Rapid BRAF mutation detection in melanoma patients by immunohistochemistry

The V600E mutation is the most common (~90%) activating mutation of the BRAF gene. BRAF mutations have been frequently investigated in melanoma, colorectal cancer and papillary thyroid carcinoma. The importance of the detection of BRAF mutations has been rising by the routine use of Braf inhibitor therapy. We evaluated the usefulness of the BRAF V600E mutation-specific monoclonal antibody (VE1) in metastatic melanoma patients. To confirm the results of immunohistochemistry (IHC), we used COBAS 4800 BRAF V600 mutation test and PCR amplification followed by Sanger sequencing.36 of 105 patients have wild-type BRAF gene, 64 have V600E mutation and 5 of 105 have V600K mutation. Predicting the mutation only by IHC using VE1 antibody, all 58 positively scored specimen were V600E mutant. The V600K, the wild-type patients and 7 patients from the V600E mutant group scored as negative. Thus the specificity is 100% and the positive predictive value is 1 of the IHC method. After processing our data we could establish a cheaper diagnostic algorithm for rapid detection ofBRAF mutation.

Generating CHARMM compatible force field parameters for atrazine

There are many synthetic, drug-like molecules whose interactions with large biomolecules could be partly described by molecular dynamics studies. The parameters necessary to perform an MD simulation are available for biomolecules (proteins, nucleic acids, lipids, carbohydrates) and for many other small chemical compounds with biological relevance. In case of uncharacterized molecules, parameter sets can be calculated using quantummechanical calculations. The optimized geometry, van der Waals, charge, bond, angle and torsion parameters for the photosystem II-inhibitor herbicide, atrazine, were calculated and integrated into a CHARMM-compatible parameter file. The file (.par) is available, along with the coordinates (.pdb), structure (.psf) and topology (.top), and with this four type of data, atrazine may be part of CHARMM-based molecular dynamics simulations, therefore, its interactions with biomolecules can be studied.

Classification of glycosyl hydrolases based on structural homology

Glycosyl hydrolases are a well-known group of enzymes, which hydrolyze the glycosidic bond between carbohydrates, or between a carbohydrate and different molecules. Glycosyl hydrolases play a vital role in the human body, and are widely used in industrial applications. Glycosyl hydrolases classification is based on substrate specificity and amino acid or nucleotide sequence similarity which reflects their evolutionary relationship. Our aim, in this study, was to carry out the classification of glycosyl hydrolases, based solely on structural similarity which was made possible by the several structures available in the databases and the availability of computing power to conduct such a computationally intensive task, in a reasonable time-frame. It was also aimed that the structural similarity based classification be compared to the present classification system. Based on an all-against-all comparison, we conducted a structural comparison of glycosyl hydrolases. The results are presented graphically. The graphical representation defined 24 structurally homologous classes. The classification was validated using Cα - Cα distance analysis and amino acid sequence cluster analysis. Advantages of this method are that – being an automated method – it is fast, simple and reproducible. Glycosyl hydrolases could be classified into 24 separate classes. N-glycosyl and O-glycosyl hydrolases (both forming binding and catalytic domain classes as well) were clearly different, the former consisting of 8 classes, and the latter consisting of 16 classes. Structural classes simplified the previous classification system. This classification represents the current glycosyl hydrolase family system, but also extends it especially concerning the clan system.

General symmetry properties of incommensurately modulated crystals described by projective representations of line groups

After a detailed investigation of some fundamental general orthogonal symmetry properties of incommensurate condensed systems, the line groups are applied for describing the structure of such modulated crystals. It is demonstrated, that use of projective representations of these groups may give a more refined description of such structures and significantly extends applicability of the diffuse scattering formalism.

Molecular modeling of DDT's and it's major metabolites adsorption in the interlaminar space of montmorillonite

A simple adsorption mechanism of the organochloride insecticide DDT and it's most common metabolites DDD and DDE in the interlaminar layer of montmorillonite mineral is discussed in this paper, based on the results of molecular modeling. A model of a simple fragment of the montmorillonite crystal with the interlaminar layer was created and used. The interlaminar layer contained water as a solvent and the ionic forms of sodium or calcium as exchangeable cations along with the molecules of DDT/DDD/DDE. The molecular interactions were simulated by force fields and the results of the simulation could be explained by the physical characteristics of the models which were studied with bioinformatics tools as well. Based on the observed mechanisms, the adsorption of DDT and it's metabolites in the interlaminar layer of montmorillonite is possible and it is partly responsible for the persistent nature of these insecticides.

