No evidence for constitutional chromosome instability in testicular cancer

Summary Chromosome aberrations in 20 lymphocytes of 20 patients with testicular germ cell tumors (TGCT) treated with surgery alone were compared with those of 20 cells from 20 healthy controls using standard G-banding technique. No increase in structural aberrations was found in the cancer group. An unexpected finding was that of more cells with losses of chromosomes being present in the control group. These losses predominantly affected small chromosomes in the control group, whereas the pattern of chromosome loss was different in the cancer group. The literature claiming increased chromosome instability in TGCT patients is reviewed. Point estimates and 95% confidence intervals to exclude such a hypothesis based on our results were calculated.     

Dynamics of coexisting Calanus finmarchicus, Calanus glacialis and Calanus hyperboreus populations in a high-Arctic fjord

We studied the population dynamics of Calanus finmarchicus, Calanus glacialis and Calanus hyperboreus in Billefjorden, Svalbard (78°40N). All three species reproduced in the fjord with different timing. The maximum abundance of Calanus spp. copepodite stages peaked on the 11th of July (29,000 ind m^–2). C. glacialis was the dominant species accounting for 60–80% of the total Calanus abundance. C. finmarchicus appear to thrive in the fjord despite the low temperatures (–1.86°C to 5°C) and accounted for 20–30% of the total population. C. hyperboreus contributed less to the total abundance (5–20%). A 1-year life cycle is suggested for C. finmarchicus and C. hyperboreus in the fjord, C. glacialis has a 1- to 2-year life cycle. Highest mortality rates were observed for copepodite stage CV in C. finmarchicus and C. glacialis (0.09 and 0.075 d^–1, respectively) and for females in C. hyperboreus (0.149 d^–1). Mortality of copepodite stages was substantially lower in C. glacialis than in the other species. This is particularly obvious in the early and numerous copepodite stages (CI + CII) during the period of recruitment to these stages. This suggests that differences in secondary production in Arctic pelagic ecosystems are controlled partly by population loss rates.     

Community composition of a hypersaline endoevaporitic microbial mat

A hypersaline, endoevaporitic microbial community in Eilat, Israel, was studied by microscopy and by PCR amplification of genes for 16S rRNA from different layers. In terms of biomass, the oxygenic layers of the community were dominated by Cyanobacteria of the Halothece, Spirulina, and Phormidium types, but cell counts (based on 4',6'-diamidino-2-phenylindole staining) and molecular surveys (clone libraries of PCR-amplified genes for 16S rRNA) showed that oxygenic phototrophs were outnumbered by the other constituents of the community, including chemotrophs and anoxygenic phototrophs. Bacterial clone libraries were dominated by phylotypes affiliated with the Bacteroidetes group and both photo- and chemotrophic groups of alpha-proteobacteria. Green filaments related to the Chloroflexi were less abundant than reported from hypersaline microbial mats growing at lower salinities and were only detected in the deepest part of the anoxygenic phototrophic zone. Also detected were nonphototrophic gamma- and delta-proteobacteria, Planctomycetes, the TM6 group, Firmicutes, and Spirochetes. Several of the phylotypes showed a distinct vertical distribution in the crust, suggesting specific adaptations to the presence or absence of oxygen and light. Archaea were less abundant than Bacteria, their diversity was lower, and the community was less stratified. Detected archaeal groups included organisms affiliated with the Methanosarcinales, the Halobacteriales, and uncultured groups of Euryarchaeota.     

Activation of the epidermal growth factor (EGF) receptor induces formation of EGF receptor- and Grb2-containing clathrin-coated pits

In HeLa cells depleted of adaptor protein 2 complex (AP2) by small interfering RNA (siRNA) to the mu2 or alpha subunit or by transient overexpression of an AP2 sequestering mutant of Eps15, endocytosis of the transferrin receptor (TfR) was strongly inhibited. However, epidermal growth factor (EGF)-induced endocytosis of the EGF receptor (EGFR) was inhibited only in cells where the alpha subunit had been knocked down. By immunoelectron microscopy, we found that in AP2-depleted cells, the number of clathrin-coated pits was strongly reduced. When such cells were incubated with EGF, new coated pits were formed. These contained EGF, EGFR, clathrin, and Grb2 but not the TfR. The induced coated pits contained the alpha subunit, but labeling density was reduced compared to control cells. Induction of clathrin-coated pits required EGFR kinase activity. Overexpression of Grb2 with inactivating point mutations in N- or C-terminal SH3 domains or in both SH3 domains inhibited EGF-induced formation of coated pits efficiently, even though Grb2 SH3 mutations did not block activation of mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K). Our data demonstrate that EGFR-induced signaling and Grb2 are essential for formation of clathrin-coated pits accommodating the EGFR, while activation of MAPK and PI3K is not required.     

