bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions
Authors: Hosokawa Kazuya , Ohnishi Tomoko , Sameshima Hisayo , Miura Naoki , Ito Takashi , Koide Takehiko , Maruyama Ikuro
Published: November 2012

High residual platelet aggregability and circulating platelet-monocyte aggregates in patients administered aspirin and clopidogrel are associated with ischaemic vascular events. To determine the relevance of these factors with residual thrombogenicity, we measured platelet thrombus formation using a microchip-based flow-chamber system in cardiac patients receiving aspirin and/or clopidogrel, and evaluated its correlation with agonist-inducible platelet aggregation and platelet-monocyte aggregates. Platelet thrombus formation was analysed by measuring flow pressure changes due to the occlusion of micro-capillaries and was quantified by calculating AUC10 (area under the flow pressure curve). The growth and stability of platelet thrombi that formed inside microchips at shear rates of 1000, 1500, and 2000 s-1 were markedly reduced in patients receiving aspirin and/or thienopyridine compared to healthy controls (n=33). AUC10 values of aspirin therapy patients (n=20) were significantly lower and higher than those of healthy controls and dual antiplatelet therapy patients (n=19), respectively, and showed relatively good correlations with collagen-induced platelet aggregation and platelet-monocyte aggregates at 1000 and 1500 s-1 (r

s
>0.59, p<0.01). In contrast, AUC10 in dual antiplatelet therapy patients was significantly correlated with ADP-induced platelet aggregation at all examined shear rates (r

s
>0.59, p<0.01), but did not correlate with collagen-induced aggregation. Aspirin monotherapy patients with high residual platelet thrombogenicity also exhibited significant elevations in both collagen-induced platelet aggregation and platelet-monocyte aggregates. Our results, although preliminary, suggest that residual platelet thrombogenicity in aspirin-treated patients is associated with either collagen-induced platelet aggregation or circulating platelet-monocyte aggregates, but it is predominantly dependent on ADP-induced platelet aggregation in patients receiving dual antiplatelet therapy.
Evaluation of the Global Climate Models in the CMIP5 over the Tibetan Plateau
Authors: Su Fengge , Duan Xiaolan , Chen Deliang , Hao Zhenchun , Cuo Lan
Published: November 2012

The performance of 24 GCMs available in the fifth phase of the Coupled Model Intercomparison Project (CMIP5) is evaluated over the eastern Tibetan Plateau (TP) by comparing the model outputs with ground observations for the period 1961–2005. The twenty-first century trends of precipitation and temperature based on the GCMs’ projections over the TP are also analyzed. The results suggest that for temperature most GCMs reasonably capture the climatological patterns and spatial variations of the observed climate. However, the majority of the models have cold biases, with a mean underestimation of 1.1°–2.5°C for the months December–May, and less than 1°C for June–October. For precipitation, the simulations of all models overestimate the observations in climatological annual means by 62.0%–183.0%, and only half of the 24 GCMs are able to reproduce the observed seasonal pattern, which demonstrates a critical need to improve precipitation-related processes in these models. All models produce a warming trend in the twenty-first century under the Representative Concentration Pathway 8.5 (rcp8.5) scenario; in contrast, the rcp2.6 scenario predicts a lower average warming rate for the near term, and a small cooling trend in the long-term period with the decreasing radiative forcing. In the near term, the projected precipitation change is about 3.2% higher than the 1961–2005 annual mean, whereas in the long term the precipitation is projected to increase 6.0% under rcp2.6 and 12.0% under the rcp8.5 scenario. Relative to the 1961–2005 mean, the annual temperature is projected to increase by 1.2°–1.3°C in the short term; the warmings under the rcp2.6 and rcp8.5 scenarios are 1.8° and 4.1°C, respectively, for the long term.
Facing the Nonresponse Challenge
Authors: Kreuter Frauke
Published: November 2012

This article provides a brief overview of key trends in the survey research to address the nonresponse challenge. Noteworthy are efforts to develop new quality measures and to combine several data sources to enhance either the data collection process or the quality of resulting survey estimates. Mixtures of survey data collection modes and less burdensome survey designs are additional steps taken by survey researchers to address nonresponse.
Where Do We Go from Here? Nonresponse and Social Measurement
Authors: Massey Douglas S. , Tourangeau Roger
Published: November 2012

Surveys undergird government statistical systems and social scientific research throughout the world. Rates of nonresponse are rising in cross-sectional surveys (those conducted during a fixed period of time and not repeated). Although this trend worries those concerned with the validity of survey data, there is no necessary relationship between the rate of nonresponse and the degree of bias. A high rate of nonresponse merely creates the potential for bias, but the degree of bias depends on how factors promoting nonresponse are related to variables of interest. Nonresponse can be reduced by offering financial incentives to respondents and by careful design before entering the field, creating a trade-off between cost and potential bias. When bias is suspected, it can be countered by weighting individual cases by the inverse of their response propensity. Response propensities are typically estimated using a logistic regression equation to predict the dichotomous outcome of survey participation as a function of auxiliary variables. The Multi-level Integrated Database Approach employs multiple databases to collect as much information as possible about the target sample during the initial sampling stage and at all possible levels of aggregation to maximize the accuracy of estimated response propensities.
Turnout Under Semipresidentialism
Authors: Elgie Robert , Fauvelle-Aymar Christine
Published: November 2012

