Rhinovirus Load Is High despite Preserved Interferon-β Response in Cystic Fibrosis Bronchial Epithelial Cells

Lung disease in cystic fibrosis (CF) is often exacerbated following acute upper respiratory tract infections caused by the human rhinovirus (HRV). Pathophysiology of these exacerbations is presently unclear and may involve deficient innate antiviral or exaggerated inflammatory responses in CF airway epithelial cells. Furthermore, responses of CF cells to HRV may be adversely affected by pre-exposure to virulence factors of Pseudomonas (P.) aeruginosa, the microorganism that frequently colonizes CF airways. Here we examined production of antiviral cytokine interferon-β and inflammatory chemokine interleukin-8, expression of the interferon-responsive antiviral gene 2’-5’-oligoadenylate synthetase 1 (OAS1), and intracellular virus RNA load in primary CF (delF508 CFTR) and healthy airway epithelial cells following inoculation with HRV16. Parallel cells were exposed to virulence factors of P. aeruginosa prior to and during HRV16 inoculation. CF cells exhibited production of interferon-β and interleukin-8, and expression of OAS1 at levels comparable to those in healthy cells, yet significantly higher HRV16 RNA load during early hours post-inoculation with HRV16. In line with this, HRV16 RNA load was higher in the CFBE41o- dF cell line overexpessing delF508 CFTR, compared with the isogenic control CFBE41o- WT (wild-type CFTR). Pre-exposure to virulence factors of P. aeruginosa did not affect OAS1 expression or HRV16 RNA load, but potentiated interleukin-8 production. In conclusion, CF cells demonstrate elevated HRV RNA load despite preserved interferon-β and OAS1 responses. High HRV load in CF airway epithelial cells appears to be due to deficiencies manifesting early during HRV infection, and may not be related to interferon-β.     

Antioxidant properties of cystic fibrosis sputum

Oxidative stress is a likely contributor to the pathogenesis of cystic fibrosis (CF) lung disease. However, hydrogen peroxide (H(2)O(2)), a physiological oxidant, is not elevated in CF exhalates. H(2)O(2) may be neutralized by antioxidants in CF airway secretions. The H(2)O(2)-detoxifying capacity of CF airway secretions, obtained via sputum induction, was studied in an in vitro H(2)O(2) cytotoxicity model. 16HBE14o- cells were exposed to H(2)O(2) in culture medium containing either 0 or 10% fetal bovine serum (FBS) or 10% CF sputum supernatant (extracted without use of dithiothreitol). The efficiency of H(2)O(2) neutralization was estimated by measuring intracellular oxidant levels (dihydrorhodamine 123) after 2 h and cell viability (propidium iodide) after 24 h of H(2)O(2) exposure. Furthermore, the presence of reduced thiols (DTNB assay) and reduced glutathione (recycling assay) in CF sputum samples was evaluated. CF sputum extracts completely prevented intracellular oxidant accumulation seen in cells incubated with H(2)O(2) in both control media (i.e., 0 or 10% FBS). Furthermore, CF sputum abolished cell death in 16HBE14o- cells exposed to up to 1 mM H(2)O(2). In contrast, there was 100% cytotoxicity in cells exposed to 600 microM H(2)O(2) in both control media. The H(2)O(2)-detoxifying potential of CF sputum was sustained after catalase and heme peroxidases were inactivated by sodium azide, which does not affect glutathione peroxidase. In addition, reduced protein thiols were found in abundance in CF sputum. In conclusion, CF sputum is capable to neutralize H(2)O(2) and abundant reduced thiols and/or glutathione peroxidase are fully sufficient to detoxify H(2)O(2).     

