bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Th2 Adaptive Immune Responses and Pulmonary Inflammation by Leukocyte Ig-Like Receptor B4 on Dendritic Cells
Authors: Breslow Rebecca G. , Rao Jayanti J. , Xing Wei , Hong David I. , Barrett Nora A. , Katz Howard R. 
Published: December 2009

Abstract
We previously established that the inhibitory receptor LILRB4 mitigates LPS-induced, neutrophil-dependent pathologic effector mechanisms in inflammation. We now report that LILRB4 on dendritic cells (DCs) counterregulates development of an adaptive Th2 immune response and ensuing inflammation in a model of allergic pulmonary inflammation, initiated by inhalation sensitization with OVA and LPS followed by airway challenge with OVA. We found that Lilrb4−/− mice had significantly exacerbated eosinophilic pulmonary inflammation, as assessed in bronchoalveolar lavage and lung tissue, as well as elevated levels of OVA-specific IgE and Th2 cytokines produced by OVA-restimulated lymph node cells. LILRB4 was preferentially expressed on MHC class IIhighCD86high OVA-bearing DCs in lung-draining lymph nodes after sensitization or challenge. Moreover, the lymph nodes of Lilrb4−/− mice had significantly more of these mature DCs after challenge with OVA, which was accompanied by significantly more IL-4–producing lymphocytes, compared with Lilrb4+/+ mice. Sensitization of naive Lilrb4+/+ mice by transfer of OVA-LPS-pulsed Lilrb4−/− bone marrow-derived DCs was sufficient to confer exacerbated allergic lung pathology upon challenge with OVA, compared with mice that received Lilrb4+/+ bone marrow-derived DCs. Our findings establish that maturation and migration of pulmonary DCs to lymph nodes in response to Ag and an innate immune stimulus is associated with upregulated expression of LILRB4. In addition, this receptor attenuates the number of these mature DCs and attendant IL-4–producing lymphocytes in the lymph nodes, and accordingly, the ability of DCs to elicit pathologic Th2 pulmonary inflammation.
Regulatory B Cells Shape the Development of Th2 Immune Responses in BALB/c Mice Infected with Leishmania major Through IL-10 Production
Authors: Ronet Catherine , Torre Yazmin Hauyon-La , Revaz-Breton Mélanie , Mastelic Béatris , Tacchini-Cottier Fabienne , Louis Jacques , Launois Pascal 
Published: December 2009

Abstract
Recent evidence indicates that B cells are required for susceptibility to infection with Leishmania major in BALB/c mice. In this study, we analyzed the role of the IL-10 produced by B cells in this process. We showed that B cells purified from the spleen of BALB/c mice produced IL-10 in response to stimulation with L. major in vitro. In vivo, early IL-10 mRNA expression is detected after L. major infection in B cells from draining lymph nodes of susceptible BALB/c, but not of resistant C57BL/6 mice. Although adoptive transfer of naive wild-type B cells prior to infection in B cell-deficient BALB/c mice restored Th2 cell development and susceptibility to infection with L. major of these otherwise resistant mice, adoptive transfer of IL-10−/− B cells mice did not. B cells stimulated by L. major, following in vitro or in vivo encounter, express the CD1d and CD5 molecules and the IL-10 produced by these cells downregulate IL-12 production by L. major-stimulated dendritic cells. These observations indicate that IL-10 secreting B cells are phenotypically and functionally regulatory B cells. Altogether these results demonstrate that the IL-10 produced by regulatory CD1d+ CD5+ B cells in response to L. major is critical for Th2 cell development in BALB/c mice.
Immunostimulatory RNA Blocks Suppression by Regulatory T Cells
Authors: Anz David , Koelzer Viktor H. , Moder Stefan , Thaler Raffael , Schwerd Tobias , Lahl Katharina , Sparwasser Tim , Besch Robert , Poeck Hendrik , Hornung Veit , Hartmann Gunther , Rothenfusser Simon , Bourquin Carole , Endres Stefan 
Published: December 2009

