Source Apportionment of Trace Element Pollution in Surface Sediments Using Positive Matrix Factorization Combined Support Vector Machines: Application to the Jinjiang River, China

In this study, a method of positive matrix factorization (PMF) combined support vector machines (SVMs) was adopted to identify possible sources and apportion contributions for trace element pollution in surface sediments from the Jinjiang River, Southeastern China. Utilizing diagnostics tools, four significant factors were extracted from sediment samplers, which were collected in December 2010 at 15 different sites. By treating source identification as a pattern recognition problem, the factor loadings derived from PMF were classified by SVM classifiers which have been trained and validated with fingerprints of eight potential source categories. Using SVM, industrial wastewater from lead ore mining and metal handcraft manufacture, atmospheric deposition, and natural background were identified as main sources of trace element pollution in surface sediments from the Jinjiang River, which were affirmed by visually comparing compound patterns and the differences between the predicted and actual fractional compositions. Apportionment results showed that source of lead ore mining made the largest contribution (33.62 %), followed by atmospheric deposition (30.99 %), metal handcraft manufacture (30.09 %), and natural background (5.29 %).     

Manganese-Induced Effects on Cerebral Trace Element and Nitric Oxide of Hyline Cocks

Exposure to Manganese (Mn) is a common phenomenon due to its environmental pervasiveness. To investigate the Mn-induced toxicity on cerebral trace element levels and crucial nitric oxide parameters on brain of birds, 50-day-old male Hyline cocks were fed either a commercial diet or a Mn-supplemented diet containing 600, 900, 1,800 mg kg^?1. After being treated with Mn for 30, 60, and 90 days, the following were determined: the changes in contents of copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), selenium (Se) in brain; inducible nitric oxide synthase-nitric oxide (iNOS-NO) system activity in brain; and histopathology and ultrastructure changes of cerebral cortex. The results showed that Mn was accumulated in brain and the content of Cu and Fe increased. However, the levels of Zn and Se decreased and the Ca content presented no obvious regularity. Exposure to Mn significantly elevated the content of NO and the expression of iNOS mRNA. Activity of total NO synthase (T NOS) and iNOS appeared with an increased tendency. These findings suggested that Mn exposure resulted in the imbalance of cerebral trace elements and influenced iNOS in the molecular level, which are possible underlying nervous system injury mechanisms induced by Mn exposure.     

Regulation of Focal Adhesion Kinase Activation,Breast Cancer Cell Motility,and Amoeboid Invasion by the RhoA Guanine Nucleotide Exchange Factor Net1

Net1 is a RhoA guanine nucleotide exchange factor (GEF) that is overexpressed in a subset of human cancers and contributes to cancer cell motility and invasion in vitro. However, the molecular mechanism accounting for its role in cell motility and invasion has not been described. In the present work, we show that expression of both Net1 isoforms in breast cancer cells is required for efficient cell motility. Although loss of Net1 isoform expression only partially blocks RhoA activation, it inhibits lysophosphatidic acid (LPA)-stimulated migration as efficiently as knockdown of RhoA itself. However, we demonstrate that the Net1A isoform predominantly controls myosin light-chain phosphorylation and is required for trailing edge retraction during migration. Net1A interacts with focal adhesion kinase (FAK), localizes to focal adhesions, and is necessary for FAK activation and focal adhesion maturation during cell spreading. Net1A expression is also required for efficient invasion through a Matrigel matrix. Analysis of invading cells demonstrates that Net1A is required for amoeboid invasion, and loss of Net1A expression causes cells to shift to a mesenchymal phenotype characterized by high β₁-integrin activity and membrane type 1 matrix metalloproteinase (MT1-MMP) expression. These results demonstrate a previously unrecognized role for the Net1A isoform in controlling FAK activation during planar cell movement and amoeboid motility during extracellular matrix (ECM) invasion.     

