bluuebunny/crossref_metadata_2025 huggingface dataset:
Características morfológicas em plantas de cultivares de aveia como indicadoras do potencial competitivo com plantas daninhas
Authors: Schaedler Carlos Eduardo , Fleck Nilson Gilberto , Ferreira Fausto Borges , Lazaroto Carlos Alberto , Rizzardi Mauro Antônio
Published: April 2009

O objetivo do experimento foi comparar cultivares de aveia quanto a características morfológicas de plantas no início do desenvolvimento que possam mostrar relação com a capacidade de competir com plantas daninhas. Para tanto, foi realizado um experimento a campo na Universidade Federal do Rio Grande do Sul, em Eldorado do Sul, Rio Grande do Sul (RS), durante a estação fria de 2005. O delineamento experimental utilizado foi o de blocos completamente casualizados, com quatro repetições. Foram investigadas 10 cultivares de aveia, a saber: 'ALBASUL', 'CFT 1', 'FAPA 5', 'FAPA 6', 'UFRGS 19', 'UPF 16', 'UPFA 20', 'UPFA 22', 'URS 21' e 'URS 22'. As características de planta avaliadas foram: estatura de planta, matéria seca da parte aérea, cobertura foliar do solo, incrementos em estatura, matéria seca e cobertura, potencial competitivo, produtividade biológica, produtividade de grãos e índice de colheita. Constatou-se que cultivares de aveia mostram variações acentuadas em características morfológicas no início do ciclo. As cultivares 'UPF 16' e 'UPFA 22' apresentam características típicas de plantas competidoras devido à elevada cobertura proporcionada por seus dosséis e aos rápidos incrementos em estatura e cobertura do solo na fase inicial de desenvolvimento. A cultivar 'ALBASUL', por outro lado, não é portadora de atributos morfológicos que a caracterizem como portadora de perfil competidor com plantas concorrentes no início do ciclo, embora apresente elevada produtividade de grãos e elevado índice de colheita.
Biocompatibilidade dos materiais em Ortodontia: mito ou realidade?
Authors: Menezes Luciane Macedo de , Freitas Maria Perpétua Mota , Gonçalves Tatiana Siqueira
Published: April 2009

O objetivo deste trabalho é apresentar uma revisão sobre os conceitos relacionados à biocompatibilidade dos materiais empregados em Ortodontia. Fatos relacionados às reações de hipersensibilidade aos diversos materiais ortodônticos são discutidos, sendo apresentadas as condutas recomendáveis nestas situações.
A institucionalização das estratégias de negócios: o caso das start-ups na internet brasileira em uma perspectiva construtivista
Authors: Vasconcelos Flávio Carvalho de
Published: April 2009

A abordagem objetivista da realidade social não é a única alternativa metodológica possível, embora predominante no campo de estratégia empresarial. Abordagens interpretativas aplicadas à estratégia empresarial foram sugeridas por diversos autores, desde as décadas de 1960 e 1970. Este artigo procura sistematizar as principais conseqüências de uma abordagem construtivista em estratégia empresarial, focando as suas conseqüências pra a prática da decisão estratégica: (1) O abandono da prescrição de que as organizações devem adaptar-se aos seus ambientes. (2) A redefinição de oportunidades, ameaças e restrições a partir de uma teoria cognitiva, e (3) a possibilidade de pensar diferentemente o papel da Estratégia Empresarial, dando maior ênfase aos processos de tomada de decisão. Neste artigo os estilos estratégicos das empresas que atuam na Internet no Brasil são avaliados a partir de uma análise neo-institucionalista, procurando ilustrar aspectos práticos da pesquisa em estratégia a partir de uma abordagem construtivista.
A heterogeneidade do desempenho, suas causas e o conceito de vantagem competitiva: proposta de uma métrica
Authors: Brito Luiz Artur Ledur , Vasconcelos Flávio Carvalho de
Published: April 2009

O desempenho das empresas, contrariamente ao que prevê o modelo econômico neoclássico, apresenta grande heterogeneidade. A estratégia em especial tem-se preocupado em entender esta heterogeneidade, explicá-la e prevê-la. As diversas correntes do pensamento estratégico apresentam diferentes abordagens para isto. Uma noção fundamental neste processo é o conceito de vantagem competitiva. Este trabalho inspira-se nas análises de componentes de variância de desempenho para sugerir uma definição mais precisa de vantagem competitiva e uma métrica para medi-la e compará-la. A proposta é ilustrada com um trabalho empírico que analisa resultados de 252 empresas brasileiras entre os anos 1998 a 2001.
Fish associated with aquatic macrophytes in the Chacororé-Sinhá Mariana Lake system and Mutum River, Pantanal of Mato Grosso, Brazil
Authors: Pacheco EB. , Da-Silva CJ.
Published: April 2009

On the left bank of the Cuibá River, one of the main tributaries of the Pantanal in Mato Grosso, are located the Chacororé and Sinhá Mariana Lakes and the Mutum River, the littoral regions of which are covered with aquatic macrophytes, dominated by the species Eichhornia crassipes and Eichhornia azurea. To examine the ichthyofauna associated with this vegetation, in the year 2003, 3510 fish were collected, distributed among 83 species, and the limnological variables verified near the macrophyte stands where they were sampled. The most abundant and richest order was the Characiformes, followed by the Gymnotiformes and Siluriformes. Analysis of similarity showed a very low, or null, index that the limnological conditions and morphology of the aquatic macrophyte species provide habitat sufficiently homogeneous to give. The limnological conditions and morphology of the aquatic macrophyte species provide a sufficient habitat heterogeneity to give very low, or null, index values. Thus, environmental conservation measures should be more effective in promoting the conservation of the species, given the high levels of biological diversity found in the habitats studied.
Two new species of Leporinus Agassiz, 1829 from Araguaia-Tocantins system, Amazon basin, Brazil (Ostariophysi, Anostomidae)
Authors: Garavello JC. , Santos GM.
Published: April 2009

