Fleeting activation of NMDA receptors (NMDARs) induces long-term modification of synaptic connections and refinement of neuronal circuits, which may underlie learning and memory and contribute to pathogenesis of a diversity of neurological diseases, including epilepsy. Here, we found that NR2A and NR2B subunit-containing NMDARs were coupled to distinct intracellular signaling, resulting in differential BDNF expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Selective activation of NR2A-containing NMDARs increased BDNF gene expression. Activation of NR2B-containing NMDARs led to ERK1/2 phosphorylation. Furthermore, selectively blocking NR2A-containing NMDARs impaired epileptogenesis and the development of mossy fiber sprouting in the kindling and pilocarpine rat models of limbic epilepsy, whereas inhibiting NR2B-containing NMDARs had no effects in epileptogenesis and mossy fiber sprouting. Interestingly, blocking either NR2A- or NR2B-containing NMDARs decreased status epilepticus-induced neuronal cell death. The specific requirement of NR2A and its downstream signaling for epileptogenesis implicates attractive new targets for the development of drugs that prevent epilepsy in patients with brain injury.
PurposeThe increasing “globalisation” and complexity of construction design implies that the project team may involve subcontractors in the construction supply chain from widely distributed geographic areas. Thus communication is a vital process for the design. The aim of the present work is to investigate how construction design under supply chain partnering can be improved through a study of communication issues and problems.Design/methodology/approachA questionnaire survey is initially conducted to investigate communication issues and problems in construction design. Based on the survey results, a case study is carried out to gain further insights into these issues and problems, exploring how the procurement like supply chain partnering influences the multi‐team communications in construction design.FindingsThe paper finds that partnering can eliminate many communication barriers and has a positive impact on social collaboration in the design process. It could have a negative impact on the team communications if proper procedures have not been put in place. In addition, co‐location can increase the degree of interaction, communication and technical collaboration in the partnership.Originality/valueThis paper may help construction project practitioners to focus their attention on the necessary respects of multi‐team communications between supply chain partners in construction design, leading to high cooperation and ultimately improving the quality of the design outcomes.
Menthol is a widely-used cooling and flavoring agent derived from mint leaves. In the peripheral nervous system, menthol regulates sensory transduction by activating TRPM8 channels residing specifically in primary sensory neurons. Although behavioral studies have implicated menthol actions in the brain, no direct central target of menthol has been identified. Here we show that menthol reduces the excitation of rat hippocampal neurons in culture and suppresses the epileptic activity induced by pentylenetetrazole injection and electrical kindling in vivo. We found menthol not only enhanced the currents induced by low concentrations of GABA but also directly activated GABAA receptor (GABAAR) in hippocampal neurons in culture. Furthermore, in the CA1 region of rat hippocampal slices, menthol enhanced tonic GABAergic inhibition although phasic GABAergic inhibition was unaffected. Finally, the structure-effect relationship of menthol indicated that hydroxyl plays a critical role in menthol enhancement of tonic GABAAR. Our results thus reveal a novel cellular mechanism that may underlie the ambivalent perception and psychophysical effects of menthol and underscore the importance of tonic inhibition by GABAARs in regulating neuronal activity.
PurposeThis research is designed to explore Chinese customers' wine purchasing behaviours and to investigate the effect of country‐of‐origin (COO) information on their wine evaluations.Design/methodology/approachData were collected from the shopping malls both in Shanghai and Hangzhou, China, using the systematic sampling method. A total 148 usable questionnaires were returned and analysed by SPSS.FindingsThe results confirmed that Chinese customers consider COO as the most important factor in their wine evaluation when a single‐cue approach is applied. When a multi‐cue approach is used however the results showed that there was no significant difference in the importance in COO and price as indicators. This research also revealed some salient characteristics of Chinese consumers buying behaviour associated with Chinese culture. When the Chinese are evaluating wine for gift giving and consuming wine in public, they tend to attach more importance to COO than to other variables and are more likely to purchase foreign or imported wine instead of domestic brands.Research limitations/implicationsOnly respondents from Shanghai and Hangzhou were chosen, limiting the representativeness of the sample. Future research will be benefited from increased sample size from different geographical regions and by examining the relationship between the consumer demographic characteristics and the COO effects.Originality/valueThe results from this study stand in contrast to previous studies relating to the role of COO in product evaluation. It illustrates the importance of culture in relation to COO.
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