2020). The proportion of blood cultures contaminated with coagulase-negative
Long-Term Gastrointestinal Outcomes Of Covid-19, Evan Xu, Yan Xie, Ziyad Al-Aly
Long-Term Gastrointestinal Outcomes Of Covid-19, Evan Xu, Yan Xie, Ziyad Al-Aly
2020-Current year OA Pubs
A comprehensive evaluation of the risks and 1-year burdens of gastrointestinal disorders in the post-acute phase of COVID-19 is needed but is not yet available. Here we use the US Department of Veterans Affairs national health care databases to build a cohort of 154,068 people with COVID-19, 5,638,795 contemporary controls, and 5,859,621 historical controls to estimate the risks and 1-year burdens of a set of pre-specified incident gastrointestinal outcomes. We show that beyond the first 30 days of infection, people with COVID-19 exhibited increased risks and 1-year burdens of incident gastrointestinal disorders spanning several disease categories including motility disorders, acid …
Charge-Voltage Curves Of Shaker Potassium Channel Are Not Hysteretic At Steady State, John Cowgill, Baron Chanda
Charge-Voltage Curves Of Shaker Potassium Channel Are Not Hysteretic At Steady State, John Cowgill, Baron Chanda
2020-Current year OA Pubs
Charge-voltage curves of many voltage-gated ion channels exhibit hysteresis but such curves are also a direct measure of free energy of channel gating and, hence, should be path-independent. Here, we identify conditions to measure steady-state charge-voltage curves and show that these are curves are not hysteretic. Charged residues in transmembrane segments of voltage-gated ion channels (VGICs) sense and respond to changes in the electric field. The movement of these gating charges underpins voltage-dependent activation and is also a direct metric of the net free-energy of channel activation. However, for most voltage-gated ion channels, the charge-voltage (Q-V) curves appear to be …
Predicting Locations Of Cryptic Pockets From Single Protein Structures Using The Pocketminer Graph Neural Network, Artur Meller, Michael Ward, Jonathan Borowsky, Meghana Kshirsagar, Jeffrey M Lotthammer, Felipe Oviedo, Juan Lavista Ferres, Gregory R Bowman
Predicting Locations Of Cryptic Pockets From Single Protein Structures Using The Pocketminer Graph Neural Network, Artur Meller, Michael Ward, Jonathan Borowsky, Meghana Kshirsagar, Jeffrey M Lotthammer, Felipe Oviedo, Juan Lavista Ferres, Gregory R Bowman
2020-Current year OA Pubs
Cryptic pockets expand the scope of drug discovery by enabling targeting of proteins currently considered undruggable because they lack pockets in their ground state structures. However, identifying cryptic pockets is labor-intensive and slow. The ability to accurately and rapidly predict if and where cryptic pockets are likely to form from a structure would greatly accelerate the search for druggable pockets. Here, we present PocketMiner, a graph neural network trained to predict where pockets are likely to open in molecular dynamics simulations. Applying PocketMiner to single structures from a newly curated dataset of 39 experimentally confirmed cryptic pockets demonstrates that it …
Prospective Associations Between Accelerometry-Derived Physical Activity And Sedentary Behaviors And Mortality Among Cancer Survivors, Elizabeth A Salerno, Pedro F Saint-Maurice, Fei Wan, Lindsay L Peterson, Yikyung Park, Yin Cao, Ryan P Duncan, Richard P Troiano, Charles E Matthews
Prospective Associations Between Accelerometry-Derived Physical Activity And Sedentary Behaviors And Mortality Among Cancer Survivors, Elizabeth A Salerno, Pedro F Saint-Maurice, Fei Wan, Lindsay L Peterson, Yikyung Park, Yin Cao, Ryan P Duncan, Richard P Troiano, Charles E Matthews
2020-Current year OA Pubs
BACKGROUND: Survival benefits of self-reported recreational physical activity (PA) during cancer survivorship are well-documented in common cancer types, yet there are limited data on the associations between accelerometer-derived PA of all domains, sedentary behavior, and mortality in large, diverse cohorts of cancer survivors.
