bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Condom-Use Self-Efficacy Over 36 Months Among Early Adolescents
Authors: Chen Xinguang , Dinaj-Koci Veronica , Brathwaite Nanika , Cottrell Lesley , Deveaux Lynette , Gomez Perry , Harris Carole , Li Xiaoming , Lunn Sonja , Marshall Sharon , Stanton Bonita
Published: October 2011

This research evaluates condom-use self-efficacy and its increase throughout adolescence. Documentation of the development of condom-use self-efficacy would be important for prevention efforts given the influence of self-efficacy on actual condom usage. This study assesses a hypothesized mediation mechanism of the development of self-efficacy using a mediation analysis approach. The participants, 497 Grade-6 Bahamian students, were randomly assigned to the control condition in a 3-year longitudinal HIV prevention program trial. Condom–use self-efficacy consistently increased and condom-use self-efficacy assessed at earlier periods was positively associated with its values at subsequent periods. Additionally, self-efficacy assessed between two time points 1 year apart or longer (e.g., 6 months between baseline and 12 months) significantly mediated the impact of its levels at the previous assessment on the level at the subsequent assessment. To sustain program effect, HIV prevention programs should strive to enhance self-efficacy and provide reinforcing “boosters” no later than 12 months postintervention.
Reflections on Foreign Direct Investment and Development with Reference to Non-Governmental Organizations and Corporate Social Responsibility
Authors: Hasan Rumy
Published: October 2011

It is clear that the process of ‘globalization’ has presented acute economic challenges to developing countries. Great importance has been accorded to foreign direct investment (FDI) as a driver of development, a consequence of which is the further empowerment of transnational corporations (TNCs). Competition for FDI prevents host governments from implementing tough regulatory measures. In their stead have stepped in non-governmental organizations whose lobbying has had an appreciable impact on TNC activities and strongly contributed to the rise of corporate social responsibility (CSR). The article posits the concept of an ‘efficiency CSR hypothesis’. Though CSR is a positive outcome, it does not detract from the profound problems of development for the weakest developing countries via the route of inducing FDI in a globalized economic environment. Contrary to expectations, the increasing interdependence in the world economy presents formidable challenges to development and poverty alleviation for such economies.
Building the History Museum to Stop History: Nicolas Sarkozy’s New Presidential Museum of French History
Authors: Bancel Nicolas , Lebovics Herman
Published: October 2011

When he ran for president in 2007 Nicolas Sarkozy promised to build a museum of French history. He declared that he was troubled by the lack of a coherent account of the nation’s great moments and great heroes. On being elected, he started the planning process, finally settling on the Hôtel de Soubise, part of the Archives nationales, as the site of the future Maison de l’histoire de France. Although his project was supported by a certain number of intellectuals, many university scholars, especially the historians, raised strong objections to a concept that returned to the old Third Republic civic history in the style of Ernest Lavisse. The future museum was to offer visitors old-fashioned narrative history of male achievements, with no account taken of new insights that women’s, gender, social, cultural, colonial and immigration history have added to any discussion of what France is or might be. It rejects the idea that there have been, and can be, many ways of being French. The critics of the museum project deplored the instrumentalisation of the nation’s past – one of several such presidential ventures – for short-term political gain. The strike of archive employees, which lasted for several months, scuttled that site as the future home of the history museum. The story is not finished. The discussion of the presidential museum initiative is placed in a larger context in which increased economic neo-liberalism, greater state interventions at home and overseas, and the propagation of a nostalgic-conservative vision of the nation’s past reinforce each other, even as they coexist in uneasy union.
Marguerite Duras ou les contradictions d’une intellectuelle aux prises avec l’espace public
Authors: Hugueny-Léger Elise
Published: October 2011

Proche de Mitterrand, figure active de la résistance, collaboratrice à des revues et journaux ‘engagés’, faisant entendre sa voix pendant la guerre d’Algérie et mai 68, Marguerite Duras fut indubitablement une intellectuelle profondément ancrée dans la vie sociopolitique de son époque. Or ses engagements l’ont souvent positionnée en porte-à-faux à la fois avec d’autres figures d’intellectuels et d’écrivains, et avec l’opinion publique. Cet article a pour objectif de mettre en relief certaines des contradictions qui modèlent les interventions de Duras dans l’espace public et journalistique. En prenant appui sur trois sources – la revue Le 14 juillet parue en 1958–9, l’article ‘Sublime’ écrit en réaction passionnée à l’affaire Villemin en 1985, et les entretiens avec Mitterrand parus en 1986 dans la revue L’Autre Journal – il s’agit d’analyser comment Duras incarne certains des paradoxes qui entourent la figure de l’intellectuel(le) et les modalités de ses relations vis-à-vis de l’opinion publique.
Creole in the Public Eye: Written Instances of Creole in Public Spaces in Guadeloupe
Authors: Pooser C. L.
Published: October 2011

