Role of Microglial α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator in Neuroinflammatory Pain Models in Mice

Neuroinflammatory pain affects about 1.5% of the United States population. Around 20-40% patients having neurological disorders are affected with neuroinflammatory pain. As a part of the limbic system, hippocampus is known to play a critical role in pain perception and processing, and is densely populated with microglial cells and α7 nicotinic acetylcholine receptors (nAChRs). Given the role of microglial α7 nAChRs in neuroinflammation, the α7 nAChRs have emerged as potential target for neuroinflammatory pain treatment. We hypothesized that microglial α7 nAChRs positive allosteric modulation in the hippocampus will decrease neuroinflammatory pain at behavioral, cellular, biochemical, and molecular level. The primary objective of current study was to examine the role of an α7 nAChR positive allosteric modulator (PAM), TQS, in neuroinflammatory pain and to determine biochemical, cellular, and molecular mechanisms associated with neuroinflammatory pain in the hippocampus using mouse models. We demonstrated that TQS reduced neuroinflammatory pain-like symptoms, including tactile allodynia and thermal hyperalgesia in mice. Methyllcaconitine, an α7 nAChR antagonist, reversed antiallodynic and antihyperalgesic effects of TQS suggesting the involvement of α7 nAChR. The TQS decreased the expression of ionized calcium binding adapter molecule 1 and cluster of differentiation 11b, microglial activation markers, in the hippocampus. We determined that TQS reduced inhibitor of kappa B, a downstream mediator that decreases due to nuclear factor-κB (NF-κB) inactivation, and p-NF-κB p65 expression in the hippocampus. In addition, TQS reduced the expression of tumor necrosis factor (TNF) and increased the level of norepinephrine in the hippocampus. We determined that TQS decreased the expression of brain-derived neurotrophic factor (BDNF). Similarly, we determined that TQS reduced the activation of Na-K-Cl cotransporter 1 and increased K-Cl co-transporter 2 expression. Taken together, our results indicated that TQS decreased microglial TNF and BDNF expression and associated signaling in neuroinflammatory pain involving α7 nAChR and microglial activation. Our findings provided strong and novel evidence that microglial α7 nAChR positive allostetric modulation-mediated signaling regulate behavioral, cellular, biochemical, and molecular mechanisms underlying neuroinflammatory pain. Therefore, targeting microglial α7 nAChR positive allosteric modulation in the hippocampus might be a novel strategy for the treatment of neuroinflammatory pain

Влияние трансформационного лидерства на организационную и лидерскую эффективность: эмпирический пример Пакистана

Modern dynamic era and today’s cognizant society compels the new leaders to face real challenges for leaders around the globe; based on the strong ties of knowledge integration companies focus on nurturing innovation for survival and strive for improvements to compete and sustain in the market. However, organizations sometimes fail to achieve viable competitive advantage due to their limited understanding of the relationships amid these premeditated variables. This study investigates the impact of transformational leadership on organizational performance; employing organizational innovation as the mediating role. The study explores that the relationship between “transformational leadership” and “organizational performance” is convincing. “Convenience sampling techniques” are employed to gather information i.e. data is collected by using questionnaire employed to evaluate transformational leaders. Questionnaires consist of 25 question items have been distributed among multiple tier leaders working in MIA Group and is subsequently analyzed by using SPSS. The current research will assist the managers/leading role professionals to develop a required leadership style in one's organizations. Most of the organizations require an environment where employees are encouraged by motivated leaders and become more effective and creative in leading successful organizations. Further, it provides persuasive evidence for the significance of continuing the efforts to understand the nature of the leadership behaviors-effectiveness connection.La era dinámica moderna y la sociedad consciente de hoy obliga a los nuevos líderes a enfrentar desafíos reales para los líderes de todo el mundo; basadas en los fuertes lazos de integración de conocimiento, las empresas se centran en fomentar la innovación para la supervivencia y se esfuerzan por mejorar para competir y mantenerse en el mercado. Sin embargo, las organizaciones a veces no logran una ventaja competitiva viable debido a su comprensión limitada de las relaciones en medio de estas variables premeditadas. Este estudio investiga el impacto del liderazgo transformacional en el desempeño organizacional; Empleando la innovación organizativa como el papel mediador. El estudio explora que la relación entre "liderazgo transformacional" y "desempeño organizacional" es convincente. Las "técnicas de muestreo de conveniencia" se emplean para recopilar información, es decir, los datos se recopilan mediante el cuestionario empleado para evaluar a los líderes transformacionales. Los cuestionarios consisten en 25 preguntas que se han distribuido entre líderes de múltiples niveles que trabajan en el Grupo MIA y se analizan posteriormente mediante el uso de SPSS. La investigación actual ayudará a los gerentes / profesionales de rol líder a desarrollar un estilo de liderazgo requerido en las organizaciones de uno. La mayoría de las organizaciones requieren un entorno donde los empleados estén motivados por líderes motivados y sean más efectivos y creativos para liderar organizaciones exitosas. Además, proporciona evidencia persuasiva de la importancia de continuar los esfuerzos para comprender la naturaleza de la conexión entre el comportamiento y la eficacia del liderazgo.Современная динамичная эпоха и современное сознательное общество заставляют новых лидеров сталкиваться с реальными проблемами для лидеров во всем мире; Основываясь на прочных связях в области интеграции знаний, компании сосредоточены на развитии инноваций для выживания и стремятся к улучшениям, чтобы конкурировать и поддерживать на рынке. Однако организациям иногда не удается добиться жизнеспособного конкурентного преимущества из-за их ограниченного понимания взаимоотношений среди этих преднамеренных переменных. Это исследование исследует влияние трансформационного лидерства на организационные показатели; использование организационных инноваций в качестве посреднической роли. В исследовании исследуется, что связь между «трансформационным лидерством» и «эффективностью организации» является убедительной. «Удобные методы выборки» используются для сбора информации, то есть данные собираются с использованием вопросника, используемого для оценки лидеров трансформации. Анкеты состоят из 25 вопросов, которые были распределены среди лидеров нескольких уровней, работающих в MIA Group, и впоследствии анализируются с использованием SPSS. Текущее исследование поможет менеджерам / ведущим специалистам по ролям выработать необходимый стиль руководства в своих организациях. Большинству организаций требуется среда, в которой мотивированные лидеры поощряют сотрудников и становятся более эффективными и креативными в ведущих успешных организациях. Кроме того, он предоставляет убедительные доказательства значимости продолжения усилий по пониманию природы связи между поведением и эффективностью руководства

