Molecular Mechanisms Underlying Alcohol-Induced Cerebral Artery Smooth Muscle Bk Channel Inhibition And Eventual Cerebral Vasoconstriction,
2015
University of Tennessee Health Science Center
Molecular Mechanisms Underlying Alcohol-Induced Cerebral Artery Smooth Muscle Bk Channel Inhibition And Eventual Cerebral Vasoconstriction, Guruprasad Kuntamallappanavar
Theses and Dissertations (ETD)
Introduction and Rationale: Ethanol (EtOH) at concentrations obtained in circulation during moderate to heavy episodic drinking, such as during binge drinking (30-60 mM) causes cerebral vasoconstriction in many species, including humans. Using rodents as a model to study ethanolinduced cerebral artery constriction, our laboratory demonstrated that ethanol-induced cerebral artery constriction is due to drug-induced reduction of STOCs (Spontaneous Transient Outward Currents) in cerebral artery smooth muscle. In this tissue, STOCs result from the activity of large conductance, calcium-and voltage-gated potassium (BK) channels. Indeed, ethanol (50 mM) decreases the steady-state activity (NPo) of vascular myocyte BK channels leading to an increase …
Role Of Ataxia Telangiectasia Mutated Kinase In The Healing Process Of The Heart Following Myocardial Infarction,
2015
East Tennessee State University
Role Of Ataxia Telangiectasia Mutated Kinase In The Healing Process Of The Heart Following Myocardial Infarction, Laura L. Daniel
Electronic Theses and Dissertations
Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. AT individuals exhibit neuronal degeneration and are predisposed to cancer. Carriers of this disorder are predisposed to cancer and ischemic heart disease. Heart disease, mostly due to myocardial infarction (MI), is a leading cause of death in the US. Following MI, release of catecholamines in the heart stimulates β- adrenergic receptors (β-AR). Our lab has shown that β-AR stimulation increases ATM expression in the heart and myocytes, and ATM plays an important role in β-AR-stimulated myocardial remodeling with effects …
Post-Transcriptional Modifications To Trna--A Response To The Genetic Code Degeneracy.,
2015
Department of Biochemistry and Molecular Biology, Thomas Jefferson University
Post-Transcriptional Modifications To Trna--A Response To The Genetic Code Degeneracy., Ya-Ming Hou, Wei Yang
Department of Biochemistry and Molecular Biology Faculty Papers
No abstract provided.
G Protein Βγ Subunits Regulate Cardiomyocyte Hypertrophy Through A Perinuclear Golgi Phosphatidylinositol 4-Phosphate Hydrolysis Pathway.,
2015
Department of Pharmacology and Physiology, University of Rochester
G Protein Βγ Subunits Regulate Cardiomyocyte Hypertrophy Through A Perinuclear Golgi Phosphatidylinositol 4-Phosphate Hydrolysis Pathway., S Malik, R G Derubio, M Trembley, R Irannejad, Philip B Wedegaertner, A V Smrcka
Department of Biochemistry and Molecular Biology Faculty Papers
We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCε, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCε is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. …
Targeting Egf-Receptor(S) - Stat1 Axis Attenuates Tumor Growth And Metastasis Through Downregulation Of Muc4 Mucin In Human Pancreatic Cancer.,
2015
University of Nebraska Medical Center
Targeting Egf-Receptor(S) - Stat1 Axis Attenuates Tumor Growth And Metastasis Through Downregulation Of Muc4 Mucin In Human Pancreatic Cancer., Parthasarathy Seshacharyulu, Moorthy P. Ponnusamy, Satyanarayana Rachagani, Imayavaramban Lakshmanan, Dhanya Haridas, Y Yan, Apar Kishor Ganti, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
Transmembrane proteins MUC4, EGFR and HER2 are shown to be critical in invasion and metastasis of pancreatic cancer. Besides, we and others have demonstrated de novo expression of MUC4 in ~70-90% of pancreatic cancer patients and its stabilizing effects on HER2 downstream signaling in pancreatic cancer. Here, we found that use of canertinib or afatinib resulted in reduction of MUC4 and abrogation of in vitro and in vivo oncogenic functions of MUC4 in pancreatic cancer cells. Notably, silencing of EGFR family member in pancreatic cancer cells decreased MUC4 expression through reduced phospho-STAT1. Furthermore, canertinib and afatinib treatment also inhibited proliferation, …
