Zebrafish Microenvironment Elevates EMT and CSC-Like Phenotype of Engrafted Prostate Cancer Cells.

To visually and genetically trace single-cell dynamics of human prostate cancer (PCa) cells at the early stage of metastasis, a zebrafish (ZF) xenograft model was employed. The phenotypes of intravenously transplanted fluorescent cells were monitored by high-resolution, single-cell intravital confocal and light-sheet imaging. Engrafted osteotropic, androgen independent PCa cells were extravasated from caudle vein, invaded the neighboring tissue, proliferated and formed experimental metastases around caudal hematopoietic tissue (CHT) in four days. Gene expression comparison between cells in culture and in CHT revealed that engrafted PCa cells responded to the ZF microenvironment by elevating expression of epithelial-mesenchymal transition (EMT) and stemness markers. Next, metastatic potentials of ALDHhi cancer stem-like cells (CSCs) and ALDHlow non-CSCs were analyzed in ZF. Engraftment of CSCs induced faster metastatic onset, however after six days both cell subpopulations equally responded to the ZF microenvironment, resulting in the same increase of stemness genes expression including Nanog, Oct-4 and Cripto. Knockdown of Cripto significantly reduced the vimentin/E-cadherin ratio in engrafted cells, indicating that Cripto is required for transduction of the microenvironment signals from the ZF niche to increase mesenchymal potential of cells. Targeting of either Cripto or EMT transcriptional factors Snail 1 and Zeb1 significantly suppressed metastatic growth. These data indicated that zebrafish microenvironment governed the CSC/EMT plasticity of human PCa cells promoting metastasis initiation

The diagnostic value of synovial histopathology in undifferentiated inflammatory arthritis: a prospective study in 154 consecutive patients

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On-line Excited-State Laser Spectroscopy of Trapped Short-Lived Ra+^+ Ions

As an important step towards an atomic parity violation experiment in one single trapped Ra$^+$ ion, laser spectroscopy experiments were performed with on-line produced short-lived $^{212,213,214}$Ra$^+$ ions. The isotope shift of the 6\,^2D$_{3/2}$\,-\,7\,^2P$_{1/2}$ and 6\,^2D$_{3/2}$\,-\,7\,^2P$_{3/2}$ transitions and the hyperfine structure constant of the 7\,^2S$_{1/2}$ and 6\,^2D$_{3/2}$ states in $^{213}$Ra$^+$ were measured. These values provide a benchmark for the required atomic theory. A lower limit of $232(4)$ ms for the lifetime of the metastable 6\,^2D$_{5/2}$ state was measured by optical shelving.Comment: 4.2 pages, 6 figures, 2 tables

The SFXC software correlator for Very Long Baseline Interferometry: Algorithms and Implementation

In this paper a description is given of the SFXC software correlator, developed and maintained at the Joint Institute for VLBI in Europe (JIVE). The software is designed to run on generic Linux-based computing clusters. The correlation algorithm is explained in detail, as are some of the novel modes that software correlation has enabled, such as wide-field VLBI imaging through the use of multiple phase centres and pulsar gating and binning. This is followed by an overview of the software architecture. Finally, the performance of the correlator as a function of number of CPU cores, telescopes and spectral channels is shown.Comment: Accepted by Experimental Astronom

Isotope Shifts of the 6d\,^2D3/2 _{3/2}\, - 7p\,^2P1/2 _{1/2}\, Transition in Trapped Short-Lived 209−214^{209-214}Ra+^+

Laser spectroscopy of short-lived radium isotopes in a linear Paul trap has been performed. The isotope shifts of the 6d\,^2D$_{3/2}\,$ - 7p\,^2P$_{1/2}\,$ transition in $^{209-214}$Ra$^+$ were measured, which are sensitive to the short range part of the atomic wavefunctions. The results are essential experimental input for improving the precision of atomic structure calculation. This is indispensable for parity violation in Ra$^+$ aiming at the determination of the weak mixing angle.Comment: Accepted for publication in Physical Review A as a Rapid Communicatio

Inguinal microbiome in patients undergoing an endovascular aneurysm repair:Application of next-generation sequencing of the 16S-23S rRNA regions

Background: Surgical site infection (SSI) remains a hazardous complication after vascular surgery. In this pilot study we investigated the inguinal microbiome in skin biopsies using histology and 16S-23S rDNA Next Generation Sequencing (NGS). Our hypothesis was that causative microorganisms of SSI are present in the inguinal microbiome. Methods: Data on surgical site infections and skin samples from the Percutaneous in Endovascular Repair versus Open (PiERO) trail were evaluated. Two patients with SSI were matched for age and comorbidity to eight matching patients of the PiERO trial. All patients were treated for an abdominal aortic aneurysm with endovascular repair. Nasal and perineal cultures were taken preoperatively to detect Staphylococcus aureus carriage. After disinfection with chlorhexidine, groin biopsies were taken to identify bacteria in deeper skin layers. All samples were subjected to histological analysis and culture-free 16S-23S rDNA NGS. Results: Staphylococcus aureus species were cultured in 5 out of 20 preoperative nasal and perineal swaps. Histology detected only a few bacteria, NGS of the 16S-23S rRNA regions identified DNA of bacterial species in all biopsies (20/20). Most identified genera and species proved to be known skin flora bacteria. No relation was found between SSIs and the preoperative microbiome. Conclusion: In this pilot study, an innovative analysis of the preoperative microbiome using 16S-23S rDNA NGS did not show a relation with the occurrence of a surgical site infection. No pathogenic bacterial species were present in the inguinal skin after disinfection with chiorhexidine

Modulation of the plasminogen activation system by inflammatory cytokines in human colon carcinoma cells.

Inflammation may promote malignant invasion by enhancing cancer cell-associated proteolysis. Here we present the effect of inflammatory cytokines on the plasminogen activation system of eight human colon carcinoma cell lines. Tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) increased in several, but not all, cell lines the production of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and plasminogen activator inhibitor type 1 (PAI-1) as analysed by zymography, enzyme immunoassays and Northern analysis. Interleukin 6 (IL-6) had no effect. uPA receptor (uPAR) mRNA levels were also upregulated. However, each individual cell line responded differently following exposure to TNF-alpha or IL-1 beta. For example, there was a dose-dependent up-regulation of uPA and PAI-1 in SW 620 cells, whereas increased uPA production in SW 1116 cells was not accompanied by an increase in PAI-1. The TNF-alpha stimulatory effect was blocked by anti-TNF-alpha Fab fragments. All cell lines expressed both types of TNF receptor mRNAs, whereas no transcript for TNF-alpha, IL-1 beta, IL-6, IL-6 receptor or the IL-1 receptors was found. Our results demonstrate that TNF-alpha and IL-1 beta stimulate the plasminogen activation system in tumour cell but the responses differed even in cells derived from the same tissue origin

Magnetoresistance of a 2-dimensional electron gas in a random magnetic field

We report magnetoresistance measurements on a two-dimensional electron gas (2DEG) made from a high mobility GaAs/AlGaAs heterostructure, where the externally applied magnetic field was expelled from regions of the semiconductor by means of superconducting lead grains randomly distributed on the surface of the sample. A theoretical explanation in excellent agreement with the experiment is given within the framework of the semiclassical Boltzmann equation.Comment: REVTEX 3.0, 11 pages, 3 Postscript figures appended. The manuscript can also be obtained from our World Wide Web server: http://roemer.fys.ku.dk/randmag.ht