HIV-1 Replication through hHR23A-Mediated Interaction of Vpr with 26S Proteasome

HIV-1 Vpr is a virion-associated protein. Its activities link to viral pathogenesis and disease progression of HIV-infected patients. In vitro, Vpr moderately activates HIV-1 replication in proliferating T cells, but it is required for efficient viral infection and replication in vivo in non-dividing cells such as macrophages. How exactly Vpr contributes to viral replication remains elusive. We show here that Vpr stimulates HIV-1 replication at least in part through its interaction with hHR23A, a protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation. The Vpr-proteasome interaction was initially discovered in fission yeast, where Vpr was shown to associate with Mts4 and Mts2, two 19S-associated proteins. The interaction of Vpr with the 19S subunit of the proteasome was further confirmed in mammalian cells where Vpr associates with the mammalian orthologues of fission yeast Mts4 and S5a. Consistently, depletion of hHR23A interrupts interaction of Vpr with proteasome in mammalian cells. Furthermore, Vpr promotes hHR23A-mediated protein-ubiquitination, and down-regulation of hHR23A using RNAi significantly reduced viral replication in non-proliferating MAGI-CCR5 cells and primary macrophages. These findings suggest that Vpr-proteasome interaction might counteract certain host restriction factor(s) to stimulate viral replication in non-dividing cells

The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis

<p>Abstract</p> <p>Background</p> <p>Previous studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp). However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression.</p> <p>Results</p> <p>Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.</p> <p>Conclusions</p> <p>Our results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.</p

Development of Photonic Crystal Fiber Based Gas/ Chemical Sensors

The development of highly-sensitive and miniaturized sensors that capable of real-time analytes detection is highly desirable. Nowadays, toxic or colorless gas detection, air pollution monitoring, harmful chemical, pressure, strain, humidity, and temperature sensors based on photonic crystal fiber (PCF) are increasing rapidly due to its compact structure, fast response and efficient light controlling capabilities. The propagating light through the PCF can be controlled by varying the structural parameters and core-cladding materials, as a result, evanescent field can be enhanced significantly which is the main component of the PCF based gas/chemical sensors. The aim of this chapter is to (1) describe the principle operation of PCF based gas/ chemical sensors, (2) discuss the important PCF properties for optical sensors, (3) extensively discuss the different types of microstructured optical fiber based gas/ chemical sensors, (4) study the effects of different core-cladding shapes, and fiber background materials on sensing performance, and (5) highlight the main challenges of PCF based gas/ chemical sensors and possible solutions

The interaction of HAb18G/CD147 with integrin α6β1 and its implications for the invasion potential of human hepatoma cells

<p>Abstract</p> <p>Background</p> <p>HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin α3β1. However, it has never been investigated whether α3β1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells.</p> <p>Methods</p> <p>Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin α6β1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin α6β1. Invasion potential was evaluated with an invasion assay and gelatin zymography.</p> <p>Results</p> <p>We found that integrin α6β1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs) were partially blocked by integrin α6β1 antibodies (<it>P </it>< 0.01). Wortmannin, a specific phosphatidylinositol kinase (PI3K) inhibitor that reverses the effect of HAb18G/CD147 on the regulation of intracellular Ca²⁺mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (<it>P </it>< 0.05). Importantly, no additive effect between Wortmannin and α6β1 antibodies was observed, indicating that α6β1 and PI3K transmit the signal in an upstream-downstream relationship.</p> <p>Conclusion</p> <p>These results suggest that α6β1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.</p

Electrospun fluorescent nanofibers for explosive detection

Development of an instant on-site visual detection method for 2,4,6 trinitrotoluene (TNT) has become a significant requirement of the hour towards a secured society and a greener environment. Despite momentous advances in the respective field, a portable and reliable method for quick and selective detection of TNT still poses a challenge to many reasons attributing to inappropriate usage in subordinate areas and untrained personnel. The recent effort on the fluorescent based detection represents as one of easy method in terms of fast response time and simple on/off detection. Therefore, this chapter provides a consolidation of information relating to recent advances in fluorescence based TNT detection.Further, the main focus will be towards advances in the nanofibers based TNT detection and their reason to improving thesensitivity. © Springer International Publishing Switzerland 2015