Open Access. Powered by Scholars. Published by Universities.®
- Discipline
- Keyword
-
- Humans (321)
- Animals (227)
- Female (168)
- Male (153)
- Mice (151)
-
- Middle Aged (67)
- Adult (64)
- Aged (60)
- Mice, Inbred C57BL (44)
- Disease Models, Animal (42)
- Signal Transduction (42)
- Mice, Knockout (40)
- COVID-19 (37)
- SARS-CoV-2 (32)
- Mutation (30)
- Brain (26)
- Young Adult (23)
- Adolescent (22)
- Aged, 80 and over (22)
- Child (22)
- Cells, Cultured (21)
- Neurons (21)
- Cell Line, Tumor (20)
- Mice, Transgenic (20)
- Child, Preschool (18)
- Protein Binding (17)
- Alzheimer Disease (16)
- Cell Line (16)
- Cell Proliferation (15)
- Gastrointestinal Microbiome (15)
Articles 1891 - 1920 of 5949
Full-Text Articles in Entire DC Network
Site-1 Protease Deficiency Causes Human Skeletal Dysplasia Due To Defective Inter-Organelle Protein Trafficking, Yuji Kondo, Debabrata Patra, Et Al
Site-1 Protease Deficiency Causes Human Skeletal Dysplasia Due To Defective Inter-Organelle Protein Trafficking, Yuji Kondo, Debabrata Patra, Et Al
Open Access Publications
Site-1 protease (S1P), encoded by MBTPS1, is a serine protease in the Golgi. S1P regulates lipogenesis, endoplasmic reticulum (ER) function, and lysosome biogenesis in mice and in cultured cells. However, how S1P differentially regulates these diverse functions in humans has been unclear. In addition, no human disease with S1P deficiency has been identified. Here, we report a pediatric patient with an amorphic and a severely hypomorphic mutation in MBTPS1. The unique combination of these mutations results in a frequency of functional MBTPS1 transcripts of approximately 1%, a finding that is associated with skeletal dysplasia and elevated blood lysosomal enzymes. We …
Human Fibroblast And Stem Cell Resource From The Dominantly Inherited Alzheimer Network, Celeste M Karch, Damián Hernández, Jen-Chyong Wang, Jacob Marsh, Alex W Hewitt, Simon Hsu, Joanne Norton, Denise Levitch, Tamara Donahue, Wendy Sigurdson, Bernardino Ghetti, Martin Farlow, Jasmeer Chhatwal, Sarah Berman, Carlos Cruchaga, John C Morris, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Alice Pébay, Alison M Goate
Human Fibroblast And Stem Cell Resource From The Dominantly Inherited Alzheimer Network, Celeste M Karch, Damián Hernández, Jen-Chyong Wang, Jacob Marsh, Alex W Hewitt, Simon Hsu, Joanne Norton, Denise Levitch, Tamara Donahue, Wendy Sigurdson, Bernardino Ghetti, Martin Farlow, Jasmeer Chhatwal, Sarah Berman, Carlos Cruchaga, John C Morris, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Alice Pébay, Alison M Goate
Open Access Publications
BACKGROUND: Mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause autosomal dominant forms of Alzheimer disease (ADAD). More than 280 pathogenic mutations have been reported in APP, PSEN1, and PSEN2. However, understanding of the basic biological mechanisms that drive the disease are limited. The Dominantly Inherited Alzheimer Network (DIAN) is an international observational study of APP, PSEN1, and PSEN2 mutation carriers with the goal of determining the sequence of changes in presymptomatic mutation carriers who are destined to develop Alzheimer disease.
