Carbon Monoxide-Driven Reduction of Ferric Heme and Heme Proteins

Oxidized cytochrome c oxidase in a carbon monoxide atmosphere slowly becomes reduced as shown by changes in its visible spectra and its reactivity toward oxygen. The \u27autoreduction\u27 of cytochrome c oxidase by this procedure has been used to prepare mixed valence hybrids. We have found that this process is a general phenomenon for oxygen-binding heme proteins, and even for isolated hemin in basic aqueous solution. This reductive reaction may have physiological significance. It also explains why oxygen-binding heme proteins become oxidized much more slowly and appear to be more stable when they are kept under a CO atmosphere. Oxidized α and β chains of human hemoglobin become reduced under CO much more slowly than does cytochrome c oxidase, where the CO-binding heme is coupled with another electron accepting metal center. By observing the reaction in both the forward and reverse direction, we have concluded that the heme is reduced by an equivalent of the water-gas shift reaction (CO + H2O → CO2 + 2e- + 2H+). The reaction does not require molecular oxygen. However, when the CO-driven reduction of cytochrome c oxidase occurs in the presence of oxygen, there is a competition between CO and oxygen for the reduced heme and copper of cytochrome a3. Under certain conditions when both CO and oxygen are present, a peroxide adduct derived from oxygen reduction can be observed. This \u27607 nm complex\u27, described in 1981 by Nicholls and Chanady, forms and decays with kinetics in accord with the rate constants for CO dissociation, oxygen association and reduction, and dissociation of the peroxide adduct. In the absence of oxygen, if a mixture of cytochrome c and cytochrome c oxidase is incubated under a CO atmosphere, autoreduction of the cytochrome c as well as of the cytochrome c oxidase occurs. By our proposed mechanism this involves a redistribution of electrons from cytochrome a3 to cytochrome a and cytochrome c

Kinetics of Reduction of Cytochrome \u3ci\u3ec\u3c/i\u3e Oxidase by Dithionite and the Effect of Hydrogen Peroxide

The reduction of cytochrome c oxidase by dithionite was reinvestigated with a flow-flash technique and with varied enzyme preparations. Since cytochrome a3 may be defined as the heme in oxidase which can form a photolabile CO adduct in the reduced state, it is possible to follow the time course of cytochrome a3 reduction by monitoring the onset of photosensitivity. The onset of photosensitivity and the overall rate of heme reduction were compared for Yonetani and Hartzell-Beinert preparations of cytochrome c oxidase and for the enzyme isolated from blue marlin and hammer-head shark. For all of these preparations the faster phase of heme reduction, which is dithionite concentration-dependent, is almost completed when the fraction of photosensitive material is still small. We conclude that cytochrome a3 in the resting enzyme is consistently reduced by an intramolecular electron transfer mechanism. To determine if this is true also for the pulsed enzyme, we examined the time course of dithionite reduction of the peroxide complex of the pulsed enzyme. It has been previously shown that pulsed cytochrome c oxidase can interact with H2O2 and form a stable room temperature peroxide adduct (Bickar, D., Bonaventura, J., and Bonaventura, C. (1982) Biochemistry 21, 2661-2666). Rather complex kinetics of heme reduction are observed when dithionite is added to enzyme preparations that contain H2O2. The time courses observed provide unequivocal evidence that H2O2 can, under these conditions, be used by cytochrome c oxidase as an electron acceptor. Experiments carried out in the presence of CO show that a direct dithionite reduction of cytochrome a3 in the peroxide complex of the pulsed enzyme does not occur

Keck Imaging of Binary L Dwarfs

We present Keck near-infrared imaging of three binary L dwarf systems, all of which are likely to be sub-stellar. Two are lithium dwarfs, and a third exhibits an L7 spectral type, making it the coolest binary known to date. All have component flux ratios near 1 and projected physical separations between 5 and 10 AU, assuming distances of 18 to 26 pc from recent measurements of trigonometric parallax. These surprisingly similar binaries represent the sole detections of companions in ten L dwarf systems which were analyzed in the preliminary phase of a much larger dual-epoch imaging survey. The detection rate prompts us to speculate that binary companions to L dwarfs are common, that similar-mass systems predominate, and that their distribution peaks at radial distances in accord both with M dwarf binaries and with the radial location of Jovian planets in our own solar system. To fully establish these conjectures against doubts raised by biases inherent in this small preliminary survey, however, will require quantitative analysis of a larger volume-limited sample which has been observed with high resolution and dynamic range.Comment: LaTex manuscript in 13 pages, 3 postscript figures, Accepted for publication in the Letters of the Astrophysical Journal; Postscript pre-print version available at: http://www.hep.upenn.edu/PORG/papers/koerner99a.p

The ontogeny of haematopoiesis in the marine teleost Leiostomus xanthurus and a comparison of the site of initial haematopoiesis with Opsanus tau

