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Evpedia: A Community Web Portal For Extracellular Vesicles Research, D. K. Kim, J. Lee, S. R. Kim, D. S. Choi, Y. J. Yoon, J. H. Kim, G. Go, L. Blanc, S. Sahoo, Y. S. Gho, +85 Additional Authors Jan 2014

Evpedia: A Community Web Portal For Extracellular Vesicles Research, D. K. Kim, J. Lee, S. R. Kim, D. S. Choi, Y. J. Yoon, J. H. Kim, G. Go, L. Blanc, S. Sahoo, Y. S. Gho, +85 Additional Authors

Journal Articles

MOTIVATION: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. RESULTS: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 …

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Exploiting Pre-Rrna Processing In Diamond Blackfan Anemia Gene Discovery And Diagnosis, J. E. Farrar, P. Quarello, R. Fisher, K. A. O'Brien, A. Aspesi, S. Parrella, E. Atsidaftos, A. Vlachos, J. M. Lipton, S. R. Ellis, +9 Additional Authors Jan 2014

Exploiting Pre-Rrna Processing In Diamond Blackfan Anemia Gene Discovery And Diagnosis, J. E. Farrar, P. Quarello, R. Fisher, K. A. O'Brien, A. Aspesi, S. Parrella, E. Atsidaftos, A. Vlachos, J. M. Lipton, S. R. Ellis, +9 Additional Authors

Journal Articles

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in …

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In Utero Exposure To A Maternal High-Fat Diet Alters The Epigenetic Histone Code In A Murine Model, M. A. Suter, J. Ma, P. M. Vuguin, K. Hartil, A. Fiallo, R. A. Harris, M. J. Charron, K. M. Aagaard Jan 2014

In Utero Exposure To A Maternal High-Fat Diet Alters The Epigenetic Histone Code In A Murine Model, M. A. Suter, J. Ma, P. M. Vuguin, K. Hartil, A. Fiallo, R. A. Harris, M. J. Charron, K. M. Aagaard

Journal Articles

OBJECTIVE: Data from animal models show that in utero exposure to a maternal high-fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. …

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P53-Independent Cell Cycle And Erythroid Differentiation Defects In Murine Embryonic Stem Cells Haploinsufficient For Diamond Blackfan Anemia-Proteins: Rps19 Versus Rpl5, S. A. Singh, T. A. Goldberg, A. L. Henson, S. Husain-Krautter, A. Nihrane, L. Blanc, S. R. Ellis, J. M. Lipton, J. M. Liu Jan 2014

P53-Independent Cell Cycle And Erythroid Differentiation Defects In Murine Embryonic Stem Cells Haploinsufficient For Diamond Blackfan Anemia-Proteins: Rps19 Versus Rpl5, S. A. Singh, T. A. Goldberg, A. L. Henson, S. Husain-Krautter, A. Nihrane, L. Blanc, S. R. Ellis, J. M. Lipton, J. M. Liu

Journal Articles

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome caused by ribosomal protein haploinsufficiency. DBA exhibits marked phenotypic variability, commonly presenting with erythroid hypoplasia, less consistently with non-erythroid features. The p53 pathway, activated by abortive ribosome assembly, is hypothesized to contribute to the erythroid failure of DBA. We studied murine embryonic stem (ES) cell lines harboring a gene trap mutation in a ribosomal protein gene, either Rps19 or Rpl5. Both mutants exhibited ribosomal protein haploinsufficiency and polysome defects. Rps19 mutant ES cells showed significant increase in p53 protein expression, however, there was no similar increase in the …

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X-Linked Agammaglobulinemia Presenting As Polymicrobial Pneumonia, Including Pneumocystis Jirovecii, A. M. Jongco, J. D. Gough, K. Sarnataro, D. W. Rosenthal, J. Moreau, P. Ponda, V. R. Bonagura Jan 2014

X-Linked Agammaglobulinemia Presenting As Polymicrobial Pneumonia, Including Pneumocystis Jirovecii, A. M. Jongco, J. D. Gough, K. Sarnataro, D. W. Rosenthal, J. Moreau, P. Ponda, V. R. Bonagura

Journal Articles

No abstract provided.