桑疫病病原拮抗菌的分离、鉴定及发酵条件优化北大核心CSCD

【目的】从健康桑树内生菌中分离获得对桑疫病病原菌(Pseudomonas syringae pv.mori)具有显著拮抗作用的菌株,优化其产生抑菌活性物质的发酵条件,为其生防利用奠定基础。【方法】从严格表面消毒的桑树根茎中分离内生菌,采用平板划线法纯化内生菌,用抑菌圈法筛选拮抗菌;根据菌株的形态与培养特征、生理生化特性、16S rDNA序列分析对其进行鉴定。通过单因素试验和正交设计试验优化培养基组分及发酵条件。【结果】从健康桑树中分离获得内生菌77株,其中,编号为SWg2的菌株对桑疫病病原菌具有强而稳定的抑制作用。菌株SWg2的形态与培养特征、生理生化特性和泛菌属(Pantoea sp.)相符,而16S rDNA序列分析结果显示它与成团泛菌(P.agglomerans)的亲缘关系接近。研究表明其最佳发酵配方和培养条件为:甘油(2.00%)、硝酸铵(2.00%)、KH2PO4(0.10%)和MgSO4·7H2O(0.15%),起始pH为7.5,装瓶量20 mL/100 mL,最适培养温度为28℃,转速为170 r/min,种子液接种量为4%,摇瓶培养5 d。【结论】经鉴定,对桑疫病病原具拮抗作用的桑树内生菌SWg2为成团泛菌(P.agglomerans),命名为成团泛菌SWg2。对其发酵条件进行优化后对桑疫病病原菌显示出更强的拮抗作用。     

Association between rs10118757(A/G) in methylthioadenosine phosphorylase gene and coronary artery disease in Chinese Hans

Studies focusing on the association of gene methylthioadenosine phosphorylase (MTAP) with the risk of coronary artery disease (CAD) and myocardial infarction (MI) are limited.     

3D-QSAR studies of checkpoint kinase 1 inhibitors based on molecular docking and CoMFA

Three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed on a series of substituted 1,4-dihydroindeno[1,2-c]pyrazoles inhibitors, using molecular docking and comparative molecular field analysis (CoMFA). The docking results from GOLD 3.0.1 provide a reliable conformational alignment scheme for the 3D-QSAR model. Based on the docking conformations and alignments, highly predictive CoMFA model was built with cross-validated q ² value of 0.534 and non-cross-validated partial least-squares analysis with the optimum components of six showed a conventional r ² value of 0.911. The predictive ability of this model was validated by the testing set with a conventional r ² value of 0.812. Based on the docking and CoMFA, we have identified some key features of the 1,4-dihydroindeno[1,2-c]pyrazoles derivatives that are responsible for checkpoint kinase 1 inhibitory activity. The analyses may be used to design more potent 1,4-dihydroindeno[1,2-c]pyrazoles derivatives and predict their activity prior to synthesis.     

Involvement of Volume-Activated Chloride Channels in H2O2 Preconditioning Against Oxidant-Induced Injury Through Modulating Cell Volume Regulation Mechanisms and Membrane Permeability in PC12 Cells

The functions of chloride channels in preconditioning-induced cell protection remain unclear. In this report, we show that the volume-activated chloride channels play a key role in hydrogen peroxide (H₂O₂) preconditioning-induced cell protection in pheochromocytoma PC12 cells. The preconditioning with 100 μM H₂O₂ for 90 min protected the cells from injury induced by long period exposure to 300 μM H₂O₂. The protective effect was attenuated by pretreatment with the chloride channel blockers, 5-nitro-2-3-phenylpropylamino benzoic acid (NPPB) and tamoxifen. H₂O₂ preconditioning directly activated a chloride current, which was moderately outward-rectified and sensitive to the chloride channel blockers and hypertonicity-induced cell shrinkage. H₂O₂ preconditioning functionally up-regulated the activities of volume-activated chloride channels and enhanced the regulatory volume decrease when exposure to extracellular hypotonic challenges. In addition, acute application of H₂O₂ showed distinctive actions on cell volume and membrane permeability in H₂O₂ preconditioned cells. In H₂O₂ preconditioned cells, acute application of 300 μM H₂O₂ first promptly induced a decrease of cell volume and enhancement of cell membrane permeability, and then, cell volume was maintained at a relatively stable level and the facilitation of membrane permeability was reduced. Conversely, in control cells, 300 μM H₂O₂ induced a slow but persistent apoptotic volume decrease (AVD) and facilitation of membrane permeability. H₂O₂ preconditioning also significantly up-regulated the expression of ClC-3 protein, the molecular candidate of the volume-activated chloride channel. These results suggest that H₂O₂ preconditioning can enhance the expression and functional activities of volume-activated chloride channels, thereby modulate cell volume and cell membrane permeability, which may contribute to neuroprotection against oxidant-induced injury.     