Two new species of genus Leporinus from the Araguaia-Tocantins system, Amazon, Brazil, are described. Leporinus unitaeniatus n. sp. is distinguished from the remaining species of this genus by the presence of a conspicuous longitudinal dark brown bar along the lateral line on the flanks, and Leporinus geminis n. sp. is distinguished by an inconspicuous dark bar combined with three large and vertically elongated brown blotches on the trunk; the first on the dorsal fin region, the second anterior to the adipose fin and the third on the caudal peduncle. Both are medium-sized species of the genus (up to 150 mm SL) and share the following combination of meristic characters: 4 teeth on each premaxillary and dentary; 40-43 scales in the lateral line, 6/I/5 scales on the transversal line, and 16 series of scales around the caudal peduncle. L. unitaeniatus n. sp. has a sub-terminal mouth and tooth series formed by incisive-like elongated teeth frontally turned and with only a straight cutting edge decreasing in size like the steps of stairs from the teeth pair of symphysis. Leporinus geminis n. sp. has a sub-inferior mouth and the tooth series shaped by large incisive-like teeth forming an arched cutting edge, decreasing in size from the symphysal pair of teeth.
The effect of iron supplementation in the diet of Dasypus novemcinctus (Linnaeus, 1758) armadillos in captivity
Authors: Rosa PS. , Pinke CAE. , Pedrini SCB. , Silva EA.
Published: April 2009

Armadillos of the species Dasypus novemcinctus have been used as an experimental model of leprosy. Besides non-human primates, they are the only species naturally infected with Mycobacterium leprae and when experimentally inoculated, reproduce the lepromatous form of the disease producing large quantities of bacilli. This species has been maintained in captivity by numerous researchers and specific housing and feeding requirements have been developed to guarantee their survival during long experimental periods. In the "Lauro de Souza Lima" Institute, armadillos receive dog food, ground beef, boiled eggs and vitamin C. However, despite the balanced diet, anemia has been observed in some captive animals, especially in armadillos inoculated with M. leprae in advanced stages of infection. Thus, the objective of the present study was to evaluate the effect of iron sulfate supplementation in the feed provided for armadillos, both inoculated and non-inoculated with M. leprae, by means of the evaluation of their hematological profile. Fourteen armadillos received 10 mg/animal of iron sulfate (Hematofer®) diluted in sterile water mixed with their daily feed for 50 days. Hemograms and serum iron dosages for each armadillo were performed before and after supplementation. The hematocrit values increased significantly after iron supplementation, both in armadillos inoculated and non-inoculated with M. leprae. It is possible that the amount of iron in the feed is insufficient for the formation of hemoglobin, leading to microcytic anemia. Dietary supplementation with iron sulfate reversed this state, showing the importance of understanding the metabolism of exotic species for their maintenance in captivity, and thus ensuring their well-being.
Regression models for explaining and predicting concentrations of organochlorine pesticides in fish from streams in the United States
Authors: Nowell Lisa H. , Crawford Charles G. , Gilliom Robert J. , Nakagaki Naomi , Stone Wesley W. , Thelin Gail P. , Wolock David M.
Published: April 2009

Empirical regression models were developed for estimating concentrations of dieldrin, total chlordane, and total DDT in whole fish from U.S. streams. Models were based on pesticide concentrations measured in whole fish at 648 stream sites nationwide (1992–2001) as part of the U.S. Geological Survey's National Water Quality Assessment Program. Explanatory variables included fish lipid content, estimates (or surrogates) representing historical agricultural and urban sources, watershed characteristics, and geographic location. Models were developed using Tobit regression methods appropriate for data with censoring. Typically, the models explain approximately 50 to 70% of the variability in pesticide concentrations measured in whole fish. The models were used to predict pesticide concentrations in whole fish for streams nationwide using the U.S. Environmental Protection Agency's River Reach File 1 and to estimate the probability that whole-fish concentrations exceed benchmarks for protection of fish-eating wildlife. Predicted concentrations were highest for dieldrin in the Corn Belt, Texas, and scattered urban areas; for total chlordane in the Corn Belt, Texas, the Southeast, and urbanized Northeast; and for total DDT in the Southeast, Texas, California, and urban areas nationwide. The probability of exceeding wildlife benchmarks for dieldrin and chlordane was predicted to be low for most U.S. streams. The probability of exceeding wildlife benchmarks for total DDT is higher but varies depending on the fish taxon and on the benchmark used. Because the models in the present study are based on fish data collected during the 1990s and organochlorine pesticide residues in the environment continue to decline decades after their uses were discontinued, these models may overestimate present-day pesticide concentrations in fish.
Postoperative Results of Off-Pump Coronary By-pass Grafting in Elderly Patients: A Single Center Experience
Authors: Biçer M , Özdemir B , İşçimen R , Saba D , Yanar M , Tüydeş O , Şenkaya I , Cengiz M
Published: April 2009

Aim:

We aimed to report our postoperative results in elderly patients that had off-pump coronary bypass grafting.

Method:

Data of 173 patients with isolated coronary bypass 70 years of age or older were retrospectively evaluated. One month follow-up data were evaluated in all patients. After getting verbal informed consent a total of 91 patients were included in the quality of life assessment via EuroQoL form. The data of patients with age of 70-74 and 75 or older were compared.

Results:

The mean ages of patients at age of 70-74 and ≥75 were 71.69±0.16 and 76.81±0.23 years; respectively. Eleven cases had in-hospital mortality (%6 of 173 patients). The mean follow-up period for the group that were reached for EuroQoL assessment was 46,3 ± 20,8 months. The percent of cases among the whole study group that had participated in the quality of life questionnaire were in good condition in terms of mobility, self-care, usual activities, pain/discomfort, anxiety/depression were %75, %87, %81, %92 and %89; respectively.

