Kinetics and mechanism of formation and properties of polymers composed of paired macromolecules

The influence of formation conditions on structure and properties of reaction products from two different macromolecules (paired polymers) such as polystyrene and poly(1,1,2-trichlorobutadiene) or polystyrene and poly(vinyl chloride) is investigated. Mechanical properties, molecular mobility, heat resistance, thermostability, and fire resistance are shown to be regulated over a wide range by changing the molecular weight of the initial polymers, their ratio in the reaction mixture, etc. The interaction of different macromolecules in solution to form paired polymers is analyzed theoretically and experimentally. An analysis of structure and properties of the resulting products by refractometry, viscometry, sedimentation velocity, statistical analysis, and others shows that paired polymers are systems of the “coil-in-coil” type held together by chemical bonds in the zones of mutual penetration.     

Reusable heterogeneous catalysts of α-amino acid racemization, 2. Factors affecting the activity of heterogeneous catalysts based on strongly basic anion exchangers in OH− form and 4-hydroxy-3-formylbenzenesulfonic acid (5-sulfosalicylaldehyde)

The kinetics of (S)-Ala racemization on heterogeneous catalysts based on eight strongly basic anion exchangers modified with 4-hydroxy-3-formylbenzenesulfonic acid (5-sulfosalicylaldehyde) (SSA) in the presence of Cu(II) ions at 25 °C was studied. The “internal capacity” value f = m_p/(V₀ — V_p) was introduced to characterize the polymers, (m_p : number of quaternary ammonium groups of the polymer sample, V₀ : total volume of the swollen polymer, V_p : volume of the inert polymeric matrix). The correlation of the observed first-order rate constants of (S)-Ala racemization with the f values of the anion exchangers was established. According to this correlation the selected anion exchangers could be divided into two types with respect to the chemical nature of the groups attached to the quaternary nitrogen atom. The chemical nature, physical structure and the degree of cross-linking of the polymeric matrix do not affect the correlation. Anion exchangers of the first type have at least one ß-hydroxyalkyl substituent at the Anion exchangers of the second type have (CH₃)₃ cationic groups. Catalysts prepared with the first type anion exchangers have greater activity as compared with catalysts based on the second type anion exchangers with the same f values. The increase in activity of heterogeneous catalysts can be partially attributed to the 10 to 68 fold increase in OH^? concentration in the internal phase of the catalysts as compared to the model homogeneous system, which contains the same amounts of the components as the heterogeneous one. Moreover, an additional acceleration is observed in the heterogeneous racemization as compared to the homogeneous one, ca. 5 fold for the second type anion exchangers and ca. 14 fold for the first type anion exchangers.     

On the role of peptide hydrolysis for fibrillation kinetics and amyloid fibril morphology

Self-assembly of proteins into amyloid-like nanofibrils is not only a key event in several diseases, but such fibrils are also associated with intriguing biological function and constitute promising components for new biobased materials. The bovine whey protein β-lactoglobulin has emerged as an important model protein for the development of such materials. We here report that peptide hydrolysis is the rate-determining step for fibrillation of β-lactoglobulin in whey protein isolate. We also explore the observation that β-lactoglobulin nanofibrils of distinct morphologies are obtained by simply changing the initial protein concentration. We find that the morphological switch is related to different nucleation mechanisms and that the two classes of nanofibrils are associated with variations of the peptide building blocks. Based on the results, we propose that the balance between protein concentration and the hydrolysis rate determines the structure of the formed nanofibrils.

Peptide hydrolysis determines the fibrillation rate and the morphology of amyloid-like nanofibrils formed by β-lactoglobulin at low pH.     

Asymmetric 1,3-dipolar cycloaddition reaction of chiral 1-alkyl-1,2-diphospholes with diphenyldiazomethane

The 1,3-dipolar cycloaddition of chiral 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes ((1-(−)-menthyl)oxymethyl-1,2-diphosphole and 1-(+)-neomenthyl-1,2-diphosphole) with diphenyldiazomethane leads to novel P-chiral bicyclic phosphiranes having six chiral centers. The degree of diastereoselectivity depends on the substituent at phosphorus, and dramatically increases in the case of (+)-neomenthyl group (de up to 71%). DFT calculations indicate that the cycloaddition is thermodynamically controlled.

The 1,3-dipolar cycloaddition of chiral 1-alkyl-1,2-diphosphacyclopenta-2,4-dienes with diphenyldiazomethane leads to novel P-chiral bicyclic phosphiranes having six chiral centers.     

Efficacy of acne vulgaris treatment protocols according to its clinical forms

To compare results of different treatment regimens based on stratification of acne to prescribe the right treatment protocol according to clinical form and grade of acne. A transversal, cohort study conducted in 230 patients with acne vulgaris. Patients were divided into three groups according to acne severity and the results of each protocol determined in 0, 4, 6, 8, 12, 18 and 24 weeks. Statistical analysis was conducted using Wilcoxon and Mann‐Whitney tests 230 patients (99 females and 131 males) took part in the study. In first grade acne (70 patients), the most effective drug for papulo‐pustular lesions was azelaic acid, where the average value of the reduction was 1.03% per week. For comedone reduction, the most effective drug resulted retinol with 17.7% mean reduction per week. In second grade acne (66 patients), the most effective scheme was: doxycycline + topical retinoid + benzoyl peroxide. In the third grade (92 patients), the most effective drug was oral isotretinoin. Accurate stratification, based on clinical characteristics is required for better outcome. Treatment success is related to the respective individually tailored treatment schemes in patients with acne.     