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Anti-Inflammatory Actions Of Endogenous And Exogenous Interleukin-10 Versus Glucocorticoids On Macrophage Functions Of The Newly Born, K. Kasat, H. Patel, O. Predtechenska, I. Vancurova, D. Davidson Jan 2014

Anti-Inflammatory Actions Of Endogenous And Exogenous Interleukin-10 Versus Glucocorticoids On Macrophage Functions Of The Newly Born, K. Kasat, H. Patel, O. Predtechenska, I. Vancurova, D. Davidson

Journal Articles

OBJECTIVE: To determine whether specific macrophage immune functions of the newly born are insensitive to the actions of therapeutic levels of dexamethasone (DEX), previously measured in infants with bronchopulmonary dysplasia (BPD), compared with betamethasone (BETA) and exogenous or endogenous interleukin-10 (IL-10). STUDY DESIGN: Macrophages were differentiated from cord blood monocytes (N=18). A serial dose-response (around 10(-8)M), in vitro study was used to examine the effect of DEX, BETA and IL-10, on proinflammatory (PI) cytokine release, phagocytosis and respiratory burst. RESULT: Exogenous IL-10 (10(-8)M) significantly (P < 0.05) inhibited the endotoxin-stimulated release of IL-6, IL-8 and tumor necrosis factor by 63 to 82% with no significant effect by DEX and BETA. There was no inhibition by these three agents at 10(-8)M on phagocytosis and respiratory burst. Inhibition of endogenous IL-10 with a monoclonal antibody significantly increased endotoxin-stimulated cytokine release by at least fourfold. CONCLUSION: Macrophages were relatively insensitive to therapeutic levels of DEX and BETA with regard to PI cytokine release. This study provides rationale for translational and preclinical research using airway instillation of IL-10 for the treatment of BPD.

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Bisphenol A Exposure Is Associated With Decreased Lung Function, A. J. Spanier, E. K. Fiorino, L. Trasande Jan 2014

Bisphenol A Exposure Is Associated With Decreased Lung Function, A. J. Spanier, E. K. Fiorino, L. Trasande

Journal Articles

Objective To examine the associations of bisphenol A (BPA) exposure with lung function measures and exhaled nitric oxide (FeNO) in children. Study design We performed a cross-sectional analysis of a subsample of US children age 6-19 years who participated in the 2007-2010 National Health and Nutrition Examination Survey. We assessed univariate and multivariable associations of urinary BPA concentration with the predicted pulmonary function measures for age, sex, race/ethnicity and height (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], forced expiratory flow 25%-75%, and FEV1 divided by FVC) and with FeNO. Results Exposure and outcome data were available …

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Photoreceptor Perturbation Around Subretinal Drusenoid Deposits As Revealed By Adaptive Optics Scanning Laser Ophthalmoscopy, Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, C. A. Curcio Jan 2014

Photoreceptor Perturbation Around Subretinal Drusenoid Deposits As Revealed By Adaptive Optics Scanning Laser Ophthalmoscopy, Y. Zhang, X. Wang, E. B. Rivero, M. E. Clark, C. D. Witherspoon, R. F. Spaide, C. A. Girkin, C. Owsley, C. A. Curcio

Journal Articles

PURPOSE: To describe the microscopic structure of photoreceptors impacted by subretinal drusenoid deposits, also called pseudodrusen, an extracellular lesion associated with age-related macular degeneration (AMD), using adaptive optics scanning laser ophthalmoscopy (AOSLO). DESIGN: Observational case series. METHODS: We recruited 53 patients with AMD and 10 age-similar subjects who had normal retinal health. All subjects underwent color fundus photography, infrared reflectance, red-free reflectance, autofluorescence, and spectral-domain optical coherence tomography (OCT). Subretinal drusenoid deposits were classified by a 3-stage OCT-based grading system. Lesions and surrounding photoreceptors were examined by AOSLO. RESULTS: Subretinal drusenoid deposits were found in 26 eyes of 13 patients …

