bluuebunny/crossref_metadata_2025_split huggingface dataset:
L'État de facto du Haut-Karabagh arménien
Authors: Petithomme Mathieu 
Published: March 2013

Cet article se focalise sur les ambivalences du processus de démocratisation mis en avant par les élites de la République du Haut-Karabagh (RHK) afin de renforcer leur légitimité face au déficit de reconnaissance internationale du territoire. Il montre aussi comment les élites locales modifient les conditions de sortie du conflit en promouvant une politique de citoyenneté exclusive qui « ethnicise » l’enclave et empêche un éventuel droit au retour des déplacés azéris. Malgré une réalité en trompe-l’œil, tant la démocratisation de façade que la politique de citoyenneté ont pour but stratégique de défendre la souveraineté interne de l’entité. L’ambivalence de ces processus s’explique par la nécessité de créer une entité dotée d’une identité propre, tout en maintenant une ambiguïté entre indépendantisme et volonté de rattachement avec l’Arménie.
Lacan et l'oubli du rire de Marx
Authors: Morel Geneviève 
Published: March 2013

Il s’agit de traiter trois propositions qui s’articulent étroitement : premièrement, le côté spirituel de Lacan, justement inimitable sauf à sombrer dans le ridicule, et son intérêt pour le Witz sont au cœur de ce qu’on a appelé le « retour à Freud » de Lacan dans les années 1950. Deuxièmement, son abord de la parole et du langage par le mot d’esprit définit une position matérialiste dans l’approche du symptôme analytique, dans un sens que je tente de préciser ici. Troisièmement, un levier essentiel de cette approche est l’appui pris, dès les années 1950, sur la lecture de Marx, qu’on oublie souvent parce que Lacan l’a lui-même mise entre parenthèses jusqu’à la presque fin des années 1960. Or, cette lecture recèle des oublis répétés de Marx qui témoignent d’un vertige de Lacan quant à la cause du célèbre rire du capitaliste dans Le capital de Marx.
Lacan et la psychiatrie organo-dynamique : retour sur un dialogue avec Henri Ey
Authors: de Calan Ronan 
Published: March 2013

L’organo-dynamisme de Henri Ey constitue incontestablement, pour qui s’intéresse au matérialisme en général et à la psychiatrie en particulier, une doctrine médicale d’un matérialisme extraordinairement sophistiqué. Les critiques que lui adresse Lacan sont alors l’occasion de faire le point aussi bien sur les préoccupations de clinicien qui sont à l’origine de sa démarche que sur le sens qu’il faudrait, selon lui, donner à un point de vue matérialiste en psychologie. S’affrontent là une théorie du nexus causal dans la droite ligne de la grande métaphysique (Ey) et une « topique causale » propre aux empirismes, qui accorde une portée nouvelle à la dimension de la parole dans la clinique et à celle du langage dans la théorie (Lacan).
Le motérialisme du symptôme dans la clinique lacanienne de la psychose
Authors: Meyer zum Wischen Michael 
Published: March 2013

Dans sa « Conférence à Genève sur le symptôme » (1975), Jacques Lacan introduit le terme « motérialisme », rendant compte de la matérialité des mots qui sont la matière de l’inconscient. Cette formulation implique la critique d’une conception abstraite de l’inconscient comme composé de représentations. Lacan souligne que « c’est dans la rencontre de ces mots avec [le] corps que quelque chose se dessine ». Mon essai situe le « motérialisme » par rapport à d’autres notions du dernier enseignement de Lacan concernant l’inconscient : l’une-bévue, lalangue, le savoir-y-faire. Concernant la psychose, est posée la question des conséquences que le « motérialisme » entraîne pour les désabonnés à l’inconscient qui ne peuvent s’appuyer sur les duperies du signifiant. Cinq exemples viendront soutenir l’élaboration de cette problématique.
Differential Effects of Phenethyl Isothiocyanate and D,L-Sulforaphane on TLR3 Signaling
Authors: Zhu Jianzhong , Ghosh Arundhati , Coyle Elizabeth M. , Lee Joomin , Hahm Eun-Ryeong , Singh Shivendra V. , Sarkar Saumendra N. 
Published: March 2013

