Allosteric Regulation Of the Hsp90 Dynamics and Stability By Client Recruiter Cochaperones: Protein Structure Network Modeling

The fundamental role of the Hsp90 chaperone in supporting functional activity of diverse protein clients is anchored by specific cochaperones. A family of immune sensing client proteins is delivered to the Hsp90 system with the aid of cochaperones Sgt1 and Rar1 that act cooperatively with Hsp90 to form allosterically regulated dynamic complexes. In this work, functional dynamics and protein structure network modeling are combined to dissect molecular mechanisms of Hsp90 regulation by the client recruiter cochaperones. Dynamic signatures of the Hsp90-cochaperone complexes are manifested in differential modulation of the conformational mobility in the Hsp90 lid motif. Consistent with the experiments, we have determined that targeted reorganization of the lid dynamics is a unifying characteristic of the client recruiter cochaperones. Protein network analysis of the essential conformational space of the Hsp90-cochaperone motions has identified structurally stable interaction communities, interfacial hubs and key mediating residues of allosteric communication pathways that act concertedly with the shifts in conformational equilibrium. The results have shown that client recruiter cochaperones can orchestrate global changes in the dynamics and stability of the interaction networks that could enhance the ATPase activity and assist in the client recruitment. The network analysis has recapitulated a broad range of structural and mutagenesis experiments, particularly clarifying the elusive role of Rar1 as a regulator of the Hsp90 interactions and a stability enhancer of the Hsp90-cochaperone complexes. Small-world organization of the interaction networks in the Hsp90 regulatory complexes gives rise to a strong correspondence between highly connected local interfacial hubs, global mediator residues of allosteric interactions and key functional hot spots of the Hsp90 activity. We have found that cochaperone-induced conformational changes in Hsp90 may be determined by specific interaction networks that can inhibit or promote progression of the ATPase cycle and thus control the recruitment of client proteins

Superconducting properties of the pyrochlore oxide Cd2Re2O7

We report the superconducting properties of the pyrochlore oxide Cd2Re2O7. The bulk superconducting transition temperature Tc is about 1.0 K, and the upper critical field Hc2 determined by the measurement of specific heat under magnetic fields is 0.29 T. The superconducting coherence length is estimated to be 34 nm. Specific heat data measured on single crystals suggest that the superconducting gap of Cd2Re2O7 is nodeless.Comment: 6 pages, 6 figures, 1 table, to be published in J. Chem. Phys. Solid

An intelligent interactive visual database management system for Space Shuttle closeout image management

Status is given of an applications investigation on the potential for using an expert system shell for classification and retrieval of high resolution, digital, color space shuttle closeout photography. This NASA funded activity has focused on the use of integrated information technologies to intelligently classify and retrieve still imagery from a large, electronically stored collection. A space shuttle processing problem is identified, a working prototype system is described, and commercial applications are identified. A conclusion reached is that the developed system has distinct advantages over the present manual system and cost efficiencies will result as the system is implemented. Further, commercial potential exists for this integrated technology

Glycine max and Glycine soja are capable of cold acclimation

Soybean has been considered a cold intolerant species; based largely upon seed germination and soil emergent evaluations. This study reports a distinct acquisition of cold tolerance, in seedlings, following short acclimation periods. Diversity in cold responses was assessed in eight cultivars of Glycine max and six accessions of G. soja. All varieties of soybean significantly increased in freezing tolerance following acclimation. This study indicates soybean seedlings are indeed capable of sensing cold and acquiring cold tolerance. Germination rates after cold imbibition were negatively correlated with maturity group, but positively correlated with cold acclimation potential in G. soja. Seed fatty acid composition was varied between the species, with Glycine soja accessions containing about 2-times more linolenic acid (18:3) than G. max. Furthermore, high levels of linoleic acid (18:2) in seeds were positively correlated with germination rates following cold imbibition in G. soja only. We suggest that domestication has not impacted the overall ability of soybean to cold acclimate at the seedling stage and that there is little variation within the domesticated species for ability to cold acclimate. Thus, this brief comparative study reduces the enthusiasm for the “wild” species as an additional source of genetic diversity for cold tolerance

