Allopurinol and oxypurinol are hydroxyl radical scavengers

AbstractAllopurinol is a scavenger of the highly reactive hydroxyl radical (k2 approx. 109 M−1s−1). One product of attack of hydroxyl radical upon allopurinol is oxypurinol, which is a major metabolite of allopurinol. Oxypurinol is a better hydroxyl radical scavenger than is allopurinol (k2 approx. 4 × 109 M−1s−1) and it also reacts with the myeloperoxidase-derived oxidant hypochlorous acid. Hence the protective actions of allopurinol against reperfusion damage after hypoxia need not be entirely due to xanthine oxidase inhibition

The complete mitochondrial genome of Anoplocnemis curvipes F. (Coreinea, Coreidae, Heteroptera), a pest of fresh cowpea pods

Open Access Journal; Published online: 18 July 2017The complete 16,345-bp mitochondrial genome of the agriculturally destructive pod sucking pest, the giant coreid bug, Anoplocnemis curvipes (Hemiptera: Coreidae), was assembled from paired-end Illumina HiSeq 2500 reads. The A. curvipes mitochondrial genome consists of 13 protein coding genes (PCGs), 22 tRNAs, 2 rRNAs and a control region in the order and orientation typical among insects. PCG initiation codons (ATG, ATC, ATT and ATA) with termination codon (TAA) are used with the exception of TAG stop codons by Cytb and ND3. All tRNA genes fold into predicted cloverleaf secondary structures having requisite triplets on the anticodon loop, apart from tRNA-Ser1 (AGN) whose dihydrouridine (DHU) arm forms a simple loop. The phylogenetic analysis of hemipteran mitogenomes clusters to the family level and supports the monophyly of the five superfamilies in Pentatomomorpha of Hemiptera. The Coreoidea and Pyrrhocoroidea are sister groups, while Coreidae and Alydidae are sister groups to Rhopalidae. These analyses provide insight to mitogenomics and evolutionary relationships among pentatomoid insects

Exploiting topology-directed nanoparticle disassembly for triggered drug delivery

YesThe physical properties of cyclic and linear polymers are markedly different; however, there are few examples which exploit these differences in clinical applications. In this study, we demonstrate that self-assemblies comprised of cyclic-linear graft copolymers are significantly more stable than the equivalent linear-linear graft copolymer assemblies. This difference in stability can be exploited to allow for triggered disassembly by cleavage of just a single bond within the cyclic polymer backbone, via disulfide reduction, in the presence of intracellular levels of l-glutathione. This topological effect was exploited to demonstrate the first example of topology-controlled particle disassembly for the controlled release of an anti-cancer drug in vitro. This approach represents a markedly different strategy for controlled release from polymer nanoparticles and highlights for the first time that a change in polymer topology can be used as a trigger in the design of delivery vehicles. We propose such constructs, which demonstrate disassembly behavior upon a change in polymer topology, could find application in the targeted delivery of therapeutic agents.ERC are acknowledged for support to M.C.A., A.P.D. (grant number: 681559) and R.O.R. (grant number: 615142)

Differential effects of lower limb revascularisation on organ injury and the role of the amino acid taurine

Lower torso revascularisation following ischaemia results in a systemic inflammatory response. Endothelial barrier function is disrupted by neutrophil-derived proteases and oxidants. Taurine, an amino acid found in large quantities in neutrophils, is a powerful endogeneous anti-oxidant. The aims of this study were to investigate the systemic effects of reperfusion following lower limb revascularisation and to evaluate the role of taurine administration in preventing this injury. A rat model of aortic occlusion (30 min) followed by 2 h of reperfusion was used. Animals were randomised to one of three groups (n = 10 per group): control; ischaemia reperfusion untreated (IR) and taurine-treated. Taurine (4% solution) was administrated orally for 48 h prior to the experiment. Neutrophil infiltration and microvascular permeability were assessed by measuring tissue myeloperoxidase activity and wet/dry weights respectively in lung, liver, kidney, and in cardiac and skeletal muscle. Statistical analysis was by means of analysis of variance (ANOVA). Reperfusion resulted in pulmonary and renal microvascular injury as assessed by organ oedema. Hepatic tissue, skeletal and cardiac muscle were unaffected by lower limb revascularisation. Taurine was effective in preventing neutrophil-mediated pulmonary but not renal microvascular injury. These data suggest that, whilst reperfusion-induced pulmonary injury is predominantly neutrophilmediated, agents other than neutrophil-derived oxidative metabolites, capable of independently causing organ injury through direct endothelial damage, are produced during reperfusion

Dissemination of rat cytomegalovirus through infected granulocytes and monocytes in vitro and in vivo

The role of leukocytes in the in vivo dissemination of cytomegalovirus was studied in this experiment. Rat cytomegalovirus (RCMV) could be transferred to rat granulocytes and monocytes by cocultivation with RCMV-infected fibroblasts in vitro. Intravenous injection of purified infected granulocytes or monocytes resulted in a systemic infection in rats, indicating that our model is a powerful tool to gain further insight into CMV dissemination and the development of new antivirals

