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81.
Min Cen Jian Fen Fan Dong Yan Liu Xue Zeng Song Jian Liu Wei Qun Zhou He Ming Xiao 《Journal of molecular modeling》2013,19(2):601-611
Molecular dynamic (MD) simulations have been performed to study the behaviors of ten kinds of cyclo-hexa-peptides (CHPs) composed of amino acids with the diverse hydrophilic/hydrophobic side chains at the water/cyclohexane interface. All the CHPs take the “horse-saddle” conformations at the interface and the hydrophilicity/hydrophobicity of the side chains influences the backbones’ structural deformations. The orientations and distributions of the CHPs at the interface and the differences of interaction energies (ΔΔE) between the CHPs and the two liquid phases have been determined. RDF analysis shows that the H-bonds were formed between the OC atoms of the CHPs’ backbones and Hw atoms of water molecules. N atoms of the CHPs’ backbones formed the H-bonds or van der Waals interactions with the water solvent. It was found that there is a parallel relationship between ΔΔE and the lateral diffusion coefficients (D xy ) of the CHPs at the interface. The movements of water molecules close to the interface are confined to some extent, indicating that the dynamics of the CHPs and interfacial water molecules are strongly coupled. Figure
Scheme of the ten kinds of CHPs formed by even alternating D- and L- amino acids with the different hydrophilic/hydrophobic side chains. The letters in the parentheses stand for the abbreviations of the composed amino acids in the CHPs 相似文献
82.
Haiyang He Zhirong Mou Wanling Li Lei Fei Yan Tang Ji Zhang Ping Yan Zhengqiong Chen Xia Yang Zigang Shen Jintao Li Yuzhang Wu 《Proteomics》2013,13(7):1121-1132
Rotavirus (RV) infection is the main cause of acute dehydrating diarrhea in infants and young children below 5 years old worldwide. RV infection causes a global shutoff of host proteins as many other viruses do. However, previous studies revealed that RV could selectively upregulated the expression of some host proteins that then played important roles in RV infection. To globally explor such host proteins that were upregulated in early human rotavirus (HRV) infection, proteomic methods were used and a total of ten upregulated host proteins were unambiguously identified. Cyclophilin A (CYPA), a peptidyl‐prolyl cis‐trans isomerase, was among these upregulated host proteins. Following infection, CYPA was recruited to the viroplasm and interacted with HRV structural protein VP2; CYPA reduced host susceptibility to HRV infection and inhibited replication of HRV by repressing the expression of viral proteins. Furthermore, we found that the increased expression of CYPA in enterocytes of small intestine correlated to the period when BALB/c mice became resistant to RV diarrhea. Together, we identified CYPA as a novel host restriction factor that confered protection against RV infection and might contribute to host susceptibility to RV diarrhea. 相似文献
83.
Kejian Wang Jiazhi Sun Shufeng Zhou Chunling Wan Shengying Qin Can Li Lin He Lun Yang 《PLoS computational biology》2013,9(11)
Small drug molecules usually bind to multiple protein targets or even unintended off-targets. Such drug promiscuity has often led to unwanted or unexplained drug reactions, resulting in side effects or drug repositioning opportunities. So it is always an important issue in pharmacology to identify potential drug-target interactions (DTI). However, DTI discovery by experiment remains a challenging task, due to high expense of time and resources. Many computational methods are therefore developed to predict DTI with high throughput biological and clinical data. Here, we initiatively demonstrate that the on-target and off-target effects could be characterized by drug-induced in vitro genomic expression changes, e.g. the data in Connectivity Map (CMap). Thus, unknown ligands of a certain target can be found from the compounds showing high gene-expression similarity to the known ligands. Then to clarify the detailed practice of CMap based DTI prediction, we objectively evaluate how well each target is characterized by CMap. The results suggest that (1) some targets are better characterized than others, so the prediction models specific to these well characterized targets would be more accurate and reliable; (2) in some cases, a family of ligands for the same target tend to interact with common off-targets, which may help increase the efficiency of DTI discovery and explain the mechanisms of complicated drug actions. In the present study, CMap expression similarity is proposed as a novel indicator of drug-target interactions. The detailed strategies of improving data quality by decreasing the batch effect and building prediction models are also effectively established. We believe the success in CMap can be further translated into other public and commercial data of genomic expression, thus increasing research productivity towards valid drug repositioning and minimal side effects. 相似文献
84.
