bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Monocytes in HIV-1-Infected Viremic Subjects Exhibit an Antiapoptosis Gene Signature and Virus- and Host-Mediated Apoptosis Resistance
Authors: Giri Malavika S. , Nebozyhn Michael , Raymond Andrea , Gekonge Bethsebah , Hancock Aidan , Creer Shenoa , Nicols Calen , Yousef Malik , Foulkes Andrea S. , Mounzer Karam , Shull Jane , Silvestri Guido , Kostman Jay , Collman Ronald G. , Showe Louise , Montaner Luis J. 
Published: March 2009

Abstract
Mechanisms that may allow circulating monocytes to persist as CD4 T cells diminish in HIV-1 infection have not been investigated. We have characterized steady-state gene expression signatures in circulating monocytes from HIV-infected subjects and have identified a stable antiapoptosis gene signature comprised of 38 genes associated with p53, CD40L, TNF, and MAPK signaling networks. The significance of this gene signature is indicated by our demonstration of cadmium chloride- or Fas ligand-induced apoptosis resistance in circulating monocytes in contrast to increasing apoptosis in CD4 T cells from the same infected subjects. As potential mechanisms in vivo, we show that monocyte CCR5 binding by HIV-1 virus or agonist chemokines serves as independent viral and host modulators resulting in increased monocyte apoptosis resistance in vitro. We also show evidence for concordance between circulating monocyte apoptosis-related gene expression in HIV-1 infection in vivo and available datasets following viral infection or envelope exposure in monocyte-derived macrophages in vitro. The identification of in vivo gene expression associated with monocyte resistance to apoptosis is of relevance to AIDS pathogenesis since it would contribute to: 1) maintaining viability of infection targets and long-term reservoirs of HIV-1 infection in the monocyte/macrophage populations, and 2) protecting a cell subset critical to host survival despite sustained high viral replication.
Histoplasma capsulatum Cell Wall β-Glucan Induces Lipid Body Formation through CD18, TLR2, and Dectin-1 Receptors: Correlation with Leukotriene B4 Generation and Role in HIV-1 Infection
Authors: Sorgi Carlos Artério , Secatto Adriana , Fontanari Caroline , Turato Walter Miguel , Belangér Caroline , de Medeiros Alexandra Ivo , Kashima Simone , Marleau Sylvie , Covas Dimas Tadeu , Bozza Patrícia Torres , Faccioli Lúcia Helena 
Published: March 2009

Abstract
Histoplasma capsulatum (Hc) is a facultative, intracellular parasite of worldwide significance. Infection with Hc produces a broad spectrum of diseases and may progress to a life-threatening systemic disease, particularly in individuals with HIV infection. Resolution of histoplasmosis is associated with the activation of cell-mediated immunity, and leukotriene B4 plays an important role in this event. Lipid bodies (LBs) are increasingly being recognized as multifunctional organelles with roles in inflammation and infection. In this study, we investigated LB formation in histoplasmosis and its putative function in innate immunity. LB formation in leukocytes harvested from Hc-infected C57BL/6 mice peaks on day 2 postinfection and correlates with enhanced generation of lipid mediators, including leukotriene B4 and PGE2. Pretreatment of leukocytes with platelet-activating factor and BLT1 receptor antagonists showed that both lipid mediators are involved in cell signaling for LB formation. Alveolar leukocytes cultured with live or dead Hc also presented an increase in LB numbers. The yeast alkali-insoluble fraction 1, which contains mainly β-glucan isolated from the Hc cell wall, induced a dose- and time-dependent increase in LB numbers, indicating that β-glucan plays a signaling role in LB formation. In agreement with this hypothesis, β-glucan-elicited LB formation was inhibited in leukocytes from 5-LO−/−, CD18low and TLR2−/− mice, as well as in leukocytes pretreated with anti-Dectin-1 Ab. Interestingly, human monocytes from HIV-1-infected patients failed to produce LBs after β-glucan stimulation. These results demonstrate that Hc induces LB formation, an event correlated with eicosanoid production, and suggest a role for these lipid-enriched organelles in host defense during fungal infection.
Airway and Lung Pathology Due to Mucosal Surface Dehydration in β-Epithelial Na+ Channel-Overexpressing Mice: Role of TNF-α and IL-4Rα Signaling, Influence of Neonatal Development, and Limited Efficacy of Glucocorticoid Treatment
Authors: Livraghi Alessandra , Grubb Barbara R. , Hudson Elizabeth J. , Wilkinson Kristen J. , Sheehan John K. , Mall Marcus A. , O'Neal Wanda K. , Boucher Richard C. , Randell Scott H. 
Published: March 2009

