Regulation of centrosome movements by numb and the collapsin response mediator protein during Drosophila sensory progenitor asymmetric division.

Asymmetric cell division generates cell fate diversity during development and adult life. Recent findings have demonstrated that during stem cell divisions, the movement of centrosomes is asymmetric in prophase and that such asymmetry participates in mitotic spindle orientation and cell polarization. Here, we have investigated the dynamics of centrosomes during Drosophila sensory organ precursor asymmetric divisions and find that centrosome movements are asymmetric during cytokinesis. We demonstrate that centrosome movements are controlled by the cell fate determinant Numb, which does not act via its classical effectors, Sanpodo and α-Adaptin, but via the Collapsin Response Mediator Protein (CRMP). Furthermore, we find that CRMP is necessary for efficient Notch signalling and that it regulates the duration of the pericentriolar accumulation of Rab11-positive endosomes, through which the Notch ligand, Delta is recycled. Our work characterizes an additional mode of asymmetric centrosome movement during asymmetric divisions and suggests a model whereby the asymmetry in centrosome movements participates in differential Notch activation to regulate cell fate specification.

High-resolution multislice computerized tomography with multiplanar and 3-dimensional reformation imaging in rapid palatal expansion.

INTRODUCTION: The purpose of this study was to evaluate whether high-resolution multislice computerized tomography (CT) with multiplanar reformation and 3-dimensional (3D) imaging is helpful in demonstrating the effects on midfacial sutures induced by rapid palatal expansion (RPE), thereby appraising and corroborating the current state of the art or possibly adding new findings. METHODS: Two patients in different stages of skeletal maturity (aged 10 and 16 years) underwent CT examinations immediately after active opening with the RPE appliance. RESULTS: The 3D CT imaging method proved to be valuable in visualizing skeletal effects on not only the midpalatal suture, but also adjacent sutures. It allowed precise 3D location of tooth positions. In the 3D CT images of 1 patient, the complete opening of the midpalatal suture was visible. The median dissection of the incisal foramen at the point of unification of the 2 nasopalatine channels could be visualized. Additionally, the positions of severely displaced maxillary canines could be located precisely. In the other patient, apart from the completely open midpalatal suture, the opening or widening of the internasal suture, the nasomaxillary sutures, and the frontomaxillary sutures were visible. CONCLUSIONS: The 3D imaging of high-resolution multislice CT opens up a new dimension in orofacial diagnosis. Improvements of the quantity and the exactness of diagnostic parameters were attained. The imaging method is helpful and indicated in RPE patients with additional diagnostic objectives related to the development of occlusion. This imaging method is recommended in borderline cases (juvenile or adult patients with questionable sutural response) to determine whether the suture is completely open or whether surgical support is needed.

Per-sextant localization and staging of prostate cancer: correlation of imaging findings with whole-mount step section histopathology.

OBJECTIVE: The objective of our study was to determine the diagnostic accuracy and interobserver agreement of 1.5-T prostatic MRI for per-sextant tumor localization and staging of prostate cancer as compared with whole-mount step section histopathology. MATERIALS AND METHODS: Combined endorectal-pelvic phased-array prostatic MRI scans obtained at 1.5 T of 106 patients with biopsy-proven prostate cancer who had undergone radical prostatectomy with whole-mount step section histopathology within 28 days of MRI were retrospectively analyzed by three independent abdominal radiologists (reviewers 1, 2, and 3). Sextants of the prostate (right and left base, middle, and apex) were evaluated for the presence of prostate cancer and extracapsular extension (ECE) using a 5-point confidence scale. Data were statistically analyzed using receiver operating characteristic (ROC) analysis. Interobserver variability was assessed by kappa statistics. For calculation of sensitivity and specificity, data from the 5-point confidence scale were dichotomized into negative (score of 1-3) or positive (score of 4 or 5) findings. RESULTS: Forty-one patients had ECE (tumor stage T3), and 65 patients had organ-confined disease (stage T2). Of 636 prostatic sextants, 417 were positive for prostate cancer and 135 were positive for ECE at histopathology. For prostate cancer localization, ROC analysis yielded area under the ROC curve (AUC) values ranging from 0.776 +/- 0.023 (SD) to 0.832 +/- 0.027. For the detection of ECE, the AUC values ranged from 0.740 +/- 0.054 to 0.812 +/- 0.045. Interobserver agreement (kappa) ranged from 0.49 to 0.60 for prostate cancer localization and from 0.59 to 0.67 for the detection of ECE. CONCLUSION: Using the sextant framework, independent observers reach similar accuracy with moderate to substantial agreement for the localization of prostate cancer and ECE by means of MRI of the prostate.

MRI-based PSA density and PSA density of the transitional zone compared with PSA alone: correlation with prostate cancer Gleason score.

OBJECTIVES: The tumor Gleason score is an important prognostic factor in prostate cancer (PCA). This retrospective study analyzes whether serum prostate-specific antigen (PSA), or magnetic resonance imaging (MRI)-based PSA density of the entire prostate (PSAD) or the prostatic transitional zone (PSAT) distinguishes between PCA of Gleason scores 6 or lower (G6-) and 7 or higher (G7+). MATERIALS AND METHODS: Total prostate and transitional zone volumes were planimetrically determined in axial, T2-weighted fast spin echo (FSE) MRI images of the prostate in 61 patients with previously untreated PCA. Automated standardized microparticle enzyme immuno-assay (EIAs) measured PSA. RESULTS: Thirty patients had G6- and 31 patients had G7+. PSA values ranged from 1.0 to 57.2 ng/mL. Assignment to G6- or G7+, respectively, was correct in 49 of 61 (80%) cases (odds ratio [OR], 17.1; 95% confidence interval [CI], 4.8-61.5) for PSA above the optimal cutoff level of 10.35 ng/mL, 48 cases (79%; OR, 13.7; 95% CI, 4.0-46.8) for PSAD above the optimal cutoff level of 0.23 ng/mL/cm, and 45 cases (74%; OR, 6.9; 95% CI, 2.2-21.3) for PSAT above the optimal cutoff level of 0.38 ng/mL/cm (no significant differences, McNemar test). CONCLUSIONS: In patients with biopsy-proven PCA, serum PSA level alone and MRI-based PSAD and PSAT help distinguish between G6- and G7+. PSAD and PSAT do not improve the level of confidence at which this discrimination is made.

The exocyst component Sec5 is present on endocytic vesicles in the oocyte of Drosophila melanogaster.

The exocyst is an octameric complex required for polarized secretion. Some components of the exocyst are found on the plasma membrane, whereas others are recruited to Golgi membranes, suggesting that exocyst assembly tethers vesicles to their site of fusion. We have found that in Drosophila melanogaster oocytes the majority of the exocyst component Sec5 is unexpectedly present in clathrin-coated pits and vesicles at the plasma membrane. In oocytes, the major substrate for clathrin-dependent endocytosis is the vitellogenin receptor Yolkless. A truncation mutant of Sec5 (sec5(E13)) allows the formation of normally sized oocytes but with greatly reduced yolk uptake. We find that in sec5(E13) oocytes Yolkless accumulates aberrantly in late endocytic compartments, indicating a defect in the endocytic cycling of the receptor. An analogous truncation of the yeast SEC5 gene results in normal secretion but a temperature-sensitive defect in endocytic recycling. Thus, the exocyst may act in both Golgi to plasma membrane traffic and endocytic cycling, and hence in oocytes is recruited to clathrin-coated pits to facilitate the rapid recycling of Yolkless.