Abstract
Naturally occurring isothiocyanates (ITCs) from cruciferous vegetables are widely studied for their cancer chemopreventive effects. In this study, we investigated the effects of ITCs on TLR signaling, and found that the two most promising ITCs, phenethyl ITCs (PEITC) and D,L-sulforaphane (SFN), have differential effects on dsRNA-mediated innate immune signaling through TLR3. PEITC preferentially inhibited TLR3-mediated IFN regulatory factor 3 (IRF3) signaling and downstream gene expression in vivo and in vitro, whereas SFN caused inhibition of TLR3-mediated NF-κB signaling and downstream gene expression. Mechanistically, PEITC inhibited ligand (dsRNA)-dependent dimerization of TLR3, resulting in inhibition of signaling through IFN regulatory factor 3. In contrast, SFN did not disrupt TLR3 dimerization, indicating that it affects further downstream pathway resulting in NF-κB inhibition. To examine the biological significance of these findings in the context of antitumor activities of these compounds, we used two approaches: first, we showed that dsRNA-mediated apoptosis of tumor cells via TLR3 was inhibited in the presence of PEITC, whereas this response was augmented by SFN treatment; second, in a separate assay measuring anchorage-independent growth and colony formation by immortalized fibroblasts, we made similar observations. Again in this study, PEITC antagonized dsRNA-mediated inhibition of colony formation, whereas SFN enhanced the inhibition. These results indicate biologically relevant functional differences between two structurally similar ITCs and may provide important insights in therapeutic development of these compounds targeted to specific cancer.
A Novel Small-Molecule Enantiomeric Analogue of Traditional (−)-Morphinans Has Specific TLR9 Antagonist Properties and Reduces Sterile Inflammation-Induced Organ Damage
Authors: Hoque Rafaz , Farooq Ahmad , Malik Ahsan , Trawick Bobby N. , Berberich David W. , McClurg Joseph P. , Galen Karen P. , Mehal Wajahat 
Published: March 2013

Abstract
TLR9 is a key determinant of the innate immune responses in both infectious and sterile injury. Specific antagonism of TLR9 is of great clinical interest to reduce tissue damage in a wide range of pathologies, and has been approached by modification of nucleic acids, the recognized ligand for TLR9. Such oligonucleotide-derived pharmacotherapeutics have limitations in specificity for nucleic acid receptors, significant potential for immunologic recognition with generation of innate and adaptive immune responses, and limited bioavailability. We have identified enantiomeric analogues of traditional (−)-morphinans as having TLR9 antagonist properties on reporter cell lines. One of these analogues (COV08-0064) is demonstrated to be a novel small-molecule antagonist of TLR9 with greater specificity for TLR9 than oligo-based antagonists. COV08-0064 has wide bioavailability, including the s.c. and oral routes. It specifically inhibits the action of TLR9 antagonists on reporter cells lines and the production of cytokines by TLR9 agonists from primary cells. It also has efficacy in limiting TLR9-mediated sterile inflammation in in vivo models of acute liver injury and acute pancreatitis. The identification of a morphinan-based novel small-molecule structure with TLR9 antagonism is a significant step in expanding therapeutic strategies in the field of sterile inflammatory injury.
Inflammation Induced by MMP-9 Enhances Tumor Regression of Experimental Breast Cancer
Authors: Leifler Karin Söderlund , Svensson Susanne , Abrahamsson Annelie , Bendrik Christina , Robertson Jennifer , Gauldie Jack , Olsson Anna-Karin , Dabrosin Charlotta 
Published: March 2013

Abstract
Matrix metalloproteinases (MMPs) have been suggested as therapeutic targets in cancer treatment, but broad-spectrum MMP inhibitors have failed in clinical trials. Recent data suggest that several MMPs including MMP-9 exert both pro- and antitumorigenic properties. This is also the case of the natural inhibitors of MMPs, tissue inhibitor of metalloproteinases (TIMPs). The inhibitor of MMP-9 is TIMP-1, and high levels of this enzyme have been associated with decreased survival in breast cancer. Inflammation is one hallmark of cancer progression, and MMPs/TIMPs may be involved in the local immune regulation. We investigated the role of MMP-9/TIMP-1 in regulating innate antitumor immunity in breast cancer. Breast cancers were established in nude mice and treated with intratumoral injections of adenoviruses carrying the human TIMP-1 or MMP-9 gene (AdMMP-9). In vivo microdialysis for sampling of cancer cell–derived (human) and stroma-derived (murine) proteins, immunostainings, as well as cell cultures were performed. We report a dose-dependent decrease of tumor growth and angiogenesis after AdMMP-9 treatment. In addition to increased generation of endostatin, AdMMP-9 promoted an antitumor immune response by inducing massive neutrophil infiltration. Neutrophil depletion prior to gene transfer abolished the therapeutic effects of AdMMP-9. Additionally, AdMMP-9 activated tumor-infiltrating macrophages into a tumor-inhibiting phenotype both in vivo and in vitro. AdMMP-9 also inhibited tumor growth in immune-competent mice bearing breast cancers. Adenoviruses carrying the human TIMP-1 gene had no effect on tumor growth or the immune response. Our novel data identify MMP-9 as a potent player in modulating the innate immune response into antitumor activities.
An Extracellular Matrix–Based Mechanism of Rapid Neutrophil Extracellular Trap Formation in Response toCandida albicans
Authors: Byrd Angel S. , O’Brien Xian M. , Johnson Courtney M. , Lavigne Liz M. , Reichner Jonathan S. 
Published: March 2013