Creole is the maternal language of the majority population of Guadeloupe, but French is the language of education, commerce, government and most written communication. Although the vast majority of Guadeloupians are bilingual and educated exclusively in French, Creole is also found in written form in the public domain in advertising, the public service sector, tourism, graffiti and political posters, among others. This article explores the various domains of written Creole usage with an additional focus upon the purposes and/or motives behind its use. It is argued that Creole is used variously to add local colour, to solidify connections with the creolophone community, to reinforce pride in one’s heritage and identity, and to exclude certain parties from political and social discourse.
Chemoprotection of ethylene glycol monoethyl ether-induced reproductive toxicity in male rats by kolaviron, isolated biflavonoid from Garcinia kola seed
Authors: Adedara IA , Farombi EO
Published: October 2011

The present study investigated the protective effect of kolaviron, a biflavonoid from the seed of Garcinia kola, on ethylene glycol monoethyl ether (EGEE)–induced reproductive toxicity in male rats. The protective effect of kolaviron was validated using vitamin E, a standard antioxidant. EGEE was administered at a dose of 200 mg/kg. Other groups of rats were simultaneously treated with kolaviron (100 and 200 mg/kg) and vitamin E (50 mg/kg) for 14 days. EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities but markedly increased the glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities in the testes. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GPx, GST and LDH as well as in the level of GSH but significantly increased SOD activity with concomitant increase in hydrogen peroxide and malondialdehyde levels in both testes and spermatozoa. EGEE-exposed rats showed marked testicular degeneration with concomitant decrease in spermatozoa quantity and quality. Overall, EGEE causes reproductive dysfunction in rats by altering antioxidant systems in the testes and spermatozoa. Kolaviron or vitamin E exhibited protective effects against EGEE-induced male reproductive toxicity by enhancement of antioxidant status and improvement in spermatozoa quantity and quality.
Organic anion transporter 1 (OAT1) involved in renal cell transport of aristolochic acid I
Authors: Zeng Y , Zhang R , Wu J , Liu M , Peng W , Yu X , Yang X
Published: October 2011

Aristolochic acids (AAs) are a family of structurally related nitrophenanthrene carboxylic acids that are present in medicinal herbs such as Aristolochia species. The organic anion transporters (OATs) of the solute carrier ( SLC22) gene family located in the renal proximal tubules play a key role in the excretion of a variety of exogenous and endogenous compounds. However, it is unclear how AAs permeate into renal epithelial cells. In this regard, we investigated the role of rat OAT1 ([rOAT1] SLC22A6) in the cellular uptake of AAI in vitro and in vivo. A concentration- and time-dependent intracellular accumulation of AAI was observed in rOAT1-transfected human embryonic kidney 293 (HEK293) cells, which was 2- to 6-fold higher than the control cells. There was a significantly increased rate of cellular apoptosis in rOAT1-transfected HEK293 cells than control cells after AAI treatment. Para-aminohippuric acid (PAH) significantly reduced the intracellular accumulation of AAI in rOAT1-transfected HEK293 cells. Administration of AAI for 35 days in rats caused significantly reduced expression of OAT1 in basolateral membrane and declined renal clearance of PAH as well as renal proximal tubule injuries. These findings indicate that AAI is taken up by OAT1, which then exert its intracellular toxic effects on renal proximal tubule cells, which in turn damage functional OAT1 and may further disturb the transport of its substrates.
Caffeic acid and quercetin protect erythrocytes against the oxidative stress and the genotoxic effects of lambda-cyhalothrin in vitro
Authors: Abdallah F Ben , Fetoui H , Fakhfakh F , Keskes L
Published: October 2011

Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control wide range of insect pests in a variety of applications. The aim of this study was to examine (i) the potency of LTC to induce oxidative stress response in rat erythrocytes in vitro and (ii) the role of caffeic acid (20 μM) and/or quercetin (10 μM) in preventing the cytotoxic effects. Erythrocytes were divided into four portions. The erythrocytes of the first portion were incubated for 4 h at 37°C with different concentrations (0, 50 and 100 μM) of LTC. The others portions were pretreated with caffeic acid and/or quercetin for 30 min prior to LTC incubation. Lipid peroxidation, protein oxidation, antioxidant enzyme activities and DNA damage were examined. LTC at different concentrations causes increased levels of lipid peroxidation, protein oxidation, DNA damage and decreased antioxidant enzyme activities. Combined caffeic acid and quercetin pretreatments significantly reduced the levels of lipid peroxidation markers, that is thiobarbituric acid reactive substance (TBARS), protein carbonyls (PCO) and decreased DNA damage in LTC portion. Further, combined caffeic acid and quercetin pretreatment maintain antioxidant enzyme activities and glutathione content near to normal values. These results suggest that LTC exerts its toxic effect by increasing lipid peroxidation, altering the antioxidant enzyme activities and DNA damage. Caffeic acid and quercetin pretreatments prevent the toxic effects of LTC, suggesting their role as a potential antioxidant.
The infant development timeline and its application to robot shaping
Authors: Law James , Lee Mark , Hülse Martin , Tomassetti Alessandra
Published: October 2011

