bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectopic Activation of Mycobacterium tuberculosis-Specific CD4+ T Cells in Lungs of CCR7−/− Mice
Authors: Olmos Sofia , Stukes Sabriya , Ernst Joel D. 
Published: December 2009

Abstract
Initiation of an adaptive cellular immune response depends on intimate interactions with APCs and naive T lymphocytes. We previously reported that activation of naive Mycobacterium tuberculosis-specific CD4+ T cells depends on dendritic cell (DC) transport of live bacteria from the lungs to the mediastinal lymph node (MDLN). Because the migratory paths of DCs are largely governed by the chemokine receptor CCR7, which is expressed on DCs upon maturation by proinflammatory stimuli, we examined the quantitative contribution of CCR7-dependent DC migration in the context of tuberculosis. We found that early trafficking of DCs from the lungs to the MDLN depended on CCR7-mediated signaling, but alternative mechanism(s) are used later in infection. Impaired migration of DCs in CCR7−/− mice resulted in delayed dissemination of bacteria to MDLN and spleen and in delayed kinetics of activation of adoptively transferred Ag85B-specific CD4+ T cells. Furthermore, in contrast to control mice, we found that naive Ag85B-specific CD4+ T cells are activated to proliferate in the lungs of CCR7−/− mice and, when infected with higher doses of bacteria, resistance to M. tuberculosis infection in CCR7−/− mice is compromised compared with wild-type mice.
Pronounced Phenotype in Activated Regulatory T Cells during a Chronic Helminth Infection
Authors: Layland Laura E. , Mages Jörg , Loddenkemper Christoph , Hoerauf Achim , Wagner Hermann , Lang Roland , Prazeres da Costa Clarissa U. 
Published: December 2009

AbstractAlthough several markers have been associated with the characterization of regulatory T cells (Tregs) and their function, no studies have investigated the dynamics of their phenotype during infection. Since the necessity of Tregs to control immunopathology has been demonstrated, we used the chronic helminth infection model Schistosoma mansoni to address the impact on the Treg gene repertoire. Before gene expression profiling, we first studied the localization and Ag-specific suppressive nature of classically defined Tregs during infection. The presence of Foxp3+ cells was predominantly found in the periphery of granulomas and isolated CD4+CD25hiFoxp3+ Tregs from infected mice and blocked IFN-γ and IL-10 cytokine secretion from infected CD4+CD25− effector T cells. Furthermore, the gene expression patterns of Tregs and effector T cells showed that 474 genes were significantly regulated during schistosomiasis. After k-means clustering, we identified genes exclusively regulated in all four populations, including Foxp3, CD103, GITR, OX40, and CTLA-4—classic Treg markers. During infection, however, several nonclassical genes were upregulated solely within the Treg population, such as Slpi, Gzmb, Mt1, Fabp5, Nfil3, Socs2, Gpr177, and Klrg1. Using RT-PCR, we confirmed aspects of the microarray data and also showed that the expression profile of Tregs from S. mansoni-infected mice is simultaneously unique and comparable with Tregs derived from other infections.
Decreased Levels of Secretory Leucoprotease Inhibitor in the Pseudomonas-Infected Cystic Fibrosis Lung Are Due to Neutrophil Elastase Degradation
Authors: Weldon Sinéad , McNally Paul , McElvaney Noel G. , Elborn J. Stuart , McAuley Danny F. , Wartelle Julien , Belaaouaj Abderrazzaq , Levine Rodney L. , Taggart Clifford C. 
Published: December 2009