Inhibition Of Hedgehog Signaling Improves The Anti-Carcinogenic Effects Of Docetaxel In Prostate Cancer.,
2015
University of Nebraska Medical Center
Inhibition Of Hedgehog Signaling Improves The Anti-Carcinogenic Effects Of Docetaxel In Prostate Cancer., Murielle Mimeault, Satyanarayana Rachagani, Sakthivel Muniyan, Parthasarathy Seshacharyulu, Sonny L. Johansson, Kkaustubh Datta, Ming-Fong Lin, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
The establishment of docetaxel-based chemotherapeutic treatments has improved the survival of castration-resistant prostate cancer (CRPC) patients. However, most patients develop resistance supporting the development of therapy. The current study was undertaken to establish the therapeutic benefit to target hedgehog signaling cascade using GDC-0449 to improve the efficacy of chemotherapeutic drug, docetaxel. Here, we show that the combination of GDC-0449 plus docetaxel inhibited the proliferation of WPE1-NB26 cells and PC3 cells via a blockade of G1 and G2M phases. The combined treatment significantly inhibited PC cell migration in vitro. Moreover, the apoptotic effect induced by GDC-0449 plus docetaxel on PC3 cells …
Amyloid Precursor-Like Protein 2 (Aplp2) Affects The Actin Cytoskeleton And Increases Pancreatic Cancer Growth And Metastasis.,
2015
University of Nebraska Medical Center
Amyloid Precursor-Like Protein 2 (Aplp2) Affects The Actin Cytoskeleton And Increases Pancreatic Cancer Growth And Metastasis., Poomy Pandey, Satyanarayana Rachagani, Srustidhar Das, Parthasarathy Seshacharyulu, Yuri Sheinin, Naava Naslavsky, Zenggang Pan, Brittney L. Smith, Haley L. Peters, Prakash Radhakrishnan, Nicole R. Mckenna, Sai Srinivas Panapakkam Giridharan, Dhanya Haridas, Sukhwinder Kaur, Michael A. Hollingsworth, Richard G. Macdonald, Jane L. Meza, Steve Caplan, Surinder K. Batra, Joyce C. Solheim
Journal Articles: Biochemistry & Molecular Biology
Amyloid precursor-like protein 2 (APLP2) is aberrantly expressed in pancreatic cancer. Here we showed that APLP2 is increased in pancreatic cancer metastases, particularly in metastatic lesions found in the diaphragm and intestine. Examination of matched human primary tumor-liver metastasis pairs showed that 38.1% of the patients had positive APLP2 expression in both the primary tumor and the corresponding liver metastasis. Stable knock-down of APLP2 expression (with inducible shRNA) in pancreatic cancer cells reduced the ability of these cells to migrate and invade. Loss of APLP2 decreased cortical actin and increased intracellular actin filaments in pancreatic cancer cells. Down-regulation of APLP2 …
Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains,
2015
Dartmouth College
Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers
Dartmouth Scholarship
Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their …
Overview Of Microrna Biology,
2015
University of Nebraska Medical Center
Overview Of Microrna Biology, Ashley M. Mohr, Justin L. Mott
Journal Articles: Biochemistry & Molecular Biology
In considering an overview of microRNA biology, it is useful to consider microRNAs as a part of cellular communication. At the simplest level, microRNAs act to decrease the expression of mRNAs that contain stretches of sequence complementary to the microRNA. This function can be likened to the function of endogenous or synthetic short interfering RNA (siRNA). However, microRNA function is more complicated and nuanced than this ‘on-off’ model would suggest. Further, many microRNA targets are themselves non-coding RNAs. In this review, we will discuss the role of microRNAs in shaping the proteome of the cell in a way that is …
A Critical Role For The Host Mediator Macrophage Migration Inhibitory Factor In The Pathogenesis Of Malarial Anemia,
2015
Northwell Health
A Critical Role For The Host Mediator Macrophage Migration Inhibitory Factor In The Pathogenesis Of Malarial Anemia, M. A. Mcdevitt, J. Xie, S. Ganapathy-Kanniappan, J. Griffith, A. Liu, C. Mcdonald, P. Thuma, V. R. Gordeuk, C. N. Metz, R. Mitchell, J. Keefer, J. David, L. Leng, R. Bucala
Journal Articles
No abstract provided.