Early infancy is a time of remarkable sensorimotor learning and rapid cognitive growth. Such development offers a rich source of inspiration for models that might allow robotic systems to learn cumulatively and autonomously. This article consists of three parts. The first part introduces the key issues from a robotics perspective. In particular, we promote a constructivist approach in which synthesis provides complementary insights to analytical methods. The second part presents the findings of a detailed review of infant development, from conception to 12 months. This produced explicit timelines that display the relative ordering of emergent competencies and concomitant stages in behavior. The final part shows how this infant framework can be mapped into the robotic domain in order to construct and explore developmental algorithms for robots. This work explores the use of constraints on perception, cognition, and action in shaping emergent activity, and how constraints relate to staged behavior and competence learning. We draw on examples from our previous experiments and show how we are applying this developmental approach to an iCub humanoid robot.
Motion control of a cruise ship by using active stabilizing fins
Authors: Kim J-H , Kim Y-H
Published: October 2011

The present study considers the motion control of a cruise ship by using active stabilizing fins. One or two pairs of stabilizing fins are equipped to reduce the roll and/or pitch motions of the cruise ship. Each fin is controlled by algorithms based on proportional–integral–derivative (PID) and linear quadratic Gaussian (LQG) control. Numerical analysis of the wave-induced motion of a cruise ship with stabilizing fins is carried out by using the time-domain ship motion program which has been developed through this study. The resultant motion response as the performance of each controller is compared between different control algorithms. Based on the present simulation results, the stabilizing fin can be considered a good instrument to reduce pitch motion as well as roll motion of the present cruise ship model. The present results show that the PID control algorithm, a simple but practical algorithm, can be an appropriate method to reduce the roll motion in a moderate sea state, while the LQG control algorithm shows good performance in reducing not only the roll motion but also the coupled roll and pitch motions simultaneously in all of environmental conditions considered.
Exploratory analysis of genomic segmentations with Segtools
Authors: Buske Orion J , Hoffman Michael M , Ponts Nadia , Le Roch Karine G , Noble William Stafford
Published: October 2011

Background

As genome-wide experiments and annotations become more prevalent, researchers increasingly require tools to help interpret data at this scale. Many functional genomics experiments involve partitioning the genome into labeled segments, such that segments sharing the same label exhibit one or more biochemical or functional traits. For example, a collection of ChlP-seq experiments yields a compendium of peaks, each labeled with one or more associated DNA-binding proteins. Similarly, manually or automatically generated annotations of functional genomic elements, including cis-regulatory modules and protein-coding or RNA genes, can also be summarized as genomic segmentations.

Results

We present a software toolkit called Segtools that simplifies and automates the exploration of genomic segmentations. The software operates as a series of interacting tools, each of which provides one mode of summarization. These various tools can be pipelined and summarized in a single HTML page. We describe the Segtools toolkit and demonstrate its use in interpreting a collection of human histone modification data sets and Plasmodium falciparum local chromatin structure data sets.

Conclusions

Segtools provides a convenient, powerful means of interpreting a genomic segmentation.
Musashi1 expression cells derived from mouse embryonic stem cells can be enriched in side population isolated by fluorescence activated cell sorter
Authors: Yu Tao , Zhao Li-Na , Lan Shao-Yang , Fan Miao-Jing , Gong Yu , Shi Liu , Yuan Yu-Hong , Huang Kai-Hong , Chen Qi-Kui
Published: October 2011

Background

Purifying stem cells is an inevitable process for further investigation and cell-therapy. Sorting side population (SP) cells is generally regarded as an effective method to enrich for progenitor cells. This study was to explore whether sorting SP could enrich for the Musashi1 (Msi1) positive cells from Msi1 high expression cells (Msi1high cells) derived from mouse embryonic stem cells (ESCs) in vitro.

Results

In this study, Msi1high cell population derived from ESCs were stained by Hoechst 33342, and then the SP and non-SP (NSP) fractions were analyzed and sorted by fluorescence activated cell sorter. Subsequently, the expressions of Msi1 and other markers for neural and intestinal stem cells in SP and NSP were respectively detected. SP and NSP cells were hypodermically engrafted into the backs of NOD/SCID mice to form grafts. The developments of neural and intestinal epithelial cells in these grafts were investigated. SP fraction was identified and isolated from Msi1high cell population. The expression of Msi1 in SP fraction was significantly higher than that in NSP fraction and unsorted Msi1high cells (P< 0.05). Furthermore, the markers for neural cells and intestinal epithelial cells were more highly expressed in the grafts from SP fraction than those from NSP fraction (P< 0.05).