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Maternal Magnesium Deficiency In Mice Leads To Maternal Metabolic Dysfunction And Altered Lipid Metabolism With Fetal Growth Restriction, M. Gupta, M. H. Solanki, P. K. Chatterjee, X. Y. Xue, A. Roman, N. Desai, B. Rochelson, C. N. Metz Jan 2014

Maternal Magnesium Deficiency In Mice Leads To Maternal Metabolic Dysfunction And Altered Lipid Metabolism With Fetal Growth Restriction, M. Gupta, M. H. Solanki, P. K. Chatterjee, X. Y. Xue, A. Roman, N. Desai, B. Rochelson, C. N. Metz

Journal Articles

Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher …

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Pregnancy Associated Plasma Protein-A2: A Novel Biomarker For Down Syndrome, S. Munnangi, S. J. Gross, R. Madankumar, G. Salcedo, S. E. Reznik Jan 2014

Pregnancy Associated Plasma Protein-A2: A Novel Biomarker For Down Syndrome, S. Munnangi, S. J. Gross, R. Madankumar, G. Salcedo, S. E. Reznik

Journal Articles

Introduction: In an effort to improve prenatal screening for Trisomy 21, we evaluated pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for Trisomy 21. Methods: Trisomy 21 and normal control mid-trimester placental samples were subjected to quantitative rt PCR analysis of seven genes we had previously found to be differentially expressed in Trisomy 21 placentae. The localization and differential expression of PAPP-A2 in second trimester placentae from normal and Trisomy 21 pregnancies was determined by immunohistochemistry. PAPP-A2 maternal serum protein levels in ten Trisomy 21 and ten diploid pregnancies were compared by Western blotting. Maternal serum …

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Thalamocortical Connectivity Correlates With Phenotypic Variability In Dystonia, An Vo, W. Sako, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg Jan 2014

Thalamocortical Connectivity Correlates With Phenotypic Variability In Dystonia, An Vo, W. Sako, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg

Journal Articles

Dystonia is a brain disorder characterized by abnormal involuntary movements without defining neuropathological changes. The disease is often inherited as an autosomal-dominant trait with incomplete penetrance. Individuals with dystonia, whether inherited or sporadic, exhibit striking phenotypic variability, with marked differences in the somatic distribution and severity of clinical manifestations. In the current study, we used magnetic resonance diffusion tensor imaging to identify microstructural changes associated with specific limb manifestations. Functional MRI was used to localize specific limb regions within the somatosensory cortex. Microstructural integrity was preserved when assessed in subrolandic white matter regions somatotopically related to the clinically involved limbs, …

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Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond Jan 2014

Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond

Journal Articles

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and antinuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb + mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb + mice, metabolism declined at the site of BBB breach in the first 2 …

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Consistent Abnormalities In Metabolic Network Activity In Idiopathic Rapid Eye Movement Sleep Behaviour Disorder, P. Wu, H. Yu, S. C. Peng, Y. Dauvilliers, J. Wang, J. J. Ge, H. W. Zhang, D. Eidelberg, Y. L. Ma, C. T. Zuo Jan 2014

Consistent Abnormalities In Metabolic Network Activity In Idiopathic Rapid Eye Movement Sleep Behaviour Disorder, P. Wu, H. Yu, S. C. Peng, Y. Dauvilliers, J. Wang, J. J. Ge, H. W. Zhang, D. Eidelberg, Y. L. Ma, C. T. Zuo

Journal Articles

Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. F-18-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0 +/- 5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5 +/- 7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6 +/- 5.0 years) and 16 moderate parkinsonian patients (age 56.9 +/- 12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network …

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Circulating Biomarkers For Detection Of Ovarian Cancer And Predicting Cancer Outcomes, I. Shapira, M. Oswald, J. Lovecchio, H. Khalili, A. Menzin, Jill Whyte, L. Dos Santos, S. Liang, T. Bhuiya, M. Keogh, C. Mason, K. Sultan, D. Budman, P. K. Gregersen, A. T. Lee Jan 2014

