Exercise-Induced 4-Hydroxynonenal Alters Myotube Cellular Redox Homeostasis and Mitochondrial Metabolism

Regular physical exercise is associated with numerous health benefits and physiological adaptations. Mild and reversible oxidative stress induced by skeletal muscle contractions during exercise can result in long-term systemic redox adaptations. However, strenuous exercise can alter redox homeostasis and induce oxidative damage to macromolecules triggering a chain reaction of lipid peroxidation. Lipid peroxidation, yields formation of reactive aldehydes among which is biologically active 4-hydroxynonenal (4-HNE). 4-HNE can easily diffuse through membranes and covalently binds to macromolecules, such as proteins, altering cellular functions. Still little is known about the possible pathophysiological role of exercise induced 4-HNE on mitochondrial performance. In this work the effect of a caffeine, frequently used as an effective ergogenic aid by athletes, on the myotube mitochondrial metabolism, signaling and cellular redox homeostasis was studied using mouse C2C12, rat L6 and human HSMM skeletal muscle cells. Furthermore, the role of 4-HNE on myotube redox homeostasis, mitochondrial energy metabolism, mitochondrial transcriptome and mitochondrial density was investigated. Finally, the effect of physical exercise on 4-HNE post-translational modifications of proteins was studied using skeletal muscle samples from exercised animals by genuine mass spectrometry method. Obtained data indicate that short and long-term stimulation of myotubes with caffeine promotes reactive oxygen species formation and peroxidation of lipids leading to formation of 4-HNE protein adducts. 4-HNE further altered cellular redox homeostasis, mitochondrial metabolism and significantly increased mitochondrial density. Both caffeine and 4-HNE were found to regulate mitochondrial respiration and biogenesis gene expression. Finally, proteomics analysis of tissue samples from exercised mice revealed modifications of proteins susceptible to 6 oxidative stress. In conclusion, the findings signify the importance of skeletal muscle cells hormesis in response to acute stress and also suggest an important role of caffeine and 4-HNE on regulation of myotube’s metabolism and cellular energy production

Capillary trapping of CO2 in oil reservoirs: observations in a mixed-wet carbonate rock

Early deployment of carbon dioxide storage is likely to focus on injection into mature oil reservoirs, most of which occur in carbonate rock units. Observations and modeling have shown how capillary trapping leads to the immobilization of CO2 in saline aquifers, enhancing the security and capacity of storage. There are, however, no observations of trapping in rocks with a mixed-wet-state characteristic of hydrocarbon-bearing carbonate reservoirs. Here, we found that residual trapping of supercritical CO2 in a limestone altered to a mixed-wet state with oil was significantly less than trapping in the unaltered rock. In unaltered samples, the trapping of CO2 and N2 were indistinguishable, with a maximum residual saturation of 24%. After the alteration of the wetting state, the trapping of N2 was reduced, with a maximum residual saturation of 19%. The trapping of CO2 was reduced even further, with a maximum residual saturation of 15%. Best-fit Land-model constants shifted from C = 1.73 in the water-wet rock to C = 2.82 for N2 and C = 4.11 for the CO2 in the mixed-wet rock. The results indicate that plume migration will be less constrained by capillary trapping for CO2 storage projects using oil fields compared with those for saline aquifers

