Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium

Intracellular transduction of Hedgehog (Hh) signals in mammals requires functional primary cilia. The Hh signaling effectors, the Gli family of transcription factors, and their negative regulator, Suppressor of Fused (Sufu), accumulate at the tips of cilia; however, the molecular mechanism regulating this localization remains elusive. In the current study, we show that the ciliary localization of mammalian Gli proteins depends on both their N-terminal domains and a central region lying C-terminal to the zinc-finger DNA-binding domains. Invertebrate Gli homologs Ci and Tra1, when over-expressed in ciliated mouse fibroblasts, fail to localize to the cilia, suggesting the lack of a vertebrate-specific structural feature required for ciliary localization. We further show that activation of protein kinase A (PKA) efficiently inhibits ciliary localization of Gli2 and Gli3, but only moderately affects the ciliary localization of Gli1. Interestingly, variants of Gli2 mimicking the phosphorylated or non-phosphorylated states of Gli2 are both localized to the cilia, and their ciliary localizations are subjected to the inhibitory effect of PKA activation, suggesting a likely indirect mechanism underlying the roles of PKA in Gli ciliary localization. Finally, we show that ciliary localization of Sufu is dependent on ciliary-localized Gli proteins, and is inhibited by PKA activation, suggesting a coordinated mechanism for the ciliary translocation of Sufu and Gli proteins

An evaluation of CT-scan to locate the femoral head centre and its implication for hip surgeons

The aim of this preliminary study was to determine the accuracy of CT-scan to locate the femoral head centre. METHODS: Eleven dried femurs were included for study. Three techniques were compared to determine femoral head centre (FHC) location: CT-scan, Motion Analysis and Faro-Arm. Markers were stuck on each femur to create a system of coordinates. Femurs lied on their posterior parts (bicondylar plane). Several points around the femoral head were palpated (Motion Analysis and Faro-Arm) or determined (Amira software for CT-scans). By a least-square regression method, the FHC location in 3D was defined for each technique. RESULTS: The results of the FHC location determined by the CT-scan technique were compared with those measured by the faro-arm and the Motion Analysis techniques. The coordinates (X, Y, Z) of the FHC were compared between the three methods, and no statistical difference was found (p = 0.99). In a 3D plot, this gave a mean difference of 1.3 mm. The mean radius of the femoral head was of 22.5 mm (p = 0.6). CONCLUSIONS: CT-scan is as accurate and reliable as gold-standard techniques (motion and faro-arm). Locating FHC before and after hip arthroplasty would allow hip surgeons to determine and compare 3D orientation of the upper-end of femur: offset, height and anteversion

Can the Acetabular Position be Derived from a Pelvic Frame of Reference?

Acetabular center positioning has an effect on hip function. However, reported clinical and plain radiographic methods are inaccurate and unreliable for ascertaining acetabular implant location. In an exploratory study we asked whether the normal acetabular position can be derived from simple radiographically measurable pelvic dimensions. We analyzed computed tomographic scans of 37 normal hips using a pelvic frame of reference centered on the ipsilateral anterior-superior iliac spine. We defined the x-, y-, and z-coordinates of the hip center (Cx,Cy,Cz) as a percentage of the corresponding pelvic dimensions (Dx,Dy,Dz). Cx/Dx averaged 9%, Cy/Dy 34%, and Cz/Dz 37%. These ratios had narrow distributions with small confidence intervals. Interobserver agreement tests showed a mean intraclass correlation coefficient of 0.95. We observed gender differences in the ratios of as much as 4%, which correspond to differences of as much as 9 mm in the hip center position. The ratios provide a simple and reliable way of deriving the normal position of the hip center from the pelvic dimensions alone. This gives the surgeon a simple way of planning where the hip center should be and may be particularly helpful in revision hip arthroplasty or in cases involving extensive osteophytes, dysplasia, or protrusio