AbstractOverexpression of the epithelial Na+ channel β subunit (Scnn1b gene, βENaC protein) in transgenic (Tg) mouse airways dehydrates mucosal surfaces, producing mucus obstruction, inflammation, and neonatal mortality. Airway inflammation includes macrophage activation, neutrophil and eosinophil recruitment, and elevated KC, TNF-α, and chitinase levels. These changes recapitulate aspects of complex human obstructive airway diseases, but their molecular mechanisms are poorly understood. We used genetic and pharmacologic approaches to identify pathways relevant to the development of Scnn1b-Tg mouse lung pathology. Genetic deletion of TNF-α or its receptor, TNFR1, had no measurable effect on the phenotype. Deletion of IL-4Rα abolished transient mucous secretory cell (MuSC) abundance and eosinophilia normally observed in neonatal wild-type mice. Similarly, IL-4Rα deficiency decreased MuSC and eosinophils in neonatal Scnn1b-Tg mice, which correlated with improved neonatal survival. However, chronic lung pathology in adult Scnn1b-Tg mice was not affected by IL-4Rα status. Prednisolone treatment ablated eosinophilia and MuSC in adult Scnn1b-Tg mice, but did not decrease mucus plugging or neutrophilia. These studies demonstrate that: 1) normal neonatal mouse airway development entails an IL-4Rα-dependent, transient abundance of MuSC and eosinophils; 2) absence of IL-4Rα improved neonatal survival of Scnn1b-Tg mice, likely reflecting decreased formation of asphyxiating mucus plugs; and 3) in Scnn1b-Tg mice, neutrophilia, mucus obstruction, and airspace enlargement are IL-4Rα- and TNF-α-independent, and only MuSC and eosinophilia are sensitive to glucocorticoids. Thus, manipulation of multiple pathways will likely be required to treat the complex pathogenesis caused by airway surface dehydration.
Cutting Edge: Ikaros Null Thymocytes Mature into the CD4 Lineage with Reduced TCR Signal: A Study Using CD3ζ Immunoreceptor Tyrosine-Based Activation Motif Transgenic Mice
Authors: Urban Julie A. , Brugmann William , Winandy Susan 
Published: March 2009

Abstract
Positive selection is a critical T cell developmental checkpoint that is driven by TCR signals. Enhanced positive selection toward the CD4 lineage occurs in the absence of Ikaros. One explanation for this phenotype is that Ikaros establishes the TCR signaling threshold that must be overcome for positive selection to occur. In the current study, this possibility is explored through the use of CD3ζ ITAM transgenic mice that express a CD3 ζ-chain with zero, one, or three ITAMs and an MHC class II (DO11.10)- or MHC class I (H-Y)-restricted TCR transgene. Using this system, we demonstrate that in the absence of Ikaros, thymocytes are able to mature into the CD4 lineage with reduced TCR signaling potential compared with that required to drive the maturation of wild-type thymocytes. We also demonstrate that maturation into the CD8 lineage is enhanced under conditions of reduced TCR signaling potential in the absence of Ikaros.
The Cyclic AMP Response Element Modulator α Suppresses CD86 Expression and APC Function
Authors: Ahlmann Martina , Varga Georg , Sturm Karsten , Lippe Ralph , Benedyk Konrad , Viemann Dorothee , Scholzen Thomas , Ehrchen Jan , Müller Frank U. , Seidl Matthias , Matus Marek , Tsokos George C. , Roth Johannes , Tenbrock Klaus 
Published: March 2009

Abstract
The cAMP response element modulator (CREM)α is a widely expressed transcriptional repressor that is important for the termination of the T cell immune response and contributes to the abnormal T cell function in patients with systemic lupus erythematosus. We present evidence that APCs of Crem−/− mice express increased amounts of the costimulatory molecule CD86 and induce enhanced Ag-dependent and Ag-independent T cell proliferation. Similarly, human APCs in which CREMα was selectively suppressed expressed more CD86 on the surface membrane. CREMα was found to bind to the CD86 promoter and suppressed its activity. Transfer of APCs from Crem−/− mice into naive mice facilitated a significantly stronger contact dermatitis response compared with mice into which APCs from Crem+/+ mice had been transferred. We conclude that CREMα is an important negative regulator of costimulation and APC-dependent T cell function both in vitro and in vivo.
Cross-Linking of GM1 Ganglioside by Galectin-1 Mediates Regulatory T Cell Activity Involving TRPC5 Channel Activation: Possible Role in Suppressing Experimental Autoimmune Encephalomyelitis
Authors: Wang Jianfeng , Lu Zi-Hua , Gabius Hans-Joachim , Rohowsky-Kochan Christine , Ledeen Robert W. , Wu Gusheng 
Published: March 2009

