Sensitivity of the synaptic membrane Na+/Ca2+ exchanger and the expressed NCX1 isoform to reactive oxygen species

AbstractTwo plasma membrane proteins, the Na+/Ca2+ exchanger (NCX) and the Ca2+-ATPase, are major regulators of free intraneuronal Ca2+ levels as they are responsible for extrusion of Ca2+ from the intracellular to the extracellular medium. Because disruption of cellular Ca2+ regulation plays a role in damage occurring under conditions of oxidative stress, studies were conducted to assess the sensitivity of the NCX to reactive oxygen species (ROS). Exchanger activity in brain synaptic plasma membranes and in transfected CHO-K1 cells was inhibited following brief exposure to the peroxyl radical generating azo initiator 2,2′-azobis(2-amidinopropane)dihydrochloride (AAPH) and to peroxynitrite. Incubation with hydrogen peroxide did not alter NCX activity, even at 800 μM concentration. In CHO-K1 cells transiently transfected with the NCX1 isoform of the exchanger, AAPH treatment decreased the maximal transport capacity (Vmax), whereas the Kact remained unchanged. Peroxynitrite led to an increase in Kact with no change in Vmax. Loss of activity following exposure to either AAPH or peroxynitrite was associated with the formation of high molecular weight aggregates of NCX, and AAPH also caused fragmentation of the exchanger protein. These findings suggest that the NCX is sensitive to biologically relevant ROS and could be involved in the loss of Ca2+ homeostasis observed under oxidative stress

DEFECTIVE CALCIUM PUMPS IN NEURONS IN THE AGING BRAIN AND IN PARKINSON’S DISEASE

The plasma membrane Ca2+-ATPase (PMCA) pumps play an important role in the maintenance of precise levels of intracellular Ca2+, quintessential for the optimal functioning and long term survival of neurons. In this paper, we review evidence showing alterations in the PMCAs in aging brain. Additionally, we provide evidence showing defects in these transporters in Parkinson’s disease (PD). PMCA activity and protein levels in brain synaptic plasma membranes (SPMs) decline progressively with increasing age. The PMCAs undergo functional and structural changes when exposed to reactive oxygen species known to be generated in the aging brain and in neurodegenerative disorders such as PD. The major changes in the PMCAs include rapid inactivation, formation of aggregates, internalization from the plasma membrane and fragmentation by proteases. Reduction of PMCA levels as occurs in aging and under conditions of oxidative stress may play an important role in compromised neuronal function in the aging brain and in PD. Therapeutic strategies that protect the PMCAs and stabilize [Ca2+]i homeostasis have the potential of serving as novel interventions in preventing and/or slowing down the degeneration of neurons in various chronic neurodegenerative disorders

Exploring the interrelationships among operations management practices, customer perceptions of service quality and performance of hotels