METHODS: Participants included adults who reported a cancer diagnosis in the National Health and Nutrition Examination Survey and wore an accelerometer for up to 7 days in 2003-2006. Participants were followed for subsequent mortality through 2015. We examined the association of light PA, moderate to vigorous PA, total PA, and sedentary behavior, with all-cause mortality. Cox proportional …
Targeted Deletion Of Fgf9 In Tendon Disrupts Mineralization Of The Developing Enthesis, Elahe Ganji, Connor Leek, William Duncan, Debabrata Patra, David M Ornitz, Megan L Killian
Targeted Deletion Of Fgf9 In Tendon Disrupts Mineralization Of The Developing Enthesis, Elahe Ganji, Connor Leek, William Duncan, Debabrata Patra, David M Ornitz, Megan L Killian
2020-Current year OA Pubs
The enthesis is a transitional tissue between tendon and bone that matures postnatally. The development and maturation of the enthesis involve cellular processes likened to an arrested growth plate. In this study, we explored the role of fibroblast growth factor 9 (Fgf9), a known regulator of chondrogenesis and vascularization during bone development, on the structure and function of the postnatal enthesis. First, we confirmed spatial expression of Fgf9 in the tendon and enthesis using in situ hybridization. We then used Cre-lox recombinase to conditionally knockout Fgf9 in mouse tendon and enthesis (Scx-Cre) and characterized enthesis morphology as well as mechanical …
A New Mouse Model Of Elastin Haploinsufficiency Highlights The Importance Of Elastin To Vascular Development And Blood Pressure Regulation, Bridget M Brengle, Michelle Lin, Robyn A Roth, Kara D Jones, Jessica E Wagenseil, Robert P Mecham, Carmen M Halabi
A New Mouse Model Of Elastin Haploinsufficiency Highlights The Importance Of Elastin To Vascular Development And Blood Pressure Regulation, Bridget M Brengle, Michelle Lin, Robyn A Roth, Kara D Jones, Jessica E Wagenseil, Robert P Mecham, Carmen M Halabi
2020-Current year OA Pubs
Supravalvular aortic stenosis (SVAS) is an autosomal dominant disease resulting from elastin (ELN) haploinsufficiency. Individuals with SVAS typically develop a thickened arterial media with an increased number of elastic lamellae and smooth muscle cell (SMC) layers and stenosis superior to the aortic valve. A mouse model of SVAS (Eln
Society For Immunotherapy Of Cancer (Sitc) Consensus Definitions For Resistance To Combinations Of Immune Checkpoint Inhibitors With Chemotherapy, Naiyer Rizvi, Foluso O. Ademuyiwa, Z Alexander Cao, Helen X. Chen, Robert L. Ferris, Sarah B. Goldberg, Matthew D. Hellmann, Ranee Mehra, Ina Rhee, Jong Chul Park, Harriet Kluger, Hussein Tawbi, Ryan J. Sullivan
Society For Immunotherapy Of Cancer (Sitc) Consensus Definitions For Resistance To Combinations Of Immune Checkpoint Inhibitors With Chemotherapy, Naiyer Rizvi, Foluso O. Ademuyiwa, Z Alexander Cao, Helen X. Chen, Robert L. Ferris, Sarah B. Goldberg, Matthew D. Hellmann, Ranee Mehra, Ina Rhee, Jong Chul Park, Harriet Kluger, Hussein Tawbi, Ryan J. Sullivan
2020-Current year OA Pubs
Although immunotherapy can offer profound clinical benefit for patients with a variety of difficult-to-treat cancers, many tumors either do not respond to upfront treatment with immune checkpoint inhibitors (ICIs) or progressive/recurrent disease occurs after an interval of initial control. Improved response rates have been demonstrated with the addition of ICIs to cytotoxic therapies, leading to approvals from the US Food and Drug Administration and regulatory agencies in other countries for ICI-chemotherapy combinations in a number of solid tumor indications, including breast, head and neck, gastric, and lung cancer. Designing trials for patients with tumors that do not respond or stop …
Harmonization And Standardization Of Nucleus Pulposus Cell Extraction And Culture Methods, Shaghayegh Basatvat, Liufang Jing, Lori Setton, Xiaohong Tan, Et Al.
Harmonization And Standardization Of Nucleus Pulposus Cell Extraction And Culture Methods, Shaghayegh Basatvat, Liufang Jing, Lori Setton, Xiaohong Tan, Et Al.
2020-Current year OA Pubs
BACKGROUND: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.
METHODS: The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, …
Genomic Patterns Of Malignant Peripheral Nerve Sheath Tumor (Mpnst) Evolution Correlate With Clinical Outcome And Are Detectable In Cell-Free Dna, Isidro Cortes-Ciriano, Dana C Borcherding, Jeffrey J Szymanski, Angela C Hirbe, Et Al.
Genomic Patterns Of Malignant Peripheral Nerve Sheath Tumor (Mpnst) Evolution Correlate With Clinical Outcome And Are Detectable In Cell-Free Dna, Isidro Cortes-Ciriano, Dana C Borcherding, Jeffrey J Szymanski, Angela C Hirbe, Et Al.
