Withania somnitera and withanolide a mediated restoration of AMPA and NMDA receptor function in pilocarpine induced temporal lobe epilepsy

The onset of spontaneous seizures triggers a cascade of molecular and cellular events that eventually leads to neuronal injury and cognitive decline. The present study investigated the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in restoring behavioural deficit by inhibiting oxidative stress induced alteration in glutamergic neurotransmission. The subdued performance in behavioural tests shows impaired motor coordination and memory. Histopathological investigations revealed significant neuronal loss in hippocampus of epileptic rats indicating glutamate mediated excitotoxicity. The treatment with WS and WA restored behavioural deficit and ameliorated neuronal loss. An altered redox homeostasis leading to oxidative stress is a hallmark of TLE. The antioxidant potential was afflicted in epileptic rats, evident from altered activity of SOD and CAT, down regulation of SOD and GPX expression and enhanced lipid peroxidation. The antioxidant property of WS and WA restored altered antioxidant capacity. Alteration in GDH activity and down regulation of GLAST expression resulted in enhanced glutamate content in the brain regions. The metabolism of glutamate was altered in the form of down regulated GAD expression. The alteration in synthesis, transport and metabolism resulted in further increase of the glutamate concentration at the synapse leading to glutamate mediated excitotoxicity. The decreased NMDA and AMPA receptor binding and down regulated NMDA R1, NMDA 2B and AMPA (GluR2) mRNA expression indicated altered glutamergic receptor function. The treatment with WS and WA reversed altered glutamergic receptor function, synthesis, transport and metabolism. The enhanced levels of second messenger IP3 responsible for Ca2+ mediated toxicity was reversed after treatment with WS and WA. Neurotoxics concentration of glutamate resulted in up regulation of pro apoptotic factors Bax and Caspase 8 and down regulation of anti apoptotic factor Akt resulting in neuronal death. The treatment with WS and WA resulted in activation of Akt and down regulation of Bax and caspase 8 leading to blocking of apoptotic pathway. The treatment with WS and WA resulted in reduced seizure frequency and amelioration of associated alterations suggesting the therapeutic role of Withania somnifera in temporal lobe epilepsy

Product and Process Innovation: Antecedents and Performance outcomes in small IT firms in India

Innovation is a strategic necessity for the survival of today’s organizations. The wide recognition of innovation as a competitive necessity, particularly in dynamic market environments, makes it an evergreen domain for research. This dissertation deals with innovation in small Information Technology (IT) firms in India. The IT industry in India has been a phenomenal success story of the last three decades, and is today facing a crucial phase in its history characterized by the need for fundamental changes in strategies, driven by innovation. This study, while motivated by the dynamics of changing times, importantly addresses the research gap on small firm innovation in Indian IT.This study addresses three main objectives: (a) drivers of innovation in small IT firms in India (b) impact of innovation on firm performance (c) variation in the extent of innovation adoption in small firms. Product and process innovation were identified as the two most contextually relevant types of innovation for small IT firms. The antecedents of innovation were identified as Intellectual Capital, Creative Capability, Top Management Support, Organization Learning Capability, Customer Involvement, External Networking and Employee Involvement.Survey method was adopted for data collection and the study unit was the firm. Surveys were conducted in 2014 across five South Indian cities. Small firm was defined as one with 10-499 employees. Responses from 205 firms were chosen for analysis. Rigorous statistical analysis was done to generate meaningful insights. The set of drivers of product innovation (Intellectual Capital, Creative Capability, Top Management Support, Customer Involvement, External Networking, and Employee Involvement)were different from that of process innovation (Creative Capability, Organization Learning Capability, External Networking, and Employee Involvement). Both product and process innovation had strong impact on firm performance. It was found that firms that adopted a combination of product innovation and process innovation had the highest levels of firm performance. Product innovation and process innovation fully mediated the relationship between all the seven antecedents and firm performance The results of this study have several important theoretical and practical implications. To the best of the researcher’s knowledge, this is the first time that an empirical study of firm level innovation of this kind has been undertaken in India. A measurement model for product and process innovation was developed, and the drivers of innovation were established statistically. Customer Involvement, External Networking and Employee Involvement are elements of Open Innovation, and all three had strong association with product innovation, and the latter twohad strong association with process innovation. The results showed that proclivity for Open Innovation is healthy in the Indian context. Practical implications have been outlined along how firms can organize themselves for innovation, the human talent for innovation, the right culture for innovation and for open innovation. While some specific examples of possible future studies have been recommended, the researcher believes that the study provides numerous opportunities to further this line of enquiry.