Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo

Vascular endothelial cell (VEC) apoptosis is the main event occurring during the development of atherosclerosis. Pterostilbene (PT), a natural dimethylated analog of resveratrol, has been the subject of intense research in cancer and inflammation. However, the protective effects of PT against oxidized low-density lipoprotein (oxLDL)-induced apoptosis in VECs have not been clarified. We investigated the anti-apoptotic effects of PT in vitro and in vivo in mice. PT at 0.1–5 μM possessed antioxidant properties comparable to that of trolox in a cell-free system. Exposure of human umbilical vein VECs (HUVECs) to oxLDL (200 μg/ml) induced cell shrinkage, chromatin condensation, nuclear fragmentation, and cell apoptosis, but PT protected against such injuries. In addition, PT injection strongly decreased the number of TUNEL-positive cells in the endothelium of atherosclerotic plaque from apoE^−/− mice. OxLDL increased reactive oxygen species (ROS) levels, NF-κB activation, p53 accumulation, apoptotic protein levels and caspases-9 and -3 activities and decreased mitochondrial membrane potential (MMP) and cytochrome c release in HUVECs. These alterations were attenuated by pretreatment with PT. PT inhibited the expression of lectin-like oxLDL receptor-1 (LOX-1) expression in vitro and in vivo. Cotreatment with PT and siRNA of LOX-1 synergistically reduced oxLDL-induced apoptosis in HUVECs. Overexpression of LOX-1 attenuated the protection by PT and suppressed the effects of PT on oxLDL-induced oxidative stress. PT may protect HUVECs against oxLDL-induced apoptosis by downregulating LOX-1-mediated activation through a pathway involving oxidative stress, p53, mitochondria, cytochrome c and caspase protease. PT might be a potential natural anti-apoptotic agent for the treatment of atherosclerosis.     

CVTree在454高通量测序分析菌群结构中的应用

目的探究将基于短串频度的CVTree方法用于反映菌群结构的16S rRNA基因的454高通量测序数据分析的可行性,为快速分析高通量菌群结构数据提供新的方法。方法对一个四世同堂的中国家庭7名成员肠道菌群和不同基因型及饮食类型的小鼠肠道菌群用454高通量方法获得16S rRNA基因的V3区的测序数据,用CVTree的方法进行菌群结构的比较分析。结果通过选取合适的短串长度,CVTree的方法能准确检测到各样本间的聚类关系,其结果与之前文献报道的基于Unifrac算法的结果相一致。结论CVTree能快速、有效地处理16S rRNA基因的454高通量测序数据,实现对不同菌群结构相似性的比较分析。     

一个新水稻温敏感叶色突变体的遗传分析及其基因分子定位

在粳稻品种嘉花1号(Oryza sativa L. ssp. japonica ‘Jiahua No.1’)种子经⁶⁰Co γ射线辐照处理的后代中, 发现了1个低温敏感叶色突变体mr21。在较低温度(<25.0°C)条件下, 该突变体幼苗叶色呈黄色; 随着温度逐渐升高, 叶色由黄转绿,其临界温度约为27.5°C; 在低温条件下, 突变体幼苗总叶绿素含量以及叶绿素a、b的含量均较野生型嘉花1号明显下降, 表明该突变体的叶色性状具有明显的温敏感性。遗传分析表明, 该突变体叶色性状受1对隐性核基因控制, 暂将该突变基因命名为thermo-sensitive leaf-color 1(tsl-1)。以该突变体与籼稻9311(Oryza sativa L. ssp. indica ‘9311’)杂交的F₂代分离群体作为定位群体, 利用SSR分子标记将tsl-1基因初步定位在水稻(Oryza sativa)第1号染色体短臂上的MM1799与RM8132分子标记之间, 其遗传距离分别为2.4 cM和3.0 cM; 然后, 进一步利用扩大F₂代群体及新发展的分子标记将tsl-1基因定位在分子标记InDel2与InDel4之间的198 kb内。研究结果为今后对该基因的克隆和功能分析奠定了基础。     

Subspecies-specific intron length polymorphism markers reveal clear genetic differentiation in common wild rice （Oryza rufipogon L.） in relation to the domestication of cultivated rice （O. sativa L.）