We test the effect of the importance of elections by focusing on turnout at presidential and legislative elections in countries with semipresidential constitutions. These countries have two potentially first-order elections, but they vary considerably in the powers that are granted to their presidents and prime ministers. We hypothesize that turnout at legislative elections will vary inversely with presidential power and that above a certain degree of presidential power turnout at presidential elections will be higher than turnout at legislative elections. We test these hypotheses on the set of electoral democracies from 1989 to 2010 inclusive. Controlling for standard social, political, and institutional variables, we find strong support for our propositions. The findings show that the importance of the electoral contest is a determining factor for turnout at legislative elections and that the relative importance of presidential and legislative elections can be understood as a continuous scale, and not merely dichotomously.
Investigation on the impact and compression-after-impact properties of warp-knitted spacer fabrics
Authors: Guo Xiaofang , Long Hairu , Zhao Li
Published: November 2012

The paper reports an experimental study on the influence of spacer fabrics' structures, that is, different surface stitches, fabric thicknesses, and diameters of spacer yarns, on the impact and compression-after-impact properties of warp-knitted spacer fabrics. Low-velocity impact tests, damage deformation characterizations, and compression tests after impacts were performed on six spacer-fabric specimens knitted on a double needle bar Raschel knitting machine. The impact method was flat-sphere (a flat striker contacted with a fabric wrapped on a hemispherical steel anvil). Deformation processes of typical spacer fabrics, force–displacement/time and energy–time curves, impact damage, and residual strength were analyzed and discussed; moreover, peak force, absorbed energy, damage depth, and the drop-off rate of residual strength were involved to estimate impact and compression-after-impact properties of the spacer fabrics with different structures. The results show that with the closed surface structure and coarser spacer yarns, the fabrics have the characteristics of lower peak forces, higher energy-absorption ability, lower damage depths, and higher drop-off rates of residual strength. Fabrics with higher thickness are of the features above but they do have lower drop-off rates
Anticoagulant Use in Real Time
Authors: Srinivasan Divyamani , Watzak Bree
Published: November 2012

Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). Each year, VTE affects about 300 000 to 600 000 people in the United States, and death is the first manifestation in one-fourth of this population.1{Beckman, 2010 #79} Moreover, approximately 10% of the US population has genetic factors that increase their risk for developing thrombosis.1 In addition to inherited disorders, factors that contribute to VTE include prolonged immobilization, trauma, surgery, cancer, and critically ill patients.2 Routine assessment and prophylaxis are recommended in these groups to avoid DVT-related complications.2 Anticoagulants are the mainstay of drugs used in DVT/PE prevention and treatment. Despite the availability of evidence-based guidelines for anticoagulant therapy, there is suboptimal implementation of DVT prophylaxis in hospitalized patients.3 All anticoagulants are “high-alert” drugs, and judicious use is mandatory to prevent bleeding complications.4 This review discusses treatment guidelines, monitoring, side effects, and reversal agents available for some anticoagulant drugs approved for VTE. Dissemination of the knowledge via pharmacy education programs significantly improves the adherence to VTE prophylaxis.5 Understanding the clinical aspects of anticoagulant dispensing as presented in this review is hoped to facilitate implementation of the theoretical knowledge as well as evidence-based guidelines in order to maximize patient benefit.
Retrospective Analysis of Estimated Cost Avoidance Following Pharmacist-Provided Medication Therapy Management Services
Authors: Branham Ashley R. , Katz Aaron J. , Moose Joseph S. , Ferreri Stefanie P. , Farley Joel F. , Marciniak Macary W.
Published: November 2012

Objective: To compare the estimated cost avoidance (ECA) of pharmacist-provided medication therapy management (MTM) services among common disease states encountered in community pharmacy practice. Design: Retrospective analysis. Setting: Nine community pharmacies in North Carolina. Patients: Three hundred and sixty-four patients who are 65 years of age or older, a Medicare Part D beneficiary and a North Carolina resident. Interventions: An MTM pharmacist-provider conducted medication reviews to eligible patients between July 2009 and October 2009. For each encounter, patient interventions, pharmacist recommendations, and ECA were recorded. Main outcome measure: ECA. Results: In 9 pharmacy locations, 634 MTM interventions were documented during the study period. The ECA in a 4-month period yielded approximately $494 000. Comprehensive medication reviews, new prescription counseling and appropriate medication administration, and technique counseling made up nearly two-thirds of interventions. Overall, the probability that an MTM intervention would result in an ECA greater than $0 was .35. Conclusions: Pharmacist-provided MTM effectively reduced costs associated with patient medication use. Such interventions reduced costs in overall health care specifically in the areas of cardiovascular, gastroesophageal reflux disease, pulmonary, and diabetes groups.
Modulation of Human Visual Evoked Potentials in 3-Dimensional Perception After Stimuli Produced With an Integral Imaging Method
Authors: Omoto Shu , Kuroiwa Yoshiyuki , Otsuka Saika , Wang Chuanwei , Mizuki Nobuhisa , Nagatani Hiroyuki , Hirayama Yuzo
Published: November 2012