Discussion:

Off-pump coronary bypass operation may be safely used in elderly patients with high quality of life and low morbidity and mortality.
Sex Differences in Drug Addiction: A Review of Animal and Human Studies
Authors: Fattore Liana , Altea Silvia , Fratta Walter
Published: April 2009

Addiction research has historically neglected research on women, and most studies have been conducted on men only, with the concluding results generalized to the female population. The role of sex differences in vulnerability to drug abuse, their repercussions on prevention and treatment strategies all require detailed studies, as does the progression from recreational drug use to dependence. This review synthesizes evidence of gender differences in drug addiction, with particular emphasis on women's health and implications. We first reviewed behavioral studies showing sex differences in the preference for and self-administration of licit (i.e., alcohol and nicotine) and illicit (i.e., cocaine, amphetamine, heroin and cannabis) substances as revealed by animal models of addiction. Clinical studies demonstrating differences between men and women in craving, drug use, abstinence and relapse will then be examined. For both animal and human studies, the effects of hormones and estrous/menstrual cycle will be reviewed. Finally, neurobiological factors underlying gender differences in vulnerability to drug addiction (i.e., brain morphology and neurotransmission) and need for gender-specific detoxification treatments will be discussed.
SOME VARIABLES PREDICTING SOCIAL SELF-EFFICACY EXPECTATION
Authors: Bilgin Mehmet , Akkapulu Emine
Published: April 2009

The rate at which adolescents' social self-efficacy levels can be predicted by variables such as the level of the adolescents' attachment to their parents and their peers, problem-solving skills, learned resourcefulness, perceived marital adjustment of their parents, and their
mothers' interpersonal relationships was examined. Volunteer high school students (N = 194), and their mothers were the participants. Students completed the Social Self-Efficacy Expectation Scale for Adolescents (SSES-A; Bilgin, 1999). Data were collected through the Inventory
of Parent Attachment (IPA; Hortaçsu & Oral, 1991), the Inventory of Peer Attachment (IPA; Hortaçsu & Oral, 1991), the Interpersonal Relationship Scale (IPRS; Sahin, Durak, & Yasak, 1994), the Problem Solving Inventory (PSI; Savas¸ir & Şahin, 1997),
Rosenbaum's (1980) Learned Resourcefulness Schedule (RLRS), and the Perceived Marital Adjustment Questionnaire (PMAQ; Akkapulu, 2005). The result of the stepwise regression analyses revealed that learned resourcefulness, problem-solving skills, perceived marital adjustment, the level
of peer attachment, the mothers' nourishing interpersonal relations, and parental attachment levels, were all significant predictors of social self-efficacy.
LATENT CLASS ANALYSIS OF RISK BEHAVIORS AMONG BAHAMIAN YOUNG ADOLESCENTS: RELATIONSHIP BETWEEN VALUES PRIORITIZATION AND LATENT CLASS
Authors: Cole Matthew , Stanton Bonita , Deveaux Linette , Harris Carole , Cottrell Lesley , Clemens Rebecca , Li Xiaoming , Marshall Sharon , Baine Rosa Mae
Published: April 2009

To explore an association between values and risk behaviors among early adolescents, baseline data from 689 Bahamian youth (median age = 10) were collected from the Portrait Values Questionnaire (Schwartz et al., 2001) and The Bahamian Youth Health Risk Behavioral Inventory. Latent
class analysis identified three classes of youth in differing patterns of risk behavior: (7.8%) high levels of drug and delinquency risk behaviors; (2.8%) high levels of sexual risk behavior; (89.4%) low risk takers. Results showed low risk takers included more females,
while at least twice as many males comprised the two risk behavior classes. ANOVA found Benevolence, Conformity, Security, Tradition and Universalism values were associated with low risk takers, and logistic regressions for ordered categorical (ordinal) dependent variables showed both values
and latent class predicted intentions for future risk behavior. Latent class analysis and values assessment are discussed as tools to guide adolescent riskreduction interventions.
The A2B Adenosine Receptor Impairs the Maturation and Immunogenicity of Dendritic Cells
Authors: Wilson Jeffrey M. , Ross William G. , Agbai Oma N. , Frazier Renea , Figler Robert A. , Rieger Jayson , Linden Joel , Ernst Peter B.
Published: April 2009

The endogenous purine nucleoside adenosine is an important antiinflammatory mediator that contributes to the control of CD4+ T cell responses. While adenosine clearly has direct effects on CD4+ T cells, it remains to be determined whether actions on APC such as dendritic cells (DC) are also important. In this report we characterize DC maturation and function in BMDC stimulated with LPS in the presence or absence of the nonselective adenosine receptor agonist NECA (5′-N-ethylcarboxamidoadenosine). We found that NECA inhibited TNF-α and IL-12 in a concentration-dependent manner, whereas IL-10 production was increased. NECA-treated BMDC also expressed reduced levels of MHC class II and CD86 and were less effective at stimulating CD4+ T cell proliferation and IL-2 production compared with BMDC exposed to vehicle control. Based on real-time RT-PCR, the A2A adenosine receptor (A2AAR) and A2BAR were the predominant adenosine receptors expressed in BMDC. Using adenosine receptor subtype selective antagonists and BMDC derived from A2AAR−/− and A2BAR−/−mice, it was shown that NECA modulates TNF-α, IL-12, IL-10, and CD86 responses predominantly via A2BAR. These data indicate that engagement of A2BAR modifies murine BMDC maturation and suggest that adenosine regulates CD4+ T cell responses by selecting for DC with impaired immunogencity.
FcγRIIA and FcγRIIIB Mediate Nuclear Factor Activation through Separate Signaling Pathways in Human Neutrophils
Authors: García-García Erick , Nieto-Castañeda Georgina , Ruiz-Saldaña Melissa , Mora Nancy , Rosales Carlos
Published: April 2009