Attendance patterns and factors affecting participation in organized walks: an investigation of Natural England's Walking for Health programme

This paper examines the Natural England database of registered walkers to identify patterns of attendance in organized walks and differences in walking behaviour based on the profile of participants in Walking for Health (WfH), one of the largest public health interventions for physical activity in the UK. The investigation is informed by walk-history data relating to more than 79,000 participants over a two-year period. Methods used include measures of participant adherence and chi-squared automatic interaction detector analysis. The results indicate that absolute participation numbers have a strong seasonal element, with a marked decline occurring around the Christmas period. Age emerges as the most significant determinant of organized walking behaviour, with older age groups exhibiting higher intensity of participation relative to younger age groups. The research facilitates a better understanding of participation in WfH and can serve to inform future delivery and the marketing of organized walking initiatives

Enhancing deprescribing : a qualitative understanding of the complexities of pharmacist-led deprescribing in care homes

Funding statement This research is funded by the National Institute for Health Research (NIHR) Policy Research Programme (project reference NIHR202053). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Acknowledgements Thank you to the pharmacists, GP practice and care home staff who took part in the interviews. We would also like to acknowledge the Norfolk and Waveney Clinical Commissioning Group as the study sponsor and our patient and public involvement colleagues Janet Gray and Christine Hanford who were supported by Jacqueline Romero, manager of PPIRes.Peer reviewedPublisher PD

Superconductivity in the Correlated Pyrochlore Cd_2Re_2O_7

We report the observation of superconductivity in high-quality Cd$_2$Re$_2$O$_7$ single crystals with room-temperature pyrochlore structure. Resistivity and ac susceptibility measurements establish an onset transition temperature T$_c^{onset}$ = 1.47 K with transition width $\Delta$T$_c$ = 0.25 K. In applied magnetic field, the resistive transition shows a type-II character, with an approximately linear temperature-dependence of the upper critical field H$_{c2}$. The bulk nature of the superconductivity is confirmed by the specific heat jump with $\Delta$C = 37.9 mJ/mol-K. Using the $\gamma$ value extracted from normal-state specific heat data, we obtain $\Delta$C/$\gamma$T$_c$ = 1.29, close to the weak coupling BCS value. In the normal state, a negative Hall coefficient below 100 K suggests electron-like conduction in this material. The resistivity exhibits a quadratic T-dependence between 2 and 60 K, i.e., $\rho =\rho_0$+AT$^2$, indicative of Fermi-liquid behavior. The values of the Kadowaki-Woods ratio A/$\gamma^2$ and the Wilson ratio are comparable to that for strongly correlated materials.Comment: 4 pages, 5 figure

Stochastic virtual tests for fiber composites

We will describe a Virtual Test system for continuous fiber composites. The virtual test draws from a new wave of advanced experiments and theory that address physical, mathematical, and engineering aspects of material definition and failure prediction. The methods go far beyond currently standard tests and conventional FEM analysis to challenge our conception of what can constitute a practicable engineering approach. Emphasis will be given to high temperature ceramic matrix composites with textile reinforcement, which have been the subject material of the National Hypersonic Science Center, Materials and Structures, a joint AFOSR/NASA program. However, thematic topics also address generic fiber composites. Development has been organized as a “pipeline” that links the separate disciplinary efforts of groups housed in seven institutions spread across the United States. The main research steps are: high resolution three-dimensional (3D) imaging of the microstructure, statistical characterization of the microstructure, formulation of a probabilistic generator for creating virtual specimens that replicate the measured statistics, creation of a computational model for a virtual specimen that allows general representation of discrete damage events, calibration of the model using room and high temperature tests, simulation of failure, and model validation. Key new experiments include digital surface image correlation and µm-resolution 3D computed tomography imaging of the microstructure and evolving damage, both executed at temperatures exceeding 1500°C. Conceptual advances include using both geometry and topology to characterize stochastic microstructures. Computational methods include new probabilistic algorithms for generating stochastic virtual specimens and a new Augmented Finite Element Method that yields extreme efficiency in dealing with arbitrary cracking in heterogeneous materials. The challenge of relating variance in engineering properties to stochastic microstructure in a computationally tractable manner, while retaining necessary physical details in models, will be discussed