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991.
Juhwan Kim Miyoung Yang Sung-Ho Kim Jong-Choon Kim Hongbing Wang Taekyun Shin Changjong Moon 《PloS one》2013,8(8)
Trimethyltin (TMT) is an organotin compound with potent neurotoxic effects characterized by neuronal destruction in selective regions, including the hippocampus. Glycogen synthase kinase-3 (GSK-3) regulates many cellular processes, and is implicated in several neurodegenerative disorders. In this study, we evaluated the therapeutic effect of lithium, a selective GSK-3 inhibitor, on the hippocampus of adult C57BL/6 mice with TMT treatment (2.6 mg/kg, intraperitoneal [i.p.]) and on cultured hippocampal neurons (12 days in vitro) with TMT treatment (5 µM). Lithium (50 mg/kg, i.p., 0 and 24 h after TMT injection) significantly attenuated TMT-induced hippocampal cell degeneration, seizure, and memory deficits in mice. In cultured hippocampal neurons, lithium treatment (0–10 mM; 1 h before TMT application) significantly reduced TMT-induced cytotoxicity in a dose-dependent manner. Additionally, the dynamic changes in GSK-3/β-catenin signaling were observed in the mouse hippocampus and cultured hippocampal neurons after TMT treatment with or without lithium. Therefore, lithium inhibited the detrimental effects of TMT on the hippocampal neurons in vivo and in vitro, suggesting involvement of the GSK-3/β-catenin signaling pathway in TMT-induced hippocampal cell degeneration and dysfunction. 相似文献
992.
Yang Wang Xu Li Xiaoliang Wang Waynebond Lau Yajing Wang Yuan Xing Xing Zhang Xinliang Ma Feng Gao 《PloS one》2013,8(8)
Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive oxygen species (ROS) formation. Current study determined the effect of GSRd on myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS production is significantly increased) and investigated the underlying mechanisms. The current study utilized an in vivo rat model of MI/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS accumulation and apoptosis were assessed by flow cytometry. Mitochondrial membrane potential (MMP) was determined by 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetrathylbenzimidazol carbocyanine iodide (JC-1). Cytosolic translocation of mitochondrial cytochrome c and expression of caspase-9, caspase-3, Bcl-2 family proteins, and phosphorylated Akt and GSK-3β were determined by western blot. Pretreatment with GSRd (50 mg/kg) significantly augmented rat cardiac function, as evidenced by increased left ventricular ejection fraction (LVEF) and ±dP/dt. GSRd reduced myocardial infarct size, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels after MI/R. In NRCs, GSRd (10 µM) inhibited SI/R-induced ROS generation (P<0.01), decreased cellular apoptosis, stabilized the mitochondrial membrane potential (MMP), and attenuated cytosolic translocation of mitochondrial cytochrome c. GSRd inhibited activation of caspase-9 and caspase-3, increased the phosphorylated Akt and GSK-3β, and increased the Bcl-2/Bax ratio. Together, these data demonstrate GSRd mediated cardioprotective effect against MI/R–induced apoptosis via a mitochondrial-dependent apoptotic pathway. 相似文献
993.
994.
2008年至2009年间,在湖南和湖北两省的活禽市场中分离到了14株H6亚型禽流感病毒,为了解这14株病毒之间的分子特征和差异,我们运用PCR和测序鉴定对这14株病毒的NA基因进行了分型,并对其表面基因HA和NA进行序列测定及序列分析.14株H6亚型病毒中,H6N2亚型12株,H6N6亚型2株.序列测定和进化分析结果显示:DK/HN/284的HA基因与其它13株的HA差异性较大,差异性达到19.4%~20.2%,其余13株毒同源性在94.2%~99.9%;N2亚型NA基因的同源性在91.1%~99.9%,差异性比较大;两株N6亚型NA基因同源性为89.5%,差异明显.这些数据表明:不同毒株呈现一定的地域性差异.与我国周边其它地区的H6亚型禽流感毒株序列进行比较发现,只有DK/HN/284的HA基因与香港早期的毒株可能有着共同的来源,其余都与香港和韩国等的毒株有着较大的差异性,并且各个毒株的HA基因上潜在的糖基化位点和受体结合位点也有所不同,这些数据表明,这些毒株表现出明显的异源性. 相似文献
995.
Lee CH 《Applied microbiology and biotechnology》2012,93(2):517-523
One of the primary limitations of cancer therapy is lack of selectivity of therapeutic agents to tumor cells. Current efforts
are focused on discovering and developing anticancer agents that selectively target only tumor cells and spare normal cells
to improve the therapeutic index. The use of preferentially replicating bacteria as an oncolytic agent is one of the innovative
approaches for the treatment of cancer. This is based on the observation that some obligate or facultative anaerobic bacteria
are capable of multiplying selectively in tumors and inhibiting their growth. Meanwhile, bacteria have been demonstrated to
colonize and destroy tumor, and have emerged as biological gene vectors to tumor microenvironment. To improve the efficacy
and safety of the bacterial therapy, a further understanding of bacteria between with immune system is required. Furthermore,
we want to evaluate how bacterial infection facilitates the “bystander effect” of chemotherapeutic agent and assess if it
can be used for additional antitumor effect when combined with chemotherapy. This study may not only evaluate therapeutic
efficacy of bacteria for the treatment of cancer but also elucidate the mechanisms underlying antitumor activities mediated
by bacteria, which involve host immune responses and the cellular molecular responses. 相似文献
996.