Receptors for IgG Abs (Fcγ receptors) are capable of triggering diverse cell responses in leukocytes. In neutrophils, two Fcγ receptors, namely FcγRIIA and FcγRIIIB, are constitutively expressed. The signaling pathways that regulate FcγRIIA-mediated phagocytosis have been relatively well described. However, the different signaling pathways that lead to NF activation after engagement of each Fcγ receptor have only been partially described. To address this problem, neutrophils were stimulated by cross-linking selectively each type of Fcγ receptor with specific mAbs, and NF activation was then analyzed. FcγRIIIB, but not FcγRIIA, promoted a robust increase in phosphorylated ERK in the nucleus, and also efficient phosphorylation of the NF Elk-1. Complete mAb 3G8 (anti-FcγRIIIB) induced a higher response than did F(ab′)2 fragments of mAb 3G8, suggesting a possible synergistic effect of both FcγR receptors. However, mAb IV.3 (anti-FcγRIIA) alone did not cause an increase of phosphorylated ERK in the nucleus. FcγRIIIB-induced nuclear phosphorylation of ERK, and of Elk-1, was not affected by Syk, PI3K, or MEK inhibitors. In contrast, FcγRIIA- or FcγRIIIB-mediated phosphorylation of cytoplasmic ERK depended on Syk, PI3K, and MEK. Also, ERK, but not MEK, was constitutively present in the nucleus, and FcγRIIIB cross-linking did not increase the levels of nuclear ERK or MEK. These data clearly show that different neutrophil Fcγ receptors possess different signaling capabilities. FcγRIIIB, but not FcγRIIA, activates a unique signaling pathway leading to the nuclear-restricted phosphorylation of ERK and Elk-1, independently of Syk, PI3K, or MEK.
Bruton’s Tyrosine Kinase Is Involved in miR-346-Related Regulation of IL-18 Release by Lipopolysaccharide-Activated Rheumatoid Fibroblast-Like Synoviocytes
Authors: Alsaleh Ghada , Suffert Guillaume , Semaan Noha , Juncker Tom , Frenzel Laurent , Gottenberg Jacques-Eric , Sibilia Jean , Pfeffer Sébastien , Wachsmann Dominique
Published: April 2009

MicroRNAs (miRNAs) have emerged as key players in the regulation of expression of target mRNAs expression. They have been associated with diverse biological processes, and recent studies have demonstrated that miRNAs play a role in inflammatory responses. We reported previously that LPS-activated fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients express IL-18 mRNA but they do not release IL-18. Based on the observation that this inhibition was due to a rapid degradation of IL-18 mRNA, our group has conducted a study to identify miRNAs that could play a role in the “antiinflammatory” response of LPS-activated RA FLS. LPS challenge modulated the expression of 63 miRNAs as assessed by microarray analysis. Fifteen miRNAs were up-regulated, including miR-346, for which overexpression upon LPS treatment was validated by quantitative RT-PCR. We then transfected FLS with an antisense oligonucleotide targeting miR-346 and found that, in these conditions, IL-18 release could be measured upon LPS activation of FLS. Moreover, we also demonstrated that miR-346 indirectly regulated IL-18 release by indirectly inhibiting LPS-induced Bruton’s tyrosine kinase expression in LPS-activated RA FLS. These findings suggest that miRNAs function as regulators that help to fine-tune the inflammatory response in RA.
Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer
Authors: Ostrand-Rosenberg Suzanne , Sinha Pratima
Published: April 2009

Many cancer immunotherapies developed in experimental animals have been tested in clinical trials. Although some have shown modest clinical effects, most have not been effective. Recent studies have identified myeloid-origin cells that are potent suppressors of tumor immunity and therefore a significant impediment to cancer immunotherapy. “Myeloid-derived suppressor cells” (MDSC) accumulate in the blood, lymph nodes, and bone marrow and at tumor sites in most patients and experimental animals with cancer and inhibit both adaptive and innate immunity. MDSC are induced by tumor-secreted and host-secreted factors, many of which are proinflammatory molecules. The induction of MDSC by proinflammatory mediators led to the hypothesis that inflammation promotes the accumulation of MDSC that down-regulate immune surveillance and antitumor immunity, thereby facilitating tumor growth. This article reviews the characterization and suppressive mechanisms used by MDSC to block tumor immunity and describes the mechanisms by which inflammation promotes tumor progression through the induction of MDSC.
The Generation of Influenza-Specific Humoral Responses Is Impaired in ST6Gal I-Deficient Mice
Authors: Zeng Junwei , Joo Hye Mee , Rajini Bheemreddy , Wrammert Jens P. , Sangster Mark Y. , Onami Thandi M.
Published: April 2009