We investigated the neurophysiological correlates of stereoscopic 3-dimensional (3-D) depth perception by studying human visual evoked potentials (VEPs) with an integral imaging method characterized by horizontal but not vertical disparity. The VEPs were recorded in 10 healthy men under 4 conditions. In condition I, stimuli A (flat, 2-dimensional [2-D] image) and B (concave 3-D image) were presented at random. In condition II, stimuli A and C (convex 3-D image) were presented at random. In condition III, stimuli B and C were presented at random. In condition IV, stimuli A, B, and C were presented at random. The data for flat VEPs to stimulus A were combined in conditions I and II. The data for concave VEPs to stimulus B were combined in conditions I and III. The data for convex VEPs to stimulus C were combined in conditions II and III. When 2-way analysis of variance (ANOVA) for 2 factors, stimulus conditions (flat VEPs, concave VEPs, and convex VEPs) and electrode positions, was applied for VEP data, the N1 and N2 peak amplitudes differed significantly among the 3 stimulus conditions. In condition IV, the N1 peak amplitudes differed significantly among the 3 stimuli. Multiple comparisons followed by Bonferroni adjustment did not detect differences in the N1 peak amplitude between stimuli A and B, between stimuli A and C, or between stimuli B and C. We concluded that VEPs to concave or convex 3-D stimuli were significantly different from VEPs to flat 2-D stimuli. This is the first report showing modulation of human VEPs in 3-D perception with an integral imaging method.
Managing Body Distress in the Control of Severe Asthma
Authors: Bakal Donald , Davidson Warren
Published: November 2012

This article provides clinicians with a patient-centered framework for the recognition and management of body distress within severe asthma patients who remain uncontrolled despite treatment with standard medical therapy. Body distress is offered as a mind–body concept with origins in psychobiological patient characteristics that are generally not identified as contributing directly to uncontrolled asthma. Dysfunctional breathing can be viewed as a proxy for these patient variables. Effortless or relaxed breathing can be used to guide the reduction of body distress from healing sensations throughout the entire body and support a larger goal of using the least amount of medication possible.
Model-based decision rules reduce the risk of molecular relapse after cessation of tyrosine kinase inhibitor therapy in chronic myeloid leukemia
Authors: Horn Matthias , Glauche Ingmar , Müller Martin C. , Hehlmann Rüdiger , Hochhaus Andreas , Loeffler Markus , Roeder Ingo
Published: November 2012

Molecular response to imatinib (IM) in chronic myeloid leukemia (CML) is associated with a biphasic but heterogeneous decline of BCR-ABL transcript levels. We analyzed this interindividual heterogeneity and provide a predictive mathematical model to prognosticate the long-term response and the individual risk of molecular relapse on treatment cessation. The parameters of the model were determined using 7-year follow-up data from a randomized clinical trial and validated by an independent dataset. Our model predicts that a subset of patients (14%) achieve complete leukemia eradication within less than 15 years and could therefore benefit from discontinuation of treatment. Furthermore, the model prognosticates that 31% of the patients will remain in deep molecular remission (MR5.0) after treatment cessation after a fixed period of 2 years in MR5.0, whereas 69% are expected to relapse. As a major result, we propose a predictor that allows to assess the patient-specific risk of molecular relapse on treatment discontinuation and to identify patients for whom cessation of therapy would be an appropriate option. Application of the suggested rule for deciding about the time point of treatment cessation is predicted to result in a significant reduction in rate of molecular relapse.
Investigations into genome diversity of Haemophilus influenzae using whole genome sequencing of clinical isolates and laboratory transformants
Authors: Power Peter M , Bentley Stephen D , Parkhill Julian , Moxon E Richard , Hood Derek W
Published: November 2012

Background

Haemophilus influenzae is an important human commensal pathogen associated with significant levels of disease. High-throughput DNA sequencing was used to investigate differences in genome content within this species.

Results

Genomic DNA sequence was obtained from 85 strains of H. influenzae and from other related species, selected based on geographical site of isolation, disease association and documented genotypic and phenotypic differences. When compared by Mauve alignment these indicated groupings of H. influenzae that were consistent with previously published analyses; c apsule expressing strains fell into two distinct groups and those of serotype b (Hib) were found in two closely positioned lineages. For 18 Hib strains representing both lineages we found many discrete regions (up to 40% of the total genome) displaying sequence variation when compared to a common reference strain. Evidence that this naturally occurring pattern of inter-strain variation in H. influenzae can be mediated by transformation was obtained through sequencing DNA obtained from a pool of 200 independent transformants of a recipient (strain Rd) using donor DNA from a heterologous Hib strain (Eagan).

Conclusion

Much of the inter-strain variation in genome sequence in H. influenzae is likely the result of inter-strain exchanges of DNA, most plausibly through transformation.
Complex sputum microbial composition in patients with pulmonary tuberculosis
Authors: Cui Zelin , Zhou Yuhua , Li Hong , Zhang Yan , Zhang Shulin , Tang Shenjie , Guo Xiaokui
Published: November 2012

Background

An increasing number of studies have implicated the microbiome in certain diseases, especially chronic diseases. In this study, the bacterial communities in the sputum of pulmonary tuberculosis patients were explored. Total DNA was extracted from sputum samples from 31 pulmonary tuberculosis patients and respiratory secretions of 24 healthy participants. The 16S rRNA V3 hyper-variable regions were amplified using bar-coded primers and pyro-sequenced using Roche 454 FLX.

