Digital Commons Network^™

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 …

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 …

Molecular Mechanism And Therapeutic Modulation Of High Mobility Group Box 1 Release And Action: An Updated Review, B. Lu, C. Wang, M. Wang, W. Li, F. P. Chen, K. J. Tracey, H. C. Wang

Journal Articles

High mobility group box 1 (HMGB1) is an evolutionarily conserved protein, and is constitutively expressed in virtually all types of cells. Infection and injury converge on common inflammatory responses that are mediated by HMGB1 secreted from immunologically activated immune cells or passively released from pathologically damaged cells. Herein we review the emerging molecular mechanisms underlying the regulation of pathogen-associated molecular patterns (PAMPs)-induced HMGB1 secretion, and summarize many HMGB1-targeting therapeutic strategies for the treatment of infection- and injury-elicited inflammatory diseases. It may well be possible to develop strategies that specifically attenuate damage-associated molecular patterns (DAMPs)-mediated inflammatory responses without compromising the PAMPs-mediated …

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 …

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 …

Dopaminergic Influences On Emotional Decision Making In Euthymic Bipolar Patients, K. E. Burdick, R. J. Braga, C. B. Gopin, A. K. Malhotra

Journal Articles

We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson's disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre- and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky …

Apoe Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites In The Aging Brain, J. J. Gomar, M. L. Gordon, P. B. Kingsley, A. M. Ulug, L. Keehlisen, S. Huet, J. J. Buthorn, J. Koppel, E. Christen, C. Conejero-Goldberg, P. Davies, T. E. Goldberg, +1 Additional Author

Journal Articles

Background: Proton magnetic resonance spectroscopy (H-1-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. Methods: We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of H-1-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures …

Cb2 Receptor Deficiency Increases Amyloid Pathology And Alters Tau Processing In A Transgenic Mouse Model Of Alzheimer's Disease, Jeremy Koppel, V. Vingtdeux, P. Marambaud, C. D'Abramo, H. Jimenez, M. Stauber, R. Friedman, P. Davies

Journal Articles

The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer's disease (AD). In order to investigate the impact of the CB2 receptor system on AD pathology, a colony of mice with a deleted CB2 receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB2 receptor-sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2(-/-) (Cnr2(tm1Dgen)/J) mice to produce a colony of J20 CNR2(+/+) and J20 CNR2(-/-)mice. Seventeen J20 CNR2(+/+) mice (12 females, 5 males) and 16 J20 CNR2(-/-) mice (11 females, 5 males) were killed at …

Alpha 7 Nicotinic Acetylcholine Receptor Signaling Inhibits Inflammasome Activation By Preventing Mitochondrial Dna Release, B. Lu, K. Kwan, Y. A. Levine, P. S. Olofsson, H. Yang, J. H. Li, S. Joshi, H. C. Wang, U. Andersson, S. S. Chavan, K. J. Tracey

Journal Articles

The mammalian immune system and the nervous system coevolved under the influence of cellular and environmental stress. Cellular stress is associated with changes in immunity and activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, a key component of innate immunity. Here we show that alpha 7 nicotinic acetylcholine receptor (alpha 7 nAchR)-signaling inhibits inflammasome activation and prevents release of mitochondrial DNA, an NLRP3 ligand. Cholinergic receptor agonists or vagus nerve stimulation significantly inhibits inflammasome activation, whereas genetic deletion of alpha 7 nAchR significantly enhances inflammasome activation. Acetylcholine accumulates in macrophage cytoplasm after adenosine triphosphate (ATP) stimulation …

The Content Of Attenuated Psychotic Symptoms In Those At Clinical High Risk For Psychosis, C. Marshall, E. Denny, K. S. Cadenhead, T. D. Cannon, Barbara Cornblatt, T. H. Mcglashan, D. O. Perkins, L. J. Seidman, M. T. Tsuang, J. Addington, +2 Additional Authors

