Development of Avian Avulavirus 1 Epitope-Based Vaccine Pattern Based on Epitope Prediction and Molecular Docking Analysis: An Immunoinformatic Approach

International Journal of Peptide Research and Therapeutics - Fusion (F) and Hemagglutinin-neuraminidase (HN) glycoproteins of Newcastle disease virus containing important epitopes play crucial role...     

Application of neural networks for the prediction of cartilage stress in a musculoskeletal system

Traditional finite element (FE) analysis is computationally demanding. The computational time becomes prohibitively long when multiple loading and boundary conditions need to be considered such as in musculoskeletal movement simulations involving multiple joints and muscles. Presented in this study is an innovative approach that takes advantage of the computational efficiency of both the dynamic multibody (MB) method and neural network (NN) analysis. A NN model that captures the behavior of musculoskeletal tissue subjected to known loading situations is built, trained, and validated based on both MB and FE simulation data. It is found that nonlinear, dynamic NNs yield better predictions over their linear, static counterparts. The developed NN model is then capable of predicting stress values at regions of interest within the musculoskeletal system in only a fraction of the time required by FE simulation.     

Tumor Dynamics in Response to Antiangiogenic Therapy with Oral Metronomic Topotecan and Pazopanib in Neuroblastoma Xenografts

Metronomic chemotherapy, combined with targeted antiangiogenic drugs, has demonstrated significant anticancer efficacy in various studies. Though, tumors do acquire resistance. Here, we have investigated the effect of prolonged therapy with oral metronomic topotecan and pazopanib on tumor behavior in a neuroblastoma mouse xenograft model. SK-N-BE(2) xenograft-bearing mice were treated with either of the following regimens (daily, orally): vehicle (control), 150 mg/kg pazopanib, 1.0 mg/kg topotecan, and combination of topotecan and pazopanib. Planned durations of treatment for each regimen were 28, 56, and 80 days or until the end point, after which animals were sacrificed. We found that only combination-treated animals survived until 80 days. Combination halted tumor growth for up to 50 days, after which gradual growth was observed. Unlike single agents, all three durations of combination significantly lowered microvessel densities compared to the control. However, the tumors treated with the combination for 56 and 80 days had higher pericyte coverage compared to control and those treated for 28 days. The proliferative and mitotic indices of combination-treated tumors were higher after 28 days of treatment and comparable after 56 days and 80 days of treatment compared to control. Immunohistochemistry,Western blot, and real-time polymerase chain reaction revealed that combination treatment increased the hypoxia and angiogenic expression. Immunohistochemistry for Glut-1 and hexokinase II expression revealed a metabolic switch toward elevated glycolysis in the combination-treated tumors. We conclude that prolonged combination therapy with metronomic topotecan and pazopanib demonstrates sustained antiangiogenic activity but also incurs resistance potentially mediated by elevated glycolysis.     

The role of anti-CCD antibodies in grape allergy diagnosis

Background:

Allergens are mostly composed of glycoprotein structures. It is believed that glycan-specific antibodies may lead to false-positive reactions in immunoassays. In this study we investigated the glycosylation state of grape allergens as well as the presence of antibodies to cross-reactive carbohydrate determinants (anti-CCDs) in sera from grape-sensitive individuals.

Methods:

Grape extract proteins were electrotransferred onto PVDF membranes and their glycosylation states were analyzed by blotting methods. To assess the presence of anti-CCDs, natural and mildly deglycosylated proteins were immunoblotted with grape-allergic subjects'' sera. We also measured the IgE reactivity of each subject’s sera with other fruit extracts via an indirect ELISA.

Results:

Immunoblotting studies showed that mildly deglycosylated grape proteins had lower IgE-binding capacity than their intact natural counterparts, which could be due to the presence of anti-CCDs. Biotinylation studies confirmed that the glycosylation levels of the 24, 32, and 60 kDa IgE-reactive proteins were higher than those of the 38 and 45 kDa ones. Lectin blotting showed that the 24 and 60 kDa bands were highly mannosylated, with the highest level of mannosylation on the 24 kDa allergen.

