bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Maturity Stage and Short-Term Storage on the Biological Quality of Sweet Pepper Fruits
Authors: Kołton Anna , Wojciechowska Renata , Leja Maria 
Published: August 2011

Effect of Maturity Stage and Short-Term Storage on the Biological Quality of Sweet Pepper Fruits
Sweet pepper plants of Spartacus cultivar were grown in plastic tunnel on rockwool using the fertigation technique. The three year experiment was carried out in 2006-2008. Fruits were harvested every year in three maturity stages: green, turning and red. The contents of ascorbic acid, phenols, soluble sugars, nitrate and ammonium ions, total nitrogen, free amino acids and dry matter were determined in freshly harvested fruits as well as after short-term (two weeks) storage.
Red pepper fruits accumulated significantly more ascorbic acid, soluble sugars and phenols in comparison with the green and turning ones. The level of nitrate ions was highest in the green fruits and decreased during their ripening while the ammonium ion concentration increased. The lowest content of amino acids was observed in green fruits.
Two week storage at 5-8°C, followed by two days at room temperature caused the reduction of nitrate ions in green and red fruits. Ammonium ion content as well as phenol and soluble sugar level increased in stored fruits, irrespectively of their maturity stage. Ascorbic acid content increased in the stored turning and red pepper fruits as related to its initial concentration. Dry matter content did not change after storage. Biological quality of harvested pepper fruits depended of their maturity stage, however, their response to short-term storage was similar.
Scientific Report: Highlights of 24th ICAR, 8–11 May 2011, Sofia, Bulgaria
Authors: Hodge Anthony Vere 
Published: August 2011

The 24th ICAR meeting was held in Sofia, Bulgaria, 8–11 May 2011. This report summarizes the presentations by the ICAR award winners, Earl Kern and Brian Gowen; the keynote address by Albert (ADME) Osterhaus; the Plenary lectures by Raina Fichorova, Ralf Bartenschlager and Esteban Domingo; the invited speakers for the symposia; and a few of those by contributors. This report aims to reflect the diversity of topics across different disciplines (chemistry to biology) discussed at ICAR: old viruses (smallpox), emerging viruses (SARS, new strains of influenza and flaviviruses), problematic viruses (HIV and HCV), sporadic viruses (arenaviruses), neglected viruses (enteroviruses), new research targets (for HCV) and new approaches (lethal mutagenesis). There were timely reports on promising compounds against adenoviruses, cytomegalovirus, HCV and HIV in clinical trials. This conference illuminated the constantly evolving field of antiviral chemotherapy by providing a forum to present and discuss new antiviral compounds, new uses for old compounds and exciting clinical results. This ICAR was a fitting testament to the ‘father of antiviral chemotherapy’, Bill Prusoff, who died aged 90 in April 2011.
First-Year Experience of Chemotherapy for Advanced Retinoblastoma in Tanzania: Disease Profile, Outcomes, and Challenges in 2008
Authors: Carrim Zia I. , Kajaige Jane , Bowman Richard J. , Lavy Tim E. , Scanlan Patricia 
Published: August 2011

Purpose:
To examine the profile of retinoblastoma in a national tertiary referral center in Tanzania and to report first-year outcomes of its treatment using chemotherapy.

Methods:
All patients with retinoblastoma referred in 2008 were included. Disease was classified on clinical grounds as ocular, orbital, or metastatic. Those with ocular and orbital disease received chemotherapy. Remission was the main outcome measure and defined as absence of disease at the end of treatment.

Results:

In 2008, 37 patients (20 males and 17 females) with retinoblastoma were referred to Ocean Road Cancer Institute. The mean delay from the first sign of disease to presentation at hospital was 10.4 ± 8.7 months. Disease was ocular in 32% (12 of 37), orbital in 57% (21 of 37), and metastatic in 11% (4 of 37). Of those with ocular disease, 67% (8 of 12) completed chemotherapy and all (8 of 8) achieved remission. In contrast, 48% (10 of 21) with orbital disease completed chemotherapy and only 50% (5 of 10) achieved remission. The difference in outcome between the groups was statistically significant (
P
= .001, Fisher exact test).