It is generally accepted that Oryza rufipogon is the progenitor of Asian cultivated rice （O. sativa）. However, how the two subspecies of O. sativa （indica and japonica） were domesticated has long been debated. To investigate the genetic differentiation in O. rufipogon in relation to the domestication of O. sativa, we developed 57 subspecies-specific intron length polymorphism （SSILP） markers by comparison between 10 indica cultivars and 10 japonica cultivars and defined a standard indica rice and a standard japonica rice based on these SSILP markers. Using these SSILP markers to genotype 73 O. rufipogon accessions, we found that the indica alleles and japonica alleles of the SSILP markers were predominant in the O. rufipogon accessions, suggesting that SSILPs were highly conserved during the evolution of O. sativa. Cluster analysis based on these markers yielded a dendrogram consisting of two distinct groups： one group （Group I） comprises all the O. rufipogon accesions from tropical （South and Southeast） Asia as well as the standard indica rice; the other group （Group II） comprises all the O. rufipogon accessions from Southern China as well as the standard japonica rice. Further analysis showed that the two groups have significantly higher frequencies of indica alleles and japonica alleles, respectively. These results support the hypothesis that indica rice and japonica rice were domesticated from the O. rufipogon of tropical Asia and from that of Southern China, respectively, and suggest that the indica-japonica differentiation should have formed in O. rufipogon long before the beginning of domestication. Furthermore, with an O. glaberrima accession as an outgroup, it is suggested that the indica-japonica differentiation in O. ruffpogon might occur after its speciation from other AA-genome species.     

Morphological bases of suppressive and facilitative spatial summation in the striate cortex of the cat

In V1 of cats and monkeys, activity of neurons evoked by stimuli within the receptive field can be modulated by stimuli in the extra-receptive field (ERF). This modulating effect can be suppressive (S-ERF) or facilitatory (F-ERF) and plays different roles in visual information processing. Little is known about the cellular bases underlying the different types of ERF modulating effects. Here, we focus on the morphological differences between the S-ERF and F-ERF neurons. Single unit activities were recorded from V1 of the cat. The ERF properties of each neuron were assessed by area-response functions using sinusoidal grating stimuli. On completion of the functional tests, the cells were injected intracellularly with biocytin. The labeled cells were reconstructed and morphologically characterized in terms of the ERF modulation effects. We show that the vast majority of S-ERF neurons and F-ERF neurons are pyramidal cells and that the two types of cells clearly differ in the size of the soma, in complexity of dendrite branching, in spine size and density, and in the range of innervations of the axon collaterals. We propose that different pyramidal cell phenotypes reflect a high degree of specificity of neuronal connections associated with different types of spatial modulation.     

Identification of Critical Regions in Human SAMHD1 Required for Nuclear Localization and Vpx-Mediated Degradation

The sterile alpha motif (SAM) and HD domain-containing protein-1 (SAMHD1) inhibits the infection of resting CD4+ T cells and myeloid cells by human and related simian immunodeficiency viruses (HIV and SIV). Vpx inactivates SAMHD1 by promoting its proteasome-dependent degradation through an interaction with CRL4 (DCAF1) E3 ubiquitin ligase and the C-terminal region of SAMHD1. However, the determinants in SAMHD1 that are required for Vpx-mediated degradation have not been well characterized. SAMHD1 contains a classical nuclear localization signal (NLS), and NLS point mutants are cytoplasmic and resistant to Vpx-mediated degradation. Here, we demonstrate that NLS-mutant SAMHD1 K11A can be rescued by wild-type SAMHD1, restoring its nuclear localization; consequently, SAMHD1 K11A became sensitive to Vpx-mediated degradation in the presence of wild-type SAMHD1. Surprisingly, deletion of N-terminal regions of SAMHD1, including the classical NLS, generated mutant SAMHD1 proteins that were again sensitive to Vpx-mediated degradation. Unlike SAMHD1 K11A, these deletion mutants could be detected in the nucleus. Interestingly, NLS-defective SAMHD1 could still bind to karyopherin-β1 and other nuclear proteins. We also determined that the linker region between the SAM and HD domain and the HD domain itself is important for Vpx-mediated degradation but not Vpx interaction. Thus, SAMHD1 contains an additional nuclear targeting mechanism in addition to the classical NLS. Our data indicate that multiple regions in SAMHD1 are critical for Vpx-mediated nuclear degradation and that association with Vpx is not sufficient for Vpx-mediated degradation of SAMHD1. Since the linker region and HD domain may be involved in SAMHD1 multimerization, our results suggest that SAMHD1 multimerization may be required for Vpx-mediation degradation.     