Abstract
The role of immune suppression by regulatory T (Treg) cells in the maintenance of immune homeostasis is well established. However, little is known about how Treg cell function is inhibited on viral infection to allow the development of a protective immune response. As viral RNA is a crucial mediator for activation of antiviral immunity, we examined the effects of immunostimulatory RNA and infection with RNA viruses on Treg cell function. We show that synthetic RNA oligonucleotides potently inhibit Treg cell-induced suppression in a sequence-dependent manner. This effect is entirely dependent on TLR7 activation of APCs and subsequent IL-6 production. In addition, stimulation with the RNA viruses encephalomyocarditis virus and Sendai virus that specifically activate the RNA-sensing helicases melanoma differentiation-associated gene 5 (MDA-5) and retinoic acid-inducible gene I (RIG-I) also blocks Treg cell function. Interestingly, this effect is seen even in the absence of APCs. Consistent with this, both Treg and T effector cells express RIG-I and MDA-5. Using MDA-5–deficient mice, we demonstrate that the loss of Treg cell function on infection with encephalomyocarditis virus is strictly dependent on MDA-5 expression by Treg cells. Thus, we show in this study for the first time that activation of a RIG-I–like helicase on Treg cells blocks their suppressive function.
Neuroprotective Activities of CEP-1347 in Models of NeuroAIDS
Authors: Eggert Dawn , Dash Prasanta K. , Gorantla Santhi , Dou Huanyu , Schifitto Giovanni , Maggirwar Sanjay B. , Dewhurst Stephen , Poluektova Larisa , Gelbard Harris A. , Gendelman Howard E. 
Published: December 2009

Abstract
When the nervous system is infected with HIV-1, it commonly results in neuroinflammation leading to overt neuronal dysfunction and subsequent cognitive and behavioral impairments. The multifaceted disease process, now referred to as HIV-1–associated neurocognitive disorders (HAND), provides a range of molecular targets for adjunctive therapies. One is CEP-1347, an inhibitor of mixed lineage kinases that elicits neuroprotective and anti-inflammatory responses in models of neurodegenerative diseases. Since HAND is associated with inflammatory encephalopathy induced by virus infection and mononuclear phagocytes (perivascular macrophages and microglia) immune activation, we investigated whether CEP-1347 could ameliorate disease in laboratory models of HAND. We now demonstrate that CEP-1347 reduces the levels of secreted proinflammatory cytokines and chemokines in HIV-1–infected human macrophages and attenuates dose-dependent neurotoxicity in rodent cortical neurons. CEP-1347–treated mice readily achieve therapeutic drug levels in peripheral blood. HIV-1 encephalitis (HIVE) mice, where human virus-infected monocyte-derived macrophages are stereotactically injected into the basal ganglia of CB17 severe combined immunodeficient mice, received daily intraperitoneal injections of CEP-1347. Here, CEP-1347 treatment of HIVE mice showed a dose-dependent reduction in microgliosis. Dendritic integrity and neuronal loss were sustained and prevented, respectively. These results demonstrate that CEP-1347 elicits anti-inflammatory and neuroprotective responses in an HIVE model of human disease and as such warrants further study as an adjunctive therapy for human disease.
Ins2 Deficiency Augments Spontaneous HLA-A*0201–Restricted T Cell Responses to Insulin
Authors: Jarchum Irene , DiLorenzo Teresa P. 
Published: December 2009

Abstract
Type 1 diabetes results from the autoimmune destruction of insulin-producing β cells by T cells specific for β cell Ags, including insulin. In humans, the non-MHC locus conferring the strongest disease susceptibility is the insulin gene, and alleles yielding lower thymic insulin expression are predisposing. We sought to incorporate this characteristic into an HLA-transgenic model of the disease and to determine the influence of reduced thymic insulin expression on CD8+ T cell responses to preproinsulin. We examined NOD.Ins2−/− mice, which do not express insulin in the thymus and show accelerated disease, to determine whether they exhibit quantitative or qualitative differences in CD8+ T cell responses to preproinsulin. We also generated NOD.Ins2−/− mice expressing type 1 diabetes-associated HLA-A*0201 (designated NOD.β2m−/−.HHD.Ins2−/−) in an effort to obtain an improved humanized disease model. We found that CD8+ T cell reactivity to certain insulin peptides was more readily detected in NOD.Ins2−/− mice than in NOD mice. Furthermore, the proportion of insulin-reactive CD8+ T cells infiltrating the islets of NOD.Ins2−/− mice was increased. NOD.β2m−/−.HHD.Ins2−/− mice exhibited rapid onset of disease and had an increased proportion of HLA-A*0201–restricted insulin-reactive T cells, including those targeting the clinically relevant epitope Ins B10-18. Our results suggest that insulin alleles that predispose to type 1 diabetes in humans do so, at least in part, by facilitating CD8+ T cell responses to the protein. We propose the NOD.β2m−/−.HHD.Ins2−/− strain as an improved humanized disease model, in particular for studies seeking to develop therapeutic strategies targeting insulin-specific T cells.
Nanotube Surfactant Design: The Versatility of Water‐Soluble Perylene Bisimides
Authors: Backes Claudia , Schmidt Cordula D. , Rosenlehner Karin , Hauke Frank , Coleman Jonathan N. , Hirsch Andreas 
Published: December 2009