DRIVERS OF EMPLOYEE ENGAGEMENT AND ROLE OF TRANSACTIONAL LEADERSHIP-CASE OF PAKISTANI BANKING SECTOR

The purpose of the article: This research explored and contributes to the leadership literature by investigating the influence of transactional leadership over employee engagement at certain banks located in KPK and Punjab province of Pakistan. It observes the influence of main aspects i-e contingent reward, active management by exception (MBE active) on worker’s regular job commitmentMaterials and methods: This distinctive combination of leadership behaviors are compared with attention given specifically to everyday work settings. Twenty banks are selected involving 180 employees. Questionnaires and interviews are conducted to collect data.Results of the research: The relationships among variables are examined through the Spearman Rank-order correlation coefficient.  The moderating effects associated with corporate culture are observed by employing multiple regression analyses. A positive and significant relationship is revealed between transactional management and chosen variables except “passive management by exemption”. It is safely predicted that employee job satisfaction can be greatly elevated through transactional leadership. It is established that “contingent reward” and “active management by exemption” improve worker's engagement in contrast to passive management by exemption. Applications: This research can be used for universities, teachers, and students. Novelty/Originality: In this research, the model of Drivers of Employee Engagement and Role of Transactional Leadership-Case of Pakistani Banking Sector is presented in a comprehensive and complete manner

Knowledge Management Practices and Transformational Leadership Traits: Predicting Process Innovation in FMCG Industry

Organizations in the current competitive and challenging situation considered organizational process innovation to sustain themselves with competitive advantage and provisioning of high value products to consumers. The current study investigates the role of transformational leadership traits and knowledge management practices on predicting the process innovation in FMCG companies. Data has been collected from the 10 FMCG companies located in major two cities i.e. Lahore and Karachi, Pakistan. Sample of 200 top line managers have been selected by convenience sampling method and adapted itemized questionnaire has been presented to the top management after a brief session of face to face interviews. Response of 170 top line employees has been registered and statistical testing has been done on SPSS 22. Results indicated that the transformational leadership traits has significantly positive impact on process innovation which effectively expedites the production efficiency of manufacturing units. The knowledge management practices such as acquisition, transfer and application has strong and positively significant association with process innovation. The knowledge management practices positively mediates with transformational leadership traits and resultantly lays foundation for continuous process improvement to survive in market. This conceptual model practically helps the production and manufacturing companies to nurture positive change management attitudes, decreasing production time, expanding products range, development of skills needed to advocate and adopt change, employee involvement, commitment and benefits of large scale economy. This study is limited to FMCGs in major cities and can be expanded to services industry and test the conceptual model

