bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Requirement for the p85 PI3K Adapter Protein BCAP in the Protection of Macrophages from Apoptosis Induced by Endoplasmic Reticulum Stress
Authors: Song SungWon , Chew Claude , Dale Benjamin M. , Traum Daniel , Peacock James , Yamazaki Tetsuo , Clynes Raphael , Kurosaki Tomohiro , Greenberg Steven 
Published: June 2011

AbstractMacrophages are innate immune cells that play key roles in regulation of the immune response and in tissue injury and repair. In response to specific innate immune stimuli, macrophages may exhibit signs of endoplasmic reticulum (ER) stress and progress to apoptosis. Factors that regulate macrophage survival under these conditions are poorly understood. In this study, we identified B cell adapter protein (BCAP), a p85 PI3K-binding adapter protein, in promoting survival in response to the combined challenge of LPS and ER stress. BCAP was unique among nine PI3K adapter proteins in being induced &gt;10-fold in response to LPS. LPS-stimulated macrophages incubated with thapsigargin, a sarcoplasmic/endoplasmic reticulum calcium ATPase inhibitor that induces ER stress, underwent caspase-3 activation and apoptosis. Macrophages from BCAP−/− mice exhibited increased apoptosis in response to these stimuli. BCAP-deficient macrophages demonstrated decreased activation of Akt, but not ERK, and, unlike BCAP-deficient B cells, expressed normal amounts of the NF-κB subunits, c-Rel and RelA. Retroviral transduction of BCAP-deficient macrophages with wild-type BCAP, but not a Y4F BCAP mutant defective in binding the SH2 domain of p85 PI3K, reversed the proapoptotic phenotype observed in BCAP-deficient macrophages. We conclude that BCAP is a nonredundant PI3K adapter protein in macrophages that is required for maximal cell survival in response to ER stress. We suggest that as macrophages engage their pathogenic targets, innate immune receptors trigger increased expression of BCAP, which endows them with the capacity to withstand further challenges from ongoing cellular insults, such as ER stress.
Induction of Mucin and MUC5AC Expression by the Protease Activity of Aspergillus fumigatus in Airway Epithelial Cells
Authors: Oguma Tsuyoshi , Asano Koichiro , Tomomatsu Katsuyoshi , Kodama Motohiro , Fukunaga Koichi , Shiomi Tetsuya , Ohmori Nao , Ueda Soichiro , Takihara Takahisa , Shiraishi Yoshiki , Sayama Koichi , Kagawa Shizuko , Natori Yukikazu , Lilly Craig M. , Satoh Kazuo , Makimura Koichi , Ishizaka Akitoshi 
Published: June 2011

Abstract
Allergic bronchopulmonary mycosis, characterized by excessive mucus secretion, airflow limitation, bronchiectasis, and peripheral blood eosinophilia, is predominantly caused by a fungal pathogen, Aspergillus fumigatus. Using DNA microarray analysis of NCI-H292 cells, a human bronchial epithelial cell line, stimulated with fungal extracts from A. fumigatus, Alternaria alternata, or Penicillium notatum, we identified a mucin-related MUC5AC as one of the genes, the expression of which was selectively induced by A. fumigatus. Quantitative RT-PCR, ELISA, and histochemical analyses confirmed an induction of mucin and MUC5AC expression by A. fumigatus extracts or the culture supernatant of live microorganisms in NCI-H292 cells and primary cultures of airway epithelial cells. The expression of MUC5AC induced by A. fumigatus extracts diminished in the presence of neutralizing Abs or of inhibitors of the epidermal growth factor receptor or its ligand, TGF-α. We also found that A. fumigatus extracts activated the TNF-α–converting enzyme (TACE), critical for the cleavage of membrane-bound pro–TGF-α, and its inhibition with low-molecular weight inhibitors or small interfering RNA suppressed the expression of MUC5AC. The protease activity of A. fumigatus extracts was greater than that of other fungal extracts, and treatment with a serine protease inhibitor, but not with a cysteine protease inhibitor, eliminated its ability to activate TACE or induce the expression of MUC5AC mRNA in NCI-H292. In conclusion, the prominent serine protease activity of A. fumigatus, which caused the overproduction of mucus by the bronchial epithelium via the activation of the TACE/TGF-α/epidermal growth factor receptor pathway, may be a pathogenetic mechanism of allergic bronchopulmonary mycosis.
Lenalidomide Enhances Antigen-Specific Activity and Decreases CD45RA Expression of T Cells from Patients with Multiple Myeloma
Authors: Neuber Brigitte , Herth Isabelle , Tolliver Claudia , Schoenland Stefan , Hegenbart Ute , Hose Dirk , Witzens-Harig Mathias , Ho Anthony D. , Goldschmidt Hartmut , Klein Bernard , Hundemer Michael 
Published: June 2011

