Bioinformatics analysis of SARS coronavirus genome polymorphism

BACKGROUND: We have compared 38 isolates of the SARS-CoV complete genome. The main goal was twofold: first, to analyze and compare nucleotide sequences and to identify positions of single nucleotide polymorphism (SNP), insertions and deletions, and second, to group them according to sequence similarity, eventually pointing to phylogeny of SARS-CoV isolates. The comparison is based on genome polymorphism such as insertions or deletions and the number and positions of SNPs. RESULTS: The nucleotide structure of all 38 isolates is presented. Based on insertions and deletions and dissimilarity due to SNPs, the dataset of all the isolates has been qualitatively classified into three groups each having their own subgroups. These are the A-group with "regular" isolates (no insertions / deletions except for 5' and 3' ends), the B-group of isolates with "long insertions", and the C-group of isolates with "many individual" insertions and deletions. The isolate with the smallest average number of SNPs, compared to other isolates, has been identified (TWH). The density distribution of SNPs, insertions and deletions for each group or subgroup, as well as cumulatively for all the isolates is also presented, along with the gene map for TWH. Since individual SNPs may have occurred at random, positions corresponding to multiple SNPs (occurring in two or more isolates) are identified and presented. This result revises some previous results of a similar type. Amino acid changes caused by multiple SNPs are also identified (for the annotated sequences, as well as presupposed amino acid changes for non-annotated ones). Exact SNP positions for the isolates in each group or subgroup are presented. Finally, a phylogenetic tree for the SARS-CoV isolates has been produced using the CLUSTALW program, showing high compatibility with former qualitative classification. CONCLUSIONS: The comparative study of SARS-CoV isolates provides essential information for genome polymorphism, indication of strain differences and variants evolution. It may help with the development of effective treatment

The mechanism of the NH4 ion oscillatory transport across the excitable cell membrane

This paper presents results on typical oscillations of the membrane potential induced by the excitation of the cell membrane by different concentrations of the NH4Cl solution. The existence of four classes of oscillations of the membrane potential and several different single and local impulses rhythmically occurring were determined. It is known that the oscillatory processes of the membrane potential are in direct dependence on oscillatory transport processes of NH4 and Cl ions across the excitable cell membrane. A hypothesis on a possible mechanism of oscillatory transport processes of NH4 and Cl ions across the excitable cell membrane is also presented

Bioinformatics analysis of disordered proteins in prokaryotes

<p>Abstract</p> <p>Background</p> <p>A significant number of proteins have been shown to be intrinsically disordered, meaning that they lack a fixed 3 D structure or contain regions that do not posses a well defined 3 D structure. It has also been proven that a protein's disorder content is related to its function. We have performed an exhaustive analysis and comparison of the disorder content of proteins from prokaryotic organisms (i.e., superkingdoms Archaea and Bacteria) with respect to functional categories they belong to, i.e., Clusters of Orthologous Groups of proteins (COGs) and groups of COGs-Cellular processes (Cp), Information storage and processing (Isp), Metabolism (Me) and Poorly characterized (Pc).</p> <p>We also analyzed the disorder content of proteins with respect to various genomic, metabolic and ecological characteristics of the organism they belong to. We used correlations and association rule mining in order to identify the most confident associations between specific modalities of the characteristics considered and disorder content.</p> <p>Results</p> <p>Bacteria are shown to have a somewhat higher level of protein disorder than archaea, except for proteins in the Me functional group. It is demonstrated that the Isp and Cp functional groups in particular (L-repair function and N-cell motility and secretion COGs of proteins in specific) possess the highest disorder content, while Me proteins, in general, posses the lowest. Disorder fractions have been confirmed to have the lowest level for the so-called order-promoting amino acids and the highest level for the so-called disorder promoters.</p> <p>For each pair of organism characteristics, specific modalities are identified with the maximum disorder proteins in the corresponding organisms, e.g., high genome size-high GC content organisms, facultative anaerobic-low GC content organisms, aerobic-high genome size organisms, etc. Maximum disorder in archaea is observed for high GC content-low genome size organisms, high GC content-facultative anaerobic or aquatic or mesophilic organisms, etc. Maximum disorder in bacteria is observed for high GC content-high genome size organisms, high genome size-aerobic organisms, etc.</p> <p>Some of the most reliable association rules mined establish relationships between high GC content and high protein disorder, medium GC content and both medium and low protein disorder, anaerobic organisms and medium protein disorder, Gammaproteobacteria and low protein disorder, etc. A web site <it>Prokaryote Disorder Database </it>has been designed and implemented at the address <url>http://bioinfo.matf.bg.ac.rs/disorder</url>, which contains complete results of the analysis of protein disorder performed for 296 prokaryotic completely sequenced genomes.</p> <p>Conclusions</p> <p>Exhaustive disorder analysis has been performed by functional classes of proteins, for a larger dataset of prokaryotic organisms than previously done. Results obtained are well correlated to those previously published, with some extension in the range of disorder level and clear distinction between functional classes of proteins. Wide correlation and association analysis between protein disorder and genomic and ecological characteristics has been performed for the first time. The results obtained give insight into multi-relationships among the characteristics and protein disorder. Such analysis provides for better understanding of the evolutionary process and may be useful for taxon determination. The main drawback of the approach is the fact that the disorder considered has been predicted and not experimentally established.</p

Numerical optimisation of processes in the furnace considering NOx emission and efficiency of utility boiler