Early corrective surgery may prevent Baroreflex impairment in congenital heart diseases

Arrhythmias in tetralogy of Fallot (ToF) and transposition of the great arteries (TGA) could be the consequence of reduced baroreflex-sensitivity (BRS). Hypoxia until the first surgical correction in these patients may impair BRS. We aimed to compare the BRS of ToF, TGA and control subjects and test the effect of the timing of operation on BRS. 19 patients with ToF, 22 patients with TGA and 19 healthy controls were enrolled. Carotid pulse pressure (PPc) was similar in ToF and TGA patients but lower in controls. BRS was lower in the ToF group compared to the control or to the TGA groups. The first operation was performed later in patients with ToF than in patients with TGA. Adjustment for PPc attenuated the difference in BRS between ToF and control subjects. Adjustment for age at corrective surgery abolished the difference in BRS between the ToF and the TGA groups. In ToF patients, reduced BRS could be explained by the stiffening of central arteries and the later corrective surgery. Earlier surgical correction may prevent irreversible deterioration of baroreflex-function and arrhythmia development in ToF patients.

Some basic mathematical features of the simultaneous convection anomalous diffusion transport processes

The basic mathematical features of the anomalous diffusion processes are discussed in detail, together with some of the open research subdomains belonging to it. Due to its practical importance in engineering applications, the possibilities of the necessary mathematical refinements are proposed and justified for the general case of the simultaneous convection-anomalous diffusion processes taking place through porous bulk materials.

Growth inhibitory effects of bioactive metabolites in wood extracts of Robinia pseudoacacia L. inhibit the growth of various microorganisms

The need for more efficient use of natural resources recently became apparent. Lowering the amount of harmful chemicals released into the environment is a crucial task. Besides it is essential to seek for novel resources closer to natural origin. The aggressive growth of certain plant species is attributed to their metabolic features as well. Several plant secondary metabolites have been identified recently that are crucial for their intensive spread. These metabolites are only present in particular taxonomic groups. The most important attribute they share is that they regulate the interactions between the plant and the environment. These metabolites often possess traits that inhibit the growth of pathogen microbes. Due to their antimicrobial effects these bioactive substances may be utilized as novel pesticide agents in the future. In our project we assessed the inhibitory effects of various black locust (Robinia pseudoacacia L.) wood extracts on the growth of different microorganisms using agar plate disc diffusion method. Our results suggest that black locust wood extracts evolves comprehensive inhibition against both gram-negative and gram-positive bacteria and Fusarium proliferatum The highest bioactivity was carried by the hexane and methanolic fraction. Further purification using HPLC revealed some particular components that show significant correlation with the inhibitory effects of the extracts. Some extracts were able to lower the infection ability of Fusarium proliferatum in in-vivo infection tests.

Differentiation of food spoilage yeast strains of the Yarrowia group by microsatellite polymerase chain reaction fingerprinting

Yarrowia lipolytica is a frequently reported food spoilage yeast which occurs mainly in meat and milk products. Besides its detrimental role in the food spoilage it has many favourable properties. This yeast also has been developed as a production host for a large variety of biotechnological applications. Some species of the Yarrowia group cannot be differentiated by conventional methods based on phenotypic characteristics, so it is probable that not only Yarrowia lipolytica, but also other species of the Yarrowia group contribute to food spoilage or can have a beneficial role in the industry. A relatively fast, easy and low-cost but reliable method would be useful to differentiate and identify these species properly. Microsatellite PCR fingerprinting method is commonly used for the discrimination of species or strains within species, it is also applied for the identification of yeast species and in many yeast diversity studies, however, its reliability can be queried. The aim of this study was to assess the reliability of microsatellite PCR fingerprinting using (GAC)5 primer in the differentiation and identification of the yeast strains of the Yarrowia group by clustering them using microsatellite-PCR fingerprinting, then identifying them by sequencing the D1/D2 regions of the LSU rDNA of one or a few selected representatives of each cluster. Two hundred and nineteen yeast strains of the Yarrowia group were examined. Using this molecular biological method, yeast strains of the Yarrowia group from raw meat, raw milk, cheese and cottage cheese were assigned to seven species The food spoilage yeast strains of the Yarrowia group can be successfully differentiated by using microsatellite PCR fingerprinting method using (GAC)5 primer, even their identity, thus their diversity can be assessed.