Conclusion:
The profile of retinoblastoma in Tanzania is skewed toward severe invasive disease. Despite the introduction of chemotherapy, further improvements in mortality and morbidity can only be achieved through emphasis on early detection.
MAPK Kinase 3 Specifically Regulates FcεRI-Mediated IL-4 Production by Mast Cells
Authors: MacNeil Adam J. , Yang Yong Jun , Lin Tong-Jun 
Published: August 2011

Abstract
Mast cells play a central role in allergic inflammation and are activated through cross-linking of FcεRI receptor-bound IgE, initiating a signaling cascade resulting in production of biologically potent mediators. Signaling pathways in the regulation of specific mediators remain incompletely defined. In this study, we examined the role of MAPK kinase 3 (MKK3) in IgE-dependent mast cell activation. In an in vivo model of passive cutaneous anaphylaxis, MKK3-deficient mice showed a deficit in late-phase IgE-dependent inflammation. To characterize the mechanism of this deficiency, we cultured bone marrow-derived mast cells (BMMCs) from wild-type and MKK3-deficient mice. We found that FcεRI-mediated mast cell activation induced rapid MKK3 phosphorylation by 5 min, diminishing slowly after 6 h. In MKK3-deficient BMMCs, phosphorylation of p38 was reduced at early and later time points. Among 40 cytokines tested using a protein array, IL-4 was the only cytokine specifically downregulated in MKK3-deficient BMMCs. Reduced IL-4 expression was seen in the local skin of MKK3-deficient mice following passive cutaneous allergic reaction. Furthermore, early growth response-1 (Egr1) bound to the promoter of IL-4 in FcεRI-activated mast cells, and Egr1 transcription factor activity was diminished in MKK3-deficient BMMCs. Finally, mast cell-deficient mice reconstituted with MKK3-deficient BMMCs displayed a significantly impaired late-phase allergic inflammatory response. Thus, mast cell MKK3 signaling contributes to IgE-dependent allergic inflammation and is a specific regulator of FcεRI-induced IL-4 production.
Species-Specific Determinants in the IgG CH3 Domain Enable Fab-Arm Exchange by Affecting the Noncovalent CH3–CH3 Interaction Strength
Authors: Labrijn Aran F. , Rispens Theo , Meesters Joyce , Rose Rebecca J. , den Bleker Tamara H. , Loverix Stefan , van den Bremer Ewald T. J. , Neijssen Joost , Vink Tom , Lasters Ignace , Aalberse Rob C. , Heck Albert J. R. , van de Winkel Jan G. J. , Schuurman Janine , Parren Paul W. H. I. 
Published: August 2011

Abstract
A distinctive feature of human IgG4 is its ability to recombine half molecules (H chain and attached L chain) through a dynamic process termed Fab-arm exchange, which results in bispecific Abs. It is becoming evident that the process of Fab-arm exchange is conserved in several mammalian species, and thereby represents a mechanism that impacts humoral immunity more generally than previously thought. In humans, Fab-arm exchange has been attributed to the IgG4 core-hinge sequence (226-CPSCP-230) in combination with unknown determinants in the third constant H chain domain (CH3). In this study, we investigated the role of the CH3 domain in the mechanism of Fab-arm exchange, and thus identified amino acid position 409 as the critical CH3 determinant in human IgG, with R409 resulting in exchange and K409 resulting in stable IgG. Interestingly, studies with IgG from various species showed that Fab-arm exchange could not be assigned to a common CH3 domain amino acid motif. Accordingly, in rhesus monkeys (Macaca mulatta), aa 405 was identified as the CH3 determinant responsible (in combination with 226-CPACP-230). Using native mass spectrometry, we demonstrated that the ability to exchange Fab-arms correlated with the CH3–CH3 dissociation constant. Species-specific adaptations in the CH3 domain thus enable Fab-arm exchange by affecting the inter-CH3 domain interaction strength. The redistribution of Ag-binding domains between molecules may constitute a general immunological and evolutionary advantage. The current insights impact our view of humoral immunity and should furthermore be considered in the design and evaluation of Ab-based studies and therapeutics.
Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-β1–Dependent and –Independent Mechanisms
Authors: Mi Su , Li Zhe , Yang Hong-Zhen , Liu Hong , Wang Jia-Ping , Ma Yong-Gang , Wang Xiao-Xing , Liu Han-Zhi , Sun Wei , Hu Zhuo-Wei 
Published: August 2011