Metabolic Resting-State Brain Networks In Health And Disease,
2015
Northwell Health
Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg
Journal Articles
The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood …
Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri,
2015
Northwell Health
Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan
Journal Articles
In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in …
Association Of A Schizophrenia Risk Variant At The Drd2 Locus With Antipsychotic Treatment Response In First-Episode Psychosis,
2015
Hofstra Northwell School of Medicine
Association Of A Schizophrenia Risk Variant At The Drd2 Locus With Antipsychotic Treatment Response In First-Episode Psychosis, J. P. Zhang, D. G. Robinson, Juan Gallego, M. John, J. Yu, J. Addington, M. Tohen, John Kane, Anil Malhotra, T. Lencz
Journal Articles
Findings from the Psychiatric Genomics Consortium genome-wide association study (GWAS) showed that variation at the DRD2 locus is associated with schizophrenia risk. However, the functional significance of rs2514218, the top DRD2 single nucleotide polymorphism in the GWAS, is unknown. Dopamine D2 receptor binding is a common mechanism of action for all antipsychotic drugs, and DRD2 variants were related to antipsychotic response in previous studies. The present study examined whether rs2514218 genotype could predict antipsychotic response, including efficacy and adverse events, in a cohort of patients with first episode of psychosis treated with either risperidone or aripiprazole for 12 weeks. Subjects …
Clinical And Functional Outcomes After 2 Years In The Early Detection And Intervention For The Prevention Of Psychosis Multisite Effectiveness Trial,
2015
Hofstra Northwell School of Medicine
Clinical And Functional Outcomes After 2 Years In The Early Detection And Intervention For The Prevention Of Psychosis Multisite Effectiveness Trial, W. R. Mcfarlane, B. Levin, L. Travis, F. L. Lucas, S. Lynch, M. Verdi, Barbara Cornblatt, S. F. Taylor, A. M. Auther, E. Spring, +11 Additional Authors
Journal Articles
OBJECTIVE: To test effectiveness of the Early Detection, Intervention, and Prevention of Psychosis Program in preventing the onset of severe psychosis and improving functioning in a national sample of at-risk youth. METHODS: In a risk-based allocation study design, 337 youth (age 12-25) at risk of psychosis were assigned to treatment groups based on severity of positive symptoms. Those at clinically higher risk (CHR) or having an early first episode of psychosis (EFEP) were assigned to receive Family-aided Assertive Community Treatment (FACT); those at clinically lower risk (CLR) were assigned to receive community care. Between-groups differences on outcome variables were adjusted …
High-Density Genotyping Of Immune Loci In Koreans And Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci,
2015
Zucker School of Medicine at Hofstra/Northwell
High-Density Genotyping Of Immune Loci In Koreans And Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci, K. Kim, S. Y. Bang, H. S. Lee, S. K. Cho, C. B. Choi, Y. K. Sung, T. H. Kim, P. K. Gregersen, S. C. Bae, +32 Additional Authors
Journal Articles
OBJECTIVE: A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. METHODS: We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously …
Impact Of Early Disease Factors On Metabolic Syndrome In Systemic Lupus Erythematosus: Data From An International Inception Cohort,
2015
Zucker School of Medicine at Hofstra/Northwell
Impact Of Early Disease Factors On Metabolic Syndrome In Systemic Lupus Erythematosus: Data From An International Inception Cohort, B. Parker, M. B. Urowitz, D. D. Gladman, M. Lunt, R. Donn, S. C. Bae, J. Sanchez-Guerrero, C. Aranow, M. Mackay, I. N. Bruce, +30 Additional Authors
