14 research outputs found
Molecular mechanism of Gαi activation by non-GPCR proteins with a Gα-Binding and Activating motif
Heterotrimeric G proteins are quintessential signalling switches activated by nucleotide exchange on Gα. Although activation is predominantly carried out by G-protein-coupled receptors (GPCRs), non-receptor guanine-nucleotide exchange factors (GEFs) have emerged as critical signalling molecules and therapeutic targets. Here we characterize the molecular mechanism of G-protein activation by a family of non-receptor GEFs containing a Gα-binding and -activating (GBA) motif. We combine NMR spectroscopy, computational modelling and biochemistry to map changes in Gα caused by binding of GBA proteins with residue-level resolution. We find that the GBA motif binds to the SwitchII/α3 cleft of Gα and induces changes in the G-1/P-loop and G-2 boxes (involved in phosphate binding), but not in the G-4/G-5 boxes (guanine binding). Our findings reveal that G-protein-binding and activation mechanisms are fundamentally different between GBA proteins and GPCRs, and that GEF-mediated perturbation of nucleotide phosphate binding is sufficient for Gα activation
Infrared Renormalons and Power Corrections in Deep-Inelastic Sum Rules
Infrared renormalons and power corrections in deep-inelastic sum
rules are studied. The renormalization of operators with power divergence are
discussed. The higher-twist terms in the operator product expansion are shown
to account for the residual soft contributions survived from the
Kinoshita-Lee-Nauenberg type of cancellation in Feynman diagrams. The presence
of some degree of arbitrariness in the twist separation allows one to define
the most convenient higher-twist operators suitable for a particular
non-perturbative method. The discussion is focused on the Bjorken sum rule, for
which the corrections are considered on a lattice.Comment: 18 pages, ReVTeX, 2 figures (not available by postscript yet
Enhancing Production of Bio-Isoprene Using Hybrid MVA Pathway and Isoprene Synthase in E. coli
The depleting petroleum reserve, increasingly severe energy crisis, and global climate change are reigniting enthusiasm for seeking sustainable technologies to replace petroleum as a source of fuel and chemicals. In this paper, the efficiency of the MVA pathway on isoprene production has been improved as follows: firstly, in order to increase MVA production, the source of the âupper pathwayâ which contains HMG-CoA synthase, acetyl-CoA acetyltransferase and HMG-CoA reductase to covert acetyl-CoA into MVA has been changed from Saccharomyces cerevisiae to Enterococcus faecalis; secondly, to further enhance the production of MVA and isoprene, a alanine 110 of the mvaS gene has been mutated to a glycine. The final genetic strain YJM25 containing the optimized MVA pathway and isoprene synthase from Populus alba can accumulate isoprene up to 6.3 g/L after 40 h of fed-batch cultivation
Interventions basées sur la pleine conscience dans le traitement des symptÎmes de la psychose : un examen systématique narrative
Although there is a growing body of research on the value of mindfulness for a range of mental health conditions, evidence regarding mindfulness for individuals with psychosis is much more limited. The purpose of this article was to conduct a narrative systematic review of randomized controlled trials evaluating the effectiveness of mindfulness-based techniques with individuals experiencing symptoms of psychosis. Eligibility criteria for the studies included random allocation, a focus on participants with psychosis, implementation of mindfulness-based interventions, and inclusion of a control group. A majority of measures across studies showed no significant treatment effect. Therefore, studies to date do not indicate that mindfulness-based interventions have an impact on symptoms of psychosis. Across trials, mindfulness interventions varied greatly. Furthermore, mindfulness interventions were designed to help individuals cope with symptoms and not necessarily to make them go away. Therefore, future studies should consider measuring functional outcomes, not symptom-related outcomes.Bien quâil existe un nombre croissant de recherches sur la valeur de la pleine conscience pour une gamme de problĂšmes de santĂ© mentale, les Ă©lĂ©ments de preuve concernant la pleine conscience chez les personnes souffrant de psychose sont beaucoup plus limitĂ©s. Le but de cet article Ă©tait de procĂ©der Ă un examen systĂ©matique narratif des essais contrĂŽlĂ©s randomisĂ©s (ECR) Ă©valuant lâefficacitĂ© des techniques basĂ©es sur la pleine conscience avec des individus qui Ă©prouvent des symptĂŽmes de psychose. Les critĂšres dâadmissibilitĂ© pour les Ă©tudes comprenaient : la rĂ©partition alĂ©atoire, lâaccent sur les participants souffrant de psychose, la mise en oeuvre des interventions fondĂ©es sur la pleine conscience, et lâinclusion dâun groupe tĂ©moin. La majoritĂ© des mesures Ă travers des Ă©tudes nâa montrĂ© aucun effet significatif du traitement. Par consĂ©quent, les Ă©tudes Ă ce jour nâindiquent pas que des interventions fondĂ©es sur la pleine conscience ont un impact sur les symptĂŽmes de la psychose. Les interventions fondĂ©es sur la pleine conscience varient considĂ©rablement Ă travers les essais. De plus, les interventions fondĂ©es sur la pleine conscience ont Ă©tĂ© conçues pour aider les individus Ă composer avec les symptĂŽmes, pas nĂ©cessairement pour les faire disparaĂźtre. Par consĂ©quent, des Ă©tudes Ă venir devraient viser Ă mesurer les rĂ©sultats fonctionnels, pas les rĂ©sultats liĂ©s aux symptĂŽmes