Human Equilibrative Nucleoside Transporter Subtype 1: Structure-Function Analysis Using Cysteine Mutagenesis and Thiol Modifying Techniques

Human equilibrative nucleoside transporter 1 is the main mediator of bi-directional nucleoside flux and is found ubiquitously. Inhibitor and substrate interactions with ENT1 are known to be affected by cysteine-modifying reagents. Our aim was to investigate the importance of cysteine residues in hENT1 function and identify which residues were sensitive to thiol modification for further application of cysteine scanning mutagenesis on extracellular loop 5. Transporter function was assessed by the binding of [3H]NBMPR and the cellular uptake of [3H]2-chloroadenosine. Treatment of hENT1 with the neutral sulfhydryl-modifier methyl methanethiosulfonate (MMTS) enhanced [3H]NBMPR binding but decreased [3H]2-chloroadenosine uptake. The membrane impermeable positively charged reagent [2-(Trimethylammonium)ethyl] methane-thiosulfonate (MTSET) but not the negatively charged reagent sodium-(2-sulfonatoethyl)-methanethiosulfonate (MTSES), inhibited [3H]NBMPR binding and enhanced [3H]2-chloroadenosine uptake. Furthermore, all three sulfhydryl modifiers decreased [3H]NBMPR binding when allowed cytoplasmic access. Site-directed mutagenesis on Cys222 eliminated the effect of MMTS on NBMPR binding. Mutation of Cys378 abolished the effect of MTSET on NMBPR binding and indicated that Cys378 is an extracellular-located residue. Mutation of Cys414 led to an enhancement of the ability of MTSET to inhibit NBMPR binding and this effect was eliminated by co-mutation of Cys378. Mutation of Cys416 abolished the effect of charged sulfhydryl reagents to inhibit NBMPR binding in isolated membranes, and also eliminated transport function supporting a conformational linkage between the fifth intracellular loop and the NBMPR binding domain, and implicates this region in the translocation function of hENT1. To further confirm the importance of this region, extracellular loop 5 (EL5) was examined by cysteine scanning mutagenesis as residues in EL5 were individually mutated to cysteines. Mutation of N379, F390, E391, H392, and D393 to cysteine abolished uptake of [3H]2-chloroadenosine indicating their role in the transport mechanism of hENT1. Treatment of EL5 mutants with MTSET inhibited NBMPR binding in all but the V389C mutant. Co-incubation of NBMPR with MTSET was able to protect N379C from thiol modification while co-incubation of adenosine with MTSET protected R384C, Y385C, and L386C from MTSET effects. Our results indicate that adenosine may bind in close vicinity or in direct contact to these residues to prevent MTSET to attain access

Age-Related Effects on Gait Parameters in Healthy Normal Aging Adults

The process of aging brings a set of changes that are widespread in nature. Two of the domains in which age-related effects can be prominently seen are cognition and motor/mobility. Until more recently, gait was viewed as more of a simple and automatic motor process, but increasing evidence suggests the involvement of higher cognitive functioning and attention. The association of age-related gait changes and cognitive decline has been reported in numerous studies, and there is much potential value in examining the cognitively normal aging population to facilitate the establishment of the normal parameters in these areas that are anticipated with advancing age. In particular, a closer examination of the specific gait parameters that are anticipated with normal aging can be helpful in distinguishing pathology from normal progression. The aim of the current study was to evaluate the specific changes in the gait patterns of the normal aging population without the inclusion of the mildly cognitively impaired or cognitively demented populations. All cognitively normal aging individuals performed a series of cognitive and gait tasks. Most of the key gait measurements were collected through a computerized mat that analyzed the specific gait parameters of the subject’s gait during the task. Specifically investigating the changes in these gait patterns over time, the subjects were grouped by their age into age decades during data analysis (subjects aged 50-59, 60-69, 70-79, and 80-89). As anticipated, the results demonstrated a general slowing in gait speed as the groups increased in age, which can largely be seen by the time one reaches their 70s and 80s in age. Additionally, specific parameters relating to spatial measurements and those contributing to balance were found to be worsened with increasing age. Balance instability may potentially be experienced by the 70s age decade, with shorter and more frequent steps taken by the 80s age decade. The general pattern of results indicate that there are indeed certain age effects on gait that can be observed and quantitatively measured at various periods of age decades during normal age progression. Once this normal pattern of gait changes in age advancement is established, it would allow for the early determination of pathology and such motor-based indicators of cognitive decline can contribute immensely toward alleviating the possible confounding effects that education and personal experience may have on traditional language-based measures