AbstractThe aim of this study was to investigate whether the specific T cell response against the multiple myeloma Ag HM1.24 is enhanced by the immunomodulatory drug lenalidomide (Revlimid). Ag-specific CD3+CD8+ T cells against the HM1.24 Ag were expanded in vitro by dendritic cells in 29 healthy donors and 26 patients with plasma cell dyscrasias. Ag-specific activation was analyzed by IFN-γ, granzyme B, and perforin secretion using ELISA, ELISPOT assay, and intracellular staining, and generation of Ag-specific T cells was analyzed by tetramer staining. Expression of T cell maturation markers (CD45RA, CD45R0, CCR7, and CD28) was investigated by flow cytometry. We found that activation of HM1.24-specific T cells from healthy donors and patients with plasma cell dyscrasias was enhanced significantly by lenalidomide and furthermore that the impact of lenalidomide on T cells depends on the duration of the exposure. Notably, lenalidomide supports the downregulation of CD45RA on T cells upon activation, observed in healthy donors and in patients in vitro and also in patients during lenalidomide therapy in vivo. We showed for the first time, to our knowledge, that lenalidomide enhances the Ag-specific activation of T cells and the subsequent downregulation of CD45RA expression of T cells in vitro and in vivo.
Regulation of the Estrous Cycle by Neutrophils via Opioid Peptides
Authors: Sasaki Soichiro , Tamaki Yutaka , Nagata Kisaburo , Kobayashi Yoshiro 
Published: June 2011

AbstractWe found previously that neutrophil-depleted mice exhibited significant blockading of both the regular estrous cycle and cyclic changes of steroid hormone levels. In this study, we aimed at elucidation of the underlying mechanism. To examine the possibility that an increase in bacteria in the vaginal vault of neutrophil-depleted mice causes blockading of the estrous cycle, we treated neutrophil-depleted mice with antibiotics but failed to restore the estrous cycle. We then examined another possibility that neutrophils regulate the estrous cycle via opioid peptides, because opioid peptides regulate steroidogenesis in theca and granulosa cells in the ovaries, and because neutrophils contain opioid peptides. In support of this possibility, naloxone, an opioid antagonist, blocked the estrous cycle and a μ opioid receptor agonist restored the estrous cycle in neutrophil-depleted mice. Pro-opiomelanocortin was immunohistochemically detected in peripheral blood neutrophils but not in ones that had infiltrated into the ovaries. i.v. injection of anti–MIP-2 polyclonal Ab caused blockading of the estrous cycle, whereas MIP-2 was detected in the ovaries, suggesting a role of MIP-2 in the regulation of the estrous cycle. Moreover, i.v. injection of MIP-2 decreased the pro-opiomelanocortin signal in peripheral blood neutrophils and caused blockading of the estrous cycle. Together, these results suggest that neutrophils maintain the estrous cycle via opioid peptides.
Cutting Edge: JAM-C Controls Homeostatic Chemokine Secretion in Lymph Node Fibroblastic Reticular Cells Expressing Thrombomodulin
Authors: Frontera Vincent , Arcangeli Marie-Laure , Zimmerli Claudia , Bardin Florence , Obrados Elodie , Audebert Stéphane , Bajenoff Marc , Borg Jean-Paul , Aurrand-Lions Michel 
Published: June 2011

