Bone Morphogenetic Protein-Focused Strategies To Induce Cytotoxicity In Lung Cancer Cells,
2014
Zucker School of Medicine at Hofstra/Northwell
Bone Morphogenetic Protein-Focused Strategies To Induce Cytotoxicity In Lung Cancer Cells, A. Fotinos, N. Nagarajan, A. S. Martins, D. T. Fritz, D. Garsetti, A. T. Lee, C. C. Hong, M. B. Rogers
Journal Articles
Background: High bone morphogenetic protein (BMP)-2 expression in lung carcinoma correlates with poor patient prognosis. The present study explored strategies to repress BMP signaling. Materials and Methods: The cytotoxicity of BMP2-knockdown, dorsomorphin derivatives, and microRNAs was tested in transformed and non-transformed lung cells. Microarray analyses of 1,145 microRNAs in A549 lung adenocarcinoma cells and two other transformed lung cell types relative to BEAS-2B bronchial epithelial cells were performed. Results: Reduced BMP2 synthesis inhibited A549 cell growth. The dorsomorphin derivative LDN-193189, but not DMH1 or DMH4, was strongly cytotoxic towards A549 cells, but not towards BEAS-2B cells. Microarray analysis revealed that …
Robotic Measurement Of Arm Movements After Stroke Establishes Biomarkers Of Motor Recovery,
2014
Zucker School of Medicine at Hofstra/Northwell
Robotic Measurement Of Arm Movements After Stroke Establishes Biomarkers Of Motor Recovery, H. I. Krebs, M. Krams, D. K. Agrafiotis, A. Dibernardo, J. C. Chavez, G. S. Littman, E. Yang, G. Byttebier, L. Dipietro, B. T. Volpe, +4 Additional Authors
Journal Articles
Background and Purpose Because robotic devices record the kinematics and kinetics of human movements with high resolution, we hypothesized that robotic measures collected longitudinally in patients after stroke would bear a significant relationship to standard clinical outcome measures and, therefore, might provide superior biomarkers. Methods In patients with moderate-to-severe acute ischemic stroke, we used clinical scales and robotic devices to measure arm movement 7, 14, 21, 30, and 90 days after the event at 2 clinical sites. The robots are interactive devices that measure speed, position, and force so that calculated kinematic and kinetic parameters could be compared with clinical …
Inhibition Of Amp-Activated Protein Kinase Signaling Alleviates Impairments In Hippocampal Synaptic Plasticity Induced By Amyloid Beta,
2014
Northwell Health
Inhibition Of Amp-Activated Protein Kinase Signaling Alleviates Impairments In Hippocampal Synaptic Plasticity Induced By Amyloid Beta, T. Ma, Y. R. Chen, V. Vingtdeux, H. T. Zhao, B. Viollet, P. Marambaud, E. Klann
Journal Articles
The AMP-activated protein kinase (AMPK) is a Ser/Thr kinase that is activated in response to low-energy states to coordinate multiple signaling pathways to maintain cellular energy homeostasis. Dysregulation of AMPK signaling has been observed in Alzheimer's disease (AD), which is associated with abnormal neuronal energy metabolism. In the current study we tested the hypothesis that aberrant AMPK signaling underlies AD-associated synaptic plasticity impairments by using pharmacological and genetic approaches. We found that amyloid beta (A beta)-induced inhibition of long-term potentiation (LTP) and enhancement of long-term depression were corrected by the AMPK inhibitor compound C (CC). Similarly, LTP impairments in APP/PS1 …
Sequestering Hmgb1 Via Dna-Conjugated Beads Ameliorates Murine Colitis,
2014
Northwell Health
Sequestering Hmgb1 Via Dna-Conjugated Beads Ameliorates Murine Colitis, Z. Ju, S. S. Chavan, M. Dancho, T. Tsaava, J. Li, B. Lu, Y. Al-Abed, J. Roth, K. J. Tracey, H. Yang, +4 Additional Authors
Journal Articles
Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract that affects millions of people worldwide. Although the etiology of IBD is not clear, it is known that products from stressed cells and enteric microbes promote intestinal inflammation. High mobility group box 1 (HMGB1), originally identified as a nuclear DNA binding protein, is a cytokine-like protein mediator implicated in infection, sterile injury, autoimmune disease, and IBD. Elevated levels of HMGB1 have been detected in inflamed human intestinal tissues and in feces of IBD patients and mouse models of colitis. Neutralizing HMGB1 activity by administration of anti-HMGB1 antibodies or HMGB1-specific …
