Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base variants on the geometry of phosphoryl transfer

The hairpin ribozyme requires functional group contributions from G8 to assist in phosphodiester bond cleavage. Previously, replacement of G8 by a series of nucleobase variants showed little effect on interdomain docking, but a 3-250-fold effect on catalysis. To identify G8 features that contribute to catalysis within the hairpin ribozyme active site, structures for five base variants were determined by X-ray crystallography in a resolution range between 2.3 and 2.7 A. For comparison, a native all-RNA "G8" hairpin ribozyme structure was refined to 2.05 A resolution. The native structure revealed a scissile bond angle (tau) of 158 degrees, which is close to the requisite 180 degrees "in-line" geometry. Mutations G8(inosine), G8(diaminopurine), G8(aminopurine), G8(adenosine), and G8(uridine) folded properly, but exhibited nonideal scissile bond geometries (tau ranging from 118 degrees to 93 degrees) that paralleled their diminished solution activities. A superposition ensemble of all structures, including a previously described hairpin ribozyme-vanadate complex, indicated the scissile bond can adopt a variety of conformations resulting from perturbation of the chemical environment and provided a rationale for how the exocyclic amine of nucleobase 8 promotes productive, in-line geometry. Changes at position 8 also caused variations in the A-1 sugar pucker. In this regard, variants A8 and U8 appeared to represent nonproductive ground states in which their 2'-OH groups mimicked the pro-R, nonbridging oxygen of the vanadate transition-state complex. Finally, the results indicated that ordered water molecules bind near the 2'-hydroxyl of A-1, lending support to the hypothesis that solvent may play an important role in the reaction.     

Hydrolysis kinetics of trisaccharides consisting of glucose, galactose, and fructose residues in subcritical water

The hydrolysis kinetics of trisaccharides consisting of glucose, galactose, and fructose residues with different glycosidic bonds, 1-kestose, d-melezitose, d-raffinose, and lactosucrose, in subcritical water were conducted over the temperature range of 150-230 degrees C and at a constant pressure of 10 MPa. The hydrolysis of trisaccharides in subcritical water proceeded consecutively, i.e., one cleavage of the two bonds antedated the other. The preceding cleavage was not expressed by the first-order kinetics, but by the kinetics considering the concentration of the acidic compounds, which were produced by the degradation of the constituent monosaccharides. The hydrolysis of the constituent disaccharides, except sucrose composed of the alpha-Glc-(1-->2)-beta-Fru bond, obeyed first-order kinetics. All of the rate constants of the hydrolytic kinetics were determined, and the values were found to depend on the type of bond.     

Synthesis and study of new paramagnetic and diamagnetic verapamil derivatives

New derivatives of verapamil (1) modified with nitroxides and their precursors were synthesized and screened for reactive oxygen species (ROS)-scavenging activities. The basic structure was modified by changing the nitrile group to an amide or the methyl substituent on tertiary nitrogen with nitroxides and their reduced forms (hydroxylamine and secondary amines). Among the new verapamil derivatives compound 16B [Mohan, I. K.; Kahn, M.; Wisel, S.; Selvendiran, K.; Sridhar, A.; Carnes, C.A.; Bognár, B.; Kálai, T.; Hideg, K.; Kuppusamy, P. Am. J. Physiol. Heart Circ. Physiol. 2009, 296, 140], modified with hydroxylamine salt of 2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridine-1-yloxyl proved to be the best ROS scavenger in vitro and protected HSMC and CHO cells against H₂O₂ induced damage.     

Sleep habits of Iranian pre-school children in an urban area: Late sleeping and sleep debt in children

Using BEARS (Bedtime problems, Excessive sleepiness, Awakenings during the night, Regularity of sleep, Snoring), and CSHQ (Children’s Sleep Habits Questionnaires) screening tools with 224 participants revealed that Iranian children have shorter night sleep duration than expected (9.54 vs 12 h) for their age group. Earlier sleepers had longer night sleep duration (10:36 ± 1:12; 9:12 ± 1:06 h, P > 0.001), and total daily sleep time (11:36 ± 1:42; 10:36 ± 1:30 h, P = 0.005) than late sleepers. A majority (85%) of naptakers had sleep bedtime of 22:00 or later. The poor sleep quality of Iranian preschool children is probably due to cultural characteristics, climate differences, or harmful sleep habits.

