NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV

Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of 2.76 TeV per nucleon pair was studied using data collected with the CMS detector at the LHC. Fragmentation functions are constructed using charged-particle tracks with transverse momenta pt > 4 GeV for dijet events with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events are compared to those in pp data as a function of collision centrality, as well as dijet-pt imbalance. Special emphasis is placed on the most central PbPb events including dijets with unbalanced momentum, indicative of energy loss of the hard scattered parent partons. The fragmentation patterns for both the leading and subleading jets in PbPb collisions agree with those seen in pp data at 2.76 TeV. The results provide evidence that, despite the large parton energy loss observed in PbPb collisions, the partition of the remaining momentum within the jet cone into high-pt particles is not strongly modified in comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic

Increased Resin Collection after Parasite Challenge: A Case of Self-Medication in Honey Bees?

The constant pressure posed by parasites has caused species throughout the animal kingdom to evolve suites of mechanisms to resist infection. Individual barriers and physiological defenses are considered the main barriers against parasites in invertebrate species. However, behavioral traits and other non-immunological defenses can also effectively reduce parasite transmission and infection intensity. In social insects, behaviors that reduce colony-level parasite loads are termed “social immunity.” One example of a behavioral defense is resin collection. Honey bees forage for plant-produced resins and incorporate them into their nest architecture. This use of resins can reduce chronic elevation of an individual bee's immune response. Since high activation of individual immunity can impose colony-level fitness costs, collection of resins may benefit both the individual and colony fitness. However the use of resins as a more direct defense against pathogens is unclear. Here we present evidence that honey bee colonies may self-medicate with plant resins in response to a fungal infection. Self-medication is generally defined as an individual responding to infection by ingesting or harvesting non-nutritive compounds or plant materials. Our results show that colonies increase resin foraging rates after a challenge with a fungal parasite (Ascophaera apis: chalkbrood or CB). Additionally, colonies experimentally enriched with resin had decreased infection intensities of this fungal parasite. If considered self-medication, this is a particularly unique example because it operates at the colony level. Most instances of self-medication involve pharmacophagy, whereby individuals change their diet in response to direct infection with a parasite. In this case with honey bees, resins are not ingested but used within the hive by adult bees exposed to fungal spores. Thus the colony, as the unit of selection, may be responding to infection through self-medication by increasing the number of individuals that forage for resin

Complex I-Associated Hydrogen Peroxide Production Is Decreased and Electron Transport Chain Enzyme Activities Are Altered in n-3 Enriched fat-1 Mice

The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6∶n-3 ratio on liver mitochondrial H2O2 production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6∶n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H2O2 production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H2O2 production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I

Protein Hydrolysates Are Avoided by Herbivores but Not by Omnivores in Two-Choice Preference Tests

Background: The negative sensory properties of casein hydrolysates (HC) often limit their usage in products intended for human consumption, despite HC being nutritious and having many functional benefits. Recent, but taxonomically limited, evidence suggests that other animals also avoid consuming HC when alternatives exist. Methodology/Principal Findings: We evaluated ingestive responses of five herbivorous species (guinea pig, mountain beaver, gopher, vole, and rabbit) and five omnivorous species (rat, coyote, house mouse, white-footed mouse, and deer mouse; N = 16–18/species) using solid foods containing 20% HC in a series of two-choice preference tests that used a nonprotein, cellulose-based alternative. Individuals were also tested with collagen hydrolysate (gelatin; GE) to determine whether it would induce similar ingestive responses to those induced by HC. Despite HC and GE having very different nutritional and sensory qualities, both hydrolysates produced similar preference score patterns. We found that the herbivores generally avoided the hydrolysates while the omnivores consumed them at similar levels to the cellulose diet or, more rarely, preferred them (HC by the white-footed mouse; GE by the rat). Follow-up preference tests pairing HC and the nutritionally equivalent intact casein (C) were performed on the three mouse species and the guinea pigs. For the mice, mean HC preference scores were lower in the HC v C compared to the HC v Cel tests, indicating that HC’s sensory qualities negatively affected its consumption. However, responses were species-specific. For the guinea pigs, repeated exposure to HC or C (4.7-h sessions; N = 10) were found to increase subsequent HC preference scores in an HC v C preference test, which was interpreted in the light of conservative foraging strategies thought to typify herbivores. Conclusions/Significance: This is the first empirical study of dietary niche-related taxonomic differences in ingestive responses to protein hydrolysates using multiple species under comparable conditions. Our results provide a basis for future work in sensory, physiological, and behavioral mechanisms of hydrolysate avoidance and on the potential use of hydrolysates for pest management