Abstract
Secretory leucoprotease inhibitor (SLPI) is a neutrophil serine protease inhibitor constitutively expressed at many mucosal surfaces, including that of the lung. Originally identified as a serine protease inhibitor, it is now evident that SLPI also has antimicrobial and anti-inflammatory functions, and therefore plays an important role in host defense. Previous work has shown that some host defense proteins such as SLPI and elafin are susceptible to proteolytic degradation. Consequently, we investigated the status of SLPI in the cystic fibrosis (CF) lung. A major factor that contributes to the high mortality rate among CF patients is Pseudomonas aeruginosa infection. In this study, we report that P. aeruginosa-positive CF bronchoalveolar lavage fluid, which contains lower SLPI levels and higher neutrophil elastase (NE) activity compared with P. aeruginosa-negative samples, was particularly effective at cleaving recombinant human SLPI. Additionally, we found that only NE inhibitors were able to prevent SLPI cleavage, thereby implicating NE in this process. NE in excess was found to cleave recombinant SLPI at two novel sites in the NH2-terminal region and abrogate its ability to bind LPS and NF-κB consensus binding sites but not its ability to inhibit activity of the serine protease cathepsin G. In conclusion, this study provides evidence that SLPI is cleaved and inactivated by NE present in P. aeruginosa-positive CF lung secretions and that P. aeruginosa infection contributes to inactivation of the host defense screen in the CF lung.
IFN Regulatory Factor 5 Is Required for Disease Development in the FcγRIIB−/−Yaa and FcγRIIB−/− Mouse Models of Systemic Lupus Erythematosus
Authors: Richez Christophe , Yasuda Kei , Bonegio Ramon G. , Watkins Amanda A. , Aprahamian Tamar , Busto Patricia , Richards Rocco J. , Liu Chih Long , Cheung Regina , Utz Paul J. , Marshak-Rothstein Ann , Rifkin Ian R. 
Published: December 2009

Abstract
Polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are strongly associated in human genetic studies with an increased risk of developing the autoimmune disease systemic lupus erythematosus. However, the biological role of IRF5 in lupus pathogenesis has not previously been tested in an animal model. In this study, we show that IRF5 is absolutely required for disease development in the FcγRIIB−/−Yaa and FcγRIIB−/− lupus models. In contrast to IRF5-sufficient FcγRIIB−/−Yaa mice, IRF5-deficient FcγRIIB−/−Yaa mice do not develop lupus manifestations and have a phenotype comparable to wild-type mice. Strikingly, full expression of IRF5 is required for the development of autoimmunity, as IRF5 heterozygotes had dramatically reduced disease. One effect of IRF5 is to induce the production of the type I IFN, IFN-α, a cytokine implicated in lupus pathogenesis. To address the mechanism by which IRF5 promotes disease, we evaluated FcγRIIB−/−Yaa mice lacking the type I IFN receptor subunit 1. Unlike the IRF5-deficient and IRF5-heterozygous FcγRIIB−/−Yaa mice, type I IFN receptor subunit 1-deficient FcγRIIB−/−Yaa mice maintained a substantial level of residual disease. Furthermore, in FcγRIIB−/− mice lacking Yaa, IRF5-deficiency also markedly reduced disease manifestations, indicating that the beneficial effects of IRF5 deficiency in FcγRIIB−/−Yaa mice are not due only to inhibition of the enhanced TLR7 signaling associated with the Yaa mutation. Overall, we demonstrate that IRF5 plays an essential role in lupus pathogenesis in murine models and that this is mediated through pathways beyond that of type I IFN production.
In Vivo Induction of Type 1-Like Regulatory T Cells Using Genetically Modified B Cells Confers Long-Term IL-10-Dependent Antigen-Specific Unresponsiveness
Authors: Ahangarani Roxana Roohi , Janssens Wim , VanderElst Luc , Carlier Vincent , VandenDriessche Thierry , Chuah Marinee , Weynand Birgit , Vanoirbeek Jeroen A. J. , Jacquemin Marc , Saint-Remy Jean-Marie 
Published: December 2009