Journal Articles

Recent research has started to focus on identifying individuals who are at clinical high risk of developing psychosis as a means to try and understand the predictors and mechanisms involved in the progress to a full psychotic episode. The aim of the current study was to provide an initial description and prevalence rates of specific content found within attenuated positive symptoms. The Content of Attenuated Positive Symptoms (CAPS) codebook was used by independent raters to determine the presence of content within a sample of written vignettes. Krippendorff's alpha was used to determine inter-rater reliability. Overall, the majority of items fell …

Bdnf Val66met Polymorphism And Antipsychotic-Induced Tardive Dyskinesia Occurrence And Severity: A Meta-Analysis, I. Miura, Jianping Zhang, M. Nitta, T. Lencz, John Kane, Anil Malhotra, H. Yabe, Christoph Correll

Journal Articles

Background: Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD. Methods: Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNF Val66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges'g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score. Results: Out of 699 potentially eligible …

Matrics Cognitive Consensus Battery (Mccb) Performance In Children, Adolescents, And Young Adults, G. C. Nitzburg, P. Derosse, K. E. Burdick, B. D. Peters, C. B. Gopin, Anil Malhotra

Journal Articles

Background: Neurodevelopmental models of schizophrenia suggest that cognitive deficits may be observed during childhood and adolescence, long before the onset of psychotic symptoms. Elucidating the trajectory of normal cognitive development during childhood and adolescence may therefore provide a basis for identifying specific abnormalities related to the development of schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB), which was designed for use in clinical trials targeting cognitive deficits most common in schizophrenia, may provide a mechanism to understand this trajectory. To date, however, there is no performance data for the MCCB in healthy children and adolescents. The present study sought to establish …

Age-Related Differences In White Matter Tract Microstructure Are Associated With Cognitive Performance From Childhood To Adulthood, B. D. Peters, T. Ikuta, P. Derosse, M. John, K. E. Burdick, P. Gruner, D. M. Prendergast, Philip Szeszko, Anil Malhotra

Journal Articles

Background: Age-related differences in white matter tract microstructure have been well established across the life span. In the present cross-sectional study, we examined whether these differences are associated with neurocognitive performance from childhood to late adulthood. Methods: Diffusion tensor imaging was performed in 296 healthy subjects aged 8 to 68 years (mean = 29.6, SD = 14.6). The corpus callosum, two projection tracts, and five association tracts were traced using probabilistic tractography. A neurocognitive test battery was used to assess speed of processing, attention, spatial working memory, verbal functioning, visual learning, and executive functioning. Linear mediation models were used to …

Brain White Matter Development Is Associated With A Human-Specific Haplotype Increasing The Synthesis Of Long Chain Fatty Acids, B. D. Peters, A. N. Voineskos, P. R. Szeszko, T. A. Lett, P. Derosse, S. Guha, K. H. Karlsgodt, M. John, T. Lencz, A. K. Malhotra, +4 Additional Authors

Journal Articles

The genetic and molecular pathways driving human brain white matter (WM) development are only beginning to be discovered. Long chain polyunsaturated fatty acids (LC-PUFAs) have been implicated in myelination in animal models and humans. The biosynthesis of LC-PUFAs is regulated by the fatty acid desaturase (FADS) genes, of which a human-specific haplotype is strongly associated with omega-3 and omega-6 LC-PUFA concentrations in blood. To investigate the relationship between LC-PUFA synthesis and human brain WM development, we examined whether this FADS haplotype is associated with age-related WM differences across the life span in healthy individuals 9-86 years of age (n = …

Delineation Of Hippocampal Subregions Using T1-Weighted Magnetic Resonance Images At 3 Tesla, K. Rhindress, T. Ikuta, R. Wellington, A. K. Malhotra, P. Szeszko

Journal Articles

Although several novel approaches for hippocampal subregion delineation have been developed, they need to be applied prospectively and may be limited by long scan times, the use of high field (>3T) imaging systems, and limited reliability metrics. Moreover, the majority of MR imaging data collected to date has employed a T1-weighted acquisition, creating a critical need for an approach that provides reliable hippocampal subregion segmentation using such a contrast. We present a highly reliable approach for the identification of six subregions comprising the hippocampal formation from MR images including the subiculum, dentate gyrus/cornu Ammonis 4 (DG/CA4), entorhinal cortex, fimbria, …