Comparative Chloroplast Genomics in Phyllanthaceae Species

Family Phyllanthaceae belongs to the eudicot order Malpighiales, and its species are herbs, shrubs, and trees that are mostly distributed in tropical regions. Here, we elucidate the molecular evolution of the chloroplast genome in Phyllanthaceae and identify the polymorphic loci for phylogenetic inference. We de novo assembled the chloroplast genomes of three Phyllanthaceae species, i.e., Phyllanthus emblica, Flueggea virosa, and Leptopus cordifolius, and compared them with six other previously reported genomes. All species comprised two inverted repeat regions (size range 23,921–27,128 bp) that separated large single-copy (83,627–89,932 bp) and small single-copy (17,424–19,441 bp) regions. Chloroplast genomes contained 111–112 unique genes, including 77–78 protein-coding, 30 tRNAs, and 4 rRNAs. The deletion/pseudogenization of rps16 genes was found in only two species. High variability was seen in the number of oligonucleotide repeats, while guanine-cytosine contents, codon usage, amino acid frequency, simple sequence repeats, synonymous and non-synonymous substitutions, and transition and transversion substitutions were similar. The transition substitutions were higher in coding sequences than in non-coding sequences. Phylogenetic analysis revealed the polyphyletic nature of the genus Phyllanthus. The polymorphic protein-coding genes, including rpl22, ycf1, matK, ndhF, and rps15, were also determined, which may be helpful for reconstructing the high-resolution phylogenetic tree of the family Phyllanthaceae. Overall, the study provides insight into the chloroplast genome evolution in Phyllanthaceae

Comparative Chloroplast Genomics in Phyllanthaceae Species

Family Phyllanthaceae belongs to the eudicot order Malpighiales, and its species are herbs, shrubs, and trees that are mostly distributed in tropical regions. Here, we elucidate the molecular evolution of the chloroplast genome in Phyllanthaceae and identify the polymorphic loci for phylogenetic inference. We de novo assembled the chloroplast genomes of three Phyllanthaceae species, i.e., Phyllanthus emblica, Flueggea virosa, and Leptopus cordifolius, and compared them with six other previously reported genomes. All species comprised two inverted repeat regions (size range 23,921–27,128 bp) that separated large single-copy (83,627–89,932 bp) and small single-copy (17,424–19,441 bp) regions. Chloroplast genomes contained 111–112 unique genes, including 77–78 protein-coding, 30 tRNAs, and 4 rRNAs. The deletion/pseudogenization of rps16 genes was found in only two species. High variability was seen in the number of oligonucleotide repeats, while guanine-cytosine contents, codon usage, amino acid frequency, simple sequence repeats, synonymous and non-synonymous substitutions, and transition and transversion substitutions were similar. The transition substitutions were higher in coding sequences than in non-coding sequences. Phylogenetic analysis revealed the polyphyletic nature of the genus Phyllanthus. The polymorphic protein-coding genes, including rpl22, ycf1, matK, ndhF, and rps15, were also determined, which may be helpful for reconstructing the high-resolution phylogenetic tree of the family Phyllanthaceae. Overall, the study provides insight into the chloroplast genome evolution in Phyllanthaceae

Organizational Performance and Entrepreneurial Orientation: The Intervening Role of Organizational Learning

Many past studies have examined the association between entrepreneurial orientation (E.O.) and organizational performance (O.P.). However, these studies have not adequately addressed the mediating roles of acquisition learning (A.L.) and experiential learning (E.L.) on organizational performance. Given this gap, we have developed a new model that contains six direct relationships, three mediating relationships, and one multi-mediating relationship. The focus of the study was on Indonesian Pharmaceutical SMEs. We have collected a sample of 365 respondents non-randomly. For statistical analysis, we have used Smart PLS version 3.2. The statistical analysis includes reliability, validity, and descriptive statistics. The results confirm that acquisition learning (A.L.), experiential learning (E.L.), and entrepreneurial orientation (E.O.) promote organizational performance (O.P.). We also found that entrepreneurial orientation (E.O.) impacts acquisition learning (A.L.) and innovative performance (I.P.) but does not affect organizational performance (O.P.). However, the results suggest that acquisition learning (A.L.) and experiential learning (E.L.) are positively linked. Our results also support all the mediating relationships

The Benzimidazole Derivatives, B1 (N-[(1H-Benzimidazol-2-yl)Methyl]-4-Methoxyaniline) and B8 (N-{4-[(1H-Benzimidazol-2-yl)Methoxy]Phenyl}Acetamide) Attenuate Morphine-Induced Paradoxical Pain in Mice

Despite being routinely used for pain management, opioid use is limited due to adverse effects such as development of tolerance and paradoxical pain, including thermal hyperalgesia and mechanical allodynia. Evidence indicates that continued morphine administration causes increased expression of proinflammatory mediators such as tumor necrosis factor-alpha (TNF-α). The objectives of the present study were to determine the effects of B1 (N-[(1H-benzimidazol-2-yl)methyl]-4-methoxyaniline) and B8 (N-{4-[(1H-benzimidazol-2-yl)methoxy]phenyl}acetamide), benzimidazole derivatives, on thermal nociception and mechanical allodynia during repeated morphine (intraperitoneal; 5 mg/kg twice daily for 6 days)-induced paradoxical pain and TNF-α expression in the spinal cord in mice. Our data indicate that administration of benzimidazole derivatives attenuated morphine-induced thermal hyperalgesia and mechanical allodynia. Benzimidazole derivatives also reduced TNF-α expression in mice. Taken together, these results suggest that benzimidazole derivatives might be useful for the treatment of neuroinflammatory consequences of continued morphine administration and could be potential drug candidates for the management of opioid-induced paradoxical pain