Prediction of peptides binding to MHC class I alleles by partial periodic pattern mining

MHC (Major Histocompatibility Complex) is a key player in the immune response of an organism. It is important to be able to predict which antigenic peptides will bind to a specific MHC allele and which will not, creating possibilities for controlling immune response and for the applications of immunotherapy. However, a problem for MHC class I is the presence of bulges and loops in the peptides, changing the total length. Most machine learning methods in use today require the sequences to be of same length to successfully mine the binding motifs. We propose the use of time-based data mining methods in motif mining to be able to mine motifs position-independently. Also, the information for both binding and non-binding peptides is used on the contrary to the other methods which only rely on binding peptides. The prediction results are between 60-95% for the tested alleles

Prediction of peptides binding to MHC class I alleles by partial periodic pattern mining

MHC (Major Histocompatibility Complex) is a key player in the immune response of an organism. It is important to be able to predict which antigenic peptides will bind to a spe-cific MHC allele and which will not, creating possibilities for controlling immune response and for the applications of immunotherapy. However a problem encountered in the computational binding prediction methods for MHC class I is the presence of bulges and loops in the peptides, changing the total length. Most machine learning methods in use to-day require the sequences to be of same length to success-fully mine the binding motifs. We propose the use of time-based data mining methods in motif mining to be able to mine motifs position-independently. Also, the information for both binding and non-binding peptides are used on the contrary to the other methods which only rely on binding peptides. The prediction results are between 70-80% for the tested alleles

The Internationalization of Sources of Labor Law

This article examines in depth an important but underappreciated development in international labor law: how norms promulgated by the International Labor Organization (ILO) have affected the development and implementation of domestic labor laws and practices since the early 1990s. The newly globalized focus of labor law—energized by substantial expansions in international trade and investment—has been recognized by scholars, practitioners, and governments, but it has not previously been explored and analyzed in this systematic way. The article focuses on two central regulatory areas—child labor and freedom of association—and relies on doctrinal and policy developments in these areas, as evidenced by the actions of legislatures, courts, and executive branches in more than 20 countries. In doing so, the article addresses how international labor standards have influenced national labor law and practice in the Americas (excluding the U.S.)—directly through the soft-law route of convention ratification and ILO supervisory monitoring, and indirectly through trade agreement labor provisions that incorporate ILO norms. The resultant changes in domestic laws and practices have been evolutionary rather than transformative, and developments in law outpace those in practice, but within these parameters the changes have been substantial. The article then places this internationalizing trend in the context of two recognized theories that seek to explain the socialization of human rights law

Prediction of peptides binding to MHC class I and II alleles by temporal motif mining

Background: MHC (Major Histocompatibility Complex) is a key player in the immune response of most vertebrates. The computational prediction of whether a given antigenic peptide will bind to a specific MHC allele is important in the development of vaccines for emerging pathogens, the creation of possibilities for controlling immune response, and for the applications of immunotherapy. One of the problems that make this computational prediction difficult is the detection of the binding core region in peptides, coupled with the presence of bulges and loops causing variations in the total sequence length. Most machine learning methods require the sequences to be of the same length to successfully discover the binding motifs, ignoring the length variance in both motif mining and prediction steps. In order to overcome this limitation, we propose the use of time-based motif mining methods that work position-independently. Results: The prediction method was tested on a benchmark set of 28 different alleles for MHC class I and 27 different alleles for MHC class II. The obtained results are comparable to the state of the art methods for both MHC classes, surpassing the published results for some alleles. The average prediction AUC values are 0.897 for class I, and 0.858 for class II. Conclusions: Temporal motif mining using partial periodic patterns can capture information about the sequences well enough to predict the binding of the peptides and is comparable to state of the art methods in the literature. Unlike neural networks or matrix based predictors, our proposed method does not depend on peptide length and can work with both short and long fragments. This advantage allows better use of the available training data and the prediction of peptides of uncommon lengths

Clustering of protein families into functional subtypes using Relative Complexity Measure with reduced amino acid alphabets

Background: Phylogenetic analysis can be used to divide a protein family into subfamilies in the absence of experimental information. Most phylogenetic analysis methods utilize multiple alignment of sequences and are based on an evolutionary model. However, multiple alignment is not an automated procedure and requires human intervention to maintain alignment integrity and to produce phylogenies consistent with the functional splits in underlying sequences. To address this problem, we propose to use the alignment-free Relative Complexity Measure (RCM) combined with reduced amino acid alphabets to cluster protein families into functional subtypes purely on sequence criteria. Comparison with an alignment-based approach was also carried out to test the quality of the clustering. Results: We demonstrate the robustness of RCM with reduced alphabets in clustering of protein sequences into families in a simulated dataset and seven well-characterized protein datasets. On protein datasets, crotonases, mandelate racemases, nucleotidyl cyclases and glycoside hydrolase family 2 were clustered into subfamilies with 100% accuracy whereas acyl transferase domains, haloacid dehalogenases, and vicinal oxygen chelates could be assigned to subfamilies with 97.2%, 96.9% and 92.2% accuracies, respectively. Conclusions: The overall combination of methods in this paper is useful for clustering protein families into subtypes based on solely protein sequence information. The method is also flexible and computationally fast because it does not require multiple alignment of sequences