Hospitality and tourism are important sectors of any economy. In the service sector, achieving a level of service quality that satisfies customers usually results in a competitive advantage in the market. The concept of service quality in hotels has been the subject of many research studies and there are numerous published works in the field. However, only a few studies have focused on the determinants of service quality for hotels using a set of comprehensive criteria. Thus, conceptualizing a service quality model that identifies the dimensions of service quality that affect customers' satisfaction is needed for hotels. In addition, the role of operations management practices in managing service quality cannot be denied. The available literature on the hotel industry in terms of managerial practices is unfortunately poor and needs to be enriched. Logically, better operations management practices in managing hotels' service quality would have a direct positive impact on performance, but there could also be some indirect (mediating) impact on performance through customer satisfaction. The purpose of this research is to build an effective model for measuring service quality in the hotel industry through critical evaluation of the available literature in service in general and hotels in particular. The built model has aspects of customer's perceptions of service quality, management's perceptions of operations management practices and of performance. The existing literature has been used to conceptualize a service quality model that meets the purpose of this research. The conceptualized model has eleven dimensions; seven for customer perceptions on service quality and four for management perceptions of operations management practices in managing service and on performance. The dimensions of customer's perceptions are: employee behaviour/attitude, price fairness, non-technological tangibility, technological tangibility, in-consumption positive emotions, in-consumption negative emotions and overall customer satisfaction. The introductions of technology and in-consumption emotions are one of the main contributions of this research. Though previous researchers have supported the use of these two criteria in evaluating service quality of hotels, the researcher is not aware of any quantitative service quality study that used these two dimensions. Of particular note is that emotion is evaluated in terms of its frequency of occurrence during the service experience, unlike previous studies. The dimensions of operations management practices are managing employees, managing process and customer feedback. Managers' perceptions on hotel performance were also included in the conceptualized model. Linking operations management practices to overall customer satisfaction is another contribution of this research. Many previous studies attempted to understand the direct link between service quality and performance; although there is an equally dominant view in the literature that the relationship between service quality and performance could be more complex. Hence, there could also be some indirect (mediating) impact on performance through customer satisfaction. This research tested whether there is a mediating effect by customer satisfaction between operations management practices and performance. This test also contributed to the existing literature on service as a whole and on hotels in particular. Moreover, a moderation test of customers' characteristics; gender, purpose of hotel stay, age and education, is also performed in this research, further strengthening the value of this research. Responses from two independently administered surveys have been used in this research, one for hotel customers and a second for hotel managers. Data has been collected in two international airports and a number of hotels in Oman. A sample size of 689 observations was used to test the relationships developed in the conceptualized model. First, factor analysis was carried out on the data to validate the developed dimensions. Exploratory factor analysis (EF A) was performed to explore the dimensions and then confirmatory factor analysis (CFA) was performed to confirm the validity of the dimensions. The measurement model has been checked for its reliability and validity using criteria developed from the available literature. Then, the developed hypotheses were tested using a structural equation model (SEM) using partial least square approach (PLS-SEM). The results have generally confirmed the original conceptualizations. All service quality dimensions, namely employee behaviour/attitude, non-technological tangibility, technological tangibility, positive in-consumption emotions and negative in-consumption emotions and operations management practices, namely managing employees, managing process and customer feedback, have been found to have a statistically significant influence on the overall satisfaction of guests. The hypotheses on the moderating effects of customers' characteristics were partially supported. The results proved that management practices have direct and significant effects on performance. In addition, customer satisfaction was found to be partially mediating the relationship between operations management practices and performance. Knowledge about the dimensions of service quality and operations management practices in hotel industry is valuable for managers in the context of managing and assessing the quality of their service. This research has used the available literature to build a model that has interrelationships between operations management practices, customer perceptions of service quality and performance in the hotel industry. The model has introduced two new dimensions, technology and emotions, which has enriched the literature of service quality evaluation. There is no doubt that managerial awareness of the dimensions influencing customer satisfaction will help in developing competitive advantages for their hotels. In addition, linking operational management practices to overall customer satisfaction and testing its direct and indirect effect on performance has also contributed to knowledge. Thus, in order for managers to increase the hotels' performance in terms of customer satisfaction, special considerations need to be carried through their practices. Moreover, managers' awareness of the moderating role of the customers' characteristics will help in better managing the quality of service provided. The findings of this study in particular will open new directions for future research in the hotel industry in particular and the service industries as a whole

Effects of Paraquat-induced Oxidative Stress on the Neuronal Plasma Membrane Ca2+-ATPase