2020-Current year OA Pubs
UNLABELLED: Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling …
Resolution Of Hepatic Fibrosis After Zfn-Mediated Gene Editing In The Piz Mouse Model Of Human Α1-Antitrypsin Deficiency, Yanfeng Li, Chandan Guha, Patrik Asp, Xia Wang, Tatyana L. Tchaikovskya, Kenneth Kim, Matthew Mendel, Gregory J. Cost, David H. Perlmutter, Namita Roy-Chowdhury, Ira J. Fox, Anthony Conway, Jayanta Roy-Chowdhury
Resolution Of Hepatic Fibrosis After Zfn-Mediated Gene Editing In The Piz Mouse Model Of Human Α1-Antitrypsin Deficiency, Yanfeng Li, Chandan Guha, Patrik Asp, Xia Wang, Tatyana L. Tchaikovskya, Kenneth Kim, Matthew Mendel, Gregory J. Cost, David H. Perlmutter, Namita Roy-Chowdhury, Ira J. Fox, Anthony Conway, Jayanta Roy-Chowdhury
2020-Current year OA Pubs
BACKGROUND: α1-antitrypsin deficiency is most commonly caused by a mutation in exon-7 of SERPINA1 (SA1-ATZ), resulting in hepatocellular accumulation of a misfolded variant (ATZ). Human SA1-ATZ-transgenic (PiZ) mice exhibit hepatocellular ATZ accumulation and liver fibrosis. We hypothesized that disrupting the SA1-ATZ transgene in PiZ mice by in vivo genome editing would confer a proliferative advantage to the genome-edited hepatocytes, enabling them to repopulate the liver.
METHODS: To create a targeted DNA break in exon-7 of the SA1-ATZ transgene, we generated 2 recombinant adeno-associated viruses (rAAV) expressing a zinc-finger nuclease pair (rAAV-ZFN), and another rAAV for gene correction by targeted insertion …
Hiv Increases The Risk Of Cigarette Smoke-Induced Emphysema Through Mmp-9, Bashar S. Staitieh, Simran Malik, Sara C. Auld, Gregory W. Wigger, Xian Fan, Andrew T. Roth, Tanima Chatterjee, Itika Arora, S. Vamsee Raju, Sonya Heath, Saurabh Aggrawal
Hiv Increases The Risk Of Cigarette Smoke-Induced Emphysema Through Mmp-9, Bashar S. Staitieh, Simran Malik, Sara C. Auld, Gregory W. Wigger, Xian Fan, Andrew T. Roth, Tanima Chatterjee, Itika Arora, S. Vamsee Raju, Sonya Heath, Saurabh Aggrawal
2020-Current year OA Pubs
BACKGROUND: HIV is associated with an increased risk for emphysema. Matrix metalloproteinase 9 (MMP-9) is a lung tissue remodeling enzyme associated with emphysema. We previously found MMP-9 activity increases with increases in oxidative stress and that HIV increases alveolar oxidative stress. We hypothesized that HIV proteins would increase the risk of cigarette smoke-induced emphysema due to MMP-9.
METHODS: HIV-1 transgenic rats and wild-type littermates were exposed to cigarette smoke or sham for 8 weeks. Lung compliance and histology were assessed. Bronchoalveolar lavage (BAL), primary alveolar macrophages (AM), and serum samples were obtained. A rat alveolar macrophage cell line was exposed …
Effect Of Fecal Microbial Transplantation On Clostridioides Difficile Infection: Dysbiosis, Metabolites And Health Related Quality Of Life, Kevin W Garey, Paul Feuerstadt, Erik R Dubberke, Amy Guo, Glenn S Tillotson
Effect Of Fecal Microbial Transplantation On Clostridioides Difficile Infection: Dysbiosis, Metabolites And Health Related Quality Of Life, Kevin W Garey, Paul Feuerstadt, Erik R Dubberke, Amy Guo, Glenn S Tillotson
2020-Current year OA Pubs
No abstract provided.
