Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: <i>In–silico</i> study

<div><p>Recent evidences suggest that human gut microbiota with major component as bacteria can induce immunity. It is also known that gut lining depletes with ageing and that there is increased risk of autoimmune and inflammatory disorders with ageing. It is therefore likely that both may be correlated as depletion of gut lining exposes the gut bacterial antigens to host immune mechanisms, which may induce immunity to certain bacterial proteins, but at the same time such immunity may also be auto-immunogenic to host. This autoimmunity may make a protein molecule nonfunctional and thereby may be involved in late onset metabolic, autoimmune and inflammatory disorders such as, Diabetes, Rheumatoid Arthritis, Hyperlipidemias and Cancer. In this <i>in-silico</i> study we found a large number of peptides identical between human and gut bacteria which were binding to HLA-II alleles, and hence, likely to be auto-immunogenic. Further we observed that such autoimmune candidates were enriched in bacterial species belonging to <i>Firmicutes</i> and <i>Proteobacteria</i> phyla, which lead us to conclude that these phyla may have higher disease impact in genetically predisposed individuals. Functional annotation of human proteins homologous to candidate gut-bacterial peptides showed significant enrichment in metabolic processes and pathways. Cognitive trait, Ageing, Alzheimer, Type 2 diabetes, Chronic Kidney Failure (CKF), Chronic Obstructive Pulmonary Disease (COPD) and various Cancers were the major diseases represented in the dataset. This dataset provides us with gut bacterial autoimmune candidates which can be studied for their clinical significance in late onset diseases.</p></div

Methodology adopted for identifying gut bacterial peptides with auto-immunity potential (candidate peptides) and their functional annotation.

<p>Methodology adopted for identifying gut bacterial peptides with auto-immunity potential (candidate peptides) and their functional annotation.</p

Clustered heatmap of human candidate proteins associated with late onset complex diseases and their binding affinity threshold with common HLA class II alleles.

<p>Binding affinity threshold [range: 1(red)– 11(green)]. Lower the threshold higher is the binding affinity with particular HLA class II allele. Human candidate proteins and the homologous gut bacterial proteins (Hu. protein_Bac. Protein, as provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0180518#pone.0180518.s002" target="_blank">S1 Table</a>) have been indicated on the y-axis. The common HLA class II alleles tested have been indicated on x-axis. Only, human candidate proteins depicted in Fig 2 and having common HLA class II binding affinity are represented here.</p

Human candidate proteins and their significant association with different KEGG pathways.

<p>Human candidate proteins and their significant association with different KEGG pathways.</p

Human candidate proteins and their expression in different tissues.

<p>Human candidate proteins and their expression in different tissues.</p

Solid State Assemblies and Photophysical Characteristics of Linear and Bent-Core π‑Conjugated Oligophenylenevinylenes

New classes of luminescent linear, bent-core, and star-shaped oligophenylenevinylenes (OPVs) having 1,4-para and 1,3-meta rigid aromatic cores were designed and developed. 3-Pentadecylphenol, a renewable resource molecule, was chosen as the flexible unit at the longitudinal or middle position of the OPV aromatic core for solid state ordering. Depending upon the nature of the π-core, the OPVs exhibited either mosaic-type liquid crystalline textures or spherulitic crystalline solids. The enthalpies of melting transitions revealed that the bent-core OPV structure showed enhanced solid state packing compared to linear or star-shaped OPVs. Small and wide-angle X-ray diffraction analysis confirmed layered-like assemblies in OPV molecules. Photophysical experiments such as excitation, emission, and time-resolved fluorescence decay dynamics were carried out to trace the molecular self-organization of OPV chromophores. Time correlated single photon counting technique (TCSPC) luminescent decay profiles and decay lifetimes (τ₁ and τ₂ values) revealed that the OPV chromophores showed faster exciton decay in the tightly packed bent-core structure. The weakly packed star-shaped OPV showed enhanced excited state luminescence stability up to 10 ns. A direct correlation between the OPV chemical structure, solid state ordering, and photophysical characteristics was established

Interactions between Sulpha Drugs and Magnesium Chloride in Aqueous Solutions at <i>T</i> = (288.15 to 318.15) K: Volumetric and Viscometric Approach

The densities (ρ) and viscosities (η) for sulphanilamide, sulphanilic acid, and sulphosalicylic acid dihydrate in aqueous solutions of magnesium chloride hexahydrate (0.05, 0.1, 0.25, and 0.5) mol·kg^–1 at temperatures from (288.15 to 318.15) K have been measured by using vibrating tube digital densimeter and Micro–Ubbelohde type capillary viscometer, respectively. These data have been used to obtain partial molar volumes (<i>V</i>₂⁰) at infinite dilution and viscosity <i>B</i> coefficients. The present partial molar volumes and <i>B</i>-coefficient data in conjunction with that reported in water have further been used to calculate the corresponding transfer parameters (Δ_tr<i>V</i>₂⁰ and Δ_tr<i>B</i>). The results have been compared with the data already reported for these drugs in aqueous sodium chloride solutions

