Increasing blood oxygen increases an index of 5-HT synthesis in human brain as measured using alpha-[(11)C]methyl-L-tryptophan and positron emission tomography

The main objective of this investigation was to test the hypothesis that brain serotonin (5-HT) synthesis, as measured by trapping of alpha-[(11)C]methyl-L-tryptophan (alpha-MTrp) using positron emission tomography (PET), can be modulated by changes in blood oxygen. The study involved six healthy participants (three male and three female), who breathed a 15% or 60% oxygen mixture starting 15 min before the injection of tracer and continuing during the entire acquisition period. Participants were injected with up to 12m Ci of alpha-MTrp. Two sets of PET images were acquired while the participants were breathing each of the oxygen mixtures and, after reconstruction, all images were converted into brain functional images illustrating the brain trapping constant K(*) (microL/g/min). The K(*) values were obtained for 12 regions of interest outlined on the magnetic resonance images. The K(*) values obtained at high and low blood oxygen content were compared by paired statistics using Tukey's post hoc correction. As there were no difference in plasma tryptophan concentrations, these K(*) values are directly related to regional 5-HT synthesis. The results showed highly significant increases (50% on average) in brain serotonin synthesis (K(*) values) at high (mean value of 223+/-41 mmHg) relative to low (mean value 77.1+/-7.7 mmHg) blood oxygen levels. This suggests that tryptophan hydroxylase is not saturated with oxygen in the living human brain and that increases in blood oxygen can elevate brain serotonin synthesis.     

Effects of mercuric ion on the conformation and activity of Penaeus Vannamei beta-N-acetyl-d-glucosaminidase

beta-N-acetyl-d-glucosaminidase (NAGase, EC.3.2.1.52), a composition of the chitinases, catalyzes the cleavage of N-acetylglucosamine polymers into N-acetylglucosamine. In this paper, the effects of mercuric ion on the activity of NAGase from Penaeus vannamei for the hydrolysis of pNP-NAG have been studied. The results show that HgCl2 can lead to irreversible inactivation to this enzyme. The inactivation process follows a first-order reaction and the inactivation rate constants have been determined. The relationship between the inactivation rate constants and HgCl2 concentration has been studied and the result shows that only one molecule of HgCl2 binds to the enzyme molecule to lead the enzyme lose its activity. Moreover, the conformational changes of the enzyme inactivated by HgCl2 were studied by following changes in the intrinsic fluorescence emission and ultraviolet absorption spectra.     

Effects of behavioral changes in a smallpox attack model

The impact of individual and community behavioral changes in response to an outbreak of a disease with high mortality is often not appreciated. Response strategies to a smallpox bioterrorist attack have focused on interventions such as isolation of infectives, contact tracing, quarantine of contacts, ring vaccination, and mass vaccination. We formulate and analyze a mathematical model in which some individuals lower their daily contact activity rates once an epidemic has been identified in a community. Transmission parameters are estimated from data and an expression is derived for the effective reproduction number. We use computer simulations to analyze the effects of behavior change alone and in combination with other control measures. We demonstrate that the spread of the disease is highly sensitive to how rapidly people reduce their contact activity rates and to the precautions that the population takes to reduce the transmission of the disease. Even gradual and mild behavioral changes can have a dramatic impact in slowing an epidemic. When behavioral changes are combined with other interventions, the epidemic is shortened and the number of smallpox cases is reduced. We conclude that for simulations of a smallpox outbreak to be useful, they must consider the impact of behavioral changes. This is especially true if the model predictions are being used to guide public health policy.     

Influence of Ecological and Social Factors on Body Mass of Wild Chimpanzees

The chimpanzees (Pan troglodytes schweinfurthii) of Gombe National Park, Tanzania, were weighed regularly over a period of 33 yr, resulting in 1286 measurements on 31 males and 26 females aged 2–43 yr. Female growth slowed at 10 yr and that of males at 13 yr. Median adult body mass is 39 kg for males and 31.3 kg for females. Body mass varied between years. Chimpanzees were heaviest during a period of frequent banana provisioning. They were also heavier when community range size was large and population density within the range was low. Chimpanzees were heavier in the wet than in the dry season and body mass tracked rainfall in the preceding mo except for May in which mass was anomalously low. Dominance rank is significantly correlated with body mass for females but not males. High-ranking individuals tended to maintain more stable mass. Variability in body mass was greater for young and old individuals than for prime adults.     

Effect of Nucleotides on the Orientation and Mobility of Myosin Subfragment-1 in Ghost Muscle Fiber

Using polarization fluorimetry, the orientation and mobility of 1,5-IAEDANS specifically bound to Cys707 of myosin subfragment-1 (S1) were studied in ghost muscle tropomyosin-containing fibers in the absence and in the presence of MgADP, MgAMP-PNP, MgATPgammaS, or MgATP. Modeling of various intermediate states was accompanied by discrete changes in actomyosin orientation and mobility of fluorescent dye dipoles. This suggests multistep changes in the structural state of the myosin head during the ATPase cycle. Maximal differences in the probe orientation by 4 degrees and its mobility by 30% were found between actomyosin states in the presence of MgADP and MgATP. It is suggested that interaction of S1 with F-actin induces nucleotide-dependent rotation of the whole motor domain of the myosin head or only the dye-binding site and also change in the head mobility.     