White Matter Changes Associated With Antipsychotic Treatment In First-Episode Psychosis, P. Szeszko, D. G. Robinson, T. Ikuta, B. D. Peters, J. Gallego, J. Kane, A. K. Malhotra

Journal Articles

Second-generation antipsychotics are utilized extensively in the treatment of psychotic disorders and other psychiatric conditions, but the effects of these medications on human brain white matter are not well understood. We thus investigated the effects of second-generation antipsychotics on white matter integrity using tract-based spatial statistics in patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure, and how potential changes were associated with metabolic side effects. Thirty-five (26 men/9 women) patients experiencing a first episode of psychosis received diffusion tensor imaging (DTI) exams, clinical assessments, and provided fasting blood samples at the onset of antipsychotic …

Expression Of Blimp-1 In Dendritic Cells Modulates The Innate Inflammatory Response In Dextran Sodium Sulfate-Induced Colitis, S. J. Kim, J. Goldstein, K. Dorso, M. Merad, L. Mayer, J. M. Crawford, P. K. Gregersen, B. Diamond

Journal Articles

A single nucleotide polymorphism of PRDM1, the gene encoding Blimp-1, is strongly associated with inflammatory bowel disease. Here, we demonstrate that Blimp-1 in CD103(+) dendritic cells (DCs) critically contributes to the regulation of macrophage homeostasis in the colon. Dextran sodium sulfate (DSS)-exposed Blimp-1(cko) mice with a deletion of Blimp-1 in CD103(+) DCs and CD11c(hi) macrophages exhibited severe inflammatory symptoms, pronounced weight loss, high mortality, robust infiltration of neutrophils in epithelial regions of the colon, an increased expression of proinflammatory cytokines and a significant decrease in CD103(+) DCs in the colon compared with DSS exposed wild-type (WT) mice. Purified colonic macrophages …

Inhibition Of Extracellular Hmgb1 Attenuates Hyperoxia-Induced Inflammatory Acute Lung Injury, M. Entezari, M. Javdan, D. J. Antoine, D. M. Morrow, R. A. Sitapara, V. Patel, M. Wang, L. Sharma, H. Wang, L. L. Mantell, +7 Additional Authors

Journal Articles

Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to >/=99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of …

Synthesis And Biological Activity Of Indolinones, Kaleb Woodrow Cox

Browse all Theses and Dissertations

Indolinones of the type known as Arylidene oxindoles have been demonstrated to possess a broad range of activity ranging from proten kinase inhibtors, cell-death inhibitors and tau protein binding agents. Small libraries of such molecules were designed and synthesized herein in modifications involving variously substituted halogen derivatives, N-alkylation of the indolinone nitrogen, and finally a new class of molecules, namely arylidene oxindoles possessing extended conjugation. The biological activities of such molecules were examined and the results disclosed herein.

Mr. Vane And Lilith: Two Roads To Repentance?, Jonathan B. Himes

North Wind: A Journal of George MacDonald Studies

No abstract provided.

Alpha-Asarone Protects Endothelial Cells From Injury By Angiotensin Ii, Ha-Xia Shi, Jiajun Yang, Tao Yang, Yong-Liang Xue, Jun Liu, Ya-Juan Li, Dan-Dan Zhang, Ji-Wen Zhu, Ka Bian

Biochemistry and Molecular Medicine Faculty Publications

α-Asarone is the major therapeutical constituent of Acorus tatarinowii Schott. In this study, the potential protective effects of α-asarone against endothelial cell injury induced by angiotensin II were investigated in vitro. The EA.hy926 cell line derived from human umbilical vein endothelial cells was pretreated with α-asarone (10, 50, 100 µmol/L) for 1 h, followed by coincubation with Ang II (0.1 µmol/L) for 24 h. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) were detected by fluorescent dyes, and phosphorylation of endothelial nitric oxide synthase (eNOS) at was determined by Western blotting. α-Asarone dose-dependently mitigated the Ang II-induced intracellular NO …

Urban Food Corridors: Cultivating Sustainable Cities, Becky Jacobs

College of Law Faculty Scholarship

No abstract provided.