Results

The results showed that the microbiota in the sputum of pulmonary tuberculosis patients were more diverse than those of healthy participants (p<0.05). The sequences were classified into 24 phyla, all of which were found in pulmonary tuberculosis patients and 17 of which were found in healthy participants. Furthermore, many foreign bacteria, such as Stenotrophomonas, Cupriavidus, Pseudomonas, Thermus, Sphingomonas, Methylobacterium, Diaphorobacter, Comamonas, and Mobilicoccus, were unique to pulmonary tuberculosis patients.

Conclusions

This study concluded that the microbial composition of the respiratory tract of pulmonary tuberculosis patients is more complicated than that of healthy participants, and many foreign bacteria were found in the sputum of pulmonary tuberculosis patients. The roles of these foreign bacteria in the onset or development of pulmonary tuberculosis shoud be considered by clinicians.
Wnt3a induces exosome secretion from primary cultured rat microglia
Authors: Hooper Claudie , Sainz-Fuertes Ricardo , Lynham Steven , Hye Abdul , Killick Richard , Warley Alice , Bolondi Cecilia , Pocock Jennifer , Lovestone Simon
Published: November 2012

Background

Microglia, the immune effector cells of the CNS and the signaling molecule Wnt, both play critical roles in neurodevelopment and neurological disease. Here we describe the inducible release of exosomes from primary cultured rat microglia following treatment with recombinant carrier-free Wnt3a.

Results

Wnt3a was internalised into microglia, being detectable in early endosomes, and secreted in exosomes through a GSK3-independent mechanism. Electron microscopy demonstrated that exosomes were elliptical, electron-dense (100 nm) vesicles that coalesced with time in vitro. In contrast to microglia, primary cortical neurons released exosomes constitutively and the quantity of exosomes released was not altered by Wnt3a treatment. The proteomic profile of the microglial-derived exosomes was characterised using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the vesicles were found to be associated with proteins involved in cellular architecture, metabolism, protein synthesis and protein degradation including β-actin, glyceraldehyde-3-phosphate dehydrogenase, ribosomal subunits and ubiquitin (45 proteins in total). Unlike lipopolysaccharide, Wnt3a did not induce a neurotoxic, pro-inflammatory phenotype in primary microglia.

Conclusion

These findings reveal a novel mechanism through which Wnt3a signals in microglia resulting in the release of exosomes loaded with proteinaceous cargo.
'Le Rouge et le Noir': A decline in flavone formation correlates with the rare color of black dahlia (Dahlia variabilis hort.) flowers
Authors: Thill Jana , Miosic Silvija , Ahmed Romel , Schlangen Karin , Muster Gerlinde , Stich Karl , Halbwirth Heidi
Published: November 2012

Background

More than 20,000 cultivars of garden dahlia (Dahlia variabilis hort.) are available showing flower colour from white, yellow and orange to every imaginable hue of red and purple tones. Thereof, only a handful of cultivars are so-called black dahlias showing distinct black-red tints. Flower colour in dahlia is a result of the accumulation of red anthocyanins, yellow anthochlors (6’-deoxychalcones and 4-deoxyaurones) and colourless flavones and flavonols, which act as copigments. White and yellow coloration occurs only if the pathway leading to anthocyanins is incomplete. Not in all cultivars the same step of the anthocyanin pathway is affected, but the lack of dihydroflavonol 4-reductase activity is frequently observed and this seems to be based on the suppression of the transcription factor DvIVS. The hitherto unknown molecular background for black colour in dahlia is here presented.

Results

Black cultivars accumulate high amounts of anthocyanins, but show drastically reduced flavone contents. High activities were observed for all enzymes from the anthocyanin pathway whereas FNS II activity could not be detected or only to a low extent in 13 of 14 cultivars. cDNA clones and genomic clones of FNS II were isolated. Independently from the colour type, heterologous expression of the cDNA clones resulted in functionally active enzymes. FNS II possesses one intron of varying length. Quantitative Real-time PCR showed that FNS II expression in black cultivars is low compared to other cultivars. No differences between black and red cultivars were observed in the expression of transcription factors IVS and possible regulatory genes WDR1, WDR2, MYB1, MYB2, 3RMYB and DEL or the structural genes of the flavonoid pathway. Despite the suppression of FHT expression, flavanone 3-hydroxylase (FHT, synonym F3H) enzyme activity was clearly present in the yellow and white cultivars.

Conclusions

An increased accumulation of anthocyanins establishes the black flowering phenotypes. In the majority of black cultivars this is due to decreased flavone accumulation and thus a lack of competition for flavanones as the common precursors of flavone formation and the anthocyanin pathway. The low FNS II activity is reflected by decreased FNS II expression.
Comparing health-related quality of life of employed women and housewives: a cross sectional study from southeast Iran
Authors: Saravi Fatihe Kerman , Navidian Ali , Rigi Shahindokht Navabi , Montazeri Ali
Published: November 2012

Background

Quality of life differs for different people in different situations and is related to one's self-satisfaction with life. Considering the role of women in family and social health and the specific cultural characteristics of our province, we aimed to compare the quality of life of employed women with housewives in Zahedan, Iran.