Conclusion:

This study showed that some grape allergens are glycosylated and that anti-CCD antibodies may cause weakly false-positive results during assessment of IgE reactivity to grape allergens.Key Words: Allergy, Grape, Cross-reactive carbohydrate determinants, Antibody     

Reference Genes Selection for Quantitative Real-Time PCR Using RankAggreg Method in Different Tissues of Capra hircus

Identification of reference genes with stable levels of gene expression is an important prerequisite for obtaining reliable results in analysis of gene expression data using quantitative real time PCR (RT-qPCR). Since the underlying assumption of reference genes is that expressed at the exact same level in all sample types, in this study, we evaluated the expression stability of nine most commonly used endogenous controls (GAPDH, ACTB, 18S rRNA, RPS18, HSP-90, ALAS, HMBS, ACAC, and B2M) in four different tissues of the domestic goat, Capra hircus, including liver, visceral, subcutaneous fat and longissimus muscles, across different experimental treatments (a standard diet prepared using the NRC computer software as control and the same diet plus one mg chromium/day). We used six different software programs for ranking of reference genes and found that individual rankings of the genes differed among them. Additionally, there was a significant difference in ranking patterns of the studied genes among different tissues. A rank aggregation method was applied to combine the ranking lists of the six programs to a consensus ranking. Our results revealed that HSP-90 was nearly always among the two most stable genes in all studied tissues. Therefore, it is recommended for accurate normalization of RT-qPCR data in goats, while GAPDH, ACTB, and RPS18 showed the most varied expressions and should be avoided as reference genes.     

Morphological divergence in the Walton's Mudskipper,Periophthalmus waltoni Koumans, 1941, from the Persian Gulf and Gulf of Oman (Gobioidei: Gobiidae)

The body shape variation among 244 specimens of Periophthalmus waltoni Koumans, 1941, collected from seven stations in the Persian Gulf and Gulf of Oman, was analysed by utilising geometric morphometrics (GM) and truss-based morphometrics methods (TBM). Discriminant function analysis did not show significant differences between the shape of females and males. Canonical variate analysis and cluster analysis classified the specimens in two separate groups of stations: those in the Persian Gulf, and those in the Strait of Hormuz plus Gulf of Oman. Potential factors contributing to the observed variation include differences in physicochemical parameters between the Persian Gulf and the Gulf of Oman.     

Nanoliposomes and Their Applications in Food Nanotechnology

Food nanotechnology involves the utilization of nanocarrier systems to stabilize the bioactive materials against a range of environmental and chemical changes as well as to improve their bioavailability. Nanoliposome technology presents exciting opportunities for food technologists in areas such as encapsulation and controlled release of food materials, as well as the enhanced bioavailability, stability, and shelf-life of sensitive ingredients. Liposomes and nanoliposomes have been used in the food industry to deliver flavors and nutrients and, more recently, have been investigated for their ability to incorporate antimicrobials that could aid in the protection of food products against microbial contamination. In this paper, the main physicochemical properties of liposomes and nanoliposomes are described and some of the industrially applicable methods for their manufacture are reviewed. A summary of the application of nanoliposomes as carrier vehicles of nutrients, nutraceuticals, enzymes, food additives, and food antimicrobials is also presented.     

Interleukin-18 enhances IL-18R/Nox1 binding,and mediates TRAF3IP2-dependent smooth muscle cell migration. Inhibition by simvastatin

We investigated the role of TRAF3 interacting protein 2 (TRAF3IP2), a redox-sensitive adapter protein and an upstream regulator of IKK and JNK in interleukin (IL)-18 induced smooth muscle cell migration, and the mechanism of its inhibition by simvastatin. The pleiotropic cytokine IL-18 induced human coronary artery SMC migration through the induction of TRAF3IP2. IL-18 induced Nox1-dependent ROS generation, TRAF3IP2 expression, and IKK/NF-κB and JNK/AP-1 activation. IL-18 induced its own expression and that of its receptor subunit IL-18Rα. Using co-IP/IB and GST pull-down assays, we show for the first time that the subunits of the IL-18R heterodimer physically associate with Nox1 under basal conditions, and IL-18 appears to enhance their binding. Importantly, the HMG-coA reductase inhibitor simvastatin attenuated IL-18-induced TRAF3IP2 induction. These inhibitory effects were reversed by mevalonate and geranylgeranylpyrophosphate (GGPP), but not by farnesylpyrophosphate (FPP). Interestingly, simvastatin, GGPP, FPP, or Rac1 inhibition did not modulate ectopically expressed TRAF3IP2. These results demonstrate that the promigratory effects of IL-18 are mediated through TRAF3IP2 in a redox-sensitive manner, and this may involve IL-18R/Nox1 physical association. Further, Simvastatin inhibits inducible, but not ectopically-xpressed TRAF3IP2. Targeting TRAF3IP2 may blunt progression of hyperplastic vascular diseases in vivo.