Dual-mechanism antimicrobial polymer-ZnO nanoparticle and crystal violet-encapsulated silicone

The prevalence of healthcare-associated infection caused by multidrug-resistant bacteria is of critical concern worldwide. It is reported on the development of a bactericidal surface prepared by use of a simple, upscalable, two-step dipping strategy to incorporate crystal violet and di(octyl)-phosphinic- acid-capped zinc oxide nanoparticles into medical grade silicone, as a strategy to reduce the risk of infection. The material is characterized by UV-vis absorbance spectroscopy, X-ray photoelectron spectroscopy (XPS), inductively coupled plasma-optical emission spectroscopy (ICP-OES) and transmission electron microscopy (TEM) and confirmed the incorporation of the ZnO nanoparticles in the polymer. The novel system proves to be a highly versatile bactericidal material when tested against both Staphylococcus aureus and Escherichia coli, key causative micro-organisms for hospital-acquired infection (HAI). Potent antimicrobial activity is noted under dark conditions, with a significant enhancement exhibits when the surfaces are illuminated with a standard hospital light source. This polymer has the potential to decrease the risk of HAI, by killing bacteria in contact with the surface

The Builders of the Junction: Roles of Junctophilin1 and Junctophilin2 in the Assembly of the Sarcoplasmic Reticulum–Plasma Membrane Junctions in Striated Muscle

Contraction of striated muscle is triggered by a massive release of calcium from the sarcoplasmic reticulum (SR) into the cytoplasm. This intracellular calcium release is initiated by membrane depolarization, which is sensed by voltage-gated calcium channels CaV1.1 (in skeletal muscle) and CaV1.2 (in cardiac muscle) in the plasma membrane (PM), which in turn activate the calcium-releasing channel ryanodine receptor (RyR) embedded in the SR membrane. This cross-communication between channels in the PM and in the SR happens at specialized regions, the SR-PM junctions, where these two compartments come in close proximity. Junctophilin1 and Junctophilin2 are responsible for the formation and stabilization of SR-PM junctions in striated muscle and actively participate in the recruitment of the two essential players in intracellular calcium release, CaV and RyR. This short review focuses on the roles of junctophilins1 and 2 in the formation and organization of SR-PM junctions in skeletal and cardiac muscle and on the functional consequences of the absence or malfunction of these proteins in striated muscle in light of recently published data and recent advancements in protein structure prediction

FLOUTING MAXIMS ON THE DIALOGUE OF CHARACTERS IN UP! ANIMATED MOVIE

This research is about flouting maxims on the dialogue of characters in UP! Animated movie. Hence, it is aimed to know flouting maxim on  UP! animated movie. This research is used qualitative research. The data of this study was taken on flouting maxims on the discourse of figure in UP! animated movie from he main characters namely old name Carl Fredrickson and Russel. There are several steps in collecting the data namely, finding a script UP! of the animated movie, next is analyzing the script with the UP! movie and the last is to list the utterances of the main personality of UP! animated movie in flouted maxims and finally analyzing them based on the chosen theory. After conducting the research, the writer found 20 sentences that flouted by Mr. Fredickson and Russel animated UP! movie. Those kinds of maxims are 6 flouted maxims of quantity, 7 flouted maxims of quality, 3 flouted maxims of relevance, and 4 flouted maxims of manner. Keywords:  Flouting maxim, Dialogue, Movi

A contribution to the understanding of percolation phenomena in binary liquids

In the present work it was shown the important role of the Ei/E parameter in the characterization of polar liquids. It could be demonstrated that the application of the broad range dielectric spectroscopy together with the analysis of the quasi-static permittivity using the modified Clausius-Mosotti-Debye equation can be used to detect percolation phenomena in binary polar liquid mixtures. It leads to a valuable insight into the structure of polar liquids and to a better understanding of binary systems. However, it has to be kept in mind, that besides of percolation thresholds as critical concentrations it is also possible to detect a change of the coordination number as a function of the volume ratio of the components, which involves a change of the lattice type. It is sometimes difficult to discriminate between pc or lattice change and more studies are needed in order to distinguish between these two processes. It might also be useful to add additional analytical methods. It was possible to clarify the non-linear behavior of the DMSO-water mixtures founded in different measured physical properties. This was possible by measuring dielectric spectroscopy parameters such as the Ei/E parameter obtained through the modified Clausius-Mossotti-Debye equation, g-values obtained from the Kirkwood-Fröhlich equation, relaxation time and dielectric constant and comparing them with literature data concerning the viscosity, adiabatic compressibility and freezing point of binary solvent mixtures. The results were interpreted in the frame of percolation theory. The values of the lower and upper percolation thresholds are comparable and it is of interest, that as a function of the parameter studied, only one or two percolation thresholds can be detected. It is necessary to remark that despite the large number of techniques that have been applied to the study of the DMSO-water system, the behavior of this system is still a mystery. For future pharmaceutical research it could be interested to extend the dielectric spectroscopy studies to the Nanotechnology. This is in my view an exciting perspective. Stromme (Proc. SPIE Int. Soc. Opt. Eng. 5118 pp 310-322, 2003) demonstrated how dielectric spectroscopy can be used as a tool to obtain insight about properties on the nanoscale of interfaces of pharmaceutical interest. An outline for studying the adhesion in terms of a compatibility factor between pharmaceutical gels and biological tissue was put forward