Abstract
The development and maintenance of secondary lymphoid organs, such as lymph nodes, occur in a highly coordinated manner involving lymphoid chemokine production by stromal cells. Although developmental pathways inducing lymphoid chemokine production during organogenesis are known, signals maintaining cytokine production in adults are still elusive. In this study, we show that thrombomodulin and platelet-derived growth factor receptor α identify a population of fibroblastic reticular cells in which chemokine secretion is controlled by JAM-C. We demonstrate that Jam-C–deficient mice and mice treated with Ab against JAM-C present significant decreases in stromal cell-derived factor 1α (CXCL12), CCL21, and CCL19 intranodal content. This effect is correlated with reduced naive T cell egress from lymph nodes of anti–JAM-C–treated mice.
Early and Transient Release of Leukocyte Pentraxin 3 during Acute Myocardial Infarction
Authors: Maugeri Norma , Rovere-Querini Patrizia , Slavich Massimo , Coppi Giovanni , Doni Andrea , Bottazzi Barbara , Garlanda Cecilia , Cianflone Domenico , Maseri Attilio , Mantovani Alberto , Manfredi Angelo A. 
Published: June 2011

Abstract
Pentraxin 3 (PTX3) plays cardioprotective and anti-atherogenic roles in murine models. PTX3 blood levels raise during early acute myocardial infarction (AMI). Neutrophils from healthy subjects physiologically contain PTX3 in secondary (also called specific) granules. In this study, we report that circulating neutrophils release preformed PTX3 in the early phase of AMI (within 6 h from the onset of clinical symptoms). Depletion of intracellular PTX3 correlates with increased plasma levels and with platelet–neutrophil heterotypic aggregates. Neutrophil PTX3 returns to normal values 48 h after the onset of symptoms; concentration does not vary in matched healthy controls or in patients with chronic stable angina. In vitro, recognition of activated P-selectin+ platelets causes the formation of neutrophil–platelet heteroaggregates and the release of neutrophil PTX3. Purified or membrane-bound P-selectin triggers PTX3 release from resting neutrophils. Released PTX3 binds to activated platelets in vitro. Moreover, PTX3 binds to a substantial fraction of platelets from patients in the circulating blood. PTX3-bound activated platelets have a reduced ability to 1) form heterotypic aggregates with neutrophils and monocytes; 2) activate neutrophils, as evaluated assessing the upregulation of leukocyte β2 integrins; 3) aggregate with other platelets; and 4) bind to fibrinogen. Our results suggest that neutrophils early release prestored PTX3 in patients undergoing AMI. PTX3 binds to activated circulating platelets and dampens their proinflammatory and prothrombotic action, thus possibly contributing to its cardioprotective effects.
Nod1 Activation by Bacterial iE-DAP Induces Maternal–Fetal Inflammation and Preterm Labor
Authors: Cardenas Ingrid , Mulla Melissa J. , Myrtolli Kledia , Sfakianaki Anna K. , Norwitz Errol R. , Tadesse Serkalem , Guller Seth , Abrahams Vikki M. 
Published: June 2011

Abstract
There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-α, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal–fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor.
Cutting Edge: Reactive Oxygen Species Inhibitors Block Priming, but Not Activation, of the NLRP3 Inflammasome
Authors: Bauernfeind Franz , Bartok Eva , Rieger Anna , Franchi Luigi , Núñez Gabriel , Hornung Veit 
Published: June 2011

Abstract
A common denominator among the multiple damage-inducing agents that ultimately lead to activation of NLRP3 has not yet been identified. Recently, production of reactive oxygen species (ROS) has been suggested to act as a common event upstream of the NLRP3 inflammasome machinery. Because de novo translation of NLRP3 is an essential step in the activation of NLRP3, we investigated the role of substances that inhibit either ROS production or its oxidative activity. Although we observe that NLRP3 inflammasome activation is unique among other known inflammasomes in its sensitivity to ROS inhibition, we have found that this phenomenon is attributable to the fact that NLRP3 strictly requires priming by a proinflammatory signal, a step that is blocked by ROS inhibitors. Although these data do not exclude a general role for ROS production in the process of NLRP3-triggered inflammation, they would put ROS upstream of NLRP3 induction, but not activation.
Developing-World Disaster Research: Present Evidence and Future Priorities
Authors: Roy Nobhojit , Thakkar Purvi , Shah Hemant 
Published: June 2011