Methods

This cross-sectional study was carried out during 2009–2010 in Zahedan, Iran. The sample consisted of 110 housewives and 110 employed women selected randomly from ten health care centers. Health-related quality of life was assessed using the SF-36. Analysis of covariance (ANCOVA) was used to compare quality of life in housewives and employed women while controlling for age, education and income.

Results

The mean (±SD) age of participants was 33.87± 8.95 years. Eighty-eight women (40%) had a university degree with a mean (±SD) official education of 10.8 (±4.9) years. The results indicated that employed women scored higher than housewives in all measures except for physical functioning. The differences were found to be remarkable for vitality, mental health and role emotional. However, after controlling for age, education and family income, none of differences reached significant level.

Conclusion

After controlling for potential confounders, the findings from this study indicated that there were no significant differences in quality of life between employed women and housewives. However, employed women scored higher on the SF-36, especially on the role emotional, vitality, and mental health. The findings suggest that associations exist between some aspects of health-related quality of life and employment. Indeed improving health-related quality of life among housewives seems essential.
Lycorine induces cell-cycle arrest in the G0/G1 phase in K562 cells via HDAC inhibition
Authors: Li Lv , Dai Hong-Juan , Ye Mao , Wang Shu-Ling , Xiao Xiao-Juan , Zheng Jie , Chen Hui-Yong , Luo Yu-hao , Liu Jing
Published: November 2012

Background

Lycorine, a natural alkaloid extracted from Amaryllidaceae, has shown various pharmacological effects. Recent studies have focused on the potential antitumor activity of lycorine. In our previous study, we found that lycorine decrease the cell viability of leukemia HL-60 cells and multiple myeloma KM3 cells and induces cell apoptosis. However, the effect and molecular mechanism of lycorine on human chronic myelocytic leukemia cells has yet to be determined.

Methods

Human chronic myelocytic leukemia cells K562 were treated with lycorine. Cell viability was monitored using the method of CCK-8. The histone deacetylase (HDAC) enzymatic activity was detected by HDAC colorimetric assay, and the cell cycle was analyzed by flow cytometry. The expression of cell-cycle related proteins were identified using Western blot.

Results

In the present study, we further revealed that lycorine can inhibit the proliferation of K562 cells. Analysis of HDAC activity showed that lycroine decreases HDAC enzymatic activities in K562 cells in a dose-dependent manner. Inhibition of HDAC activity has been associated with cell-cycle arrest and growth inhibition. We evaluated the cell cycle distribution after lycorine treatment and found that lycorine causes cell-cycle arrest in the G0/G1 phase. To investigate the mechanism behind this cell cycle arrest, G1-related proteins were assayed by Western blot. After lycorine treatment, cyclin D1 and cyclin-dependent kinase 4 expressions were inhibited and retinoblastoma protein phosphorylation was reduced. Lycorine treatment also significantly upregulated the expression of p53 and its target gene product, p21.

Conclusions

These results suggest that inhibition of HDAC activity is responsible for at least part of the induction of cell-cycle arrest in the G0/G1 phase by lycorine and provide a mechanistic framework for further exploring the use of lycorine as a novel antitumor agent.
Effect of the rest interval duration between contractions on muscle fatigue
Authors: Nogueira Daniel V , Silva Sidney B , de Abreu Luiz Carlos , Valenti Vitor E , Fujimori Mahmi , de Mello Monteiro Carlos Bandeira , Tortoza Charli , Ribeiro Wellington , Lazo-Osório Rodrigo A , Tierra-Criollo Carlos J
Published: November 2012

Background

We aimed to investigate the effect of rest interval, between successive contractions, on muscular fatigue.

Methods

Eighteen subjects performed elbow flexion and extension (30 repetitions) on an isokinetic dynamometer with 80º of range of motion. The flexion velocity was 120º/s, while for elbow extension we used 5 different velocities (30, 75, 120, 240, 360º/s), producing 5 different rest intervals (2.89, 1.28, 0.85, 0.57 and 0.54 s).

Results

We observed that when the rest interval was 2.89 s there was a reduction in fatigue. On the other hand, when the rest interval was 0.54 s the fatigue was increased.

Conclusions

When the resting time was lower (0.54 s) the decline of work in the flexor muscle group was higher compared with different rest interval duration.
A new treatment for neurogenic inflammation caused by EV71 with CR2-targeted complement inhibitor
Authors: Qiu Shaofu , Liu Nan , Jia Leili , Yang Guang , Su Wenli , Li Jing , Song Lixue , Yang Chaojie , Wang Jian , Zhang Chuanfu , Wang Zhongqiang , Qiao Fei , Tomlinson Stephen , Atkinson Carl , Sun Yansong , Huang Liuyu , Song Hongbin , Wang Yong , Li Zhenjun
Published: November 2012

Background

Enterovirus 71 (EV71), one of the most important neurotropic EVs, has caused death and long-term neurological sequelae in hundreds of thousands of young children in the Asia-Pacific region in the past decade. The neurological diseases are attributed to infection by EV71 inducing an extensive peripheral and central nervous system (CNS) inflammatory response with abnormal cytokine production and lymphocyte depletion induced by EV71 infection. In the absence of specific antiviral agents or vaccines, an effective immunosuppressive strategy would be valuable to alleviate the severity of the local inflammation induced by EV71 infection.