Posttranslational modification of proteins, such as glycosylation, can impact cell signaling and function. ST6Gal I, a glycosyltransferase expressed by B cells, catalyzes the addition of α-2,6 sialic acid to galactose, a modification found on N-linked glycoproteins such as CD22, a negative regulator of B cell activation. We show that SNA lectin, which binds α-2,6 sialic acid linked to galactose, shows high binding on plasma blasts and germinal center B cells following viral infection, suggesting ST6Gal I expression remains high on activated B cells in vivo. To understand the relevance of this modification on the antiviral B cell immune response, we infected ST6Gal I−/− mice with influenza A/HKx31. We demonstrate that the loss of ST6Gal I expression results in similar influenza infectivity in the lung, but significantly reduced early influenza-specific IgM and IgG levels in the serum, as well as significantly reduced numbers of early viral-specific Ab-secreting cells. At later memory time points, ST6Gal I−/− mice show comparable numbers of IgG influenza-specific memory B cells and long-lived plasma cells, with similarly high antiviral IgG titers, with the exception of IgG2c. Finally, we adoptively transfer purified B cells from wild-type or ST6Gal I−/− mice into B cell-deficient (μMT−/−) mice. Recipient mice that received ST6Gal I−/− B cells demonstrated reduced influenza-specific IgM levels, but similar levels of influenza-specific IgG, compared with mice that received wild-type B cells. These data suggest that a B cell intrinsic defect partially contributes to the impaired antiviral humoral response.
Inositol 1,4,5-Trisphosphate 3-Kinase B Is a Negative Regulator of BCR Signaling That Controls B Cell Selection and Tolerance Induction
Authors: Miller Andrew T. , Beisner Daniel R. , Liu Daorong , Cooke Michael P.
Published: April 2009

Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) converts inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate upon Ag receptor activation and controls the fate and function of lymphocytes. To determine the role of Itpkb in B cell tolerance, Itpkb−/− mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb−/− IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. These data establish Itpkb as a negative regulator of BCR signaling that controls the fate of developing B cells and tolerance induction.
Formyl Peptide Receptor-Like 2 Is Expressed and Functional in Plasmacytoid Dendritic Cells, Tissue-Specific Macrophage Subpopulations, and Eosinophils
Authors: Devosse Thalie , Guillabert Aude , D'Haene Nicky , Berton Alix , De Nadai Patricia , Noel Sophie , Brait Maryse , Franssen Jean-Denis , Sozzani Silvano , Salmon Isabelle , Parmentier Marc
Published: April 2009

The formyl peptide receptor (FPR) is a key player in innate immunity and host defense mechanisms. In humans and other primates, a cluster of genes encodes two related receptors, FPR-like 1 and FPR-like 2 (FPRL1 and FPRL2). Despite their high sequence similarity, the three receptors respond to different sets of ligands and display a different expression pattern in leukocyte populations. Unlike FPR and FPRL1, FPRL2 is absent from neutrophils, and two endogenous peptide agonists, F2L and humanin, were recently described. In the present work, we investigated the detailed functional distribution of FPRL2 in leukocytes by quantitative PCR, flow cytometry, immunohistochemistry, and chemotaxis assays, with the aim of raising hypotheses regarding its potential functions in the human body. We describe that FPRL2 is highly expressed and functional in plasmacytoid dendritic cells and up-regulated upon their maturation. FPRL2 is also expressed in eosinophils, which are recruited but do not degranulate in response to F2L. FPRL2 is expressed and functional in macrophages differentiated from monocytes in vitro in different conditions. However, in vivo, only specific subsets of macrophages express the receptor, particularly in the lung, colon, and skin, three organs chronically exposed to pathogens and exogenous aggressions. This distribution and the demonstration of the production of the F2L peptide in mice underline the potential role of FPRL2 in innate immunity and possibly in immune regulation and allergic diseases.
Pathogenesis of Steroid-Resistant Airway Hyperresponsiveness: Interaction between IFN-γ and TLR4/MyD88 Pathways
Authors: Yang Ming , Kumar Rakesh K. , Foster Paul S.
Published: April 2009

Chronic inflammation and airway hyperresponsiveness (AHR) in asthmatics are usually managed effectively by treatment with glucocorticoids. However, a subset of patients remains refractory to therapy. The underlying mechanisms are largely unknown, although recruitment of neutrophils (rather than eosinophils) is strongly correlated, suggesting a role for nonallergic host defense responses. Increased levels of IFN-γ and endotoxins are also related to severe asthma and because these activate host defense pathways, we investigated a possible common etiologic link to steroid-resistant disease. To be able to unravel the complexity of asthmatic inflammation, we used two model systems which permitted dissection of the relevant molecular pathways. In the first of these, we transferred transgenic OVA323–339 peptide-specific IFN-γ-producing Th1 cells into mice. These animals were subsequently challenge via the airways with OVA323–339 peptide and/or LPS. Challenge with both components, but not with either one individually, induced AHR. Importantly, AHR was resistant to treatment with dexamethasone. Development of AHR was dependent on IFN-γ, inhibited by depletion of pulmonary macrophages (but not neutrophils) and abrogated in TLR4- or MyD88-deficient mice. In contrast, in the second model in which we transferred OVA323–339 peptide-activated Th2 cells, eosinophilic inflammation and AHR were induced, and both were suppressed by steroid treatment. We conclude that cooperative signaling between IFN-γ and TLR4/MyD88 constitutes a previously unrecognized pathway that regulates macrophage-dependent steroid-resistant AHR.
Adaptor Proteins and Ras Synergistically Regulate IL-1-Induced ADAMTS-4 Expression in Human Chondrocytes
Authors: Ahmad Rasheed , Sylvester Judith , Ahmad Mushtaq , Zafarullah Muhammad
Published: April 2009