Conclusions

SP fraction, isolated from Msi1high cells, contains almost all the Msi1-positive cells and has the potential to differentiate into neural and intestinal epithelial cells in vivo. Sorting SP fraction could be a convenient and practical method to enrich for Msi1-positive cells from the differentiated cell population derived from ESCs.
Identification of genes associated with nitrogen-use efficiency by genome-wide transcriptional analysis of two soybean genotypes
Authors: Hao Qing N , Zhou Xin A , Sha Ai H , Wang Cheng , Zhou Rong , Chen Shui L
Published: October 2011

Background

Soybean is a valuable crop that provides protein and oil. Soybean requires a large amount of nitrogen (N) to accumulate high levels of N in the seed. The yield and protein content of soybean seeds are directly affected by the N-use efficiency (NUE) of the plant, and improvements in NUE will improve yields and quality of soybean products. Genetic engineering is one of the approaches to improve NUE, but at present, it is hampered by the lack of information on genes associated with NUE. Solexa sequencing is a new method for estimating gene expression in the transcription level. Here, the expression profiles were analyzed between two soybean varieties in N-limited conditions to identify genes related to NUE.

Results

Two soybean genotypes were grown under N-limited conditions; a low-N-tolerant variety (No.116) and a low-N-sensitive variety (No.84-70). The shoots and roots of soybeans were used for sequencing. Eight libraries were generated for analysis: 2 genotypes × 2 tissues (roots and shoots) × 2 time periods [short-term (0.5 to 12 h) and long-term (3 to 12 d) responses] and compared the transcriptomes by high-throughput tag-sequencing analysis. 5,739,999, 5,846,807, 5,731,901, 5,970,775, 5,476,878, 5,900,343, 5,930,716, and 5,862,642 clean tags were obtained for the eight libraries: L1, 116-shoot short-term; L2 84-70-shoot short-term; L3 116-shoot long-term; L4 84-70-shoot long-term; L5 116-root short-term; L6 84-70-root short-term; L7 116-root long-term;L8 84-70-root long-term; these corresponded to 224,154, 162,415, 191,994, 181,792, 204,639, 206,998, 233,839 and 257,077 distinct tags, respectively. The clean tags were mapped to the reference sequences for annotation of expressed genes. Many genes showed substantial differences in expression among the libraries. In total, 3,231genes involved in twenty-two metabolic and signal transduction pathways were up- or down-regulated. Twenty-four genes were randomly selected and confirmed their expression patterns by quantitative RT-PCR; Twenty-one of the twenty-four genes showed expression patterns consistent with the Digital Gene Expression (DGE) data.

Conclusions

A number of soybean genes were differentially expressed between the low-N-tolerant and low-N-sensitive varieties under N-limited conditions. Some of these genes may be candidates for improving NUE. These findings will help to provide a detailed understanding of NUE mechanisms, and also provide a basis for breeding soybean varieties that are tolerant to low-N conditions.
The relationships between exogenous and endogenous antioxidants with the lipid profile and oxidative damage in hemodialysis patients
Authors: Roehrs Miguel , Valentini Juliana , Paniz Clóvis , Moro Angela , Charão Mariele , Bulcão Rachel , Freitas Fernando , Brucker Natália , Duarte Marta , Leal Mirna , Burg Geni , Grune Tilman , Garcia Solange Cristina
Published: October 2011

Background

We sought to investigate the relationships among the plasma levels of carotenoids, tocopherols, endogenous antioxidants, oxidative damage and lipid profiles and their possible effects on the cardiovascular risk associated with hemodialysis (HD) patients.

Methods

The study groups were divided into HD and healthy subjects. Plasma carotenoid, tocopherol and malondialdehyde (MDA) levels, as well as erythrocyte reduced glutathione (GSH), were measured by HPLC. Blood antioxidant enzymes, kidney function biomarkers and the lipid profiles were analyzed by spectrophotometric methods.

Results

Plasma lycopene levels and blood glutathione peroxidase (GPx) activity were significantly decreased in HD patients compared with healthy subjects. Total cholesterol, low-density lipoprotein cholesterol (LDL-c), creatinine, urea, MDA, GSH, superoxide dismutase (SOD) and catalase (CAT) were significantly increased in HD (p < 0.05). Lycopene levels were correlated with MDA (r = -0.50; p < 0.01), LDL-c (r = -0.38; p = 0.01) levels, the LDL-c/HDL-c index (r = -0.33; p = 0.03) and GPx activity (r = 0.30; p = 0.03). Regression models showed that lycopene levels were correlated with LDL-c (β estimated = -31.59; p = 0.04), while gender was correlated with the TC/HDL-c index and triglycerides. Age did not present a correlation with the parameters evaluated. GPx activity was negatively correlated with MDA levels and with the LDL-c/HDL-c and CT/HDL-c indexes.