Dong-Sheng Cao Yi-Zeng Liang Zhe Deng Qian-Nan Hu Min He Qing-Song Xu Guang-Hua Zhou Liu-Xia Zhang Zi-xin Deng Shao Liu 《PloS one》2013,8(4)
The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via: http://sdd.whu.edu.cn/dpiki. 相似文献
85.
Hongxing Zhang Fang Zhou Chen Li Min Kong He Liu Peng Zhang Song Zhang Junli Cao Licai Zhang Hong Ma 《PloS one》2013,8(2)
Background
Dexmedetomidine (DEX) has been used under perioperative settings as an adjuvant to enhance the analgesic property of local anesthetics by some anesthesiologists. However, the analgesic mechanisms and neurotoxicity of DEX were poorly understood. This study examined the effect of DEX alone on inflammatory pain, and it also examined the underlying molecular mechanisms of DEX in the spinal cord. Furthermore, in vivo and in vitro experiments were performed to investigate the neurotoxicity of DEX on the spinal cord and cortical neurons.Methods
This study used adult, male Kunming mice. In the acute inflammatory model, the left hind-paws of mice were intradermally injected with pH 5.0 PBS while chronic constrictive injury (CCI) of the sciatic nerve was used to duplicate the neuropathic pain condition. Thermal paw withdrawal latency and mechanical paw withdrawal threshold were tested with a radiant heat test and the Von Frey method, respectively. Locomotor activity and motor coordination were evaluated using the inverted mesh test. Western blotting examined spinal ERK1/2, p-ERK1/2, caspase-3 and β-actin expressions, while spinal c-Fos protein expression was realized with immunohistochemical staining. Hematoxylin eosin (HE) staining was used to examine the pathological impacts of intrathecal DEX on the spinal cord. DAPI (4′,6-diamidino-2-phenylindole) staining was used to observe cell death under an immunofluorescence microscope.Results
Intra-plantar pH 5.0 PBS-induced acute pain required spinal ERK1/2 activation. Inhibition of spinal ERK1/2 signaling by intrathecal injection of DEX displayed a robust analgesia, via a α2-receptor dependent manner. The analgesic properties of DEX were validated in CCI mice. In vivo studies showed that intrathecal DEX has no significant pathological impacts on the spinal cord, and in vitro experiments indicated that DEX has potential protective effects of lidocaine-induced neural cell death.Conclusion
Intrathecal injection of DEX alone or as an adjuvant might be potential for pain relief. 相似文献86.
Background
Shiga toxin-producing Escherichia coli (STEC) are frequent causes of severe human diseases ranging from diarrhea to hemolytic uremic syndrome. The existing strategy for detection of STEC relies on the unique sorbitol-negative fermentation property of the O157 strains, the most commonly identified serotype has been E. coli O157. It is becoming increasingly evident, however, that numerous non-O157 STEC serotypes also cause outbreaks and severe illnesses. It is necessary to have new methods that are capable of detecting all STEC strains.Methods and Findings
Here we describe the development of a sandwich ELISA assay for detecting both O157 and non-O157 STECs by incorporating a novel polyclonal antibody (pAb) against Stx2. The newly established immunoassay was capable of detecting Stx2a spiked in environmental samples with a limit of detection between 10 and 100 pg/mL in soil and between 100 and 500 pg/mL in feces. When applied to 36 bacterial strains isolated from human and environmental samples, this assay detected Stx2 in all strains that were confirmed to be stx2-positive by real-time PCR, demonstrating a 100% sensitivity and specificity.Conclusions
The sandwich ELISA developed in this study will enable any competent laboratory to identify and characterize Stx2-producing O157 and non-O157 strains in human and environmental samples, resulting in rapid diagnosis and patient care. The results of epitope mapping from this study will be useful for further development of a peptide-based antibody and vaccine. 相似文献87.
