The microRNA-23b/-27b cluster suppresses prostate cancer metastasis via Huntingtin-interacting protein 1-related.

Deregulation of microRNAs (miRs) contributes to progression and metastasis of prostate and other cancers. miR-23b and -27b, encoded in the same miR cluster (miR-23b/-27b), are downregulated in human metastatic prostate cancer compared with primary tumors and benign tissue. Expression of miR-23b/-27b decreases prostate cancer cell migration, invasion and results in anoikis resistance. Conversely, antagomiR-mediated miR-23b and -27b silencing produces the opposite result in a more indolent prostate cancer cell line. However, neither miR-23b/-27b expression or inhibition impacts prostate cancer cell proliferation suggesting that miR-23b/-27b selectively suppresses metastasis. To examine the effects of miR-23b/-27b on prostate cancer metastasis in vivo, orthotopic prostate xenografts were established using aggressive prostate cancer cells transduced with miR-23b/-27b or non-targeting control miRNA. Although primary tumor formation was similar between miR-23b/-27b-transduced cells and controls, miR-23b/-27b expression in prostate cancer cells decreased seminal vesicle invasion and distant metastases. Gene-expression profiling identified the endocytic adaptor, Huntingtin-interacting protein 1-related (HIP1R) as being downregulated by miR-23b/-27b. Increased HIP1R expression in prostate cancer cells inversely phenocopied the effects of miR-23b/-27b overexpression on migration, invasion and anchorage-independent growth. HIP1R rescued miR-23b/-27b-mediated repression of migration in prostate cancer cells. HIP1R mRNA levels were decreased in seminal vesicle tissue from mice bearing miR-23b/-27b-transduced prostate cancer cell xenografts compared with scrambled controls, suggesting HIP1R is a key functional target of miR-23b/-27b. In addition, depletion of HIP1R led to a more rounded, less mesenchymal-like cell morphology, consistent with decreased metastatic properties. Together, these data demonstrate that the miR-23b/-27b cluster functions as a metastasis-suppressor by decreasing HIP1R levels in pre-clinical models of prostate cancer.

Paroxysmal symptoms in multiple sclerosis masquerading as transient ischaemic attacks.

Paroxysmal demyelinating events produced sudden onset, transient, recurrent symptoms that were troublesome to our patient and puzzled the referring clinician who mistook them for transient ischaemic attacks or epilepsy. It was important to recognise the true nature of the underlying problem because the symptoms could then be readily treated; this is especially critical because the symptoms, in this case, represent a relapse of multiple sclerosis and, therefore, are significant for examination during the diagnosis.

Pulmonary artery sarcoma mimicking a pulmonary embolism.

Sarcomas involving the lung are a rare occurrence, often a result of metastatic disease from primary malignancies involving the skin, liver, breast or heart. Primary pulmonary artery sarcomas are rarer still, with limited cases reported world-wide and consequently data regarding treatment modalities are sparse and largely experimental. These tumors are often mistaken for a pulmonary embolism and seemingly supported by radiological findings. Patients will often present without symptom resolution despite therapeutic anticoagulation. The following case illustrates how a soft tissue sarcoma of the pulmonary artery can mimic a pulmonary embolism, thus, resulting in both a diagnostic and therapeutic dilemma. A positron emission tomography scan was an invaluable tool in this case, showing increased radiotracer uptake and placing neoplasm at the top of the differential diagnosis. This ultimately led to a biopsy that was vimentin positive, cytokeratin negative and CD117 negative, thus consistent with soft tissue sarcoma.

Nanoscale scanning transmission electron tomography.

Electron tomography enables the study of complex three-dimensional objects with nanometre resolution. In materials science, scanning transmission electron microscopy provides images with minimal coherent diffraction effects and with high atomic number contrast that makes them ideal for electron tomographic reconstruction. In this study, we reviewed the topic of scanning transmission electron microscopy-based tomography and illustrated the power of the technique with a number of examples with critical dimensions at the nanoscale.

Embedded nanostructures revealed in three dimensions.

Nanotechnology creates a new challenge for materials characterization because device properties now depend on size and shape as much as they depend on the traditional parameters of structure and composition. Here we show that Z-contrast tomography in the scanning transmission electron microscope has been developed to determine the complete three-dimensional size and shape of embedded structures with a resolution of approximately 1 cubic nanometer. The results from a tin/silicon quantum dot system show that the positions of the quantum dots and their size, shape, structure, and formation mechanism can be determined directly. These methods are applicable to any system, providing a unique and versatile three-dimensional visualization tool.