Conclusions

Lycopene may represent an additional factor that contributes to reduced lipid peroxidation and atherogenesis in hemodialysis patients.
Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study
Authors: Han Chun-chao , Wei Hong , Guo Jianyou
Published: October 2011

Background

The roots of Sophora flavescens (Leguminosae) have been used in East Asian countries as an herbal medicine and a food ingredient for thousands of years. The aim of the present study was to investigate the effects of S. flavescens fermentation on endotoxin-induced uveitis (EIU) in rats.

Methods

EIU was induced in rats via a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, fermented and non-fermented extracts of S. flavescens (FSE and NFSE, respectively) were administered orally, and the aqueous humor was collected from both eyes 24 hours later. The anti-inflammatory effects of FSE and NFSE were examined in terms of regulation of nuclear factor kappa B (NF-κB) activation and the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular cell adhesion molecule (ICAM)-1, and cyclooxygenase-2 (COX-2). The regulation of maleic dialdehyde (MDA) levels and polymorphonuclear cell (PMN) infiltration by FSE and NFSE were also examined.

Results

Treatment with FSE significantly inhibited LPS-induced increases in IL-1β and TNF-α production and the expression of iNOS, ICAM-1 and COX-2. Moreover, FSE suppressed LPS-induced NF-κB activation, and reduced both MDA levels and infiltration by PMN.

Conclusion

These results indicate that solid state fermentation may enhance the anti-inflammatory effects of S. flavescens.
Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers
Authors: de Oliveira Carolina C , Abud Ana Paula R , de Oliveira Simone M , de SF Guimarães Fernando , de Andrade Lucas F , Di Bernardi Raffaello P , de O Coletto Ediely L , Kuczera Diogo , Da Lozzo Eneida J , Gonçalves Jenifer P , da S Trindade Edvaldo , de F Buchi Dorly
Published: October 2011

Background

In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system.

Methods

We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment.

Results

None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity.

Conclusions

Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.
Mitochondrial NAD+-dependent malic enzyme from Anopheles stephensi: a possible novel target for malaria mosquito control
Authors: Pon Jennifer , Napoli Eleonora , Luckhart Shirley , Giulivi Cecilia
Published: October 2011

Background

Anopheles stephensimitochondrial malic enzyme (ME) emerged as having a relevant role in the provision of pyruvate for the Krebs' cycle because inhibition of this enzyme results in the complete abrogation of oxygen uptake by mitochondria. Therefore, the identification of ME in mitochondria from immortalizedA. stephensi(ASE) cells and the investigation of the stereoselectivity of malate analogues are relevant in understanding the physiological role of ME in cells of this important malaria parasite vector and its potential as a possible novel target for insecticide development.

Methods

To characterize the mitochondrial ME from immortalized ASE cells (Mos. 43; ASE), mass spectrometry analyses of trypsin fragments of ME, genomic sequence analysis and biochemical assays were performed to identify the enzyme and evaluate its activity in terms of cofactor dependency and inhibitor preference.

Results

The encoding gene sequence and primary sequences of several peptides from mitochondrial ME were found to be highly homologous to the mitochondrial ME fromAnopheles gambiae(98%) and 59% homologous to the mitochondrial NADP+-dependent ME isoform fromHomo sapiens. Measurements of ME activity in mosquito mitochondria isolated from ASE cells showed that (i)Vmaxwith NAD+was 3-fold higher than that with NADP+, (ii) addition of Mg2+or Mn2+increased theVmaxby 9- to 21-fold, with Mn2+2.3-fold more effective than Mg2+, (iii) succinate and fumarate increased the activity by 2- and 5-fold, respectively, at sub-saturating concentrations of malate, (iv) among the analogs of L-malate tested as inhibitors of the NAD+-dependent ME catalyzed reaction, small (2- to 3-carbons) organic diacids carrying a 2-hydroxyl/keto group behaved as the most potent inhibitors of ME activity (e.g., oxaloacetate, tartronic acid and oxalate).

Conclusions

The biochemical characterization ofAnopheles stephensiME is of critical relevance given its important role in bioenergetics, suggesting that it is a suitable target for insecticide development.
Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders
Authors: Lehmann-Horn Klaus , Schleich Eva , Hertzenberg Deetje , Hapfelmeier Alexander , Kümpfel Tania , von Bubnoff Nikolas , Hohlfeld Reinhard , Berthele Achim , Hemmer Bernhard , Weber Martin S
Published: October 2011

Background

Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS) and neuromyelitis optica (NMO) generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE) attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders.

Methods

Myelin oligodendrocyte glycoprotein (MOG) peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg) and cytokine production of CD11b+antigen presenting cells (APC) were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression ofsignalling lymphocytic activation molecule(SLAM).

Results

We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM.

