Effect of compatibilizer on the dynamic mechanical and electrical properties of kaolin clay reinforced EPDM rubber

Industrial pollution issue and dark colour of carbon black, clay based non black filler are getting more importance for reinforcing elastomer. EPDM-Kaolin composites with various maleated EPDM concentration have been prepared by mixing on a two roll mill. The rheometry data showed the optimum cure time increases with increasing compatibilizer concentration without decreasing torque value indicating that acidic functional groups comes from compatibilizer could retard cure rate and increase the optimum cure time rather than change in the ultimate cure state. As the filler concentration increases, the edge to edge and face to edge interaction between filler and EPDM increases and the free volume between EPDM molecules is reduced, the storage modulus increases. Moreover, the dynamic mechanical analysis also showed the increase in glass transition temperature with increase in filler concentration due to the inter-tubular diffusion of EPDM inside the clay. It was also observed that with increasing filler concentration, the resistivity and dielectric strength decreases and moreover with increasing compatibilizer concentration the resistivity decreases due to better dispersion of filler helps to build conduction path. The morphological study also revealed that homogeneity of filler dispersion increases with increase in compatibilizer concentration

Differentially cleaving peptides as a strategy for controlled drug release in human retinal pigment epithelial cells

Peer reviewe

Codon optimization and factorial screening for enhanced soluble expression of human ciliary neurotrophic factor in Escherichia coli

Peer reviewe

Release of functional dexamethasone by intracellular enzymes: A modular peptide-based strategy for ocular drug delivery

Tissue barriers limit drug delivery in the eye. Therefore, retinal diseases are treated with intravitreal injections. Delivery systems with reduced dosing frequency and/or cellular drug delivery properties are needed. We present here a modular peptide-based delivery system for cell targeted release of dexamethasone in the retinal pigment epithelial cells. The peptide–dexamethasone conjugates consist of cell penetrating peptide, enzyme cleavable linker and dexamethasone that is conjugated with hydrazone bond. The conjugates are chemically stable in the vitreous, internalize into the retinal pigment epithelial cells and release dexamethasone intracellularly by en- zymatic action of cathepsin D. In vitro binding assay and molecular docking confirm binding of the released dexamethasone fragment to the human glucocorticoid receptor. In vivo rabbit studies show increased vitreal retention of dexamethasone with a peptide conjugate. Modular peptide conjugates are a promising approach for drug delivery into the retinal cells.Peer reviewe

Avoiding the Pitfalls of siRNA Delivery to the Retinal Pigment Epithelium with Physiologically Relevant Cell Models

Inflammation is involved in the pathogenesis of several age-related ocular diseases, such as macular degeneration (AMD), diabetic retinopathy, and glaucoma. The delivery of anti-inflammatory siRNA to the retinal pigment epithelium (RPE) may become a promising therapeutic option for the treatment of inflammation, if the efficient delivery of siRNA to target cells is accomplished. Unfortunately, so far, the siRNA delivery system selection performed in dividing RPE cells in vitro has been a poor predictor of the in vivo efficacy. Our study evaluates the silencing efficiency of polyplexes, lipoplexes, and lipidoid-siRNA complexes in dividing RPE cells as well as in physiologically relevant RPE cell models. We find that RPE cell differentiation alters their endocytic activity and causes a decrease in the uptake of siRNA complexes. In addition, we determine that melanosomal sequestration is another significant and previously unexplored barrier to gene silencing in pigmented cells. In summary, this study highlights the importance of choosing a physiologically relevant RPE cell model for the selection of siRNA delivery systems. Such cell models are expected to enable the identification of carriers with a high probability of success in vivo, and thus propel the development of siRNA therapeutics for ocular disease.Peer reviewe

Avoiding the Pitfalls of siRNA Delivery to the Retinal Pigment Epithelium with Physiologically Relevant Cell Models