Effect of Environmental Heat Stress on Embryonic Bone Development

Birth defects are anatomical abnormalities present at birth. The causes of birth defects are genetic, environmental and multifactorial inheritance factors. The main objective of the thesis is to determine the effects of maternal heat stress during rat pregnancy on fetal axial skeletal development and to explore some of the possible maternal and placental responses to heat stress. Experiment one: A group of 40 Wistar pregnant rats were randomly assigned to two treatment groups, a control group (non-stressed, n = 10) heat at 21°C and a heat-stressed group kept at 41 °C (n = 30) for one hour on day 9 of gestation. The objective of this experiment is to determine the effect of heat stress on some maternal physiological parameters. Following an hour of heat stress or sham treatment, blood samples were collected from orbital vein, allowed to clot, and centrifuged at 3000 r.p.m for 10 minutes to obtain serum. Serum samples were used for determination of glucose, calcium, osteocalcin, thyroxin (T4) and triiodothyronine (T3). Results showed that heat stress caused significant Increases In serum glucose and oseocalcin levels. In addition, serum calcium, T3, and T4 levels were significantly lower in treated animals than those in control group. Experiment two: A total of 34 Wistar pregnant rats were randomly assigned to three treatment groups, a control group (non-stressed, n = 10) kept at 21°C, a heat-stressed group I kept at 41°C (n = 14), and a heat-stressed group II kept at 42°C (n = 10) for one hour on day 9 of gestation. The objective of this experiment is to investigate the effect of heat stress on embryonic bone development and to demonstrate the extreme changes and severity of skeletal malformations due to temperature. Results showed that heat stress caused reduction in the implantation, number of live embryos and fetal and placental weights in comparison to control animals. These effects were significantly pronounced in the 42°C treatment group. Morphological malformations were found in fetuses due to heat treatment. Malformations in the upper and lower jaws and increased incidence of mandibular and maxillary hypoplasia were observed in heat-treated group as compared to the controls. But in comparison between 41°C and 42°C, the 41°C group showed a higher incidence of maxillary-mandibular hypoplasia and tongue protrusion. In addition, both experimental groups showed a high incidence of excencephaly, exopthamia with cataract, facial clefts, and short tails than the controls. More skeletal malformations were recorded in experimental animals than in controls. The control fetuses had well ossified bones of the skull that included the mandible, premaxilla, maxilla, zygomatic, nasal, frontal, parietal, interparietal, supraoccipital, exoccipital, temporal, tympanic ring, hyoid, ethmoid, presphenoid, basisphenoid and basioccipital bones than in the experimental animals. The comparison between 41°C and 42°C groups showed different responses in terms of skeletal defects. Also results showed that control vertebral column appeared to have higher ossified vertebra than experimental groups. In the experimental fetuses, the vertebral arches and bodies showed decrease in number and poor ossification. The higher the temperature, the higher was the reduction in number of lumbar, sacral and coccygeal arches and bodies in experimental groups. In the control group, ribs, and sternebare appeared normally ossified without any reduction in number. No instance of fused or hypoplastic ribs was found in control fetuses. There was lower incidence of hypoplastic ilium, ishchium and pubis in control fetuses than in experimental rats. In addition, higher development in forelimb skeletons was observed in the control animals than in the treated ones. Placentas of the control groups showed lower weight compared with the experimental groups. The deciduas of experimental group was thicker than that of control group. There were large areas of hyalinization and lymphatic infiltration. Multinucleated giant cells were more abundant than those with single nucleus and basophils were extremely numerous. The glycogen cell clusters were reduced or absent over a large proportion of the spongy zone. Electron microscopic examination of the placentas showed a series of degenerative changes in experimental groups higher than those in control group placentas

The Degree to Which School’s Principal Practices Behaviors That Build or Destroy Teachers’ Trust in Her in Cycle One Abu-Dhabi City Schools: Teachers’ Perspective.

This study aimed to investigate the degree of which cycle-one school principals practice behaviors that build or destroy teachers trust in them from teachers’ perspective in light of some demographic variables in public schools in Abu Dhabi City through answering the following research questions: 1. To what degree cycle one school principals in Abu Dhabi city practice behaviors that build or destroy teachers’ trust in them from the teachers’ perspectives? 2. Are there significant mean differences in teachers perceptions at the significant level (ἁ = 0.05) about the degree to which principals practice behaviors that build or destroy teachers’ trust in them according to teacher’ nationality, teachers’ year of experience and years of working with the principal? To achieve the research aim and answer its question the researcher developed an instrument based on literature review and previous studies; the research instrument consisted of 53 five point Likert scale questions representing five main dimensions of trust: benevolence, openness, reliability, honesty and competence. Validity of the instrument was tested through presenting it to a panel of experts ion the field of education; reliability coefficient Cronbach alpha was used to test the instrument reliability, the reliability coefficient for the questions related to principals’ behaviors that build trust was 0.959 and it was 0.945 for the questions related to principals’ behaviors that destroy trust at all dimensions. A convenience sample technique was used to choose the study sample, 178 female teachers participated in the study which constitute 16% of the total population. The study has reached to the following results: The degree to which principals practice behaviors that build teachers’ trust in them is high and the degree to which the practice behaviors that destroy teachers’ trust in them is low from teachers’ perspectives. There are no significant mean differences in teachers’ perceptions about the degree principals practice behaviors that build teachers trust in them on the whole instrument or any of its dimensions according to their nationality. There are significant mean differences in teachers’ perceptions about the degree principals’ practice behaviors that destroy trust on the whole instrument and each of its dimensions attributed to their nationality with higher means for Arabic nationality teachers. There are no significant mean differences in teachers’ perceptions about the degree principals practice behaviors that build and destroy teachers trust in them on the whole instrument or any of its dimensions according to their experience. There are significant mean differences in teachers’ perceptions about the degree principals’ practice behaviors that build and destroy trust according to the years of working with the principal on the openness and consistence dimensions, while there were no significant mean differences on the benevolence, honesty and competence dimensions

Compulsive buying and depressive symptoms among female citizens of the United Arab Emirates

© 2016 Elsevier Ireland Ltd. Compulsive buying is particularly relevant in nations with high levels of consumer spending. Most previous studies have focused on European and North America populations. This study explores compulsive buying amongst citizens of the United Arab Emirates, an Arab nation with high retail outlet density, and high levels of consumer spending. Female college students (N=100) completed an English/Arabic version of the compulsive buying scale along with a measure of depression. Rates of compulsive buying were higher than those reported in any previously published study. Furthermore, in line with previous findings from other nations, compulsive buying was associated with elevated depressive symptomatology

Parathyroid Hormone-Like Hormone (PTHLH): A Novel Parietal Cell Growth Factor Regulated by Gastrin.