Conclusions

These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and effectiveness may further advance by selectively targeting pathogenic B-cell function.
Efficacy of the EZ-IO® needle driver for out-of-hospital intraosseous access - a preliminary, observational, multicenter study
Authors: Schalk Richard , Schweigkofler Uwe , Lotz Gösta , Zacharowski Kai , Latasch Leo , Byhahn Christian
Published: October 2011

Background

Intraosseous (IO) access represents a reliable alternative to intravenous vascular access and is explicitly recommended in the current guidelines of the European Resuscitation Council when intravenous access is difficult or impossible. We therefore aimed to study the efficacy of the intraosseous needle driver EZ-IO® in the prehospital setting.

Methods

During a 24-month period, all cases of prehospital IO access using the EZ-IO® needle driver within three operational areas of emergency medical services were prospectively recorded by a standardized questionnaire that needed to be filled out by the rescuer immediately after the mission and sent to the primary investigator. We determined the rate of successful insertion of the IO needle, the time required, immediate procedure-related complications, the level of previous experience with IO access, and operator's subjective satisfaction with the device.

Results

77 IO needle insertions were performed in 69 adults and five infants and children by emergency physicians (n = 72 applications) and paramedics (n = 5 applications). Needle placement was successful at the first attempt in all but 2 adults (one patient with unrecognized total knee arthroplasty, one case of needle obstruction after placement). The majority of users (92%) were relative novices with less than five previous IO needle placements. Of 22 responsive patients, 18 reported pain upon fluid administration via the needle. The rescuers' subjective rating regarding handling of the device and ease of needle insertion, as described by means of an analogue scale (0 = entirely unsatisfied, 10 = most satisfied), provided a median score of 10 (range 1-10).

Conclusions

The EZ-IO® needle driver was an efficient alternative to establish immediate out-of-hospital vascular access. However, significant pain upon intramedullary infusion was observed in the majority of responsive patients.
Impact of interleukin-21 in the pathogenesis of primary Sjogren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands
Authors: Kang Kwi Young , Kim Hyun-Ok , Kwok Seung-Ki , Ju Ji Hyeon , Park Kyung-Su , Sun Dong-Il , Jhun Joo Yeon , Oh Hye Jwa , Park Sung-Hwan , Kim Ho-Youn
Published: October 2011

Introduction

Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. To test whether IL-21 participates in the pathogenesis of primary Sjögren's syndrome (SS), serum IL-21 level was measured and IL-21 expression in the labial salivary glands (LSG) was examined.

Methods

Serum IL-21 levels in 40 primary SS, 40 rheumatoid arthritis (RA), and 38 systemic lupus erythematosus (SLE) patients and 20 healthy controls were measured. Serum IL-21 levels of SS patients were assessed for correlations with laboratory data, including anti-nuclear antibody, anti-Ro/La antibodies, globulin, immunoglobulin (Ig) class, and IgG subclass. LSGs from 16 primary SS and 4 controls with sicca symptoms were evaluated for IL-21 and IL-21 receptor (IL-21R) expression by immunohistochemistry. Confocal microscopy was performed to further characterize the IL-21 positive cells.

Results

Primary SS patients had significantly higher serum IL-21 levels than controls, and these increments correlated positively with levels of IgG, IgG1. Serum IgG1 levels correlated with anti-Ro antibody titers. Immunohistochemical analyses showed that lymphocytic foci and the periductal area of the LSGs from SS patients expressed high levels of IL-21 and lower levels of IL-21R, whereas the control LSGs showed minimal expression of both antigens. The more the lymphocyte infiltrated, IL-21expression in LSGs showed a tendency to increase. Confocal microscopic analyses revealed that IL-21 expressing infiltrating lymphocytes in the LSGs of SS patients also expressed CXCR5.

Conclusions

Primary SS is associated with high serum IL-21 levels that correlate positively with serum IgG, especially IgG1, levels. The expression of IL-21 is increased as more lymphocytes infiltrated in LSGs. These observations suggest that IL-21 may play an important role in primary SS pathogenesis.
Replacement of E-cadherin by N-cadherin in the mammary gland leads to fibrocystic changes and tumor formation
Authors: Kotb Ahmed M , Hierholzer Andreas , Kemler Rolf
Published: October 2011

Introduction

E-cadherin (E-cad; cadherin 1) and N-cadherin (N-cad; cadherin 2) are the most prominent members of the cadherin family of cell adhesion molecules. Although they share many structural and functional features, they are expressed in an almost mutually exclusive manner in vivo.

Methods

To explore functional differences between the two cadherins in vivo, we recently generated a knock-in line in which N-cad is expressed from the E-cad locus. In combination with a conditional gene inactivation approach, we expressed N-cad in the absence of E-cad (referred to as Ncadk.i.) in alveolar epithelial cells of the mammary gland starting in late pregnancy.

