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991.
Journal of Biological Physics - The dynamics of ion translocation through membrane transporters is visualized from a comprehensive point of view by a Gibbs energy landscape approach. The ΔG... 相似文献
992.
Gangaraju Rajashekhar Malgorzata Kamocka Abby Marin Mark A. Suckow William R. Wolter Sunil Badve Aravind Raj Sanjeevaiah Kevin Pumiglia Elliot Rosen Matthias Clauss 《Journal of cellular physiology》2011,226(3):800-808
Chronic inflammation is tightly linked to diseases associated with endothelial dysfunction including aberrant angiogenesis. To better understand the endothelial role in pro‐inflammatory angiogenesis, we analyzed signaling pathways in continuously activated endothelial cells, which were either chronically exposed to soluble TNF or the reactive oxygen species (ROS) generating H2O2, or express active transmembrane TNF. Testing in an in vitro capillary sprout formation assay, continuous endothelial activation increased angiogenesis dependent on activation of p38 MAP kinase, NADPH oxidase, and matrix metalloproteinases (MMP). p38 MAP kinase‐ and MMP‐9‐dependent angiogenesis in our assay system may be part of a positive feed forward autocrine loop because continuously activated endothelial cells displayed up‐regulated ROS production and subsequent endothelial TNF expression. The pro‐angiogenic role of the p38 MAP kinase in continuously activated endothelial cells was in stark contrast to the anti‐angiogenic activity of the p38 MAP kinase in unstimulated control endothelial cells. In vivo, using an experimental prostate tumor, pharmacological inhibition of p38 MAP kinase demonstrated a significant reduction in tumor growth and in vessel density, suggesting a pro‐angiogenic role of the p38 MAP kinase in pathological angiogenesis in vivo. In conclusion, our results suggest that continuous activation of endothelial cells can cause a switch of the p38 MAP kinase from anti‐angiogenic to pro‐angiogenic activities in conditions which link oxidative stress and autocrine TNF production. J. Cell. Physiol. 226: 800–808, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
993.
Feed-forward and feed-backward amplification model from cochlear cytoarchitecture: an interspecies comparison 总被引:1,自引:0,他引:1
The high sensitivity and wide bandwidth of mammalian hearing are thought to derive from an active process involving the somatic and hair-bundle motility of the thousands of outer hair cells uniquely found in mammalian cochleae. To better understand this, a biophysical three-dimensional cochlear fluid model was developed for gerbil, chinchilla, cat, and human, featuring an active “push-pull” cochlear amplifier mechanism based on the cytoarchitecture of the organ of Corti and using the time-averaged Lagrangian method. Cochlear responses are simulated and compared with in vivo physiological measurements for the basilar membrane (BM) velocity, VBM, frequency tuning of the BM vibration, and Q10 values representing the sharpness of the cochlear tuning curves. The VBM simulation results for gerbil and chinchilla are consistent with in vivo cochlea measurements. Simulated mechanical tuning curves based on maintaining a constant VBM value agree with neural-tuning threshold measurements better than those based on a constant displacement value, which implies that the inner hair cells are more sensitive to VBM than to BM displacement. The Q10 values of the VBM tuning curve agree well with those of cochlear neurons across species, and appear to be related in part to the width of the basilar membrane. 相似文献
994.
995.
Jihoon Ryu Zeenia Kaul A-Rum Yoon Ye Liu Tomoko Yaguchi Youjin Na Hyo Min Ahn Ran Gao Il-Kyu Choi Chae-Ok Yun Sunil C. Kaul Renu Wadhwa 《The Journal of biological chemistry》2014,289(36):24832-24844
The Hsp70 family protein mortalin is an essential chaperone that is frequently enriched in cancer cells and exists in various subcellular sites, including the mitochondrion, plasma membrane, endoplasmic reticulum, and cytosol. Although the molecular mechanisms underlying its multiple subcellular localizations are not yet clear, their functional significance has been revealed by several studies. In this study, we examined the nuclear fractions of human cells and found that the malignantly transformed cells have more mortalin than the normal cells. We then generated a mortalin mutant that lacked a mitochondrial targeting signal peptide. It was largely localized in the nucleus, and, hence, is called nuclear mortalin (mot-N). Functional characterization of mot-N revealed that it efficiently protects cancer cells against endogenous and exogenous oxidative stress. Furthermore, compared with the full-length mortalin overexpressing cancer cells, mot-N derivatives showed increased malignant properties, including higher proliferation rate, colony forming efficacy, motility, and tumor forming capacity both in in vitro and in vivo assays. We demonstrate that mot-N promotes carcinogenesis and cancer cell metastasis by inactivation of tumor suppressor protein p53 functions and by interaction and functional activation of telomerase and heterogeneous ribonucleoprotein K (hnRNP-K) proteins. 相似文献
996.