AbstractThe armament of neutrophil-mediated host defense against pathogens includes the extrusion of a lattice of DNA and microbicidal enzymes known as neutrophil extracellular traps (NETs). The receptor/ligand interactions and intracellular signaling mechanisms responsible for elaborating NETs were determined for the response to Candida albicans. Because the host response of extravasated neutrophils to mycotic infections within tissues necessitates contact with extracellular matrix, this study also identified a novel and significant regulatory role for the ubiquitous matrix component fibronectin (Fn) in NET release. We report that recognition of purified fungal pathogen-associated molecular pattern β-glucan by human neutrophils causes rapid (≤30 min) homotypic aggregation and NET release by a mechanism that requires Fn. Alone, immobilized β-glucan induces reactive oxygen species (ROS) production but not NET release, whereas in the context of Fn, ROS production is suppressed and NETs are extruded. NET release to Fn with β-glucan is robust, accounting for 17.2 ± 3.4% of total DNA in the cell population. Release is dependent on β-glucan recognition by complement receptor 3 (CD11b/CD18), but not Dectin-1, or ROS. The process of NET release included filling of intracellular vesicles with nuclear material that was eventually extruded. We identify a role for ERK in homotypic aggregation and NET release. NET formation to C. albicans hyphae was also found to depend on β-glucan recognition by complement receptor 3, require Fn and ERK but not ROS, and result in hyphal destruction. We report a new regulatory mechanism of NETosis in which the extracellular matrix is a key component of the rapid antifungal response.
Agonistic Anti-CD40 Induces Thyrocyte Proliferation and Promotes Thyroid Autoimmunity by Increasing CD40 Expression on Thyroid Epithelial Cells
Authors: Kayes Timothy , Fang Yujiang , Yu Shiguang , Downey Edward , Wang Shufang , Braley-Mullen Helen 
Published: March 2013

Abstract
CD40 is expressed on cells of the immune system and in some tissues that are targets for autoimmune-mediated damage. It is not known if CD40 expression in target tissues plays a role in the pathology of autoimmune diseases. This study shows that agonistic anti-CD40 induces strong and sustained proliferation of thyroid epithelial cells (TECs), or thyrocytes, in IFN-γ−/− autoimmune-prone NOD and NOD.H-2h4 mice. TEC proliferation is accompanied by greatly increased expression of CD40 on TECs, development of fibrosis and hypothyroidism, and increased expression of proinflammatory molecules in thyroids. Bone marrow chimera experiments indicate that TEC expression of CD40 is required for anti-CD40–induced TEC proliferation, but lymphoid cells do not have to express CD40. TEC proliferation is reduced in wild-type mice given anti-CD40, presumably because they produce IFN-γ, which inhibits TEC proliferation. CD40 also increases on TECs during development of an autoimmune thyroid disease characterized by TEC hyperproliferation that develops spontaneously in IFN-γ−/− NOD.H-2h4 mice. TEC hyperproliferation development is accelerated in mice given agonistic anti-CD40. These studies provide new information regarding the role of target tissue expression of CD40 in development of autoimmunity and suggest that use of agonistic anti-CD40 for tumor therapy could result in autoimmune disease.
Fas-Mediated Inflammatory Response inListeria monocytogenesInfection
Authors: Uchiyama Ryosuke , Yonehara Shin , Tsutsui Hiroko 
Published: March 2013