Abstract
Regulatory T cells (Tregs) hold much promise for the therapy of allergy and autoimmunity, but their use is hampered by lack of Ag specificity (natural Tregs) and difficulty to expand in vitro or in vivo (adaptive Tregs). We designed a method for in vivo induction of Ag-specific Tregs, in BALB/c H-2d, that share characteristics with type 1 Tregs (Tr1). A retroviral vector was constructed encoding a major T cell epitope of a common allergen, Der p 2, fused to an endosomal targeting sequence (gp75) for efficient MHC class II presentation. B cells transduced with such construct were adoptively transferred to BALB/c mice before or after peptide immunization. Long-lasting Ag-specific immune tolerance was achieved in both cases. Genetically modified B cells constitutively expressed the transgene for at least 3 mo. B cells from IL-10−/− mice were unable to induce tolerance. Upon transfer, B cells induced Foxp3−CD4+ T cells showing phenotypic and functional characteristics comparable to Tr1-cells, including production of IL-10 but not of TGF-β, and high expression of CTLA-4. Adoptive transfer of such T cells conferred unresponsiveness to allergen immunization and prevented the development of Der p 2-induced asthma. Functional Tr1-like cells can therefore be induced in vivo using retrovirally transduced B cells.
The Anti-Inflammatory and Proresolving Mediator Resolvin E1 Protects Mice from Bacterial Pneumonia and Acute Lung Injury
Authors: Seki Hiroyuki , Fukunaga Koichi , Arita Makoto , Arai Hiroyuki , Nakanishi Hiroki , Taguchi Ryo , Miyasho Taku , Takamiya Rina , Asano Koichiro , Ishizaka Akitoshi , Takeda Junzo , Levy Bruce D. 
Published: December 2009

Abstract
Whereas pneumonia is the most common cause of death and disability worldwide, most cases of pneumonia spontaneously resolve. Mechanisms that promote pneumonia resolution remain to be determined. Resolvin E1 (RvE1) is an endogenous mediator that displays proresolving actions in sterile inflammation. In this study, we developed a new model of aspiration pneumonia to evaluate the effect of RvE1 on acute lung injury caused by acid aspiration and subsequent bacterial challenge. Mice received hydrochloric acid into the left lung followed by the enteric pathogen Escherichia coli. I.v. administration of RvE1 (∼0.005 mg/kg) prior to acid injury selectively decreased lung neutrophil accumulation by 55% and enhanced clearance of E. coli. RvE1 significantly decreased lung tissue levels of several proinflammatory chemokines and cytokines, including IL-1β, IL-6, HMGB-1, MIP-1α, MIP-1β, keratinocyte-derived chemokine, and MCP-1, in a manner independent of the anti-inflammatory mediators IL-10 and lipoxin A4. In addition, animals treated with RvE1 had a marked improvement in survival. These findings in experimental aspiration pneumonia have uncovered protective roles for RvE1 in pathogen-mediated inflammation that are both anti-inflammatory for neutrophils and protective for host defense, suggesting that RvE1 represents the first candidate for a novel therapeutic strategy for acute lung injury and pneumonia that harnesses natural resolution mechanisms.
Mycobacterium bovis Bacillus Calmette-Guérin Killed by Extended Freeze-Drying Targets Plasmacytoid Dendritic Cells To Regulate Lung Inflammation
Authors: Lagranderie Micheline , Abolhassani Mohammad , Vanoirbeek Jeroen A. J. , Lima Carla , Balazuc Anne-Marie , Vargaftig B. Boris , Marchal Gilles 
Published: December 2009