Oxidative stress leads to the disruption of calcium homeostasis in brain neurons; however, the direct effects of oxidants on proteins that regulate intracellular calcium [Ca2+]i are not known. The calmodulin (CaM) -stimulated plasma membrane Ca2+-ATPase (PMCA) plays a critical role in regulating [Ca2+]i. Our previous in vitro studies showed that PMCA present in brain synaptic membranes is readily inactivated by a variety of reactive oxygen species (ROS). The present studies were conducted to determine the vulnerability of PMCA to ROS generated in neurons as would likely occur in vivo. Primary cortical neurons were exposed to paraquat (PQ), a redox cycling agent that generates intracellular ROS. Low concentrations of PQ (5-10 μM) increased PMCA basal activity by 2-fold but abolished its sensitivity to CaM. Higher concentrations (25-100 μM) inhibited both components of PMCA activity. Immunoblots showed the formation of high molecular weight PMCA aggregates. Additionally, PMCA showed evidence of proteolytic degradation. PMCA proteolysis was prevented by a calpain inhibitor, suggesting a role for calpain. Our findings suggest that PMCA is a sensitive target of oxidative stress in primary neurons. Inactivation of this Ca2+ transporter under prolonged oxidative stress could alter neuronal Ca2+ signaling

Exploring the interrelationships among operations management practices, customer perceptions of service quality and performance of hotels

Hospitality and tourism are important sectors of any economy. In the service sector, achieving a level of service quality that satisfies customers usually results in a competitive advantage in the market. The concept of service quality in hotels has been the subject of many research studies and there are numerous published works in the field. However, only a few studies have focused on the determinants of service quality for hotels using a set of comprehensive criteria. Thus, conceptualizing a service quality model that identifies the dimensions of service quality that affect customers' satisfaction is needed for hotels. In addition, the role of operations management practices in managing service quality cannot be denied. The available literature on the hotel industry in terms of managerial practices is unfortunately poor and needs to be enriched. Logically, better operations management practices in managing hotels' service quality would have a direct positive impact on performance, but there could also be some indirect (mediating) impact on performance through customer satisfaction. The purpose of this research is to build an effective model for measuring service quality in the hotel industry through critical evaluation of the available literature in service in general and hotels in particular. The built model has aspects of customer's perceptions of service quality, management's perceptions of operations management practices and of performance. The existing literature has been used to conceptualize a service quality model that meets the purpose of this research. The conceptualized model has eleven dimensions; seven for customer perceptions on service quality and four for management perceptions of operations management practices in managing service and on performance. The dimensions of customer's perceptions are: employee behaviour/attitude, price fairness, non-technological tangibility, technological tangibility, in-consumption positive emotions, in-consumption negative emotions and overall customer satisfaction. The introductions of technology and in-consumption emotions are one of the main contributions of this research. Though previous researchers have supported the use of these two criteria in evaluating service quality of hotels, the researcher is not aware of any quantitative service quality study that used these two dimensions. Of particular note is that emotion is evaluated in terms of its frequency of occurrence during the service experience, unlike previous studies. The dimensions of operations management practices are managing employees, managing process and customer feedback. Managers' perceptions on hotel performance were also included in the conceptualized model. Linking operations management practices to overall customer satisfaction is another contribution of this research. Many previous studies attempted to understand the direct link between service quality and performance; although there is an equally dominant view in the literature that the relationship between service quality and performance could be more complex. Hence, there could also be some indirect (mediating) impact on performance through customer satisfaction. This research tested whether there is a mediating effect by customer satisfaction between operations management practices and performance. This test also contributed to the existing literature on service as a whole and on hotels in particular. Moreover, a moderation test of customers' characteristics; gender, purpose of hotel stay, age and education, is also performed in this research, further strengthening the value of this research. Responses from two independently administered surveys have been used in this research, one for hotel customers and a second for hotel managers. Data has been collected in two international airports and a number of hotels in Oman. A sample size of 689 observations was used to test the relationships developed in the conceptualized model. First, factor analysis was carried out on the data to validate the developed dimensions. Exploratory factor analysis (EF A) was performed to explore the dimensions and then confirmatory factor analysis (CFA) was performed to confirm the validity of the dimensions. The measurement model has been checked for its reliability and validity using criteria developed from the available literature. Then, the developed hypotheses were tested using a structural equation model (SEM) using partial least square approach (PLS-SEM). The results have generally confirmed the original conceptualizations. All service quality dimensions, namely employee behaviour/attitude, non-technological tangibility, technological tangibility, positive in-consumption emotions and negative in-consumption emotions and operations management practices, namely managing employees, managing process and customer feedback, have been found to have a statistically significant influence on the overall satisfaction of guests. The hypotheses on the moderating effects of customers' characteristics were partially supported. The results proved that management practices have direct and significant effects on performance. In addition, customer satisfaction was found to be partially mediating the relationship between operations management practices and performance. Knowledge about the dimensions of service quality and operations management practices in hotel industry is valuable for managers in the context of managing and assessing the quality of their service. This research has used the available literature to build a model that has interrelationships between operations management practices, customer perceptions of service quality and performance in the hotel industry. The model has introduced two new dimensions, technology and emotions, which has enriched the literature of service quality evaluation. There is no doubt that managerial awareness of the dimensions influencing customer satisfaction will help in developing competitive advantages for their hotels. In addition, linking operational management practices to overall customer satisfaction and testing its direct and indirect effect on performance has also contributed to knowledge. Thus, in order for managers to increase the hotels' performance in terms of customer satisfaction, special considerations need to be carried through their practices. Moreover, managers' awareness of the moderating role of the customers' characteristics will help in better managing the quality of service provided. The findings of this study in particular will open new directions for future research in the hotel industry in particular and the service industries as a whole