ABSTRACTObjectives: The technology and resource-rich solutions of the developed world may not be completely applicable to or replicable in disasters occurring in the developing world. With the current looming hazards of pandemics, climate change, global terrorism and conflicts around the world, policy makers and governments will need high-quality scientific data to make informed decisions for preparedness and mitigation. The evidence on disasters in peer-reviewed journals about the developing world was examined for quality and quantity in this systematic review.Methods: PubMed was searched using the Medical Subject Heading (MeSH) terms disasters, disaster medicine, rescue work, relief work, and conflict and then refined using the MeSH term developing country. The final list of selected manuscripts were analyzed by type of article, level of evidence, theme of the manuscript and topic, author affiliation, and region of the study.Results: After searching and refining, <1% of the citations in PubMed addressed disasters in developing countries. The majority was original research articles or reviews, and most of the original research articles were level IV or V evidence. Less than 25% of the authors were from the developing world. The predominant themes were missions, health care provision, and humanitarian aid during the acute phase of disasters in the developing world.Conclusions: Considering that 85% of disasters and 95% of disaster-related deaths occur in the developing world, the overwhelming number of casualties has contributed insignificantly to the world's peer-reviewed literature. Less than 1% of all disaster-related publications are about disasters in the developing world. This may be a publication bias, or it may be a genuine lack of submissions dealing with these disasters. Authors in this part of the world need to contribute to future disaster research through better-quality systematic research and better funding priorities. Aid for sustaining long-term disaster research may be a more useful investment in mitigating future disasters than short-term humanitarian aid missions to the developing world.(Disaster Med Public Health Preparedness. 2011;5:112–116)
Effects of the Design and Practice of Points-of-Dispensing on Patient-Reported Satisfaction: Municipal H1N1 Clinics in Rhode Island
Authors: Balbi David A. , Calcagni Kristen 
Published: June 2011

ABSTRACTObjectives: The primary objective of the study was to understand the public's perception of the effectiveness of Rhode Island's public health emergency response plans by using municipal H1N1 vaccination clinics conducted in Rhode Island in January and February 2010 as a basis for public reaction. The effect of previous exercises on public perception was also examined.Method: A survey of 926 H1N1 vaccination clinic attendees was conducted via mail during the period between March 18 and May 1, 2010.Results: A total of 579 surveys were returned, rendering a response rate of 62.5%. The majority of clinic attendees traveled ≤10 mi to the vaccination clinic (90.48%). The average self-reported wait time inside the clinic was 19.16 minutes, and 69.84% of respondents expected to have waited longer before attending the clinic. The self-reported wait time was negatively correlated with patient-reported overall clinic satisfaction. A total of 98.08% of respondents believed that the signage used at the clinics was easy to follow, 100% of respondents believed that the clinic staff was courteous and respectful, and 82.35% of respondents reported that they would rate the clinic they attended as excellent.Conclusions: Rhode Islanders prefer local public health service sites. There was a minor difference in the overall satisfaction of respondents who attended municipal clinics that had exercised emergency plans before activation for H1N1 vaccinations and those municipalities that had not previously exercised. The lack of difference between the practicing and nonpracticing points-of-dispensing may be caused by the standardization of municipal emergency plans, uniformity in the guidance and support of each clinic provided by the Rhode Island Department of Health, and municipalities that had not previously exercised had the opportunity to observe those that had exercised. Having thorough mass dispensing plans in place in advance of a public health emergency is as important as having exercised a point-of-dispensing before a real-world activation.(Disaster Med Public Health Preparedness. 2011;5:106–111)
Use of In Vivo Biotinylation for Chromatin Immunoprecipitation
Authors: Kulyyassov Arman , Shoaib Muhammad , Ogryzko Vasily 
Published: June 2011