Tonotopic reorganization and spontaneous firing in inferior colliculus during both short and long recovery periods after noise overexposure

Background

Noise induced injury of the cochlea causes shifts in activation thresholds and changes of frequency response in the inferior colliculus (IC). Noise overexposure also induces pathological changes in the cochlea, and is highly correlated to hearing loss. However, the underlying mechanism has not been fully elucidated. In this study, we hypothesized that overexposure to noise induces substantial electrophysiological changes in the IC of guinea pigs.

Results

During the noise exposure experiment, the animals were undergoing a bilateral exposure to noise. Additionally, various techniques were employed including confocal microscopy for the detection of cochlea hair cells and single neuron recording for spontaneous firing activity measurement. There were alterations among three types of frequency response area (FRA) from sound pressure levels, including V-, M-, and N-types. Our results indicate that overexposure to noise generates different patterns in the FRAs. Following a short recovery (one day after the noise treatment), the percentage of V-type FRAs considerably decreased, whereas the percentage of M-types increased. This was often caused by a notch in the frequency response that occurred at 4 kHz (noise frequency). Following a long recovery from noise exposure (11–21 days), the percentage of V-types resumed to a normal level, but the portion of M-types remained high. Interestingly, the spontaneous firing in the IC was enhanced in both short and long recovery groups.

Conclusion

Our data suggest that noise overexposure changes the pattern of the FRAs and stimulates spontaneous firing in the IC in a unique way, which may likely relate to the mechanism of tinnitus.     

DNA Transfection of Bone Marrow Stromal Cells Using Microbubble-Mediated Ultrasound and Polyethylenimine: An In Vitro Study

Non-viral vector transfection efficiency is an issue affecting the clinical application of stem cell gene therapy. This study makes use of the synergistic effect of combining ultrasound (US) with microbubbles (MB) and polyethylenimine (PEI) to increase DNA transfection efficiency, which will enhance the efficiency of gene transfer to bone marrow stromal cells (BMSCs). The optimal parameters for primary-cultured rat-BMSC DNA transfection were examined. The study was arranged based on uniform design. Using a construct containing hepatocyte growth factor (HGF) tagged with enhanced green fluorescent protein (pEGFP-HGF) as example, the mixture of BMSCs, MB, and PEI:DNA complex were exposed to US with frequency of 1 MHz and 10 % duty cycle pulses. Other factors such as acoustic intensity (Q), MB dosage, and total treatment time (T) were also tested. The results were analyzed by regression analysis. Using the best match of parameters, Q = 0.6 W/cm², MB = 10⁶/ml, T = 30 s, different groups were compared. The cooperativity of MB-mediated US and PEI enhanced the gene transfection efficiency by nearly 38-times compared to the DNA without US group. Furthermore, the expression of HGF protein was confirmed by Western blot. The eGFP could be not only seen mainly at the cytoplasm, but also seen in the nucleus in a small proportion of the cells (<10 %) for up to 7 observed days. The transfected BMSCs maintained their capability of multi-directional differentiation and reproductive activity. Our results provide useful information in establishing a novel non-viral transfection method, which may be applied to clinical application in stem cell gene therapy.