Circulating Biomarkers For Detection Of Ovarian Cancer And Predicting Cancer Outcomes, I. Shapira, M. Oswald, J. Lovecchio, H. Khalili, A. Menzin, Jill Whyte, L. Dos Santos, S. Liang, T. Bhuiya, M. Keogh, C. Mason, K. Sultan, D. Budman, P. K. Gregersen, A. T. Lee

Journal Articles

Background: Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early. Methods: Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass. Results: Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P

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Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov Jan 2014

Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov

Journal Articles

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune - brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels) remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum, and thalamus in mice following an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels …

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Decreased Langerhans Cell Responses To Il-36 Gamma: Altered Innate Immunity In Patients With Recurrent Respiratory Papillomatosis, J. Devoti, L. Hatam, A. Lucs, A. Afzal, A. Abramson, B. M. Steinberg, V. Bonagura Jan 2014

Decreased Langerhans Cell Responses To Il-36 Gamma: Altered Innate Immunity In Patients With Recurrent Respiratory Papillomatosis, J. Devoti, L. Hatam, A. Lucs, A. Afzal, A. Abramson, B. M. Steinberg, V. Bonagura

Journal Articles

Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease caused by human papillomaviruses (HPVs) types 6 and 11 that is characterized by the polarization of adaptive immune responses that support persistent HPV infection. Respiratory papillomas express elevated mRNA levels of IL-36 gamma, a proinflammatory cytokine in comparison to autologous clinically normal laryngeal tissues; however there is no evidence of inflammation in these lesions. Consistent with this, respiratory papillomas do not contain T(H)1-like CD4(+) T-cells or cytotoxic CD8(+) T-cells, but instead contain a predominance of T(H)2-like and T regulatory cells (Tregs). In addition, papillomas also are infiltrated with immature Langerhans cells …

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Overexpressed Beta-Catenin Localizes To Plasma Membrane In Respiratory Papillomas, A. V. Lucs, A. L. Abramson, B. M. Steinberg Jan 2014

Overexpressed Beta-Catenin Localizes To Plasma Membrane In Respiratory Papillomas, A. V. Lucs, A. L. Abramson, B. M. Steinberg

Journal Articles

No abstract provided.

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Early Efficacy Trial Of Anakinra In Corticosteroid-Resistant Autoimmune Inner Ear Disease, A. Vambutas, M. Lesser, V. Mullooly, S. Pathak, G. Zahtz, L. M. Rosen, E. Goldofsky Jan 2014

Early Efficacy Trial Of Anakinra In Corticosteroid-Resistant Autoimmune Inner Ear Disease, A. Vambutas, M. Lesser, V. Mullooly, S. Pathak, G. Zahtz, L. M. Rosen, E. Goldofsky

Journal Articles

BACKGROUND. Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals. METHODS. We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (= 30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection …

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Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release And Limits Acute Pancreatitis In Mice, R. Kang, Q. Zhang, W. Hou, Z. Yan, R. Chen, J. Bonaroti, P. Bansal, T. R. Billiar, A. Tsung, Q. Wang, D. L. Bartlett, D. C. Whitcomb, E. B. Chang, X. Zhu, H. Wang, B. Lu, K. J. Tracey, L. Cao, X. G. Fan, M. T. Lotze, H. J., 3rd Zeh, D. Tang Jan 2014

Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release And Limits Acute Pancreatitis In Mice, R. Kang, Q. Zhang, W. Hou, Z. Yan, R. Chen, J. Bonaroti, P. Bansal, T. R. Billiar, A. Tsung, Q. Wang, D. L. Bartlett, D. C. Whitcomb, E. B. Chang, X. Zhu, H. Wang, B. Lu, K. J. Tracey, L. Cao, X. G. Fan, M. T. Lotze, H. J., 3rd Zeh, D. Tang

Journal Articles

BACKGROUND & AIMS: High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice after induction of acute pancreatitis. METHODS: We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1(flox/flox) mice). Acute pancreatitis was induced in these mice (HMGB1(flox/flox) mice served as controls) after injection of l-arginine or cerulein. Pancreatic tissues and acinar cells were …