NUP-1 Is a Large Coiled-Coil Nucleoskeletal Protein in Trypanosomes with Lamin-Like Functions

NUP1, the first example of a nuclear lamin analog in nonmetazoans, performs roles similar to those of lamins in maintaining the structure and organization of the nucleus in Trypanosoma brucei

Renormalization Group Running of Lepton Mixing Parameters in See-Saw Models with S4S_4 Flavor Symmetry

We study the renormalization group running of the tri-bimaximal mixing predicted by the two typical $S_4$ flavor models at leading order. Although the textures of the mass matrices are completely different, the evolution of neutrino mass and mixing parameters is found to display approximately the same pattern. For both normal hierarchy and inverted hierarchy spectrum, the quantum corrections to both atmospheric and reactor neutrino mixing angles are so small that they can be neglected. The evolution of the solar mixing angle $\theta_{12}$ depends on $\tan\beta$ and neutrino mass spectrum, the deviation from its tri-bimaximal value could be large. Taking into account the renormalization group running effect, the neutrino spectrum is constrained by experimental data on $\theta_{12}$ in addition to the self-consistency conditions of the models, and the inverted hierarchy spectrum is disfavored for large $\tan\beta$. The evolution of light-neutrino masses is approximately described by a common scaling factor.Comment: 23 pages, 6figure

Nickel and platinum group metal nanoparticle production by <i>Desulfovibrio alaskensis</i> G20

Desulfovibrio alaskensis G20 is an anaerobic sulfate reducing bacteria. While Desulfovibrio species have previously been shown to reduce palladium and platinum to the zero-state, forming nanoparticles in the process; there have been no reports that D. alaskensis is able to form these nanoparticles. Metal nanoparticles have properties that make them ideal for use in many industrial and medical applications, such as their size and shape giving them higher catalytic activity than the bulk form of the same metal. Nanoparticles of the platinum group metals in particular are highly sought after for their catalytic ability and herein we report the formation of both palladium and platinum nanoparticles by D. alaskensis and the biotransformation of solvated nickel ions to nanoparticle form

The 3-3-1 model with S_4 flavor symmetry

We construct a 3-3-1 model based on family symmetry S_4 responsible for the neutrino and quark masses. The tribimaximal neutrino mixing and the diagonal quark mixing have been obtained. The new lepton charge \mathcal{L} related to the ordinary lepton charge L and a SU(3) charge by L=2/\sqrt{3} T_8+\mathcal{L} and the lepton parity P_l=(-)^L known as a residual symmetry of L have been introduced which provide insights in this kind of model. The expected vacuum alignments resulting in potential minimization can origin from appropriate violation terms of S_4 and \mathcal{L}. The smallness of seesaw contributions can be explained from the existence of such terms too. If P_l is not broken by the vacuum values of the scalar fields, there is no mixing between the exotic and the ordinary quarks at the tree level.Comment: 20 pages, revised versio

Residual plaque burden in patients with acute coronary syndromes after successful percutaneous coronary intervention

Objectives: The aim of this study was to characterize and evaluate the clinical impact of untreated atherosclerotic disease after percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS). Background: Residual atherosclerotic disease after successful PCI may predispose future major adverse cardiovascular events (MACE). Compared with intravascular ultrasound (IVUS), angiography underestimates the presence and severity of coronary artery disease. Methods: Following successful PCI of all clinically significant lesions in 697 patients with ACS, 3-vessel grayscale and radiofrequency IVUS was performed. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. A total of 3,229 untreated lesions (4.89 ± 1.98 lesions/patient) were identified by IVUS, with mean plaque burden (PB) of 49.6 ± 4.2%. Results: By angiography these nonculprit lesions were mild, with mean diameter stenosis of 38.9 ± 15.3%. At least 1 lesion with a PB <70% (PB70 lesion) was found in 220 (33%) patients. By multivariable analysis, a history of prior PCI and angiographic 3-vessel disease were independent predictors of PB70 lesions. Patients with PB70 lesions had greater total percent plaque volume, normalized PB, fibroatheromas, thin-cap fibroatheromas, and normalized volumes of necrotic core and dense calcium. Patients with PB70 lesions had greater 3-year rates of MACE due to untreated nonculprit lesions (20.8% vs. 7.7%, p < 0.0001). Among imaged nonculprit lesions, the proportion of PB70 lesions causing MACE was significantly greater than non-PB70 lesions (8.7% vs. 1.0%, p < 0.0001). Conclusions: After successful PCI of all angiographically significant lesions, overall untreated atherosclerotic burden remains high, and PB70 lesions are frequently present in the proximal and mid-coronary tree. Patients with PB70 lesions have greater atherosclerosis throughout the coronary tree, have more thin-cap fibroatheromas, and are at increased risk for future cardiovascular events. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466