Parietal cells play a fundamental role in stomach physiology, not only by creating a pathogen free environment through the production of gastric acid, but also by secreting essential growth factors thought to be important for cellular homeostasis of the gastric glands. The gastrointestinal hormone gastrin is known to be a critical regulator of parietal cell function as well as proliferation and differentiation of the gastric glands. High gastrin levels in the body are frequently associated with gastric hyperplasia, yet the mechanism has not been defined. Since parietal cells contain gastrin receptors, one hypothesis is that the proliferation effect of hypergastrinemia is due to gastrin stimulation of growth factor(s) from parietal cells. Recent gene expression microarray studies of mouse stomach mucosa identified parathyroid hormone-like hormone (Pthlh) as a potential new gastric growth factor. Pthlh is expressed widely and has been described to orchestrate key cellular events in different tissues, such as cell proliferation and differentiation. Although Pthlh is highly expressed in gastric tumors, its normal expression, function and regulation in the stomach have not been studied. In this dissertation I examined the physiological importance of Pthlh in the mouse stomach. I used pharmacologic and genetic mouse models as well as human gastric cancer cell lines to determine the cellular localization and regulation of this growth factor by the hormone gastrin. Analysis of PthlhLacZ/+ reporter mice localized Pthlh to parietal cells in the gastric corpus. Acute treatment of mice with gastrin rapidly and transiently increased Pthlh mRNA abundance. Accordingly, Pthlh expression was significantly reduced in gastrin-deficient mice. Together these data suggested that gastrin is a physiologic regulator of Pthlh in the gastric mucosa. To examine the mechanism, human gastric AGS-E cells treated with gastrin exhibited a robust induction of endogenous Pthlh mRNA via stimulation of the gastrin receptor (Cckbr). Furthermore, gastrin induced Pthlh mRNA isoforms that arose from different promoters. Moreover, measurement of mRNA half-life confirmed that gastrin slowed the degradation of Pthlh transcripts. Collectively, this dissertation identified Pthlh as a novel parietal cell growth factor. It also identified Pthlh as a potential mediator of gastrin growth factor activity in the stomach.Ph.D.Molecular and Integrative PhysiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91456/1/asmaaa_1.pd

Lipid peroxidation is involved in calcium dependent upregulation of mitochondrial metabolism in skeletal muscle

BACKGROUND: Skeletal muscle cells continuously generate reactive oxygen species (ROS). Excessive ROS can affect lipids resulting in lipid peroxidation (LPO). Here we investigated the effects of myotube intracellular calcium-induced signaling eliciting contractions on the LPO induction and the impact of LPO-product 4-hydroxynonenal (4-HNE) on physiology/pathology of myotubes using C2C12 myoblasts. METHODS: C2C12 myoblasts were differentiated into myotubes, stimulated with caffeine and analyzed for the induction of LPO and formation of 4-HNE protein adducts. Further effects of 4-HNE on mitochondrial bioenergetics, NADH level, mitochondrial density and expression of mitochondrial metabolism genes were determined. RESULTS: Short and long-term caffeine stimulation of myotubes promoted superoxide production, LPO and formation of 4-HNE protein adducts. Furthermore, low 4-HNE concentrations had no effect on myotube viability and cellular redox homeostasis, while concentrations from 10 μM and above reduced myotube viability and significantly disrupted homeostasis. A time and dose-dependent 4-HNE effect on superoxide production and mitochondrial NADH-autofluorescence was observed. Finally, 4-HNE had strong impact on maximal respiration, spare respiratory capacity, ATP production, coupling efficiency of mitochondria and mitochondrial density. CONCLUSION: Data presented in this work make evident for the first time that pathological 4-HNE levels elicit damaging effects on skeletal muscle cells while acute exposure to physiological 4-HNE induces transient adaptation. GENERAL SIGNIFICANCE: This work suggests an important role of 4-HNE on the regulation of myotube's mitochondrial metabolism and cellular energy production. It further signifies the importance of skeletal muscle cells hormesis in response to acute stress in order to maintain essential biological functions