AbstractThis unit describes a system for expression of biotinylated proteins in mammalian cells in vivo, and its application to chromatin immunoprecipitation (ChIP). The system is based on co‐expression of the target protein fused to a short biotin acceptor domain, together with the biotinylating enzyme BirA from Escherichia coli. The superior strength of the biotin‐avidin interaction in the modified ChIP protocol presented here allows one to employ more stringent washing conditions, resulting in a better signal/noise ratio. Methods for interpreting the data obtained from ChIP samples analyzed by qPCR, and methods for testing the efficiency of biotinylation using a streptavidin gel‐shift are also presented. In addition, a complementary method, based on isothermal multiple strand displacement amplification (IMDA) of circular concatemers generated from the DNA fragments obtained after ChIP, is described. This method helps to decrease bias in DNA amplification and is useful for the analysis of complex mixtures of DNA fragments typically generated in miniscale ChIP experiments. Curr. Protoc. Cell Biol. 51:17.12.1‐17.12.22. © 2011 by John Wiley & Sons, Inc.
Correlates of physical activity and inactivity in urban Mexican youth
Authors: Siegel Shannon R. , Malina Robert M. , Peña Reyes Maria Eugenia , Cárdenas Barahona Eyra E. , Cumming Sean P. 
Published: June 2011

AbstractObjectives:To evaluate correlates of physical activity in Mexico City school youth.Methods:A cross‐sectional survey was conducted with 1,004 school youth (490 males and 514 females), 9–18 years of age resident in Mexico City. Age, height, body mass index (BMI), socioeconomic status (SES), time viewing television and playing video games (physical inactivity), and perceived sport/physical activity status of mother and father were evaluated as potential correlates of physical activity [Physical Activity Questionnaire (PAQ)]. Multiple linear regression analyses (backward elimination) by age group and sex were used.Results:Physical activity declined in older adolescents, while differences between the two younger age groups were minimal. Television time showed a similar tendency. Overall, fathers were perceived as being active in sport/physical activity more frequently than mothers. Significant predictors of activity differed by age group and sex. For the total sample, age (negative) and perceived sport/activity status of the mother (positive) were significant predictors of the PAQ in boys, and age and the BMI (negative) and height and perceived sport/activity status of both parents (positive) were significant predictors for girls. Age (negative) was the main predictor for inactivity in both males and females.Conclusions:Potential correlates of physical activity and inactivity considered in this analysis were limited and accounted for relatively little of the variance in physical activity. The role of perceived sport/activity of the parents, especially among younger boys and girls, is particularly of interest and merits more detailed study. Nevertheless, many other variables also need to be considered. Am. J. Hum. Biol. 2011. © 2011 Wiley‐Liss, Inc.
No association observed between schizophrenia and non‐HLA coeliac disease genes: Integration with the initial MYO9B association with coeliac disease
Authors: Law Matthew H. , Bradford Matilda , McNamara Neil , Gajda Andy , Wei Jun 
Published: June 2011

AbstractSchizophrenia is a severe psychotic illness with a heterogeneous presentation and a devastating impact on social and occupational function. Worldwide variations in schizophrenia incidence rates suggest that local conditions may modify disease risk. The human leukocyte antigen (HLA) region has been confirmed to be associated with schizophrenia by genome‐wide association studies in populations across the world. While the presence of autoimmune processes in a subgroup of schizophrenia cases is contentious, the immune system could allow environmental exposures to lead to schizophrenia by generating improper immune response. To investigate this topic, we reviewed the current evidence of the relationship between schizophrenia and coeliac disease. Based on this review, we performed genetic analysis of the MYO9B gene and the IL‐2/IL‐21 locus by genotyping SNPs that have been previously associated with coeliac disease or schizophrenia in 223 families, 108 unrelated individuals with schizophrenia and 120 controls. Finding no evidence for association with these two loci in our study samples, we applied meta‐analytic techniques to combine our findings with previous reports. This synthesis, in light of our review of previous reports, suggests a differing developmental trajectory for schizophrenia and coeliac disease. It is possible that these two conditions do not share any functional overlap. © 2011 Wiley‐Liss, Inc.