Identification of predictors of patient survival with TSPAN8 as a mediator of tumor aggressiveness in clear cell renal cell carcinoma

With the help of a patient-derived clear cell renal cell carcinoma (ccRCC) model system previously established in our laboratory, which recapitulates the heterogeneity of the originating tumor, we were able to study ccRCC on a functional level. In five rounds and in four biological replicates of an in vivo selection, we transplanted lung metastases of orthotopically transplanted tumor cells into the renal capsules of NOD scid gamma (NSG) mice. The tumor was enriched for cells with increased growth and higher metastatic potential compared to the initial heterogeneous population. Comparative gene expression analysis revealed candidate genes associated with enhanced malignant growth and metastasis. Least absolute shrinkage and selection operator (LASSO) regression identified a gene signature that can robustly predict cancer specific patient survival. The prognostic power of our signature was additionally verified in independent patient cohorts suggesting that this approach leverages efficient stratification of patients into distinctive risk groups. Intra- and intertumor heterogeneity remains a clinical challenge as estimated survival rates could vary substantially when comparing different tumor regions. Tetraspanin-8 (TSPAN8) was identified as one of the hallmark genes in the generated ccRCC signature and is known to alter cellular signaling. Therefore, we hypothesized that TSPAN8 contributes to tumor aggressiveness and thus to growth and metastasis of ccRCC. In fact, in knockdown and overexpression xenografts experiments, we could confirm an essential role for tumor aggressiveness in vivo suggesting that TSPAN8 is an attractive target for treatment of clear cell renal cell carcinoma

A Dibismuthane with Olefin Functional Groups: Towards Tridentate Hybrid Chalcogen/Olefin Ligands

Bis[dibenzobismepine], a dibismuthane composed of two bismepine units (R2Bi BiR2), was synthesized and fully characterized (R2=(C6H4CH)2). Reactions of this dibismuthane with diphenyl dichalcogenides, dibenzoylperoxide, and elemental chalcogens have been investigated. All products of these reactions have been isolated and fully characterized, including a series of compounds R2Bi E BiR2 (E=O Te). These species contain two olefin units of the bismepine moieties and a chalcogen atom as potential coordination sites. The potential of these species to act as hybrid tridentate chalcogen/olefin ligands with bismuth atoms as structure-determining elements in the backbone has been investigated by theoretical approaches, aiming at the complexation of CoI, RhI, IrI and Ni0, Pd0, Pt0. The analytical techniques applied in this work include heteronuclear and 2D NMR spectroscopy, elemental analysis, single-crystal X-ray diffraction analysis, and DFT calculations

Das Dimethylbismut-Kation: Zugang zu dativen Bi-Bi-Bindungen und unkonventionellem Methylaustausch

Die Isolierung einfacher, hochreaktiver metallorganischer Verbindungen von grundlegendem Interesse gehört nach wie vor zu den schwierigsten Aufgaben in der Synthesechemie. Die detaillierte Charakterisierung solcher Verbindungen ist der Schlüssel zum Verständnis neuer Bindungsszenarien und Reaktivitäten. Das Dimethylbismut-Kation, [BiMe2(SbF6)] (1), wurde isoliert und charakterisiert. Seine Reaktion mit BiMe3 ermöglicht den Zugang zu einer bislang unbekannten dativen Bindung, der Bi→Bi-Donor/Akzeptor-Wechselwirkung. Der Austausch von Methylgruppen (der wohl einfachsten Kohlenwasserstoffeinheit) zwischen verschiedenen Metallatomen gehört zu den wichtigsten Reaktionstypen in der metallorganischen Chemie. Die Reaktion von 1 mit BiMe3 ermöglicht einen Methylaustausch über eine Rückseiten-SE2-Reaktion, welche zum ersten Mal im Detail für isolierbare, (pseudo-)homoleptische Hauptgruppenverbindungen untersucht wird

