Structural Integrity of the Greek Key Motif in beta gamma-Crystallins Is Vital for Central Eye Lens Transparency

Background: We highlight an unrecognized physiological role for the Greek key motif, an evolutionarily conserved super-secondary structural topology of the beta gamma-crystallins. These proteins constitute the bulk of the human eye lens, packed at very high concentrations in a compact, globular, short-range order, generating transparency. Congenital cataract (affecting 400,000 newborns yearly worldwide), associated with 54 mutations in beta gamma-crystallins, occurs in two major phenotypes nuclear cataract, which blocks the central visual axis, hampering the development of the growing eye and demanding earliest intervention, and the milder peripheral progressive cataract where surgery can wait. In order to understand this phenotypic dichotomy at the molecular level, we have studied the structural and aggregation features of representative mutations. Methods: Wild type and several representative mutant proteins were cloned, expressed and purified and their secondary and tertiary structural details, as well as structural stability, were compared in solution, using spectroscopy. Their tendencies to aggregate in vitro and in cellulo were also compared. In addition, we analyzed their structural differences by molecular modeling in silico. Results: Based on their properties, mutants are seen to fall into two classes. Mutants A36P, L45PL54P, R140X, and G165fs display lowered solubility and structural stability, expose several buried residues to the surface, aggregate in vitro and in cellulo, and disturb/distort the Greek key motif. And they are associated with nuclear cataract. In contrast, mutants P24T and R77S, associated with peripheral cataract, behave quite similar to the wild type molecule, and do not affect the Greek key topology. Conclusion: When a mutation distorts even one of the four Greek key motifs, the protein readily self-aggregates and precipitates, consistent with the phenotype of nuclear cataract, while mutations not affecting the motif display `native state aggregation', leading to peripheral cataract, thus offering a protein structural rationale for the cataract phenotypic dichotomy ``distort motif, lose central vision''.

Effect of Heat Pipe Figure of Merit on an Evaporating Thin Film

The performance of a two-phase heat transport device such as the loop heat pipe is influenced by the evaporative heat transfer coefficient in the evaporator. From previous experiments with loop heat pipes, it has been observed that fluids with a high heat pipe figure of merit have a high heat transfer coefficient. Considering an evaporating extended thin film, this paper theoretically corroborates this experimental observation by deriving a direct link between the evaporative heat flux at the interface and the fluid figures of merit (namely interline heat flow parameter and heat pipe figure of merit) in the thin film. Numerical experiments with different working fluids clearly show that a fluid with high figure of merit also has a high cumulative heat transfer in the microregion encompassing the evaporating thin film. Thus, a loop heat pipe or heat pipe that uses a working fluid with a high interline heat flow parameter and heat pipe figure of merit will lead to a high evaporative heat transfer coefficient.