Determınatıon of toxıcıty of gaseous ozone agaınst adult stages of German Cockroach (Blatella germanıca L.): Poster

In this study, the effects of two different concentrations of ozone gas (16.7 and 33.3 mg / L) against Blatella germanica adults at different exposure times (10, 20, 30, 40 and 50 minutes) were investigated under laboratory conditions. It was determined that the ozone gas had a noticeable effect on mortality of B. germanica adults. In general, ozone gas caused higher paralyisis-mortality rates of B. germanica adults than mortality rates of B.germanica adults at both concentrations and all exposure times. A concentration of 33.3 mg / L of ozone gas with 40 and 50 minute exposure times killed all cockroach adults after 24 hours. On the other hand, 16.7 mg / L concentration of ozone gas with 50 minute exposure time killed 90% of the B. germanica adults after 24 hours. When ozone gas is evaluated in terms of exposure time to B. germanica adults, the concentration of 33.3 mg / L of ozone gas with 10-20 minute exposure times caused 65 % adult mortality, with 30 minute exposure time caused 90% adult mortality and with 50 minute exposure times caused 100 % adult mortality after 24 hours. At a concentration of 16.7 mg / L of ozone gas, as the exposure times increased, the adult mortalities gradually increased after 24 hours and the adult mortality reached 90% with 50 minute exposure times. All these results show that ozone gas (33.3 mg / L) with 40-50 minute exposure times can successfully control B.germanica adults.In this study, the effects of two different concentrations of ozone gas (16.7 and 33.3 mg / L) against Blatella germanica adults at different exposure times (10, 20, 30, 40 and 50 minutes) were investigated under laboratory conditions. It was determined that the ozone gas had a noticeable effect on mortality of B. germanica adults. In general, ozone gas caused higher paralyisis-mortality rates of B. germanica adults than mortality rates of B.germanica adults at both concentrations and all exposure times. A concentration of 33.3 mg / L of ozone gas with 40 and 50 minute exposure times killed all cockroach adults after 24 hours. On the other hand, 16.7 mg / L concentration of ozone gas with 50 minute exposure time killed 90% of the B. germanica adults after 24 hours. When ozone gas is evaluated in terms of exposure time to B. germanica adults, the concentration of 33.3 mg / L of ozone gas with 10-20 minute exposure times caused 65 % adult mortality, with 30 minute exposure time caused 90% adult mortality and with 50 minute exposure times caused 100 % adult mortality after 24 hours. At a concentration of 16.7 mg / L of ozone gas, as the exposure times increased, the adult mortalities gradually increased after 24 hours and the adult mortality reached 90% with 50 minute exposure times. All these results show that ozone gas (33.3 mg / L) with 40-50 minute exposure times can successfully control B.germanica adults

Preparation and characterization of non-viral gene delivery systems with pEGFP-C1 Plasmid DNA

In recent years, non-viral delivery systems for plasmid DNA have become particularly important. They can overcome the disadvantages of viral systems such as insertional mutagenesis and unpredicted immunogenicity. Some additional advantages of non-viral gene delivery systems are; good stability, low cost, targetability, delivery of a high amount of genetic materials. The aim of the study was to develop novel non-viral nanosystems suitable for gene delivery. Two formulations were developed for this purpose: water-in-oil microemulsion (ME) and solid lipid nanoparticles (SLN). The microemulsion was composed of Peceol, Tween 80, Plurol oleique, ethanol and water. The SLN was consisting of Precirol, Esterquat-1 (EQ1), Tween 80, Lecithin, ethanol and water. Characterization studies were carried out by measuring particle size, zeta potential, viscosity and pH. TEM imaging was performed on SLN formulations. Protection against DNase I degradation was examined. Cytotoxicity and transfection efficacy of selected formulations were tested on L929 mouse fibroblast cells. Particle sizes of complexes were below 100 nm and with high positive zeta potential. TEM images revealed that SLNs are spherical. The SLN:DNA complexes have low toxicity and good transfection ability. All results showed that the developed SLN formulations can be considered as suitable non-viral gene delivery systems

Sulfur dioxide derivative prevents the prolongation of action potential during the isoproterenol-induced hypertrophy of rat cardiomyocytes