Abstract
We have previously shown that bacillus Calmette-Guérin (BCG) inactivated by extended freeze-drying (EFD) reduces airway hyperresponsiveness, whereas live and heat-killed BCG fail to do so. However, the cells involved in the protective effect and the signaling and transcriptional networks that could reprogram T cell commitment after EFD BCG treatment remained to be elucidated. We investigated whether EFD BCG targets plasmacytoid dendritic cells (pDCs) potentially involved in the polarization of regulatory T cells (Tregs) and the transcriptional factors that regulate allergic inflammation. OVA-sensitized mice were s.c. injected with EFD, live, or heat-killed BCG. We analyzed after the injection of the various BCG preparations: 1) pDCs recruited in the draining lymph nodes (day 4); 2) transcription factors involved in inflammation and T cell commitment in spleen and lungs after OVA challenge (day 28). Airway hyperresponsiveness and transcription factors were determined after in vivo depletion of pDCs or Tregs in EFD BCG-treated and OVA-challenged mice. EFD BCG reduced inflammation via the recruitment of pDCs polarizing the differentiation of naive CD4+ T lymphocytes into Tregs. In vivo, pDC or Treg depletion at the time of EFD BCG treatment abrogated the protection against inflammation. EFD BCG treatment upregulated Forkhead-winged helix transcription factor (Treg signature) and downregulated GATA-3 and RORγt (Th2 and Th17 signatures) more efficiently than live and heat-killed BCG. Moreover, only EFD BCG enhanced peroxisome proliferator-activated receptor γ expression and blocked NF-κB activation, cyclooxygenase expression, and p38 MAPK phosphorylation. EFD BCG reduced allergic inflammation by recruiting pDCs that promoted Tregs; EFD BCG acted as a peroxisome proliferator-activated receptor γ agonist and thus could be used in asthma and other inflammatory diseases.
Peptide-MHC Class II Complex Stability Governs CD4 T Cell Clonal Selection
Authors: Baumgartner Christina K. , Ferrante Andrea , Nagaoka Mika , Gorski Jack , Malherbe Laurent P. 
Published: December 2009

Abstract
The clonal composition of the T cell response can affect its ability to mediate infection control or to induce autoimmunity, but the mechanisms regulating the responding TCR repertoire remain poorly defined. In this study, we immunized mice with wild-type or mutated peptides displaying varying binding half-lives with MHC class II molecules to measure the impact of peptide-MHC class II stability on the clonal composition of the CD4 T cell response. We found that, although all peptides elicited similar T cell response size on immunization, the clonotypic diversity of the CD4 T cell response correlated directly with the half-life of the immunizing peptide. Peptides with short half-lives focused CD4 T cell response toward high-affinity clonotypes expressing restricted public TCR, whereas peptides with longer half-lives broadened CD4 T cell response by recruiting lower-affinity clonotypes expressing more diverse TCR. Peptides with longer half-lives did not cause the elimination of high-affinity clonotypes, and at a low dose, they also skewed CD4 T cell response toward higher-affinity clonotypes. Taken collectively, our results suggest the half-life of peptide-MHC class II complexes is the primary parameter that dictates the clonotypic diversity of the responding CD4 T cell compartment.
Photoenzymatic Reduction of CC Double Bonds
Authors: Grau Maria Mifsud , van der Toorn John C. , Otten Linda G. , Macheroux Peter , Taglieber Andreas , Zilly Felipe E. , Arends Isabel W. C. E. , Hollmann Frank 
Published: December 2009

AbstractA simplified procedure for cell‐free biocatalytic reductions of conjugated CC double bonds using old yellow enzymes (OYEs) is reported. Instead of indirectly regenerating YqjM (an OYE homologue from B. subtilis) or NemA (N‐ethylmaleimide reductase from E. coli) via regeneration of reduced nicotinamide cofactors, we demonstrate that direct regeneration of catalytically active reduced flavins is an efficient and convenient approach. Reducing equivalents are provided from simple sacrificial electron donors such as ethylenediaminetetraacetate (EDTA), formate, or phosphite via photocatalytic oxidation. This novel photoenzymatic reaction scheme was characterized. Up to 65% rates of the NADH‐driven reaction were obtained while preserving enantioselectivity. The chemoselectivity of the novel approach was exclusive. Even when using crude cell extracts as biocatalyst preparations, only CC bond reduction was observed while ketone and aldehyde groups remained unaltered. Overall, a simple and practical approach for photobiocatalytic reductions is presented.
Ruthenium Catalyzed Selective Regio‐and‐Mono‐Allylation of Cyclic 1,3‐Diketones Using Allyl Alcohols as Substrates
Authors: Gruber Stefan , Pregosin Paul S. 
Published: December 2009