Results

We found that the sole presence of N-cad induces constitutively active fibroblast growth factor (Fgf) signaling and a precocious involution resulting in massive apoptosis of alveolar cells. To block apoptosis, we conditionally deleted one allele of p53 in Ncadk.i. mice and observed a temporal rescue of alveolar morphology and function. However, an accumulation of fibrotic tissue and cysts with increasing age and lactation cycles was observed. This phenotype closely resembled fibrocystic mastopathy (FM), a common disorder in humans, which is thought to precede breast cancer. Concordantly, 55% of Ncadk.i. mice harboring a heterozygous p53 deletion developed malignant and invasive tumors.

Conclusions

Our results demonstrate a possible role for N-cad in the formation of fibrosis and cysts in the mammary gland. Moreover, we show that these lesions precede the development of malignant tumors. Thus, we provide a new mouse model to investigate the molecular mechanisms of fibrocystic mastopathy and the transition from benign to malignant tumors.
Mobilization of hematopoietic stem and leukemia cells
Authors: Schroeder Mark A , DiPersio John F
Published: October 2011

HSC mobilization is an essential homeostatic process during inflammation and for the maintenance of hematopoietic progenitors. It has been exploited for the therapeutic application of HSC transplantation. Recent evidence suggests that leukemic cells share surface molecules in common with stem cells and may be mobilized under similar conditions. This effect could be used for therapeutic interventions. In this review, we will provide evidence showing that leukemia cells and stem cells traffic similarly and may share a common niche. Studies are discussed comparing and contrasting the mechanism of normal stem cells and leukemic cell mobilization through the CXCR4/CXCL12 axis and other key intermediaries.
Fc receptor-like 5 promotes B cell proliferation and drives the development of cells displaying switched isotypes
Authors: Dement-Brown Jessica , Newton Christopher S , Ise Tomoko , Damdinsuren Bazarragchaa , Nagata Satoshi , Tolnay Mate
Published: October 2011

The biological roles of B cell membrane proteins in the FCRL family are enigmatic. FCRL proteins, including FCRL5, were shown to modulate early BCR signaling, although the subsequent, functional consequences of receptor engagement are poorly understood. We found that FCRL5 surface protein itself was induced temporarily upon BCR stimulation of human, naive B cells, indicating precise control over timing of FCRL5 engagement. Cross-linking of FCRL5 on cells induced to express FCRL5 enhanced B cell proliferation significantly. This enhancement required costimulation of the BCR and TLR9, two signals required for optimal proliferation of naive B cells, whereas T cell help in the form of anti-CD40 and IL-2 was dispensable. In addition, we found that FCRL5 stimulation generated a high proportion of cells displaying surface IgG and IgA. Optimal development of cells expressing switched isotypes required T cell help, in addition to stimuli found necessary for enhanced proliferation. Surprisingly, cells that developed upon FCRL5 stimulation simultaneously displayed surface IgM, IgG, and IgA. Cells expressing multiple Ig isotypes were described in hairy cell leukemia, a disease in which FCRL5 is overexpressed. Enhanced proliferation and downstream isotype expression upon FCRL5 stimulation could reflect a physiological role for FCRL5 in the expansion and development of antigen-primed B cells. In addition, FCRL5 may promote growth of malignant cells in hairy cell leukemia and other FCRL5-expressing tumors.
Histone deacetylase inhibition facilitates GM-CSF-mediated expansion of myeloid-derived suppressor cells in vitro and in vivo
Authors: Rosborough Brian R , Castellaneta Antonino , Natarajan Sudha , Thomson Angus W , Turnquist Hēth R
Published: October 2011

Chromatin-modifying HDACi exhibit anti-inflammatory properties that reflect their ability to suppress DC function and enhance regulatory T cells. The influence of HDACi on MDSCs, an emerging regulatory leukocyte population that potently inhibits T cell proliferation, has not been examined. Exposure of GM-CSF-stimulated murine BM cells to HDACi led to a robust expansion of monocytic MDSC (CD11b+Ly6C+F4/80intCD115+), which suppressed allogeneic T cell proliferation in a NOS- and HO-1-dependent manner with similar potency to control MDSCs. The increased yield of MDSCs correlated with blocked differentiation of BM cells and an overall increase in HSPCs (Lin–Sca-1+c-Kit+). In vivo, TSA enhanced the mobilization of splenic HSPCs following GM-CSF administration and increased the number of CD11b+Gr1+ cells in BM and spleen. Increased numbers of Gr1+ cells, which suppressed T cell proliferation, were recovered from spleens of TSA-treated mice. Overall, HDACi enhance MDSC expansion in vitro and in vivo, suggesting that acetylation regulates myeloid cell differentiation. These findings establish a clinically applicable approach to augment this rare and potent suppressive immune cell population and support a novel mechanism underlying the anti-inflammatory action of HDACi.
Soluble β-glucan fromGrifola frondosainduces proliferation and Dectin-1/Syk signaling in resident macrophages via the GM-CSF autocrine pathway
Authors: Masuda Yuki , Togo Takuya , Mizuno Shigeto , Konishi Morichika , Nanba Hiroaki
Published: October 2011