AbstractThe molecular mechanisms of Fas (CD95/Apo-1)-mediated apoptosis are increasingly understood. However, the role of Fas-mediated production of proinflammatory cytokines such as IL-18 and IL-1β in bacterial infection is unclear. We demonstrate the importance of Fas-mediated signaling in IL-18/IL-1β production postinfection with Listeria monocytogenes without the contribution of caspase-1 inflammasome. IL-18/IL-1β production in L. monocytogenes–infected peritoneal exudate cells from Fas-deficient mice was lower than those from wild type mice, indicating that Fas signaling contributes to cytokine production. L. monocytogenes infection induced Fas ligand expression on NK cells, which stimulates Fas expressed on the infected macrophages, leading to the production of IL-18/IL-1β. This was independent of caspase-1, caspase-11, and nucleotide-binding domain and leucine-rich repeat–containing receptors (NLRs) such as Nlrp3 and Nlrc4, but dependent on apoptosis-associated speck-like protein containing a caspase recruitment domain. Wild type cells exhibited caspase-8 activation, whereas Fas-deficient cells did not. L. monocytogenes–induced caspase-8 activation was abrogated by inhibitor for intracellular reactive oxygen species, N-acetyl-L-cysteine. L. monocytogenes–infected macrophages produced type-I IFNs such as IFN-β1, which was required for Il18 gene expression. Thus, Fas signaling regulates innate inflammatory cytokine production in L. monocytogenes infection.
Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process
Authors: Mikami Norihisa , Miyagi Yayoi , Sueda Kaori , Takatsuji Miku , Fukada So-ichiro , Yamamoto Hiroshi , Tsujikawa Kazutake 
Published: March 2013

Abstract
Th9 cells are a novel Th cell subset that produces IL-9 and is involved in type I hypersensitivity such as airway inflammation. Although its critical roles in asthma have attracted interest, the physiological regulatory mechanisms of Th9 cell differentiation and function are largely unknown. Asthma is easily affected by psychological factors. Therefore, we investigated one of the physiological mediators derived from the nervous system, calcitonin gene-related peptide (CGRP), in asthma and Th9 cells because CGRP and activation of the cAMP/protein kinase A (PKA) pathway by CGRP are known to be important regulators in several immune responses and allergic diseases. In this study, we demonstrated that the CGRP/cAMP/PKA pathway promotes IL-9 production via NFATc2 activation by PKA-dependent glycogen synthase kinase-3β inactivation. Moreover, CGRP also induces the expression of PU.1, a critical transcriptional factor in Th9 cells, which depends on PKA, but not NFATc2. Additionally, we demonstrated the physiological importance of CGRP in IL-9 production and Th9 differentiation using an OVA-induced airway inflammation model and T cell–specific CGRP receptor-deficient mice. The present study revealed a novel regulatory mechanism comprising G protein–coupled receptor ligands and nervous system-derived substances in Th9 cell differentiation and type I hypersensitivity.
Essential Roles of K63-Linked Polyubiquitin-Binding Proteins TAB2 and TAB3 in B Cell Activation via MAPKs
Authors: Ori Daisuke , Kato Hiroki , Sanjo Hideki , Tartey Sarang , Mino Takashi , Akira Shizuo , Takeuchi Osamu 
Published: March 2013

Abstract
Polyubiquitination of proteins plays a critical role in the activation of immune cells. K63-linked polyubiquitin-binding proteins TGF-β–activated kinase 1 (TAK1)–binding protein (TAB)2 and TAB3 are implicated in NF-κB signaling via TAK1 activation. However, TAB2 alone is dispensable for NF-κB activation in embryonic fibroblasts, and the functional roles of TAB2 and TAB3 in immune cells has yet to be clarified. In this study, we demonstrate that TAB2 and TAB3 are essential for B cell activation leading to Ag-specific Ab responses, as well as B-1 and marginal zone B cell development. TAB2 and TAB3 are critical for the activation of MAPKs, especially ERK, but not NF-κB, in response to TLR and CD40 stimulation in B cells. Surprisingly, TAB2 and TAB3 are dispensable for TAK1 activation in B cells, indicating that TAB2 and TAB3 activate MAPKs via a pathway independent of TAK1. In contrast to B cells, macrophages lacking TAB2 and TAB3 did not show any defects in the cytokine production and the signaling pathway in response to TLR stimulation. Furthermore, TAB2 and TAB3 were dispensable for TNF-induced cytokine production in embryonic fibroblasts. Thus, TAB2- and TAB3-mediated K63-linked polyubiquitin recognition controls B cell activation via MAPKs, but not the TAK1/NF-κB axis.
Access Guide to Human Proteinpedia
Authors: Muthusamy Babylakshmi , Thomas Joji Kurian , Prasad T.S. Keshava , Pandey Akhilesh 
Published: March 2013