Captive breeding of European freshwater mussels as aconservation tool: A review

1. Freshwater mussels are declining throughout their range. Their importantecological functions along with insufficient levels of natural recruitment haveprompted captive breeding for population augmentation and questions about the usefulness and applicability of such measures. 2. This article reviews the current state of captive breeding and rearing programmes for freshwater mussels in Europe. It considers the various species, strategies, andtechniques of propagation, as well as the different levels of effort requiredaccording to rearing method, highlighting the key factors of success. 3. Within the last 30 years, 46 breeding activities in 16 European countries have been reported, mainly of Margaritifera margaritifera and Unio crassus. Some facilities propagate species that are in a very critical situation, such as Pseudunio auricularius, Unio mancus, and Unio ravoisieri, or multiple species concurrently. Insome streams, the number of released captive-bred mussels already exceeds the size of the remaining natural population. 4. Rearing efforts range from highly intensive laboratory incubation to lowerintensity methods using in-river mussel cages or silos. Most breeding efforts are funded by national and EU LIFE(+) grants, are well documented, and consider the genetic integrity of the propagated mussels. Limited long-term funding perspectives, the availability of experienced staff, water quality, and feeding/survival during early life stages are seen as the most important challenges. 5. Successful captive breeding programmes need to be combined with restoration ofthe habitats into which the mussels are released. This work will benefit from anevidence-based approach, knowledge exchange among facilities, and an overall breeding strategy comprising multiple countries and conservation units. aquaculture, captive breeding, conservation translocation, freshwater mussel culturing, Margaritifera margaritifera, propagation, reintroduction, Unio crassusCaptive breeding of European freshwater mussels as aconservation tool: A reviewpublishedVersio

Arp3 controls the podocyte architecture at the kidney filtration barrier

Podocytes, highly specialized epithelial cells, build the outer part of the kidney filtration barrier and withstand high mechanical forces through a complex network of cellular protrusions. Here, we show that Arp2/3-dependent actin polymerization controls actomyosin contractility and focal adhesion maturation of podocyte protrusions and thereby regulates formation, maintenance, and capacity to adapt to mechanical requirements of the filtration barrier. We find that N-WASP-Arp2/3 define the development of complex arborized podocyte protrusions in vitro and in vivo. Loss of dendritic actin networks results in a pronounced activation of the actomyosin cytoskeleton and the generation of over-maturated but less efficient adhesion, leading to detachment of podocytes. Our data provide a model to explain podocyte protrusion morphology and their mechanical stability based on a tripartite relationship between actin polymerization, contractility, and adhesion

Between a Rock and a Hard Place: Habitat Selection in Female-Calf Humpback Whale (Megaptera novaeangliae) Pairs on the Hawaiian Breeding Grounds

The Au'au Channel between the islands of Maui and Lanai, Hawaii comprises critical breeding habitat for humpback whales (Megaptera novaeangliae) of the Central North Pacific stock. However, like many regions where marine mega-fauna gather, these waters are also the focus of a flourishing local eco-tourism and whale watching industry. Our aim was to establish current trends in habitat preference in female-calf humpback whale pairs within this region, focusing specifically on the busy, eastern portions of the channel. We used an equally-spaced zigzag transect survey design, compiled our results in a GIS model to identify spatial trends and calculated Neu's Indices to quantify levels of habitat use. Our study revealed that while mysticete female-calf pairs on breeding grounds typically favor shallow, inshore waters, female-calf pairs in the Au'au Channel avoided shallow waters (<20 m) and regions within 2 km of the shoreline. Preferred regions for female-calf pairs comprised water depths between 40–60 m, regions of rugged bottom topography and regions that lay between 4 and 6 km from a small boat harbor (Lahaina Harbor) that fell within the study area. In contrast to other humpback whale breeding grounds, there was only minimal evidence of typical patterns of stratification or segregation according to group composition. A review of habitat use by maternal females across Hawaiian waters indicates that maternal habitat choice varies between localities within the Hawaiian Islands, suggesting that maternal females alter their use of habitat according to locally varying pressures. This ability to respond to varying environments may be the key that allows wildlife species to persist in regions where human activity and critical habitat overlap

CMS physics technical design report : Addendum on high density QCD with heavy ions

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