Soiling and decay of N.M.E.P. limestone tablets.

The British National Materials Exposure Programme (N.M.E.P.) ran from 1987 to 1995 and involved exposure of a range of materials samples (including tablets of Monks Park and Portland Limestones) at over 20 sites around Britain for 1-, 2-, 4- and 8-year periods, under known climate and pollution conditions. Deterioration of the limestone tablets has previously been recorded in terms of weight change, contents of soluble salts, and visual soiling. In the present study samples from exposed and sheltered positions at Wells, Bolsover and Lough Navar have been studied using a spectrophotometer, optical microscopy and scanning electron microscopy (SEM) to investigate the distribution and nature of particulate material and its role in soiling and decay. Clearly, recognisable pollutant particles such as perforated cenospheres, are only rarely present. Organisms and organic remains, including filamentous microorganisms and pollen grains, are widely distributed. At each site, soiling has different characteristics in terms of composition and change over time related in part to differences in climate and pollution histories. There is no general link between degree of soiling and amount of decay (in terms of surface recession) as the nature of decay is a key influence on the relation between soiling and decay.

Ecto-ATPase activity of vertebrate blood cells.

Ecto-ATPase activity was measured for red blood cells, white blood cells, and whole blood from a variety of vertebrates. A large range of red blood cell ecto-ATPase activity was observed; for example, at 10 degrees C, red blood cells from a catastomid fish (Catostomus macrocheilus) and a newt (Taricha rivularis) had activities of 56 +/- 9 and 25,000,000 +/- 14,000,000 pmol ATP per 10(6) red blood cells per hour, respectively (mean +/- SD). Several control experiments verified that the measured ATPase activity was not the result of intracellular ATPases released due to cell damage or lysis nor due to the release of intracellular nucleoside triphosphate or uptake of extracellular ATP. Red blood cell ecto-ATPase activity was relatively low within the teleosts, was high within the reptiles, and had the greatest range and single highest value within the amphibians. Within the endotherms, avian red blood cell ecto-ATPase activities were greater than mammalian red blood cell ecto-ATPase activities, which were the lowest for all vertebrates examined. The lowest ecto-ATPase activities measured were for human and skunk red blood cells, which had activities of 13 +/- 1 and 11 +/- 2 pmol ATP per 10(6) red blood cells per hour, respectively, at 35 degrees C. Ecto-ATPase activity was measured in white blood cells of several vertebrate species and appeared generally high and less variable than red blood cell ecto-ATPase activity. Measured whole blood ecto-ATPase activity showed a range of three orders of magnitude and correlated positively with red blood cell ecto-ATPase activities. Ecto-ATPase activity was also determined for red blood cells from fetal, 1-3 d old neonatal, and pregnant garter snakes (Thamnophis elegans); these activities were not significantly different from the activity of red blood cells from nonpregnant adult females. Overall, the data from the present study demonstrate a wide range of red blood cell and whole blood ecto-ATPase activities among vertebrates and include some of the highest ecto-ATPase activities reported to date.

The effects of hedges on spray deposition and on the biological impact of pesticide spray drift.

Two series of drift deposition measurements were carried out at different wind speeds using sodium fluorescein as a tracer dye sprayed over a grass field 6 m upwind of a hedge. Efficient receptors were placed below and above hedge height (1.6 m) between 1 and 20 m downwind from the sprayed area. Receptors below hedge height reflected a sudden decrease in deposition immediately behind the hedge, followed by a gradual increase again up to 15 m, i.e., nine times the height of the hedge. The sheltering effect of a hedge from the biological impact of spray drift was studied by bioassays using tomato and Lychnis flos-cuculi plants for the herbicide MCPA and young Pieris brassicae larvae for the insecticide cypermethrin. These demonstrated that the protection afforded to sensitive species in strong winds may be quite limited, and severe damage may be inflicted over considerable distances. In intermediate cases, a protected zone is followed by a zone of further significant damage before drift depositions cease to have further effect. In some cases, the sheltered zone may extend to a distance where drift deposition, even in the absence of a hedge, has minimal effect.