HPV16-E7 Protein T Cell Epitope Prediction and Global Therapeutic Peptide Vaccine Design Based on Human Leukocyte Antigen Frequency: An In-Silico Study

International Journal of Peptide Research and Therapeutics - Cervical cancer is the second most common leading cause of women's death due to cancer worldwide, about 528,000 patients’...     

When to estimate sex ratio in natural populations of insects? A study on sex ratio variations of gall midges within a generation

Precise estimation of arthropods' sex ratio is an important issue in a wide range of ecological studies and biological control programs. Although, in many cases changes in arthropods' sex ratio may be under the control of parents or some symbiotic microorganisms, biased sex ratios in some other species are caused by some extrinsic factors, neglect of which may lead to under/overestimation of true sex ratio. In this paper, we pursued those factors that cause false estimation of sex ratio in insects' species. We studied the predatory gall midge, Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae), an important biological control agent of aphids, that shows protandry (i.e. early male emergence), differential lifespan of sexes, and differential distribution of sexes across habitat. Ten populations of A. aphidimyza were released separately in transparent cages and their sex ratio variations were recorded every 12 hours. The primary sex ratio in this species seems to be slightly male‐biased (52.41% males), however early emergence of males biases the sex ratio up to 72% males in a few hours after emergence. Shortly after the emergence of females, the sex ratio reaches its primary situation, but as a result of male‐biased mortality after mating, the proportion of females increases gradually to 97% by the fourth and fifth days after emergence. These results explicitly suggest that direct estimation of sex ratio in natural populations may be affected by some secondary factors such as differential mortality of sexes, protandry, and differential distribution of males and females over time and/or across habitat.     

Revealing substitution effects on the strength and nature of halogen-hydride interactions: a theoretical study

A quantum chemistry study was carried out to investigate the strength and nature of halogen bond interactions in HXeH···XCCY complexes, where X = Cl, Br and Y = H, F, Cl, Br, CN, NC, C₂H, CH₃, OH, SH, NH₂. Examination of the electrostatic potentials V(r) of the XCCY molecules reveals that the addition of substituents has a significant effect upon the most positive electrostatic potential on the surface of the interacting halogen atom. We found that the magnitude of atomic charges and multipole moments depends upon the halogen atom X and is rather sensitive to the electron-withdrawing/donating power of the remainder of the molecule. An excellent correlation was found between the most positive electrostatic potentials on the halogen atom and the interaction energies. For either HXeH···ClCCY or HXeH···BrCCY complexes, an approximate linear correlation between the interaction energies and halogens multipole moments are established, indicating that the electrostatic and polarization interactions are responsible for the stability of the complexes. According to energy decomposition analysis, it is revealed that the electrostatic interactions are the major source of the attraction in the HXeH···XCCY complexes. Furthermore, the changes in the electrostatic term are mainly responsible for the dependence of interaction energy on the halogen atom.

A Hybrid Likelihood Model for Sequence-Based Disease Association Studies

In the past few years, case-control studies of common diseases have shifted their focus from single genes to whole exomes. New sequencing technologies now routinely detect hundreds of thousands of sequence variants in a single study, many of which are rare or even novel. The limitation of classical single-marker association analysis for rare variants has been a challenge in such studies. A new generation of statistical methods for case-control association studies has been developed to meet this challenge. A common approach to association analysis of rare variants is the burden-style collapsing methods to combine rare variant data within individuals across or within genes. Here, we propose a new hybrid likelihood model that combines a burden test with a test of the position distribution of variants. In extensive simulations and on empirical data from the Dallas Heart Study, the new model demonstrates consistently good power, in particular when applied to a gene set (e.g., multiple candidate genes with shared biological function or pathway), when rare variants cluster in key functional regions of a gene, and when protective variants are present. When applied to data from an ongoing sequencing study of bipolar disorder (191 cases, 107 controls), the model identifies seven gene sets with nominal p-values0.05, of which one MAPK signaling pathway (KEGG) reaches trend-level significance after correcting for multiple testing.     

