Biochemical characterization and DNA repair pathway interactions of Mag1-mediated base excision repair in Schizosaccharomyces pombe

The Schizosaccharomyces pombe mag1 gene encodes a DNA repair enzyme with sequence similarity to the AlkA family of DNA glycosylases, which are essential for the removal of cytotoxic alkylation products, the premutagenic deamination product hypoxanthine and certain cyclic ethenoadducts such as ethenoadenine. In this paper, we have purified the Mag1 protein and characterized its substrate specificity. It appears that the substrate range of Mag1 is limited to the major alkylation products, such as 3-mA, 3-mG and 7-mG, whereas no significant activity was found towards deamination products, ethenoadducts or oxidation products. The efficiency of 3-mA and 3-mG removal was 5–10 times slower for Mag1 than for Escherichia coli AlkA whereas the rate of 7-mG removal was similar to the two enzymes. The relatively low efficiency for the removal of cytotoxic 3-methylpurines is consistent with the moderate sensitivity of the mag1 mutant to methylating agents. Furthermore, we studied the initial steps of Mag1-dependent base excision repair (BER) and genetic interactions with other repair pathways by mutant analysis. The double mutants mag1 nth1, mag1 apn2 and mag1 rad2 displayed increased resistance to methyl methanesulfonate (MMS) compared with the single mutants nth1, apn2 and rad2, respectively, indicating that Mag1 initiates both short-patch (Nth1-dependent) and long-patch (Rad2-dependent) BER of MMS-induced damage. Spontaneous intrachromosomal recombination frequencies increased 3-fold in the mag1 mutant suggesting that Mag1 and recombinational repair (RR) are both involved in repair of alkylated bases. Finally, we show that the deletion of mag1 in the background of rad16, nth1 and rad2 single mutants reduced the total recombination frequencies of all three double mutants, indicating that abasic sites formed as a result of Mag1 removal of spontaneous base lesions are substrates for nucleotide excision repair, long- and short-patch BER and RR

Evaluating e-Government services from a citizens' prespective: A reference process model

Evaluating and optimizing e-government services is imperative for governments especially due to the capacity of e-services to transform public administrations and assist the interactions of governments with citizens, businesses and other government agencies. Existing widely applied evaluation approaches neglect to incorporate citizens’ satisfaction measures. Several citizen satisfaction models and indicators have been suggested in academia; however a reference process model that can assist practitioners to apply these performance measures is missing. In this paper we draw upon the evaluation approach proposed by the EU funded project CEES and propose a reference process model that captures re-usable practices for e-government evaluation from a citizens’ perspective. The novelty of the proposed approach is that using DEA for evaluating the e-services the assessment results in suggestions for strategic improvement of the e-services.EU FP7 Marie Curie People Project “CEES - Citizen oriented Evaluation of E-Government Systems” (reference IAPP-2008-230658

Seismic Performance of Steel Frames with Semirigid Connections

The nonlinear stiffness matrix method was incorporated to investigate the structural performance of steel portal frames with semirigid connections. A portal frame with unstiffened extended end-plate connection was designed to demonstrate the adequacy of the proposed method. Besides, the seismic performance of steel portal frames with semirigid connections was investigated through time history analysis where kinematic hysteresis model was assigned to semirigid connections to account for energy dissipation and unloading stiffness. Based on the results of the study, it was found that generally semirigid connections influenced the force distribution which resulted in the decrease in base shear and lighter frame compared to the rigid one. The results also indicated that there was no direct relationship between maximum displacement at the top and connection stiffness in high-rise frames

Evaluation of Biological Activities of Extracts and Chemical Constituents of Mimusops elengi

