bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic Cell Activation and Memory Cell Development Are Impaired among Mice Administered Medroxyprogesterone Acetate Prior to Mucosal Herpes Simplex Virus Type 1 Infection
Authors: Vicetti Miguel Rodolfo D. , Hendricks Robert L. , Aguirre Alfredo J. , Melan Melissa A. , Harvey Stephen A. K. , Terry-Allison Tracy , St. Leger Anthony J. , Thomson Angus W. , Cherpes Thomas L. 
Published: September 2012

Abstract
Epidemiological studies indicate that the exogenous sex steroid medroxyprogesterone acetate (MPA) can impair cell-mediated immunity, but mechanisms responsible for this observation are not well defined. In this study, MPA administered to mice 1 wk prior to HSV type 1 (HSV-1) infection of their corneal mucosa impaired initial expansion of viral-specific effector and memory precursor T cells and reduced the number of viral-specific memory T cells found in latently infected mice. MPA treatment also dampened expression of the costimulatory molecules CD40, CD70, and CD80 by dendritic cells (DC) in lymph nodes draining acute infection, whereas coculture of such DC with T cells from uninfected mice dramatically impaired ex vivo T cell proliferation compared with the use of DC from mice that did not receive MPA prior to HSV-1 infection. In addition, T cell expansion was comparable to that seen in untreated controls if MPA-treated mice were administered recombinant soluble CD154 (CD40L) concomitant with their mucosal infection. In contrast, the immunomodulatory effects of MPA were infection site dependent, because MPA-treated mice exhibited normal expansion of virus-specific T cells when infection was systemic rather than mucosal. Taken together, our results reveal that the administration of MPA prior to viral infection of mucosal tissue impairs DC activation, virus-specific T cell expansion, and development of virus-specific immunological memory.
Epithelial Cell-Derived IL-25, but Not Th17 Cell-Derived IL-17 or IL-17F, Is Crucial for Murine Asthma
Authors: Suzukawa Maho , Morita Hideaki , Nambu Aya , Arae Ken , Shimura Eri , Shibui Akiko , Yamaguchi Sachiko , Suzukawa Keigo , Nakanishi Wakako , Oboki Keisuke , Kajiwara Naoki , Ohno Tatsukuni , Ishii Akina , Körner Heinrich , Cua Daniel J. , Suto Hajime , Yoshimoto Takayuki , Iwakura Yoichiro , Yamasoba Tatsuya , Ohta Ken , Sudo Katsuko , Saito Hirohisa , Okumura Ko , Broide David H. , Matsumoto Kenji , Nakae Susumu 
Published: September 2012

Abstract
IL-17A, IL-17F, and IL-25 are ligands for IL-17RA. In the current study, we demonstrated that IL-25–deficient mice—but not IL-17A–, IL-17F–, IL-17A/F–, IL-23p19–, or retinoic acid-related orphan receptor (ROR)-γt–deficient mice—showed significant suppression of 1) the number of eosinophils and the levels of proinflammatory mediators in bronchoalveolar lavage fluids, 2) airway hyperresponsiveness to methacholine, and 3) OVA-specific IgG1 and IgE levels in the serum during OVA-induced Th2-type/eosinophilic airway inflammation. The IL-25 deficiency did not affect lung dendritic cell migration or Ag-specific memory–Th2 cell expansion during Ag sensitization. Adoptive transfer of T cells, mast cells, or bone marrow cells from IL-25–deficient mice revealed that induction of Th2-type/eosinophilic airway inflammation was dependent on activation of lung epithelial cells and eosinophils by IL-25 produced by airway structural cells such as epithelial cells but not by such hematopoietic stem-cell-origin immune cells as T cells and mast cells. Therefore, airway structural cell-derived IL-25—rather than Th17 cell-derived IL-17A and IL-17F—is responsible for induction of local inflammation by promoting activation of lung epithelial cells and eosinophils in the elicitation phase of Th2-type/eosinophilic airway inflammation. It is not required for Ag-specific Th2 cell differentiation in the sensitization phase.
Lyn Signaling To Upregulate GANP Is Critical for the Survival of High-Affinity B Cells in Germinal Centers of Lymphoid Organs
Authors: Kuwahara Kazuhiko , Nakaya Teruo , Phimsen Suchada , Toda Teppei , Kitabatake Masahiro , Kaji Tomohiro , Takemori Toshitada , Watanabe Takeshi , Sakaguchi Nobuo 
Published: September 2012

