Abortive Infection of L Cells by Influenza B Virus: Defect in Bud Formation

Host-dependent restriction of influenza B virus replication in L cells was analysed in comparison with productive infection in MDCK or 1–5C-4 cells. The synthesis and intracellular distribution of virus-specific proteins and the production of cytoplasmic ribonucleoproteins in nonpermissive L cells were similar to those in permissive MDCK cells. However, an electron microscopic study of infected L cells showed neither extracellular virions nor budding virus particles on the cell surface, in contrast to MDCK cells which produced numerous virus particles. PAGE analysis of the plasma membrane isolated from the cells demonstrated no significant difference in the composition of viral polypeptides between permissive 1-5C-4 and nonpermissive L cells. It was noted that the abortiveness of influenza B virus infection in L cells may be due to a defect in host cell function involved in the initiation of virus budding.     

Synthesis and luminescence properties of two novel lanthanide (III) complexes of acetophenonylcarboxymethyl sulphoxide

A novel ligand containing multiple coordinating groups (sulfinyl, carboxyl and carbonyl groups), acetophenonylcarboxymethyl sulphoxide, was synthesized. Its corresponding two lanthanide (III) binary complexes were synthesized and characterized by element analysis, molar conductivity, FT‐IR, TG‐DTA and UV spectroscopy. Results showed that the composition of these complexes was REL₃L^‐ (ClO₄)₂·3H₂O (RE = Eu (III), Tb (III); L = C₆H₅COCH₂SOCH₂COOH; L^‐ = C₆H₅COCH₂SOCH₂COO^‐). FT‐IR results indicated that acetophenonylcarboxymethyl sulphoxide was bonded with an RE (III) ion by an oxygen atom of the sulfinyl and carboxyl groups and not by an oxygen atom of the carbonyl group due to high steric hinderance. Fluorescent spectra showed that the Tb (III) complex had excellent luminescence as a result of a transfer of energy from the ligand to the excitation state energy level (⁵D₄) of Tb (III). The Eu (III) complex displayed weak luminescence, attributed to low energy transfer efficiency between the triplet state energy level of its ligand and the excited state (⁵D₀) of Eu (III). As a result, the Tb (III) complex displayed a good antenna effect for luminescence. The fluorescence decay curves of Eu (III) and Tb (III) complexes were also measured. Copyright © 2012 John Wiley & Sons, Ltd.     

Repeatability of and Relationship between Potential COPD Biomarkers in Bronchoalveolar Lavage,Bronchial Biopsies,Serum, and Induced Sputum

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease, primarily affecting the airways. Stable biomarkers characterizing the inflammatory phenotype of the disease, relevant for disease activity and suited to predict disease progression are needed to monitor the efficacy and safety of drug interventions. We therefore analyzed a large panel of markers in bronchoalveolar lavage, bronchial biopsies, serum and induced sputum of 23 healthy smokers and 24 smoking COPD patients (GOLD II) matched for age and gender. Sample collection was performed twice within a period of 6 weeks. Assays for over 100 different markers were validated for the respective matrices prior to analysis. In our study, we found 51 markers with a sufficient repeatability (intraclass correlation coefficient >0.6), most of these in serum. Differences between groups were observed for markers from all compartments, which extends (von-Willebrand-factor) and confirms (e.g. C-reactive-protein, interleukin-6) previous findings. No correlations between lung and serum markers were observed, including A1AT. Airway inflammation defined by sputum neutrophils showed only a moderate repeatability. This could be improved, when a combination of neutrophils and four sputum fluid phase markers was used to define the inflammatory phenotype.In summary, our study provides comprehensive information on the repeatability and interrelationship of pulmonary and systemic COPD-related markers. These results are relevant for ongoing large clinical trials and future COPD research. While serum markers can discriminate between smokers with and without COPD, they do not seem to sufficiently reflect the disease-associated inflammatory processes within the airways.     

Chronopharmacology of roflumilast: a comparative pharmacokinetic study of morning versus evening administration in healthy adults

The human circadian system is known to affect the pharmacokinetics and pharmacodynamics of several classes of respiratory disease medications. The current study involving 16 healthy adults investigated if the time-of-day of dosing of roflumilast, a novel phosphodiesterase-4 inhibitor, affects its pharmacokinetics. The rate of drug absorption (t(max): 1.50 versus 2.00 h) and peak concentration at t(max) (C(max): 3.79 versus 3.06 μg/L) was slightly greater with morning than evening administration, but without clinical significance. The extent of drug absorption (AUC) and drug elimination (t(1/2)) did not differ between the two dosing times. The pharmacokinetics of the active main metabolite, roflumilast N-oxide, also was not affected by the time of drug administration. Finally, the safety and tolerability of roflumilast did not differ between the two different times of administration.     