RESULTS: We generated a library of 98 dermal fibroblast lines from 42 ADAD families …
Plasticity Of Differentiated Cells In Wound Repair And Tumorigenesis, Part I: Stomach And Pancreas, Joseph Burclaff, Jason C Mills
Plasticity Of Differentiated Cells In Wound Repair And Tumorigenesis, Part I: Stomach And Pancreas, Joseph Burclaff, Jason C Mills
Open Access Publications
For the last century or so, the mature, differentiated cells throughout the body have been regarded as largely inert with respect to their regenerative potential, yet recent research shows that they can become progenitor-like and re-enter the cell cycle. Indeed, we recently proposed that mature cells can become regenerative via a conserved set of molecular mechanisms ('paligenosis'), suggesting that a program for regeneration exists alongside programs for death (apoptosis) and division (mitosis). In two Reviews describing how emerging concepts of cellular plasticity are changing how the field views regeneration and tumorigenesis, we present the commonalities in the molecular and cellular …
Discovery And Validation Of Autosomal Dominant Alzheimer's Disease Mutations, Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric Mcdade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Celeste M Karch
Discovery And Validation Of Autosomal Dominant Alzheimer's Disease Mutations, Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric Mcdade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Celeste M Karch
Open Access Publications
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. Mutations in amyloid-β precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the pathogenic cause of autosomal dominant AD (ADAD). However, polymorphisms also exist within these genes.
METHODS: In order to distinguish polymorphisms from pathogenic mutations, the DIAN Expanded Registry has implemented an algorithm for determining ADAD pathogenicity using available information from multiple domains, including genetic, bioinformatic, clinical, imaging, and biofluid measures and in vitro analyses.
RESULTS: We propose that PSEN1 M84V, PSEN1 A396T, PSEN2 R284G, and APP T719N are likely pathogenic …
Dysregulation Of Nad+ Metabolism Induces A Schwann Cell Dedifferentiation Program, Yo Sasaki, Amber R. Hackett, Sungsu Kim, Amy Strickland, Jeffrey Milbrandt
Dysregulation Of Nad+ Metabolism Induces A Schwann Cell Dedifferentiation Program, Yo Sasaki, Amber R. Hackett, Sungsu Kim, Amy Strickland, Jeffrey Milbrandt
Open Access Publications
The Schwann cell (SC) is the major component of the peripheral nervous system (PNS) that provides metabolic and functional support for peripheral axons. The emerging roles of SC mitochondrial function for PNS development and axonal stability indicate the importance of SC metabolism in nerve function and in peripheral neuropathies associated with metabolic disorders. Nicotinamide adenine dinucleotide (NAD
Association Of Inferior Vena Cava Filter Placement For Venous Thromboembolic Disease And A Contraindication To Anticoagulation With 30-Day Mortality, Tyson E. Turner, Mohammed J. Saeed, Eric Novak, David L. Brown
Association Of Inferior Vena Cava Filter Placement For Venous Thromboembolic Disease And A Contraindication To Anticoagulation With 30-Day Mortality, Tyson E. Turner, Mohammed J. Saeed, Eric Novak, David L. Brown
Open Access Publications
Importance: Despite the absence of data from randomized clinical trials, professional societies recommend inferior vena cava (IVC) filters for patients with venous thromboembolic disease (VTE) and a contraindication to anticoagulation therapy. Prior observational studies of IVC filters have suggested a mortality benefit associated with IVC filter insertion but have often failed to adjust for immortal time bias, which is the time before IVC filter insertion, during which death can only occur in the control group.
Objective: To determine the association of IVC filter placement with 30-day mortality after adjustment for immortal time bias.
Design, Setting, and Participants: This comparative effectiveness, …
Epigenomics And Metabolomics Reveal The Mechanism Of The Apoa2-Saturated Fat Intake Interaction Affecting Obesity, Chao-Qiang Lai, Caren E Smith, Laurence D Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A Hidalgo, Stella Aslibekyan, Michael A Province, Devin Absher, Donna K Arnett, Katherine L Tucker, Jose M Ordovas
Epigenomics And Metabolomics Reveal The Mechanism Of The Apoa2-Saturated Fat Intake Interaction Affecting Obesity, Chao-Qiang Lai, Caren E Smith, Laurence D Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A Hidalgo, Stella Aslibekyan, Michael A Province, Devin Absher, Donna K Arnett, Katherine L Tucker, Jose M Ordovas
Open Access Publications
Background: The putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.
Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.
Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites.