Disposition of arsenobetaine in two marine fish species following administration of a single oral dose of [14C]arsenobetaine

The distribution and excretion of arsenobetaine in fish were investigated using whole body autoradiography and liquid scintillation counting. A single dose of synthesised [(14)C]arsenobetaine was orally administered to Atlantic salmon, Salmo salar L., and Atlantic cod, Gadus morhua L. Arsenobetaine was distributed to most organs within both species. Nevertheless, there were species differences in tissue distribution and excretory pattern. The highest level of arsenobetaine in Atlantic salmon was present in muscle tissue, while high levels of arsenobetaine were found in both muscle and liver (including gall bladder) from Atlantic cod. The results suggest that the major route of excretion was via urine, which seemed to be more important in Atlantic cod than in Atlantic salmon. Elimination of arsenobetaine via bile appeared to be negligible in both species.     

RBR: library-less repeat detection for ESTs

MOTIVATION: Repeat sequences in ESTs are a source of problems, in particular for clustering. ESTs are therefore commonly masked against a library of known repeats. High quality repeat libraries are available for the widely studied organisms, but for most other organisms the lack of such libraries is likely to compromise the quality of EST analysis. RESULTS: We present a fast, flexible and library-less method for masking repeats in EST sequences, based on match statistics within the EST collection. The method is not linked to a particular clustering algorithm. Extensive testing on datasets using different clustering methods and a genomic mapping as reference shows that this method gives results that are better than or as good as those obtained using RepeatMasker with a repeat library. AVAILABILITY: The implementation of RBR is available under the terms of the GPL from http://www.ii.uib.no/~ketil/bioinformatics CONTACT: ketil.malde@bccs.uib.no SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

Zoledronic acid repolarizes tumour‐associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway

It is unknown whether zoledronic acid (ZA) at clinically relevant doses is active against tumours not located in bone. Mice transgenic for the activated ErbB‐2 oncogene were treated with a cumulative number of doses equivalent to that recommended in human beings. A significant increase in tumour‐free and overall survival was observed in mice treated with ZA. At clinically compatible concentrations, ZA modulated the mevalonate pathway and affected protein prenylation in both tumour cells and macrophages. A marked reduction in the number of tumour‐associated macrophages was paralleled by a significant decrease in tumour vascularization. The local production of vascular endothelial growth factor and interleukin‐10 was drastically down‐regulated in favour of interferon‐γ production. Peritoneal macrophages and tumour‐associated macrophages of ZA‐treated mice recovered a full M1 antitumoral phenotype, as shown by nuclear translocation of nuclear factor kB, inducible nitric oxide synthase expression and nitric oxide production. These data indicate that clinically achievable doses of ZA inhibit spontaneous mammary cancerogenesis by targeting the local microenvironment, as shown by a decreased tumour vascularization, a reduced number of tumour‐associated macrophages and their reverted polarization from M2 to M1 phenotype.     

Low-Dose Micro-CT Imaging for Vascular Segmentation and Analysis Using Sparse-View Acquisitions

The aim of this study is to investigate whether reliable and accurate 3D geometrical models of the murine aortic arch can be constructed from sparse-view data in vivo micro-CT acquisitions. This would considerably reduce acquisition time and X-ray dose. In vivo contrast-enhanced micro-CT datasets were reconstructed using a conventional filtered back projection algorithm (FDK), the image space reconstruction algorithm (ISRA) and total variation regularized ISRA (ISRA-TV). The reconstructed images were then semi-automatically segmented. Segmentations of high- and low-dose protocols were compared and evaluated based on voxel classification, 3D model diameters and centerline differences. FDK reconstruction does not lead to accurate segmentation in the case of low-view acquisitions. ISRA manages accurate segmentation with 1024 or more projection views. ISRA-TV needs a minimum of 256 views. These results indicate that accurate vascular models can be obtained from micro-CT scans with 8 times less X-ray dose and acquisition time, as long as regularized iterative reconstruction is used.