AbstractSignals through BCR and costimulatory molecules play essential roles in selecting high-affinity B cells with Ig V-region mutations in the germinal centers (GCs) of peripheral lymphoid organs. Lyn-deficient (lyn−/−) mice show impaired BCR signal triggering for cell proliferation and GC formation, causing hyper-IgM, and display autoimmunity after aging. In this study, we demonstrate that Lyn-mediated signaling to upregulate GANP is essential for the survival of mature GC-like (mGC) B cells with high-affinity type BCR mutations upon Ag immunization. Transgenic ganp expression into lyn−/− mice did not recover the Lyn-deficient phenotype with regard to B cell differentiation, serum Igs, and impaired GC formation in spleens after immunization with nitrophenyl-chicken γ-globulin, but it markedly rescued cell survival of mGC B cells by suppressing DNA damage, thereby increasing the frequency of the Trp33-to-Leu mutation in the IgVH-186.2 region and affinity maturation of nitrophenyl-binding B cells. GANP may play a critical role in Lyn-mediated signaling for the selection of high-affinity B cells in peripheral lymphoid organs.
Efficient Clearance of Early Apoptotic Cells by Human Macrophages Requires M2c Polarization and MerTK Induction
Authors: Zizzo Gaetano , Hilliard Brendan A. , Monestier Marc , Cohen Philip L. 
Published: September 2012

Abstract
Mer tyrosine kinase (MerTK) is a major macrophage apoptotic cell (AC) receptor. Its functional impairment promotes autoimmunity and atherosclerosis, whereas overexpression correlates with poor prognosis in cancer. However, little is known about mechanisms regulating MerTK expression in humans. We found that MerTK expression is heterogenous among macrophage subsets, being mostly restricted to anti-inflammatory M2c (CD14+CD16+CD163+CD204+CD206+CD209−) cells, differentiated by M-CSF or glucocorticoids. Small numbers of MerTK+ “M2c-like” cells are also detectable among circulating CD14brightCD16+ monocytes. MerTK expression levels adapt to changing immunologic environment, being suppressed in M1 and M2a macrophages and in dendritic cells. Remarkably, although glucocorticoid-induced differentiation is IL-10 independent, M-CSF–driven M2c polarization and related MerTK upregulation require IL-10. However, neither IL-10 alone nor TGF-β are sufficient to fully differentiate M2c (CD16+CD163+MerTK+) macrophages. M-CSF and IL-10, both released by T lymphocytes, may thus be required together to promote regulatory T cell–mediated induction of anti-inflammatory monocytes-macrophages. MerTK enables M2c macrophages to clear early ACs more efficiently than other macrophage subsets, and it mediates AC clearance by CD14brightCD16+ monocytes. Moreover, M2c cells release Gas6, which in turn amplifies IL-10 secretion via MerTK. IL-10–dependent induction of the Gas6/MerTK pathway may, therefore, constitute a positive loop for M2c macrophage homeostasis and a critical checkpoint for maintenance of anti-inflammatory conditions. Our findings give new insight into human macrophage polarization and favor a central role for MerTK in regulation of macrophage functions. Eliciting M2c polarization can have therapeutic utility for diseases such as lupus, in which a defective AC clearance contributes to initiate and perpetuate the pathological process.
Selective Sequestration of STAT1 in the Cytoplasm via Phosphorylated SHP-2 Ameliorates Murine Experimental Colitis
Authors: Wu Xingxin , Guo Wenjie , Wu Limei , Gu Yanhong , Gu Liyun , Xu Suhai , Wu Xuefeng , Shen Yan , Ke Yuehai , Tan Renxiang , Sun Yang , Xu Qiang 
Published: September 2012

Abstract
The side effects of current immunosuppressive drugs have impeded the development of therapies for immune diseases. Selective regulation of STAT signaling is an attractive strategy for treating immune disorders. In this study, we used a small-molecule compound to explore possible means of targeting STAT1 for the treatment of Th1-mediated inflammation. Selective regulation of STAT1 signaling in T cells from C57BL/6 mice was accomplished using fusaruside, a small-molecule compound that triggers the tyrosine phosphorylation of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2). The interaction of tyrosine phosphorylated SHP-2 (pY-SHP-2) with cytosolic STAT1 prevented the recruitment of STAT1 to IFN-γR and specifically inhibited STAT1 signaling, resulting in a reduction in Th1 cytokine production and an improvement in 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in mice. Blocking the pY-SHP-2–STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside, resulting in STAT1 activation and worsened colitis. The fusaruside-induced ability of pY-SHP-2 to selectively sequestrate STAT1 from recruitment to the receptor is independent of its function as a phosphatase, demonstrating a novel role for SHP-2 in regulating both STAT1 signaling and Th1-type immune responses. These findings could lead to increased options for the treatment of Crohn’s disease and other Th1-mediated inflammatory diseases.
Inducible Tertiary Lymphoid Structures, Autoimmunity, and Exocrine Dysfunction in a Novel Model of Salivary Gland Inflammation in C57BL/6 Mice
Authors: Bombardieri Michele , Barone Francesca , Lucchesi Davide , Nayar Saba , van den Berg Wim B. , Proctor Gordon , Buckley Christopher D. , Pitzalis Costantino 
Published: September 2012