AbstractThe synthesis of perylene‐based single‐walled carbon nanotube (SWCNT) surfactants and the dispersion and exfoliation of SWCNTs in water by a variety of designed surfactants is investigated. The quality of the nanotube dispersions is evaluated by optical absorption and emission spectroscopy, zeta‐potential measurements and statistical atomic force microscopy (AFM). Significantly the dispersion efficiency can be increased at higher pH, as water solubility of the surfactants is ensured by peripheral derivatization with carboxyl‐functionalized first‐ and second‐order Newkome dendrimers. Even at very low perylene concentrations of 0.1 g L−1 and a nanotube‐to‐surfactant ratio of 1:1, the nanotube supernatant after centrifugation contains up to 73% of the pristine material with exfoliation degrees (the number of fractions of individualized nanotubes NI/NT) of up to 76%. The adsorption of the perylene core to the nanotube scaffold is indicated by red‐shifted perylene‐absorption and SWCNT‐emission features except for the smallest perylene amphiphile, where solubilization is presumably based on a micellar arrangement. The nanotube fluorescence is significantly altered and reduced in intensity compared to nanotubes dispersed in sodium dodecylbenzene sulfonate (SDBS) being strongly dependent on the structure of the perylene surfactant. We attribute this observation to the homogeneity of the surfactant coverage, e.g., the supramolecular arrangement onto the nanotube backbone. This study represents a step forward in understanding the structure–property relationship of nanotube surfactants. Furthermore high‐quality nanotube dispersions with increased degrees of exfoliation are highly desirable, as the efficiency of nanotube separation techniques relies on highly individualized samples.
Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease
Authors: Kauwe J.S.K. , Bertelsen S. , Mayo K. , Cruchaga C. , Abraham R. , Hollingworth P. , Harold D. , Owen M.J. , Williams J. , Lovestone S. , Morris J.C. , Goate A.M. ,   the Alzheimer's Disease Neuroimaging Initiative
Published: December 2009

AbstractAlzheimer's disease (AD) is a complex disease that is likely influenced by many genetic and environmental factors. Citing evidence that iron may play a role in AD pathology, Robson et al. [Robson et al. (2004); J Med Genet 41:261–265] reported that epistatic interaction between rs1049296 (P589S) in the transferrin gene (TF) and rs1800562 (C282Y) in the hemochromatosis gene (HFE) results in significant association with risk for AD. In this study we attempted to replicate their findings in a total of 1,166 cases and 1,404 controls from three European and European American populations. Allele and genotype frequencies were consistent across the three populations. Using synergy factor analysis (SFA) and Logistic Regression analysis we tested each population and the combined sample for interactions between these two SNPs and risk for AD. We observed significant association between bi‐carriers of the minor alleles of rs1049296 and rs1800562 in the combined sample using SFA (P = 0.0016, synergy factor = 2.71) and adjusted SFA adjusting for age and presence of the APOE epsilon 4 allele (P = 0.002, OR = 2.4). These results validate those of the previous report and support the hypothesis that iron transport and regulation play a role in AD pathology. © 2009 Wiley‐Liss, Inc.
Interval Estimation of the Effective Population Size from Heterozygote‐Excess in SNP Markers
Authors: Nomura Tetsuro 
Published: December 2009