997.
Gene expression can be altered by small molecules that target DNA; sequence as well as shape selectivities are both extremely important for DNA recognition by intercalating and groove‐binding ligands. We have characterized a carbohydrate scaffold (1) exhibiting DNA “shape readout” properties. Thermodynamic studies with 1 and model duplex DNAs demonstrate the molecule's high affinity and selectivity towards B* form (continuous AT‐rich) DNA. Isothermal titration calorimetry (ITC), circular dichroism (CD) titration, ultraviolet (UV) thermal denaturation, and Differential Scanning Calorimetry were used to characterize the binding of 1 with a B* form AT‐rich DNA duplex d[5′‐G2A6T6C2‐3′]. The binding constant was determined using ITC at various temperatures, salt concentrations, and pH. ITC titrations were fit using a two‐binding site model. The first binding event was shown to have a 1:1 binding stoichiometry and was predominantly entropy‐driven with a binding constant of approximately 108 M?1. ITC‐derived binding enthalpies were used to obtain the binding‐induced change in heat capacity (ΔCp) of ?225 ± 19 cal/mol·K. The ionic strength dependence of the binding constant indicated a significant electrolytic contribution in ligand:DNA binding, with approximately four to five ion pairs involved in binding. Ligand 1 displayed a significantly higher affinity towards AT‐tract DNA over sequences containing GC inserts, and binding experiments revealed the order of binding affinity for 1 with DNA duplexes: contiguous B* form AT‐rich DNA (d[5′‐G2A6T6C2‐3′]) >B form alternate AT‐rich DNA (d[5′‐G2(AT)6C2‐3′]) > A form GC‐rich DNA (d[5′‐A2G6C6T2‐3′]), demonstrating the preference of ligand 1 for B* form DNA. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 720–732, 2014. 相似文献
998.
Antisense RNA ribozymes have intrinsic endonucleolytic activity to effect cleavage of the target RNA. However, this activity in vivo is often controlled by the dominance of antisense or other double-stranded RNA mechanism. In this work, we demonstrate the in planta activity of a hammerhead ribozyme designed to target rep-mRNA of a phytopathogen Mungbean Yellow Mosaic India virus (MYMIV) as an antiviral agent. We also found RNA-silencing is induced on introduction of catalytically active as well as inactive ribozymes. Using RNA-silencing suppressors (RSS), we demonstrate that the endonucleolytic activity of ribozymes is a true phenomenon, even while a mutated version may demonstrate a similar down-regulation of the target RNA. This helps to ease the confusion over the action mechanism of ribozymes in vivo. 相似文献
999.
Keshavamurthy Vinay Geeti Khullar Savita Yadav Amrinder J. Kanwar Uma N. Saikia M. R. Shivaprakash Arunaloke Chakrabarti Sunil Dogra 《Mycopathologia》2014,177(3-4):179-185
Cutaneous aspergillosis is a common systemic mycosis affecting immunosuppressed patients. Here, we describe a novel morphological type of cutaneous aspergillosis in a young immunocompetent woman who presented with a chronic history of multiple nodules and discharging sinuses over left side of the face, mimicking cervicofacial actinomycosis. Skin biopsy showed granulomatous inflammation, and of septate fungal hyphae with acute-angled branching, morphologically resembling Aspergillus. This was confirmed on fungal culture as Aspergillus flavus. 相似文献
1000.
Genetic diversity of 70 isolates of Fusarium oxysporum f. sp. ciceris originated from various states of India representing eight races causing wilt in chickpea (Cicer arietinum) was analyzed using translation elongation factor-1α (TEF-1α), β-tubulin, and internal transcribed spacer (ITS) gene regions. TEF-1α, β-tubulin, and ITS gene-specific markers produced ~720-, ~500-, and ~550-bp amplicons, respectively, in all the isolates of the pathogen. A phylogenetic tree constructed from the sequences generated in the present study along with the sequences of foreign isolates of Fusarium species available in NCBI database sharing more than 90 % nucleotide sequence similarity grouped the isolates into two major clusters. Most of the isolates of the present study showed more or less similar grouping pattern in case of the three gene sequences. Each group had the isolates representing different races as well as place of origin indicating low level of diversity among the isolates in respect of these gene sequences. Except TEF-1α, the groups generated by β-tubulin and ITS gene sequences did not correspond to the state of origin and races of the pathogen. However, the groups of TEF-1α partially corresponded to the place of origin as well as races of the pathogen. The isolates did not show any race-specific grouping patterns; however, most of the isolates representing race 1 clustered separately. 相似文献