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Hmgb1-Dna Complex-Induced Autophagy Limits Aim2 Inflammasome Activation Through Rage, L. Y. Liu, M. H. Yang, R. Kang, Y. P. Dai, X. J. Sun, X. L. Li, J. H. Li, H. C. Wang, L. Z. Cao, D. L. Tang, +3 Additional Authors Jan 2014

Hmgb1-Dna Complex-Induced Autophagy Limits Aim2 Inflammasome Activation Through Rage, L. Y. Liu, M. H. Yang, R. Kang, Y. P. Dai, X. J. Sun, X. L. Li, J. H. Li, H. C. Wang, L. Z. Cao, D. L. Tang, +3 Additional Authors

Journal Articles

High mobility group box 1 (HMGB1) is a prototype damage-associated molecular pattern (DAMP) that can induce inflammatory and immune responses alone as well as in combination with other molecules such as DNA. However, the intricate molecular mechanisms underlying HMGB1-DNA complex-mediated innate immune response remains largely elusive. In this study, we demonstrated that HMGB1-DNA complex initially induced absent in melanoma 2 (AIM2)-dependent inflammasome activation, and promoted rapid release of inflammasome-dependent early proinflammatory cytokines such as interleukin 10 (IL-1 beta). Subsequently, HMGB1 - DNA complex stimulated an ATG5-dependent cellular degradation process, autophagy, which was paralleled by a cessation of AIM2 inflammasome activation …

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Gene-Based Therapies In Parkinson's Disease, P. J. Allen, A. Feigin Jan 2014

Gene-Based Therapies In Parkinson's Disease, P. J. Allen, A. Feigin

Journal Articles

Parkinson's disease (PD) is a progressive neurological disorder characterized primarily by the degeneration of nigrostriatal dopaminergic neurons and diminution of the neurotransmitter dopamine. Though dopamine replacement therapies such as levodopa can improve the symptoms of PD, the benefits may be overshadowed by side effects and the onset of symptoms not responsive to dopaminergic treatments (e.g., autonomic symptoms, gait and balance problems, and cognitive impairment). Furthermore, no therapies have proven to slow the neurodegenerative process. Novel approaches to address these difficult problems, and others, are being sought. Over the last decade, several innovative gene therapies for PD have entered human clinical …

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Sex Differences In Anxiety And Depression Clinical Perspectives, M. Altemus, N. Sarvaiya, C. N. Epperson Jan 2014

Sex Differences In Anxiety And Depression Clinical Perspectives, M. Altemus, N. Sarvaiya, C. N. Epperson

Journal Articles

Sex differences are prominent in mood and anxiety disorders and may provide a window into mechanisms of onset and maintenance of affective disturbances in both men and women. With the plethora of sex differences in brain structure, function, and stress responsivity, as well as differences in exposure to reproductive hormones, social expectations and experiences, the challenge is to understand which sex differences are relevant to affective illness. This review will focus on clinical aspects of sex differences in affective disorders including the emergence of sex differences across developmental stages and the impact of reproductive events. Biological, cultural, and experiential factors …

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A Randomized Trial Of Family Focused Therapy With Populations At Clinical High Risk For Psychosis: Effects On Interactional Behavior, M. P. O'Brien, D. J. Miklowitz, K. A. Candan, C. Marshall, I. Domingues, B. C. Walsh, J. L. Zinberg, S. D. De Silva, K. A. Woodberry, T. D. Cannon Jan 2014

A Randomized Trial Of Family Focused Therapy With Populations At Clinical High Risk For Psychosis: Effects On Interactional Behavior, M. P. O'Brien, D. J. Miklowitz, K. A. Candan, C. Marshall, I. Domingues, B. C. Walsh, J. L. Zinberg, S. D. De Silva, K. A. Woodberry, T. D. Cannon

Journal Articles

Objective: This study investigated whether family focused therapy (FFT-CHR), an 18-session intervention that consisted of psychoeducation and training in communication and problem solving, brought about greater improvements in family communication than enhanced care (EC), a 3-session psychoeducational intervention, among individuals at clinical high risk for developing psychosis. Method: This study was conducted within a randomized controlled trial across 8 sites. We examined 10-min problem-solving discussions at baseline and 6-month reassessment among 66 adolescents and young adults and their parents. Trained coders who were blind to treatment and time of assessment achieved high levels of interrater reliability when evaluating family discussions …