Abstract
Pulmonary fibrosis is the pathologic basis for a variety of incurable human chronic lung diseases. IL-17A, a glycoprotein secreted from IL-17–producing cells, has recently been shown to be a proinflammatory cytokine involved in chronic inflammation and autoimmune disease. In this study, we report that IL-17A increased the synthesis and secretion of collagen and promoted the epithelial–mesenchymal transition in alveolar epithelial cells in a TGF-β1–dependent manner. Using in vivo fibrotic models, we found IL-17A expression to be elevated and IL-17A–associated signaling pathways to be activated in fibrotic lung tissues. Neutralization of IL-17A in vivo promoted the resolution of bleomycin-induced acute inflammation, attenuated pulmonary fibrosis, and increased survival. Additionally, IL-17A antagonism inhibited silica-induced chronic inflammation and pulmonary fibrosis. Targeting IL-17A resulted in a shift of the suppressive immune response in fibrotic lung tissue toward a Th1-type immune response, and it effectively induced autophagy, which promoted the autophagic degradation of collagen and autophagy-associated cell death. Moreover, IL-17A was found to attenuate the starvation-induced autophagy, and autophagy modulators regulated collagen degradation in the alveolar epithelial cells in a TGF-β1–independent manner. Administration of 3-methylamphetamine, an autophagy inhibitor, reversed the therapeutic efficacy of IL-17A antagonism in pulmonary fibrosis. Our studies indicate that IL-17A participates in the development and progression of pulmonary fibrosis in both TGF-β1–dependent and –independent manners and that the components of the IL-17A signaling pathway are potential therapeutic targets for the treatment of fibroproliferative lung diseases.
Activation of TLR2 Enhances Tight Junction Barrier in Epidermal Keratinocytes
Authors: Yuki Takuo , Yoshida Hiroyuki , Akazawa Yumiko , Komiya Aya , Sugiyama Yoshinori , Inoue Shintaro 
Published: August 2011

Abstract
The epidermis has developed physical and immunological barriers that prevent infiltration of deleterious chemicals and pathogens. As a first step to understanding the relationship between these barriers, we investigated whether TLR2 activation functionally alters tight junctions (TJs) in cultured human keratinocytes. Stimulation with peptidoglycan, a ligand for TLR2, elevated the TJ-associated barrier in the space of 3 h. The increase in TJ-associated barrier function due to peptidoglycan stimulation was suppressed by the knockdown of TLR adaptor MyD88 or the pretreatment with TLR2-neutralizing Ab, indicating that TLR2 activation enhanced TJ-associated barrier. One and 3 h after peptidoglycan stimulation, expression levels of the TJ proteins occludin, claudin-1, claudin-4, and ZO-1 were unchanged. However, immunoprecipitation studies demonstrated that the association of phospho-atypical protein kinase Cζ/ι, crucial for TJ biogenesis, with occludin was increased. Significantly, inhibition of atypical protein kinase Cζ/ι activity completely blocked the immediate elevation of the TJ-associated barrier. Finally, peptidoglycan was applied to the stratum corneum surface of a human skin equivalent, and the TJ barrier was evaluated. In the space of 3 h after the stimulation, the amount of intercellular tracer in the stratum corneum incubated from the dermal side was reduced, indicating that the TJ barrier is strengthened via TLR2 activation. Taken together, our findings indicated that infiltration of pathogens into the epidermis immediately enhanced TJ function via TLR2 signaling. Furthermore, the dynamically controlled TJs in skin are considered fundamental in preventing further invasion of pathogens and maintaining cutaneous barrier homeostasis.
B Cells and TCR Avidity Determine Distinct Functions of CD4+ T Cells in Retroviral Infection
Authors: Ploquin Mickaël J.-Y. , Eksmond Urszula , Kassiotis George 
Published: August 2011

Abstract
The T cell-dependent B cell response relies on cognate interaction between B cells and CD4+ Th cells. However, the consequences of this interaction for CD4+ T cells are not entirely known. B cells generally promote CD4+ T cell responses to pathogens, albeit to a variable degree. In contrast, CD4+ T cell responses to self- or tumor Ags are often suppressed by B cells. In this study, we demonstrated that interaction with B cells dramatically inhibited the function of virus-specific CD4+ T cells in retroviral infection. We have used Friend virus infection of mice as a model for retroviral infection, in which the behavior of virus-specific CD4+ T cells was monitored according to their TCR avidity. We report that avidity for Ag and interaction with B cells determine distinct aspects of the primary CD4+ T cell response to Friend virus infection. Virus-specific CD4+ T cells followed exclusive Th1 and T follicular helper (Tfh) differentiation. High avidity for Ag facilitated expansion during priming and enhanced the capacity for IFN-γ and IL-21 production. In contrast, Tfh differentiation was not affected by avidity for Ag. By reducing or preventing B cell interaction, we found that B cells promoted Tfh differentiation, induced programmed death 1 expression, and inhibited IFN-γ production by virus-specific CD4+ T cells. Ultimately, B cells protected hosts from CD4+ T cell-mediated immune pathology, at the detriment of CD4+ T cell-mediated protective immunity. Our results suggest that B cell presentation of vaccine Ags could be manipulated to direct the appropriate CD4+ T cell response.
Mutations in a Dominant Nef Epitope of Simian Immunodeficiency Virus Diminish TCR:Epitope Peptide Affinity but not Epitope Peptide:MHC Class I Binding
Authors: Cale Evan M. , Bazick Heidi S. , Rianprakaisang Tony A. , Alam S. Munir , Letvin Norman L. 
Published: August 2011

