Xiap Antagonist Embelin Inhibited Proliferation Of Cholangiocarcinoma Cells.,
2014
University of Nebraska Medical Center
Xiap Antagonist Embelin Inhibited Proliferation Of Cholangiocarcinoma Cells., Cody J. Wehrkamp, Ashley R. Gutwein, Sathish Kumar Natarajan, Mary Anne Phillippi, Justin L. Mott
Journal Articles: Biochemistry & Molecular Biology
Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 …
Retinoic Acid Regulation Of Thyroid Hormone Action In Bone Cells,
2014
Loma Linda University
Retinoic Acid Regulation Of Thyroid Hormone Action In Bone Cells, Anjali Babbar
Loma Linda University Electronic Theses, Dissertations & Projects
Retinoic acid and thyroid hormone are known to play key roles in the regulation of endochondral ossification. However, the issue of whether these two hormones interact with each other to regulate bone functions remains to be established. We investigated how thyroid hormone and retinoic acid interact to regulate cells involved in endochondral bone formation. We demonstrate that thyroid hormone treatment stimulates differentiation of ATDC5 chondrocytes and promotes formation of mineralized nodules while retinoic acid treatment at high dose inhibits chondrocyte differentiation and formation of mineralized nodules. Furthermore, thyroid hormone induced mineralized nodule formation is inhibited by co-treatment with retinoic acid …
Molecular Genetic Evidence For Overlap Between General Cognitive Ability And Risk For Schizophrenia: A Report From The Cognitive Genomics Consortium (Cogent),
2014
Hofstra Northwell School of Medicine
Molecular Genetic Evidence For Overlap Between General Cognitive Ability And Risk For Schizophrenia: A Report From The Cognitive Genomics Consortium (Cogent), T. Lencz, E. Knowles, G. Davies, S. Guha, D. C. Liewald, J. M. Starr, S. Djurovic, I. Melle, K. Sundet, A. Christoforou, I. Reinvang, S. Mukherjee, P. Derosse, A. Lundervold, V. M. Steen, M. John, T. Espeseth, K. Raikkonen, E. Widen, A. Palotie, J. G. Eriksson, I. Giegling, B. Konte, M. Ikeda, P. Roussos, S. Giakoumaki, K. E. Burdick, A. Payton, W. Ollier, M. Horan, G. Donohoe, D. Morris, A. Corvin, M. Gill, N. Pendleton, N. Iwata, A. Darvasi, P. Bitsios, D. Rujescu, J. Lahti, S. L. Hellard, M. C. Keller, O. A. Andreassen, I. J. Deary, D. C. Glahn, Anil Malhotra
Journal Articles
It has long been recognized that generalized deficits in cognitive ability represent a core component of schizophrenia (SCZ), evident before full illness onset and independent of medication. The possibility of genetic overlap between risk for SCZ and cognitive phenotypes has been suggested by the presence of cognitive deficits in first-degree relatives of patients with SCZ; however, until recently, molecular genetic approaches to test this overlap have been lacking. Within the last few years, large-scale genome-wide association studies (GWAS) of SCZ have demonstrated that a substantial proportion of the heritability of the disorder is explained by a polygenic component consisting of …
The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging,
2014
Hofstra Northwell School of Medicine
The Relationship Between Fasting Serum Glucose And Cerebral Glucose Metabolism In Late-Life Depression And Normal Aging, C. M. Marano, C. I. Workman, C. H. Lyman, E. Kramer, C. R. Hermann, Y. L. Ma, V. Dhawan, T. Chaly, D. Eidelberg, G. S. Smith
Journal Articles
Evidence exists for late-life depression (LLD) as both a prodrome of and risk factor for Alzheimer's disease (AD). The underlying neurobiological mechanisms are poorly understood. Impaired peripheral glucose metabolism may explain the association between depression and AD given the connection between type 2 diabetes mellitus with both depression and AD. Positron emission tomography (PET) measures of cerebral glucose metabolism are sensitive to detecting changes in neural circuitry in LLD and AD. Fasting serum glucose (FSG) in non-diabetic young (YC; n=20) and elderly controls (EC; n=12) and LLD patients (n = 16) was correlated with PET scans of cerebral glucose metabolism …
Biological Insights From 108 Schizophrenia-Associated Genetic Loci,
2014
Hofstra Northwell School of Medicine
Biological Insights From 108 Schizophrenia-Associated Genetic Loci, S. Ripke, B. M. Neale, A. Corvin, J. T. R. Walters, K. H. Farh, T. Lencz, A. K. Malhotra, Consortium Psychiat Genomics, Conso Psychosis Endophenotypes Int, Consor Wellcome Trust Case-Control, +292 Additional Authors
Journal Articles
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and …
Aggression In Schizophrenia And Its Relationship To Neural Circuitry Of Urgency,
2014
Hofstra Northwell School of Medicine
Aggression In Schizophrenia And Its Relationship To Neural Circuitry Of Urgency, P. Szeszko
Journal Articles
No abstract provided.