AbstractThe new ruthenium‐sulfonate catalyst Ru(Cp*)(η3‐C3H5) (p‐CH3C6H4SO3)2, (Cp*=pentamethylcyclopentadienyl), rapidly and regioselectively mono‐allylates dimedone to the branched products using substituted allyl alcohols as substrates, without acid, base or other additives, under relatively mild conditions. We consider the ruthenium sulfonate to be a “green” alternative in that it uses allyl alcohols as substrate, (rather than carbonates, acetates, etc.) and therefore does not waste the leaving group. The catalyst induces rapid double allylation of various 1,3‐diketones in high yield using allylic alcohol.
Pyranoside Phosphite‐Oxazoline Ligand Library: Highly Efficient Modular P,N Ligands for Palladium‐Catalyzed Allylic Substitution Reactions. A Study of the Key Palladium Allyl Intermediates
Authors: Mata Yvette , Pàmies Oscar , Diéguez Montserrat 
Published: December 2009

AbstractWe have screened a library of modular phosphite‐oxazoline ligands for asymmetric allylic substitution reactions. The library is efficiently prepared from the commercially available and cheap D‐glucosamine. The introduction of a phosphite moiety into the ligand design is highly advantageous for the product outcome. Therefore, this ligand library affords good‐to‐excellent reaction rates [TOFs up to 600 mol substrate×(mol Pd×h)−1] and enantioselectivities (ees up to 99%) and, at the same time, shows a broad scope for mono‐, di‐ and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR studies on the palladium allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity.
Catalytic Asymmetric Synthesis of Branched Chiral Allylic Phenyl Ethers from (E)‐Allylic Alcohols
Authors: Olson Angela C. , Overman Larry E. , Sneddon Helen F. , Ziller Joseph W. 
Published: December 2009

AbstractThe first di‐μ‐amidate dipalladium complexes and a new di‐μ‐carboxylate dipalladium complex of the COP (cobalt oxazoline palladacycle) palladium(II) catalyst family are reported and characterized crystallographically. The di‐μ‐amidate complex 3 and its enantiomer (ent‐3) are the first asymmetric catalysts that allow commercially available, or readily accessible, (E)‐2‐alken‐1‐ols to be transformed to enantioenriched branched allylic aryl ethers upon reaction of their trichloroacetimidate derivatives with phenols. The 3‐aryloxy‐1‐alkene products are formed in high enantiomeric purity (typically 90–98% ee) and useful yields (61–88%).
Binuclear Iron(III) Phthalocyanine(μ‐Oxodimer)‐Catalyzed Oxygenation of Aromatic Hydrocarbons with Iodosylbenzene Sulfate and Iodosylbenzene as the Oxidants
Authors: Neu Heather M. , Yusubov Mekhman S. , Zhdankin Viktor V. , Nemykin Victor N. 
Published: December 2009

AbstractTwo binuclear iron(III) phthalocyanine‐(μ‐oxodimer) complexes were tested in catalytic oxygenation reactions of several aromatic hydrocarbons using iodosylbenzene (PhIO)n or oligomeric iodosylbenzene sulfate [(PhIO)3SO3]n as the oxidants. Results of this study demonstrate that [(PhIO)3SO3]n is the most reactive oxygenating reagent that can be used as a safe and convenient alternative to the thermally unstable and potentially explosive iodosylbenzene. The pyridine‐containing binuclear μ‐oxobis{iron(III)‐pyridino[3,4]‐9(10),16(17),23(24)‐tri‐tert‐butyltribenzoporphyrazine} is significantly more active as compared to the traditional μ‐oxobis[iron(III)‐2,9(10),16(17),23(24)‐tetra‐tert‐butylphthalocyanine].
Organocatalysis in Natural Product Synthesis: A Simple One‐Pot Approach to Optically Active β‐Diols
Authors: Andersen Nikolaj Røjkjær , Hansen Signe Grann , Bertelsen Søren , Jørgensen Karl Anker 
Published: December 2009

