bluuebunny/crossref_metadata_2025_split huggingface dataset:
T Cell–Dendritic Cell Interaction Dynamics during the Induction of Respiratory Tolerance and Immunity
Authors: Bakočević Nadja , Worbs Tim , Davalos-Misslitz Ana , Förster Reinhold 
Published: December 2009

Abstract
Dendritic cells (DCs) residing in the lung are known to acquire inhaled Ag and, after migration to the draining bronchial lymph node (brLN), to present it to naive T cells in an either tolerogenic or immunogenic context. To visualize endogenous lung-derived DCs, we applied fluorescent latex beads (LXs) intratracheally, thereby in vivo labeling the majority of phagocytic cells within the lung. Of note, LX-bearing cells subsequently arriving in the draining brLN were found to represent lung-derived migratory DCs. Imaging explanted brLN by two-photon laser-scanning microscopy, we quantitatively analyzed the migration and interaction behavior of naive CD4+ T cells and endogenous, lung-derived DC presenting airway-delivered Ag under inflammatory or noninflammatory conditions. Ag-specific naive CD4+ T cells engaged in stable as well as transient contacts with LX-bearing DCs in both situations and displayed similar overall motility kinetics, including a pronounced decrease in motility at 16–20 h after antigenic challenge. In contrast, the comparative analysis of T cell–DC cluster sizes as well as contact durations strongly suggests that lung-derived migratory DCs and naive CD4+ T cells form more stable, long-lasting contacts under inflammatory conditions favoring the induction of respiratory immunity.
Formation of a Mast Cell Synapse: FcεRI Membrane Dynamics upon Binding Mobile or Immobilized Ligands on Surfaces
Authors: Carroll-Portillo Amanda , Spendier Kathrin , Pfeiffer Janet , Griffiths Gary , Li Haitao , Lidke Keith A. , Oliver Janet M. , Lidke Diane S. , Thomas James L. , Wilson Bridget S. , Timlin Jerilyn A. 
Published: December 2009

Abstract
FcεRI on mast cells form a synapse when presented with mobile, bilayer-incorporated Ag. In this study, we show that receptor reorganization within the contacting mast cell membrane is markedly different upon binding of mobile and immobilized ligands. Rat basophilic leukemia mast cells primed with fluorescent anti-DNP IgE were engaged by surfaces presenting either bilayer-incorporated, monovalent DNP-lipid (mobile ligand), or chemically cross-linked, multivalent DNP (immobilized ligand). Total internal reflection fluorescence imaging and electron microscopy methods were used to visualize receptor reorganization at the contact site. The spatial relationships of FcεRI to other cellular components at the synapse, such as actin, cholesterol, and linker for activation of T cells, were also analyzed. Stimulation of mast cells with immobilized polyvalent ligand resulted in typical levels of degranulation. Remarkably, degranulation also followed interaction of mast cells, with bilayers presenting mobile, monovalent ligand. Receptors engaged with mobile ligand coalesce into large, cholesterol-rich clusters that occupy the central portion of the contacting membrane. These data indicate that FcεRI cross-linking is not an obligatory step in triggering mast cell signaling and suggest that dense populations of mobile receptors are capable of initiating low-level degranulation upon ligand recognition.
Mammalian Clock Gene Cryptochrome Regulates Arthritis via Proinflammatory Cytokine TNF-α
Authors: Hashiramoto Akira , Yamane Takashi , Tsumiyama Ken , Yoshida Kohsuke , Komai Koichiro , Yamada Hiroyuki , Yamazaki Fumiyoshi , Doi Masao , Okamura Hitoshi , Shiozawa Shunichi 
Published: December 2009

