The effect of a synthetic neuromelanin on yield of free hydroxyl radicals generated in model systems

Neuromelanin is an amorphous pigment of the catecholamine origin that accumulates in certain dopaminergic neurons of the substantia nigra of human brain. In Parkinson's disease, there appears to be selective degeneration of the most heavily pigmented neurons of the substantia nigra, and this process has been linked to the presence of neuromelanin. It has been postulated that neuromelanin could increase the risk of oxidative stress reactions. On the other hand, melanin is usually considered to be an efficient antioxidant. Here we analyze experimental conditions that stimulate, or inhibit, antioxidant properties of neuromelanin. Using electron spin resonance (ESR)--spin trapping technique and salicylate hydroxylation assay, we monitored the formation of free hydroxyl radicals generated by a Fenton system in the presence of varying concentration of dopamine-melanin, a synthetic model for neuromelanin. Our data clearly indicate that the antioxidant action of neuromelanin is predominantly due to its ability to sequester redox-active metal ions such as iron. Using direct ESR spectroscopy, we have shown that ferric complexes with neuromelanin are resistant to reduction by mild biological reductants such as ascorbate. We have demonstrated that dopamine-melanin saturated with ferric ions, could enhance the formation of free hydroxyl radicals by redox activation of the ions. Thus, under the conditions that stimulate the release of accumulated metal ions, neuromelanin may actually become an efficient prooxidant. It is conceivable that neuromelanin, which normally is able to protect pigmented dopaminergic neurons against metal-ion related toxicity, could under extreme conditions have a cytotoxic role.     

Query-oriented topical influential users detection for top-k trending topics in twitter

Applied Intelligence - Online Social Networks (OSNs) have become inevitable for any new methodology both for viral promoting applications and instructing the creation of inciting information and...     

Associations between skeletal muscle properties, physical fitness, physical activity and coronary heart disease risk factors in men

High physical fitness and physical activity are associated with favourable lipid levels, especially a high level of high density lipoprotein cholesterol (HDL-C). A person's skeletal muscle properties, metabolism and percentage of different muscle fibres (ST-%), which may modify coronary heart disease (CHD) risk factors, such as serum insulin, obesity and serum sex hormones may also influence his fitness level and leisure-time physical activity. We studied the associations of physical fitness, physical activity and ST-% with serum lipids and lipoproteins in 72 healthy men. Their parameters were compared with those of 20 men with defined CHD. Significant interrelationships between ST-%, fitness and leisure-time physical activity index (LTPAI) were observed. Multiple regression analysis showed that ST-%, fitness and leisure-time physical activity explained about 32% of the variation in HDL-C in the healthy men. In healthy men ST-% correlated positively with fitness (r(s) = 0.62, P < 0.001) and with LTPAI (r(s) = 0.62, P < 0.001). Fitness level also correlated significantly with LTPAI (r(s) = 0.81, P < 0.001). Serum insulin showed negative associations with ST-% (r(s) = -0.63, P < 0.001) and fitness (r(s) = -0.54, P < 0.001) and LTPAI (r(s) = -0.62, P < 0.001). Free fraction of testosterone correlated negatively with serum HDL-C level (r(s) = -0.34, P < 0.01), with fitness (r(s) = -0.41, P < 0.001) and with LTPAI (r(s) = -0.54, P < 0.001). In sedentary men with the lowest fitness and physical activity the mean of ST-% (45%) was similar to that in CHD patients (44%). However, ST-% in men in the highest tertile of physical activity and fitness (68%) was significantly higher than in CHD patients and in men in the lowest tertile of physical activity and fitness. Skeletal muscle enzyme activity in lipid metabolism was significantly lower in both CHD patients and in sedentary and low-fit men than that in fitter and physically active men. The present data imply that skeletal muscle properties are important determinants of risk profiles, such as physical activity, fitness and serum lipid and lipoprotein patterns. Although fitness is a graded, independent predictor of mortality from CHD, a relatively high fitness level is not enough. This was clearly observed in the clustering analysis, in which the healthy men, according to their ST-%, fitness, leisure-time physical activity and serum sex hormone binding globulin (SHBG), fell into three natural groups: (i) Inactive men with lowest ST-% (mean 42%), lowest fitness (10.7 METs) and lowest HDL-C (1.36 mm/l); (ii) Fit men with high ST-% (66%), high fitness (14.5 METs) and moderately high HDL-C (1.54 mol/l); (iii) Active men with high ST-% (66%), highest fitness (14.9 METs) and highest serum HDL (1.83 mmol/l). The results support the idea that both fitness and physical activity give further protection against CHD by modifying risk factors. Our findings also suggest that skeletal muscle properties should be considered in the studies which assess CHD risk factors and their modifications especially in the field of health-related fitness.     

