Sequence and phylogenetic analyses of the twin-arginine targeting (Tat) protein export system

Twin-arginine targeting (Tat) protein secretion systems consist of two protein types, members of the TatA and TatC families. Homologues of these proteins are found in many archaea, bacteria, chloroplasts and mitochondria. Every prokaryotic organism with a fully sequenced genome exhibits either neither family member, or between one and three paralogues of these two family members. The Arabidopsis thaliana genome encodes three of each. Although many mitochondrially encoded TatC homologues have been identified, corresponding TatA homologues have not been found in this organelle. Phylogenetic analyses reveal that most prokaryotic Tat systems consist of one TatC homologue and two sequence-divergent TatA homologues (TatA and TatB). When only one TatA homologue is present, TatB is missing, and when three TatA homologues are present, the third one arose by duplication of TatA, not TatB. Further, homologues most resembling TatB are more sequence-divergent than those more closely resembling TatA. In contrast to the TatA family, the TatC family shows phylogenetic clustering in strict accordance with organismal type. These results are discussed in terms of their probable structural, functional and evolutionary significance

Andrographolide Inhibits PI3K/AKT-Dependent NOX2 and iNOS Expression Protecting Mice against Hypoxia/Ischemia-Induced Oxidative Brain Injury

This study aimed to explore the mechanisms by which andrographolide protects against hypoxia-induced oxidative/nitrosative brain injury provoked by cerebral ischemic/reperfusion (CI/R) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone CI/R injury with andrographolide (10-100 mu g/kg, i.v.) at 1 h after hypoxia ameliorated CI/R-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. CI/R induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (NOX2), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b cells due to activation of nuclear factor-kappa B (NF-kappa B) and hypoxia-inducible factor 1-alpha (HIF-1 alpha). All these changes were significantly diminished by andrographolide. In BV-2 cells, OGD induced ROS and nitric oxide production by upregulating NOX2 and iNOS via the phosphatidylinositol-3-kinase (PI3K)/AKT-dependent NF-kappa B and HIF-1 alpha pathways, and these changes were suppressed by andrographolide and LY294002. Our results indicate that andrographolide reduces NOX2 and iNOS expression possibly by impairing PI3K/AKT-dependent NF-kappa B and HIF-1 alpha activation. This compromises microglial activation, which then, in turn, mediates andrographolide's protective effect in the CI/R mice

TNF-α and TNF-β Gene Polymorphism in Saudi Rheumatoid Arthritis Patients

Background Tumor necrosis factor (TNF)-α and -β are cytokines with a wide range of inflammatory, apoptotic and immunomodulatory activities. TNF-α promoter –308 G < A polymorphism has been reported to be associated with rheumatoid arthritis (RA) with inconsistent results. Objective The aim of this study is to elucidate a possible association of TNF-α (G–308A) and TNF-β (A+252G) polymorphisms with the susceptibility of RA in Saudi patients. Patients and Methods This case control study consisted of 232 Saudi subjects including 106 RA patients and 126 matched controls. Genomic DNA was extracted using QIAamp R DNA mini kit (Qiagen CA, USA). TNF-α and TNF-β genes were amplified using Arms primers. Results The frequencies of TNF-α (–308) allele G and genotype GG were significantly higher in RA patients as compared to controls while allele A and genotype AA were predominant in control group. On the other hand the frequency of TNF-β (+252) GG and AA genotypes were significantly higher in RA patients as compared to controls while GA genotype was predominant in controls. It was inferred that genotype GG positive individuals at position –308 of TNF-α were susceptible to RA while genotype AA might has a protective effect on RA susceptibility in Saudis. Whereas GG and AA genotype of TNF-β at +252 position might exert additive susceptibility to RA and GA might be refractory. However, there was no significant association between duration of morning stiffness, RF positivity and number of joints involved and distribution of alleles/genotypes of TNF-α (–308) or TNF-β (+252) polymorphism. It may be concluded that the TNF-α (–308) and TNF-β (+252) polymorphisms might influence the susceptibility to RA in Saudi population. These results might have prognostic value for future clinical observations

Selenium uptake and associated anti-oxidant properties in Pleurotus fossulatus cultivated on wheat straw from seleniferous fields

The present study was carried out to examine the antioxidant activity in oyster mushroom cultivated on selenium (Se) rich substrate. Pleurotus fossulatus was cultivated on Se-rich wheat straw collected from the seleniferous belt of Punjab (India) and its potential to accumulate Se from substrate was examined. Using different assay systems the modulations in the anti-oxidant profile of Se enriched mushroom was studied in comparison to the mushrooms cultivated on normal straw. The oyster mushrooms were observed to potentially mobilize Se from Se-rich substrates to fruiting bodies, resulting in significantly high uptake (37.2±0.6 μg g−1) as compared to control (3.57±0.53 mg g−1). The antioxidant activity, as determined by various assays, such as reducing power, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, and metal chelating activity, was higher in the experimental mushrooms when compared to control. The results obtained demonstrate that Se-fortified mushrooms through cultivation on straw containing organic forms of Se can be considered as natural and effective dietary supplements of organic Se for humans. The present study proposes the use of Se-rich agricultural residues as substrates for mushroom cultivation for human and livestock supplementation

Search for Neutrinoless Double- β Decay with the Complete EXO-200 Dataset

A search for neutrinoless double-β decay (0νββ) in Xe136 is performed with the full EXO-200 dataset using a deep neural network to discriminate between 0νββ and background events. Relative to previous analyses, the signal detection efficiency has been raised from 80.8% to 96.4±3.0%, and the energy resolution of the detector at the Q value of Xe136 0νββ has been improved from σ/E=1.23% to 1.15±0.02% with the upgraded detector. Accounting for the new data, the median 90% confidence level 0νββ half-life sensitivity for this analysis is 5.0×1025 yr with a total Xe136 exposure of 234.1 kg yr. No statistically significant evidence for 0νββ is observed, leading to a lower limit on the 0νββ half-life of 3.5×1025 yr at the 90% confidence level

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Search for Neutrinoless Double-Beta Decay with the Upgraded EXO-200 Detector

Results from a search for neutrinoless double-beta decay (0νββ) of Xe136 are presented using the first year of data taken with the upgraded EXO-200 detector. Relative to previous searches by EXO-200, the energy resolution of the