Abstract
Several animal autoimmune disorders are suppressed by treatment with the GM1 cross-linking units of certain toxins such as B subunit of cholera toxin (CtxB). Due to the recent observation of GM1 being a binding partner for the endogenous lectin galectin-1 (Gal-1), which is known to ameliorate symptoms in certain animal models of autoimmune disorders, we tested the hypothesis that an operative Gal-1/GM1 interplay induces immunosuppression in a manner evidenced by both in vivo and in vitro systems. Our study of murine experimental autoimmune encephalomyelitis (EAE) indicated suppressive effects by both CtxB and Gal-1 and further highlighted the role of GM1 in demonstrating enhanced susceptibility to EAE in mice lacking this ganglioside. At the in vitro level, polyclonal activation of murine regulatory T (Treg) cells caused up-regulation of Gal-1 that was both cell bound and released to the medium. Similar activation of murine CD4+ and CD8+ effector T (Teff) cells resulted in significant elevation of GM1 and GD1a, the neuraminidase-reactive precursor to GM1. Activation of Teff cells also up-regulated TRPC5 channels which mediated Ca2+ influx upon GM1 cross-linking by Gal-1 or CtxB. This involved co-cross-linking of heterodimeric integrin due to close association of these α4β1 and α5β1 glycoproteins with GM1. Short hairpin RNA (shRNA) knockdown of TRPC5 in Teff cells blocked contact-dependent proliferation inhibition by Treg cells as well as Gal-1/CtxB-triggered Ca2+ influx. Our results thus indicate GM1 in Teff cells to be the primary target of Gal-1 expressed by Treg cells, the resulting co-cross-linking and TRPC5 channel activation contributing importantly to the mechanism of autoimmune suppression.
Inhibition of cAMP Degradation Improves Regulatory T Cell-Mediated Suppression
Authors: Bopp Tobias , Dehzad Nina , Reuter Sebastian , Klein Matthias , Ullrich Nina , Stassen Michael , Schild Hansjörg , Buhl Roland , Schmitt Edgar , Taube Christian 
Published: March 2009

AbstractNaturally occurring regulatory T cells (nTreg cells) are crucial for the maintenance of peripheral tolerance. We have previously shown that a key mechanism of their suppressive action is based on a contact-dependent transfer of cAMP from nTreg cells to responder T cells. Herein, we further elucidate the important role of cAMP for the suppressive properties of nTreg cells. Prevention of cAMP degradation by application of the phosphodiesterase 4 inhibitor rolipram led to strongly increased suppressive potency of nTreg cells for Th2 cells in vitro and in vivo. Detailed analyses revealed that rolipram caused, in the presence of nTreg cells, a synergistic increase of cAMP in responder Th2 cells. In vivo, the application of nTreg cells in a strictly Th2-dependent preclinical model of asthma had only a marginal effect. However, the additional treatment with rolipram led to a considerable reduction of airway hyperresponsiveness and inflammation in a prophylactic as well as in a therapeutic model. This amelioration was correlated with enhanced cAMP-levels in lung Th2 cells in vivo. Collectively, these data support our observation that cAMP has a key function for nTreg cell-based suppression and they clearly demonstrate that the effect of cAMP on T responder cells can be greatly enhanced upon application of phosphodiesterase 4 inhibitors.
Cutting Edge: Dok-1 and Dok-2 Adaptor Molecules Are Regulated by Phosphatidylinositol 5-Phosphate Production in T Cells
Authors: Guittard Geoffrey , Gérard Audrey , Dupuis-Coronas Sophie , Tronchère Hélène , Mortier Eva , Favre Cédric , Olive Daniel , Zimmermann Pascale , Payrastre Bernard , Nunès Jacques A. 
Published: March 2009

