Intraflagellar transport speed is sensitive to genetic and mechanical perturbations to flagellar beating.

Two sets of motor proteins underpin motile cilia/flagella function. The axoneme-associated inner and outer dynein arms drive sliding of adjacent axoneme microtubule doublets to periodically bend the flagellum for beating, while intraflagellar transport (IFT) kinesins and dyneins carry IFT trains bidirectionally along the axoneme. Despite assembling motile cilia and flagella, IFT train speeds have only previously been quantified in immobilized flagella-mechanical immobilization or genetic paralysis. This has limited investigation of the interaction between IFT and flagellar beating. Here, in uniflagellate Leishmania parasites, we use high-frequency, dual-color fluorescence microscopy to visualize IFT train movement in beating flagella. We discovered that adhesion of flagella to a microscope slide is detrimental, reducing IFT train speed and increasing train stalling. In flagella free to move, IFT train speed is not strongly dependent on flagella beat type; however, permanent disruption of flagella beating by deletion of genes necessary for formation or regulation of beating showed an inverse correlation of beat frequency and IFT train speed.

Morphometric growth changes of the nasopharyngeal space in subjects with different vertical craniofacial features.

INTRODUCTION: The purpose of this study was to morphometrically investigate the growth pattern of the adenoids in growing subjects with hyperdivergent and hypodivergent vertical craniofacial features. METHODS: In this retrospective study, we used a longitudinal sample of lateral cephalometric radiographs of 28 hyperdivergent and 30 hypodivergent subjects from 4 to 13 years of age. The radiographs were obtained from the American Association of Orthodontists Foundation Craniofacial Growth Legacy Collection. Measurements were made using digital tracings of the lateral cephalograms and point distribution models. Mixed-model analyses were used for statistical analysis. RESULTS: The mean distance between the sphenoid bone and the posterior nasal spine increased up to 5.3 mm over a 9-year span (95% CI, 4.1-6.5 mm; P <0.001). Furthermore, the mean distance between the sphenoid bone and the posterior nasal spine differed significantly (P = 0.029) between facial types; it was consistently greater (1.8 mm; 95% CI, 0.2-3.3 mm) in the hyperdivergent group. The nasopharyngeal airway area showed a trend to increase with age up to 12-fold (P <0.001). A significant interaction (P = 0.004) was found between age and facial type. Assessment of the adenoid shapes showed greater convexities in the hyperdivergent group, which were observable from an earlier age and for a longer duration. CONCLUSIONS: Clear differences in the morphometric growth pattern of the adenoids were found between facial types. Evaluation of adenoid shapes showed more prominent convexities that lasted longer in the long facial types than in the short facial types.

HOX transcription factors are potential targets and markers in malignant mesothelioma.

BACKGROUND: The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos. METHODS: We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model. RESULTS: We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival. CONCLUSION: HOX genes are a potential therapeutic target in mesothelioma, and HOXB4 expression correlates with overall survival.

Colorectal Liver Metastasis, Primary Gallbladder Carcinoma and Myelofibrosis Present Simultaneously in a Liver Resection Specimen.

Myelofibrosis and gallbladder carcinoma are both very rare diseases. This case report describes a patient with a history of myelofibrosis and colorectal carcinoma who was diagnosed with colorectal liver metastases. Surgery was performed to remove the metastases, and on site, the gallbladder was removed because of involvement in one of the liver lesions. After pathological examination, a primary gallbladder carcinoma and myelofibrosis were found in addition to the liver metastases. The combination of diseases was not likely to be interconnected but rather an unlucky course of events for the patient.

[A woman with a symptomatic abdominal swelling]. / Een vrouw met een symptomatische zwelling in de buik.

A 51-year-old woman visited the surgery outpatient clinic with an abdominal swelling. The swelling had become larger over the past few years and caused mechanical complaints. With MRI a liver cyst measuring 14 x 11 cm was diagnosed. The patient underwent laparoscopic deroofing of the liver cyst.

Herbal medicines--a cautionary tale.

We report an extensive intra-operative bleed which may have occurred as a result of the patient taking a herbal medicine. The patient underwent orthognathic surgery as a part of his orthodontic treatment, and lost approximately 3.5 litres of blood during the procedure. Preoperative blood tests were normal; the patient took no prescription medications and an appendectomy had been performed without incident. To aid healing, however, the patient had taken arnica the day before his operation. A concise literature review is presented which outlines the causes of surgical bleeding and discusses some of the bleeding concerns that herbal medicine use may raise for clinicians. Herbal medicines may contribute to unexplained surgical bleeding in the absence of other causative factors; it would therefore be useful to include an enquiry about the taking of herbal remedies at the history-taking stage for dental and maxillofacial surgical procedures.

HOX genes in pancreatic development and cancer.

The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to subsequent adult disease, and their potential both as diagnostic markers and therapeutic targets.