AbstractOptically active β‐diols have been prepared using an organocatalytic one‐pot approach from α,β‐unsaturated aldehydes using (E)‐benzaldehyde oxime as nucleophile in an oxa‐Michael reaction with subsequent in situ reduction or Grignard addition. With this protocol at hand, two biologically active compounds, an insect sex pheromone and a glycerol kinase substrate have been synthesized.
Social dynamics and individual plasticity of infant care behavior in cooperatively breeding cotton‐top tamarins
Authors: Zahed Sofia Refetoff , Kurian Aimee V. , Snowdon Charles T. 
Published: December 2009

AbstractIndividual variation in infant caretaking behavior is prevalent among marmoset and tamarin monkeys. Although most group members participate in infant care, the timing and amount provided differs greatly. In this study, we quantified general trends in infant carrying behavior by using a longitudinal database that included 11 years of instantaneous scan observations following 80 births of cotton‐top tamarins. Using detailed focal observations on a subset of the same families (10 births) we identified influences that affected expression of infant care at the group and individual levels. Fathers were the primary carriers and paternal carry time gradually decreased with increasing infant age. Paternal carry time also decreased significantly with an increasing number of older sibling helpers. Most fathers began to carry on the first day postpartum. However, we report circumstances in which fathers delayed carrying until almost a month postpartum. Fathers retrieved infants the most, although adult brothers' rates of retrievals peaked and surpassed fathers' rates during week 4 postpartum. Fathers delayed rejection of infants until week 4, whereas mothers rejected infants immediately and throughout the eight weeks. Nonetheless, infants climbed onto their mothers more than onto any other family member. Mothers showed a high initial investment in carrying during the first two weeks, decreasing quickly thereafter. Maternal contributions to infant carrying remained low and relatively consistent regardless of group size. However, mothers dramatically increased their infant carrying behavior in families in which fathers were absent. Older siblings cared for infants more than did younger siblings, and brothers retrieved and carried infants more than did sisters. Individual expression of infant care changed to accommodate infant needs and changed according to varying social dynamics and circumstances across litters. Am. J. Primatol. 72:296–306, 2010. © 2009 Wiley‐Liss, Inc.
Ontogeny of robusticity of craniofacial traits in modern humans: A study of South American populations
Authors: Gonzalez Paula N. , Perez S. Ivan , Bernal Valeria 
Published: December 2009

AbstractTo date, differences in craniofacial robusticity among modern and fossil humans have been primarily addressed by analyzing adult individuals; thus, the developmental basis of such differentiation remains poorly understood. This article aims to analyze the ontogenetic development of craniofacial robusticity in human populations from South America. Geometric morphometric methods were used to describe cranial traits in lateral view by using landmarks and semilandmarks. We compare the patterns of variation among populations obtained with subadults and adults to determine whether population‐specific differences are evident at early postnatal ontogeny, compare ontogenetic allometric trajectories to ascertain whether changes in the ontogeny of shape contribute to the differentiation of adult morphologies, and estimate the amount of size change that occurs during growth along each population‐specific trajectory. The results obtained indicate that the pattern of interpopulation variation in shape and size is already established at the age of 5 years, meaning that processes acting early during ontogeny contribute to the adult variation. The ontogenetic allometric trajectories are not parallel among all samples, suggesting the divergence in the size‐related shape changes. Finally, the extension of ontogenetic trajectories also seems to contribute to shape variation observed among adults. Am J Phys Anthropol 2010. © 2009 Wiley‐Liss, Inc.