Presentation of the hypothesis

The complement system plays a pivotal role in the inflammatory response. Inappropriate or excessive activation of the complement system results in a severe inflammatory reaction or numerous pathological injuries. Previous studies have revealed that EV71 infection can induce complement activation and an inflammatory response of the CNS. CR2-targeted complement inhibition has been proved to be a potential therapeutic strategy for many diseases, such as influenza virus-induced lung tissue injury, postischemic cerebral injury and spinal cord injury. In this paper, a mouse model is proposed to test whether a recombinant fusion protein consisting of CR2 and a region of Crry (CR2-Crry) is able to specifically inhibit the local complement activation induced by EV71 infection, and to observe whether this treatment strategy can alleviate or even cure the neurogenic inflammation.

Testing the hypothesis

CR2-Crry is expressed in CHO cells, and its biological activity is determined by complement inhibition assays. 7-day-old ICR mice are inoculated intracranially with EV71 to duplicate the neurological symptoms. The mice are then divided into two groups, in one of which the mice are treated with CR2-Crry targeted complement inhibitor, and in the other with phosphate-buffered saline. A group of mice deficient in complement C3, the breakdown products of which bind to CR2, are also infected with EV71 virus. The potential bioavailability and efficacy of the targeted complement inhibitor are evaluated by histology, immunofluorescence staining and radiolabeling.

Implications of the hypothesis

CR2-Crry-mediated targeting complement inhibition will alleviate the local inflammation and provide an effective treatment for the severe neurological diseases associated with EV71 infection.
Engineering of plants with improved properties as biofuels feedstocks by vessel-specific complementation of xylan biosynthesis mutants
Authors: Petersen Pia Damm , Lau Jane , Ebert Berit , Yang Fan , Verhertbruggen Yves , Kim Jin Sun , Varanasi Patanjali , Suttangkakul Anongpat , Auer Manfred , Loqué Dominique , Scheller Henrik Vibe
Published: November 2012

Background

Cost-efficient generation of second-generation biofuels requires plant biomass that can easily be degraded into sugars and further fermented into fuels. However, lignocellulosic biomass is inherently recalcitrant toward deconstruction technologies due to the abundant lignin and cross-linked hemicelluloses. Furthermore, lignocellulosic biomass has a high content of pentoses, which are more difficult to ferment into fuels than hexoses. Engineered plants with decreased amounts of xylan in their secondary walls have the potential to render plant biomass a more desirable feedstock for biofuel production.

Results

Xylan is the major non-cellulosic polysaccharide in secondary cell walls, and the xylan deficient irregular xylem (irx) mutants irx7, irx8 and irx9 exhibit severe dwarf growth phenotypes. The main reason for the growth phenotype appears to be xylem vessel collapse and the resulting impaired transport of water and nutrients. We developed a xylan-engineering approach to reintroduce xylan biosynthesis specifically into the xylem vessels in the Arabidopsis irx7, irx8 and irx9 mutant backgrounds by driving the expression of the respective glycosyltransferases with the vessel-specific promoters of the VND6 and VND7 transcription factor genes. The growth phenotype, stem breaking strength, and irx morphology was recovered to varying degrees. Some of the plants even exhibited increased stem strength compared to the wild type. We obtained Arabidopsis plants with up to 23% reduction in xylose levels and 18% reduction in lignin content compared to wild-type plants, while exhibiting wild-type growth patterns and morphology, as well as normal xylem vessels. These plants showed a 42% increase in saccharification yield after hot water pretreatment. The VND7 promoter yielded a more complete complementation of the irx phenotype than the VND6 promoter.

Conclusions

Spatial and temporal deposition of xylan in the secondary cell wall of Arabidopsis can be manipulated by using the promoter regions of vessel-specific genes to express xylan biosynthetic genes. The expression of xylan specifically in the xylem vessels is sufficient to complement the irx phenotype of xylan deficient mutants, while maintaining low overall amounts of xylan and lignin in the cell wall. This engineering approach has the potential to yield bioenergy crop plants that are more easily deconstructed and fermented into biofuels.
High diversity and no significant selection signal of human ADH1B gene in Tibet
Authors: Lu Yan , Kang Longli , Hu Kang , Wang Chuanchao , Sun Xiaoji , Chen Feng , Kidd Judith R , Kidd Kenneth K , Li Hui
Published: November 2012

Background

ADH1B is one of the most studied human genes with many polymorphic sites. One of the single nucleotide polymorphism (SNP), rs1229984, coding for the Arg48His substitution, have been associated with many serious diseases including alcoholism and cancers of the digestive system. The derived allele, ADH1B*48His, reaches high frequency only in East Asia and Southwest Asia, and is highly associated with agriculture. Micro-evolutionary study has defined seven haplogroups for ADH1B based on seven SNPs encompassing the gene. Three of those haplogroups, H5, H6, and H7, contain the ADH1B*48His allele. H5 occurs in Southwest Asia and the other two are found in East Asia. H7 is derived from H6 by the derived allele of rs3811801. The H7 haplotype has been shown to have undergone significant positive selection in Han Chinese, Hmong, Koreans, Japanese, Khazak, Mongols, and so on.