Results: In the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar …
22>Cellular Trafficking Of Sn-2 Phosphatidylcholine Prodrugs Studied With Fluorescence Lifetime Imaging And Super-Resolution Microscopy, Dolonchampa Maji, Jin Lu, Pinaki Sarder, Anne H Schmieder, Grace Cui, Xiaoxia Yang, Dipanjan Pan, Matthew D Lew, Samuel Achilefu, Gregory M Lanza
Cellular Trafficking Of Sn-2 Phosphatidylcholine Prodrugs Studied With Fluorescence Lifetime Imaging And Super-Resolution Microscopy, Dolonchampa Maji, Jin Lu, Pinaki Sarder, Anne H Schmieder, Grace Cui, Xiaoxia Yang, Dipanjan Pan, Matthew D Lew, Samuel Achilefu, Gregory M Lanza
Open Access Publications
While the
Hepatic Ketogenic Insufficiency Reprograms Hepatic Glycogen Metabolism And The Lipidome, D. André D'Avignon, Patrycja Puchalska, Baris Ercal, Yingju Chang, Shannon E. Martin, Mark J. Graham, Gary J. Patti, Xianlin Han, Peter A. Crawford
Hepatic Ketogenic Insufficiency Reprograms Hepatic Glycogen Metabolism And The Lipidome, D. André D'Avignon, Patrycja Puchalska, Baris Ercal, Yingju Chang, Shannon E. Martin, Mark J. Graham, Gary J. Patti, Xianlin Han, Peter A. Crawford
Open Access Publications
While several molecular targets are under consideration, mechanistic underpinnings of the transition from uncomplicated nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) remain unresolved. Here we apply multiscale chemical profiling technologies to mouse models of deranged hepatic ketogenesis to uncover potential NAFLD driver signatures. Use of stable-isotope tracers, quantitatively tracked by nuclear magnetic resonance (NMR) spectroscopy, supported previous observations that livers of wild-type mice maintained long term on a high-fat diet (HFD) exhibit a marked increase in hepatic energy charge. Fed-state ketogenesis rates increased nearly 3-fold in livers of HFD-fed mice, a greater proportionate increase than that observed for …
Modulation Of Subsets Of Cardiac B Lymphocytes Improves Cardiac Function After Acute Injury, Luigi Adamo, Lora J Staloch, Cibele Rocha-Resende, Scot J Matkovich, Wenlong Jiang, Geetika Bajpai, Carla J Weinheimer, Attila Kovacs, Joel D Schilling, Philip M Barger, Deepta Bhattacharya, Douglas L Mann
Modulation Of Subsets Of Cardiac B Lymphocytes Improves Cardiac Function After Acute Injury, Luigi Adamo, Lora J Staloch, Cibele Rocha-Resende, Scot J Matkovich, Wenlong Jiang, Geetika Bajpai, Carla J Weinheimer, Attila Kovacs, Joel D Schilling, Philip M Barger, Deepta Bhattacharya, Douglas L Mann
Open Access Publications
Despite the long-standing recognition that the immune response to acute myocardial injury contributes to adverse left ventricular (LV) remodeling, it has not been possible to effectively target this clinically. Using 2 different in vivo models of acute myocardial injury, we show that pirfenidone confers beneficial effects in the murine heart through an unexpected mechanism that depends on cardiac B lymphocytes. Naive hearts contained a large population of CD19+CD11b-CD23-CD21-IgD+IgMlo lymphocytes, and 2 smaller populations of CD19+CD11b+ B1a and B1b cells. In response to tissue injury, there was an increase in neutrophils, monocytes, macrophages, as well as an increase in CD19+ CD11b- …
Intensity-Modulated Radiotherapy For Prostate Cancer, Ben W Fischer-Valuck, Yuan James Rao, Jeff M Michalski
Intensity-Modulated Radiotherapy For Prostate Cancer, Ben W Fischer-Valuck, Yuan James Rao, Jeff M Michalski
Open Access Publications
Radiation therapy (RT) is a curative treatment modality for localized prostate cancer. Over the past two decades, advances in technology and imaging have considerably changed RT in prostate cancer treatment. Treatment has evolved from 2-dimensional (2D) planning using X-ray fields based on pelvic bony landmarks to 3-dimensional (3D) conformal RT (CRT) which uses computed tomography (CT) based planning. Despite improvements with 3D-CRT, dose distributions often remained suboptimal with portions of the rectum and bladder receiving unacceptably high doses. In more recent years, intensity-modulated radiation therapy (IMRT) has become the standard of care to deliver external beam RT. IMRT uses multiple …