Functional Development In Clinical High Risk Youth: Prediction Of Schizophrenia Versus Other Psychotic Disorders,
2014
Hofstra Northwell School of Medicine
Functional Development In Clinical High Risk Youth: Prediction Of Schizophrenia Versus Other Psychotic Disorders, S. I. Tarbox, J. Addington, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, D. O. Perkins, L. J. Seidman, M. T. Tsuang, E. F. Walker, S. W. Woods, +2 Additional Authors
Journal Articles
This study evaluates premorbid social and academic functioning in clinical high-risk individuals as predictors of transition to schizophrenia versus another psychotic disorder. Participants were 54 individuals enrolled in phase one of the North American Prodrome Longitudinal Study who over two and a half years of follow-up met criteria for schizophrenia/schizophreniform disorder (n=28) or another psychotic disorder (n=26). Social and academic functioning in childhood, early adolescence, and late adolescence was assessed at baseline using the Cannon-Spoor Premorbid Adjustment Scale. Social maladjustment in late adolescence predicted significantly higher odds of transition to schizophrenia versus another psychotic disorder independent of childhood and early …
Stress Exposure And Sensitivity In The Clinical High-Risk Syndrome: Initial Findings From The North American Prodrome Longitudinal Study (Napls),
2014
Hofstra Northwell School of Medicine
Stress Exposure And Sensitivity In The Clinical High-Risk Syndrome: Initial Findings From The North American Prodrome Longitudinal Study (Napls), H. D. Trotman, C. W. Holtzman, E. F. Walker, J. M. Addington, C. E. Bearden, K. S. Cadenhead, T. D. Cannon, B. Cornblatt, R. K. Heinssen, T. H. Mcglashan, +5 Additional Authors
Journal Articles
There is inconsistent evidence for increased stress exposure among individuals at clinical high risk (CHR) for psychosis. Yet similar to patients with a diagnosed psychotic illness, the preponderance of evidence suggests that CHR individuals tend to experience stressful life events (LE) and daily hassles (DH) as more subjectively stressful than healthy individuals. The present study utilizes data from the North American Prodrome Longitudinal Study Phase 2 (NAPLS-2) to test the hypotheses that (1) CHR individuals manifest higher self-reported stress in response to both LE and DH when compared to healthy controls (HC), (2) group differences in self-reported stress increase with …
Moderator Effects Of Working Memory On The Stability Of Adhd Symptoms By Dopamine Receptor Gene Polymorphisms During Development,
2014
Hofstra Northwell School of Medicine
Moderator Effects Of Working Memory On The Stability Of Adhd Symptoms By Dopamine Receptor Gene Polymorphisms During Development, J. Trampush, M. M. Jacobs, Y. L. Hurd, J. H. Newcorn, J. M. Halperin
Journal Articles
We tested the hypothesis that dopamine D1 and D2 receptor gene (DRD1 and DRD2, respectively) polymorphisms and the development of working memory skills can interact to influence symptom change over 10 years in children with attention-deficit/hyperactivity disorder (ADHD). Specifically, we examined whether improvements in working memory maintenance and manipulation from childhood to early adulthood predicted the reduction of ADHD symptoms as a function of allelic variation in DRD1 and DRD2. Participants were 76 7-11-year-old children with ADHD who were genotyped and prospectively followed for almost 10 years. ADHD symptoms were rated using the Attention Problems scale on the Child Behavior …
Rdocs Redux,
2014
Hofstra Northwell School of Medicine
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 …
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.
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.
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 …
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 …
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 …
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.
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 …
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 …