AbstractThe effective population size Ne is an important parameter in population genetics and conservation biology. In recent years, there has been great interest in the use of molecular markers to estimate Ne. Although the point estimates from molecular markers in general suffer from a low reliability, the use of single nucleotide polymorphism (SNP) markers over a wide range of genome is expected to remarkably improve the reliability. In this study, expressions were derived for interval estimates of Ne from one published method, the heterozygote‐excess method, when it is applied to SNP markers. The conditional variance theory is applied to the derivation of a confidence interval for Ne under random union of gametes, monogamy and polygyny. Stochastic simulation shows that the obtained confidence interval is slightly conservative, but fairly useful for practical applications. The result is illustrated with real data on SNP markers in a pig strain.
Binary Au/MWCNT and Ternary Au/ZnO/MWCNT Nanocomposites: Synthesis, Characterisation and Catalytic Performance
Authors: Khanderi Jayaprakash , Hoffmann Rudolf C. , Engstler Jörg , Schneider Jörg J. , Arras Jürgen , Claus Peter , Cherkashinin Gennady 
Published: December 2009

AbstractGold nanoparticles of 10–24 and 5–8 nm in size were obtained by chemical citrate reduction and UV photoreduction, respectively, on acid‐treated multiwalled carbon nanotubes (MWCNTs) and on ZnO/MWCNT composites. The shape and size of the deposited Au nanoparticles were found to be dependent upon the synthetic method used. Single‐crystalline, hexagonal gold particles were produced in the case of UV photoreduction on ZnO/MWCNT, whereas spherical Au particles were deposited on MWCNT when the chemical citrate reduction method was used. In the UV photoreduction route, n‐doped ZnO serves as the e− donor, whereas the solvent is the hole trap. All materials were fully characterised by UV/Vis spectroscopy, scanning electron microscopy, transmission electron microscopy, X‐ray photoelectron spectroscopy, Raman spectroscopy and BET surface analysis. The catalytic activity of the composites was studied for the selective hydrogenation of α,β‐unsaturated carbonyl compound 3,7‐dimethyl‐2,6‐octadienal (citral). The Au/ZnO/MWCNT composite favours the formation of unsaturated alcohols (selectivity=50 % at a citral conversion of 20 %) due to the presence of single‐crystalline, hexagonal gold particles, whereas saturated aldehyde formation is favoured in the case of the Au/MWCNT nanocomposite that contains spherical gold particles.
Antithyroid Drugs and their Analogues Protect Against Peroxynitrite‐Mediated Protein Tyrosine Nitration—A Mechanistic Study
Authors: Bhabak Krishna P. , Mugesh Govindasamy 
Published: December 2009

AbstractIn this paper, the effect of some commonly used antithyroid drugs and their analogues on peroxynitrite‐mediated nitration of proteins is described. The nitration of tyrosine residues in bovine serum albumin (BSA) and cytochrome c was studied by Western blot analysis. These studies reveal that the antithyroid drugs methimazole (MMI), 6‐n‐propyl‐2‐thiouracil (PTU), and 6‐methyl‐2‐thiouracil (MTU), which contain thione moieties, significantly reduce the tyrosine nitration of both BSA and cytochrome c. While MMI exhibits good peroxynitrite (PN) scavenging activity, the thiouracil compounds PTU and MTU are slightly less effective than MMI. The S‐ and Se‐ methylated compounds show a weak inhibitory effect in the nitration of tyrosine, indicating that the presence of a thione or selone moiety is important for an efficient inhibition. Similarly, the replacement of NH moiety in MMI by N‐methyl or N‐m‐methoxybenzyl substituents dramatically reduces the antioxidant activity of the parent compound. Theoretical studies indicate that the substitution of NH moiety by NMe significantly increases the energy required for the oxidation of sulfur center by PN. However, such substitution in the selenium analogue of MMI increases the activity of parent compound. This is due to the facile oxidation of the selone moiety to the corresponding selenenic and seleninic acids. Unlike N,N′‐disubstituted thiones, the corresponding selones efficiently scavenge PN, as they predominantly exist in their zwitterionic forms in which the selenium atom carries a large negative charge.
Adaptable cache service and application to grid caching
Authors: d'Orazio Laurent , Roncancio Claudia , Labbé Cyril 
Published: December 2009