Abstract
The mammalian clock genes, Period and Cryptochrome (Cry), regulate circadian rhythm. We show that circadian rhythmicity and rhythmic expression of Period in the nuclei of inflammatory synovial cells and spleen cells are disturbed in mouse models of experimental arthritis. Expressions of other clock genes, Bmal1 and Dbp, are also disturbed in spleen cells by arthritis induction. Deletion of Cry1 and Cry2 results in an increase in the number of activated CD3+ CD69+ T cells and a higher production of TNF-α from spleen cells. When arthritis is induced, Cry1−/−Cry2−/− mice develop maximal exacerbation of joint swelling, and upregulation of essential mediators of arthritis, including TNF-α, IL-1β and IL-6, and matrix metalloproteinase-3. Wee-1 kinase is solely upregulated in Cry1−/−Cry2−/− mice, in line with upregulation of c-Fos and Wee-1 kinase in human rheumatoid arthritis. The treatment with anti–TNF-α Ab significantly reduced the severity and halted the progression of the arthritis of Cry1−/−Cry2−/− mice and vice versa, ectopic expression of Cry1 in the mouse embryonic fibroblast from Cry1−/−Cry2−/− mice significantly reduced the trans activation of TNF-α gene. Thus, the biological clock and arthritis influence each other, and this interplay can influence human health and disease.
Long‐interval T2‐weighted subtraction magnetic resonance imaging: A powerful new outcome measure in multiple sclerosis trials
Authors: Moraal Bastiaan , van den Elskamp Ivo J. , Knol Dirk L. , Uitdehaag Bernard M. J. , Geurts Jeroen J. G. , Vrenken Hugo , Pouwels Petra J. W. , van Schijndel Ronald A. , Meier Dominik S. , Guttmann Charles R. G. , Barkhof Frederik 
Published: December 2009

AbstractObjectiveTo compare long‐interval T2‐weighted subtraction (T2w‐Sub) imaging with monthly gadolinium‐enhanced T1‐weighted (Gd‐T1w) imaging for (1) detection of active lesions, (2) assessment of treatment efficacy, and (3) statistical power, in a multiple sclerosis (MS), phase 2, clinical trial setting.MethodsMagnetic resonance imaging (MRI) data over 9 months from 120 patients (61 treatment, 59 placebo) from the oral temsirolimus trial were used. T2w‐Sub images were scored for active lesions, independent of the original reading of the monthly Gd‐T1w images. Treatment efficacy was evaluated using the nonparametric Mann‐Whitney U test, and parametric negative binomial (NB)‐regression and power calculations were conducted.ResultsDatasets from 116 patients (58 treatment, 58 placebo) were evaluated. The mean number of T2w‐Sub lesions in the treatment group was 3.0 (±4.6) versus 5.9 (±8.8) for placebo; the mean cumulative number of new Gd‐T1w lesions in the treatment group was 5.5(±9.1) versus 9.1(±17.2) for placebo. T2w‐Sub imaging showed increased power to assess treatment efficacy compared with Gd‐T1w imaging, when evaluated by Mann‐Whitney U test (p = 0.017 vs p = 0.177), or NB‐regression without (p = 0.011 vs p = 0.092) or with baseline adjustment (p < 0.001 vs p = 0.002). Depending on the magnitude of the simulated treatment effect, sample size calculations showed reductions of 22 to 34% in the number of patients (translating into reductions of 81–83% in the number of MRI scans) needed to detect a significant treatment effect in favor of T2w‐Sub imaging.InterpretationCompared with monthly Gd‐T1w imaging, long‐interval T2w‐Sub MRI exhibited increased power to assess treatment efficacy, and could greatly increase the cost‐effectiveness of phase 2 MS trials by limiting the number of patients, contrast injections, and MRI scans needed. ANN NEUROL 2010;67:667–675
Zwitterionische Verwandte kationischer Platinmetallkomplexe: Anwendungen in der stöchiometrischen und katalytischen σ‐Bindungsaktivierung
Authors: Stradiotto Mark , Hesp Kevin D. , Lundgren Rylan J. 
Published: January 2010