Razvijen je matematički model, namenjen za predviđanje procesa u energetskim parnim kotlovima TE Kostolac B tangencijalno loženim sprašenim lignitom. Model je primenjen za numeričku analizu rada kotla radi smanjenja emisije NOx, uz istovremeno održavanje visokog stepena korisnosti kotla. Kompleksni dvofazni tok gas-čestice modeliran je Ojler-Lagranževim pristupom. Povezivanje faza je ostvareno kuplovanjem pomoću PSI-Cell koncepta. Radi ostvarivanja željenih analiza, ugrađen je pod-model formiranja/destrukcije NO, unutar složenog koda za sagorevanje, koji se koristi za predviđanje emisije na izlazu iz ložišta. Modelirani su termički i gorivi NO, kao najuticajniji oksidi azota pri sagorevanju ugljenog praha. Proračunski program je razvijen radi lakše upotrebe od strane inženjerskog osoblja prilikom analiza procesa u kotlovskim postrojenjima. Numeričke simulacije su izvršene za različite radne uslove kotla, prilikom loženja lignitom sa kopa Drmno. Suprotstavljeni zahtevi a smanjenjem emisije i efikasnim sagorevanjem, sa osvrtom na bezbedan rad pregrejača pare često zahtevaju rad kotla u uskim granicama radnih parametara, koji su utvrđeni pomoću termičkog proračuna kotla.Mathematical model, aimed for prediction of processes in TE Kostolac B power plant utility boiler furnace tangentially fired by pulverized lignite, was developed in-house. The model was applied in numerical analysis of boiler operation, in order to reduce NOx emission by combustion modifications in the furnace, while maintaining high efficiency of the boiler unit. Complex two-phase gas-particle flow was modelled using Euler-Lagrange approach. Coupling between phases was done by using PSI-Cell concept. In order to perform necessary analysis, NO formation/destruction sub-model was implemented, within comprehensive combustion code, used to predict emission from the furnace. Thermal and fuel NO were modelled, as the most influential nitrogen oxides during pulverized coal combustion process. The computational code was developed to be easily used by engineering staff dealing with the process analysis in boiler units. Numerical simulations were performed for the boiler fired by the lignite Drmno, under different operating conditions. Contradictory requirements with respect to emission reduction and efficient combustion with safe operation of super-heaters often require boiler to operate within narrow limits of operation parameters, which is determined by means of the boiler thermal calculation

Statistička zavisnost sekundarne strukture proteina od frekvencije digrama aminokiselina

The statistical dependence of protein secondary structure on amino acid bigram frequencies was studied. Proteins in the PDBSELECT subset of the Protein Data Bank database were investigated. Protein secondary structures were determined using DSSP software. The conditional probabilities of protein secondary structures were calculated and presented. The results on bigrams show the frequencies of all the possible bigrams in all secondary structure types. These results elucidate some factors important for the prediction of the secondary structures of proteins based on the amino acid sequence. © 2017, CI and CEQ. All rights reserved.U radu je opisana statistička zavisnost sekundarne strukture proteina od bigrama aminokiselina. Istraživanje je urađeno na proteinima koji se nalaze u podskupu PDBSELECT baze podataka o proteinima Protein Data Bank (PDB). Sekundarne strukture proteina su određene primenom programa DSSP. Izračunate su i prikazane uslovne verovatnoće pojavljivanja različitih sekundarnih struktura. Rezultati za bigrame su prikazani za sve tipove sekundarnih struktura. Rezultati ukazuju na faktore koji su značajni za predviđanje sekundarne strukture proteina koje je zasnovano na redosledu aminokiselina u proteinu

The Impact of EU Norms and Policies on Consumer Protection Enforcement in Serbia

Pursuant to its 2008 Stabilization and Association Agreement governing the process of EU integration, Serbia is obliged to align its consumer protection standards (including those related to enforcement) with those of the EU. This article considers the overall approach to enforcement of consumer law in Serbia, focussing in particular on the extent to which EU enforcement principles have been successfully exported to Serbia and whether the goals of EU consumer policy have been achieved. It argues that the incorporation of EU norms has brought fundamental changes to Serbian enforcement mechanisms at a formal level, such as in relation to mediation processes as well as the introduction of injunctions for the protection of collective consumer interests. In practice, however, the impact of this incorporation is quite limited. A number of factors that restrict the practical effectiveness of the mediation processes and injunctions required by EU law are explored in the article, including weak sanctions, excessive reliance on poorly resourced consumer organizations, absence of a business culture of compliance or a sophisticated and determined consumer protection enforcement culture sufficiently grounded in expertise, as well as an overarching political, legislative, and institutional instability. These factors also undermine the general aim of EU policy to achieve effective consumer protection enforcement in the Serbian context

Role of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Axis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is primarily diagnosed in the latter stages of disease progression and is the third leading cause of cancer deaths worldwide. Thus, there is a need to find biomarkers of early HCC as well as the development of more effective treatments for the disease. Sphingosine-1-phosphate (S1P) is a pleiotropic lipid signaling molecule produced by two isoforms of sphingosine kinase (SphK1 and SphK2) that is involved in regulation of many aspects of mammalian physiology and pathophysiology, including inflammation, epithelial and endothelial barrier function, cancer, and metastasis, among many others. Abundant evidence indicates that SphK1 and S1P promote cancer progression and metastasis in multiple types of cancers. However, the role of SphK/S1P in HCC is less well studied. Here, we review the current state of knowledge of SphKs and S1P in HCC, including evidence for the correlation of SphK1 expression and S1P levels with progression of HCC and negative outcomes, and discuss how this information could lead to the design of more effective diagnostic and treatment modalities for HCC

Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells

Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships