BackgroundAcinetobacter baumannii has emerged as a significant nosocomial pathogen during the last few years, exhibiting resistance to almost all major classes of antibiotics. Alternative treatment options such as vaccines tend to be most promising and cost effective approaches against this resistant pathogen. In the current study, we have explored the pan-genome of A. baumannii followed by immune-proteomics and reverse vaccinology approaches to identify potential core vaccine targets.ResultsThe pan-genome of all available A. baumannii strains (30 complete genomes) is estimated to contain 7,606 gene families and the core genome consists of 2,445 gene families (~32 % of the pan-genome). Phylogenetic tree, comparative genomic and proteomic analysis revealed both intra- and inter genomic similarities and evolutionary relationships. Among the conserved core genome, thirteen proteins, including P pilus assembly protein, pili assembly chaperone, AdeK, PonA, OmpA, general secretion pathway protein D, FhuE receptor, Type VI secretion system OmpA/MotB, TonB dependent siderophore receptor, general secretion pathway protein D, outer membrane protein, peptidoglycan associated lipoprotein and peptidyl-prolyl cis-trans isomerase are identified as highly antigenic. Epitope mapping of the target proteins revealed the presence of antigenic surface exposed 9-mer T-cell epitopes. Protein-protein interaction and functional annotation have shown their involvement in significant biological and molecular processes. The pipeline is validated by predicting already known immunogenic targets against Gram negative pathogen Helicobacter pylori as a positive control.ConclusionThe study, based upon combinatorial approach of pan-genomics, core genomics, proteomics and reverse vaccinology led us to find out potential vaccine candidates against A. baumannii. The comprehensive analysis of all the completely sequenced genomes revealed thirteen putative antigens which could elicit substantial immune response. The integration of computational vaccinology strategies would facilitate in tackling the rapid dissemination of resistant A.baumannii strains. The scarcity of effective antibiotics and the global expansion of sequencing data making this approach desirable in the development of effective vaccines against A. baumannii and other bacterial pathogens.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2951-4) contains supplementary material, which is available to authorized users.

Hepatitis C virus (HCV) vaccines, designed to augment specific T-cell responses, have been designated as an important aspect of effective antiviral treatment. However, despite the current satisfactory progress of these vaccines, extensive past efforts largely remained unsuccessful in mediating clinically relevant anti-HCV activity in humans. In this study, we used a series of immunoinformatics approaches to propose a multiepitope vaccine against HCV by prioritizing 16 conserved epitopes from three viral proteins (i.e., NS34A, NS5A, and NS5B). The prioritised epitopes were tested for their possible antigenic combinations with each other along with linker AAY using structural modelling and epitope–epitope interactions analysis. An adjuvant (β-defensin) at the N-terminal of the construct was added to enhance the immunogenicity of the vaccine construct. Molecular dynamics (MD) simulation revealed the most stable structure of the proposed vaccine. The designed vaccine is potentially antigenic in nature and can form stable and significant interactions with Toll-like receptor 3 and Toll-like receptor 8. The proposed vaccine was also subjected to an in silico cloning approach, which confirmed its expression efficiency. These analyses suggest that the proposed vaccine can elicit specific immune responses against HCV; however, experimental validation is required to confirm the safety and immunogenicity profile of the proposed vaccine construct.

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Hepatocellular carcinoma (HCC) is the world’s third most widespread cancer. Currently available circulating biomarkers for this silently progressing malignancy are not sufficiently specific and sensitive to meet all clinical needs. There is an imminent and pressing need for the identification of novel circulating biomarkers to increase disease-free survival rate. In order to facilitate the selection of the most promising circulating protein biomarkers, we attempted to define an objective method likely to have a significant impact on the analysis of vast data generated from cutting-edge technologies. Current study exploits data available in seven publicly accessible gene and protein databases, unveiling 731 liver-specific proteins through initial enrichment analysis. Verification of expression profiles followed by integration of proteomic datasets, enriched for the cancer secretome, filtered out 20 proteins including 6 previously characterized circulating HCC biomarkers. Finally, interactome analysis of these proteins with midkine (MDK), dickkopf-1 (DKK-1), current standard HCC biomarker alpha-fetoprotein (AFP), its interacting partners in conjunction with HCC-specific circulating and liver deregulated miRNAs target filtration highlighted seven novel statistically significant putative biomarkers including complement component 8, alpha (C8A), mannose binding lectin (MBL2), antithrombin III (SERPINC1), 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), alcohol dehydrogenase 6 (ADH6), beta-ureidopropionase (UPB1) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6). Our proposed methodology provides a swift assortment process for biomarker prioritization that eventually reduces the economic burden of experimental evaluation. Further dedicated validation studies of potential putative biomarkers on HCC patient blood samples are warranted. We hope that the use of such integrative secretome, interactome and miRNAs target filtration approach will accelerate the selection of high-priority biomarkers for other diseases as well, that are more amenable to downstream clinical validation experiments.

