The Role of Rab27 in Inflammation

Rab27 is a member of the Rab family of Ras-like GTPases and is expressed in two isoforms, Rab27a and Rab27b that share 72% amino acid identity. Previous studies have suggested Rab27a and Rab27b to regulate inflammation through exocytosis in a variety of leukocytes including T lymphocytes, NK cells, mast cells and neutrophils. A key process in inflammation is mast cell secretion, a process in which Rab27b has been established as a positive regulator but the role of Rab27a remains unclear. In this study we confirm that in response to IgE crosslinking, Rab27a appears to play a negative role in secretion, however Rab27a was observed to promote secretion in absence of Rab27b, so this effect is likely due to abnormally distributed cortical F-actin and enhanced granule docking in absence of Rab27a. Furthermore Rab27a may exert this regulation through effector Melanophilin. We also confirm that the effector Munc13-4 is important for promoting mast cell secretion, likely through interaction with both Rab27a and Rab27b. Rab27 has also been suggested to regulate inflammation by promoting granule secretion in neutrophils. Here we find that Rab27a was localised to structures at the uropod and that Rab27a deficient neutrophils display defective chemotaxis due to impaired uropod release. Inhibition of extracellular serine proteases inhibited wild-type but not Rab27a deficient neutrophil chemotaxis suggesting that defective protease secretion may underlie Rab27a deficient neutrophil chemotaxis defect. Analysis of αMβ2 integrin subunit CD11b after chemokine stimulation revealed that CD11b surface expression was sustained on Rab27a deficient neutrophils compared to wild-type, suggesting that cleavage of CD11b may be impaired. Inhibition of other proteins known to promote primary granule secretion, Rab27b and Rab27 effectors Slp1 and Munc13-4 also impaired neutrophil chemotaxis. Together these data suggest that Rab27a promotes uropod detachment through release of proteases contained in primary granules to promote neutrophil chemotaxis

Spatial ordering due to hydrodynamic interactions between a pair of colliding drops in a confined shear

Pair-collision between viscous drops in a confined shear is numerically simulated to show that the confinement drastically alters the trajectories of the drops. In contrast to free shear, drops here move towards the centerline giving rise to a zero cross-stream separation and a net stream-wise separation. The latter varies as inverse of capillary number and the cube of the confinement (distance between the walls). The stream-wise separation does not depend on the initial positions of the drops. An analytical theory for the phenomenon is offered

Screening of certain Ayurvedic plants extracts against E. turcicum

The use of chemicals against pathogens is environmentally dangerous, so use of natural inhibitors for disease management is needed. In this work we screen botanical extracts from ayurvedic plants for their antifungal properties against economically important plant fungal pathogen. As a test fungal pathogen, we select E. turcicum, a potent fungal pathogen responsible for Northern leaf corn blight of Maize. This fungal pathogen was challenged by the leaf extract prepared from certain Ayurvedic plants and these observations have shown a promising future in biocontrol of fungus by using such environmentally friendly
antifungal agents

Corrosion protection of transport vehicles by nanocoating of decahydrobenzxo[8] annulene-5, 10 dihyrazone and SiC filter in H O O (moist), CO , 2 3 2 2 SO environments and weather change

Transport industries use epoxy-coating for corrosion protection of stainlesssteel but this coating cannot provide protection in long duration in H O, O (moist), CO 2 2 2 and SO environment and weather change. Pollutants can create acidic medium for 2 epoxy-coated stainless steel. These corrosive agents penetrate epoxy-coating by osmosis or diffusion process produce and produce chemical and corrosion reactions with base metal. These reactions enhance internal and external corrosion and accelerate internal disbonding in epoxy-coating and disintegrate base metal. This coating does not protect themselves and base metal. These pollutants and weather change elevate galvanic, pitting, stress, crevice, intergranular, blistering and embrittlemint corrosion whereas epoxy polymer exhibits swelling and dissolving corrosion. Pollutants and weather change can alter their physical, chemical and mechanical properties and tarnish their facial appearance. They can also change morphology epoxy-coated stainless steel. Corrosion mitigation of epoxy-coated stainless steel in ambient of H O, O (moist), CO 2 2 2 and SO and weather change used nanocoating and filler technology. For this work 2 decahydrobenzo[8] annulene-5, 10-dihydrazone and SiC used as nanocoating and fillermaterials. Nanocoating and filling work were completed by nozzle spray The corrosion rate of epoxy-coated stainless steel coupons was determined at 278, 283, 288, 293 and 2980K temperatures and times mentioned at these temperatures was 24, 48, 72, 96 and 120 hours in different weather without coating and with nanocoating of decahydrobenzo[8] annulene-5, 10-dihydrazone and SiC filler by help of weight loss experiment. Corrosion potential and corrosion current were determined by potentiostat. Coating efficiency and surface coverage area were calculated by gravimetric methods. The surface composite barrier formation was studied by activation energy, heat of adsorption, free energy, entropy and enthalpy

Characterization of the Ubiquitin/Nedd8 E3 ligase activity of the Mdm2/MdmX complex

The RING finger proteins Mdm2 and MdmX share significant structural similarity with each other and are major antagonists of the tumor suppressor protein p53. Mdm2 is a member of the RING finger family of E3 ligases and targets p53 for ubiquitination and degradation by the 26S proteasome system. Unlike Mdm2, MdmX does not have appreciable E3 ligase activity and, hence, does not induce p53 degradation on its own. However, our group previously reported that MdmX enhances the E3 ligase activity of Mdm2 in vitro. To obtain insight into the mechanism by which MdmX enhances the E3 ligase activity of Mdm2, a mutational analysis of the RING finger domains of Mdm2 and MdmX was performed. We identified several residues within the RING finger domain of Mdm2 that are essential for its E3 ligase activity. Mutation of some of these residues impairs the ability of Mdm2 to interact with itself or with MdmX indicating that oligomerization is required for Mdm2 to function as an E3 ligase. Mutation of other residues does not detectably interfere with the ability of Mdm2 to interact with itself or with MdmX. However, the ability of these mutants to interact with the ubiquitin conjugating enzyme UbcH5b is impaired. Interestingly, MdmX rescues the E3 ligase activity of the latter Mdm2 mutants, both in vitro and within cells indicating that Mdm2/MdmX hetero-oligomers can function as an E3 ligase for p53 within cells. Furthermore, we present evidence that Mdm2/MdmX hetero-oligomeric complexes not only function as ubiquitin E3 ligases for p53 but also facilitate modification of p53 with the ubiquitin-like molecule Nedd8. Moreover, all the Mdm2 mutants impaired for their ubiquitin ligase activity are also impaired for their Nedd8 ligase activity and some of them are rescued in their activity by MdmX. This suggests that Mdm2 employs similar molecular mechanisms to transfer both ubiquitin and Nedd8 to p53. In addition, we show that ubiquitin and Nedd8 can be attached to the same p53 molecule indicating that ubiquitin and Nedd8 may form mixed chains within cells. Finally, using several mutants of ubiquitin and Nedd8, we present evidence that Nedd8, when attached to ubiquitin, may function as chain terminator in cells