Screening for C283Y gamma-sarcoglycan mutation in a high-risk group of Bulgarian Gypsies: evidence for a geographical localization and a non-random distribution among Gypsy subgroups

Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive disorder caused by mutations in the gamma-sarcoglycan gene. A 'private' Gypsy C283Y mutation was detected in this gene. Recently, a number of LGMD2C-affected families belonging to a Xoroxane Gypsy group have been detected in eastern Bulgaria and all of these cases were due to the same mutation. We have screened 300 unrelated individuals of reproductive age from this high-risk Xoroxane Gypsy group, settled in Sliven. The genetic test by PCR-SSCP analysis for the C283Y mutation revealed a carrier frequency of 7.7%. The screened sample was ethnically not homogeneous. It was divided in ethnonym groups on the basis of social and economic status, language characteristics and trades. We found that the C283Y was not randomly distributed among the Gypsy subgroups. The disease seemed to be limited to the Xoroxane Gypsy group and geographically localized in eastern Bulgaria.     

The effect of orthophosphate on the gravimetric determination of pyrophosphate

The effect of orthophosphate on the precipitation of zinc pyrophosphate has been examined and it is shown that co-precipitation of the orthophosphate at pH 3.4-3.6 is serious if the orthophosphate concentration is >0.02M. Even with lower concentrations an error of up to +2% may occur.     

Determination of photolysis constants of some aliphatic amines in the mixed solvent 80% dimethylsulfoxide/20% water and assessment of titration conditions

The pK_b values of some aliphatic amines in 80% dimethylsulfoxide—20% water are reported. The mixed solvent offers worse titration conditions than water for the determination of these bases. The only advantage of using this solvent for titration of bases is its excellent solvating ability.     

Synthesis,Antitumor and Antibacterial Studies of New Shortened Analogues of (KLAKLAK)2-NH2 and Their Conjugates Containing Unnatural Amino Acids

(1) Background: (KLAKLAK)₂ is a representative of the antimicrobial peptide group which also shows good anticancer properties. (2) Methods: Herein, we report synthesis using SPPS and characterization by HPLC/MS of a series of shortened analogues of (KLAKLAK)₂. They contain single sequence KLAKLAK as C-terminal amides. In addition, substitution of some natural amino acids with unnatural β-Ala and nor-Leu is realized. In addition, these structures are conjugated with second pharmacophore with well proven anticancer properties 1,8-naphthalimide or caffeic acid. Cytotoxicity, antiproliferative effect and antimicrobial activity of newly synthesized structures were studied. (3) Results: The obtained experimental results reveal significant selective index for substances with common chemical structure KLβAKLβAK-NH₂. The antibacterial properties of newly synthesized analogues at two different concentrations 10 μM and 20 μM, were tested against Gram-negative microorganisms Escherichia coli K12 407. Only two of the studied compounds KLAKLAK-NH₂ and the one conjugated with second pharmacophore 1,8-naphthalimide and unnatural amino acid nor-Leu showed moderate activity against tested strains at concentration of 20 μM. (4) Conclusions: The obtained results reveal that the introducing of 1,8-naphthalimideGly- and Caf- increase the cytotoxicity and antiproliferative activity of the peptides but not their selectivity. Only two compounds KLAKLAK-NH₂ and 1,8-naphthalimideGKnLAKnLAK-NH₂ show moderate activity against Escherichia coli K12 at low concentration of 20 μM.     

Synthesis and Biological Studies on (KLAKLAK)2-NH2 Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore

(1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)₂ is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)₂-NH₂. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)₂-NH₂ and Caf-(KLAKLAK)₂-NH₂. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLβ-AKLβ-AK)₂-NH₂ containing β-Ala in its structures exhibited good antimicrobial activity against Escherichia coli K12 407 and Bacillus subtilis 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents.     

Low-temperature heterogeneous oxidation of sulfide ions on a higher Co oxide system in aqueous medium

Low-temperature heterogenous oxidation of sulfide ions on a higher Co oxide system in aqueous medium has been studied. The effects of pH, temperature and catalyst amount on the kinetic parameters as well as on the selectivity of the oxidation process were investigated. An oxidation mechanism has been proposed based on the results of kinetic investigations and on the data obtained by IR and XPS spectroscopic studies of Co oxide before and after sulfide ion oxidation.     

Angular and power characteristics of noncollinear acousto-optic tunable filters

The angular and the power characteristics of noncollinear acousto-optic tunable filters are investigated both experimentally and theoretically. The dependencies of the acoustic wave frequency, the bandpass width and the diffraction efficiency of the filter are studied as functions of the angle of incidence of the optical wave and of the acoustic signal power density. These dependencies are illustrated and tested on the basis of a realized such a filter based on tellurium dioxide (TeO₂). A good agreement of theory and experiment is demonstrated, which indicates that the approach used can be effective in designing such devices.