Optimisation and feature selection of poly-beta-amino-ester as a drug delivery system for cartilage

Drug localisation is still one of the main challenges in treating pathologies affecting cartilage; poly-beta-amino-esters (PBAEs) drug conjugates are a possible solution; however, their efficacy highly depends on the polymer structure hence the full potential of this delivery system is still unknown. For the purpose of optimising the delivery system design, a large library of PBAEs was synthesised and dexamethasone (DEX) uptake in cartilage was determined. All three components of PBAE (amine, acrylate and end-capping) impacted the outcome. The most effective PBAE identified enhanced DEX uptake by 8 folds compared to an equivalent dose of the commercial formulation and also prevented, through delivery of DEX, the cartilage degradation caused by IL-1α (interleukine1α). A chemometrics based predictive model was constructed and PBAEs properties most affecting the performance of the drug delivery systems were identified. This model will allow further computer based PBAEs optimisation and fast track the bench to market process for this delivery system

Neuronal junctophilins recruit specific Cav and RyR isoforms to ER-PM junctions and functionally alter Cav2.1 and Cav2.2

Junctions between the endoplasmic reticulum and plasma membrane that are induced by the neuronal junctophilins are of demonstrated importance, but their molecular architecture is still poorly understood and challenging to address in neurons. This is due to the small size of the junctions and the multiple isoforms of candidate junctional proteins in different brain areas. Using colocalization of tagged proteins expressed in tsA201 cells, and electrophysiology, we compared the interactions of JPH3 and JPH4 with different calcium channels. We found that JPH3 and JPH4 caused junctional accumulation of all the tested high-voltage-activated CaV isoforms, but not a low-voltage-activated CaV. Also, JPH3 and JPH4 noticeably modify CaV2.1 and CaV2.2 inactivation rate. RyR3 moderately colocalized at junctions with JPH4, whereas RyR1 and RyR2 did not. By contrast, RyR1 and RyR3 strongly colocalized with JPH3, and RyR2 moderately. Likely contributing to this difference, JPH3 binds to cytoplasmic domain constructs of RyR1 and RyR3, but not of RyR2

Junctophilins 1, 2, and 3 all support voltage-induced Ca2+ release despite considerable divergence

In skeletal muscle, depolarization of the plasma membrane (PM) causes conformational changes of the calcium channel CaV1.1 that then activate RYR1 to release calcium from the SR. Being independent of extracellular calcium entry, this process is termed voltage-induced calcium release. In skeletal muscle, junctophilins (JPHs) 1 and 2 form the SR–PM junctions at which voltageinduced calcium release occurs. Previous work demonstrated that JPH2 is able to recapitulate voltage-induced calcium release when expressed in HEK293 cells together with CaV1.1, β1a, Stac3, and RYR1. However, it is unknown whether JPH1 and the more distantly related neuronal JPH3 and JPH4 might also function in this manner, a question of interest because different JPH isoforms diverge in their interactions with RYR1. Here, we show that, like JPH2, JPH1 and JPH3, coexpressed with CaV1.1, β1a, Stac3, and RYR1 in HEK293 cells, cause colocalization of CaV1.1 and RYR1 at ER–PM junctions. Furthermore, potassium depolarization elicited cytoplasmic calcium transients in cells in which WT CaV1.1 was replaced with the calcium impermeant mutant CaV1.1(N617D), indicating that JPH1, JPH2, and JPH3 can all support voltage-induced calcium release, despite sequence divergence and differences in interaction with RYR1. Conversely, JPH4-induced ER–PM junctions contain CaV1.1 but not RYR1, and cells expressing JPH4 are unable to produce depolarization-induced calcium transients. Thus, JPHs seem to act primarily to form ER–PM junctions and to recruit the necessary signaling proteins to these junctions but appear not to be directly involved in the functional interactions between these proteins

Antenatal Assessment of Discordant Umbilical Arteries in Singleton Pregnancies

Aim: To assess the relationship between discordant umbilical arterial size and resultant blood flow parameters and determine the impact of discordance on fetal outcome. Methods: This is a descriptive, cross-sectional study of 200 patients with a singleton gestation, who underwent a fetal anatomy survey between 18 to 23 weeks of gestation, with documented umbilical cord morphological patterns and blood flow characteristics. Umbilical vessel diameters and Doppler parameters (umbilical vein blood flow volume, mean resistance index, and peak-systolic velocity) were analyzed for discordance. Discordances encountered were examined for their possible association with perinatal outcome. Results: We had adequate ultrasound umbilical cord images, Doppler flow parameters, and all necessary demographic data for 154 patients. Umbilical artery discordance averaged 13.1% and was significantly correlated with both the expected and the true percent of difference in resistance index values (RI, P<0.001). In 12 patients (7.8%), a significant discordance of more than 29.5%, or 95th percentile, was observed between the two umbilical artery diameters. However, in these cases no associated adverse perinatal outcome or significant placental pathology was noted. There was no significant difference between patients with discordant and concordant umbilical artery in terms of maternal, labor, and neonatal data. Conclusion: The magnitude of umbilical arteries’ luminal discordance directly influences the corresponding blood flow parameters. In our sample of patients, the presence of discordant-in-size umbilical arteries was not associated with umbilical cord or placental abnormalities