Abstract
Salivary glands in patients with Sjögren’s syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules, follicular dendritic cell networks, functional B cell activation with expression of activation-induced cytidine deaminase, as well as local differentiation of autoreactive plasma cells. The mechanisms that trigger ELS formation, autoimmunity, and exocrine dysfunction in SS are largely unknown. In this article, we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance, and salivary hypofunction after delivery of a replication-deficient adenovirus-5 in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration toward the development of SS-like periductal lymphoid aggregates within 2 wk from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7+/activation-induced cytidine deaminase+ germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19, and lymphotoxin-β, and is associated with development of anti-nuclear Abs in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 wk post-AdV infection, consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms that regulate ELS formation and their role in exocrine dysfunction and autoimmunity in SS.
Cutting Edge: Krüppel-like Factor 2 Is Required for Phenotypic Maintenance but Not Development of B1 B Cells
Authors: Hart Geoffrey T. , Peery Stephen L. , Hamilton Sara E. , Jameson Stephen C. 
Published: September 2012

Abstract
Several recent studies reported that Krüppel-like factor (KLF)2 controls trafficking, development, and function of B cells. Conditional B cell KLF2 knockout mice have increased numbers of marginal zone B cells and decreased numbers of B1 phenoytpe cells. However, it was unclear whether KLF2 is required for B1 B cell development, survival, or phenotypic maintenance. We show that B1 phenotype B cells are present in neonatal mice with B cell-specific KLF2 deficiency, suggesting that B1 differentiation can occur even in the absence of KLF2. Furthermore, by use of an inducible knockout strategy, we show that deletion of KLF2 in mature B1 cells causes loss of phenotypic markers associated with B1 cell identity, but it has a minimal effect on short-term cell survival. Taken together, our findings suggest that KLF2 is necessary for the maintenance of B1 cell identity rather than differentiation or survival of the population.
TCR Bias and HLA Cross-Restriction Are Strategies of Human Brain-Infiltrating JC Virus-Specific CD4+ T Cells during Viral Infection
Authors: Yousef Sara , Planas Raquel , Chakroun Karima , Hoffmeister-Ullerich Sabine , Binder Thomas M. C. , Eiermann Thomas H. , Martin Roland , Sospedra Mireia 
Published: September 2012

Abstract
Virus-specific CD4+ T cells play a central role in control of viral pathogens including JC polyoma virus (JCV) infection. JCV is a ubiquitous small DNA virus that leads to persistent infection of humans with no clinical consequences. However, under circumstances of immunocompromise, it is able to cause an opportunistic and often fatal infection of the brain called progressive multifocal leukoencephalopathy (PML). PML has emerged as a serious adverse event in multiple sclerosis patients treated with the anti–VLA-4 mAb natalizumab, which selectively inhibits cell migration across the blood–brain barrier and the gut’s vascular endothelium thus compromising immune surveillance in the CNS and gut. In a multiple sclerosis patient who developed PML under natalizumab treatment and a vigorous immune response against JCV after Ab washout, we had the unique opportunity to characterize in detail JCV-specific CD4+ T cell clones from the infected tissue during acute viral infection. The in-depth analysis of 14 brain-infiltrating, JCV-specific CD4+ T cell clones demonstrated that these cells use an unexpectedly broad spectrum of different strategies to mount an efficient JCV-specific immune response including TCR bias, HLA cross-restriction that increases avidity and influences in vivo expansion, and a combination of Th1 and Th1-2 functional phenotypes. The level of combinatorial diversity in TCR– and HLA–peptide interactions used by brain-infiltrating, JCV-specific CD4+ T cells has not, to our knowledge, been reported before in humans for other viral infections and confirms the exceptional plasticity that characterizes virus-specific immune responses.
High-Resolution Melting Analysis as a Sensitive Prescreening Diagnostic Tool to Detect KRAS, BRAF, PIK3CA, and AKT1 Mutations in Formalin-Fixed, Paraffin-Embedded Tissues
Authors: Ney Jasmin Teresa , Froehner Stefanie , Roesler Angelika , Buettner Reinhard , Merkelbach-Bruse Sabine 
Published: September 2012