影响阜康荒漠-绿洲过渡带荒漠植物数量特征的土壤驱动力分析

荒漠-绿洲过渡带是绿洲向沙漠系统的过渡地带,荒漠植物是绿洲扩展或荒漠化加速的缓冲器,土壤环境是影响植物演变的重要影响因素,土壤环境因素是整个过渡带演化的重要驱动力。通过对阜康荒漠-绿洲过渡带荒漠植物群落实地调查,利用通用植物数量分析软件CANOCO 5.0中冗余度分析(RDA),探讨过渡带影响荒漠植物群落数量特征指标的土壤驱动因子。结果表明:(1)土壤含水量、全N、全P和有机质是影响荒漠植物群落数量特征的主要驱动力因子,环境解释量累计达到69%,而总盐、p H和全K对荒漠植物群落数量特征影响较弱;(2)4个土壤主要驱动力对荒漠植物群落数量特征重要性大小顺序:土壤含水量有机质全N全P;(3)荒漠植物群落数量特征与土壤含水量、有机质和全P呈正相关,但与全N为负相关关系,揭示了土壤含水量、有机质和全P是利于荒漠植物群落稳定的正驱动力,而全N为抑制荒漠植物生长的负驱动力。综上所述,土壤各因子的驱动力作用不尽相同,存在正、负差异,协同维护荒漠植物群落数量特征的稳定和发展。     

Down-regulation of cytokine-induced interleukin-8 requires inhibition of p38 mitogen-activated protein kinase (MAPK) via MAPK phosphatase 1-dependent and -independent mechanisms

Down-regulation of overabundant interleukin (IL)-8 present in cystic fibrosis (CF) airways could ease excessive neutrophil burden and its deleterious consequences for the lung. IL-8 production in airway epithelial cells, stimulated with e.g. inflammatory cytokines IL-1β and tumor necrosis factor (TNF)-α, is regulated by several signaling pathways including nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). We previously demonstrated that the anti-inflammatory drugs dexamethasone and ibuprofen suppress NF-κB; however, only dexamethasone down-regulates cytokine-induced IL-8, highlighting the importance of non-NF-κB mechanisms. Here, we tested the hypothesis that down-regulation of cytokine-induced IL-8 requires modulation of the MAPK phosphatase (MKP)-1/p38 MAPK/mRNA stability pathway. The effects of dexamethasone (5 nm) and ibuprofen (480 μm) on this pathway and IL-8 were studied in CF (CFTE29o-, CFBE41o-) and non-CF (1HAEo-) airway epithelial cells. We observed that dexamethasone, but not ibuprofen, destabilizes IL-8 mRNA and up-regulates MKP-1 mRNA. Further, siRNA silencing of MKP-1, via p38 MAPK, leads to IL-8 overproduction and diminishes the anti-IL-8 potential of dexamethasone. However, MKP-1 overexpression does not significantly alter IL-8 production. By contrast, direct inhibition of p38 MAPK (inhibitor SB203580) efficiently suppresses IL-8 with potency comparable with dexamethasone. Similar to dexamethasone, SB203580 decreases IL-8 mRNA stability. Dexamethasone does not affect p38 MAPK activation, which excludes its effects upstream of p38 MAPK. In conclusion, normal levels of MKP-1 are necessary for a full anti-IL-8 potential of pharmacological agents; however, efficient pharmacological down-regulation of cytokine-induced IL-8 also requires direct effects on p38 MAPK and mRNA stability independently of MKP-1.     

Molecular and genetic analysis of NS gene from high pathogenic strains of the avian influenza (H5N1) virus isolated in Kazakhstan

The high pathogenic strains of the avian influenza H5N1 virus isolated in Kazakhstan have NS of different genotypes. The influenza virus strains isolated in 2005 is of NS1E Qinghai genotype. A/swan/Mangystau/3/2006 strain is of NS2A genotype that is typical for Gs/Gd-like strains. The results of the analysis allow assuming that A/swan/Mangystau/3/2006 strain has been brought onto the territory of Kazakhstan from the European part of the continent along the Black Sea-Mediterranean flyway.     