Candidate Chromosome 1 Disease Susceptibility Genes For Sjogren's Syndrome Xerostomia Are Narrowed By Novel Nod.B10 Congenic Mice,
2014
Zucker School of Medicine at Hofstra/Northwell
Candidate Chromosome 1 Disease Susceptibility Genes For Sjogren's Syndrome Xerostomia Are Narrowed By Novel Nod.B10 Congenic Mice, P. K. A. Mongini, J. M. Kramer, T. Ishikawa, H. Herschman, D. Esposito
Journal Articles
Sjogren's syndrome (SS) is characterized by salivary gland leukocytic infiltrates and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1 within the span of the Aec2 region. In an attempt to demonstrate that COX-2 drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox-2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking genes failed manifest xerostomia. Further backcrossing yielded disease-susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that critical Aec2 genes lie within a 1.56 to 2.17 Mb span of DNA downstream of Cox-2. Bioinformatics analysis revealed that susceptible and non-susceptible lines exhibit non-synonymous coding SNPs in …
Effect Of The Calhm1 G330d And R154h Human Variants On The Control Of Cytosolic Ca2+ And A Beta Levels,
2014
Northwell Health
Effect Of The Calhm1 G330d And R154h Human Variants On The Control Of Cytosolic Ca2+ And A Beta Levels, V. Vingtdeux, J. E. Tanis, P. Chandakkar, H. T. Zhao, U. Dreses-Werringloer, F. Campagne, J. K. Foskett, P. Marambaud
Journal Articles
CALHM1 is a plasma membrane voltage-gated Ca2+-permeable ion channel that controls amyloid-beta (A beta) metabolism and is potentially involved in the onset of Alzheimer's disease (AD). Recently, Rubio-Moscardo et al. (PLoS One (2013) 8: e74203) reported the identification of two CALHM1 variants, G330D and R154H, in early-onset AD (EOAD) patients. The authors provided evidence that these two human variants were rare and resulted in a complete loss of CALHM1 function. Recent publicly available large-scale exome sequencing data confirmed that R154H is a rare CALHM1 variant (minor allele frequency (MAF) = 0.015%), but that G330D is not (MAF = 3.5% in …
Salty Taste Deficits In Calhm1 Knockout Mice,
2014
Northwell Health
Salty Taste Deficits In Calhm1 Knockout Mice, M. G. Tordoff, H. T. Ellis, T. R. Aleman, A. Downing, P. Marambaud, J. K. Foskett, R. M. Dana, S. A. Mccaughey
Journal Articles
Genetic ablation of calcium homeostasis modulator 1 (CALHM1), which releases adenosine triphosphate from Type 2 taste cells, severely compromises the behavioral and electrophysiological responses to tastes detected by G protein-coupled receptors, such as sweet and bitter. However, the contribution of CALHM1 to salty taste perception is less clear. Here, we evaluated several salty taste-related phenotypes of CALHM1 knockout (KO) mice and their wild-type (WT) controls: 1) In a conditioned aversion test, CALHM1 WT and KO mice had similar NaCl avoidance thresholds. 2) In two-bottle choice tests, CALHM1 WT mice showed the classic inverted U-shaped NaCl concentration-preference function but CALHM1 KO …
Sucrose-Conditioned Flavor Preferences In Sweet Ageusic T1r3 And Calhm1 Knockout Mice,
2014
Northwell Health
Sucrose-Conditioned Flavor Preferences In Sweet Ageusic T1r3 And Calhm1 Knockout Mice, A. Sclafani, P. Marambaud, K. Ackroff
Journal Articles
The present study compared the ability of sweet ageusic T1r3 knockout (KO) and Calhm1 KO mice to acquire preferences for a sucrose-paired flavor as well as for unflavored sucrose. The KO and wildtype (WT) mice were given 24-h one-bottle access to 8% sucrose containing one flavor CS+, e.g., grape) and to water containing a different flavor (CS-, e.g., cherry) over 4 training days. In subsequent two-bottle tests with the flavors in water only, the T1r3 KO and Calhm1 KO mice, like WT mice, preferred the CS+ to the CS-. After training with flavored solutions, both KO groups also preferred unflavored …
Evaluation Of Amniotic-Derived Membrane Biomaterial As An Adjunct For Repair Of Critical Sized Bone Defects,
2014
Northwell Health
Evaluation Of Amniotic-Derived Membrane Biomaterial As An Adjunct For Repair Of Critical Sized Bone Defects, M. Starecki, J. A. Schwartz, D. A. Grande
Journal Articles
No abstract provided.