Financialization or Capitalization? Debating Capitalist Power in South Korea in the Context of Neoliberal Globalization

capital as power chaebol developmental state financialization institutional political economy Marxian economics post-Keynesian economics South KoreaThe article reviews debates concerning financialization in South Korea, with a focus on ongoing arguments between liberal, post-Keynesian, institutionalist and Marxist economists. It argues that post-Keynesian and institutionalist perspectives in particular neglect important class processes through which the financial circuit operates within the Korean economy, especially the power of Korea’s large, family-led conglomerates, or chaebol. In order to build upon Marxist approaches to Korean finance, we argue that Nitzen and Bichler’s approach to the ‘capitalization’ of capitalist class power provides a useful heuristic for understanding the differential power of Korean chaebol and their integration into global capital

Systematic Modification of Zingerone Reveals Structural Requirements for Attraction of Jarvis’s Fruit Fly

Tephritid fruit flies are amongst the most significant horticultural pests globally and male chemical lures are important for monitoring and control. Zingerone has emerged as a unique male fruit fly lure that can attract dacine fruit flies that are weakly or non-responsive to methyl eugenol and cuelure. However, the key features of zingerone that mediate this attraction are unknown. As Jarvis’s fruit fly, Bactrocera jarvisi (Tryon), is strongly attracted to zingerone, we evaluated the response of B. jarvisi to 37 zingerone analogues in a series of field trials to elucidate the functional groups involved in attraction. The most attractive analogues were alkoxy derivatives, with isopropoxy being the most attractive, followed by ethoxy and trifluoromethoxy analogues. All of the phenolic esters tested were also attractive with the response typically decreasing with increasing size of the ester. Results indicate that the carbonyl group, methoxy group, and phenol of zingerone are key sites for the attraction of B. jarvisi and identify some constraints on the range of structural modifications that can be made to zingerone without compromising attraction. These findings are important for future work in developing and optimising novel male chemical lures for fruit flies

Antecedents of Job Satisfaction among Intimate Partner Violence Shelter Staff: Coworker Relational Maintenance Strategies, Communication Satisfaction, Burnout and Organizational Commitment

poster abstractThis study sought to extend prior research by examining the prevalence of relational maintenance strategies between coworkers and the impact of such strategies on work related attitude of job satisfaction, organizational commitment, communication satisfaction, and burnout with work. The targeted samples for this research were the employees of a battered women’s shelter located in Indianapolis, Indiana. A questionnaire was constructed that included established scales in order to measure independent and dependent variables. The questionnaires were distributed among the employees and 47.82% agreed to participate in this study. Regression analyses were conducted to analyze the collected data. The findings indicated the importance of assurances and conflict management among staffs in mitigating their job stresses and increasing their personal accomplishment, communication satisfaction, organizational commitment and job satisfaction

Current Dyspnea Among Long-Term Survivors of Early-Stage Non-small Cell Lung Cancer

IntroductionDyspnea is common among lung cancer patients. As most studies of dyspnea have reviewed patients with active cancer or immediately after treatment, its prevalence during the longer-term period once treatment has been completed is not well characterized. This study quantifies the prevalence of dyspnea among lung cancer survivors and identifies potential correlates that may be amenable to intervention.MethodsCross-sectional survey of 342 patients with disease-free, stage I, non-small cell lung cancer, assessed 1 to 6 years after surgical resection. Dyspnea was quantified using the Baseline Dyspnea Index. Any moderate/strenuous physical activity was measured using the Godin Leisure-Time Exercise Questionnaire. Mood disorder symptoms were assessed using the Hospital Anxiety and Depression Scale. Multiple regression analyses were used to examine demographic, medical, and health-related correlates of dyspnea.ResultsMean age was 68.9 years. Average predicted preoperative forced expiratory volume in 1 second was 89.0%. Current dyspnea, defined by a Baseline Dyspnea Index score of 9 or less, existed among 205 (60%) individuals. For 133 (65%) of these patients, dyspnea was absent preoperatively. Multivariate correlates of current dyspnea included preoperative dyspnea (odds ratio [OR] = 5.31), preoperative diffusing capacity (OR = 0.98), lack of moderate/strenuous physical activity (OR = 0.41), and the presence of clinically significant depression symptoms (OR = 4.10).ConclusionsDyspnea is common 1 to 6 years after lung cancer resection, and is associated with the presence of preoperative dyspnea, reduced diffusing capacity, clinically significant depression symptoms, and lack of physical activity. Further research is needed to test whether strategies that identify and treat patients with these conditions attenuate dyspnea among lung cancer survivors