Immune suppression remains a consistent obstacle to successful anti-tumor immune responses. As tumors develop, they create
a microenvironment that not only supports tumor growth and metastasis but also reduces potential adaptive immunity to tumor
antigens. Among the many components of this tumor microenvironment is a population of dendritic cells which exert profound
immune suppressive effects on T cells. In this review, we discuss our recent findings related to these tumor-associated dendritic
cells and how targeting them may serve to generate more durable anti-tumor immune responses. 相似文献
997.
Chen CT Peng HP Jian JW Tsai KC Chang JY Yang EW Chen JB Ho SY Hsu WL Yang AS 《PloS one》2012,7(6):e37706
Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI) sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins) and were tested on an independent dataset (consisting of 142 proteins). The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted correctly with the physicochemical complementarity features based on the non-covalent interaction data derived from protein interiors. 相似文献
998.
In contrast to many studies on the habitat quality of road verges for butterflies in relation to management regimes, little
is known about whether road verges also function as corridors linking fragmented grassland habitats. We experimentally compared
movements of four model species, two small blues and two medium browns, with one habitat specialist and one habitat generalist
in each size and phylogenetic category. A total of 425 individual butterflies were caught and translocated to an experimental
arena with three 2 × 30 m grassland strips that approximated road verges; one with adult feeding resources, one sheltered
from the wind, and one without food and shelter. Movements in grassland strips were compared to movements in continuous grassland
habitat. Results indicated that (1) individuals did not use the low-quality strip, (2) only specialists used strips but not
in the same way according to their size and phylogenic category, and (3) strip use could not be predicted from habitat selection.
This finding supports the idea that corridors of intermediate quality are the most efficient to promote dispersal rates in
fragmented landscapes. Road verges cover 250,000 ha in Sweden, which is nearly the total amount of seminatural grasslands.
Our results suggest that, to benefit butterfly dispersal among grassland patches, road verges should be managed to create
a more favourable microclimate (e.g. sheltered from wind, high temperatures). 相似文献
999.
Lynn S. Dahleen Muthusamy Manoharan 《In vitro cellular & developmental biology. Plant》2007,43(6):493-506
Barley, an important member of the cereals, has been successfully transformed through various methods such as particle bombardment,
Agrobacterium tumefaciens, DNA uptake, and electroporation. Initially, the transformation in barley concentrated on developing protocols using marker
genes such as gus, bar, and hpt. Immature embryos and callus derived from immature embryos were targeted for transformation. Subsequently, genes of agronomic
and malting importance have been deployed in barley. Particle bombardment appears to be the preferred choice for barley transformation
in the majority of the reports, although Agrobacterium-mediated transformation is being used more often. The current review focuses on the challenges encountered in barley transformation
such as somaclonal variation, development of transformation systems for commercial cultivars, gene expression, stability and
inheritance, and gene flow. Newer markers such as the green fluorescent protein (gfp), firefly luciferase, and phosphomannose isomerase were found to be useful in the selection of transgenic plants. Tissue-specific
promoters such as those for B1-hordein and D-hordein genes, and spike-specific promoters, are increasingly used to drive gene
expression. The review also describes recent research on gene-tagging through transformation, insertion of disease resistance,
and abiotic stress resistance genes, transformation with genes for improved malting quality, nutrient content, feed quality,
and the production of feed enzymes and pharmaceutical compounds. 相似文献
1000.
The red king crab (Paralithodes camtschaticus) was introduced in the Barents Sea in the 1960s and soon established a viable population. Proper management and exploitation
of the Barents Sea king crab stock require better understanding of the spatial dynamics at different scales. This study examines
the small-scale movement patterns of seven adult male crabs tracked for a period of up to one month from mid July to mid August
at 150 m depth in a semi-enclosed fjord on the Russo-Norwegian border. The crabs were tagged with acoustic transmitters and
their movements monitored with an acoustic positioning system. Low walking speeds (<0.01 m s−1) were most frequent but the crabs could move at a maximum speed of 0.15 m s−1 and walk an actual distance of up to 270 m over a period of one hour. However, the crabs usually moved within a relatively
restricted area with mean hourly longest rectilinear distance varying from 26 to 64 m. The crabs alternated between periods
of low and high activity, which could reflect feeding in and movements between food patches. The lack of a diel activity rhythm
may be due to high light levels during the polar summer night, or a chemically mediated food search strategy. 相似文献