Inhibition of oxidative hemolysis in erythrocytes by mitochondria-targeted antioxidants of SkQ series

In the present work we studied the effect of antioxidants of the SkQ1 family (10-(6′-plastoquinonyl)decyltriphenylphosphonium) on the oxidative hemolysis of erythrocytes induced by a lipophilic free radical initiator 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN) and a water-soluble free radical initiator 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). SkQ1 was found to protect erythrocytes from hemolysis, 2 μM being the optimal concentration. Both the oxidized and reduced SkQ1 forms exhibited protective properties. Both forms of SkQ1 also inhibited lipid peroxidation in erythrocytes induced by the lipophilic free radical initiator AMVN as detected by accumulation of malondialdehyde. However, in the case of induction of erythrocyte oxidation by AAPH, the accumulation of malondialdehyde was not inhibited by SkQ1. In the case of AAPH-induced hemolysis, the rhodamine-containing analog SkQR1 exerted a comparable protective effect at the concentration of 0.2 μM. At higher SkQ1 and SkQR1 concentrations, the protective effect was smaller, which was attributed to the ability of these compounds to facilitate hemolysis in the absence of oxidative stress. We found that plastoquinone in the oxidized form of SkQ1 could be reduced by erythrocytes, which apparently accounted for its protective action. Thus, the protective effect of SkQ in erythrocytes, which lack mitochondria, proceeded at concentrations that are two to three orders of magnitude higher than those that were active in isolated mitochondria.     

高糖通过诱导HT22细胞衰老和凋亡抑制细胞生长

目的探讨高糖(High glucose,HG)对小鼠海马神经元细胞HT22细胞的生长抑制作用,分析其是否通过HG诱导细胞衰老以及凋亡而实现。方法采用台盼蓝染色计数法检测细胞生长状况并绘制生长曲线,β-半乳糖苷酶(Senescence associated acidic-β-galactosidas,SA-β-Gal)染色法检测衰老的HT22细胞,Hoechst 33258染色法检测HT22细胞凋亡形态。结果(1)HG(13.5、27、40.5mg/ml,48h)能显著抑制HT22细胞生长(P0.05,P0.01);(2)HG(13.5、27、40.5mg/ml)处理48h可明显诱导SA-β-Gal染色阳性率增加(P0.001);(3)HG(13.5、27、40.5mg/ml,48h)能诱导HT22细胞发生凋亡(P0.001),且呈浓度依赖性。结论 HG可通过诱导HT22细胞衰老和凋亡而抑制HT22细胞生长。     

Small Heat-Shock Proteins,IbpAB, Protect Non-Pathogenic Escherichia coli from Killing by Macrophage-Derived Reactive Oxygen Species

Many intracellular bacterial pathogens possess virulence factors that prevent detection and killing by macrophages. However, similar virulence factors in non-pathogenic bacteria are less well-characterized and may contribute to the pathogenesis of chronic inflammatory conditions such as Crohn’s disease. We hypothesize that the small heat shock proteins IbpAB, which have previously been shown to reduce oxidative damage to proteins in vitro and be upregulated in luminal non-pathogenic Escherichia strain NC101 during experimental colitis in vivo, protect commensal E. coli from killing by macrophage-derived reactive oxygen species (ROS). Using real-time PCR, we measured ibpAB expression in commensal E. coli NC101 within wild-type (wt) and ROS-deficient (gp91phox^-/-) macrophages and in NC101 treated with the ROS generator paraquat. We also quantified survival of NC101 and isogenic mutants in wt and gp91phox^-/- macrophages using gentamicin protection assays. Similar assays were performed using a pathogenic E. coli strain O157:H7. We show that non-pathogenic E. coli NC101inside macrophages upregulate ibpAB within 2 hrs of phagocytosis in a ROS-dependent manner and that ibpAB protect E. coli from killing by macrophage-derived ROS. Moreover, we demonstrate that ROS-induced ibpAB expression is mediated by the small E. coli regulatory RNA, oxyS. IbpAB are not upregulated in pathogenic E. coli O157:H7 and do not affect its survival within macrophages. Together, these findings indicate that ibpAB may be novel virulence factors for certain non-pathogenic E. coli strains.     

豫东平原聚落景观格局变化

中国的快速城镇化必然导致聚落景观格局的变化,但目前相关研究对平原地区关注相对较少。文中选取豫东平原地区的开封、商丘、周口市,运用GIS空间分析方法和ENVI遥感影像处理技术,对该地区1972、2015年市域中观尺度上的聚落规模、聚落景观空间变化特征进行分析。结果显示:(1)在聚落发展过程中,1972—2015年聚落斑块数量有所减少,聚落规模逐渐扩张,市域内最大聚落斑块扩张相对更为明显;对聚落斑块扩张强度的分析发现,城市市辖区及周边乡镇聚落扩张强度相对较高。(2)地区内聚落斑块空间分布表现出聚集分布特征,但该时期聚集程度有所减弱;两个年份聚落核密度分布格局大致相似,局部地区存在多核扩散现象,市域尺度上的核密度分布存在地区差异。(3)对斑块形状指数的分析发现,研究区狭长或曲折聚落斑块在空间上分散布局,整体上区域内聚落形状趋于规则。(4)随着距河流、道路距离的增加,聚落斑块总面积和数量有所减少,且道路对聚落分布仅在一定范围内存在较大影响,距中心城市0—6km范围内聚落受中心城区发展辐射影响较大。本文的分析可为平原地区聚落景观的优化布局和聚落用地的集约化发展提供一定的参考。     