Systematic review of the global epidemiology, clinical and laboratory profile of enteric fever

Background: Children suffer the highest burden of enteric fever among populations in South Asian countries. The clinical features are non-specific, vary in populations, and are often difficult to distinguish clinically from other febrile illnesses, leading to delayed or inappropriate diagnosis and treatment. We undertook a systematic review to assess the clinical profile and laboratory features of enteric fever across age groups, economic regions, level of care and antibiotic susceptibility patterns.Methods: We searched PubMed (January 1964-December 2013) for studies describing clinical features in defined cohorts of patients over varying time periods. Studies with all culture-confirmed cases or those with at least 50% culture-confirmed cases were included. 242 reports were screened out of 4398 relevant articles and 180 reports were included for final review.Results: 96% of studies were from an urban location, 96% were hospital-based studies, with 41% of studies were from South Asia. Common clinical features in hospitalized children include high-grade fever, coated tongue, anaemia, nausea/vomiting, diarrhea, constipation, hepatomegaly, splenomegaly neutrophilia, abdominal distension and GI bleeding. In adults\u27 nausea/vomiting, thrombocytopenia and GI perforation predominate. The case-fatality rate in children under 5 years is higher than school aged children and adolescents, and is highest in Sub Saharan Africa and North Africa/Middle East regions. Multi-drug resistant enteric fever has higher rates of complications than drug sensitive enteric fever, but case fatality rates were comparable in both.CONCLUSIONS: Our findings indicate variability in disease presentation in adults compared to children, in different regions and in resistant vs sensitive cases. Majority of studies are from hospitalized cases, and are not disaggregated by age. Despite higher complications in MDR enteric fever, case fatality rate is comparable to sensitive cases, with an overall hospital based CFR of 2%, which is similar to recent global estimates. This review underscores the importance of further epidemiological studies in community settings among children and adults, and the need for further preventable measures to curtail the burden of disease

Single-Molecule Dynamics of the Calcium-Dependent Activation of Plasma-Membrane Ca2+-ATPase by Calmodulin