Palladin Is A Neuron-Specific Translational Target Of Mtor Signaling That Regulates Axon Morphogenesis, Yusuke Umegaki, Antonio Martínez Brotons, Yui Nakanishi, Zhongyue Luo, Hanlu Zhang, Azad Bonni, Yoshiho Ikeuchi
Palladin Is A Neuron-Specific Translational Target Of Mtor Signaling That Regulates Axon Morphogenesis, Yusuke Umegaki, Antonio Martínez Brotons, Yui Nakanishi, Zhongyue Luo, Hanlu Zhang, Azad Bonni, Yoshiho Ikeuchi
Open Access Publications
The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates …
Parabiosis And Single-Cell Rna Sequencing Reveal A Limited Contribution Of Monocytes To Myofibroblasts In Kidney Fibrosis, Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K Schneider, Benjamin D Humphreys
Parabiosis And Single-Cell Rna Sequencing Reveal A Limited Contribution Of Monocytes To Myofibroblasts In Kidney Fibrosis, Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K Schneider, Benjamin D Humphreys
Open Access Publications
Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney …
Aberrant Atrx Protein Expression Is Associated With Poor Overall Survival In Nf1-Mpnst, Hsiang-Chih Lu, Vanessa Eulo, Anthony J. Apicelli, Melike Pekmezci, Yu Tao, Jingqin Luo, Angela C. Hirbe, Sonika Dahiya
Aberrant Atrx Protein Expression Is Associated With Poor Overall Survival In Nf1-Mpnst, Hsiang-Chih Lu, Vanessa Eulo, Anthony J. Apicelli, Melike Pekmezci, Yu Tao, Jingqin Luo, Angela C. Hirbe, Sonika Dahiya
Open Access Publications
Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive soft tissue sarcomas that can occur sporadically or in the setting of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. These tumors carry a dismal overall survival. Previous work in our lab had identified ATRX chromatin remodeler (
Validation Of A Novel Scoring System For Changes In Skeletal Manifestations Of Hypophosphatasia In Newborns, Infants, And Children: The Radiographic Global Impression Of Change Scale, Michael P Whyte, Kenji P Fujita, Scott Moseley, David D Thompson, William H Mcalister
Validation Of A Novel Scoring System For Changes In Skeletal Manifestations Of Hypophosphatasia In Newborns, Infants, And Children: The Radiographic Global Impression Of Change Scale, Michael P Whyte, Kenji P Fujita, Scott Moseley, David D Thompson, William H Mcalister
Open Access Publications
Hypophosphatasia (HPP) is the heritable metabolic disease characterized by impaired skeletal mineralization due to low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Although HPP during growth often manifests with distinctive radiographic skeletal features, no validated method was available to quantify them, including changes over time. We created the Radiographic Global Impression of Change (RGI-C) scale to assess changes in the skeletal burden of pediatric HPP. Site-specific pairs of radiographs of newborns, infants, and children with HPP from three clinical studies of asfotase alfa, an enzyme replacement therapy for HPP, were obtained at baseline and during treatment. Each pair was …
Sall1 Functions As A Tumor Suppressor In Breast Cancer By Regulating Cancer Cell Senescence And Metastasis Through The Nurd Complex, Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C Hsueh, Lynn Robbins, Susan M Kiefer, Yanping Zhang, Pamela Hunborg, Mark A Varvares, Michael Rauchman, Guangyong Peng
Sall1 Functions As A Tumor Suppressor In Breast Cancer By Regulating Cancer Cell Senescence And Metastasis Through The Nurd Complex, Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C Hsueh, Lynn Robbins, Susan M Kiefer, Yanping Zhang, Pamela Hunborg, Mark A Varvares, Michael Rauchman, Guangyong Peng
Open Access Publications
BACKGROUND: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown.