Abstract
Viruses like HIV and SIV escape from containment by CD8+ T lymphocytes through generating mutations that interfere with epitope peptide:MHC class I binding. However, mutations in some viral epitopes are selected for that have no impact on this binding. We explored the mechanism underlying the evolution of such epitopes by studying CD8+ T lymphocyte recognition of a dominant Nef epitope of SIVmac251 in infected Mamu-A*02+ rhesus monkeys. Clonal analysis of the p199RY-specific CD8+ T lymphocyte repertoire in these monkeys indicated that identical T cell clones were capable of recognizing wild-type (WT) and mutant epitope sequences. However, we found that the functional avidity of these CD8+ T lymphocytes for the mutant peptide:Mamu-A*02 complex was diminished. Using surface plasmon resonance to measure the binding affinity of the p199RY-specific TCR repertoire for WT and mutant p199RY peptide:Mamu-A*02 monomeric complexes, we found that the mutant p199RY peptide:Mamu-A*02 complexes had a lower affinity for TCRs purified from CD8+ T lymphocytes than did the WT p199RY peptide:Mamu-A*02 complexes. These studies demonstrated that differences in TCR affinity for peptide:MHC class I ligands can alter functional p199RY-specific CD8+ T lymphocyte responses to mutated epitopes, decreasing the capacity of these cells to contain SIVmac251 replication.
Cytoplasmic Igα Serine/Threonines Fine-Tune Igα Tyrosine Phosphorylation and Limit Bone Marrow Plasma Cell Formation
Authors: Patterson Heide Christine , Kraus Manfred , Wang Donghai , Shahsafaei Aliakbar , Henderson Joel M. , Seagal Jane , Otipoby Kevin L. , Thai To-Ha , Rajewsky Klaus 
Published: August 2011

Abstract
Igα serine 191 and 197 and threonine 203, which are located in proximity of the Igα ITAM, dampen Igα ITAM tyrosine phosphorylation. In this study, we show that mice with targeted mutations of Igα S191, 197, and T203 displayed elevated serum IgG2c and IgG2b concentrations and had elevated numbers of IgG2c- and IgG2b-secreting cells in the bone marrow. BCR-induced Igα tyrosine phosphorylation was slightly increased in splenic B cells. Our results suggest that Igα serine/threonines limit formation of IgG2c- and IgG2b-secreting bone marrow plasma cells, possibly by fine-tuning Igα tyrosine-mediated BCR signaling.
Loss of CD20 and Bound CD20 Antibody from Opsonized B Cells Occurs More Rapidly Because of Trogocytosis Mediated by Fc Receptor-Expressing Effector Cells Than Direct Internalization by the B Cells
Authors: Beum Paul V. , Peek Elizabeth M. , Lindorfer Margaret A. , Beurskens Frank J. , Engelberts Patrick J. , Parren Paul W. H. I. , van de Winkel Jan G. J. , Taylor Ronald P. 
Published: August 2011

Abstract
We previously reported that 1 h after infusion of CD20 mAb rituximab in patients with chronic lymphocytic leukemia (CLL), &gt;80% of CD20 was removed from circulating B cells, and we replicated this finding, based on in vitro models. This reaction occurs via an endocytic process called shaving/trogocytosis, mediated by FcγR on acceptor cells including monocytes/macrophages, which remove and internalize rituximab–CD20 immune complexes from B cells. Beers et al. reported that CD20 mAb-induced antigenic modulation occurs as a result of internalization of B cell-bound mAb–CD20 complexes by the B cells themselves, with internalization of ∼40% observed after 2 h at 37°C. These findings raise fundamental questions regarding the relative importance of shaving versus internalization in promoting CD20 loss and have substantial implications for the design of mAb-based cancer therapies. Therefore, we performed direct comparisons, based on flow cytometry, to determine the relative rates and extent of shaving versus internalization. B cells, from cell lines, from patients with CLL, and from normal donors, were opsonized with CD20 mAbs rituximab or ofatumumab and incubated for varying times and then reacted with acceptor THP-1 monocytes to promote shaving. We find that shaving induces considerably greater loss of CD20 and bound mAb from opsonized B cells in much shorter time periods (75–90% in &lt;45 min) than is observed for internalization. Both shaving/trogocytosis and internalization could contribute to CD20 loss when CLL patients receive rituximab therapy, but shaving should occur more rapidly and is most likely to be the key mechanism of CD20 loss.
Intra-Golgi Formation of IgM–Glycosaminoglycan Complexes Promotes Ig Deposition
Authors: Khan Salar N. , Cox John V. , Nishimoto Satoru K. , Chen Ching , Fritzler Marvin J. , Hendershot Linda M. , Weigert Martin , Radic Marko 
Published: August 2011