Purpose: To isolate some compounds from the leaves and bark of Mimusops elengi, and examine them for their antibacterial and anti-inflammatory properties.Experimental: The compounds were isolated from the leaf and bark chloroform extracts using column chromatography, and characterized using physical and spectroscopic methods. The isolated compounds and their respective extracts were tested for antibacterial activity by micro-dilution antibacterial assay, and for anti-inflammatory activity by cyclooxygenase inhibitory assay.Results: of the compounds isolated include spinasterol (1), ursolic acid (2) and 3β, 6β, 19α, 23- tetrahydroxyurs-12-en-28-oic acid (3) from the leaves; and taraxerol (4) and spinasterol β-Dglucopyranoside (5) from the bark. A majority of the samples showed good activity against Staphylococcus aureus (9.7 ─ 78.0 μg/mL), while moderate activity was observed against Gramnegative bacteria (78.0 ─ 156 μg/mL). Strong COX inhibition was observed for the leaf extract, and (1); selective COX-2 inhibition for (2) and (3); and selective COX-1 inhibition for bark extract, (4) and (5).Conclusion: This is the first report describing the anti-inflammatory potential of M. elengi on the basis of its isolated constituents. The results of this study support the traditional use of the plant as antibacterial and anti-inflammatory remedy.Keywords: Mimusops elengi, Sapotaceae, Steroids; Triterpenoids, Antibacterial, Antiinflammatory

Exploring the Power and Promise of In Silico Clinical Trials with Application in COVID-19 Infection

Background: COVID-19 pandemic has dramatically engulfed the world causing catastrophic damage to human society. Several therapeutic and vaccines have been suggested for the disease in the past months, with over 150 clinical trials currently running or under process. Nevertheless, these trials are extremely expensive and require a long time, which presents the need for alternative cost-effective methods to tackle this urgent requirement for validated therapeutics and vaccines. Bearing this in mind, here we assess the use of in silico clinical trials as a significant development in the field of clinical research, which holds the possibility to reduce the time and cost needed for clinical trials on COVID-19 and other diseases. Methods: Using the PubMed database, we analyzed six relevant scientific articles regarding the possible application of in silico clinical trials in testing the therapeutic and investigational methods of managing different diseases. Results: Successful use of in silico trials was observed in many of the reviewed evidence. Conclusion: In silico clinical trials can be used in refining clinical trials for COVID-19 infection. Keywords: in silico, clinical trials, COVID-19, SARS-CoV-2, vaccine Ho

Taste function in early stage treated and untreated Parkinson’s disease

Since brain stem regions associated with early Parkinson’s disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated wholemouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue. The PD cohort was tested both on and off dopamine-related medications in counterbalanced test sessions. While whole-mouth taste identification test scores for all stimuli were, on average, nominally lower for the PD patients than for the controls, a trend in the opposite direction was noted for the intensity ratings at the lower stimulus concentrations for all stimuli except caffeine. Moreover, regional testing found that PD subjects tended to rate the stimuli, relative to the controls, as more intense on the anterior tongue and less intense on the posterior tongue. No significant associations were evident between taste test scores and UPDRS scores, L-DOPA medication equivalency values, or [99mTc]TRODAT-1 SPECT imaging of dopamine transporter uptake within the striatum and associated regions. Our findings suggest that suprathreshold measures of taste function are influenced by PD and that this disease differentially influences taste function on anterior (CN VII) and posterior (CN IX) tongue regions. Conceivably PD-related damage to CN IX releases central inhibition on CN VII at the level of the brainstem, resulting in enhanced taste intensity on the anterior tongue

Flow Analysis on Fusiform Aneurysm during Exercise Condition

The dilation of fusiform aneurysm can yield unexpected predicament. The aneurysm is prone to rupture if not immediately treated. This study is focuses on investigate the flow behaviour inside the fusiform aneurysm during exercise condition under normal blood pressure (NBP) and high blood pressure (HBP). The results of this study shows the presence of the flow recirculation is observed at aneurysm region during exercise condition. The presence of the flow recirculation is proportional to the increase of flow activity at the aneurysm. The flow activity is much higher at distal end compared to proximal end region. The different of flow activity shows the different strength of the flow recirculation occurred at the aneurysm bulge. The results also show HBPE peak systole distribute the highest value of the pressure among others condition which is exhibits the high risk of the aneurysm from rupture

Molecular characterization of cytochrome P450 1B1 and effect of benzo(a) pyrene on its expression in Nile tilapia (Oreochromis niloticus)