METHODS: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor …
Dynamic Changes During The Treatment Of Pancreatic Cancer, Robert A. Wolff, Andrea Wang-Gillam, Et Al
Dynamic Changes During The Treatment Of Pancreatic Cancer, Robert A. Wolff, Andrea Wang-Gillam, Et Al
Open Access Publications
This manuscript follows a single patient with pancreatic adenocarcinoma for a five year period, detailing the clinical record, pathology, the dynamic evolution of molecular and cellular alterations as well as the responses to treatments with chemotherapies, targeted therapies and immunotherapies. DNA and RNA samples from biopsies and blood identified a dynamic set of changes in allelic imbalances and copy number variations in response to therapies. Organoid cultures established from biopsies over time were employed for extensive drug testing to determine if this approach was feasible for treatments. When an unusual drug response was detected, an extensive RNA sequencing analysis was …
Interleukin-7 Restores Lymphocytes In Septic Shock: The Iris-7 Randomized Clinical Trial, Bruno Francois, Andrew H Walton, Jacqueline Unsinger, Teresa Blood, Jane Blood, Richard S Hotchkiss, Et Al
Interleukin-7 Restores Lymphocytes In Septic Shock: The Iris-7 Randomized Clinical Trial, Bruno Francois, Andrew H Walton, Jacqueline Unsinger, Teresa Blood, Jane Blood, Richard S Hotchkiss, Et Al
Open Access Publications
BACKGROUND: A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity.
METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia. Twenty-seven patients at academic sites in France and the United States received CYT107 or placebo for 4 …
Physiological Mechanisms Of Sustained Fumagillin-Induced Weight Loss, Jie An, Michael L Patnode, Vanessa K Ridaura, Jeffrey I Gordon, Et Al
Physiological Mechanisms Of Sustained Fumagillin-Induced Weight Loss, Jie An, Michael L Patnode, Vanessa K Ridaura, Jeffrey I Gordon, Et Al
Open Access Publications
Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by …
Subclones Dominate At Mds Progression Following Allogeneic Hematopoietic Cell Transplant, Meagan A Jacoby, Eric J Duncavage, Gue Su Chang, Christopher A Miller, Jin Shao, Kevin Elliott, Joshua Robinson, Robert S Fulton, Catrina C Fronick, Michelle O'Laughlin, Sharon E Heath, Iskra Pusic, John S Welch, Daniel C Link, John F Dipersio, Peter Westervelt, Timothy J Ley, Timothy A Graubert, Matthew J Walter
Subclones Dominate At Mds Progression Following Allogeneic Hematopoietic Cell Transplant, Meagan A Jacoby, Eric J Duncavage, Gue Su Chang, Christopher A Miller, Jin Shao, Kevin Elliott, Joshua Robinson, Robert S Fulton, Catrina C Fronick, Michelle O'Laughlin, Sharon E Heath, Iskra Pusic, John S Welch, Daniel C Link, John F Dipersio, Peter Westervelt, Timothy J Ley, Timothy A Graubert, Matthew J Walter
Open Access Publications
Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for myelodysplastic syndromes (MDS), but patients who relapse after transplant have poor outcomes. In order to understand the contribution of tumor clonal evolution to disease progression,we applied exome and error-corrected targeted sequencing coupled with copy number analysis to comprehensively define changes in the clonal architecture of MDS in response to therapy using 51 serially acquired tumor samples from 9 patients who progressed after an alloHCT. We show that small subclones before alloHCT can drive progression after alloHCT. Notably, at least one subclone expanded or emerged at progression in all patients. …