Aggrecanases (a dystrophin and metalloproteinase with thrombospondin motif, ADAMTSs) are principal proteases involved in cartilage extracellular matrix aggrecan degradation. The role and relative contribution of MyD88, IRAK1, and TRAF6 adaptor proteins in IL-1β regulation of aggrecanase-1 (ADAMTS-4) is unknown. By small interfering RNAs-mediated knockdown, we show that IL-1β-induced up-regulation of ADAMTS-4 in chondrocytes requires MyD88, IRAK1, and TRAF6 adaptor proteins. However, partial inhibition of ADAMTS-4 induction by their knockdown suggested the involvement of additional signaling proteins. Because IL-1β is also known to induce reactive oxygen species (ROS) through Ras-mediated activation of NADPH oxidase, we investigated the implication of Ras in ADAMTS-4 regulation. Ras knockdown, or inhibition of ROS by antioxidants along with the ablation of MyD88, IRAK1, or TRAF6 more potently down-regulated IL-1β-induced ADAMTS-4. In addition, IL-1β-induced phosphorylation of downstream effectors, IκB kinase αβ, IκBα, and activation of transcription factor NF-κB was significantly reduced in the MyD88-, IRAK1-, TRAF6-, or Ras-deficient cells. The combined knockdown of Ras and individual adaptor proteins strongly blocked the activation of IKKαβ, IκBα, and NF-κB. These findings suggest that Ras, ROS along with MyD88, IRAK1, or TRAF6 synergistically mediate ADAMTS-4 regulation by IL1-β. Thus, complete ablation of ADAMTS-4 induction could be achieved by combined inhibition of Ras and individual adaptor proteins, which may be of therapeutic value in arthritis.
A Single-Chain H-2Db Molecule Presenting an Influenza Virus Nucleoprotein Epitope Shows Enhanced Ability at Stimulating CD8+ T Cell Responses In Vivo
Authors: Palmowski Michael J. , Parker Mathew , Choudhuri Kaushik , Chiu Christopher , Callan Margaret F. C. , van der Merwe P. Anton , Cerundolo Vincenzo , Gould Keith G.
Published: April 2009

We have generated a construct encoding a single-chain H-2Db mouse MHC class I molecule in which an influenza virus nucleoprotein (NP) epitope, amino acid sequence ASNENMDAM, is fused to mouse β2-microglobulin and the Db H chain via flexible linker sequences. This single-chain trimer (SCT) was efficiently expressed at the cell surface independently of TAP and endogenous β2-microglobulin, and it was recognized directly and efficiently by specific T cells in vitro. A recombinant vaccinia virus encoding the Db NP SCT primed a CD8+ T cell response in C57BL/6 mice 4-fold greater than an equivalent virus expressing the NP epitope as a minigene, as shown by tetramer staining, whether or not the minigene was directed into the endoplasmic reticulum by a signal sequence. This response was functional as shown by in vivo lysis assays with peptide-pulsed target cells, and it was greatly expanded following secondary challenge in vivo with influenza virus. The SCT was also significantly more immunostimulatory for CD8+ cells than the NP minigene in adoptive transfer experiments using F5 TCR transgenic spleen cells, in which the magnitude of the T cell response was much greater. Our results extend previous DNA vaccination studies using SCTs, which demonstrated that such molecules are capable of generating functional CD8+ T cell responses. We have shown that class I SCTs are more immunogenic than even preprocessed Ag in the form of an epitope minigene, and they therefore should be considered for use when the generation of optimal CD8+ T cell responses is required.
Steric Hindrance and Fast Dissociation Explain the Lack of Immunogenicity of the Minor Histocompatibility HA-1Arg Null Allele
Authors: Spierings Eric , Gras Stéphanie , Reiser Jean-Baptiste , Mommaas Bregje , Almekinders Mathilde , Kester Michel G. D. , Chouquet Anne , Le Gorrec Madalen , Drijfhout Jan W. , Ossendorp Ferry , Housset Dominique , Goulmy Els
Published: April 2009

The di-allelic HLA-A2 restricted minor histocompatibility Ag HA-1 locus codes for the highly immunogenic HA-1His and the nonimmunogenic HA-1Arg nonapeptides, differing in one amino acid. The HA-1His peptide is currently used for boosting the graft-vs-tumor responses after HLA matched HA-1 mismatched stem cell transplantation; usage of the HA-1Arg peptide would significantly enlarge the applicability for this therapy. Our studies on mechanisms causing the HA-1 unidirectional immunogenicity revealed marginal differences in proteasomal digestion, TAP translocation, and binding affinity, whereas both dissociation rates and structural analyses clearly showed marked differences in the stability of these two HLA-A2 bound alleles. These data provide a rationale for the lack of HA-1Arg peptide immunogenicity essential for the choice of tumor peptides for stem cell-based immunotherapeutic application.
Important Role for CC Chemokine Ligand 2-Dependent Lung Mononuclear Phagocyte Recruitment to Inhibit Sepsis in Mice Infected with Streptococcus pneumoniae
Authors: Winter Christine , Herbold Wiebke , Maus Regina , Länger Florian , Briles David E. , Paton James C. , Welte Tobias , Maus Ulrich A.
Published: April 2009

The monocyte chemoattractant CCL2 is of major importance in inflammatory monocyte recruitment to the lungs in response to bacterial infection. Streptococcus pneumoniae is the most prevalent pathogen in community-acquired pneumonia causing significant morbidity and mortality worldwide. In the current study, we examined the role of CCL2 in lung-protective immunity against two strains of S. pneumoniae exhibiting different virulence profiles. Both wild-type mice and CCL2 knockout (KO) mice became septic within 24 h of infection with serotype 3 S. pneumoniae and died of infection by day 4 after challenge. In contrast, wild-type mice challenged with serotype 19 S. pneumoniae did not become septic or succumb to pneumococcal pneumonia, whereas CCL2 KO mice showed an early bacterial outgrowth in their lungs and sepsis starting by day 2 after infection, finally resulting in ∼50% decreased survival compared with wild-type mice. This phenotype was not due to impaired lung neutrophil recruitment in the KO mice, but was characterized by a significantly reduced recruitment of lung exudate macrophages and conventional lung dendritic cells, suggesting that these two phagocyte subsets critically regulate protection against septic disease progression in mice. In conclusion, we show here a differential role for CCL2-dependent lung exudate macrophage and conventional dendritic cell recruitment that critically contributes to lung protective immunity against S. pneumoniae.
Cutting Edge: IL-2 Immune Complexes As a Therapy for Persistent Virus Infection
Authors: Molloy Michael J. , Zhang Weijun , Usherwood Edward J.
Published: April 2009

