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

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

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

Detrusor Underactivity and Underactive Bladder in Women : What Is New?

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Novel organometallic catalyst for efficient valorization of lipids extracted from Prunus domestica kernel shell in sustainable fuel production.

This study focuses on converting Plum Kernel Shell (PKS) waste biomass into biodiesel using a novel synthesized heterogeneous catalyst, contributing to the pursuit of renewable fuel from sustainable resources. Plum Kernel Shell (PKS) is waste biomass generated from plum fruit and available abundantly; utilizing it can help in many ways, such as overcoming environmental issues and promoting a circular economy. The precursor for the heterogeneous catalyst is derived from post-oil extraction waste biomass and further modified with metallic oxides (CuO and Mo) due to its acidic nature to enhance its efficacy for biodiesel production. Thorough characterization of the synthesized catalyst was conducted using analytical techniques such as XRD (X-ray diffraction), SEM (Scanning Electron Microscopy), EDS (Energy-Dispersive X-ray Spectroscopy), BET (Brunauer-Emmett-Teller), and XPS (X-ray Photoelectron Spectroscopy) to elucidate its nature and performance. The transesterification process was systematically optimized by varying parameters such as temperature, time, methanol-to-oil ratio, and catalyst loading. The optimized yield of 92.61% of biodiesel resulted under ideal conditions, specifically at 65°C, 150 min, 5 wt% catalyst loading, and an 18:1 M ratio. The biodiesel derived from PKS oil exhibited promising fuel properties encompassing cold flow properties, density, viscosity, cetane number, and flash point, validating its potential as a viable alternative fuel source. Furthermore, the synthesized novel catalyst demonstrated exceptional efficiency, retaining stability over five cycles without significant reduction in biodiesel yield. These findings underscore the viability of PKS biomass as a renewable and sustainable source for both catalyst synthesis and biodiesel production