Context.—As the availability of targeted therapies for several tumor types increases, the need for rapid and sensitive mutation screening is growing. KRAS mutations constitutively activate the RAS/RAF/mitogen-activated protein kinase (MAPK) pathway and therefore play an important role in anti–epidermal growth factor receptor therapy for patients with colorectal cancers. Mutationally activated PIK3CA and AKT1 genes are promising therapeutic targets in breast cancer. In 60% to 70% of malignant melanomas, a mutation in BRAF can be found. Thus, the blocking of the oncogenic signaling induced by this mutation is now used as treatment approach.Objective.—To establish high-resolution melting assays for routinely used predictive analyses of KRAS, AKT1, PIK3CA, and BRAF mutations.Design.—High-resolution melting assays were developed by using specifically designed primers and genomic DNA isolated either from cell lines or formalin-fixed paraffin-embedded tissues, oligonucleotides, or plasmids. Melting curve analyses were performed on the LightCyler platform and mutation analyses were additionally confirmed by Sanger sequencing.Results.—We developed high-resolution melting assays by using genomic DNA containing the desired mutation, which enabled us to detect percentages of mutated DNA (3.1% to 12.5%) mixed in a wild-type background. Assays were evaluated by hybridization probes and/or Sanger sequencing to exclude pseudogene amplification. The high-resolution melting assays were validated with genomic DNA from different tumor entities. The concordance between Sanger sequencing and high-resolution melting was 99% for KRAS exon 2 and PIK3CA exon 20 and 100% for the remaining assays.Conclusions.—High-resolution melting provides a valid and powerful tool for detecting genomic mutations efficiently.
Brigitte Bardot, ou le « problème » de la comédie au féminin
Authors: Vincendeau Ginette 
Published: September 2012

Cet article examine les rapports entre comédie etgenderdans le contexte du cinéma français en prenant comme cas d’étude les comédies de Brigitte Bardot. Il s’inscrit dans la double perspective des études anglo-américaines sur le genre, d’une part, notamment les travaux d’inspiration féministe et psychanalytique de Kathleen Rowe sur la comédie, et sur lesstar studiesinaugurées par Richard Dyer, d’autre part. Après une réflexion sur les rapports entre récits féminins comiques et vedettariat, l’article analyse l’évolution des personnages de la star dans ses comédies populaires, de la « gamine » des débuts, aux personnages qui la positionnent dans le registre de lasex comedypuis de ladumb blonde. Cette étude offre ainsi une perspective sur la dimension genrée des films comiques en France ainsi que sur un aspect central mais d’habitude occulté de lastar personade Brigitte Bardot.
Les enquêtrices dans le film policier français des années 1970 et 1980 : des femmes qui en savent trop ?
Authors: Le Gras Gwénaëlle 
Published: September 2012

Alors que dans le cinéma policier français, les rôles attribués aux femmes sont habituellement des rôles de garce ou de victime, apparaissent sous l’Occupation des figures d’enquêtrices, essentiellement dans la comédie policière, qui ne ressurgiront de manière significative qu’au tournant des années 1970. Ces nouvelles héroïnes, jouées par des vedettes, incarnent la Loi, officieusement ou officiellement, et bénéficient de prérogatives traditionnellement masculines, en réponse aux changements législatifs qui permettent aux femmes d’accéder à des métiers « d’hommes » et d’avoir, en théorie, un statut faisant d’elles leurs égales. Après une analyse statistique de la présence et de l’évolution de cette figure nouvelle dans le film policier français, l’auteure étudiera les effets contradictoires, sur le plan narratif et esthétique, qu’elle a sur le genre, entre fétichisme et féminisme populaire, à travers sa construction et sa réception dans La femme flic (Boisset, 1980) et dans Vivement dimanche ! (Truffaut, 1983).
Femme active et femme au foyer dans le woman’s horror film américain des années 2000 : ambivalences, contradictions et impasse post-féministe
Authors: Fakhry Pascale 
Published: September 2012