AbstractHuman Proteinpedia (http://www.humanproteinpedia.org) is a publicly available proteome repository for sharing human protein data derived from multiple experimental platforms. It incorporates diverse features of the human proteome including protein‐protein interactions, enzyme‐substrate relationships, PTMs, subcellular localization, and expression of proteins in various human tissues and cell lines in diverse biological conditions including diseases. Through a publicly distributed annotation system developed especially for proteomic data, investigators across the globe can upload, view, and edit proteomic data even before they are published. Inclusion of information on investigators and laboratories that generated the data, as well as visualization of tandem mass spectra, stained tissue sections, protein/peptide microarrays, fluorescent micrographs, and western blots, ensures quality of proteomic data assimilated in Human Proteinpedia. Many of the protein annotations submitted to Human Proteinpedia have also been made available to the scientific community through Human Protein Reference Database (http://www.hprd.org), another resource developed by our group. In this protocol, we describe how to submit, edit, and retrieve proteomic data in Human Proteinpedia. Curr. Protoc. Bioinform. 41:1.21.1‐1.21.15. © 2013 by John Wiley & Sons, Inc.
Using MEMo to Discover Mutual Exclusivity Modules in Cancer
Authors: Ciriello Giovanni , Cerami Ethan , Aksoy Bulent Arman , Sander Chris , Schultz Nikolaus 
Published: March 2013

AbstractAlthough individual tumors show surprisingly diverse genomic alterations, these events tend to occur in a limited number of pathways, and alterations that affect the same pathway tend to not co‐occur in the same patient. While pathway analysis has been a powerful tool in cancer genomics, our knowledge of oncogenic pathway modules is incomplete. To systematically identify such modules, we have developed a novel method, Mutual Exclusivity Modules in Cancer (MEMo). The method searches and identifies modules characterized by three properties: (1) member genes are recurrently altered across a set of tumor samples; (2) member genes are known to or are likely to participate in the same biological process; and (3) alteration events within the modules are mutually exclusive. MEMo integrates multiple data types and maps genomic alterations to biological pathways. MEMo's mutual exclusivity uses a statistical model that preserves the number of alterations per gene and per sample. The MEMo software, source code and sample data sets are available for download at: http://cbio.mskcc.org/memo. Curr. Protoc. Bioinform. 41:8.17.1‐8.17.12. © 2013 by John Wiley & Sons, Inc.
Proteomics and the Analysis of Proteomic Data: 2013 Overview of Current Protein‐Profiling Technologies
Authors: Bruce Can , Stone Kathryn , Gulcicek Erol , Williams Kenneth 
Published: March 2013

AbstractMass spectrometry has become a major tool in the study of proteomes. The analysis of proteolytic peptides and their fragment ions by this technique enables the identification and quantitation of the precursor proteins in a mixture. However, deducing chemical structures and then protein sequences from mass‐to‐charge ratios is a challenging computational task. Software tools incorporating powerful algorithms and statistical methods improved our ability to process the large quantities of proteomics data. Repositories of spectral data make both data analysis and experimental design more efficient. New approaches in quantitative and statistical proteomics make possible a greater coverage of the proteome, the identification of more post‐translational modifications, and a greater sensitivity in the quantitation of targeted proteins. Curr. Protoc. Bioinform. 41:13.21.1‐13.21.17. © 2013 by John Wiley & Sons, Inc.
X‐Ray Fluorescence in Forensic ScienceUpdate based on the original article by Claude Roux and Chris Lennard,Encyclopedia of Analytical Chemistry, © 2000, John Wiley & Sons, Ltd.
Authors: Roux Claude , Taudte Regina Verena , Lennard Chris 
Published: March 2013

AbstractThis article describes the applications of X‐ray fluorescence (XRF) as an analytical tool in forensic science, including its limitations and practical aspects. The use of XRF is specifically discussed for the analysis of materials of forensic interest such as metals, gunshot residues (GSRs), paint, glass, soil, fibers, plastic and general polymers, documents, and miscellaneous types of evidence. Developments such as biological tissues micro‐XRF, 3‐D micro‐XRF — an adaptation of micro‐XRF — and total XRF are also described. These specialized techniques have highly desirable characteristics for the elemental profiling of a wide range of forensic samples, and hence we can anticipate that they will find significant use in forensic laboratories in the future.