Bovine serum albumin/gold nanoparticles as a drug delivery system for Curcumin: experimental and computational studies

Abstract

Communicated by Ramaswamy H. Sarma     

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm

Mesenchymal stem cells (MSCs) have been revealed to hold great potential for the development of new treatment approaches for various diseases. However, the clinical use of these cells is limited due to their tumorigenic effects. The therapeutic benefits of MSCs are largely dependent on paracrine factors including extracellular vesicles (EVs). EVs are nano-sized bilayer membrane structures containing lipids, microRNAs and proteins which play key roles in cell-to-cell communications. Because of their lower immunogenicity, tumorigenicity, and easier management, EVs have emerged as a new promising alternative to whole-cell therapy. Therefore, this paper reviews current preclinical studies on the use of EVs derived from human umbilical cord MSCs (hucMSCs) as a therapeutic approach in treatment of several diseases including neurological, cardiovascular, liver, kidney, and bone diseases as well as the cutaneous wound, inflammatory bowel disease, cancers, infertility, and other disorders.     

Aspartyl Protease-Mediated Cleavage of BAG6 Is Necessary for Autophagy and Fungal Resistance in Plants

The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved group of cochaperones that modulate numerous cellular processes. Previously we found that Arabidopsis thaliana BAG6 is required for basal immunity against the fungal phytopathogen Botrytis cinerea. However, the mechanisms by which BAG6 controls immunity are obscure. Here, we address this important question by determining the molecular mechanisms responsible for BAG6-mediated basal resistance. We show that Arabidopsis BAG6 is cleaved in vivo in a caspase-1-like-dependent manner and via a combination of pull-downs, mass spectrometry, yeast two-hybrid assays, and chemical genomics, we demonstrate that BAG6 interacts with a C2 GRAM domain protein (BAGP1) and an aspartyl protease (APCB1), both of which are required for BAG6 processing. Furthermore, fluorescence and transmission electron microscopy established that BAG6 cleavage triggers autophagy in the host that coincides with disease resistance. Targeted inactivation of BAGP1 or APCB1 results in the blocking of BAG6 processing and loss of resistance. Mutation of the cleavage site blocks cleavage and inhibits autophagy in plants; disease resistance is also compromised. Taken together, these results identify a mechanism that couples an aspartyl protease with a molecular cochaperone to trigger autophagy and plant defense, providing a key link between fungal recognition and the induction of cell death and resistance.     

Diversity and Antimicrobial Activity of Actinomycetes Isolated from Lut Desert: The Extremely Arid Climatic Zones of Iran

Lut desert is situated in one of the extremely arid climatic zones of Iran and is one of the hottest deserts in our plant with the extreme fluctuation of temperature over a day. The main objective of this study is to characterize the diversity of the culturable actinomycetes and preliminary evaluation of their extracts as antimicrobial components on drug resistant pathogens. Twenty-four soil samples were collected, successively diluted and inoculated into the different culture media to support the growth of most culturable bacteria including actinomycetes. Phenotypic and molecular methods were used for accurate identification of recovered isolates particularly actinomycetes at the genus and species levels. The isolates were also evaluated for their inhibitory activities against drug resistant Acinetobacter baumannii, Enterococcus faecium, Klebsiella pneumoniae and Staphylococcus aureus. A total of 56 isolates recovered from the samples. Based on phenotypic tests, 41 isolates were identified as actinomycetes, amongst them 8 isolates were active against drug resistant pathogens. Our study revealed Lut desert, as one of the hottest deserts in the world, is the habitat to diverse taxa of bacteria particularly actinomycetes which have potential novel antimicrobial components.

     

Insulin-like growth factor type-1 receptor transactivation in vasoactive peptide and oxidant-induced signaling pathways in vascular smooth muscle cells

Transactivation of epidermal growth factor receptor (EGFR) is a well-documented mechanism by which vasoactive peptides and H2O2 elicit their cellular responses. However, a role for the insulin-like growth factor type-1 receptor (IGF-1R) transactivation in mediating the effects of angiotensin II (Ang II) and H2O2 in vascular smooth muscle cells from different artery types have also been recently recognized. By using a series of pharmacological inhibitors of various growth factor receptor tyrosine kinases and a direct analysis of the phosphorylation status of the beta-subunit of IGF-1R, a requirement of this growth factor receptor in Ang II and H2O2 response has been demonstrated. This review discusses some of the studies that highlight the importance of IGF-1R transactivation in mediating Ang II- and H2O2-induced mitogen-activated protein kinase and protein kinase B signaling pathways.