Zebrafish, as a model for teleost fish, have two paralogous troponin C (TnC) genes that are expressed in the heart differentially in response to temperature acclimation. Upon Ca(2+) binding, TnC changes conformation and exposes a hydrophobic patch that interacts with troponin I and initiates cardiac muscle contraction. Teleost-specific TnC paralogs have not yet been functionally characterized. In this study we have modeled the structures of the paralogs using molecular dynamics simulations at 18°C and 28°C and calculated the different Ca(2+)-binding properties between the teleost cardiac (cTnC or TnC1a) and slow-skeletal (ssTnC or TnC1b) paralogs through potential-of-mean-force calculations. These values are compared with thermodynamic binding properties obtained through isothermal titration calorimetry (ITC). The modeled structures of each of the paralogs are similar at each temperature, with the exception of helix C, which flanks the Ca(2+) binding site; this region is also home to paralog-specific sequence substitutions that we predict have an influence on protein function. The short timescale of the potential-of-mean-force calculation precludes the inclusion of the conformational change on the ΔG of Ca(2+) interaction, whereas the ITC analysis includes the Ca(2+) binding and conformational change of the TnC molecule. ITC analysis has revealed that ssTnC has higher Ca(2+) affinity than cTnC for Ca(2+) overall, whereas each of the paralogs has increased affinity at 28°C compared to 18°C. Microsecond-timescale simulations have calculated that the cTnC paralog transitions from the closed to the open state more readily than the ssTnC paralog, an unfavorable transition that would decrease the ITC-derived Ca(2+) affinity while simultaneously increasing the Ca(2+) sensitivity of the myofilament. We propose that the preferential expression of cTnC at lower temperatures increases myofilament Ca(2+) sensitivity by this mechanism, despite the lower Ca(2+) affinity that we have measured by ITC.

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This review found that generic patient-reported outcome measures were used most often, construct validity was used most frequently, physical functioning domains had the highest reliability, and the number of items or cost of a patient-reported outcome measure was not related to its frequency of use. Considered together, this information may inform the future development or selection of patient-reported outcome measures in pediatric plastic surgery.

Background Macrotextured breast implants are associated with double capsules. There is little agreement as to what defines double capsules, how they present, and whether different degrees of double capsule exist. Objectives This study aimed to define double capsules and report an association between double-capsule type and degree of tissue adherence. Methods Consecutive aesthetic patients undergoing explantation of Biocell (Allergan, Inc., Irvine, CA) implants between May 2018 and November 2018 were included if they were found to have double capsules intraoperatively. Patient demographics, implant characteristics, explantation reason, implant adherence, and intraoperative findings were recorded. Both adherent and double capsules were histologically examined. Data were analyzed by descriptive statistics. Results Eleven patients had 22 Biocell implants explanted during the study period. The average explantation time was 8.0 years. Sixteen implants were found to have some degree of nonadherence, and all areas of nonadherence were associated with double-capsule formation. Double capsules were either partial or complete. The architecture of the inner layer of double capsules varied between an organized capsular layer and a thin area of nascent capsule. Histologically, all capsular specimens demonstrated an overall hypocellular fibrous capsule with scattered chronic inflammatory infiltrates. Synovial metaplasia was present in all capsule types and spaces/cracks in the capsule were disproportionately represented in partially adherent capsules. Conclusions This is the first study to identify a clinical and pathological correlation between double capsules and failed tissue adherence. Double capsules represent a spectrum of inner capsule formation ranging between nascent capsular tissue to a mature inner capsular layer. Level of Evidence: 4