Low Vitamin D Level Is An Independent Predictor Of Poor Outcomes In Clostridium Difficile-Associated Diarrhea,
2014
Zucker School of Medicine at Hofstra/Northwell
Low Vitamin D Level Is An Independent Predictor Of Poor Outcomes In Clostridium Difficile-Associated Diarrhea, W. J. Wang, S. Gray, C. Sison, S. Arramraju, B. K. John, S. A. Hussain, S. H. Kim, P. Mehta, M. Rubin
Journal Articles
Background: The incidence, recurrence, and all-cause mortality rate for Clostridium difficile-associated diarrhea (CDAD) has increased markedly over the past 10 years despite treatment. Low vitamin D levels are known to impair immune responses to infection and are associated with increased mortality. We compared the role of patient comorbidity measured by the Charlson Comorbidity Index (CCI) with vitamin D levels to ascertain whether vitamin D levels were an independent variable affecting the outcome of CDAD or a marker of overall comorbidity. Methods: A prospective cohort study studied 62 patients hospitalized between 2008 and 2009 with manifestations of CDAD and a positive …
Overexpression Of Extracellular Superoxide Dismutase Protects Against Brain Injury Induced By Chronic Hypoxia,
2014
Northwell Health
Overexpression Of Extracellular Superoxide Dismutase Protects Against Brain Injury Induced By Chronic Hypoxia, N. Zaghloul, H. Patel, C. Codipilly, P. Marambaud, S. Dewey, S. Frattini, P. T. Huerta, M. Nasim, E. J. Miller, M. Ahmed
Journal Articles
Extracellular superoxide dismutase (EC-SOD) is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1%) for 10 days (H-KI) and compared to transgenic animals housed in room air (RA-KI), wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT). Overall brain metabolism evaluated by positron emission tomography (PET) showed that H-WT mice had significantly higher uptake of (18)FDG in the brain …
Low-Dose T-3 Replacement Restores Depressed Cardiac T-3 Levels, Preserves Coronary Microvasculature And Attenuates Cardiac Dysfunction In Experimental Diabetes Mellitus,
2014
Zucker School of Medicine at Hofstra/Northwell
Low-Dose T-3 Replacement Restores Depressed Cardiac T-3 Levels, Preserves Coronary Microvasculature And Attenuates Cardiac Dysfunction In Experimental Diabetes Mellitus, N. Y. Weltman, K. Ojamaa, E. H. Schlenker, Y. F. Chen, R. Zucchi, A. Saba, D. Colligiani, V. Rajagopalan, C. J. Pol, A. M. Gerdes
Journal Articles
Thyroid dysfunction is common in individuals with diabetes mellitus (DM) and may contribute to the associated cardiac dysfunction. However, little is known about the extent and pathophysiological consequences of low thyroid conditions on the heart in DM. DM was induced in adult female Sprague Dawley (SD) rats by injection of nicotinamide (N; 200 mg/kg) followed by streptozotocin (STZ; 65 mg/kg). One month after STZ/N, rats were randomized to the following groups (N = 10/group): STZ/N or STZ/N + 0.03 g/mL T-3; age-matched vehicle-treated rats served as nondiabetic controls (C). After 2 months of T-3 treatment (3 months post-DM induction), left …
Autoimmunity To Vimentin And Lupus Nephritis,
2014
Zucker School of Medicine at Hofstra/Northwell
Autoimmunity To Vimentin And Lupus Nephritis, A. Davidson
Journal Articles
No abstract provided.