There is an urgent need to develop novel therapies for controlling recurrent virus infections in immune suppressed patients. Disease associated with persistent γ-herpesvirus infection (EBV, HHV-8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Disease occurs because of a failure in immune surveillance to control the persistent infection, which arises in AIDS patients principally because of an erosion of the CD4+ T cell compartment. Immune surveillance failure followed by γ-herpesvirus recrudescence can be modeled using murine γ-herpesvirus in CD4 T cell-depleted mice. We show that enhancement of IL-2 signaling using IL-2/anti-IL-2 immune complexes substantially improves immune surveillance in the context of suppressed immunity and enhances control of the infection. This effect was not due solely to increased numbers of virus-specific CD8 T cells but rather to enhanced cytotoxicity mediated by the perforin-granzyme pathway.
A Protective Role for C5a in the Development of Allergic Asthma Associated with Altered Levels of B7-H1 and B7-DC on Plasmacytoid Dendritic Cells
Authors: Zhang Xun , Lewkowich Ian P. , Köhl Gabriele , Clark Jennifer R. , Wills-Karp Marsha , Köhl Jörg
Published: April 2009

The role of complement in the development of maladaptive immunity in experimental allergic asthma is unclear. In this study, we show that C3a receptor (C3aR)-deficient mice are protected from the development of Th2 immunity in a model of house dust mite-induced asthma. C5a receptor (C5aR)-targeting of C3aR-deficient mice during allergen sensitization not only reversed the protective effect but enhanced Th2 cytokine production, airway inflammation, and airway responsiveness, suggesting that the reduced allergic phenotype in C3aR-deficient mice results from protective C5aR signaling. In support of this view, C5aR expression in C3aR-deficient pulmonary dendritic cells (DCs) was increased when compared with wild-type DCs. Moreover, C5aR targeting regulated the frequency of pulmonary plasmacytoid DCs expressing costimulatory molecules B7-H1 and B7-DC. Ex vivo targeting of B7-H1 and B7-DC increased Th2 cytokine production from T cells of wild-type but not of C5aR-targeted mice, suggesting a protective role for C5a through regulation of B7 molecule expression on plasmacytoid DCs.
DNA Cloning and Engineering by Uracil Excision
Authors: Bitinaite Jurate , Nichols Nicole M.
Published: April 2009

This unit describes a simple and efficient DNA engineering method that combines nucleotide sequence alteration, multiple PCR fragment assembly, and directional cloning. PCR primers contain a single deoxyuracil residue (dU), and can be designed to accommodate nucleotide substitutions, insertions, and/or deletions. The primers are then used to amplify DNA in discrete fragments that incorporate a dU at each end. Excision of deoxyuracils results in PCR fragments flanked by unique, overlapping, single‐stranded extensions that allow the seamless and directional assembly of customized DNA molecules into a linearized vector. In this way, multi‐fragment assemblies, as well as various mutagenic changes, can all be accomplished in a single‐format experiment. Two basic protocols on the methods of uracil excision‐based engineering are presented, and special attention is given to primer design. The use of a commercially available cloning vector and the preparation of custom vectors are also presented. Curr. Protoc. Mol. Biol. 86:3.21.1‐3.21.16. © 2009 by John Wiley & Sons, Inc.
Versatile Structure‐Directing Roles of Deep‐Eutectic Solvents and Their Implication in the Generation of Porosity and Open Metal Sites for Gas Storage
Authors: Zhang Jian , Wu Tao , Chen Shumei , Feng Pingyun , Bu Xianhui
Published: April 2009

Erst eingesperrt, dann ausgetrieben: Ein tiefschmelzendes Eutektikum ist ein vielseitiges Medium für den Aufbau stabiler poröser Netzwerke, die neutrale Liganden einschließen. Beim Erhitzen werden diese koordinierten Moleküle aus den Poren abgegeben, und es entstehen permanent poröse Kristalle mit koordinativ ungesättigten Metallzentren, die sich als Gasspeicher oder für Anwendungen in der Katalyse eignen könnten.

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Fluorescent Logic Gates Chemically Attached to Silicon Nanowires
Authors: Mu Lixuan , Shi Wensheng , She Guangwei , Chang Jack C. , Lee Shuit‐Tong
Published: April 2009

I′m in the mood for dansyl: A chemically controlled fluorescent logic gate was formed by grafting a dansyl unit onto silicon nanowires (SiNWs; see picture). The logic gate was operated by utilizing pH changes, HgII, and Cl− or Br− ions as inputs and the fluorescence of the modified SiNWs as output. The modified SiNWs could perform as a three‐input logic gate that combines the YES and INH operations.

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A Single Residue Influences the Reaction Mechanism of Ammonia Lyases and Mutases
Authors: Bartsch Sebastian , Bornscheuer Uwe T.
Published: April 2009

All ways lead to Rome? Computer modeling and kinetic measurements identified a distinct residue in Phe/Tyr ammonia lyases (PAL/TAL) which controls whether the Friedel–Crafts or an E1cB reaction mechanism takes place. Hence, Glu484 in pcPAL favors the Friedel–Crafts reaction (see picture, MIO=4‐methylidene imidazol‐5‐one) whereas an Asn in TAL gives an elimination reaction. These mechanistic investigations also reveal activity of a PAL mutant and a TAL towards an amino alcohol.

