RASSF8-mediated transport of Echinoid via the exocyst promotes Drosophila wing elongation and epithelial ordering

Cell-cell junctions are dynamic structures that maintain cell cohesion and shape in epithelial tissues. During development, junctions undergo extensive rearrangements to drive the epithelial remodelling required for morphogenesis. This is particularly evident during axis elongation, where neighbour exchanges, cell-cell rearrangements and oriented cell divisions lead to large-scale alterations in tissue shape. Polarised vesicle trafficking of junctional components by the exocyst complex has been proposed to promote junctional rearrangements during epithelial remodelling, but the receptors that allow exocyst docking to the target membranes remain poorly understood. Here, we show that the adherens junction component Ras Association domain family 8 (RASSF8) is required for the epithelial re-ordering that occurs during Drosophila pupal wing proximo-distal elongation. We identify the exocyst component Sec15 as a RASSF8 interactor. RASSF8 loss elicits cytoplasmic accumulation of Sec15 and Rab11-containing vesicles. These vesicles also contain the nectin-like homophilic adhesion molecule Echinoid, whose depletion phenocopies the wing elongation and epithelial packing defects observed in RASSF8 mutants. Thus, our results suggest that RASSF8 promotes exocyst-dependent docking of Echinoid-containing vesicles during morphogenesis.

Formulation and in-vitro evaluation of niosomal gel of gatifloxacin

A novel drug delivery system provides the delivery of drugs at a required rate into the body during the period of treatment as directed by the body. Formulation and evaluation of Noisome containing gatifloxacin using different concentrations of the polymer for controlled release. Pre-formulation study confirms the purity of the drug and compatibility of the drug with excipients using FT-IR. Tween 80 was found significant with the experimental results. An extensive investigation is needed concerning the depth of penetration into the skin, determination of zeta potential, and confirmation of configuration of phospholipids in the lipid bilayer. A significant loss of entrapped drug was found at the end of three month period when liposomal dispersions were stored at high temperature i.e. 25±20C. All gels were found under pH range 7.0 to 7.4, Spreadability under the range 6.6 to 7.6 cm, % drug content 98 to 100%, the viscosity of gels 98 to 115cp, and % permeation found in rage 75 to 91%. Excellent % Permeation Gel formulation GF-4 was found 91%. The drug release at raised temperatures may be associated with the lipid degradation in the bilayers results in membrane packing defects them leaky.

The study of the behavior of Al impurity in ZnO lattice by a fullerene like model

The fullerene like Zn32Al4O36 clusters were investigated and the oxygen interstitial Oi acceptor intrinsic defect formation energy as well as Al ionization energy were calculated. The effect of lattice packing defects on the electroactivity of Al impurity was investigated. Analysis of the defects formation energies shows the smaller formation energy of interstitial Oi in a comparison with a formation of Zn vacancy. This allows us to formulate recommendations of technological conditions for films deposition, with improved electroactivity of Al donor.

Exceptional stability of a perilipin on lipid droplets depends on its polar residues, suggesting multimeric assembly

Numerous proteins target lipid droplets (LDs) through amphipathic helices (AHs). It is generally assumed that AHs insert bulky hydrophobic residues in packing defects at the LD surface. However, this model does not explain the targeting of perilipins, the most abundant and specific amphipathic proteins of LDs, which are weakly hydrophobic. A striking example is Plin4, whose gigantic and repetitive AH lacks bulky hydrophobic residues. Using a range of complementary approaches, we show that Plin4 forms a remarkably immobile and stable protein layer at the surface of cellular or in vitro generated oil droplets, and decreases LD size. Plin4 AH stability on LDs is exquisitely sensitive to the nature and distribution of its polar residues. These results suggest that Plin4 forms stable arrangements of adjacent AHs via polar/electrostatic interactions, reminiscent of the organization of apolipoproteins in lipoprotein particles, thus pointing to a general mechanism of AH stabilization via lateral interactions.

Structural origins of protein conformational entropy

The thermodynamics of molecular recognition by proteins is a central determinant of complex biochemistry. For over a half-century detailed cryogenic structures have provided deep insight into the energetic contributions to ligand binding by proteins1. More recently, a dynamical proxy based on NMR-relaxation methods has revealed an unexpected richness in the contributions of conformational entropy to the thermodynamics of ligand binding2,3,4,5. There remains, however, a discomforting absence of an understanding of the structural origins of fast internal motion and the conformational entropy that this motion represents. Here we report the pressure-dependence of fast internal motion within the ribonuclease barnase and its complex with the protein barstar. Distinctive clustering of the pressure sensitivity correlates with the presence of small packing defects or voids surrounding affected side chains. Prompted by this observation, we performed an analysis of the voids surrounding over 2,500 methyl-bearing side chains having experimentally determined order parameters. We find that changes in unoccupied volume as small as a single water molecule surrounding buried side chains greatly affects motion on the subnanosecond timescale. The discovered relationship begins to permit construction of a united view of the relationship between changes in the internal energy, as exposed by detailed structural analysis, and the conformational entropy, as represented by fast internal motion, in the thermodynamics of protein function.

Improving parameters of planar pulse diode using gettering

Pulse diodes are widely used as part of high-frequency pulse circuits. However, it should be noted that the cost of pulsed diodes remains relatively high, due to the low yield of suitable devices when they are sorted according to the criteria of reverse current and rated capacitance. This is largely caused by the significant dependence of their electrical parameters on the density of structural defects and impurities in the active regions of the diodes. The study is devoted to identifying the causes and mechanisms of the low yield of diodes when they are sorted according to the criteria of reverse current and rated capacitance, as well as determining the possibility of using gettering operations to increase the yield of suitable devices. It is found that the low yield of the diodes is caused by the structural defects that are formed in the active areas of the diodes during high-temperature technological operations. The paper describes the mechanisms in which the structural defects affect the electrical parameters of diodes. The proposed technology for manufacturing diode structures using gettering of structural impurity defects by means of high-temperature annealing in an inert medium before the thermal oxidation operation is considered. It is shown that high-temperature annealing of silicon structures before thermal oxidation eliminates packing defects formed during epitaxy, cleans the active areas of the diodes from nuclei of defects and unwanted impurities, and prevents the formation of structural defects in them during the subsequent high-temperature thermal operations. The use of the proposed technology allows increasing the yield of suitable diode structures by 8.9% when sorted according to rated capacitance and by 9.4% when sorted according to reverse current, the level of reverse currents reducing by 2—9 times.

Effect of Cholesterol on Membrane Partitioning Dynamics of Hepatitis A Virus-2B peptide

ABSTRACTUnderstanding the viral peptide detection, partitioning and subsequent host membrane composition-based response is required for gaining insights into viral mechanism. Here, we probe the crucial role of presence of membrane lipid packing defects, depending on the membrane composition, in allowing the viral peptide belonging to C-terminal Hepatitis A Virus-2B (HAV-2B) to detect, attach and subsequently partition into the host cell membrane mimics. We conclusively show that the hydrophobic residues in the viral peptide detect the transiently present lipid packing defects, insert themselves into such defects, form anchor points and facilitate the partitioning of the peptide. We also show that the presence of cholesterol significantly alters such lipid packing defects, both in size and in number, thus mitigating the partitioning of the membrane active viral peptide into cholesterol-rich membranes. These results show differential ways in which presence and absence of cholesterol can alter the permeability of the host membranes to the membrane active viral peptide component of HAV-2B virus, via lipid packing defects, and can possibly be a part of general membrane detection mechanism for the viroporin class of viruses.