Dextran sulfate provides a quantitative and quick microarray hybridization reaction

Hypoxic pulmonary hypertension (HPH) is an important pathophysiological process of a variety of cardiac and pulmonary diseases. But the mechanisms responsible for HPH are still not fully understood. The discoveries of endogenous gas signal molecules, nitric oxide (NO), and carbon monoxide (CO), have been moving the research of HPH to a new phase. Hydrogen sulfide (H2S), which is now being considered as the third new gas transmitter, was found to be possibly involved in the pathogenesis of HPH. But whether there exists an interaction between H2S and CO has not been clear in the pathogenesis of HPH. In this study, we found that H2S was significantly decreased in the pathogenesis of HPH. However, plasma CO level and the expressions of heme oxygenase (HO-1) protein and HO-1 mRNA were significantly increased. Exogenous supply of H2S could alleviate the elevation of pulmonary arterial pressure. At the same time, plasma CO level and the expressions of HO-1 protein and mRNA in pulmonary arteries were significantly increased. Whereas, exogenous supply of propargylglycine (PPG), an inhibitor of cystathionine gamma-lyase (CSE), decreased the plasma H2S content and worsened HPH. At the same time, plasma CO level and the expressions of HO-1 protein and mRNA in pulmonary arteries were decreased. The results showed that H2S could play a regulatory role in the pathogenesis of HPH through up-regulating CO/HO pathway.     

Effect of Oxygen on Temporary Stabilization of Photoreduced Quinone Acceptors in Rhodobacter sphaeroides Reaction Centers

The effect of molecular oxygen on the photochemical activity of the Rhodobacter sphaeroides reaction centers frozen to 160 K under actinic illumination was investigated by the ESR method. About 90% of initially photochemically active bacteriochlorophyll (P) were fixed at 160 K for a long time in aerobic samples in an inactive form. In anaerobic samples, not more than 65% were fixed in an inactive form under the same conditions. In aerobic preparations, a small portion of photochemically active bacteriochlorophyll (about 10%) that retains its photochemical activity at 160 K after freezing under illumination has dark reduction kinetics similar to that of samples at room temperature after several seconds of actinic illumination. In anaerobic samples frozen under illumination, the remaining photochemically active reaction centers (35%) have the same dark reduction kinetics as samples illuminated at 295 K for 1-2 min. The conclusion is that the irreversible stabilization of bacteriochlorophyll P in the oxidized inactive state formed in the reaction centers frozen under illumination is brought about by light-induced conformational changes fixed under low temperatures.     

Comparison of ligand-induced conformational changes and domain closure mechanisms, between prokaryotic and eukaryotic dehydroquinate synthases

Dehydroquinate synthase (DHQS) is a potential target for the development of novel broad-spectrum antimicrobial drugs, active against both prokaryotes and lower eukaryotes. Structures have been reported for Aspergillus nidulans DHQS (AnDHQS) in complexes with a range of ligands. Analysis of these AnDHQS structures showed that a large-scale domain movement occurs during the normal catalytic cycle, with a complex series of structural elements propagating substrate binding-induced conformational changes away from the active site to distal locations. Compared to corresponding fungal enzymes, DHQS from bacterial species are both mono-functional and significantly smaller. We have therefore determined the structure of Staphylococcus aureus DHQS (SaDHQS) in five liganded states, allowing comparison of ligand-induced conformational changes and mechanisms of domain closure between fungal and bacterial enzymes. This comparative analysis shows that substrate binding initiates a large-scale domain closure in both species' DHQS and that the active site stereochemistry, of the catalytically competent closed-form enzyme thus produced, is also highly conserved. However, comparison of AnDHQS and SaDHQS open-form structures, and analysis of the putative dynamic processes by which the transition to the closed-form states are made, shows a far lower degree of similarity, indicating a significant structural divergence. As a result, both the nature of the propagation of conformational change and the mechanical systems involved in this propagation are quite different between the DHQSs from the two species.     

Macropolyhedral boron-containing cluster chemistry: two-electron variations in intercluster bonding intimacy. Contrasting structures of 19-vertex [(η-C5Me5)HIrB18H19(PHPh2)] and [(η-C5Me5)IrB18H18(PH2Ph)]

Fused double-cluster [(η⁵-C₅Me₅)IrB₁₈H₁₈(PH₂Ph)] (8), from syn-[(η⁵-C₅Me₅)IrB₁₈H₂₀] (1) and PH₂Ph, retains the three-atoms-in-common cluster fusion intimacy of 1, in contrast to [(η⁵-C₅Me₅)HIrB₁₈H₁₉(PHPh₂)] (6), from PHPh₂ with 1, which exhibits an opening to a two atoms-in-common cluster fusion intimacy. Compound 8 forms via spontaneous dihydrogen loss from its precursor [(η⁵-C₅Me₅)HIrB₁₈H₁₉(PH₂Ph)] (7), which has two-atoms-in-common cluster-fusion intimacy and is structurally analogous to 6.     

Functional independence of a peptide with the sequence of human apolipoprotein A-I central region

Previous results [J. Biol. Chem. 276 (2001) 16978] indicated that an apolipoprotein A-I (apoAI) central region swings away from lipid contact in discoidal high density lipoproteins (HDL), but it is able to penetrate into the bilayer of lipid vesicles. In this work, we have studied the interaction with lipid membranes of a synthetic peptide with the sequence of apoAI region between residues 77 and 120 (AI 77-120). Like apoAI, AI 77-120 binds to phospholipid vesicles and shows selectivity for cholesterol-containing membranes. Moreover, AI 77-120 promotes cholesterol desorption from membranes in a similar fashion as apoAI and can stimulate cholesterol efflux from Chinese hamster ovary cells. AI 77-120 has a considerable alpha-helical content in water solution, and its secondary structure is not largely modified after binding to membranes. Both apoA-I and AI 77-120 are oligomeric in the lipid-bound state, suggesting that dimerization of the central domain could be required for the membrane binding activity of apoA-I in HDL.