Functional diversification of hsp40: distinct j-protein functional requirements for two prions allow for chaperone-dependent prion selection.

Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion fragmentation. Chaperone interactions with prions, however, can be affected by variations in amyloid-core structure resulting in distinct prion variants or 'strains'. Our genetic analysis revealed that Sis1 domain requirements by distinct variants of [PSI+] are strongly dependent upon overall variant stability. Notably, multiple strong [PSI+] variants can be maintained by a minimal construct of Sis1 consisting of only the J-domain and glycine/phenylalanine-rich (G/F) region that was previously shown to be sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak [PSI+] variants are lost under the same conditions but maintained by the expression of an Sis1 construct that lacks only the G/F region and cannot support [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or dependent upon a particular yeast genetic background. These observations necessitate that Sis1 must have at least two distinct functional roles that individual prions differentially require for propagation and which are localized to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1 plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion selection for either prion. We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1. This conservation of function is also prion-variant dependent, indicating that only one of the two Sis1-prion functions may have been maintained in eukaryotic chaperone evolution.

Effect of inhalation on oropharynx collapse via flow visualisation.

Computational fluid dynamics (CFD) modelling has made significant contributions to the analysis and treatment of obstructive sleep apnoea (OSA). While several investigations have considered the flow field within the airway and its effect on airway collapse, the effect of breathing on the pharynx region is still poorly understood. We address this gap via a combined experimental and numerical study of the flow field within the pharynx and its impacts upon airway collapse. Two 3D experimental models of the upper airway were constructed based upon computerised tomography scans of a specific patient diagnosed with severe OSA; (i) a transparent, rigid model for flow visualisation, and (ii) a semi-flexible model for understanding the effect of flow on pharynx collapse. Validated simulation results for this geometry indicate that during inhalation, negative pressure (with respect to atmospheric pressure) caused by vortices drives significant narrowing of the pharynx. This narrowing is strongly dependent upon whether inhalation occurs through the nostrils. Thus, the methodology presented here can be used to improve OSA treatment by improving the design methodology for personalised, mandibular advancement splints (MAS) that minimise OSA during sleep.

Modeling film formation of polymer-clay nanocomposite particles.

Polymer films may be formed by drying aqueous suspensions of colloidal polymer particles (latexes) on a substrate. Higher-performance films may be obtained by using nanocomposite particles in the latexes. In particular, polymer-clay nanocomposites show good potential in producing stiff, optically transparent, scratch-resistant coatings. The final film must be continuous (i.e., crack-free). This work predicts the minimum temperature, relative to the glass-transition temperature, at which a given suspension forms a crack-free nanocomposite film. The model extends a previous model for film formation with inclusion-free latexes (Routh, A. F.; Russel, W. B. Langmuir 1999, 15, 7762-7773). The inclusions are modeled as rigid cylinders, and the polymer is modeled as linearly viscoelastic. The major term arising in the extended model is the interfacial shear stress between the polymer and the inclusions. Film formation slows as the shear stress increases, and this effect is proportional to the magnitude of the stress, the inclusion volume fraction, and the inclusion aspect ratio.