Pattern Recognition of Canine Duodenal Contractile Activity

An application of statistical pattern recognition technique to the classification of canine duodenal contractile activity resulting from the ingestion of three different test meals, viz. water, acid, and solid, is described. Feature vectors were extracted from the contractile activities recorded by means of strain gauges, and were based on average duration, number, and intensities of contractions, as well as their frequency and propagational characteristics. Pattern training and classification were performed via the Bayes decision rule. The resuits indicate that the three different meals give rise to three different kinds of contractile activities. An improvement in the classifier's performance was observed when it was updated with correctly classified patterns. The results appear to suggest that pattern analysis techniques add a new dimension to the study of gastrointestinal motility in health and disease. For example, pattern recognition techniques can also be extended to identify contractile patterns altered due to such pathological conditions as irritable bowel syndrome and postoperative diarrhea and, hence, elucidate the underlying relationship between contractile activity and distal propulsion of contents.     

A Computer Model of Human Colonic Electrical Control Activity (ECA)

Human colonic electrical control activity (ECA) was recorded from 17 subjects postoperatively by chronically implanted electrodes. The ECA pattern showed phase-unlocked control waves with variable frequencies and waxing and waning amplitudes. This was modeled by a tubular structure of bidirectionally coupled rings of bidirectionally coupled synthesized relaxation oscillators. The model explores the basis of the observed organization of ECA which is consistent with the colonic function of temporary storage of contents.     

Shared genes, shared experiences, and similarity of personality: Data from 14,288 adult Finnish co-twins.

Similarities for Extraversion (E) and Neuroticism (N) scale scores from the Eysenck Personality Inventory were evaluated in 7,144 adult twin pairs, drawn from the population-based Finnish Twin Cohort, as a function of the co-twins' genetic resemblance, gender, age, and the frequency of their social interaction with each other. To separate effects of shared genes from those of shared experience, we performed hierarchical multiple regressions of double-entry data matrices. Results establish the predictive significance of both genetic and experiential influences: Genetic effects remained significant when tested after the effects of social contact were first removed; conversely, for N scores, the effects of social contact remained significant when assessed after genetic influences were first removed. These findings establish genetic variance in major dimensions of adult personality but assign a significant role to common experience as well. The first finding constructively replicates reports by others; the second challenges the widespread assumption that shared experiences have a negligible impact on sibling similarity in adult personality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A fluorogenic peptide containing the processing site of human SARS corona virus S-protein: kinetic evaluation and NMR structure elucidation

Human severe acute respiratory syndrome coronavirus (hSARS-CoV) is the causative agent for SARS infection. Its surface glycoprotein (spike protein) is considered to be one of the prime targets for SARS therapeutics and intervention because its proteolytic maturation by a host protease is crucial for host-virus fusion. Using intramolecularly quenched fluorogenic (IQF) peptides based on hSARS-CoV spike protein (Abz-(755)Glu-Gln-Asp-Arg-Asn-Thr-Arg-Glu-Val-Phe-Ala-Gln(766)-Tyx-NH(2)) and in vitro studies, we show that besides furin, other PCs, like PC5 and PC7, might also be involved in this cleavage event. Through kinetic measurements with recombinant PCs, we observed that the peptide was cleaved efficiently by both furin and PC5, but very poorly by PC7. The cleavage could be blocked by a PC-inhibitor, alpha1-PDX, in a dose-dependent manner. Circular dichroism spectra indicated that this peptide possesses a high degree of sheet structure. Following cleavage by furin, the sheet content increased, possibly at the expense of turn and random structures. (1)H NMR spectra from 2D COSY and ROESY experiments under physiological buffer and pH conditions indicated that this peptide possesses a structure with a turn at its C-terminal segment, close to the cleavage site. The data suggest that the cleavable peptide bond is located within the most exposed domain; this is supported by the nearby turn structure. Several strong to weak NMR ROESY correlations were detected, and a 3D structure of the spike IQF peptide that contains the crucial cleavage site R(761) E has been proposed.     

Preparation of thermotrophic liquid crystalline polymers involving a novel spacer unit based on vinylacetic acid

Summary Liquid crystaline polymers (LCPs) involving a polysiloxane backbone and a novel vinylacetic acid unit in the spacer have been synthesised, These polymers all show dramatically lower clearing points (T_cl) than polymers with similar chain lengths but involving established polymethylene spacer groups.Part of this work was presented at the 12th National Conference of the Organic Chemistry Division of the Royal Australian Chemical Institute, Brisbane, Queensland, Australia, July 1991.