The Brookhaven muon storage ring magnet Danby, G.T.; Addessi, L.; Armoza, Z. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2001, Letnik:
457, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The muon g-2 experiment at Brookhaven National Laboratory has the goal of determining the muon anomalous
g-value
a
μ
(=(g−2)/2)
to the very high precision of 0.35 parts per million and thus requires ...a storage ring magnet with great stability and homogeniety. A superferric storage ring with a radius of 7.11 m and a magnetic field of 1.45 T has been constructed in which the field quality is largely determined by the iron, and the excitation is provided by superconducting coils operating at a current of 5200 A. The storage ring has been constructed with maximum attention to azimuthal symmetry and to tight mechanical tolerances and with many features to allow obtaining a homogenous magnetic field. The fabrication of the storage ring, its cryogenics and quench protection systems, and its initial testing and operation are described.
In the 2001–2002 running period of the Relativistic Heavy Ion Collider (RHIC), transversely polarized protons were accelerated to 100 GeV for the first time, with collisions at s=200 GeV. We present ...results from this run for single transverse-spin asymmetries for inclusive production of neutral pions, photons and neutrons of the energy region 20–100 GeV for forward and backward production for angles between 0.3 mrad and 2.2 mrad with respect to the polarized proton direction. An asymmetry of AN=(−0.090±0.006±0.009)×(1.0−0.24+0.47) was observed for forward neutron production, where the errors are statistical and systematic, and the scale error is from the beam polarization uncertainty. The forward photon and π0, and backward neutron, photon, and π0 asymmetries were consistent with zero. The large neutron asymmetry indicates a strong interference between a spin–flip amplitude, such as one pion exchange which dominates lower energy neutron production, and remaining spin–non-flip amplitudes such as reggeon exchange.
•Universal structural properties shared by CCO enzymes are described.•We propose working enzymatic mechanisms for CCO action.•Catalytic mechanisms of non-heme iron-mediated reactions by CCOs are ...discussed.•Some human hereditary diseases caused by genetic alternations in RPE65.
Carotenoids and their metabolic derivatives serve critical functions in both prokaryotic and eukaryotic cells, including pigmentation, photoprotection and photosynthesis as well as cell signaling. These organic compounds are also important for visual function in vertebrate and non-vertebrate organisms. Enzymatic transformations of carotenoids to various apocarotenoid products are catalyzed by a family of evolutionarily conserved, non-heme iron-containing enzymes named carotenoid cleavage oxygenases (CCOs). Studies have revealed that CCOs are critically involved in carotenoid homeostasis and essential for the health of organisms including humans. These enzymes typically display a high degree of regio- and stereo-selectivity, acting on specific positions of the polyene backbone located in their substrates. By oxidatively cleaving and/or isomerizing specific double bonds, CCOs generate a variety of apocarotenoid isomer products. Recent structural studies have helped illuminate the mechanisms by which CCOs mobilize their lipophilic substrates from biological membranes to perform their characteristic double bond cleavage and/or isomerization reactions. In this review, we aim to integrate structural and biochemical information about CCOs to provide insights into their catalytic mechanisms.
The enzyme β-carotene oxygenase 2 (BCO2) converts carotenoids into more polar metabolites. Studies in mammals, fish, and birds revealed that BCO2 controls carotenoid homeostasis and is involved in ...the pathway for vitamin A production. However, it is controversial whether BCO2 function is conserved in humans, because of a 4-amino acid long insertion caused by a splice acceptor site polymorphism. We here show that human BCO2 splice variants, BCO2a and BCO2b, are expressed as pre-proteins with mitochondrial targeting sequence (MTS). The MTS of BCO2a directed a green fluorescent reporter protein to the mitochondria when expressed in ARPE-19 cells. Removal of the MTS increased solubility of BCO2a when expressed in Escherichia coli and rendered the recombinant protein enzymatically active. The expression of the enzymatically active recombinant human BCO2a was further improved by codon optimization and its fusion with maltose-binding protein. Introduction of the 4-amino acid insertion into mouse Bco2 did not impede the chimeric enzyme's catalytic proficiency. We further showed that the chimeric BCO2 displayed broad substrate specificity and converted carotenoids into two ionones and a central C14-apocarotendial by oxidative cleavage reactions at C9,C10 and C9‘,C10‘. Thus, our study demonstrates that human BCO2 is a catalytically competent enzyme. Consequently, information on BCO2 becomes broadly applicable in human biology with important implications for the physiology of the eyes and other tissues.
Scope
β,β‐Carotene‐9′,10′‐dioxygenase 2 (BCO2) is a carotenoid cleavage enzyme localized to the inner mitochondrial membrane in mammals. This study was aimed to assess the impact of genetic ablation ...of BCO2 on hepatic oxidative stress through mitochondrial function in mice.
Methods and results
Liver samples from 6‐wk‐old male BCO2−/− knockout (KO) and isogenic wild‐type (WT) mice were subjected to proteomics and functional activity assays. Compared to the WT, KO mice consumed more food (by 18%) yet displayed significantly lower body weight (by 12%). Mitochondrial proteomic results demonstrated that loss of BCO2 was associated with quantitative changes of the mitochondrial proteome mainly shown by suppressed expression of enzymes and/or proteins involved in fatty acid β‐oxidation, the tricarboxylic acid cycle, and the electron transport chain. The mitochondrial basal respiratory rate, proton leak, and electron transport chain complex II capacity were significantly elevated in the livers of KO compared to WT mice. Moreover, elevated reactive oxygen species and increased mitochondrial protein carbonylation were also demonstrated in liver of KO mice.