Les années 2000 voient la sortie d’un grand nombre de films d’horreur qui sont aussi des woman’s films. Ces oeuvres montrent une femme confrontée à des créatures monstrueuses, souvent d’origine surnaturelle, et à des problèmes spécifiquement féminins, tels que la maternité et le conflit travail/foyer. À travers l’analyse détaillée de deux woman’s horror films de l’époque — The Ring (Gore Verbinski, 2002) et The Others (Alejandro Amenábar, 2001) —, l’auteure se propose de comparer, dans un premier temps, le traitement réservé à la femme active et à la femme au foyer dans leur relation à la maternité et aux rôles de victime, de monstre ou d’héroïne qu’on leur attribue au sein du récit d’horreur. L’ambivalence du discours tenu par le woman’s horror film sur ses personnages principaux féminins est, dans un deuxième temps, mise en relation avec l’émergence du post-féminisme et son influence grandissante sur la culture populaire américaine des années 2000.
Photoresponsive Molecules in Well‐Defined Nanoscale Environments
Authors: Zheng Yue Bing , Pathem Bala Krishna , Hohman J. Nathan , Thomas John C. , Kim Moonhee , Weiss Paul S. 
Published: August 2012

AbstractStimuli‐responsive molecules are key building blocks of functional molecular materials and devices. These molecules can operate in a range of environments. A molecule's local environment will dictate its conformation, reactivity, and function; by controlling the local environment we can ultimately develop interfaces of individual molecules with the macroscopic environment. By isolating molecules in well‐defined environments, we are able to obtain both accurate measurements and precise control. We exploit defect sites in self‐assembled monolayers (SAMs) to direct the functional molecules into precise locations, providing a basis for the measurements and engineering of functional molecular systems. The structure and functional moieties of the SAM can be tuned to control not only the intermolecular interactions but also molecule‐substrate interactions, resulting in extraction or control of desired molecular functions. Herein, we report our progress toward the assembly and measurements of photoresponsive molecules and their precise assemblies in SAM matrices.
Integration of Photoswitchable Proteins, Photosynthetic Reaction Centers and Semiconductor/Biomolecule Hybrids with Electrode Supports for Optobioelectronic Applications
Authors: Wang Fuan , Liu Xiaoqing , Willner Itamar 
Published: August 2012

AbstractLight‐triggered biological processes provide the principles for the development of man‐made optobioelectronic systems. This Review addresses three recently developed topics in the area of optobioelectronics, while addressing the potential applications of these systems. The topics discussed include: (i) the reversible photoswitching of the bioelectrocatalytic functions of redox proteins by the modification of proteins with photoisomerizable units or by the integration of proteins with photoisomerizable environments; (ii) the integration of natural photosynthetic reaction centers with electrodes and the construction of photobioelectrochemical cells and photobiofuel cells; and (iii) the synthesis of biomolecule/semiconductor quantum dots hybrid systems and their immobilization on electrodes to yield photobioelectrochemical and photobiofuel cell elements. The fundamental challenge in the tailoring of optobioelectronic systems is the development of means to electrically contact photoactive biomolecular assemblies with the electrode supports. Different methods to establish electrical communication between the photoactive biomolecular assemblies and electrodes are discussed. These include the nanoscale engineering of the biomolecular nanostructures on surfaces, the development of photoactive molecular wires and the coupling of photoinduced electron transfer reactions with the redox functions of proteins. The different possible applications of optobioelectronic systems are discussed, including their use as photosensors, the design of biosensors, and the construction of solar energy conversion and storage systems.
Facile synthesis and micellization of biodegradable poly(decamethylene succinate)‐graft‐poly(ethylene glycol)
Authors: Zhu Guixiang , Wang Ying , Zhu Weipu , Zhu Kui , Xu Xiaoyan , Shen Zhiquan 
Published: August 2012

AbstractIn this article, we report the facile one‐pot synthesis of poly(decamethylene succinate) (PDS) with multiple hydroxyl groups by direct polycondensation with malic acid (MA) as the functional monomer and dysprosium triflate as the chemoselective catalyst at 80°C. The secondary hydroxyl groups of malic units were inactive during the polycondensation process. The density of hydroxyl groups of the copolymer could be well‐controlled by the molar ratio of succinic acid and MA in the feed. These hydroxylated PDSs were grafted by poly(ethylene glycol) (PEG) through a simple esterification reaction; this resulted in amphiphilic PDS‐g‐PEG copolymers, which could undergo micellization in aqueous media to form nanosized aggregates with diverse morphologies and diameters. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013.