Cost-Effectiveness Comparison of Genechip and Conventional Drug Susceptibility Test for Detecting Multidrug-Resistant Tuberculosis in China

Background

Genechip (CapitalBio, Beijing, China) is a system for diagnosing resistance to rifampin and isoniazid, which shows high efficiency in detecting drug-resistant tuberculosis. Here, we firstly evaluated the costs of Genechip for detecting the drug susceptibility of Mycobacterium tuberculosis, compared to conventional drug susceptibility test (DST) in laboratories in China.

Methodology/Principal Findings

Data on the costs of the two tests were collected at four hospitals. Costs were calculated using the essential factor cost calculation method. The costs of diagnosing a single case of multidrug-resistant tuberculosis (MDR-TB) using Genechip and DST were US$22.38 and $53.03, respectively. Taking into account the effect on costs from failure of a certain number of tests to accurately diagnose MDR-TB, the costs of Genechip and DST increased by 17.65% and 5.22%, respectively. The cost of both tests decreased with the increasing prevalence of MDR-TB disease, and the cost of Genechip at a sensitivity of more than 50% was lower than that of DST. When price of Genechip was varied to 50%, 80%, 150%, and 200% of the original price, the cost of Genechip at sensitivities of more than 30%, 40%, 60%, and 70%, respectively, was also lower than that of DST.

Conclusions/Significance

This study showed that Genechip was a more cost-effective method of diagnosing MDR-TB compared to conventional DST.     

The Joint Effect of hOGG1, APE1, and ADPRT Polymorphisms and Cooking Oil Fumes on the Risk of Lung Adenocarcinoma in Chinese Non-Smoking Females

Background

The human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl transferase (ADPRT) genes play an important role in the DNA base excision repair pathway. Single nucleotide polymorphisms (SNPs) in critical genes are suspected to be associated with the risk of lung cancer. This study aimed to identify the association between the polymorphisms of hOGG1 Ser326Cys, APE1 Asp148Glu, and ADPRT Val762Ala, and the risk of lung adenocarcinoma in the non-smoking female population, and investigated the interaction between genetic polymorphisms and environmental exposure in lung adenocarcinoma.

Methods

We performed a hospital-based case-control study, including 410 lung adenocarcinoma patients and 410 cancer-free hospital control subjects who were matched for age. Each case and control was interviewed to collect information by well-trained interviewers. A total of 10 ml of venous blood was collected for genotype testing. Three polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism technique.

Results

We found that individuals who were homozygous for the variant hOGG1 326Cys/Cys showed a significantly increased risk of lung adenocarcinoma (OR = 1.54; 95% CI: 1.01–2.36; P = 0.045). When the combined effect of variant alleles was analyzed, we found an increased OR of 1.89 (95% CI: 1.24–2.88, P = 0.003) for lung adenocarcinoma individuals with more than one homozygous variant allele. In stratified analyses, we found that the OR for the gene-environment interaction between Ser/Cys and Cys/Cys genotypes of hOGG1 codon 326 and cooking oil fumes for the risk of lung adenocarcinoma was 1.37 (95% CI: 0.77–2.44; P = 0.279) and 2.79 (95% CI: 1.50–5.18; P = 0.001), respectively.

Conclusions

The hOGG1 Ser326Cys polymorphism might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, there is a significant gene-environment association between cooking oil fumes and hOGG1 326 Cys/Cys genotype in lung adenocarcinoma among female non-smokers.     

Batch‐to‐Batch Variation of Polymeric Photovoltaic Materials: its Origin and Impacts on Charge Carrier Transport and Device Performances

A detailed investigation of the impact of molecular weight distribution of a photoactive polymer, poly[N‐9′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole)] (PCDTBT), on photovoltaic device performance and carrier transport properties is reported. It is found that different batches of as‐received polymers have substantial differences in their molecular weight distribution. As revealed by gel permeation chromatography (GPC), two peaks can generally be observed. One of the peaks corresponds to a high molecular weight component and the other peak corresponds to a low molecular weight component. Photovoltaic devices fabricated with a higher proportion of low molecular weight component have power conversion efficiencies (PCEs) reduced from 5.7% to 2.5%. The corresponding charge carrier mobility at the short‐circuit region is also significantly reduced from 2.7 × 10^?5 to 1.6 × 10^?8 cm² V^?1 s^?1. The carrier transport properties of the polymers at various temperatures are further analyzed by the Gaussian disorder model (GDM). All polymers have similar energetic disorders. However, they appear to have significant differences in carrier hopping distances. This result provides insight into the origin of the molecular weight effect on carrier transport in polymeric semiconducting materials.