Yang Xuefang He Yingying Song Xi’E Yuan Xiangyang Li Yongfeng Sun Dasheng 《Plant and Soil》2020,448(1-2):369-381
Plant and Soil - The incidence of herbicide-resistant blackgrass is escalating in wheat fields; the development of alternatives to traditional herbicides is crucial. Allelopathic wheat can suppress... 相似文献
88.
Yongjian Zang Dongxiao Hao He Wang Huadong Liu 《Journal of biomolecular structure & dynamics》2020,38(15):4617-4624
Communicated by Ramaswamy H. Sarma 相似文献
89.
Zhenpeng Li Zeqiong Cai Weixin Fu Ying Liu Chenglei Tian He Wang Tongtong Fu Zhenzhou Wu Donghai Wu Yongxin Jin Zhihui Cheng Naohiro Terada Lin Liu Weihui Wu Shouguang Jin Fang Bai 《Biotechnology and bioengineering》2020,117(3):816-831
Intracellular delivery of functional proteins is of great interest for basic biological research as well as for clinical applications. Transfection is the most commonly used method, however, it is not applicable to large-scale manipulation and inefficient in important cell types implicated in biomedical applications, such as epithelial, immune and pluripotent stem cells. In this study, we explored a bacterial type III secretion system (Bac-T3SS)-mediated proteofection method to overcome these limitations. An attenuated Pseudomonas aeruginosa vector was constructed, which has features of low toxicity, high T3SS activity, and self-limiting growth. Compared to the method of transfection, the Bac-T3SS showed significantly higher efficiencies of Cre recombinase translocation and target site recombination for hard-to-transfect human cell lines. Furthermore, through the delivery of β-lactamase in live animals, we demonstrated the feasibility and biosafety of in vivo application of the Bac-T3SS. This study provided an efficient and low-cost proteofection strategy for laboratory use as well as for application in large-scale cell manipulations. 相似文献
90.
Junying Liu Xiping YanQingqing Li Guosong WangHehe Liu Jiwen WangLiang Li Xiaohui DuChunchun Han Hua He 《Journal of thermal biology》2013
Avian embryos are easily influenced by their environment during incubation. Previous studies have demonstrated that incubation temperature changes could influence muscle development and body weight, which subsequently determine the adult phenotype. The objective of this study was to investigate whether the development of immune organs in ducklings could be influenced by thermal manipulation during the middle stage of incubation. To evaluate this hypothesis, a control group was incubated under a normal temperature from E11 to E24, while the incubation temperature of the experimental group was increased by 1 °C. Our results indicated that slight changes in the incubation temperature significantly repressed the bursa of Fabricius index of the duck embryo on E25 (F1, 58=122.51, P<0.0001) and significantly repressed the spleen index of neonatal ducklings (F1, 58=74.38, P<0.0001). At 0 day posthatching (dph) and 14 dph, ducklings hatched from eggs incubated under the higher temperature had a lower percentage of globulin than the control group (F1, 10=19.97, P=0.0111; F1, 10=9.8, P=0.0352). The IFN-γ concentration of ducklings at 14 dph displayed the same trend (F1, 10=284.49, P<0.0001). These results suggested that thermal manipulation during the middle stage of incubation had a repressive effect on the development of immune organs and reduced the concentrations of serum globulin and IFN-γ. These results demonstrated that the subtle alteration of incubation temperature may weaken ducklings' immunity. 相似文献