37 research outputs found

    Work to Family Enrichment as Mediator between Organizational Support and Employees’ Performance

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    This study investigates the relationship between work to family organizational support and employees’ performance, mediated by work to family enrichment. It analyses primary data, collected from the various commercial banks, operating in Sindh, Pakistan (N=401). A five point Likert type of survey questionnaire was distributed to respondents. The study applies the structural equation modeling approach (SEM) for data analysis purpose. Mediation analysis has been conducted following the procedure of Preacher and Hayes (2004, 2008) and Rucker, Preacher, Tormala, & Petty (2011). Results show the significant main effect of work to family organizational support and the indirect effect, through work to family enrichment on employees’ performance. Overall, this study establishes work to family enrichment as the missing link in the relationship between work to family organizational support and employees’ performance. The study contributes theoretically by incorporating the role of social exchange theory and work family enrichment theory. Empirical contribution of this study is to confirm the effect of work to family organizational support on employees’ performance and work to family enrichment as the mediator

    Tyrosinase inhibition: conformational analysis based studies on molecular dynamics calculations of bipiperidine based inhibitors.

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    Two series of variably N-substituted biperidines were synthesized by condensing various acid chlorides, alkyl halides and anhydrides with 1,4-bipiperidine. The new compounds were tested as tyrosinase inhibitors and a structure-activity relationship (SAR) study was carried out. Potent inhibition was observed in the case of the 4'-methylbenzyl substitution on this atom (IC50 = 1.72 microM) with this compound being a lead for future drug design. Additionally, calculations of the important QSAR molecular descriptors were done on the biperidine analogues after their 2 ps molecular dynamics (MD) simulations using molecular mechanics force field (MMFF) approaches. Using MD simulations potential and total energies were calculated for the energy minimized models of bipiperidine and the most active analogs 2, 3, 4, 6, 8 and 10

    Designed Inhibitors of Insulin-Degrading Enzyme Regulate the Catabolism and Activity of Insulin

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    Background: Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, potent and selective inhibitors of IDE have not yet emerged. Methodology/Principal Findings: We used a rational design approach based on analysis of combinatorial peptide mixtures and focused compound libraries to develop novel peptide hydroxamic acid inhibitors of IDE. The resulting compounds are ∼106 times more potent than existing inhibitors, non-toxic, and surprisingly selective for IDE vis-à-vis conventional zinc-metalloproteases. Crystallographic analysis of an IDE-inhibitor complex reveals a novel mode of inhibition based on stabilization of IDE's “closed,” inactive conformation. We show further that pharmacological inhibition of IDE potentiates insulin signaling by a mechanism involving reduced catabolism of internalized insulin. Conclusions/Significance: The inhibitors we describe are the first to potently and selectively inhibit IDE or indeed any member of this atypical zinc-metalloprotease superfamily. The distinctive structure of IDE's active site, and the mode of action of our inhibitors, suggests that it may be possible to develop inhibitors that cross-react minimally with conventional zinc-metalloproteases. Significantly, our results reveal that insulin signaling is normally regulated by IDE activity not only extracellularly but also within cells, supporting the longstanding view that IDE inhibitors could hold therapeutic value for the treatment of diabetes

    Impact of Work from Home on Organizational Commitment: The Moderating Role of Emotional Intelligence

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    Many organizations adopted new working patterns to cope with the situation brought about by the pandemic in the year 2020. The prime objective behind this study was to investigate the potential predictor of organizational commitment during working from home while measuring the moderating effect of emotional intelligence. A quantitative approach is used to meet the objective of the research. The appropriate sample size was 200 employees of education sector and the obtained responses were examined with the usage of Smart PLS software. The study was able to bridge the gap by measuring work from home as a new working atmosphere and the results indicated there exists a notable relation between Work from Home and Organizational commitment. Moreover, the quantitative results can be generalized to the education sector of Pakistan and support the belief that working from home can be a positive change in the pre-existing working model in organizations

    How leader member exchange affects effectiveness of performance appraisal system: A chain of reactions model

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    AbstractThe main purpose of the current study was to evaluate the effectiveness of performance appraisal system that highlights the role of performance appraisal reactions (i.e. performance appraisal fairness and performance appraisal satisfaction) in the relationship between leader-member exchange and effectiveness of performance appraisal. Fairness of performance appraisal reactions (i.e. distributive and procedural) mediates at step one and satisfaction with performance appraisal reaction mediates at step two, in a serial mediation model. The study was a cross-sectional quantitative study in which survey approach was used for data collection. The data were collected through a survey questionnaire, from 557 teachers, working in school education department of Punjab, Pakistan, using proportionate random sampling technique. The findings of this study showed the significant effect of the quality of the leader member exchange relationship on effectiveness of performance appraisal system. Further, in a serial mediation model, performance appraisal reactions, i.e. fairness of performance appraisal (distributive and procedural), were found as mediators at step one and satisfaction with performance appraisal as mediator at step two in the aforementioned relationship

    Lipoxygenase Inhibitory Tetraketones: Potential Remedial Source for Inflammation and Asthma: Las Tetracetonas Inhibidoras de la Lipoxigenasa: Fuente Potencial Remedial para la Inflamación y el Asma