Methods

In the present study, we tested whether Tibetans also showed evidence for selection by typing 23 SNPs in the region covering the ADH1B gene in 1,175 individuals from 12 Tibetan populations representing all districts of the Tibet Autonomous Region. Multiple statistics were estimated to examine the gene diversities and positive selection signals among the Tibetans and other populations in East Asia.

Results

The larger Tibetan populations (Qamdo, Lhasa, Nagqu, Nyingchi, Shannan, and Shigatse) comprised mostly farmers, have around 12% of H7, and 2% of H6. The smaller populations, living on hunting or recently switched to farming, have lower H7 frequencies (Tingri 9%, Gongbo 8%, Monba and Sherpa 6%). Luoba (2%) and Deng (0%) have even lower frequencies. Long-range haplotype analyses revealed very weak signals of positive selection for H7 among Tibetans. Interestingly, the haplotype diversity of H7 is higher in Tibetans than in any other populations studied, indicating a longer diversification history for that haplogroup in Tibetans. Network analysis on the long-range haplotypes revealed that H7 in the Han Chinese did not come from the Tibetans but from a common ancestor of the two populations.

Conclusions

We argue that H7 of ADH1B originated in the ancestors of Sino-Tibetan populations and flowed to Tibetans very early. However, as Tibetans depend less on crops, and therefore were not significantly affected by selection. Thus, H7 has not risen to a high frequency, whereas the diversity of the haplogroup has accumulated to a very high level.
A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid arthritis
Authors: Liu Rui , Wu Qian , Su Dinglei , Che Nan , Chen Haifeng , Geng Linyu , Chen Jinyun , Chen Wanjun , Li Xia , Sun Lingyun
Published: November 2012

Introduction

Interleukin (IL)-21 is a member of type I cytokine family. Recent studies indicate that IL-21 can promote T follicular helper (Tfh) cell differentiation and survival, a specialized T cell subset which provides help for B cell. It can also regulate the activation, proliferation and differentiation of human B cell and immunoglobulin (Ig) production as well as isotype switching of plasma cell. Rheumatoid arthritis (RA) is characterized by auto-antibodies overproduction such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, suggesting a pivotal role of Tfh cell and B cell in the pathogenesis of RA. This study aimed to investigate whether IL-21 had a regulatory effect on Tfh cell and B cell in RA.

Methods

Serum IL-21 concentrations were measured by ELISA. The correlations between serum IL-21 levels and clinical features of RA patients were analyzed by Spearman's rank test. The percentages of Tfh-like cells, IL-21 receptor (R) expression on Tfh-like cells and B cells in peripheral blood (PB) were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) were stimulated by rIL-21 (100 ng/ml) in the presence or absence of anti-CD40 and/or anti-IgM, and changes of IL-21R, activation-associated surface markers (CD25, CD69 and CD40), the proliferation, apoptosis and differentiation of B cells were analyzed by flow cytometry. Production of IgG and IgM in the culture supernatants was determined by ELISA.

Results

The results showed that the serum IL-21 levels in RA patients were significantly higher than that of healthy controls (HC). IL-21 concentrations were positively correlated with 28-joint count disease activity score (DAS28) and anti-CCP antibody in RA patients with high IL-21 levels. Furthermore, the frequencies of peripheral CXCR5+PD-1+CD4+ Tfh-like cells markedly increased in RA patients and the percentages of Tfh-like cells were positively correlated with DAS28 and anti-CCP antibody levels. Moreover, elevated IL-21 levels were also correlated with the frequencies of Tfh-like cells. IL-21R expression on both Tfh-like cells and B cells were significantly enhanced in RA patients. In cultures vitro, exogenous IL-21 upregulated IL-21R expression and activation-associated surface markers on B cells and promoted more B cell proliferation in RA than in HC. This IL-21-mediated effect could be reversed by IL-21R-specific neutralizing antibody. Importantly, IL-21 promoted more differentiation of B cell into plasmablast and higher levels of IgG and IgM production in RA than in HC.

Conclusions

Increased serum IL-21 levels in RA patients correlate with DAS28, anti-CCP antibody and frequencies of Tfh-like cells. IL-21 supports B cell activation, proliferation and antibody secretion via IL-21R pathway. Thus, IL-21 may be involved in the pathogenesis of RA and antagonizing IL-21 could be a novel strategy for the therapy of RA.
ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone
Authors: Mourskaia Anna A , Amir Eitan , Dong Zhifeng , Tiedemann Kerstin , Cory Sean , Omeroglu Atilla , Bertos Nicholas , Ouellet Véronique , Clemons Mark , Scheffer George L , Park Morag , Hallett Michael , Komarova Svetlana V , Siegel Peter M
Published: November 2012

Introduction

Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases.

Methods

To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture microdissected trephine biopsies of both breast cancer bone metastases and independent primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared with primary, bone-metastatic breast tumors.

Results

ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary breast tumors. In addition, ABCC5 was significantly upregulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 substantially reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers in vivo. Finally, conditioned media from breast cancer cells with reduced ABCC5 expression failed to induce in vitro osteoclastogenesis to the same extent as conditioned media from breast cancer cells expressing ABCC5.