Largest Gwas Of Ptsd (N=20 070) Yields Genetic Overlap With Schizophrenia And Sex Differences In Heritability., L E Duncan, A Ratanatharathorn, A E Aiello, L M Almli, A B Amstadter, A E Ashley-Koch, D G Baker, J C Beckham, L J Bierut, J Bisson, B Bradley, C-Y Chen, S Dalvie, L A Farrer, S Galea, M E Garrett, J E Gelernter, G Guffanti, M A Hauser, E O Johnson, R C Kessler, N A Kimbrel, A King, N Koen, H R Kranzler, M W Logue, A X Maihofer, A R Martin, M W Miller, R A Morey, N R Nugent, J P Rice, S Ripke, A L Roberts, N L Saccone, J W Smoller, D J Stein, M B Stein, J A Sumner, M Uddin, R J Ursano, D E Wildman, R Yehuda, H Zhao, M J Daly, I Liberzon, K J Ressler, C M Nievergelt, K C Koenen
Largest Gwas Of Ptsd (N=20 070) Yields Genetic Overlap With Schizophrenia And Sex Differences In Heritability., L E Duncan, A Ratanatharathorn, A E Aiello, L M Almli, A B Amstadter, A E Ashley-Koch, D G Baker, J C Beckham, L J Bierut, J Bisson, B Bradley, C-Y Chen, S Dalvie, L A Farrer, S Galea, M E Garrett, J E Gelernter, G Guffanti, M A Hauser, E O Johnson, R C Kessler, N A Kimbrel, A King, N Koen, H R Kranzler, M W Logue, A X Maihofer, A R Martin, M W Miller, R A Morey, N R Nugent, J P Rice, S Ripke, A L Roberts, N L Saccone, J W Smoller, D J Stein, M B Stein, J A Sumner, M Uddin, R J Ursano, D E Wildman, R Yehuda, H Zhao, M J Daly, I Liberzon, K J Ressler, C M Nievergelt, K C Koenen
Open Access Publications
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h
Tnf Receptor-Activated Factor 2 Mediates Cardiac Protection Through Noncanonical Nf-Κb Signaling, Sarah Evans, Huei-Ping Tzeng, Deborah J Veis, Scot Matkovich, Carla Weinheimer, Attila Kovacs, Philip M Barger, Douglas L Mann
Tnf Receptor-Activated Factor 2 Mediates Cardiac Protection Through Noncanonical Nf-Κb Signaling, Sarah Evans, Huei-Ping Tzeng, Deborah J Veis, Scot Matkovich, Carla Weinheimer, Attila Kovacs, Philip M Barger, Douglas L Mann
Open Access Publications
To elucidate the mechanisms responsible for cytoprotective effects of TNF receptor-activated factor 2 (TRAF2) in the heart, we employed genetic gain- and loss-of-function studies ex vivo and in vivo in mice with cardiac-restricted overexpression of TRAF2 (Myh6-TRAF2LC). Crossing Myh6-TRAF2LC mice with mice lacking canonical signaling (Myh6-TRAF2LC/Myh6-IκBαΔN) abrogated the cytoprotective effects of TRAF2 ex vivo. In contrast, inhibiting the JAK/STAT pathway did not abrogate the cytoprotective effects of TRAF2. Transcriptional profiling of WT, Myh6-TRAF2LC, and Myh6-TRAF2LC/Myh6-IκBαΔN mouse hearts suggested that the noncanonical NF-κB signaling pathway was upregulated in the Myh6-TRAF2LC mouse hearts. Western blotting and ELISA for the NF-κB family proteins …
Phase 1b/2a Trial Of The Superoxide Dismutase Mimetic Gc4419 To Reduce Chemoradiotherapy-Induced Oral Mucositis In Patients With Oral Cavity Or Oropharyngeal Carcinoma, Carryn M Anderson, Stephen T Sonis, Christopher M Lee, Douglas Adkins, Bryan G Allen, Wenqing Sun, Sanjiv S Agarwala, Madhavi L Venigalla, Yuhchyau Chen, Weining Zhen, Diane R Mould, Jon T Holmlund, Jeffrey M Brill, John M Buatti
Phase 1b/2a Trial Of The Superoxide Dismutase Mimetic Gc4419 To Reduce Chemoradiotherapy-Induced Oral Mucositis In Patients With Oral Cavity Or Oropharyngeal Carcinoma, Carryn M Anderson, Stephen T Sonis, Christopher M Lee, Douglas Adkins, Bryan G Allen, Wenqing Sun, Sanjiv S Agarwala, Madhavi L Venigalla, Yuhchyau Chen, Weining Zhen, Diane R Mould, Jon T Holmlund, Jeffrey M Brill, John M Buatti
Open Access Publications
PURPOSE: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM).
PATIENTS AND METHODS: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending <60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT.