Theoretical study on the nature of S···H and O ··· H hydrogen bonds

<div><p>Hydrogen bond acceptor ability of sulfur and oxygen has been analyzed in the adducts of dimethyl sulfide ((CH₃)₂S) and dimethyl ether ((CH₃)₂O) with H₂O, CH₃OH, HCOOH, NH₂OH, CH₃NH₂, NH₂NH₂, HCONH₂, HF and HCl. The stabilization energies have been evaluated using MP2/aug-cc-pVDZ, B3LYP/aug-cc-pVDZ, gaussian2 (G2) and complete basis set (CBS) theoretical levels. The contributors to stabilization energies are explored by employing symmetry adapted perturbation theory analysis, natural bond orbital analysis in addition to molecular orbital methods. Electrostatic component is the major contributor toward stabilization energy in both the type of adducts involving (CH₃)₂S and (CH₃)₂O which has been assigned to secondary electrostatic interactions. The second important contributor to comparable stabilization energies in the two series is the repulsive <i>E</i>_exch component which is relatively higher in adducts of (CH₃)₂O because of the relatively longer proximity of the monomeric units arising from smaller size of oxygen.</p></div

DataSheet_1_Genome-wide characterization of FK506-binding proteins, parvulins and phospho-tyrosyl phosphatase activators in wheat and their regulation by heat stress.pdf

Peptidyl-prolyl cis-trans isomerases (PPIases) are ubiquitous proteins which are essential for cis-trans isomerisation of peptide bonds preceding the proline residue. PPIases are categorized into four sub-families viz., cyclophilins, FK506-binding proteins (FKBPs), parvulins and protein phosphatase 2A phosphatase activators (PTPAs). Apart from catalysing the cis-trans isomerization, these proteins have also been implicated in diverse cellular functions. Though PPIases have been identified in several important crop plants, information on these proteins, except cyclophilins, is scanty in wheat. In order to understand the role of these genes in wheat, we carried out genome-wide identification using computational approaches. The present study resulted in identification of 71 FKBP (TaFKBP) 12 parvulin (TaPar) and 3 PTPA (TaPTPA) genes in hexaploid wheat genome, which are distributed on different chromosomes with uneven gene densities. The TaFKBP and TaPar proteins, besides PPIase domain, also contain additional domains, indicating functional diversification. In silico prediction also revealed that TaFKBPs are localized to ER, nucleus, chloroplast and cytoplasm, while the TaPars are confined to cytoplasm and nucleus. The TaPTPAs, on the contrary, appear to be present only in the cytoplasm. Evolutionary studies predicted that most of the TaFKBP, TaPar and TaPTPA genes in hexaploid wheat have been derived from their progenitor species, with some events of loss or gain. Syntenic analysis revealed the presence of many collinear blocks of TaFKBP genes in wheat and its sub-genome donors. qRT-PCR analysis demonstrated that expression of TaFKBP and TaPar genes is regulated differentially by heat stress, suggesting their likely involvement in thermotolerance. The findings of this study will provide basis for further functional characterization of these genes and their likely applications in crop improvement.</p

DataSheet1_Exported J domain proteins of the human malaria parasite.DOCX

The heat shock protein 40 (Hsp40) family, also called J domain proteins (JDPs), regulate their Hsp70 partners by ensuring that they are engaging the right substrate at the right time and in the right location within the cell. A number of JDPs can serve as co-chaperone for a particular Hsp70, and so one generally finds many more JDPs than Hsp70s in the cell. In humans there are 13 Hsp70s and 49 JDPs. The human malaria parasite, Plasmodium falciparum, has dedicated an unusually large proportion of its genome to molecular chaperones, with a disproportionately high number of JDPs (PfJDPs) of 49 members. Interestingly, just under half of the PfJDPs are exported into the host cell during the asexual stage of the life cycle, when the malaria parasite invades mature red blood cells. Recent evidence suggests that these PfJDPs may be functionalizing both host and parasite Hsp70s within the infected red blood cell, and thereby driving the renovation of the host cell towards pathological ends. PfJDPs have been found to localize to the host cytosol, mobile structures within the host cytosol (so called “J Dots”), the host plasma membrane, and specialized structures associated with malaria pathology such as the knobs. A number of these exported PfJDPs are essential, and there is growing experimental evidence that they are important for the survival and pathogenesis of the malaria parasite. This review critiques our understanding of the important role these exported PfJDPs play at the host-parasite interface.</p