The ontogeny of haematopoiesis in the perciform fish, spot Leiostomus xanthurus, differed from that reported as the norm for fishes, as exemplified by the cypriniform zebrafish Danio rerio, and observed in the batrachoidiform oyster toadfish Opsanus tau. Erythropoiesis in spot was first evident in the head kidney of yolk-sac larvae 3 days after hatching (DAH). No embryonic intermediate cell mass (ICM) of primitive stem cells or blood islands on the yolk were apparent within embryos. Erythrocytes were first evident in circulation near the completion of yolk absorption, c. 5 DAH, when larvae were c. 20 mm notochord length (LN). Erythrocyte abundance increased rapidly with larval development for c. 14 to 16 DAH, then became highly variable following changes in cardiac chamber morphology and volume. Erythrocytic haemoglobin (Hb) was not detected within whole larvae until they were 12 DAH or c. 31 mm LN, well after yolk and oil-globule absorption. The Hb was not quantified until larvae were >47 DAH or >7 mm standard length. The delayed appearance of erythrocytes and Hb in spot was similar to that reported for other marine fishes with small embryos and larvae. In oyster toadfish, a marine teleost that exhibits large embryos and larvae, the ICM and Hb were first evident in two bilateral slips of erythropoietic tissue in the embryos, c. 5 days after fertilization. Soon thereafter, erythrocytes were evident in the heart, and peripheral and vitelline circulation. Initial haematopoiesis in oyster toadfish conformed with that described for zebrafish. While the genes that code for the development of haematopoiesis are conserved among vertebrates, gene expression lacks phylogenetic pattern among fishes and appears to conform more closely with phenotypic expression related to physiological and ecological influences of overall body size and environmental oxygen availability

The effect of group size and individual characteristics on between-group encounters in primates

Between-group encounters are common in non-human primates and can vary from affiliative to aggressive. We extracted data from the literature to test five different hypotheses: 1) where there are group size differences between opposing groups, whether the larger group is more likely to win a between-group encounter than the smaller group; 2) whether the likelihood of a group engaging in aggressive between-group encounters increases with group size; and 3-5) whether dominant, older animals, and/or males are more likely to participate aggressively in between-group encounters than subordinate, younger animals and/or females. Our dataset comprised 52 studies on 31 primate species (3 lemur species, 5 New World monkeys, 19 Old World monkeys and 4 apes). We found that the larger group is more likely to win an encounter against a smaller group than vice-versa. We found no significant relationship between group size and propensity to be aggressive during between-group encounters. We found weak/no support for the effect of age, dominance rank and sex on the frequency of aggression displayed towards outgroup animals during between-group encounters. Species- and population-specific differences in between- and within-group competition and in the degree of the unequal distribution of resources across group members may explain why age, dominance rank and sex are not strong predictors of aggression during between-group encounters

Histopathology of Skeletal Muscle in a Distal Motor Neuropathy Associated with a Mutant CCT5 Subunit: Clues for Future Developments to Improve Differential Diagnosis and Personalized Therapy

Genetic chaperonopathies are rare but, because of misdiagnosis, there are probably more cases than those that are recorded in the literature and databases. This occurs because practitioners are generally unaware of the existence and/or the symptoms and signs of chaperonopathies. It is necessary to educate the medical community about these diseases and, with research, to unveil their mechanisms. The structure and functions of various chaperones in vitro have been studied, but information on the impact of mutant chaperones in humans, in vivo, is scarce. Here, we present a succinct review of the most salient abnormalities of skeletal muscle, based on our earlier report of a patient who carried a mutation in the chaperonin CCT5 subunit and suffered from a distal motor neuropathy of early onset. We discuss our results in relation to the very few other published pertinent reports we were able to find. A complex picture of multiple muscle-tissue abnormalities was evident, with signs of atrophy, apoptosis, and abnormally low levels and atypical distribution patterns of some components of muscle and the chaperone system. In-silico analysis predicts that the mutation affects CCT5 in a way that could interfere with the recognition and handling of substrate. Thus, it is possible that some of the abnormalities are the direct consequence of defective chaperoning, but others may be indirectly related to defective chaperoning or caused by other different pathogenic pathways. Biochemical, and molecular biologic and genetic analyses should now help in understanding the mechanisms underpinning the histologic abnormalities and, thus, provide clues to facilitate diagnosis and guide the development of therapeutic tools

Acute Renal Failure in a Caucasian Traveler with Severe\ud Malaria: A Case Report

Acute renal failure (ARF) secondary to severe malaria is uncommon. We report a case of a patient visiting Africa for the first time presenting with malaria and ARF. There was complete recovery after hemodialysis. Early initiation of hemodialysis proves to be useful in restoration of renal function

Systematic data analysis-based validation of simulation models with heterogeneous data sources

Complex networked computer systems are subjected to upgrades on a continuous basis. Modeling and simulation (M&S) of such systems helps with guiding their engineering processes when testing design options on the real system is not an option. Too often many system’s operational conditions need to be assumed in order to focus on the questions at hand, a typical case being the exogenous workload. Meanwhile, soaring amounts of monitoring information is logged to analyze the system’s performance in search for improvement opportunities. Concurrently, research questions mutate as operational conditions vary throughout its lifetime. This context poses many challenges to assess the validity of simulation models. As the empirical knowledge base of the system grows, the question arises whether a simulation model that was once deemed valid could be invalidated in the context of unprecedented operation conditions. This work presents a conceptual framework and a practical prototype that helps with answering this question in a systematic, automated way. MASADA parses recorded operation intervals and automatically parameterizes, launches, and validates simulation experiments. MASADA has been tested in the data acquisition network of the ATLAS particle physics experiment at CERN. The result is an efficient framework for validating our models on a continuous basis as new particle collisions impose unpredictable network workloads.Sociedad Argentina de Informática e Investigación Operativa (SADIO