RESULTS: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in …
60>A Systematic, Intensive Statistical Investigation Of Data From The Comprehensive Analysis Of Reported Drugs (Card) For Compliance And Illicit Opioid Abstinence In Substance Addiction Treatment With Buprenorphine/Naloxone, Kenneth Blum, David Han, Edward J Modestino, Scott Saunders, A Kennison Roy 3rd, W Jacobs, Darryl S Inaba, David Baron, Marlene Oscar-Berman, Mary Hauser, Rajendra D Badgaiyan, David E Smith, John Femino, Mark S Gold
A Systematic, Intensive Statistical Investigation Of Data From The Comprehensive Analysis Of Reported Drugs (Card) For Compliance And Illicit Opioid Abstinence In Substance Addiction Treatment With Buprenorphine/Naloxone, Kenneth Blum, David Han, Edward J Modestino, Scott Saunders, A Kennison Roy 3rd, W Jacobs, Darryl S Inaba, David Baron, Marlene Oscar-Berman, Mary Hauser, Rajendra D Badgaiyan, David E Smith, John Femino, Mark S Gold
Open Access Publications
BACKGROUND: Buprenorphine and naloxone (bup/nal), a combination partial mu receptor agonist and low-dose delta mu antagonist, is presently recommended and used to treat opioid-use disorder. However, a literature review revealed a paucity of research involving data from urine drug tests that looked at compliance and abstinence in one sample.
METHOD: Statistical analysis of data from the Comprehensive Analysis of Reported Drugs (CARD) was used to assess compliance and abstinence during treatment in a large cohort of bup/nal patients attending chemical-dependency programs from eastern USA in 2010 and 2011.
RESULTS: Part 1: Bup/nal was present in 93.4% of first (n = …
Zinc Inhibits Trpv1 To Alleviate Chemotherapy-Induced Neuropathic Pain, Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu
Zinc Inhibits Trpv1 To Alleviate Chemotherapy-Induced Neuropathic Pain, Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu
Open Access Publications
Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 …
Incorporating Reflection Boundary Conditions In The Neumann Series Radiative Transport Equation: Application To Photon Propagation And Reconstruction In Diffuse Optical Imaging, Abhinav K. Jha, Yansong Zhu, Simon Arridge, Dean F. Wong, Arman Rahmim
Incorporating Reflection Boundary Conditions In The Neumann Series Radiative Transport Equation: Application To Photon Propagation And Reconstruction In Diffuse Optical Imaging, Abhinav K. Jha, Yansong Zhu, Simon Arridge, Dean F. Wong, Arman Rahmim
Open Access Publications
No abstract provided.
Deletion Of Tsc2 In Nociceptors Reduces Target Innervation, Ion Channel Expression, And Sensitivity To Heat, Dan Carlin, Judith P. Golden, Amit Mogha, Vijay K. Samineni, Kelly R. Monk, Robert W. Gereau, Valeria Cavalli
Deletion Of Tsc2 In Nociceptors Reduces Target Innervation, Ion Channel Expression, And Sensitivity To Heat, Dan Carlin, Judith P. Golden, Amit Mogha, Vijay K. Samineni, Kelly R. Monk, Robert W. Gereau, Valeria Cavalli
Open Access Publications
No abstract provided.
Trpv1 Agonist, Capsaicin, Induces Axon Outgrowth After Injury Via Ca2+/Pka Signaling, Erin Frey, Scott Karney-Grobe, Trevor Krolak, Jeff Milbrandt, Aaron Diantonio
Trpv1 Agonist, Capsaicin, Induces Axon Outgrowth After Injury Via Ca2+/Pka Signaling, Erin Frey, Scott Karney-Grobe, Trevor Krolak, Jeff Milbrandt, Aaron Diantonio
Open Access Publications
No abstract provided.
The Genetic Underpinnings Of Variation In Ages At Menarche And Natural Menopause Among Women From The Multi-Ethnic Population Architecture Using Genomics And Epidemiology (Page) Study: A Trans-Ethnic Meta-Analysis, D. C. Rao, Karen Schwander, Et Al.
The Genetic Underpinnings Of Variation In Ages At Menarche And Natural Menopause Among Women From The Multi-Ethnic Population Architecture Using Genomics And Epidemiology (Page) Study: A Trans-Ethnic Meta-Analysis, D. C. Rao, Karen Schwander, Et Al.
Open Access Publications
No abstract provided.
Amphiregulin Modifies The Minnesota Acute Graft-Versus-Host Disease Risk Score: Results From Bmt Ctn 0302/0802, Iskra Pusic
Amphiregulin Modifies The Minnesota Acute Graft-Versus-Host Disease Risk Score: Results From Bmt Ctn 0302/0802, Iskra Pusic
Open Access Publications
No abstract provided.