Autophagy, an evolutionary conserved multifaceted lysosome-mediated bulk degradation system, plays a vital role in liver pathologies including hepatocellular carcinoma (HCC). Post-translational modifications (PTMs) and genetic variations in autophagy components have emerged as significant determinants of autophagy related proteins. Identification of a comprehensive spectrum of genetic variations and PTMs of autophagy related proteins and their impact at molecular level will greatly expand our understanding of autophagy based regulation. In this study, we attempted to identify high risk missense mutations that are highly damaging to the structure as well as function of autophagy related proteins including LC3A, LC3B, BECN1 and SCD1. Number of putative structural and functional residues, including several sites that undergo PTMs were also identified. In total, 16 high-risk SNPs in LC3A, 18 in LC3B, 40 in BECN1 and 43 in SCD1 were prioritized. Out of these, 2 in LC3A (K49A, K51A), 1 in LC3B (S92C), 6 in BECN1 (S113R, R292C, R292H, Y338C, S346Y, Y352H) and 6 in SCD1 (Y41C, Y55D, R131W, R135Q, R135W, Y151C) coincide with potential PTM sites. Our integrated analysis found LC3B Y113C, BECN1 I403T, SCD1 R126S and SCD1 Y218C as highly deleterious HCC-associated mutations. This study is the first extensive in silico mutational analysis of the LC3A, LC3B, BECN1 and SCD1 proteins. We hope that the observed results will be a valuable resource for in-depth mechanistic insight into future investigations of pathological missense SNPs using an integrated computational platform.

Circular RNAs (circRNAs) are ubiquitously expressed, covalently closed rings, produced by pre-mRNA splicing in a reversed order during post-transcriptional processing. Circularity endows 3′-5′-linked circRNAs with stability and resistance to exonucleolytic degradation which raises the question whether circRNAs may be relevant as potential therapeutic targets or agents. High stability in biological systems is the most remarkable property and a major criterion for why circRNAs could be exploited for a range of RNA-centred medical applications. Even though various biological roles and regulatory functions of circRNAs have been reported, their in-depth study is challenging because of their circular structure and sequence-overlap with linear mRNA counterparts. Moreover, little is known about their role in viral infections and in antiviral immune responses. We believe that an in-depth and detailed understanding of circRNA mediated viral protein regulations will increase our knowledge of the biology of these novel molecules. In this review, we aimed to provide a comprehensive basis and overview on the biogenesis, significance and regulatory roles of circRNAs in the context of antiviral immune responses and viral infections including hepatitis C virus infection, hepatitis B virus infection, hepatitis delta virus infection, influenza A virus infection, Epstein-Barr virus infection, kaposi's sarcoma herpesvirus infection, human cytomegalovirus infection, herpes simplex virus infection, human immunodeficiency virus infection, porcine epidemic diarrhoea virus infection, ORF virus infection, avian leukosis virus infection, simian vacuolating virus 40 infection, transmissible gastroenteritis coronavirus infection, and bovine viral diarrhoea virus infection. We have also discussed the critical regulatory role of circRNAs in provoking antiviral immunity, providing evidence for implications as therapeutic agents and as diagnostic markers.

Among solid tumors, hepatocellular carcinoma (HCC) emerges as a prototypical therapy-resistant tumor. Considering the emerging sorafenib resistance crisis in HCC, future studies are urgently required to overcome resistance. Recently noncoding RNAs (ncRNAs) have emerged as significant regulators in signalling pathways involved in cancer drug resistance and pharmacologically targeting these ncRNAs might be a novel stratagem to reverse drug resistance. In the current study, using a hybrid Petri net based computational model, we have investigated the harmonious effect of miR-17-92 cluster inhibitors/mimics and circular RNAs on sorafenib resistant HCC cells in order to explore potential resistance mechanisms and to identify putative targets for sorafenib-resistant HCC cells. An integrated model was developed that incorporates seven miRNAs belonging to miR-17-92 cluster (hsa-miR-17-5p, hsa-miR-17-3p, hsa-miR-19a, hsa-miR-19b, hsa-miR-18a, hsa-miR-20a and hsa-miR-92) and crosstalk of two signaling pathways (EGFR and IL-6) that are differentially regulated by these miRNAs. The mechanistic connection was proposed by the correlation between members belonging to miR-17-92 cluster and corresponding changes in the protein levels of their targets in HCC, specifically those targets that have verified importance in sorafenib resistance. Current findings uncovered potential pathway features, underlining the significance of developing modulators of this cluster to combat drug resistance in HCC.

The scope of optical sensors and scanners in aquatic media, fluids, and medical diagnostics has been limited by paucity of transparent shielding materials with antifouling potential. In this research endeavor, facile synthesis, characterization, and bioassay of antifouling transparent functional copolymers are reported. Copolymers of 3-sulfopropyl methacrylate (SPMA) and methyl methacrylate (MMA) were synthesized by free radical polymerization in various proportions. Samples PSM20, PSM30, PSM40, PSM50, and PSM60 contain 20%, 30%, 40%, 50%, and 60% SPMA by weight, respectively. Resultant products were characterized by FTIR and 1H-NMR spectroscopy. The synthesized copolymers have exhibited excellent transparency, i.e., 75% to 88%, as determined by the UV-Vis spectroscopic analysis. Transmittance was decreased from 6% to 2% in these copolymers upon changing the concentration of 3-sulfopropyl methacrylate from 20% to 50% owing to bacterial and algal biofilm formation. Water contact angle values were ranged from 18° to 63° and decreased with the increase in the polarity of copolymers. The surface energy lowest value 58 mJ/m2 and highest value 72 mJ/m2 were calculated for PSM20 and PSM50, respectively, by the Chibowski approach and Young equation. Sample PSM50 has exhibited the highest antibacterial activities, i.e., 18 mm and 19 mm, against Escherichia coli and Staphylococcus aureus, respectively, by the disk diffusion method. Copolymer PSM50 has shown minimum algal adhesion for Dictyosphaerium algae as observed by optical microscopy. This lower bacterial and algal adhesion is attributed to higher concentrations of anionic SPMA monomer that cause electrostatic repulsion between functional groups of the polymer and microorganisms. Thus, the resultant PSM50 product has exhibited good potential for optronics shielding application in aquatic medium and medical diagnostics.