AbstractZwitterionische Komplexe von Platinmetallen, die sich durch eine formale Ladungstrennung zwischen einem kationischen Metallfragment und einem negativ geladenen Hilfsliganden auszeichnen, vereinigen das wünschenswerte Reaktivitätsprofil verwandter kationischer Komplexe mit der besseren Löslichkeit und Lösungsmitteltoleranz neutraler Spezies. Daher sind zwitterionische Komplexe dieser Art interessante Kandidaten für vielfältige Anwendungen, insbesondere für Reaktionen, in denen E‐H‐ und E‐C‐σ‐Bindungen zu Hauptgruppenelementen E gespalten und/oder gebildet werden. Hier werden Fortschritte bei der Entwicklung von Hilfsliganden vorgestellt, die die Synthese von Zwitterionen der Platinmetalle ermöglichten, und die Ergebnisse stöchiometrischer und katalytischer Untersuchungen werden zusammengefasst, wobei die Reaktivitäten der Zwitterionen und ihrer üblicherweise eingesetzten kationischen Verwandten bei der σ‐Bindungsaktivierung verglichen werden.
A longitudinal analysis of urinary biochemical markers and bone mineral density in STR/Ort mice as a model of spontaneous osteoarthritis
Authors: Sarukawa Junichiro , Takahashi Masaaki , Doi Mitsuhito , Suzuki Daisuke , Nagano Akira 
Published: January 2010

AbstractObjectiveTo investigate the longitudinal changes both in the urinary concentrations of biochemical markers and in bone mineral density (BMD) during disease progression in the STR/Ort mouse model of osteoarthritis (OA).MethodsMale STR/Ort mice were studied, with CBA mice used as nonarthritic controls. Radiographic evaluation and grading of the knee and measurements of urinary C‐terminal crosslinking telopeptide of type II collagen (CTX‐II), pyridinoline (Pyr), and deoxypyridinoline were performed between 8 weeks and 40 weeks of age. The BMD of the femoral shaft was measured from 20 weeks to 40 weeks of age and adjusted for body weight. Histologic evaluation and grading were performed at 40 weeks of age. STR/Ort mice were divided into 2 subgroups (STR OA and STR non‐OA) based on histologic grading.ResultsNo significant differences between STR/Ort and CBA mice were observed for any biochemical marker or BMD at any time point. Urinary CTX‐II levels and BMD in the STR OA subgroup were higher than those in the STR non‐OA subgroup before radiographic changes of OA were apparent. Higher urinary Pyr levels in the STR OA subgroup were observed at the advanced stage of OA.ConclusionUrinary CTX‐II could be a useful marker in the early diagnosis and predicting the progression of OA, and urinary Pyr may be a potential marker to assess the severity of OA at an advanced stage. An increase in BMD prior to the establishment of radiographic OA may be related to the induction of OA.
Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model
Authors: Lin Philana Ling , Myers Amy , Smith Le'Kneitah , Bigbee Carolyn , Bigbee Matthew , Fuhrman Carl , Grieser Heather , Chiosea Ion , Voitenek Nikolai N. , Capuano Saverio V. , Klein Edwin , Flynn JoAnne L. 
Published: January 2010

AbstractObjectiveAn increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor α (TNFα)–neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non‐human primate model.MethodsCynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6–8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF‐neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55‐TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison.ResultsAdministration of TNF‐neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin‐12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria‐induced interferon‐γ production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes.ConclusionThese findings have important clinical implications for determining the mechanism of TNF neutralization–related tuberculosis.
Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll‐like receptors
Authors: Sacre Sandra , Medghalchi Mino , Gregory Bernard , Brennan Fionula , Williams Richard 
Published: January 2010