Abstract
Downstream of tyrosine kinase (Dok) proteins Dok-1 and Dok-2 are involved in T cell homeostasis maintenance. Dok protein tyrosine phosphorylation plays a key role in establishing negative feedback loops of T cell signaling. These structurally related adapter molecules contain a pleckstrin homology (PH) domain generally acting as a lipid/protein-interacting module. We show that the presence of this PH domain is necessary for the tyrosine phosphorylation of Dok proteins and their negative functions in T cells. We find that Dok-1/Dok-2 PH domains bind in vitro to the rare phosphoinositide species, phosphatidylinositol 5-phosphate (PtdIns5P). Dok tyrosine phosphorylation correlates with PtdIns5P production in T cells upon TCR triggering. Furthermore, we demonstrate that PtdIns5P increase regulates Dok tyrosine phosphorylation in vivo. Together, our data identify a novel lipid mediator in T cell signaling and suggest that PH-PtdIns5P interactions regulate T cell responses.
Inorganic Drug‐Delivery Nanovehicle Conjugated with Cancer‐Cell‐Specific Ligand
Authors: Oh Jae‐Min , Choi Soo‐Jin , Lee Go‐Eun , Han Sun‐Ho , Choy Jin‐Ho 
Published: March 2009

AbstractThe surface of layered double hydroxide nanoparticles, a potential drug‐delivery nanovehicle, is modified with the cancer‐cell‐specific ligand, folic acid. The surface modification is successfully accomplished through step‐by‐step coupling reactions with aminopropyltriethoxysilane and 1‐ethyl‐3‐(3‐dimethyl aminopropyl)‐carbodiimide. In order to evaluate the cancer‐cell targeting effect of folic‐acid‐grafted layered double hydroxide utilizing fluorescence‐related assay, both layered double hydroxide with and without folic acid moiety are labeled with fluorescein 5′‐isothiocyanate. The uptake of layered double hydroxide and folic acid conjugated into KB and A549 cells is visualized using fluorescence microscopy and measured by flow cytometry. Both chemical and biological assay results demonstrate that the folic acid molecules are indeed conjugated to the surface of layered double hydroxide and thus the selectivity of nanovehicles to cancer cells overexpressing folate receptors increases. In this study, it is suggested that layered double hydroxide nanoparticles can be used as drug‐delivery carriers with a targeting function due to the chemical conjugation with specific ligand.
Stabilization of PbS Nanocrystals by Bovine Serum Albumin in its Native and Denatured States
Authors: Bakshi Mandeep Singh , Thakur Pankaj , Kaur Gurinder , Kaur Harpreet , Banipal Tarlok Singh , Possmayer Fred , Petersen Nils O. 
Published: March 2009

AbstractPbS nanocrystals (NCs) are synthesized in aqueous phase within a temperature range of 40–80 °C in the presence of native and denatured states of bovine serum albumen (BSA) as the capping/stabilizing agent. The NCs are characterized with the help of field‐emission scanning electron microscopy, high‐resolution transmission electron microscopy, X‐ray diffraction, and energy‐dispersive X‐ray analysis. At 40 °C, large ball‐shaped NCs (145 ± 37 nm) with small surface protrusions are formed when 1 × 10−4 g mL−1 BSA is used. As the reaction temperature is increased towards 80 °C, the size of NCs decreases and they acquire somewhat cubic geometries (49.1 ± 7.0 nm) due to a change in the capping behavior of BSA between its native and denatured states. The native and denatured states of BSA are simultaneously studied by fluorescence spectroscopy using tryptophan emission, and pH measurements with respect to time and temperature. Gel electrophoresis is used to determine the polarity of the BSA capped NCs. Only the small sized NCs conjugated with relatively larger amounts of BSA show a displacement towards the positively charged electrode in comparison to larger NCs with lower amounts of BSA capping. It was concluded that the denatured state of BSA is more effective in controlling the crystal growth of PbS than its native state especially in the low concentration range.
Photocatalytic Carbon‐Nanotube–TiO2 Composites
Authors: Woan Karran , Pyrgiotakis Georgios , Sigmund Wolfgang 
Published: March 2009

AbstractThe literature and advances in photocatalysis based on the combination of titania (TiO2) and carbon nanotubes is presented. The semiconductor basis for photocatalysis is introduced for anatase and rutile. Furthermore, the proposed mechanisms of catalytic enhancement resulting from the pairing of the titania semiconductor with either metallic, semiconducting, or defect‐rich carbon nanotubes (CNT) is discussed. Differences are apparent for the mixtures and chemically bonded CNT–TiO2 composites. The article then highlights the recent advances in the synthesis techniques for these composites and their photocatalytic reactions with organic, inorganic, and biological agents. Finally, various applications and challenges for these composite materials are reported.
A comparison of physiological variables in aged and young women during and following submaximal exercise
Authors: Deschenes Michael R. , Connell Alastair M. , Jackson Erica M. , Taylor Jessica L. , Glass Emily K. 
Published: March 2009