Aim18p And Aim46p Are Chalcone Isomerase Domain-Containing Mitochondrial Hemoproteins In Saccharomyces Cerevisiae, Jonathan M Schmitz, John F Wolters, Nathan H Murray, Rachel M Guerra, Craig A Bingman, Chris Todd Hittinger, David J Pagliarini
Aim18p And Aim46p Are Chalcone Isomerase Domain-Containing Mitochondrial Hemoproteins In Saccharomyces Cerevisiae, Jonathan M Schmitz, John F Wolters, Nathan H Murray, Rachel M Guerra, Craig A Bingman, Chris Todd Hittinger, David J Pagliarini
2020-Current year OA Pubs
Chalcone isomerases (CHIs) have well-established roles in the biosynthesis of plant flavonoid metabolites. Saccharomyces cerevisiae possesses two predicted CHI-like proteins, Aim18p (encoded by YHR198C) and Aim46p (YHR199C), but it lacks other enzymes of the flavonoid pathway, suggesting that Aim18p and Aim46p employ the CHI fold for distinct purposes. Here, we demonstrate using proteinase K protection assays, sodium carbonate extractions, and crystallography that Aim18p and Aim46p reside on the mitochondrial inner membrane and adopt CHI folds, but they lack select active site residues and possess an extra fungal-specific loop. Consistent with these differences, Aim18p and Aim46p lack CHI activity and also …
Computational Modeling Of The N-Back Task In The Abcd Study: Associations Of Drift Diffusion Model Parameters To Polygenic Scores Of Mental Disorders And Cardiometabolic Diseases, Mads L Pedersen, Dag Alnæs, Dennis Van Der Meer, Sara Fernandez-Cabello, Pierre Berthet, Andreas Dahl, Rikka Kjelkenes, Emanuel Schwarz, Wesley K Thompson, Deanna M Barch, Ole A Andreassen, Lars T Westlye
Computational Modeling Of The N-Back Task In The Abcd Study: Associations Of Drift Diffusion Model Parameters To Polygenic Scores Of Mental Disorders And Cardiometabolic Diseases, Mads L Pedersen, Dag Alnæs, Dennis Van Der Meer, Sara Fernandez-Cabello, Pierre Berthet, Andreas Dahl, Rikka Kjelkenes, Emanuel Schwarz, Wesley K Thompson, Deanna M Barch, Ole A Andreassen, Lars T Westlye
2020-Current year OA Pubs
BACKGROUND: Cognitive dysfunction is common in mental disorders and represents a potential risk factor in childhood. The nature and extent of associations between childhood cognitive function and polygenic risk for mental disorders is unclear. We applied computational modeling to gain insight into mechanistic processes underlying decision making and working memory in childhood and their associations with polygenic risk scores (PRSs) for mental disorders and comorbid cardiometabolic diseases.
METHODS: We used the drift diffusion model to infer latent computational processes underlying decision making and working memory during the n-back task in 3707 children ages 9 to 10 years from the Adolescent …
Aging And Obesity Prime The Methylome And Transcriptome Of Adipose Stem Cells For Disease And Dysfunction, Shaojun Xie, Sulbha Choudhari, Chia-Lung Wu, Karen Abramson, David Corcoran, Simon G Gregory, Jyothi Thimmapuram, Farshid Guilak, Dianne Little
Aging And Obesity Prime The Methylome And Transcriptome Of Adipose Stem Cells For Disease And Dysfunction, Shaojun Xie, Sulbha Choudhari, Chia-Lung Wu, Karen Abramson, David Corcoran, Simon G Gregory, Jyothi Thimmapuram, Farshid Guilak, Dianne Little
2020-Current year OA Pubs
The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12-months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to …
Nitric Oxide-Driven Modifications Of Lipoic Arm Inhibit Α-Ketoacid Dehydrogenases, Gretchen L Seim, Steven V John, Nicholas L Arp, Zixiang Fang, David J Pagliarini, Jing Fan
Nitric Oxide-Driven Modifications Of Lipoic Arm Inhibit Α-Ketoacid Dehydrogenases, Gretchen L Seim, Steven V John, Nicholas L Arp, Zixiang Fang, David J Pagliarini, Jing Fan
2020-Current year OA Pubs
Pyruvate dehydrogenase complex (PDHC) and oxoglutarate dehydrogenase complex (OGDC), which belong to the mitochondrial α-ketoacid dehydrogenase family, play crucial roles in cellular metabolism. These multi-subunit enzyme complexes use lipoic arms covalently attached to their E2 subunits to transfer an acyl group to coenzyme A (CoA). Here, we report a novel mechanism capable of substantially inhibiting PDHC and OGDC: reactive nitrogen species (RNS) can covalently modify the thiols on their lipoic arms, generating a series of adducts that block catalytic activity. S-Nitroso-CoA, a product between RNS and the E2 subunit's natural substrate, CoA, can efficiently deliver these modifications onto the lipoic …
Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty
Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty
2020-Current year OA Pubs
In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene