Elements of the rat tropoelastin gene associated with alternative splicing

Multiple isoforms of tropoelastin, the soluble precursor of elastin, are the products of translation of splice-variant mRNAs derived from the single-copy tropoelastin gene. Previous data had demonstrated DNA sequence heterogeneity in three domains of rat tropoelastin mRNA, indicating alternative splicing of several exons of the rat tropoelastin gene. Rat tropoelastin genomic clones encompassing the sites of alternative splicing were isolated and sequenced. Two sites of alternative splicing identified in rat tropoelastin mRNA sequences corresponded to exons 13-15 and exon 33 of the rat tropoelastin gene. Furthermore, the variable inclusion of an alanine codon in exon 16 resulted from two functional acceptor sites separated by three nucleotides. DNA sequences flanking exons subject to alternative splicing were analyzed. These exons contained splicing signals that differed from consensus sequences and from splicing signals of constitutively spliced exons. Introns immediately 5' of exons 14 and 33, for example, lacked typical polypyrimidine tracts and had weak, overlapping branch point sequences. Further, a region of secondary structure encompassing the acceptor site of exon 13 may influence alternative splicing of this exon. These results demonstrate that multiple cis-acting sequence elements may contribute to alternative splicing of rat tropoelastin pre-mRNA.     

The role of infectious agents in sudden infant death syndrome

Abstract Epidemiological factors associated with susceptibility to respiratory infections are similar to those associated with Sudden Infant Death Syndrome. Here we review the evidence that respiratory pathogens might be involved in some cases of Sudden Infact Death Syndrome in the context of factors identified in epidemiological studies of cot deaths: the age range affected; mother's smoking; respiratory viral infections; immunisation status. Both laboratory and epidimiological evidence suggests that vulnerability of infants to infectious agents depends on interactions between genetic, developmental and environmental factors that contribute to colonisation by microorganisms, the inflammatory and specific immune responses and the infants' physiological responses to inflammatory mediators. A model is proposed to explain how microorganisms might trigger a series of events resulting in some of these unexpected deaths and discusses how the present recommendations regarding child care practices might help reduce the numbers of Sudden Infant Death Syndrome cases associated with infectious agents.     

Evidence for the role of glycoprotein G of respiratory syncytial virus in binding of Neisseria meningitidis to HEp-2 cells

Abstract Viral glycoproteins G and F are expressed on the surface of cells infected with respiratory syncytial virus (RSV). We investigated the role of these proteins in the previously reported enhanced binding of Neisseria meningitidis to RSV-infected HEp-2 cells. Virus particles attached to bacteria were detected by immunofluorescence with flow cytometry. Binding of FITC-labelled bacteria to RSV-infected cells was significantly inhibited by monoclonal antibody against glycoprotein G. Unlabelled bacteria interfered with binding of the anti-G monoclonal antibody to these cells. These interactions were not found with a monoclonal antibody against glycoprotein F. We propose that glycoprotein G of RSV expressed on the surface of infected cells might act as an additional receptor for meningococci.     

Molecular docking analysis of HER-2 inhibitor from the ZINC database as anticancer agents

The human epidermal growth factor (HER2) is a transmembrane receptor that is highly expressed in breast cancer and in different other cancers. Therefore, it is of interest to identify the new HER2 inhibitors from a selected 300 compounds in the ZINC database. The top two hit compounds (ZINC000014780728 (-11.0 kcal/mol) and ZINC000014762512 (-10.8 kcal/mol)) showed a high affinity with HER2 relative to the reference compound (lapatinib (-10.2 kcal/mol)) for further consideration.     

Dietary intake of artificial food color additives containing food products by school-going children

Nutritional risk in children is associated with food safety. This is the first study to identify the food type consumed by 6–17-year-old school-going children in Saudi Arabia. Eight permitted artificial food color additives, including Tartrazine (E102), Sunset Yellow (E110), Carmoisine (E122), Allura Red (E129), Indigo Carmine (E132), Brilliant Blue (E133), Fast Green (E143), and Black PN (E151), and two non-permitted ones, Erythrosine (E127) and Red 2G (E128), were determined using 24-h dietary recall questionnaires. Artificial color additives in 839 food products were divided into nine categories, including biscuits, cakes, chocolates, chips, ice cream, juices and drinks, candy, jelly, and chewing gum, are determined using high performance liquid chromatography and diode array detector. The results indicated a high intake of juices and drinks, ice cream, and cakes, but low consumption of chewing gum among school-going children. Among the permitted artificial food color additives, Brilliant Blue (E133) (54.1%) and Tartrazine (E102) (42.3%) were the most commonly used. Sunset Yellow (E110) in one chocolate sample, Tartrazine (E102) and Sunset Yellow (E110) in one and two juice and drink samples, respectively, and Brilliant Blue (E133) in two candy samples exceeded the permitted level. Therefore, further investigations are needed to provide insights into the possible adverse health effects of high intake of these additives in artificial food coloring on the test population are warranted.     

Mn3O4 nanoparticles: Synthesis,characterization and their antimicrobial and anticancer activity against A549 and MCF-7 cell lines

Due to their inexpensive and eco-friendly nature, and existence of manganese in various oxidation states and their natural abundance have attained significant attention for the formation of Mn₃O₄ nanoparticles (Mn₃O₄ NPs). Herein, we report the preparation of Mn₃O₄ nanoparticles using manganese nitrate as a precursor material by utilization of a precipitation technique. The as-prepared Mn₃O₄ nanoparticles (Mn₃O₄ NPs) were characterized by using X-ray powder diffraction (XRD), UV–Visible spectroscopy (UV–Vis), High-Resolution Transmission electron microscopy (HRTEM), Field emission scanning electron microscopy (FESEM), Thermal gravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FT-IR). The antimicrobial properties of the as-synthesized Mn₃O₄ nanoparticles were investigated against numerous bacterial and fungal strains including S. aureus, E. coli, B. subtilis, P. aeruginosa, A. flavus and C. albicans. The Mn₃O₄ NPs inhibited the growth of S. aureus with a minimum inhibitory concentration (MIC) of 40 μg/ml and C. albicans with a MIC of 15 μg/ml. Furthermore, the Mn₃O₄ NPs anti-cancer activity was examined using MTT essay against A549 lung and MCF-7 breast cancer cell lines. The Mn₃O₄ NPs revealed significant activity against the examined cancer cell lines A549 and MCF-7. The IC₅₀ values of Mn₃O₄ NPs with A549 cell line was found at concentration of 98 µg/mL and MCF-7 cell line was found at concentration of 25 µg/mL.     

Development of unit cost for the health services offered at King FAHD Central hospital Jazan,Saudi Arabia

BackgroundEfficiency remains one of the most important drivers of decision making in health care system. Fund allocators need to receive structured information about the cost healthcare services from hospitals for better decisions related to resource allocation and budgeting. The objective of the study was to estimate the unit cost for health services offered to inpatients in King Fahd Central hospital (KFCH) Jazan during the financial year 2018.MethodsWe applied a retrospective approach using a top-down costing method to estimate the cost of health care services. Clinical and Administrative departments divided into cost centres, and the unit cost was calculated by dividing the total cost of final care cost centres into the total number of patients discharged in one year. The average cost of inpatient services was calculated based on the average cost of each ward and the number of patients treated.ResultsThe average cost per patient stayed in KFCH was SAR 19,034, with the highest cost of SAR 108,561 for patients in the Orthopedic ward. The average cost of the patient in the Surgery ward, Plastic surgery, Neurosurgery, Medical ward, Pediatric ward and Gynecology ward was SAR 33,033, SAR 29,425, SAR 23,444, SAR 20,450, SAR 9579 and SAR 8636 respectively.ConclusionThis study provides necessary information about the cost of health care services in a tertiary care setting. This information can be used as a primary tool and reference for further studies in other regions of the country. Hence, this data can help to provide a better understanding of tertiary hospital costing in the region to achieve the privatization objective.     

Solid state production of polygalacturonase and xylanase by Trichoderma species using cantaloupe and watermelon rinds

Different solid state fermentation (SSF) sources were tested such as cantaloupe and watermelon rinds, orange and banana peels, for the production of polygalacturonase (PG) and xylanase (Xyl) by Trichoderma harzianum and Trichoderma virens. The maximum production of both PG and Xyl were obtained by T. harzianum and T. virnes grown on cantaloupe and watermelon rinds, respectively. Time course, moisture content, temperature, pH, supplementation with carbon and nitrogen sources were optimized to achieve the maximum production of both PG and Xyl of T. harzianum and T. virens using cantaloupe and watermelon rinds, respectively. The maximum production of PG and Xyl of T. harzianum and T. virens was recorded at 4–5 days of incubation, 50–66% moisture, temperature 28–35°C and pH 6–7. The influence of supplementary carbon and nitrogen sources was studied. For T. harzianum, lactose enhanced PG activity from 87 to 120 units/g solid, where starch and maltose enhanced Xyl activity from 40 to 55–60 units/g solid for T. virnes. Among the nitrogen sources, ammonium sulphate, ammonium nitrate, yeast extract and urea increased PG activity from 90 to 110–113 units/g solid for T. harzianum. Similarly, ammonium chloride, ammonium sulphate and yeast extract increased Xyl activity from 45 to 55–70 units/g solid for T. virens.     

Sestrin 2 and AMPK Connect Hyperglycemia to Nox4-Dependent Endothelial Nitric Oxide Synthase Uncoupling and Matrix Protein Expression

Mesangial matrix accumulation is an early feature of glomerular pathology in diabetes. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. Here, we demonstrate that, in glomerular mesangial cells (MCs), endothelial nitric oxide synthase (eNOS) is uncoupled upon exposure to high glucose (HG), with enhanced generation of reactive oxygen species (ROS) and decreased production of nitric oxide. Peroxynitrite mediates the effects of HG on eNOS dysfunction. HG upregulates Nox4 protein, and inhibition of Nox4 abrogates the increase in ROS and peroxynitrite generation, as well as the eNOS uncoupling triggered by HG, demonstrating that Nox4 functions upstream from eNOS. Importantly, this pathway contributes to HG-induced MC fibronectin accumulation. Nox4-mediated eNOS dysfunction was confirmed in glomeruli of a rat model of type 1 diabetes. Sestrin 2-dependent AMP-activated protein kinase (AMPK) activation attenuates HG-induced MC fibronectin synthesis through blockade of Nox4-dependent ROS and peroxynitrite generation, with subsequent eNOS uncoupling. We also find that HG negatively regulates sestrin 2 and AMPK, thereby promoting Nox4-mediated eNOS dysfunction and increased fibronectin. These data identify a protective function for sestrin 2/AMPK and potential targets for intervention to prevent fibrotic injury in diabetes.