古尔班通古特沙漠某些短命植物叶片N、P化学计量特征的季节变化

短命植物是荒漠生态系统的重要组成部分。为了解短命植物叶片N、P化学计量特征随生长季变化的特点,选择古尔班通古特沙漠6种优势短命植物(3种一年生短命植物,3种多年生类短命植物)为研究对象,对比了2种生活型短命植物叶片N、P化学计量特征随生长季变化特点。结果表明,3种一年生短命植物尖喙牻牛儿苗(Erodium oxyrrhynchum)、小花荆芥(Nepeta micrantha)以及条叶庭芥(Alyssum linifolium)N含量平均值(±标准差)分别为(11.23±7.16)、(14.11±6.38)和(10.85±6.14)mg·g–1;P含量平均值分别为(2.82±0.73)、(3.12±1.24)和(3.43±0.55)mg·g–1;3种多年生类短命植物独尾草(Eremurus chinensis)、雅葱(Scorzonera pusilla)和簇花芹(Soranthus meyeri)N含量的平均值分别为(19.97±5.94)(15.08±4.01)和(17.94±9.03)mg·g–1;P含量平均值分别为(3.55±0.83)、(2.73±1.11)和(5.03±0.65)mg·g–1。由此可见,短命植物在生长过程中叶片N-P化学计量特征存在一定差异。各物种N、P含量在生长初期都大于其它生长季节,在生长旺季随叶片生物量增加,N、P含量呈下降趋势;而在生长末季N、P含量又有所回升。相关性分析表明,不同生活型短命植物元素间的关系存在差异,但同一生活型短命植物元素间的关系并无显著差异,体现了种内一致性。     

旱生芦苇对地下水位变化的生态响应及适应机制

地下水作为干旱半干旱地区可利用水的主要存在形式,是影响植被生存的主要生态因子。通过人工模拟地下水位,探讨了旱生芦苇对不同地下水位的生态响应及适应机制。结果表明:(1)随地下水位的降低,旱生芦苇净光合速率(P_n)、蒸腾速率(T_r)、气孔导度(G_s)和胞间CO_2浓度(C_i)均呈先增后减的变化趋势,其生长季均呈单峰曲线,以7—8月为峰值;(2)旱生芦苇叶绿素(Chl)含量随地下水位的降低呈先增后减的动态变化;(3)旱生芦苇脯氨酸(Pro)、可溶性糖(SS)和可溶性蛋白质(SP)含量随地下水位及其生长季的变化规律不一致,但三者在抑制干旱胁迫过程中存在相互补偿的关系;(4)随地下水位的降低,丙二醛(MDA)含量呈先增后减的变化趋势,且随生长季变化增加显著;超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性增加显著,且SOD比CAT对干旱胁迫反应更敏感,是适应干旱胁迫的主要抗氧化酶;(5)旱生芦苇生理因子对P_n的重要性大小顺序为G_sSPChlT_rC_iSS。     

Internal exposure to neutron-activated <Superscript>56</Superscript>Mn dioxide powder in Wistar rats—Part 2: pathological effects

To fully understand the radiation effects of the atomic bombing of Hiroshima and Nagasaki among the survivors, radiation from neutron-induced radioisotopes in soil and other materials should be considered in addition to the initial radiation directly received from the bombs. This might be important for evaluating the radiation risks to the people who moved to these cities soon after the detonations and probably inhaled activated radioactive “dust.” Manganese-56 is known to be one of the dominant radioisotopes produced in soil by neutrons. Due to its short physical half-life, ⁵⁶Mn emits residual radiation during the first hours after explosion. Hence, the biological effects of internal exposure of Wistar rats to ⁵⁶Mn were investigated in the present study. MnO₂ powder was activated by a neutron beam to produce radioactive ⁵⁶Mn. Rats were divided into four groups: those exposed to ⁵⁶Mn, to non-radioactive Mn, to ⁶⁰Co γ rays (2 Gy, whole body), and those not exposed to any additional radiation (control). On days 3, 14, and 60 after exposure, the animals were killed and major organs were dissected and subjected to histopathological analysis. As described in more detail by an accompanying publication, the highest internal radiation dose was observed in the digestive system of the rats, followed by the lungs. It was found that the number of mitotic cells increased in the small intestine on day 3 after ⁵⁶Mn and ⁶⁰Co exposure, and this change persisted only in ⁵⁶Mn-exposed animals. Lung tissue was severely damaged only by exposure to ⁵⁶Mn, despite a rather low radiation dose (less than 0.1 Gy). These data suggest that internal exposure to ⁵⁶Mn has a significant biological impact on the lungs and small intestine.