Conclusions

Our data suggest that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for efficient osteoclast-mediated bone resorption. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis.
Reversible Phase Transfer of Ferromagnetic L10-FePt Nanoparticles
Authors: Yamamoto Shinpei , Tamada Yoshinori , Ono Teruo , Takano Mikio
Published: November 2012

A convenient and efficient method of reversible phase transfer of ferromagnetic L10-FePt nanoparticles between aqueous and organic phases was developed. From the SiO2-coated L10-FePt nanoparticles prepared by the “SiO2-nanoreactor” method, stable aqueous dispersions of L10-FePt nanoparticles were prepared first by using tetramethylammonium hydroxide (TMAOH). Replacement of TMAOH by mixtures of oleic acid and oleylamine enables transfer of the L10-FePt nanoparticles from aqueous to organic phase. The L10-FePt nanoparticles could be subsequently transferred to aqueous phase by replacing the hydrophobic ligands with TMAOH. Magnetic properties were unchanged during the phase transfer, suggesting that these L10-FePt nanoparticles will be of great importance not only for applications in biomedical fields but also for fabrication of high-performance magnetic devices via bottom-up processes.
Synthesis of Large-area Vertically Aligned Silicon Nanotip Arrays by Combining Silver Mirror Reaction with Metal-catalyzed Electroless Etching
Authors: Jiang Yilan , Tao Silu , Huang Jianxiong , Zhou Chun , Zhao Hua , Zhao Weiming
Published: November 2012

A novel strategy for preparing large-area, vertically aligned silicon nanotip arrays at near-room temperature by combining a silver mirror reaction with metal-catalyzed electroless etching has been developed. It has been demonstrated that silicon nanotip arrays of lengths 4–7 µm and middle part diameters ranging from 100 to 300 nm have been successfully fabricated on silicon wafers. Furthermore, the resultant large-area vertically aligned Si nanotip arrays on Si substrates are expected to be used in field-emission applications in the future and to have broad scope for development. Silicon nanotip films show very low reflectance (<10% at 300–800 nm) and strong broadband optical absorption (>90% at 500 nm). This transmission would be important for use as antireflection coatings on processed solar cells. These optical phenomena may lead to the realization of efficient solar cells based on Si nanostructures.
Formation of Diphosphate in the Presence of Vanadium(IV)–tpen Complex
Authors: Sato Kyouhei , Tsuge Kiyoshi , Kanamori Kan
Published: November 2012

The reaction of VOBr2 with N,N,N′N′-tetrakis(2-pyridylmethyl)ethylenediamine (tpen) and NaH2PO4 (2:1:2 molar ratio) in an aqueous/ethanolic solution yielded purple crystals. X-ray crystal structure analyses revealed that the purple complex was a dinuclear vanadium(IV) complex bridged by a diphosphate anion, [(VIVO)2(µ-P2O7)(µ-tpen)]·10H2O. This indicates that a condensation reaction occurred between two phosphate ions during the reaction to form a phosphate–phosphate bond. A probable mechanism is proposed for the condensation reaction of two phosphate anions.
Respiratory Symptoms and Patterns of Pulmonary Dysfunction among Roofing Fiber Cement Workers in the South of Thailand
Authors: Thepaksorn Phayong , Pongpanich Sathirakorn , Siriwong Wattasit , Chapman Robert S. , Taneepanichskul Surasak
Published: November 2012

Respiratory Symptoms and Patterns of Pulmonary Dysfunction among Roofing Fiber Cement Workers in the South of Thailand: Phayong THEPAKSORN, et al. College of Public Health Sciences, Chulalongkorn University, Thailand—

Objective

This study examined the associations between respiratory symptoms and patterns of pulmonary dysfunction of 115 male roofing cement workers compared with 134 unexposed subjects.

Methods

A cross‐sectional study was conducted. Environmental samplings and spirometry measurements were also collected.

Results

The exposed workers had higher respiratory dust exposure levels (0.65 mg/m3) compared with the unexposed groups (0.32 mg/m3). The exposed group had significantly higher prevalence than the unexposed group for shortness of breath (OR=2.19). The exposed group also had higher but insignificant prevalence of chronic cough (OR=1.34), chest tightness (OR=1.64), and wheezing (OR=1.89). The ventilatory respiratory function values (FEV1 and FVC) were slightly lower for the exposed group.

Conclusion

An association between higher cement dust levels and a decline in ventilatory function among roofing fiber cement workers suggests that the respiratory health of roofing cement workers should be protected through policies or work standards.
Phase Transitions in Pure Plutonium
Authors: Mitchell Jeremy N. , Freibert Franz, J. , Schwartz Daniel S.
Published: November 2012

The five solid-solid phase transformations of pure Pu are typically represented in idealized thermal expansion plots as having sharp onsets and finishes with linear expansion behavior between the transitions. These behaviors are in reality less common, and the various transitions may have bursting behavior, curved onsets and finishes, and non-linear thermal expansion. In this presentation we will review the transformation behavior of diverse set of pure Pu types. These types include zone-refined pure Pu, electro-refined pure Pu, pure Pu doped with 1000 appm Ga, and alpha-phase Pu within an as-cast 1.9 atomic. % Ga alloy.