Journal Articles
BACKGROUND: The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE. METHODS: Recently diagnosed (<15 >months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards. Baseline and annual assessments recorded clinical, laboratory and therapeutic data. A longitudinal analysis of factors associated with MetS in the first 2 years of follow-up was performed using random effects logistic regression. RESULTS: We …
Association Of Valine And Leucine At Hla-Drb1 Position 11 With Radiographic Progression In Rheumatoid Arthritis, Independent Of The Shared Epitope Alleles But Not Independent Of Anti-Citrullinated Protein Antibodies,
2015
Zucker School of Medicine at Hofstra/Northwell
Association Of Valine And Leucine At Hla-Drb1 Position 11 With Radiographic Progression In Rheumatoid Arthritis, Independent Of The Shared Epitope Alleles But Not Independent Of Anti-Citrullinated Protein Antibodies, H. W. Van Steenbergen, S. Raychaudhuri, L. Rodriguez-Rodriguez, S. Rantapaa-Dahlqvist, E. Berglin, R. E. M. Toes, T. W. J. Huizinga, B. Fernandez-Gutierrez, P. K. Gregersen, A. H. M. Van Der Helm-Van Mil
Journal Articles
Objective. For decades it has been known that the HLA-DRB1 shared epitope (SE) alleles are associated with an increased risk of development and progression of rheumatoid arthritis (RA). Recently, the following variations in the peptide-binding grooves of HLA molecules that predispose to RA development have been identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe at HLA-DPB1 position 9. This study was undertaken to investigate whether these variants are also associated with radiographic progression in RA, independent of SE and anti-citrullinated protein antibody (ACPA) status. Methods. A total of 4,911 radiograph sets from 1,878 …
Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America,
2015
Zucker School of Medicine at Hofstra/Northwell
Crossing The Atlantic: The Euro-Lupus Nephritis Regimen In North America, D. Wofsy, B. Diamond, F. A. Houssiau
Journal Articles
No abstract provided.
Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients,
2015
Zucker School of Medicine at Hofstra/Northwell
Dna-Containing Immunocomplexes Promote Inflammasome Assembly And Release Of Pyrogenic Cytokines By Cd14+ Cd16+ Cd64high Cd32low Inflammatory Monocytes From Malaria Patients, I. C. Hirako, C. Gallego-Marin, M. A. Ataide, W. A. Andrade, H. Gravina, B. C. Rocha, R. B. De Oliveira, D. B. Pereira, B. Diamond, R. T. Gazzinelli, +3 Additional Authors
Journal Articles
High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-kappaB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-alpha] and interleukin-1beta [IL-1beta])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14(+) CD16 (FcgammaRIIIA)(+) CD64 (FcgammaRI)(high) CD32 (FcgammaRIIB)(low) monocyte subset. Monocytes from convalescent patients were predominantly of the classical phenotype (CD14(+) …
Genome-Wide Association Study Identifies Hla 8.1 Ancestral Haplotype Alleles As Major Genetic Risk Factors For Myositis Phenotypes,
2015
Zucker School of Medicine at Hofstra/Northwell
Genome-Wide Association Study Identifies Hla 8.1 Ancestral Haplotype Alleles As Major Genetic Risk Factors For Myositis Phenotypes, F. W. Miller, W. Chen, T. P. O'Hanlon, R. G. Cooper, J. Vencovsky, L. G. Rider, K. Danko, A. Lee, P. K. Gregersen, C. I. Amos, +17 Additional Authors
Journal Articles
Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P10-8) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for …