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High Rate Of Disease-Related Copy Number Variations In Childhood Onset Schizophrenia, K. Ahn, N. Gotay, P. Gochman, Y. Lee, S. Sanders, S. Guha, H. Hakonarson, T. Lencz, M. W. State, J. L. Rapoport, +5 Additional Authors Jan 2014

High Rate Of Disease-Related Copy Number Variations In Childhood Onset Schizophrenia, K. Ahn, N. Gotay, P. Gochman, Y. Lee, S. Sanders, S. Guha, H. Hakonarson, T. Lencz, M. W. State, J. L. Rapoport, +5 Additional Authors

Journal Articles

Copy number variants (CNVs) are risk factors in neurodevelopmental disorders, including autism, epilepsy, intellectual disability (ID) and schizophrenia. Childhood onset schizophrenia (COS), defined as onset before the age of 13 years, is a rare and severe form of the disorder, with more striking array of prepsychotic developmental disorders and abnormalities in brain development. Because of the well-known phenotypic variability associated with pathogenic CNVs, we conducted whole genome genotyping to detect CNVs and then focused on a group of 46 rare CNVs that had well-documented risk for adult onset schizophrenia (AOS), autism, epilepsy and/or ID. We evaluated 126 COS probands, 69 …

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Empirical Evidence For Discrete Neurocognitive Subgroups In Bipolar Disorder: Clinical Implications, K. E. Burdick, M. Russo, S. Frangou, K. Mahon, R. J. Braga, M. Shanahan, A. K. Malhotra Jan 2014

Empirical Evidence For Discrete Neurocognitive Subgroups In Bipolar Disorder: Clinical Implications, K. E. Burdick, M. Russo, S. Frangou, K. Mahon, R. J. Braga, M. Shanahan, A. K. Malhotra

Journal Articles

Background. Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 S.D. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not. Method. A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the …

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Clinical Predictors Of Therapeutic Response To Antipsychotics In Schizophrenia, M. Carbon, C. U. Correll Jan 2014

Clinical Predictors Of Therapeutic Response To Antipsychotics In Schizophrenia, M. Carbon, C. U. Correll

Journal Articles

The search for clinical outcome predictors for schizophrenia is as old as the field of psychiatry. However, despite a wealth of large, longitudinal studies into prognostic factors, only very few clinically useful outcome predictors have been identified. The goal of future treatment is to either affect modifiable risk factors, or use nonmodifiable factors to parse patients into therapeutically meaningful subgroups. Most clinical outcome predictors are nonspecific and/or nonmodifiable. Nonmodifiable predictors for poor odds of remission include male sex, younger age at disease onset, poor premorbid adjustment, and severe baseline psychopathology. Modifiable risk factors for poor therapeutic outcomes that clinicians can …

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Sequencing An Ashkenazi Reference Panel Supports Population-Targeted Personal Genomics And Illuminates Jewish And European Origins, S. Carmi, K. Y. Hui, F. Grady, S. Guha, K. Upadhyay, D. Ben-Avraham, S. Mukherjee, B. M. Bowen, T. Lencz, I. Pe'er, +22 Additional Authors Jan 2014

Sequencing An Ashkenazi Reference Panel Supports Population-Targeted Personal Genomics And Illuminates Jewish And European Origins, S. Carmi, K. Y. Hui, F. Grady, S. Guha, K. Upadhyay, D. Ben-Avraham, S. Mukherjee, B. M. Bowen, T. Lencz, I. Pe'er, +22 Additional Authors

Journal Articles

The Ashkenazi Jewish (AJ) population is a genetic isolate close to European and Middle Eastern groups, with genetic diversity patterns conducive to disease mapping. Here we report high-depth sequencing of 128 complete genomes of AJ controls. Compared with European samples, our AJ panel has 47% more novel variants per genome and is eightfold more effective at filtering benign variants out of AJ clinical genomes. Our panel improves imputation accuracy for AJ SNP arrays by 28%, and covers at least one haplotype in approximate to 67% of any AJ genome with long, identical-by-descent segments. Reconstruction of recent AJ history from such …