AbstractCaching is an important element to tackle performance issues in largely distributed data management. However, caches are efficient only if they are well configured according to the context of use. As a consequence, they are usually built from scratch. Such an approach appears to be expensive and time consuming in grids where the various characteristics lead to many heterogeneous cache requirements. This paper proposes a framework facilitating the construction of sophisticated and dynamically adaptable caches for heterogeneous applications. Such a framework has enabled the evaluation of several configurations for distributed data querying systems and leads us to propose innovative approaches for semantic and cooperative caching. This paper also reports the results obtained in bioinformatics data management on grids showing the relevance of our proposals. Copyright © 2009 John Wiley & Sons, Ltd.
Phenotypic plasticity in number of glomeruli and sensory innervation of the antennal lobe in leaf‐cutting ant workers (A. vollenweideri)
Authors: Kelber Christina , Rössler Wolfgang , Kleineidam Christoph Johannes 
Published: December 2009

AbstractIn the leaf‐cutting ant Atta vollenweideri, the worker caste exhibits a pronounced size‐polymorphism, and division of labor is dependent on worker size (alloethism). Behavior is largely guided by olfaction, and the olfactory system is highly developed. In a recent study, two different phenotypes of the antennal lobe of Atta vollenweideri workers were found: MG‐ and RG‐phenotype (with/without a macroglomerulus). Here we ask whether the glomerular numbers are related to worker size. We found that the antennal lobes of small workers contain ∼390 glomeruli (low‐number; LN‐phenotype), and in large workers we found a substantially higher number of ∼440 glomeruli (high‐number; HN‐phenotype). All LN‐phenotype workers and some small HN‐phenotype workers do not possess an MG (LN‐RG‐phenotype and HN‐RG‐phenotype), and the remaining majority of HN‐phenotype workers do possess an MG (HN‐MG‐phenotype). Using mass‐staining of antennal olfactory receptor neurons we found that the sensory tracts divide the antennal lobe into six clusters of glomeruli (T1–T6). In LN‐phenotype workers, ∼50 glomeruli are missing in the T4‐cluster. Selective staining of single sensilla and their associated receptor neurons revealed that T4‐glomeruli are innervated by receptor neurons from the main type of olfactory sensilla, the Sensilla trichodea curvata. The other type of olfactory sensilla (Sensilla basiconica) exclusively innervates T6‐glomeruli. Quantitative analyses of differently sized workers revealed that the volume of T6 glomeruli scales with the power of 2.54 to the number of Sensilla basiconica. The results suggest that developmental plasticity leading to antennal‐lobe phenotypes promotes differences in olfactory‐guided behavior and may underlie task specialization within ant colonies. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 70: 222–234, 2010.
Enrichment and immunoprecipitation of 22 kDa human growth hormone spiked into human urine
Authors: Bane T. K. , Timmons M. S. , Kauffman S. J. , Catlin D. H. 
Published: December 2009

AbstractApproaches to detect whether an athlete has used growth hormone have been intensely investigated by sport organizations for 20 years. This effort has led to a human growth hormone (hGH) isoform ratio test in serum that has been approved by WADA and deployed at three Olympic Games, although a positive case has yet to be reported. We set out to determine whether the ratio test could be applied to urine. First we investigated various ways to extract hGH from spiked urine. We were able to recover 95% using selective centrifugal concentration. This fraction was then subjected to four different commercially available immunoprecipitation kits. The highest yield was obtained with the Invitrogen Dynabeads Protein G kit. Nevertheless it is apparent that these methods do not recover enough hGH for subsequent analysis by mass spectrometry. With further effort greater recovery of the 22 kDa isoform might be achieved, however it is very unlikely that the 20 kDa isoform could be detected. This method may be significantly improved by the application of both nanoparticle and aptamer technology. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis of Amino‐Bridged Oligosaccharide Mimetics
Authors: Neumann Janna , Thiem Joachim 
Published: December 2009

AbstractSynthesis of amino‐bridged oligosaccharides using reductive amination opens rapid access to novel glycomimetic target structures as potential ligands for the receptor protein NKR P1 of natural killer cells. Emphasis was laid on fast and facile synthetic routes. The carbonyl building blocks were easily obtained by oxidation with Dess–Martin periodinane or iodoxybenzoic acid (IBX). For the required amino‐functionalized units, reduction of azide precursors was advantageous, and generation of the novel oligosaccharides was achieved by subsequent reductive amination. The target saccharide structures feature a bridging nitrogen atom inserted between two non‐anomeric positions as well as including one anomeric position.