Inflammation is involved in the pathogenesis of several age-related ocular diseases, such as macular degeneration (AMD), diabetic retinopathy, and glaucoma. The delivery of anti-inflammatory siRNA to the retinal pigment epithelium (RPE) may become a promising therapeutic option for the treatment of inflammation, if the efficient delivery of siRNA to target cells is accomplished. Unfortunately, so far, the siRNA delivery system selection performed in dividing RPE cells in vitro has been a poor predictor of the in vivo efficacy. Our study evaluates the silencing efficiency of polyplexes, lipoplexes, and lipidoid-siRNA complexes in dividing RPE cells as well as in physiologically relevant RPE cell models. We find that RPE cell differentiation alters their endocytic activity and causes a decrease in the uptake of siRNA complexes. In addition, we determine that melanosomal sequestration is another significant and previously unexplored barrier to gene silencing in pigmented cells. In summary, this study highlights the importance of choosing a physiologically relevant RPE cell model for the selection of siRNA delivery systems. Such cell models are expected to enable the identification of carriers with a high probability of success in vivo, and thus propel the development of siRNA therapeutics for ocular disease

N-H···O, O-H···O, and C-H···O hydrogen bonds in protein-ligand complexes: strong and weak interactions in molecular recognition

The characteristics of N-H···O, O-H···O, and C-H···O hydrogen bonds are examined in a group of 28 high-resolution crystal structures of protein-ligand complexes from the Protein Data Bank and compared with interactions found in small-molecule crystal structures from the Cambridge Structural Database. It is found that both strong and weak hydrogen bonds are involved in ligand binding. Because of the prevalence of multifurcation, the restrictive geometrical criteria set up for hydrogen bonds in small-molecule crystal structures may need to be relaxed in macromolecular structures. For example, there are definite deviations from linearity for the hydrogen bonds in protein-ligand complexes. The formation of C-H···O hydrogen bonds is influenced by the activation of the CaH atoms and by the flexibility of the side-chain atoms. In contrast to small-molecule structures, anticooperative geometries are common in the macromolecular structures studied here, and there is a gradual lengthening as the extent of furcation increases. C-H···O bonds formed by Gly, Phe, and Tyr residues are noteworthy. The numbers of hydrogen bond donors and acceptors agree with Lipinski's "rule of five"that predicts drug-like properties. Hydrogen bonds formed by water are also seen to be relevant in ligand binding. Ligand C-H···Ow interactions are abundant when compared to N-H···Ow and O-H···Ow. This suggests that ligands prefer to use their stronger hydrogen bond capabilities for use with the protein residues, leaving the weaker interactions to bind with water. In summary, the interplay between strong and weak interactions in ligand binding possibly leads to a satisfactory enthalpy-entropy balance. The implications of these results to crystallographic refinement and molecular dynamics software are discussed

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Not AvailableSix Trypanosoma evansi isolates were collected from ponies (PH1 and PK6), camel (CB2), donkeys (DJ3 and DH4) and cattle (CK5) from different States of Northern India (Haryana, Rajasthan, Uttar Pradesh and Gujarat) for molecular characterization based on 18S rRNA gene. The 18S rRNA gene (2251 bp) of different isolates was amplified, cloned and custom sequenced separately. Based on sequence and phylogenetic analysis of all six isolates, collected from different hosts as well as geographical areas, were having high identity among Indian T. evansi strains (99.7%) and with other strains of T. evansi (99.2%) distributed worldwide. There is less genetic diversity among different salivarian strains of T. evansi except few nucleotide changes at significant locations in one Indian isolate of camel origin (CB2). All Indian T. evansi isolates were grouped in salivarian clade with high bootstrap values and remained far away from stercorarian clade having 88–90% nucleotide identity. The study will be helpful in understanding the evolutionary relationship, molecular epidemiology and variation in disease pathogenesis among different T. evansi strains. Further, more studies are required on large number of isolates collected from diverse host and geographical areas to reaffirm the present finding.Not Availabl