Exogenous SO2 is toxic especially to the pulmonary and cardiovascular system, similar to nitric-oxide, carbon-monoxide, and hydrogen-sulfide. Endogenous SO2 is produced in many cell types. The SO2 content of the rat heart has been observed to substantially decrease during isoproterenol-induced hypertrophy. This study sought to determine whether an SO2 derivative could inhibit the prolongation of action potentials during the isoproterenol-induced hypertrophy of rat cardiomyocytes and explore the ionic currents. Alongside electrocardiogram recordings, the voltage and current- clamped measurements were conducted in the enzymatically isolated left ventricular cardiomyocytes of Wistar rats. The consistency of the results was evaluated by the novel mathematical electrophysiology model. Our results show that SO2 significantly blocked the prolongation of QT-interval and action potential duration. Furthermore, SO2 did not substantially affect the Na+ currents and did not improve the decreased steady- state and transient outward K+ currents, but it reverted the reduced L-type Ca2+ currents (ICaL) to the physiological levels. Altered inactivation of ICaL was remarkably recovered by SO2. Interestingly, SO2 significantly increased the Ca2+ transients in hypertrophic rat hearts. Our mathematical model also confirmed the mechanism of the SO2 effect. Our findings suggest that the shortening mechanism of SO2 is related to the Ca2+ dependent inactivation kinetics of the Ca2+ current.This study was supported in part by Akdeniz University Scientific Research Coordination Unit (Project No: 2012.02.0122.009) and The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 117F020). These funding sources had no involvement in study design, writing of the report, decision to publish, or the collection, analysis, and interpretation of data

Macromolecules Influence Cellular Competence and Expression Level of IGFs Genes in Bovine Oocytes In Vitro

Simple Summary The macromolecule content of culture media can affect the maturation competence of oocytes, which influences the subsequent in vitro development of embryos. This study was designed to determine the effects of macromolecules on cellular competence and the transcript level of insulin-like growth factors (IGF1, IGF2) and their receptors in bovine oocytes. The current study showed that bovine serum albumin (BSA) and fetal calf serum (FCS) improved nuclear maturation and protein biosynthesis (especially FCS). Polyvinyl alcohol did not support the antioxidant defense mechanism due to decreased glutathione peroxidase enzyme activity. The expression of the IGF1 gene could not be detected in all experimental groups, but BSA and FCS increased the transcript level of the IGF2 gene. Moreover, oocyte maturation with BSA increased the transcript level of the IGF1R gene, whereas the transcript level of the IGF2R gene was similar among macromolecule supplementation groups. The BSA and FCS could improve in vitro bovine oocyte development due to supporting cellular characteristics. In vitro maturation (IVM) of mammalian oocytes, which influences subsequent in vitro development of embryos, is affected by the macromolecule content in culture media for the success of oocyte maturation competence, in which the cytoplasmic and nuclear reprogramming events occur. The insulin-like growth factor family (IGFs) promotes the maturation of bovine oocytes and the expansion of cumulus cells and also inhibits apoptosis. This study was, therefore, designed to examine the effects of macromolecules (bovine serum albumin, BSA; fetal calf serum, FCS; and polyvinyl alcohol, PVA) on in vitro nuclear maturation, total cellular protein, glutathione peroxidase (GPx) enzyme activity, and the gene expression level of IGF1, IGF2, and their receptor in bovine oocytes. Oocytes obtained from bovine ovaries were cultured in bicarbonate-buffered medium 199 supplemented with 4 mg/mL BSA, 10% FCS, 1 mg/mL PVA, and without macromolecule supplement (control) during 22 h in the air with a humidified atmosphere and 5% CO2 at 38.5 degrees C temperature. Supplementation of BSA and FCS increased (chi(2) = 9.84; p < 0.05) the percentages of oocytes that reached metaphase II compared to the control and PVA. The amount of protein per ml of cell extracts of oocytes matured in FCS supplemented culture media was higher (p < 0.05) than the oocytes in the PVA and control. The levels of GPx enzyme activity in cell extracts isolated from oocytes in each experimental group did not change over time, but the GPx enzyme activity in oocytes matured in PVA-supplemented culture media was lower (p < 0.05) than in oocytes in the other experimental groups. Transcript for the IGF1 gene was not detected in all experimental groups, but the supplementation of BSA and FCS significantly elevated the transcript level of the IGF2 gene. In addition, the maturation of oocytes with BSA-supplemented media increased the transcript level of the IGF1R gene, whereas the transcript level of the IGF2R gene was similar among macromolecule supplementation groups. The current study concluded that BSA and FCS could improve in vitro bovine oocyte development due to supporting nuclear maturation and increasing the total cellular protein content, GPx enzyme, and transcript activity