247th Annual Report Of The Selectmen And Other Town Officers Cornish, New Hampshire Year Ending December 31, 2013., Cornish Town Representatives

Cornish, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Annual Reports Of The Board Of Selectmen, Town Offices, Committees/ Commissions & Sau16 School District Of The Town Of Exeter, New Hampshire For Year 2013., Exeter Town Representatives

Exeter, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

The End(S) Of Art: Faith-Learning Integration Statement, Lex Thompson

Faith Learning Integration Papers

This essay demands something that is a little bit theology and a little bit art, and can only address a little bit of each. The material that follows does not presume to speak universally or systematically for either. Not only would such a thing be folly, but it would also be impossible. Systematic theology and systematic aesthetics are always a mess. Multiple volumes are written trying to sort out impossible situations gotten into by trying to systematize God, humanity, the world, the imagination, images and the complex of relationships that exist between them. We need to hold onto some of …

Central Bank Of Nigeria Annual Report And Statement Of Accounts For The Year Ended 31st December 2014, Central Bank Of Nigeria

CBN Annual Report

Annual Report and Financial Statements of the Central Bank of Nigeria (CBN) for the year ended 31st December, 2014. In general, 2014 has been a very eventful and challenging year for the Bank, the country, and the world at large. In the course of the year, the Bank underwent significant changes in its governance composition. In 2014, the global economy witnessed considerable vulnerabilities characterized by fragile growth and weak economic outlook. Global growth recovery was modest and continued to be threatened by strong downside risks, as a result of sharp drop in commodity prices, escalating geo-political tensions, and heightening threats …

Measured And Modeled Soil Moisture Compared With Cosmic-Ray Neutron Probe Estimates In A Mixed Forest, Ling Lv, Trenton E. Franz, David A. Robinson, Scott B. Jones

T.W. "Doc" Daniel Experimental Forest

Soil moisture is a key variable in most environmental processes, and the cosmic-ray neutron probe (CRNP) fills a niche for intermediate-scale soil moisture measurements. In this study, the CRNP estimated soil moisture was compared with a soil moisture measurement network including 108 time domain transmissometry (TDT) probes. We also used a Hydrus-1D numerical model of measured soil moisture at targeted locations by inversely fitting soil hydraulic parameters used to simulate soil moisture in the near surface (0.03 and 0.05 m) during the growing seasons of 2011 and 2012. Both simulated and TDT-measured soil moisture were used in constructing the depth-weighted …

Prologemena To An Future Rhetoric Of Shadows, Shades And Silhouettes, Gene Washington

English Faculty Publications

In this essay, following the implications of "prolegomena" (Greek: "to say before"), i describe what a rhetoric constructed of textual shadows (the word "shadow" in a text) would look like. Specifically, what would be the various motives and rhetorical intentions, for a writer (of all genres) to employ the word "shadow" or a member of its semantic "family."

Representing Entities: The Value Of Teaching Students How To Draft Board Resolutions And Other Similar Documentation, Joan Macleod Heminway

Scholarly Works

This edited transcript comprises a panel presentation and related Q&A at "Educating the Transactional Lawyer of Tomorrow," Emory University School of Law's biennial transactional law conference held June 6-7, 2014. The transcript includes Professor Heminway's talk and a separate presentation by Professor Marcia Narine on "How to Make Transactional Law Less Terrifying and a Bit More Interesting." The panel, "Transactional Drafting: Beyond Contracts," features approaches to teaching transactional business law courses.

Professor Heminway's presentation addresses the benefits of teaching the drafting of board resolutions, minutes, and consents in corporate finance and corporate governance courses. She describes how teaching law students …

Mathers Systematic Theology - Chapter 1, Norman W. Mathers

SOR Faculty Publications and Presentations

No abstract provided.