Abstract
Immune complexes arise from interactions between secreted Ab and Ags in the surrounding milieu. However, it is not known whether intracellular Ag–Ab interactions also contribute to the formation of extracellular immune complexes. In this study, we report that certain murine B cell hybridomas accumulate intracellular IgM and release large, spherical IgM complexes. The complexes (termed “spherons”) reach 2 μm in diameter, detach from the cell surface, and settle out of solution. The spherons contain IgM multimers that incorporate the J chain and resist degradation by endoglycosidase H, arguing for IgM passage through the Golgi. Treatment of cells with inhibitors of proteoglycan synthesis, or incubation of spherons with chondroitinase ABC, degrades spherons, indicating that spheron formation and growth depend on interactions between IgM and glycosaminoglycans. This inference is supported by direct binding of IgM to heparin and hyaluronic acid. We conclude that, as a consequence of IgM binding to glycosaminoglycans, multivalent IgM–glycan complexes form in transit of IgM to the cell surface. Intra-Golgi formation of immune complexes could represent a new pathogenic mechanism for immune complex deposition disorders.
On the Importance of the Stokes-Brinkman Equations for Computing Effective Permeability in Karst Reservoirs
Authors: Krotkiewski Marcin , Ligaarden Ingeborg S. , Lie Knut-Andreas , Schmid Daniel W. 
Published: August 2011

AbstractCavities and fractures significantly affect the flow paths in carbonate reservoirs and should be accurately accounted for in numerical models. Herein, we consider the problem of computing the effective permeability of rock samples based on high-resolution 3D CT scans containing millions of voxels. We use the Stokes-Brinkman equations in the entire domain, covering regions of free flow governed by the Stokes equations, porous Darcy flow, and transitions between them. The presence of different length scales and large (ten orders of magnitude) contrasts in permeability leads to highly ill-conditioned linear systems of equations, which are difficult to solve. To obtain a problem that is computationally tractable, we first analyze the relative importance of the Stokes and Darcy terms for a set of idealized 2D models. We find that, in terms of effective permeability, the Stokes-Brinkman equations are only applicable for a special parameter set where the effective free-flow permeability is less than four orders of magnitude different from the matrix permeability. All other cases can be accurately modeled with either the Stokes or the Darcy end-member flows, depending on if there do or do not exist percolating free-flow regions. The insights obtained are used to perform a direct computation of the effective permeability of a rock sample model with more than 8 million cells.
Globalization and Policy Making; what capabilities and competencies should policy makers obey in globalization? (Market orientation)
Authors: Azizi Firuze , Noruzi Mohammad Reza 
Published: August 2011

Globalization has effects on different issues of society especially in policy and policy making. Policy making in this era i.e. the era of globalization is different with other time. It needs policy makers to manage the situation well and look globally instead of thinking just locally. This paper aims to study globalization in general and its effects on policy and policy making.
Keyword: Globalization, Society, policy, Effects of globalization on policy making
In‐Gel Phosphatase Assay Using Fluorogenic and Radioactive Substrates
Authors: Kameshita Isamu 
Published: August 2011

AbstractTo investigate the regulatory mechanisms of cellular signaling by protein phosphorylation, it is important to analyze protein phosphatases, as well as protein kinases expressed in cells and tissues. In this unit, two different types of in‐gel phosphatase assays are described. The first is an in‐gel phosphatase assay using fluorogenic substrates. Protein samples containing phosphatase activities are resolved by native polyacrylamide gel electrophoresis (native‐PAGE) and phosphatase activities detected in situ using fluorogenic substrates, such as 4‐methylumbelliferyl phosphate (MUP) or 6,8‐difluoro‐4‐methylumbelliferyl phosphate (DiFMUP). The other assay is an in‐gel phosphatase assay using 32P‐labeled substrates. In this method, protein samples are resolved by SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE) using polyacrylamide gels containing 32P ‐labeled substrates, renatured in situ, and the dephosphorylating activities detected by autoradiography. Each method has advantages and disadvantages that are discussed in the commentary. Curr. Protoc. Protein Sci. 65:13.12.1‐13.12.10. © 2011 by John Wiley & Sons, Inc.