Cytochrome P4501 (CYP1) family enzymes are most active in hydroxylating a variety of environmental contaminants including Polyaromatic Hydrocarbons (PAH), planar polychlorinated biphenyls and arylamines. CYP1B which belongs to the cytochrome  P450 superfamily of genes, is involved in the oxidation of endogenous and exogenous compounds, and could potentially be a useful biomarker in fish for exposure to arylhydrocarbon receptors (AhR) ligands. In this study, a new complementary   DNA (cDNA) of the CYP1B subfamily encoding 1B1 was isolated from Nile tilapia (Oreochromis niloticus) liver after intracoelomic injection with benzo (a) pyrene (BaP). The full-length cDNA was 2107 base pair (bp) long and contained a 5' noncoding region of 29 bp, an open reading frame of 1527 bp coding for 508 amino acids and a stop codon, and a 3' noncoding region of 551 bp, respectively. The deduced amino acid sequence of Nile tilapia CYP1B1 shows similarities of 79.7, 70.3, 65.7, 65.4, 65.0, and 63.7% with Plaice CYP1B1, Japanese eel CYP1B1, zebra fish CYP1B1, common carp CYP1B1, common carp CYP1B2 and  Channel catfish CYP1B1, respectively. The phylogenetic tree based on the amino acid sequences clearly shows tilapia CYP1B1  and Plaice CYP1B1 to be more closely related to each other than to the other CYP1B subfamilies. Furthermore, real-time PCR  was used for measuring BaP induction of CYP1B1 mRNA in different organs of tilapia (O. niloticus), using β-actin gene as internal control, and the results revealed that there was a large increase in CYP1B1 mRNA in liver (22.8), intestine (2.0) and muscles (1.3).Keywords: Oreochromis niloticus, benzo (a) pyrene, CYP1B1 cDNA, sequence analysis, real-time PCR

Unilateral, trifocal, diaphyseal fracture of the radius with ipsilateral mid-shaft ulna fracture in an adult: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, a trifocal, diaphyseal fracture of the radius associated with ipsilateral mid-shaft fracture of the ulna in an adult has not been reported in the literature to date. The AO classification system does not include such a fracture configuration.</p> <p>Case presentation</p> <p>We report a case of trifocal, diaphyseal fracture of the radius with a mid-diaphyseal fracture of the ulna in a 53-year-old Caucasian, British, right-hand dominant woman involved in a head-on collision with another vehicle. The management of this rare fracture configuration is described and alternative treatment options discussed.</p> <p>Conclusions</p> <p>We describe an unusual, complex fracture, which with prompt surgical treatment resulted in a rapid, full and satisfactory functional recovery for our patient.</p

Comparative pharmacokinetics of ampicillin trihydrate, gentamicin sulphate and oxytetracycline hydrochloride in Nubian goats and desert sheep

In this investigation the pharmacokinetics of three commonly used antibiotics, ampicillin trihydrate (10 mg/kg), gentamicin sulphate (3 mg/kg) and oxytetracycline hydrochloride (5 mg/kg), given intravenously, were each studied in five Nubian goats and five desert sheep. The pharmacokinetic parameters were described by a two-compartment open model. The results indicated that there were significant differences between the two species in some kinetic parameters of ampicillin and oxytetracycline but not gentamicin. Ampicillin elimination half life (t1/2β) in goats (1.20 h) was shorter than that in sheep (2.48 h), and its clearance (Cl) significantly higher in goats (2921mL/h·kg) compared to sheep (262 mL/h·kg) (P < 0.01). Ampicillin volume of distribution (Vdarea) was found to be significantly larger in goats (5673 mL/kg) than in sheep (992 mL/kg) (P < 0.01). For oxytetracycline, the t1/2β in goats (3.89 h) was significantly shorter than that in sheep (6.30 h) and the Cl value in goats (437 mL/h·kg) was significantly higher than in sheep (281 mL/h·kg). The results suggest that when treating sheep and goats, the pharmacokinetic differences between the two species must be considered in order to optimize the therapeutic doses of ampicillin and oxytetracycline