AbstractPreviously, we have examined how aging affects the physiological responses of men to endurance exercise. In the present investigation, we aimed to extend our assessment of the influence of aging on exercise‐induced responses by focusing on women. Ten young (20.3 ± 0.3 years; mean ± SE) and 10 aged (75.5 ± 1.2 years) women performed 30 min of cycling at 60–65% of their predetermined peak oxygen uptake. Data for respiratory exchange ratio (RER), heart rate, blood pressure, rectal temperature, and plasma metabolites were collected before exercise, at the 15th and 30th min of exercise, and at 5 and 15 min postexercise. A two‐way, repeated measures ANOVA with main effects of age and time was conducted on each variable. Our findings showed that age affected exercise‐induced responses of each variable quantified. Although RER, heart rate, temperature, and lactate were significantly (P< 0.05) higher among young women, blood pressure and glucose values were greater among aged women. Moreover, unlike previous results noted among men where age‐related differences primarily occurred during postexercise recovery, in women the effect of aging was detected during exercise itself. The data presented here indicate that aging impacts physiological responses of women to prolonged endurance exercise even when relative intensity (% of peak oxygen uptake) is held constant. Combined with our earlier study on men, these findings suggest that gender interacts with aging to determine whether age‐related differences are manifested during exercise itself, or during postexercise recovery. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.
Analysis of fatty acids in early mid‐life in fertile women: Implications for reproductive decline and other chronic health problems
Authors: Ford Judith H. , Tavendale Roger 
Published: March 2009

AbstractThe relationship between adipose fatty acid levels and age is examined in 635 Scottish fertile women aged 25–48. Fatty acids levels are highly significantly correlated with age. Factor analysis identifies four factors that account for 79.6% of variance in the data. Three Factors show significant regressions with age and patterns of involvement of specific fatty acids suggest that these Factors represent the activity of fatty acid delta‐desaturase enzymes as follows: Factor 1—delta‐9‐desaturase, Factor 2—delta‐5‐desaturase, and Factor 4—delta‐6‐desaturase. Key changes, apparently reductions in enzyme activity, occur through the 30 and 40‐year‐old age groups. Such changes in enzyme function could account for decline in female fertility and increases in body fat and chronic disease common in early mid‐life. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.
Asbestos fibers in para‐aortic and mesenteric lymph nodes
Authors: Uibu Toomas , Vanhala Esa , Sajantila Antti , Lunetta Philippe , Mäkelä‐Bengs Päivi , Goebeler Sirkka , Jäntti Matti , Tossavainen Antti 
Published: March 2009

AbstractBackgroundAsbestos fibers are known to accumulate in lung parenchyma and thoracic lymph nodes, but their presence and translocation into the extrapulmonary tissues need clarification. We assessed the presence of asbestos in the para‐aortic (PA) and mesenteric (ME) lymph nodes.MethodsPA and ME lymph nodes and lung tissue from 17 persons who underwent medicolegal autopsy for suspicion of asbestos‐related disease and from five controls were analyzed for asbestos fibers using transmission electron microscopy.ResultsHigh concentrations of amphibole asbestos fibers were detected in several lung tissue samples and in the respective PA and ME lymph nodes. The mean concentration for the 10 persons with a lung asbestos content of ≥1 million fibers/g of dry tissue (f/g) was 0.85 (<0.05–4.36) million f/g in the PA lymph nodes and 0.55 (<0.02–2.86) million f/g in the ME lymph nodes. The respective mean values for the 12 persons with a lung asbestos concentration of <1 million f/g were 0.07 for the PA lymph nodes and 0.03 million f/g for the ME nodes. The lung asbestos burden that predicted the detection of asbestos in abdominal lymph nodes was 0.45 million f/g.ConclusionsIn addition to their accumulation in lung tissue, asbestos fibers also collect in the retroperitoneal and the mesenteric lymph nodes. Even low‐level occupational exposure results in the presence of crocidolite, amosite, anthophyllite, tremolite, or chrysotile in these abdominal lymph nodes. Our results support the hypothesis of lymph drainage as an important translocation mechanism for asbestos in the human body. Am. J. Ind. Med. 52:464–470, 2009. © 2009 Wiley‐Liss, Inc.