Biomineralization of gold in biofilms of Cupriavidus metallidurans.

Cupriavidus metallidurans, a bacterium capable of reductively precipitating toxic, aqueous gold(I/III)-complexes, dominates biofilm communities on gold (Au) grains from Australia. To examine the importance of C. metallidurans biofilms in secondary Au formation, we assessed the biomineralization potential of biofilms growing in quartz-sand-packed columns to periodic amendment with Au(I)-thiosulfate. In these experiments, >99 wt % of Au, was retained compared to <30 wt % in sterilized and abiotic controls. Biomineralization of Au occurred in the presence of viable biofilms via the formation of intra- and extra-cellular spherical nanoparticles, which aggregated into spheroidal and framboidal microparticles of up to 2 µm in diameter. Aggregates of Au formed around cells, eventually encapsulating and ultimately replacing them. These particles were morphologically analogous to Au-particles commonly observed on natural Au grains. Bacterial cells were connected via exopolymer or nanowires to µm-sized, extracellular Au-aggregates, which would intuitively improve the flow of electrons through the biofilm. This study demonstrates the importance of C. metallidurans biofilms for the detoxification of Au-complexes and demonstrates a central role for bacterial biomineralization in the formation of highly pure Au in surface environments.

[Significance of frozen section diagnosis for the management of laryngeal tumors]. / Bedeutung der Schnellschnittdiagnostik für das Management laryngealer Tumoren.

The frozen section procedure for immediate intraoperative pathological diagnosis represents a pivotal method in tumor diagnosis. In laryngeal tumors the most frequent indication for the use of this method is the documentation of the residual tumor status, while intraoperative consultation with the purpose of primary tumor diagnosis is less common. The specimen management employed in each case should be chosen depending on the clinical question: while the collection of a maximum amount of tissue is advisable for the determination of the residual tumor status, sparing a portion of the remaining tissue for possible future examinations is advisable in the case of primary tumor diagnosis. Moreover, intraoperative frozen section diagnosis with no immediate consequences should be avoided.

[Tumor microenvironment in gastrointestinal tumors]. / "Tumor microenvironment" in gastrointestinalen Tumoren.

The growing potential of modern molecular analysis tools has led to a sharp increase in the understanding of the molecular dimension of pathological processes and, consequently, to a growing influence of pathological diagnoses on the selection of therapeutic approaches. Molecular analysis tools have also led to the understanding that groups of tumors hitherto considered to belong to a single, homogeneous disease entity should rather be divided into subgroups with specific molecular attributes, growth behavior patterns and, consequently, different prognostic characteristics and therapeutic needs. A major factor contributing to the differentiation of these subgroups is the composition of the tumor microenvironment (ME), a compartment that is involved in the control of critical carcinogenetic processes such as angiogenesis and invasive growth. Consequently, the investigation of the ME promises to be a most auspicious field of research for pathologists and there is hope that the increased understanding of the interaction between neoplastic cells and the ME will lead to improved diagnostic tools and novel therapeutic approaches for the treatment of cancer patients.

A human recombinant autoantibody-based immunotoxin specific for the fetal acetylcholine receptor inhibits rhabdomyosarcoma growth in vitro and in a murine transplantation model.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) gamma-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA). While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.

Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy.

Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRAS(wt) genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.

Selection of reference genes for quantitative real-time PCR analysis in canine mammary tumors using the GeNorm algorithm.

Eleven reference genes (18s ribosomal ribonucleic acid [RNA], 28s ribosomal RNA, ubiquitin, beta-actin, glycerine aldehyde dehydrogenase, ATP-synthase subunit 5B, hydroxymethyl-bilane synthase, hypoxanthine-phosphoribosyl transferase, ribosomal protein L32, tryptophan 5-monooxygenase activation protein (zeta polypeptide), and TATA-Box binding protein) were analyzed in use as references for gene expression profiling experiments using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in canine mammary tumors. The transcription level of the candidates was measured in 22 histologically characterized excised tumor specimens from mammary gland tissue and 22 samples of non-neoplastic mammary tissue samples from the same individuals. Results were used to rank candidate reference genes using the GeNorm tool. It was determined that in samples of canine mammary gland tissue, a combination of hypoxanthine-phosphoribosyl transferase, ATP-synthase subunit 5B, ribosomal protein L32 and ubiquitin yields stable reference gene expression levels, whereas the use of glycerin aldehyde dehydrogenase or ribosomal RNA is unsuitable for normalization of qRT-PCR results in this tissue type.

[Prevalence and association of porcine circovirus type 2 (PCV2), porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV) in aborted fetuses, mummified fetuses, stillborn and nonviable neonatal piglets]. / Prävalenz sowie Assoziation von porzinem Circovirus Typ 2 (PCV2), porzinem Parvovirus (PPV) und porzinem reproductive and respiratory syndrome virus (PRRSV) in abortierten Feten, mumifizierten Feten, totgebore- nen und lebensschwach geborenen Ferkeln.

Porcine circovirus type 2 (PCV2) seems to cause reproductive failure in sows not only in experimental studies. A retrospective study was made with a total of 252 aborted fetuses, mummified fetuses, stillborn and nonviable neonatal piglets to determine the presence of PCV2, porcine parvovirus (PPV) and porcine respiratory and reproductive syndrome virus (PRRSV) by PCR. PCV2 was found in all stages of gestation in 27.1 percent of samples examined. A statistically significant association could be shown between the detection of PCV2 and PRRSV. However, no significant association was seen between the detection of PCV2 and PPV and between PPV and PRRSV.

Monoclinic superstructure of SrMgF4 with perovskite-type slabs.

Crystals of Ce-doped SrMgF4, strontium magnesium tetrafluoride, have been found to have a monoclinic P2(1) structure with doubled a and tripled c cell lengths compared with the orthorhombic Cmcm structure previously reported in the literature. The perovskite-type slabs, composed of corner-sharing MgF6 octahedra and Sr atoms, are stacked along the b axis. The six crystallographically independent MgF6 octahedra are rotated so as to provide long periodicities along a and c. The coordination numbers and bond distances around the six crystallographically independent Sr atoms are slightly different in each case. In the superstructure, the Sr atoms lie on local mirror planes which are thought to originate at the high-temperature phase transition.

Synchrotron X-ray study of Er3Al5O12 and Yb3Al5O12 garnets.

Structure factors for Er(3)Al(5)O(12) and Yb(3)Al(5)O(12) garnets were measured using focused synchrotron X-radiation, with lambda = 0.7500 (2) and 0.7000 (2) A, respectively. The difference electron density maps for Er(3)Al(5)O(12) and Yb(3)Al(5)O(12) were similar, as expected. This was attributed to the 4f electrons being shielded, which reduces their effectiveness in chemical bonding and the relative position of the rare-earth atoms in the periodic table. The symmetry of the difference electron density around the rare-earth atoms was found to reflect that of the cation geometry, emphasizing the importance of second nearest-neighbor interactions. This is consistent with the view that oxide-type structures may be regarded as a packed array of cations with anions in the interstices.