AbstractThe plasma membrane calcium-ATPase (PMCA) helps to control cytosolic calcium levels by pumping out excess Ca2+. PMCA is regulated by the Ca2+ signaling protein calmodulin (CaM), which stimulates PMCA activity by binding to an autoinhibitory domain of PMCA. We used single-molecule polarization methods to investigate the mechanism of regulation of the PMCA by CaM fluorescently labeled with tetramethylrhodamine. The orientational mobility of PMCA-CaM complexes was determined from the extent of modulation of single-molecule fluorescence upon excitation with a rotating polarization. At a high Ca2+ concentration, the distribution of modulation depths reveals that CaM bound to PMCA is orientationally mobile, as expected for a dissociated autoinhibitory domain of PMCA. In contrast, at a reduced Ca2+ concentration a population of PMCA-CaM complexes appears with significantly reduced orientational mobility. This population can be attributed to PMCA-CaM complexes in which the autoinhibitory domain is not dissociated, and thus the PMCA is inactive. The presence of these complexes demonstrates the inadequacy of a two-state model of Ca2+ pump activation and suggests a regulatory role for the low-mobility state of the complex. When ATP is present, only the high-mobility state is detected, revealing an altered interaction between the autoinhibitory and nucleotide-binding domains

Expectations in a Marriage Proposal: A Gender-Based Comparison in Pakistan

To determine the differences in expectations of males and females regarding marriage proposals. It was a cross-sectional study conducted in Karachi. Young people aged between 18 and 45 years were enrolled in the study. An online questionnaire was circulated through a convenience sampling technique. Our sample had 456 participants with n=294 64.5% females. N=387 84.9% were between 18-25 years of age. N=292 64% did not have a preference regarding spouse’s skin tone but n=269 59.0% preferred a taller spouse. Body type was a considerable factor for n=227 49.8%. N=309 67.8% preferred their partner to have a job, own a business and have a career. Love marriage was preferred by n=194 42.5%. Majority of the sample (58.1%) did not have a preference in terms of ethnicity but n=193 42.2% wanted a spouse from the same sect, denomination or caste. N=357 78.3% were against dowry. 52% of the participants said their choices were influenced by societal norms and culture to some extent. Four most important personality traits in a potential spouse were loyalty (75.7%), respect (62.7%), maturity (49.3%) and honesty (46.5%). The findings of this study are reflective of our community and culture as the majority of individuals are under societal influence. Moreover, their preference in traits emphasizes mutual understanding as opposed to physical characteristics. An adequate understanding of an individual's expectations from a marriage proposal decreases the risk of psychological distress associated with the relationship

Students’ Awareness of Green Culture in UUM

This study discusses about the student awareness of green culture in UUM. Green culture awareness could contribute to economic development as well as protecting the environment for stabilizing purposes. It is the main key for achievement of any organization and could assist university students to be aware about the Green culture in UUM. In this paper, the problems that concerning students’ awareness of green culture tin their daily lives and the level of awareness are discussed. Through this research, the awareness of green culture will be examined by looking at their behavior, attitude and lifestyle, knowledge and education of green culture among students in UUM. Hopefully through this study, students’ awareness on the importance of green culture will be increased

Enzyme inhibition and antibacterial potential of 4-Hydroxycoumarin derivatives

The 4-Hydroxycoumarin derivatives are known to show a broad spectrum of pharmacological applications. In this paper we are reporting the synthesis of a new series of 4-Hydroxycoumarin derivatives synthesized through Knovenegal condensation; they were characterized by using UV-Vis, FT-IR, NMR spectroscopies. The synthesized compounds were evaluated for antibacterial activity against Staphylococcus aureus and Salmonella typhimurium strains. The compounds (2), (3) and (8) showed favorable antibacterial activity with zone of inhibitions 26.5± 0.84, 26.0 ± 0.56 and 26.0 ± 0.26 against Staphylococcus aureus (Gram-positive) respectively. However, the compounds (5) and (9) were found more active with 19.5 ± 0.59 and 19.5 ± 0.32 zone of inhibitions against Salmonella typhimurium (Gram-negative). Whereas, in urease inhibition assay, none of the synthesized derivatives showed significant anti-urease activity; although, in carbonic anhydrase-II inhibition assay, the compound (2) and (6) showed enzyme inhibition activity with IC50 values 263±0.3 and 456±0.1, respectively