     

Safety,Health, and Environmental Risk Assessment of a Gas Power Plant: A Case Study from Southern Iran

This research was conducted to assess health, safety, and environmental risks of a gas power plant in southern Iran. In order to identify the subject risks of the power plant at operational phase a questionnaire was designed using the Delphi method. The questionnaires were put at the disposal of 99 electricity industry experts. Risk assessment was done using multicriteria decision-making methods such as technique for order of preference by similarity to ideal solution (TOPSIS), entropy, and Eigenvector technique. Following prioritization of risks at each power plant unit, top-priority risks were determined by one-way ANOVA. The obtained results indicated that the risk of working with medium voltage boards with a weight of 0.879 at the power plant's Electricity Unit is the most important safety and health risk in the studied power plant while risk of servicing the unit with fuel of gas weighting 0.807 and delivery of gas fuel with weight of 0.630 in the Exploiting Unit and work on liquid fuel clutch with weight of 0.603 in the Mechanical Unit are the most important environmental risks in the gas power plant. In conclusion, this study concludes that health, safety, and environmental risk assessment can be a structured and used as a systematic approach to plan for environmental protection and personnel health.     

Nickel oxide nanoparticles exert selective toxicity on skin mitochondria and lysosomes isolated from the mouse model of melanoma

Nickel oxide nanoparticles (NiO‐NPs) are progressively used for an immense number of new applications in modern industries sectors. Nevertheless, the toxic impact of NiO‐NPs has not been clearly elucidated on human melanoma cell lines at the cellular and molecular level. Hence, this study was designed to examine the in vitro cytotoxicity potentials of NiO‐NPs on malignant cutaneous melanoma (MCM) mitochondria. Results revealed that NiO‐NPs significantly increased reactive oxygen species level, lipid peroxidation, and mitochondrial membrane potential and decreased succinate dehydrogenase activity, glutathione level, and ATP content on skin mitochondria isolated from the mouse model of melanoma compared with the non‐cancerous mouse skin mitochondria. Our results revealed that NiO‐NPs induced lysosomal membrane labialization on mentioned mitochondria. The current study showed that NiO‐NPs could significantly induce selective cytotoxicity on MCM mitochondria. Therefore, this compound may be considered as a promising candidate for further in vivo and clinical studies to reach a new anti‐MCM drug.     

Air quality modeling for health risk assessment of ambient PM10, PM2.5 and SO2 in Iran

In this study, we have estimated the number of total mortality (T-mortality), cardiovascular morbidity (CV-mortality), respiratory mortality (R-mortality), hospital admissions due to cardiovascular diseases (HA-CVD), respiratory diseases (HA-RD), chronic obstructive pulmonary diseases (COPD) and acute myocardial infarction (AMI) due to exposure to particulate matter less than 10 µm (PM₁₀), 2.5 µm (PM_2.5) and sulfur dioxide (SO₂) in western Iran in 2016. The World Health Organization (WHO) method was used to assess the mortality and morbidity among the exposed people. The results showed that about 3.9% CM (95% CI: 2.9–7.8%), 3.9% HA-RD (95% CI: 2.4–7.8%) and 4.4% HA-CVD (95% CI: 3.0–6.8%) for ambient PM₁₀ and about 7.3% TM (95% CI: 4.2–9.7%), 12.1% CM (95% CI: 3.5–14.6%) and 3.0% RM (95% CI: 0–6.3%) for PM_2.5 are respectively attributed to concentrations exceeding 10 µg/m³. Furthermore, 3.2% HA-COPD (95% CI: 0–5.04%) and 4.2% AMI (95% CI: 1.6–4.3%) can be attributed to SO₂ concentrations greater than 10 µg/m³, respectively. To reduce the adverse health effect of PM, health advices provided by health authorities should be given to general population especially vulnerable people such as people with chronic lung and heart pathologies, elderly and children during the dusty days.     

Neuroprotective Effect of <Emphasis Type="Italic">Salvia sahendica</Emphasis> is Mediated by Restoration of Mitochondrial Function and Inhibition of Endoplasmic Reticulum Stress

Herein, we investigated the protective effect of Salvia sahendica against H₂O₂-induced cell death in rat pheochromocytoma (PC12) cells. Our data show that S. sahendica blocks apoptosis pathway by inhibition of cytochrome c release from mitochondria and leakage of calcium from endoplasmic reticulum. It also activates/inactivates two members of Bcl-2 family, Bax and Bcl-2. Bax inhibition and Bcl-2 activation suppress release of cytochrome c from mitochondria that prevents cleavage of caspase-3. Besides S. sahendica suppresses ER stress via attenuation of intracellular levels of calcium. Suppression of ER stress decreased calpain activation and subsequently cleavage of caspase-12. Altogether, these results indicate that S. sahendica protects PC12 cells treated with H₂O₂ via suppression of upstream factors of apoptosis pathway. While oxidative stress is an early event in Alzheimer disease, it seems that S. sahendica prevents deleterious effects of reactive oxygen species by stabilizing mitochondrial membranes and inhibiting ER stress.