MD-Fraction, a highly purified, soluble β-(1,3) (1,6)-glucan obtained from Grifola frondosa (an oriental edible mushroom), has been reported to inhibit tumor growth by modulating host immunity. β-Glucan, a major component of the fungal cell wall, is generally recognized by PRRs expressed on macrophages and DCs, such as Dectin-1, and the ability of β-glucans to modulate host immunity is influenced by their structure and purity. Most cellular studies have used particulate β-glucans, such as yeast zymosan (crude β-glucan) and curdlan (purified β-glucan). However, little is known about the cellular mechanism of soluble β-glucans, including MD-Fraction, despite significant therapeutic implications. In this study, we investigated the cellular mechanism of MD-Fraction in murine resident macrophages and compared it with two well-known β-glucan particles. MD-Fraction induced GM-CSF production rapidly through Dectin-1-independent ERK and p38 MAPK activation. Subsequently, MD-Fraction-induced GM-CSF enhanced proliferation and Dectin-1 expression, which permitted Dectin-1-mediated TNF-α induction through the Syk pathway. Curdlan induced not only the proliferation and activation of Dectin-1/Syk signaling in a manner similar to MD-Fraction but also the uncontrolled, proinflammatory cytokine response. Contrastingly, zymosan reduced proliferation and Dectin-1 expression significantly, indicating that the mechanism of macrophage activation by MD-Fraction differs from that of zymosan. This is the first study to demonstrate that purified β-glucans, such as MD-Fraction and curdlan, induce GM-CSF production directly, resulting in Dectin-1/Syk activation in resident macrophages. In conclusion, we demonstrated that MD-Fraction induces cell proliferation and cytokine production without excessive inflammation in resident macrophages, supporting its immunotherapeutic potential.
The emerging role of leukocyte immunoglobulin-like receptors (LILRs) in HIV-1 infection
Authors: Lichterfeld Mathias , Yu Xu G
Published: October 2011

LILRs represent a group of immunomodulatory molecules that regulate the functional properties of professional APCs and influence immune activation in a variety of disease contexts. Many members of the LILR family recognize peptide/MHC class I complexes as their physiological ligands, and increasing evidence suggests that such interactions are prominently influenced by polymorphisms in HLA class I alleles or sequence variations in the presented antigenic peptides. Emerging data show that LILRs are involved in multiple, different aspects of HIV-1 disease pathogenesis and may critically influence spontaneous HIV-1 disease progression. Here, we review recent progress in understanding the role of LILR during HIV-1 infection by focusing on the dynamic interplay between LILR and HLA class I molecules in determining HIV-1 disease progression, the effects of HIV-1 mutational escape on LILR-mediated immune recognition, the contribution of LILR to HIV-1-associated immune dysfunction, and the unique expression patterns of LILR on circulating myeloid DCs from elite controllers, a small subset of HIV-1-infected patients with natural control of HIV-1 replication. Obtaining a more complete understanding of LILR-mediated immune regulation during HIV-1 infection may ultimately allow for improved strategies to treat or prevent HIV-1-associated disease manifestations.
Heparin-Binding EGF-Like Growth Factor (HB-EGF) Mediates 5-HT-Induced Insulin Resistance Through Activation of EGF Receptor-ERK1/2-mTOR Pathway
Authors: Li Qinkai , Hosaka Toshio , Shikama Yosuke , Bando Yukiko , Kosugi Chisato , Kataoka Nanako , Nakaya Yutaka , Funaki Makoto
Published: October 2011

Although an inverse correlation between insulin sensitivity and the level of Gq/11-coupled receptor agonists, such as endothelin-1, thrombin, and 5-hydroxytryptamine (5-HT), has been reported, its precise mechanism remains unclear. In this report, we provide evidence that 5-HT induced production of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and caused insulin resistance in 3T3-L1 adipocytes, primary adipocytes, and C2C12 myotubes. In 3T3-L1 adipocytes, 5-HT stimulated HB-EGF production by promoting metalloproteinase-dependent shedding of transmembrane protein pro-HB-EGF. HB-EGF then bound and tyrosine-phosphorylated EGF receptors, which activated the mammalian target of rapamycin pathway through ERK1/2 phosphorylation. Mammalian target of rapamycin activation caused serine phosphorylation of insulin receptor substrate-1, which attenuated insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 and glucose uptake. Pharmacological inhibition of either Gq/11-coupled receptors or metalloproteinases, as well as either inhibition or knockdown of HB-EGF or Gαq/11, restored insulin signal transduction impaired by 5-HT. Inhibition of metalloproteinase activity also abolished HB-EGF production and subsequent EGF receptor activation by other Gq/11-coupled receptor agonists known to cause insulin resistance, such as endothelin-1 and thrombin. These results suggest that transactivation of the EGF receptor through HB-EGF processing plays a pivotal role in 5-HT-induced insulin resistance.