气候、植被和地形对大兴安岭林火烈度空间格局的影响

在北方森林中火干扰是森林景观变化的主导因素。林火烈度作为衡量林火动态的重要指标,较为直观地反映了火干扰对森林生态系统的破坏程度,其空间格局深刻地影响着森林景观中的多种生态过程(如树种组成、种子扩散以及植被的恢复)。解释林火烈度空间格局有助于揭示林火干扰后森林景观格局的形成机制,对预测未来林火烈度空间格局以及制定科学合理林火管理策略均有重要意义。基于LandsatTM/ETM遥感影像,将2000—2016年大兴安岭呼中林区的36场火的林火烈度划分为未过火、轻度、中度、重度4个等级。采用FRAGSTAT景观格局分析软件从类型水平上计算了斑块所占景观面积比、面积加权平均斑块面积、面积加权平均斑块分维数、面积加权边缘面积比、斑块密度5个景观指数,以对林火烈度空间格局进行了定量化描述。并且采用随机森林模型,分析了气候、地形、植被对林火烈度空间格局的影响及其边际效应。通过研究得出以下结果:(1)相对于未过火、轻度、以及中度火烧斑块,重度火烧斑块的面积更大、形状更简单;(2)海拔对重度火烧斑块的空间格局起着至关重要的作用,其次是坡向、坡度、植被覆盖度、相对湿度、温度等;(3)随着海拔的升高,面积加权...     

No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study

Background

Roflumilast is an oral, selective phosphodiesterase 4 inhibitor with anti-inflammatory effects in chronic obstructive pulmonary disease (COPD). The addition of roflumilast to long-acting bronchodilators improves lung function in patients with moderate-to-severe COPD. The present study investigated drug-drug interaction effects between inhaled formoterol and oral roflumilast.

Methods

This was a single-centre (investigational clinic), open, randomised, multiple-dose, parallel-group study. In Regimen A, healthy men were treated with roflumilast (500 μg tablet once daily; Day 2-18) and concomitant formoterol (24 μg twice daily; Day 12-18). In Regimen B, healthy men were treated with formoterol (24 μg twice daily; Day 2-18) and concomitant roflumilast (500 μg once daily; Day 9-18). Steady-state plasma pharmacokinetics of roflumilast, roflumilast N-oxide and/or formoterol (C_max and AUC_0-τ) as well as pharmacodynamics - blood pressure, transthoracic impedance cardiography (ZCG), 12-lead digital electrocardiography, peripheral blood eosinophils, and serum glucose and potassium concentrations - were evaluated through Day 1 (baseline), Day 8 (Regimen B: formoterol alone) or Day 11 (Regimen A: roflumilast alone), and Day 18 (Regimen A and B: roflumilast plus formoterol). Blood and urine samples were taken for safety assessment at screening, pharmacokinetic profiling days and Day 19. Adverse events were monitored throughout the study.

Results

Of the 27 subjects enrolled, 24 were evaluable (12 in each regimen). No relevant pharmacokinetic interactions occurred. Neither roflumilast nor formoterol were associated with significant changes in cardiovascular parameters as measured by ZCG, and these parameters were not affected during concomitant administration. Formoterol was associated with a slight increase in heart rate and a corresponding shortening of the QT interval, without changes in the heart rate-corrected QTc interval. There were small effects on the other pharmacodynamic assessments when roflumilast and formoterol were administered individually, but no interactions or safety concerns were seen after concomitant administration. No severe or serious adverse events were reported, and no adverse events led to premature study discontinuation.

Conclusions

No clinically relevant pharmacokinetic or pharmacodynamic interactions were found when oral roflumilast was administered concomitantly with inhaled formoterol, including no effect on cardiac repolarisation. Roflumilast was well tolerated.

Trial Registration

Clinicaltrials.gov NCT00940329     

气候变化背景下江西省林火空间预测

林火是森林生态系统中重要的干扰因子之一,深刻地影响森林景观结构和功能。在全球气候化背景下,揭示气候变化对林火空间分布格局的影响,可为林火管理和防火资源分配提供科学指导。因此,基于江西省2001—2015年MODIS火影像数据(MCD14ML)和年均气温、年均降水量、植被、地形、人口密度、距道路距离、距居民点距离7个因子数据,利用增强回归树模型:(1)分析林火发生影响因子的相对重要性及其边际效应;(2)将GFDL-CM3和GISS-E2-R气候变化模式中的年均气温和年均降水量作为未来的气象数据,在3个温室气体排放量情景(RCP2.6、RCP4.5、RCP8.5)下,对2050年(2041—2060的平均值)和2070年(2061—2080的平均值)江西省林火分布进行预测,生成林火发生概率图。并采用受试者工作特征(ROC曲线)和混淆矩阵评估模型预测的精度。研究结果表明:(1)年均气温和海拔与江西省林火发生的相关性较强,年均降水量、居民点距离、人口密度、道路距离与林火发生的相关性较弱,但是与林火发生密切相关的如降水、风速等也应重点关注;(2)训练数据(70%)和验证数据(30%)的AUC值(ROC曲线下面积值)均为0.736,混淆矩阵对火点预测的正确率为67.8%,表明模型能够较好地预测研究区林火的发生;(3)在RCP8.5排放情景中林火发生的增幅最明显,其增幅较大的区域由赣南向赣北移动;(4)未来2050年和2070年林火发生与当前气候(2001—2015年)下相比,赣州市、鹰潭市的增幅较为明显,其他区域不明显。江西省各林业管理部门要加强林火高发区及潜在发生区的森林监测和管理,加大防火宣传力度,提升民众的森林防火意识。     