AbstractObjectiveSelective serotonin reuptake inhibitors (SSRIs), in addition to their antidepressant effects, have been reported to have antiinflammatory effects. The aim of this study was to assess the antiarthritic potential of 2 SSRIs, fluoxetine and citalopram, in murine collagen‐induced arthritis (CIA) and in a human ex vivo disease model of rheumatoid arthritis (RA).MethodsFollowing therapeutic administration of SSRIs, paw swelling was assessed and clinical scores were determined daily in DBA/1 mice with CIA. Joint architecture was examined histologically at the end of the treatment period. Cultures of human RA synovial membranes were treated with SSRIs, and cytokine production was measured. Toll‐like receptor (TLR) function was examined in murine and human macrophages, human B cells, and human fibroblast‐like synovial cells treated with SSRIs.ResultsBoth SSRIs significantly inhibited disease progression in mice with CIA, with fluoxetine showing the greatest degree of efficacy at the clinical and histologic levels. In addition, both drugs significantly inhibited the spontaneous production of tumor necrosis factor, interleukin‐6, and interferon‐γ–inducible protein 10 in human RA synovial membrane cultures. Fluoxetine and citalopram treatment also inhibited the signaling of TLRs 3, 7, 8, and 9, providing a potential mechanism for their antiinflammatory action.ConclusionFluoxetine and citalopram treatment selectively inhibit endosomal TLR signaling, ameliorate disease in CIA, and suppress inflammatory cytokine production in human RA tissue. These data highlight the antiarthritic potential of the SSRI drug family and provide further evidence of the involvement of TLRs in the pathogenesis of RA. The SSRIs may provide a template for potential antiarthritic drug development.
Creating a new synergy on technical and vocational education via a general purpose computer interface unit
Authors: Ari Murat 
Published: January 2010

AbstractThis study is focused on improving and sustaining the analog experiment sets used in the laboratory applications of technical and vocational education (TVE) particularly in Electrical and Electronics by computerizing them to extend their usage period. The study is mainly about the improvement of the V‐LAB and D‐LAB interfaces. As the distance education has been increasingly and widely adopted in the recent years, it became apparent that some laboratory applications can also be adapted into the distance education via improvements including computerization, Internet connectivity, and remote monitoring technologies. This article describes the technical capabilities of the improved analog experiment laboratory systems and discusses the limitations and potential further improvements. The present work will also be a good reference to vocational education. © 2010 Wiley Periodicals, Inc. Comput Appl Eng Educ 20: 364–373, 2012
The tbx/bHLH transcription factor mga regulates gata4 and organogenesis
Authors: Rikin Amir , Evans Todd 
Published: December 2009

AbstractThe mga gene encodes a unique transcription factor containing both TBOX and bHLHzip DNA‐binding domains. Here we describe the structure, expression pattern, and loss‐of‐function phenotype for zebrafish mga. The mga gene is conserved with mammalian homologs for both DNA‐binding domains. It is expressed maternally, and subsequently in the developing brain, heart, and gut, and its depletion causes morphogenetic defects in each of these organ systems. The heart and gut phenotypes are similar to those described previously for loss of gata4, and the mga morphant shows increased levels of gata4 transcripts in lateral mesoderm. Knockdown of gata4 rescues the early heart‐looping defect (but not the gut defect), indicating that mga restricts the normal levels of Gata4 required for heart tube looping, while both genes are important for gut development. Transcript profiling experiments show that mga functions early to influence key regulators of mesendoderm, including tbx6, cas, and sox17. Developmental Dynamics 239:535–547, 2010. © 2009 Wiley‐Liss, Inc.
Agonist‐selective signaling of G protein‐coupled receptor: Mechanisms and implications
Authors: Zheng Hui , Loh Horace H. , Law Ping‐Yee 
Published: January 2010

AbstractAgonist‐selective signaling or ligand‐biased signaling of G protein‐coupled receptor (GPCR) has become the focus of an increasing number of laboratories. The principle of this concept is that agonist possesses different abilities to activate different signaling pathways. Current review summarizes the observations of agonist‐selective signaling of various GPCRs, indicating the significance of agonist‐selective signaling in biological processes. In addition, current review also provides an overview on how agonist‐selective signaling is initiated. Especially, the relationship between GPCR‐G protein interaction and GPCR‐β‐arrestin interaction is discussed in depth. © 2010 IUBMB IUBMB Life, 62(2): 112–119, 2010
Ab initio periodic study of the conformational behavior of glycine helical homopeptides
Authors: Ferrari Anna Maria , Civalleri Bartolomeo , Dovesi Roberto 
Published: January 2010