松嫩平原苏打盐渍化旱田土壤表观电导率空间变异

在松嫩平原西部吉林省大安市乐胜乡,于2013年4月20日选择盐碱程度不均一的典型盐渍化旱田地块,面积为4.8 hm~2作为研究样地。利用EM38大地电导率仪测定结合田间定点采样,并通过经典统计和地统计相结合的方法研究了盐渍化旱田土壤表观电导率空间变异特征,分析了土壤表观电导率与土壤盐碱指标之间的关系。结果表明,盐渍化旱田土壤水平方向表观电导率(EC_h)经对数转换后具有强空间自相关,其变异特征主要是与地形地貌和水文状况等结构性因素有关。垂直方向表观电导率(EC_v)经对数转换后具有中等空间自相关性,其变异特征受结构性因素和随机因素共同作用。EC_h和EC_v半方差模拟的最优模型分别为球状模型和指数模型。Pearson分析表明土壤表观电导率(EC_h和EC_v)与土壤盐碱指标EC_(1∶5)、pH_(1∶5)、SAR、SC、Na~+、CO_3~(2-)、HCO_3~-呈正相关关系(P0.05),EC_h与土壤盐碱指标相关系数均大于EC_v。在实际应用中可以用EC_h来指示土壤的盐碱程度。回归分析表明土壤表观电导率(EC_h和EC_v)与土壤盐碱指标呈线性相关,且EC_h回归模型的决定系数均大于EC_v回归模型的决定系数,可用水平方向土壤表观电导率(EC_h)来计算土壤盐碱指标,进行土壤盐渍化的快速评估。     

Advanced lymphoblastic clones detection in T-cell leukemia

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant neoplasm of the lymphocyte precursors that suffered malignant transformation arresting the lymphoid cell differentiation. Clinical studies revealed monoor, more rarely, oligoclonal nature of the disease. A precise identification of malignant clone markers is both the crucial stage of early diagnostics and the essential prognostic factor for therapeutic treatment. Here we present an improved system for unbiased detection of lymphoblastic clones in bone marrow aspirates of T-ALL patients. The system based on multiplex PCR of rearranged T-cell receptor locus (TRB) and straightforward sequencing of the resulted PCR fragments. Testing of the system on genomic DNA from Jurkat cell line and four clinical bone marrow aspirates revealed a set of unique TRB rearrangements that precisely characterize each of tested samples. Therefore, the outcome of the system produces highly informative molecular genetic markers for further monitoring of minimal residual disease in T-ALL patients.     

Distribution and function of prophage phiRv1 and phiRv2 among Mycobacterium tuberculosis complex

Mycobacterium tuberculosis complex (MTBC) is notorious for causing diseases, such as tuberculosis. Tuberculosis caused by M. tuberculosis remains a global public health concern. Two prophages, phiRv1 and phiRv2, can be found among most MTBC genomes. However, no precise functions have been assigned for the two prophages. In this paper, to find out the function of these two prophages, the distribution and function of phiRv1 and phiRv2 in MTBC genomes were analyzed from multiple omics data. We found that complex insertion, deletion, and reorganization appeared on the locus of two prophages in MTBC genomes; some genes of the two prophages can be translated and are functional from proteomic data; the expression of other prophage genes, such as Rv1577c, Rv2650c, Rv2652c, Rv2659c, and Rv2658c, can vary with environmental stresses and might enhance the fitness of MTBC. These data will facilitate our in-depth understanding of their function.     

The ABC’s of Suicide Risk Assessment: Applying a Tripartite Approach to Individual Evaluations

There is considerable need for accurate suicide risk assessment for clinical, screening, and research purposes. This study applied the tripartite affect-behavior-cognition theory, the suicidal barometer model, classical test theory, and item response theory (IRT), to develop a brief self-report measure of suicide risk that is theoretically-grounded, reliable and valid. An initial survey (n = 359) employed an iterative process to an item pool, resulting in the six-item Suicidal Affect-Behavior-Cognition Scale (SABCS). Three additional studies tested the SABCS and a highly endorsed comparison measure. Studies included two online surveys (Ns = 1007, and 713), and one prospective clinical survey (n = 72; Time 2, n = 54). Factor analyses demonstrated SABCS construct validity through unidimensionality. Internal reliability was high (α = .86-.93, split-half = .90-.94)). The scale was predictive of future suicidal behaviors and suicidality (r = .68, .73, respectively), showed convergent validity, and the SABCS-4 demonstrated clinically relevant sensitivity to change. IRT analyses revealed the SABCS captured more information than the comparison measure, and better defined participants at low, moderate, and high risk. The SABCS is the first suicide risk measure to demonstrate no differential item functioning by sex, age, or ethnicity. In all comparisons, the SABCS showed incremental improvements over a highly endorsed scale through stronger predictive ability, reliability, and other properties. The SABCS is in the public domain, with this publication, and is suitable for clinical evaluations, public screening, and research.