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Type And Duration Of Subsyndromal Symptoms In Youth With Bipolar I Disorder Prior To Their First Manic Episode, C. U. Correll, M. Hauser, J. B. Penzner, A. M. Auther, V. Kafantaris, E. Saito, D. Olvet, R. E. Carrion, M. Pavuluri, B. A. Cornblatt, +4 Additional Authors Jan 2014

Type And Duration Of Subsyndromal Symptoms In Youth With Bipolar I Disorder Prior To Their First Manic Episode, C. U. Correll, M. Hauser, J. B. Penzner, A. M. Auther, V. Kafantaris, E. Saito, D. Olvet, R. E. Carrion, M. Pavuluri, B. A. Cornblatt, +4 Additional Authors

Journal Articles

Objectives: The aim of the present study was to systematically evaluate the prodrome to mania in youth. Methods: New-onset/worsening symptoms/signs of >= moderate severity preceding first mania were systematically assessed in 52 youth (16.2 +/- 2.8 years) with a research diagnosis of bipolar I disorder (BD-I). Youth and/or caregivers underwent semi-structured interviews, using the Bipolar Prodrome Symptom Scale-Retrospective. Results: The mania prodrome was reported to start gradually in most youth (88.5%), with either slow (59.6%) or rapid (28.8%) deterioration, while a rapid-onset-and-deterioration prodrome was rare (11.5%). The manic prodrome, conservatively defined as requiring >= 3 symptoms, lasted 10.3 +/- 14.4 …

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Adding Insult To Injury: Childhood And Adolescent Risk Factors For Psychosis Predict Lower Fractional Anisotropy In The Superior Longitudinal Fasciculus In Healthy Adults, P. Derosse, T. Ikuta, B. D. Peters, K. Karlsgodt, P. Szeszko, A. K. Malhotra Jan 2014

Adding Insult To Injury: Childhood And Adolescent Risk Factors For Psychosis Predict Lower Fractional Anisotropy In The Superior Longitudinal Fasciculus In Healthy Adults, P. Derosse, T. Ikuta, B. D. Peters, K. Karlsgodt, P. Szeszko, A. K. Malhotra

Journal Articles

Although epidemiological studies provide strong support for demographic and environmental risk factors in psychotic disorders, few data examine how these risk factors relate to the putative aberrant neurodevelopment associated with illness. The present study examined how the accumulation of risk factors including low IQ, low parental socioeconomic status (SES), history of adolescent cannabis use and childhood trauma, and high levels of subclinical psychotic-like experiences (PLEs) contributed to aberrant neurodevelopmental outcomes in 112 otherwise healthy adults recruited from the community. Participants were studied with diffusion tensor imaging (DTI), and voxel-wise statistical analysis of fractional anisotropy (FA) using tractbased spatial statistics (TBSS) …

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The Relation Between Childhood Maltreatment And Psychosis In Patients With Schizophrenia And Non-Psychiatric Controls, P. Derosse, G. C. Nitzburg, B. Kompancaril, A. K. Malhotra Jan 2014

The Relation Between Childhood Maltreatment And Psychosis In Patients With Schizophrenia And Non-Psychiatric Controls, P. Derosse, G. C. Nitzburg, B. Kompancaril, A. K. Malhotra

Journal Articles

Several lines of evidence suggest that childhood maltreatment is associated with an increased risk for both psychotic disorders and subclinical psychotic-like experiences in the general population. Few studies, however, have sought to examine whether the strength of this relationship is comparable across patient and non-patient groups. The present study sought to compare the strength of the association between childhood maltreatment and self-reported psychotic symptoms in 447 healthy adult volunteers and 184 stable outpatients with schizophrenia or schizoaffective disorder. Strong positive correlations between childhood maltreatment and self-reported symptoms were observed in both groups. Although patients scored significantly higher than controls on …

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