An affibody in complex with a target protein: structure and coupled folding

Combinatorial protein engineering provides powerful means for functional selection of novel binding proteins. One class of engineered binding proteins, denoted affibodies, is based on the three-helix scaffold of the Z domain derived from staphylococcal protein A. The Z(SPA-1) affibody has been selected from a phage-displayed library as a binder to protein A. Z(SPA-1) also binds with micromolar affinity to its own ancestor, the Z domain. We have characterized the Z(SPA-1) affibody in its uncomplexed state and determined the solution structure of a Z:Z(SPA-1) protein-protein complex. Uncomplexed Z(SPA-1) behaves as an aggregation-prone molten globule, but folding occurs on binding, and the original (Z) three-helix bundle scaffold is fully formed in the complex. The structural basis for selection and strong binding is a large interaction interface with tight steric and polar/nonpolar complementarity that directly involves 10 of 13 mutated amino acid residues on Z(SPA-1). We also note similarities in how the surface of the Z domain responds by induced fit to binding of Z(SPA-1) and Ig Fc, respectively, suggesting that the Z(SPA-1) affibody is capable of mimicking the morphology of the natural binding partner for the Z domain.     

An update from the latest workshop on asymptomatic primary hyperparathyroidism

Considerable data have accumulated since 1990 concerning the natural history of asymptomatic primary hyperparathyroidism,the extent of target organ involvement, techniques for preoperative localization of parathyroid glands, and new surgical approaches for parathyroidectomy. Therefore a Workshop on Asymptomatic Primary Hyperparathyroidism: a Perspective for the Twenty-first Century was held in April 2002 with a goal of reevaluating the conclusions from the 1990 National Institutes of Health (NIH)Consensus Development Conference. This article presents the recommendations of the workshop panel and discusses the evidence leading to the changes in the recommendations of the 1990 NIH conference.     

Basal metabolic rate in the Yakut (Sakha) of Siberia.

Human indigenous circumpolar populations have elevated basal metabolic rates (BMRs) relative to predicted values; this metabolic elevation has been postulated to be a physiological adaptation to chronic and severe cold stress. The present study examines BMR in the Yakut, an indigenous high-latitude population from the Sakha Republic of Russia to determine (1) whether the Yakut show evidence of an elevated BMR, (2) if the Yakut display evidence of age-related changes in BMR, and (3) whether lifestyle differences influence BMR. BMR was measured during the late summer in 75 women and 50 men (ages 18-56 years) from the Siberian village of Berdygestiakh. Measured BMR (+/- SEM) of the entire sample was significantly elevated (+6.5%) compared to predictions based on body mass (6,623.7 +/- 94.9 vs. 6,218.2 +/- 84.7 kJ/day; P < 0.001). Additionally, measured BMR for the entire sample was significantly higher than predictions based on fat-free mass (+20.8%) and surface area (+8.9%). Males and females both showed significant elevations relative to all three standards. The elevated BMR of the Yakut does not appear to be attributable to extreme levels of protein, since the Yakut consume a mixed diet with a substantial proportion of carbohydrates. No significant age-related changes in BMR were found when controlled for body composition. No significant relationship was found between lifestyle variables and BMR, suggesting the possibility of a genetic or developmental mechanism. This study provides additional evidence of metabolic elevation in indigenous circumpolar groups and has important implications for estimating the nutritional requirements of these populations.     

Dialkylphosphorus metabolites in the urine and activities of esterases in the serum as biochemical indices for human absorption of organophosphorus pesticides

Ninety-seven agricultural workers were monitored for absorption of the organophosphorus pesticides methidathion, vamidothion, and azinphos-methyl, which were sprayed in an orchard during two seasons. Low levels of only one dialkylphosphorus metabolite (dimethyl phosphorothioate) were found in only eight workers in pre-exposure urine samples. More than one dialkylphosphorus metabolite was detected in almost all exposed individuals in after-exposure urine samples. The highest concentrations were measured after exposure to azinphos-methyl; the median concentrations of dimethyl phosphorodithioate and dimethyl phosphorothioate were 0.92 and 0.78 nmol/mg creatinine with a concentration range up to 14.3 and 53.7, respectively. Three diethylphosphorus metabolites were also detected in some samples, but at lower concentrations. Cholinesterase activities were decreased (31–48%) in the serum of 12 workers; four of those workers had no dialkylphosphorus metabolites in the urine. Paraoxonase and arylesterase activities in the serum were unaffected by the absorption of pesticides, and there was no correlation between the activities of these esterases and the metabolite concentrations in the urine. This study confirmed that dialkylphosphorus metabolites in the urine are a more sensitive index of absorption than cholinesterase inhibition in the serum but lack of correlation between cholinesterase inhibition and metabolite concentration indicates that both parameters should be monitored.