AbstractRepresentative helicoidal conformations of polyglycine infinite chains have been investigated by using periodic boundary conditions, the B3LYP hybrid functional, and large basis sets, by means of the CRYSTAL code. The exploitation of the helix roto‐translational symmetry permits to optimize at a relatively low cost the structure of systems whose unit cell contains more than 300 atoms, much larger than the one investigated till now. In the present calculations, the helix symmetry is exploited at three levels. First, for the automatic generation of the structure. Second, for the calculation of the one‐ and two‐electron integrals that enter into the Fock matrix definition. Only the irreducible wedge of the Fock matrix is computed. Finally, for the diagonalization of the Fock matrix, where each irreducible representation is separately treated. The efficiency and accuracy of the computational scheme are documented, by considering cells containing up to 47 glycine residues. Results are compared with previous calculations and available experimental data. The role of hydrogen bonding in stabilizing polyglycine conformers is also addressed. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Factors associated with developing cholesteatoma: A study of 45,980 children with middle ear disease
Authors: Spilsbury Katrina , Miller Ian , Semmens James B. , Lannigan Francis J. 
Published: January 2010

AbstractObjectives/Hypothesis:To identify factors associated with the rate of developing cholesteatoma following ventilation tube insertion (VTI).Study Design:A population‐based retrospective cohort study.Methods:Administrative health data from all private and public hospitals in Western Australia for children who had at least one VTI from 1980 to 2004 was used to identify subsequent hospital admissions for cholesteatoma. Main outcome measures were time to cholesteatoma (survival) outcomes, including hazard ratios, log‐rank tests, and Kaplan‐Meier failure functions.Results:There were 45,980 children who underwent at least one VTI from 1980 to 2004 with 460 subsequently developing cholesteatoma. The cumulative percentage of children who developed cholesteatoma within 15 years after one VTI procedure was 0.9% (95% confidence interval [CI], 0.8–1.0), after two VTIs 2.1% (95% CI, 1.6–2.3), after three VTIs 3.8% (95% CI, 2.9–4.8), and after four or more VTIs 5.2% (95% CI, 4.0–6.7). The rate of developing cholesteatoma increased 10% (95% CI, 6–14) for each additional year in age before first VTI. For children who underwent two or more VTIs, the rate of cholesteatoma increased 21% (95% CI, 12–32) with each additional year between VTIs. Adenoid removal was associated with a 27% (95% CI, 11–40) reduction in the rate of developing cholesteatoma.Conclusions:Children with persistent or refractory middle ear disease who required multiple VTIs were at increased risk of cholesteatoma. First ventilation tubes inserted at an early age, subsequent ventilation tubes inserted without delay, and adenoid removal were associated with a reduced rate of cholesteatoma development. Laryngoscope, 2010
Synthesis and Characterisation of Poly[oligo(ε‐caprolactone)L‐malate‐graft‐poly(L‐lactide)]
Authors: Hahn Christian , Keul Helmut , Möller Martin 
Published: January 2010

AbstractGraft copolyesters with a PCL backbone and PLLA side chains were successfully prepared in three steps avoiding transesterification. First ε‐caprolactone was polymerised with 1,6‐hexane diol as initiator to obtain hydroxytelechelic oligo(ε‐caprolactone)s. These diols were then subjected—in the second step—to polycondensation with L‐malic acid yielding in linear poly[oligo(ε‐caprolactone)L‐malate] having secondary hydroxyl functions in the side chain. For both reactions scandium triflate Sc(OTf)3 was used as a catalyst. In the third step various amounts of L‐lactide were grafted from the polymer backbone using Zn(oct)2 as catalyst. The successful reaction was confirmed by NMR and SEC (size exclusion chromatography) analysis. Further the thermal properties of the graft copolymers with different graft lengths were determined via differential scanning calorimetry.magnified image