7 resultados para HSP70 inhibitors
em Cambridge University Engineering Department Publications Database
Resumo:
Technology roadmapping workshops are essentially a social mechanism for exploring, creating, shaping and implementing ideas. The front-end of a roadmapping session is based on brainstorming in order to tap into the group's diverse knowledge. The aim of this idea stimulation activity is to capture and share as many perspectives as possible across the full scope of the area of interest. The premise to such group brainstorming is that the sharing and exchange of ideas leads to cognitive stimulation resulting in a greater overall group idea generation performance in terms of the number, variety and originality of ideas. However, it must be recognized that the ideation stage in a roadmapping workshop is a complex psychosocial phenomenon with underlying cognitive and social processes. Thus, there are downsides to group interactions and these must be addressed in order to fully benefit from the power of a roadmapping workshop. This paper will highlight and discuss the key cognitive and social inhibitors involved. These include: production blocking, evaluation apprehension, free riding/social loafing, low norm setting/matching. Facilitation actions and process adjustments to counter such negative factors will be identified so as to provide a psychosocial basis for improving the running of roadmapping workshops. © 2009 PICMET.
Resumo:
Ure2p is the protein determinant of the Saccharomyces cerevisiae prion state [URE3]. Constitutive overexpression of the HSP70 family member SSA1 cures cells of [URE3]. Here, we show that Ssa1p increases the lag time of Ure2p fibril formation in vitro in the presence or absence of nucleotide. The presence of the HSP40 co-chaperone Ydj1p has an additive effect on the inhibition of Ure2p fibril formation, whereas the Ydj1p H34Q mutant shows reduced inhibition alone and in combination with Ssa1p. In order to investigate the structural basis of these effects, we constructed and tested an Ssa1p mutant lacking the ATPase domain, as well as a series of C-terminal truncation mutants. The results indicate that Ssa1p can bind to Ure2p and delay fibril formation even in the absence of the ATPase domain, but interaction of Ure2p with the substrate-binding domain is strongly influenced by the C-terminal lid region. Dynamic light scattering, quartz crystal microbalance assays, pull-down assays and kinetic analysis indicate that Ssa1p interacts with both native Ure2p and fibril seeds, and reduces the rate of Ure2p fibril elongation in a concentration-dependent manner. These results provide new insights into the structural and mechanistic basis for inhibition of Ure2p fibril formation by Ssa1p and Ydj1p.
Resumo:
Ure2p is the protein determinant of the Saccharomyces cerevisiae prion state [URE3]. Constitutive overexpression of the HSP70 family member SSA1 cures cells of [URE3]. Here, we show that Ssa1p increases the lag time of Ure2p fibril formation in vitro in the presence or absence of nucleotide. The presence of the HSP40 co-chaperone Ydj1p has an additive effect on the inhibition of Ure2p fibril formation, whereas the Ydj1p H34Q mutant shows reduced inhibition alone and in combination with Ssa1p. In order to investigate the structural basis of these effects, we constructed and tested an Ssa1p mutant lacking the ATPase domain, as well as a series of C-terminal truncation mutants. The results indicate that Ssa1p can bind to Ure2p and delay fibril formation even in the absence of the ATPase domain, but interaction of Ure2p with the substrate-binding domain is strongly influenced by the C-terminal lid region. Dynamic light scattering, quartz crystal microbalance assays, pull-down assays and kinetic analysis indicate that Ssa1p interacts with both native Ure2p and fibril seeds, and reduces the rate of Ure2p fibril elongation in a concentration-dependent manner. These results provide new insights into the structural and mechanistic basis for inhibition of Ure2p fibril formation by Ssa1p and Ydj1p.
Resumo:
Among the variety of applications for biosensors one of the exciting frontiers is to utilize those devices as post-synaptic sensing elements in chemical coupling between neurons and solid-state systems. The first necessary step to attain this challenge is to realize highly efficient detector for neurotransmitter acetylcholine (ACh). Herein, we demonstrate that the combination of floating gate configuration of ion-sensitive field effect transistor (ISFET) together with diluted covalent anchoring of enzyme acetylcholinesterase (AChE) onto device sensing area reveals a remarkable improvement of a four orders of magnitude in dose response to ACh. This high range sensitivity in addition to the benefits of peculiar microelectronic design show, that the presented hybrid provides a competent platform for assembly of artificial chemical synapse junction. Furthermore, our system exhibits clear response to eserine, a competitive inhibitor of AChE, and therefore it can be implemented as an effective sensor of pharmacological reagents, organophosphates, and nerve gases as well. © 2007 Materials Research Society.