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A Sequential O‐Nitrosoaldol and Grignard Addition Process: An Enantio‐ and Diastereoselective Entry to Chiral 1,2‐Diols
Authors: Jiao Peng , Kawasaki Masanori , Yamamoto Hisashi
Published: April 2009

Chiral 1,2‐diols have been prepared from α‐aminoxylated aldehydes or cyclohexanone and Grignard reagents with L‐proline or its tetrazole derivative as the catalyst. The presence of the ate complex of CeCl3⋅2 LiCl is essential for the high overall yields and good selectivities (see scheme; DMSO=dimethyl sulfoxide, THF=tetrahydrofuran, Tol=tolyl).

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A novel method to control microcapsule release behavior via photo‐crosslink polyurethane acrylate shells
Authors: Wang Xiao , Li Gangqiang , Wei Jie , Guan Weiwen
Published: April 2009

A microcapsule system with polyurethane acrylate (PUA) shell is prepared by interfacial polymerization between acrylic polyurethane diisocyanate and water to achieve controlled release via UV irradiation. The size of the microcapsule is influenced by the concentration of protecting colloid and property of acrylic polyurethane diisocyanate. When concentration of polyvinyl alcohol (PVA) is 5% and molar ratio of TDI and acrylic ethoxylated pentaerythritol (acrylic PP50) rises to 1.50, average diameter of the microcapsule is only 3.3223 μm. Delivery of 4‐hydroxy‐4′‐isopropoxydiphenylsulfone (D‐8) encapsuled by PUA microcapsule in solution can be prevented effectively by 30‐min UV irradiation. Lightness (L*) is used to measure color changes of reaction between D‐8 in PUA microcapsule and 2‐anilino‐6‐dibutylamino‐3‐methylfluoran (ODB‐2) under thermal treatment. In dry state, irradiated PUA microcapsules are much harder to release D‐8 than those not irradiated. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Synthesis of zwitterionic stationary phase based on hydrophilic non‐porous poly(glycidymethacrylate‐co‐ethylenedimethacrylate) beads and their application for fast separation of proteins
Authors: Gong Bolin , Bo Chunmiao , Zhu Jinxia , Yan Chao
Published: April 2009

A new hydrophilic strong/strong type zwitterionic stationary phase for high performance liquid chromatography (HPLC) was synthesized by chemical modification of 3.0 μm non‐porous monodisperse poly(glycidylmethacrylate‐co‐ethylenedimethacrylate)(PGMA/EDMA) beads in the following steps. First, the beads were reacted with hydrochloride to obtain chlorizated beads; second, chlorizated beads were reacted with dimethylamine to obtain ammoniated beads; third, ammoniated beads were reacted with 1,3‐propanesultone to obtain non‐porous hydrophilic zwitterionic stationary phase. The stationary phase was evaluated in detail to determine its ion‐exchange properties, separability, reproducibility, hydrophilicity, and the effect of column loading and pH on the separation and retention of proteins. The highest dynamic protein loading capacity of the synthesized zwitterionic packing for bovin serum albumin and Lys were 18.3 and 27.4 mg g−1, respectively. The zwitterionic stationary phase was capable of separating two acidic and three basic proteins simultaneously in less than 2.5 min by the flow‐rates of 3.0 mL min−1. The zwitterionic resin was also used for rapid separation and purification of recombinant human interferon‐r (rhIFN‐r) and human granulocyte colony‐stimulation factor (hG‐CSF) from the crude extract solution. The satisfactory results were obtained. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Preparation of bovine serum albumin‐imprinted calcium polyacrylate/alginate hybrid microspheres via Ca2+ crosslinking
Authors: Zhao Kongyin , Wei Junfu , Cheng Guoxiang , Yang Chunxia , Chen Li
Published: April 2009

Macromolecularly imprinted calcium polyacrylate/alginate hybrid polymer microspheres with the imprinting of bovine serum albumin were prepared with sodium alginate and sodium polyacrylate by using CaCl2 as a gelling agent in inverse‐phase suspension. Infrared spectrum and conductance titration demonstrated that hybrid components were produced in these microspheres. Rebinding isotherms of the microspheres proved a greater bovine serum albumin affinity for imprinted microspheres relative to nonimprinted ones. Selectivity tests indicated that calcium polyacrylate/alginate hybrid polymer microspheres exhibited good recognition properties for the template protein with the separation factor over 5.30 comparing to the competitive proteins with a similar Mw. The influence of cross‐linker CaCl2 concentration on the imprinting efficiency (IE) and rebinding capacity was researched. It was found that the cross‐linking density and imprinting efficiency of the hybrid hydrogel could be improved simultaneously. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Synthesis, characterization, and hydrolytic degradation of biodegradable poly(ether ester)‐urethane copolymers based on ε‐caprolactone and poly(ethylene glycol)
Authors: Gong Chang Yang , Fu Shao Zhi , Gu Ying Chun , Liu Cai Bing , Kan Bing , Deng Hong Xin , Luo Feng , Qian Zhi Yong
Published: April 2009

In this article, a new kind of biodegradable poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone)‐based polyurethane (PCEC‐U) copolymers were successfully synthesized by melt‐polycondensation method from ε‐caprolactone (ε‐CL), poly(ethylene glycol) (PEG), 1,4‐butanediol (BD), and isophorone diisocyanate (IPDI). The obtained copolymers were characterized by 1H‐nuclear magnetic resonance (1H‐NMR), FTIR, and gel permeation chromatography (GPC). Thermal properties of PCEC‐U copolymers were studied by DSC and TGA/DTG under nitrogen atmosphere. Water absorption and hydrolytic degradation behavior of these copolymers were also investigated. Hydrolytic degradation behavior was studied by weight loss method. 1H‐NMR and GPC were also used to characterize the hydrolytic degradation behavior of PCEC‐U copolymers. The molecular weight of PCL block and PEG block in soft segment and the content of hard segment strongly affected the water absorption and hydrolytic degradation behavior of PCEC‐U copolymers. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009