Farewell Statement From Dr. Cerami And Dr. Tracey As Outgoing Co-Editors In Chief Of Molecular Medicine,
2014
Zucker School of Medicine at Hofstra/Northwell
Farewell Statement From Dr. Cerami And Dr. Tracey As Outgoing Co-Editors In Chief Of Molecular Medicine, A. Cerami, K. J. Tracey
Journal Articles
No abstract provided.
Genotyping Of Immune-Related Genetic Variants Identifies Tyk2 As A Novel Associated Locus For Idiopathic Inflammatory Myopathies,
2014
Zucker School of Medicine at Hofstra/Northwell
Genotyping Of Immune-Related Genetic Variants Identifies Tyk2 As A Novel Associated Locus For Idiopathic Inflammatory Myopathies, M. Jani, J. Massey, L. R. Wedderburn, J. Vencovsky, K. Danko, I. E. Lundberg, L. Padyukov, A. Lee, P. K. Gregersen, Eumyonet, +10 Additional Authors
Journal Articles
No abstract provided.
Reply: Evidence Against Volume Conduction To Explain Normal Meps In Muscles With Low Motor Power In Sci,
2014
Zucker School of Medicine at Hofstra/Northwell
Reply: Evidence Against Volume Conduction To Explain Normal Meps In Muscles With Low Motor Power In Sci, D. J. Edwards, M. Cortes, G. W. Thickbroom, A. Rykman, A. Pascual-Leone, B. T. Volpe
Journal Articles
No abstract provided.
Letter From Incoming Editor In Chief Of Molecular Medicine, Dr. Betty Diamond,
2014
Zucker School of Medicine at Hofstra/Northwell
Letter From Incoming Editor In Chief Of Molecular Medicine, Dr. Betty Diamond, B. Diamond
Journal Articles
No abstract provided.
Altered Mucins (Muc) Trafficking In Benign And Malignant Conditions.,
2014
University of Nebraska Medical Center
Altered Mucins (Muc) Trafficking In Benign And Malignant Conditions., Suhasini Joshi, Sushil Kumar, Amit Choudhury, Moorthy P. Ponnusamy, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
Mucins are high molecular weight O-glycoproteins that are predominantly expressed at the apical surface of epithelial cells and have wide range of functions. The functional diversity is attributed to their structure that comprises of a peptide chain with unique domains and multiple carbohydrate moieties added during posttranslational modifications. Tumor cells aberrantly overexpress mucins, and thereby promote proliferation, differentiation, motility, invasion and metastasis. Along with their aberrant expression, accumulating evidence suggest the critical role of altered subcellular localization of mucins under pathological conditions due to altered endocytic processes. The mislocalization of mucins and their interactions result in change in the density …
Inhibition Of Rac1 Gtpase Sensitizes Pancreatic Cancer Cells To Γ-Irradiation,
2014
University of Nebraska Medical Center
Inhibition Of Rac1 Gtpase Sensitizes Pancreatic Cancer Cells To Γ-Irradiation, Y Yan, Ashley L. Hein, Asserewou Etekpo, Katrina M. Burchett, Chi Lin, Charles A. Enke, Surinder K. Batra, Kenneth Cowan, Michel M. Ouellette
Journal Articles: Biochemistry & Molecular Biology
Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest …
A Study Of Functional Recovery And Axonal Plasticity Following Tbi And Anti-Nogo-A Immunotherapy,
2014
Loyola University Chicago
A Study Of Functional Recovery And Axonal Plasticity Following Tbi And Anti-Nogo-A Immunotherapy, Jennifer Crystal Biesiadecki
Master's Theses
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality globally and often results in long term disability. Unfortunately, the success of rehabilitation techniques as therapy for TBI is limited, which may be due to the growth restrictive environment of the adult central nervous system (CNS). This environment is thought to result from glial scars, lack of neurotrophic factors, and the presence of an array of growth-inhibitory molecules. One such growth-inhibitory molecule is the protein Nogo-A. Our laboratory has shown that neutralization of Nogo-A with anti-Nogo-A immunotherapy after ischemic stroke results in improvement in functional recovery in the …
