Thermodynamic analysis of a molecular chaperone binding to unfolded protein substrates.

Molecular chaperones are a highly diverse group of proteins that recognize and bind unfolded proteins to facilitate protein folding and prevent nonspecific protein aggregation. The mechanisms by which chaperones bind their protein substrates have been studied for decades. However, there are few reports about the affinity of molecular chaperones for their unfolded protein substrates. Thus, little is known about the relative binding affinities of different chaperones and about the relative binding affinities of chaperones for different unfolded protein substrates. Here we describe the application of SUPREX (stability of unpurified proteins from rates of H-D exchange), an H-D exchange and MALDI-based technique, in studying the binding interaction between the molecular chaperone Hsp33 and four different unfolded protein substrates, including citrate synthase, lactate dehydrogenase, malate dehydrogenase, and aldolase. The results of our studies suggest that the cooperativity of the Hsp33 folding-unfolding reaction increases upon binding with denatured protein substrates. This is consistent with the burial of significant hydrophobic surface area in Hsp33 when it interacts with its substrate proteins. The SUPREX-derived K(d) values for Hsp33 complexes with four different substrates were all found to be within the range of 3-300 nM.

Comparison of extramedullary versus intramedullary referencing for tibial component alignment in total ankle arthroplasty.

BACKGROUND: The majority of total ankle arthroplasty (TAA) systems use extramedullary alignment guides for tibial component placement. However, at least 1 system offers intramedullary referencing. In total knee arthroplasty, studies suggest that tibial component placement is more accurate with intramedullary referencing. The purpose of this study was to compare the accuracy of extramedullary referencing with intramedullary referencing for tibial component placement in total ankle arthroplasty. METHODS: The coronal and sagittal tibial component alignment was evaluated on the postoperative weight-bearing anteroposterior (AP) and lateral radiographs of 236 consecutive fixed-bearing TAAs. Radiographs were measured blindly by 2 investigators. The postoperative alignment of the prosthesis was compared with the surgeon's intended alignment in both planes. The accuracy of tibial component alignment was compared between the extramedullary and intramedullary referencing techniques using unpaired t tests. Interrater and intrarater reliabilities were assessed with intraclass correlation coefficients (ICCs). RESULTS: Eighty-three tibial components placed with an extramedullary referencing technique were compared with 153 implants placed with an intramedullary referencing technique. The accuracy of the extramedullary referencing was within a mean of 1.5 ± 1.4 degrees and 4.1 ± 2.9 degrees in the coronal and sagittal planes, respectively. The accuracy of intramedullary referencing was within a mean of 1.4 ± 1.1 degrees and 2.5 ± 1.8 degrees in the coronal and sagittal planes, respectively. There was a significant difference (P < .001) between the 2 techniques with respect to the sagittal plane alignment. Interrater ICCs for coronal and sagittal alignment were high (0.81 and 0.94, respectively). Intrarater ICCs for coronal and sagittal alignment were high for both investigators. CONCLUSIONS: Initial sagittal plane tibial component alignment was notably more accurate when intramedullary referencing was used. Further studies are needed to determine the effect of this difference on clinical outcomes and long-term survivability of the implants. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

The Cliché as Critique and Complaint

The cliché is a peripheral term in our critical vocabulary. Reviewers, critics, and editors speak of clichés, but dictionaries of critical terms rarely provide entries on the word. This paper asks whether pointing out clichés represents a form of critique or whether it is just quibbling, and how we draw the line between scrutiny and pedantry.