Conclusions
Loss of BCO2 induces mitochondrial hyperactivation, mitochondrial stress, and changes of the mitochondrial proteome, leading to mitochondrial energy insufficiency. BCO2 appears to be critical for proper hepatic mitochondrial function.
β, β‐Carotene‐9′,10′‐oxygenase 2 (BCO2) is a carotenoid cleavage enzyme localized to the mitochondrial inner membrane in mammals. The results of the current study demonstrate that the loss of BCO2 causes changes of the hepatic mitochondrial proteome, mitochondrial hyperactivation, and stress, leading to mitochondrial energy insufficiency. BCO2 appears to be critical for proper hepatic mitochondrial function in mice.
Phys.Lett.B650:325-330,2007 In the 2001-2002 running period of the Relativistic Heavy Ion Collider
(RHIC), transversely polarized protons were accelerated to 100 GeV for the
first time, with ...collisions at sqrt{s} = 200 GeV. We present results from this
run for single transverse spin asymmetries for inclusive production of neutral
pions, photons and neutrons of the energy region 20 - 100 GeV for forward and
backward production for angles between 0.3 mrad and 2.2 mrad with respect to
the polarized proton direction. An asymmetry of A_N = (-0.090 +- 0.006 +-
0.009) x (1.0^{+0.47}_{-0.24}) was observed for forward neutron production,
where the errors are statistical and systematic, and the scale error is from
the beam polarization uncertainty. The forward photon and pi^0, and backward
neutron, photon, and pi^0 asymmetries were consistent with zero. The large
neutron asymmetry indicates a strong interference between a spin-flip
amplitude, such as one pion exchange which dominates lower energy neutron
production, and remaining spin non-flip amplitudes such as Reggeon exchange.
Recently, much progress has been made in elucidating the chemistry and metabolism of retinoids and carotenoids, as well as the structures of processing proteins related to vision. Carotenoids and ...their retinoid metabolites are isoprenoids, so only a limited number of chemical transformations are possible, and just a few of these occur naturally. Although there is an intriguing evolutionary conservation of the key components involved in the production and recycling of chromophores, these genes have also adapted to the specific requirements of insect and vertebrate vision. These ‘ancestral footprints’ in animal genomes bear witness to the common origin of the chemistry of vision, and will further stimulate research across evolutionary boundaries.
Low plasma levels of carotenoids are associated with mortality and chronic disease states. Genetic studies in animals revealed that the tissue accumulation of these dietary pigments is associated ...with the genes encoding β-carotene oxygenase 2 (BCO2) and the scavenger receptor class B type 1 (SR-B1). Here we examined in mice how BCO2 and SR-B1 affect the metabolism of the model carotenoid zeaxanthin that serves as a macular pigment in the human retina.
We used mice with a lacZ reporter gene knock-in to determine Bco2 expression patterns in the small intestine. By genetic dissection, we studied the contribution of BCO2 and SR-B1 to zeaxanthin uptake homeostasis and tissue accumulation under different supply conditions (50 mg/kg and 250 mg/kg). We determined the metabolic profiles of zeaxanthin and its metabolites in different tissues by LC-MS using standard and chiral columns. An albino Isx−/−/Bco2−/− mouse homozygous for Tyrc−2J was generated to study the effect of light on ocular zeaxanthin metabolites.
We demonstrate that BCO2 is highly expressed in enterocytes of the small intestine. Genetic deletion of Bco2 led to enhanced accumulation of zeaxanthin, indicating that the enzyme serves as a gatekeeper of zeaxanthin bioavailability. Relaxing the regulation of SR-B1 expression in enterocytes by genetic deletion of the transcription factor ISX further enhanced zeaxanthin accumulation in tissues. We observed that the absorption of zeaxanthin was dose-dependent and identified the jejunum as the major zeaxanthin-absorbing intestinal region. We further showed that zeaxanthin underwent oxidation to ε,ε-3,3′-carotene-dione in mouse tissues. We detected all three enantiomers of the zeaxanthin oxidation product whereas the parent zeaxanthin only existed as (3R, 3′R)-enantiomer in the diet. The ratio of oxidized to parent zeaxanthin varied between tissues and was dependent on the supplementation dose. We further showed in an albino Isx−/−/Bco2−/− mouse that supra-physiological supplementation doses (250 mg/kg) with zeaxanthin rapidly induced hypercarotenemia with a golden skin phenotype and that light stress increased the concentration of oxidized zeaxanthin in the eyes.
We established the biochemical basis of zeaxanthin metabolism in mice and showed that tissue factors and abiotic stress affect the metabolism and homeostasis of this dietary lipid.
Display omitted
•Intestinal BCO2 expression serves as a gatekeeper of carotenoid accumulation in mice.•Interaction between ISX and SR-B1 modulates carotenoid absorption and accumulation.•Abiotic stress and tissue factors affect carotenoid homeostasis.•Albino Isx−/−/Bco2−/− mouse serves as a multifaceted model for carotenoid biology.
PDF