Heat-Stable Enterotoxin Produced by Yersinia enterocolitica Isolated from Patients

Twenty-three strains of Yersinia enterocolitica were isolated from children with gastrointestinal illness and examined for the production of enterotoxins by using both suckling mouse and Chinese hamster ovary (CHO) cell assay systems. Six strains were found to be enterotoxigenic in the suckling mouse assay, but all strains were negative in the CHO cell assay. Enterotoxin was detected in the culture supernatant when organisms were grown at 25 C but not at 37 C. Enterotoxin in a 15-fold concentrated culture supernatant was precipitated by adding absolute ethanol to a concentration of 90%. However, after being dialyzed against distilled water in Spectra/por 6 membrane tubing, it was soluble in 80% acetone. One unit dose of partially purified enterotoxin was 5.0 μg of protein/mouse in the suckling mouse assay. The molecular weight of enterotoxin was between 10,000 and 50,000 daltons as determined by ultrafiltration. It was stable to heat (121 C × 20 min or 100 C × 60 min). These observations indicate that Y. enterocolitica isolated in Japan also produce an enterotoxin similar to the heat-stable enterotoxin of Escherichia coli. However its physicochemical properties seem to be different from those of E. coli.     

Isolation and Classification of Temperature-Sensitive Mutants of Influenza B Virus

We isolated 25 temperature-sensitive mutants of B/Kanagawa/73 strain generated by mutagenesis with 5-fluorouracil and classified them into seven recombination groups by pair-wise crosses. All mutants showed a ratio of plaquing efficiency at the nonpermissive temperature (37.5 C) to the permissive temperature (32 C) of 10^–4 or less. At 37.5 C most of group I, II, and III mutants did not produce appreciable amounts of protein, but all other group mutants were protein synthesis-positive. A group VII mutant produced active hemagglutinin (HA) and neuraminidase (NA) at the nonpermissive temperature, but Group V mutants produced only active NA and were defective in the HA molecule. The other group mutants, including group IV mutants with mutation only in the NA gene (8, 10), lacked both activities at the nonpermissive temperature. One of nine influenza B virus isolates in 1989 had EOP 37.5/32 of 1/3 × 10^–2 and belonged to recombination group VII.     

Mapping QTLs of yield-related traits using RIL population derived from common wheat and Tibetan semi-wild wheat

Key message

QTLs controlling yield-related traits were mapped using a population derived from common wheat and Tibetan semi-wild wheat and they provided valuable information for using Tibetan semi-wild wheat in future wheat molecular breeding.

Abstract

Tibetan semi-wild wheat (Triticum aestivum ssp tibetanum Shao) is a kind of primitive hexaploid wheat and harbors several beneficial traits, such as tolerance to biotic and abiotic stresses. And as a wild relative of common wheat, heterosis of yield of the progeny between them was significant. This study focused on mapping QTLs controlling yield-related traits using a recombined inbred lines (RILs) population derived from a hybrid between a common wheat line NongDa3331 (ND3331) and the Tibetan semi-wild wheat accession Zang 1817. In nine location–year environments, a total of 148 putative QTLs controlling nine traits were detected, distributed on 19 chromosomes except for 1A and 2D. Single QTL explained the phenotypic variation ranging from 3.12 to 49.95 %. Of these QTLs, 56 were contributed by Zang 1817. Some stable QTLs contributed by Zang 1817 were also detected in more than four environments, such as QPh-3A1, QPh-4B1 and QPh-4D for plant height, QSl-7A1 for spike length, QEp-4B2 for ears per plant, QGws-4D for grain weight per spike, and QTgw-4D for thousand grain weight. Several QTL-rich Regions were also identified, especially on the homoeologous group 4. The TaANT gene involved in floral organ development was mapped on chromosome 4A between Xksm71 and Xcfd6 with 0.8 cM interval, and co-segregated with the QTLs controlling floret number per spikelet, explaining 4.96–11.84 % of the phenotypic variation. The current study broadens our understanding of the genetic characterization of Tibetan semi-wild wheat, which will enlarge the genetic diversity of yield-related traits in modern wheat breeding program.