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    Objective: A series of tetraketones has been synthesized by way of a one pot synthesis and screened for inhibitory activity against the enzyme lipoxygenase. Method: An efficient and high yielding one pot synthesis to tetraketones [2−22] has been developed by way of tetraethyl ammonium bromide (Et4N+Br¯) mediated condensation of cyclohexane-1, 3-dione [1] with a variety of aldehydes. Lipoxygenase enzyme solution was prepared so that enzyme concentration in reaction mixture was adjusted to give rates of 0.05 absorbance/minute. The test compounds were prepared in methanol of concentrations 50, 25, 12.5, 6.25 and 3.125 µM. The reaction mixture contained 160 µL (100 mM) sodium phosphate buffer (pH 8.0), 10µL of test-compound solution and 20µL of lipoxygenase solution. The contents were mixed and incubated for 10 minutes at 25°C. The reaction was then initiated by the addition of 10µL substrate solution (linoleic acid, 0.5 mM, 0.12% w/v tween 20 in the ratio of 1:2), with the formation of (9Z,11E)-(13S)-13 hydroperoxyoctadeca-9, 11-dienoate, the change of absorbance at 234 nm was followed for 6 minutes. The concentrations of the test compounds that inhibited the lipoxygenase activity by 50% (IC50) were determined by monitoring the effect of increasing concentrations of these compounds in the assays on the degree of inhibition. The IC 50 values were calculated by means of the EZ-Fit Enzyme-Kinetics Program (Perrella Scientific Inc., Amherst, USA). Result: The tetraketones [2 −22] were synthesized in high yields (91–98%) using mild reaction. conditions. Most of these compounds showed significant inhibitory activity against the enzyme lipoxygenase. It was found that the presence of substituents which increase delocalization of electrons enhances the inhibitory activity. Conclusion: It is concluded that the study is likely to lead to the discovery of the rapeutically efficient agents against important disorders such as inflammation and asthma. RESUMEN Objetivo: Una serie de tetracetonas han sido sintetizadas mediante síntesis de varios pasos en un solo reactor (one-pot), y examinadas en relación con su actividad inhibitoria frente a la enzima lipoxigenasa. Método: Una síntesis one-pot de un rendimiento alto y eficiente para la obtención de tetracetonas (2-22) ha sido desarrollada mediantebromuro amónico tetraetíli (Et4N+Br¯) –deciclohexano-1, 3-diona, con una variedad de aldehídos. La solución de enzima lipoxigenasa fue preparada de modo que la concentración de la enzima en las mezcla de la reacción fue ajustada para que diera tasas de 0.05 absorbancia/minuto. Los compuestos de la prueba fueron preparados en metanol de concentraciones (50, 25, 12.5, 6.25 y 3.125 µM). La mezcla de reacción contenía 160 µL (100 mM) de un tampón (buffer) de fosfato de sodio (pH 8.0), 10µL de solución de compuesto de prueba, y 20µL de solución de lipoxigenasa. Los contenidos fueron mezclados e incubados por 10 minutos a 25 °C. La reacción fue iniciada entonces por la adición de 10µL de solución substrato (ácido linoleico, 0.5 mM, 0.12% p/v tween 20 en proporción de 1:2), con la formación de (9Z, 11E)-(13S)-13-hidroperoxioctadeca-9, 11- dienoato, el cambio de absorbancia a 234 nm fue seguido por 6 minutos. Las concentraciones de los compuestos de prueba que inhibían la actividad de la lipoxigenasa en un 50% (IC50) fueron determinadas monitoreando el efecto del aumento de las concentraciones de estos compuestos en los ensayos sobre el grado de inhibición. Los valores IC50 fueron calculados mediante el Programa Cinética de la Enzima EZ-Fit (Perrella Scientific Inc., Amherst, USA). Resultados: Las tetracetonas (2-22) se sintetizaron con elevados rendimientos (91–98%) usando condiciones de reacción leve. La mayoría de estos compuestos mostraron una actividad inhibitoria significativa frente a la enzima lipoxigenasa. Se halló que la presencia de sustituyentes que aumentan la deslocalización de los electrones contribuye a mejorar la actividad inhibitoria. Conclusión: Se concluye que es probable que el estudio conduzca al descubrimiento de agentes terapéuticamente eficientes frente a trastornos importantes tales como la inflamación y el asma

    Synthesis of first tetrathiafulvalene-carbohydrate derivatives

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    In this communication a convenient and novel method for the synthesis of tetrathiafulvalene-carbohydrate (TTF) derivatives from anhydro triflyl-, iodo- and bromo-sugars is described

    Transient Pharmacologic Lowering of Aβ Production Prior to Deposition Results in Sustained Reduction of Amyloid Plaque Pathology

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    Background: Alzheimer’s disease (AD) is the leading cause of dementia among the elderly. Disease modifying therapies targeting Aβ that are in development have been proposed to be more effective if treatment was initiated prior to significant accumulation of Aβ in the brain, but optimal timing of treatment initiation has not been clearly established in the clinic. We compared the efficacy of transient pharmacologic reduction of brain Aβ with a γ-secretase inhibitor (GSI ) for 1–3 months (M) treatment windows in APP Tg2576 mice and subsequent aging of the mice to either 15M or 18M. Results: These data show that reducing Aβ production in a 2-3M windows both initiated and discontinued before detectable Aβ deposition has the most significant impact on Aβ loads up to 11M after treatment discontinuation. In contrast, initiation of treatment for 3M windows from 7-10M or 12-15M shows progressively decreasing efficacy. Conclusions: These data have major implications for clinical testing of therapeutics aimed at lowering Aβ production, indicating that; i) these therapies may have little efficacy unless tested as prophylactics or in the earliest preclinical stage of AD where there is no or minimal Aβ accumulation and ii) lowering Aβ production transiently during a critical pre-deposition window potentially provides long-lasting efficacy after discontinuation of the treatment
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