Surface energy-mediated construction of anisotropic semiconductor wires with selective crystallographic polarity.

ZnO is a wide band-gap semiconductor with piezoelectric properties suitable for opto-electronics, sensors, and as an electrode material. Controlling the shape and crystallography of any semiconducting nanomaterial is a key step towards extending their use in applications. Whilst anisotropic ZnO wires have been routinely fabricated, precise control over the specific surface facets and tailoring of polar and non-polar growth directions still requires significant refinement. Manipulating the surface energy of crystal facets is a generic approach for the rational design and growth of one-dimensional (1D) building blocks. Although the surface energy is one basic factor for governing crystal nucleation and growth of anisotropic 1D structures, structural control based on surface energy minimization has not been yet demonstrated. Here, we report an electronic configuration scheme to rationally modulate surface electrostatic energies for crystallographic-selective growth of ZnO wires. The facets and orientations of ZnO wires are transformed between hexagonal and rectangular/diamond cross-sections with polar and non-polar growth directions, exhibiting different optical and piezoelectrical properties. Our novel synthetic route for ZnO wire fabrication provides new opportunities for future opto-electronics, piezoelectronics, and electronics, with new topological properties

Zingerone in the Flower of Passiflora maliformis Attracts an Australian Fruit Fly, Bactrocera jarvisi (Tryon)

Passiflora maliformis is an introduced plant in Australia but its flowers are known to attract the native Jarvis’s fruit fly, Bactrocera jarvisi (Tryon). The present study identifies and quantifies likely attractant(s) of male B. jarvisi in P. maliformis flowers. The chemical compositions of the inner and outer coronal filaments, anther, stigma, ovary, sepal, and petal of P. maliformis were separately extracted with ethanol and analyzed using gas chromatography-mass spectrometry (GC-MS). Polyisoprenoid lipid precursors, fatty acids and their derivatives, and phenylpropanoids were detected in P. maliformis flowers. Phenylpropanoids included raspberry ketone, cuelure, zingerone, and zingerol, although compositions varied markedly amongst the flower parts. P. maliformis flowers were open for less than one day, and the amounts of some of the compounds decreased throughout the day. The attraction of male B. jarvisi to P. maliformis flowers is most readily explained by the presence of zingerone in these flowers

Implementation of Clinical Research Trials Using Web-Based and Mobile Devices: challenges and solutions.

BACKGROUND: With the increasing implementation of web-based, mobile health interventions in clinical trials, it is crucial for researchers to address the security and privacy concerns of patient information according to high ethical standards. The full process of meeting these standards is often made more complicated due to the use of internet-based technology and smartphones for treatment, telecommunication, and data collection; however, this process is not well-documented in the literature. RESULTS: The Smart Heart Trial is a single-arm feasibility study that is currently assessing the effects of a web-based, mobile lifestyle intervention for overweight and obese children and youth with congenital heart disease in Southwestern Ontario. Participants receive telephone counseling regarding nutrition and fitness; and complete goal-setting activities on a web-based application. This paper provides a detailed overview of the challenges the study faced in meeting the high standards of our Research Ethics Board, specifically regarding patient privacy. CONCLUSION: We outline our solutions, successes, limitations, and lessons learned to inform future similar studies; and model much needed transparency in ensuring high quality security and protection of patient privacy when using web-based and mobile devices for telecommunication and data collection in clinical research