Grazing Effects of Ciliates on Microcolony Formation in Bacterial Biofilms

The attachment to surfaces and the subsequent formation of biofilms are a life strategy of bacteria offering several advantages for microorganisms, for example, a protection against toxins and antibiotics and profits due to synergistic effects in biofilm environment. Moreover, biofilm formation is thought to serve as grazing protection against predators. From pelagic systems it is known that feeding of bacterivorous protists may strongly influence the morphology, taxonomic composition and physiological status of bacterial communities and thus may be an important driving force for a change in bacterial growth and shift in morphology towards filaments and flocs. Bacteria in biofilms had to evolve several other defence strategies: production of extrapolymeric substances (EPS) or toxins, formation of specific growth forms with strong attachment, specific chemical surface properties and motility. In addition, bacteria can communicate via quorum sensing and react on grazing pressure. The results of the case study presented here showed that even microcolonies in bacterial biofilms are affected by the activity of grazers, though it may depend on the nutrient supply. Feedback effects due to remineralization of nutrients because of intensive grazing may stimulate biofilm growth and thereby enhancing grazing defence. Predator effects might be much more complex than they are currently believed to be

Dancing on the junction of mathematics and bodily experience

In this experimental paper, we document an experience of artistic research, initiated by searching an answer for the question Is it possible to learn mathematics through dance? . We reflect on three different pathways towards experiencing mathematics in dance: theory, methodology and artistic experience. Following these pathways requires us to challenge established assumptions about mathematics and research and finally allows for exploring the dancing body itself as the potential space of mathematical knowledge. While we remain far from our initial aim of being able to make concrete suggestions about how to integrate dance as an integral part of school mathematics, this article reveals the emancipatory potential of dancing mathematics, facilitating positive experiences with mathematics that hitherto appeared impossible to us

Geology-structural position and specialization of granitoid the Amalat plateau

Представлены результаты изучения геолого-структурной позиции и специализации гранитоидов Амалатского плато. Определен минеральный и элементный состава гранитоидов фундамента. Установлено, что гранитоиды фундамента представлены лейкократовыми биотитовыми гранитами субщелочного ряда, определены основные породообразующие минералы, акцессорная минерализация (апатит, циркон, сфен, магнетит, монацит, ксенотим) и минералы носители урана. Установлена высокая радиоактивность гранитоидов фундамента торий-урановой и урановой природы. The results of the studying of Geology-structural position and specialization of granitoid the Amalat table land. The mineral and element structure of granitoids' base was stated. It has been stated that granitoids in basement consist of leucocratic biotite granite of subalkaline row. The major rock-forming, accessory (apatite, zircon, sphen, magnetite, monazite, xenotime),and uranium-bearing minerals have been determined. High radioactivity of basement granitoids of thorium-uranium and uranium origin was stated

Multiclass cancer classification in fresh frozen and formalin-fixed paraffin-embedded tissue by DigiWest multiplex protein analysis

Histomorphology and immunohistochemistry are the most common ways of cancer classification in routine cancer diagnostics, but often reach their limits in determining the organ origin in metastasis. These cancers of unknown primary, which are mostly adenocarcinomas or squamous cell carcinomas, therefore require more sophisticated methodologies of classification. Here, we report a multiplex protein profiling-based approach for the classification of fresh frozen and formalin-fixed paraffin-embedded (FFPE) cancer tissue samples using the digital western blot technique DigiWest. A DigiWest-compatible FFPE extraction protocol was developed, and a total of 634 antibodies were tested in an initial set of 16 FFPE samples covering tumors from different origins. Of the 303 detected antibodies, 102 yielded significant correlation of signals in 25 pairs of fresh frozen and FFPE primary tumor samples, including head and neck squamous cell carcinomas (HNSC), lung squamous cell carcinomas (LUSC), lung adenocarcinomas (LUAD), colorectal adenocarcinomas (COAD), and pancreatic adenocarcinomas (PAAD). For this signature of 102 analytes (covering 88 total proteins and 14 phosphoproteins), a support vector machine (SVM) algorithm was developed. This allowed for the classification of the tissue of origin for all five tumor types studied here with high overall accuracies in both fresh frozen (90.4%) and FFPE (77.6%) samples. In addition, the SVM classifier reached an overall accuracy of 88% in an independent validation cohort of 25 FFPE tumor samples. Our results indicate that DigiWest-based protein profiling represents a valuable method for cancer classification, yielding conclusive and decisive data not only from fresh frozen specimens but also FFPE samples, thus making this approach attractive for routine clinical applications

Diversity and substrate-specificity of green algae and other micro-eukaryotes colonizing amphibian clutches in Germany, revealed by DNA metabarcoding

Amphibian clutches are colonized by diverse but poorly studied communities of micro-organisms. One of the most noted ones is the unicellular green alga, Oophila amblystomatis, but the occurrence and role of other micro-organisms in the capsular chamber surrounding amphibian clutches have remained largely unstudied. Here, we undertook a multi-marker DNA metabarcoding study to characterize the community of algae and other micro-eukaryotes associated with agile frog (Rana dalmatina) clutches. Samplings were performed at three small ponds in Germany, from four substrates: water, sediment, tree leaves from the bottom of the pond, and R. dalmatina clutches. Sampling substrate strongly determined the community compositions of algae and other micro-eukaryotes. Therefore, as expected, the frog clutch-associated communities formed clearly distinct clusters. Clutch-associated communities in our study were structured by a plethora of not only green algae, but also diatoms and other ochrophytes. The most abundant operational taxonomic units (OTUs) in clutch samples were taxa from Chlamydomonas, Oophila, but also from Nitzschia and other ochrophytes. Sequences of Oophila “Clade B” were found exclusively in clutches. Based on additional phylogenetic analyses of 18S rDNA and of a matrix of 18 nuclear genes derived from transcriptomes, we confirmed in our samples the existence of two distinct clades of green algae assigned to Oophila in past studies. We hypothesize that “Clade B” algae correspond to the true Oophila, whereas “Clade A” algae are a series of Chlorococcum species that, along with other green algae, ochrophytes and protists, colonize amphibian clutches opportunistically and are often cultured from clutch samples due to their robust growth performance. The clutch-associated communities were subject to filtering by sampling location, suggesting that the taxa colonizing amphibian clutches can drastically differ depending on environmental conditions

Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma

Giant cadherin FAT1 is increased in HCC and is a protumorigenic factors in HCC cell

Extended half-life target module for sustainable UniCAR T-cell treatment of STn-expressing cancers

Background: Adapter chimeric antigen receptor (CAR) approaches have emerged has promising strategies to increase clinical safety of CAR T-cell therapy. In the UniCAR system, the safety switch is controlled via a target module (TM) which is characterized by a small-size and short half-life. The rapid clearance of these TMs from the blood allows a quick steering and self-limiting safety switch of UniCAR T-cells by TM dosing. This is mainly important during onset of therapy when tumor burden and the risk for severe side effects are high. For long-term UniCAR therapy, the continuous infusion of TMs may not be an optimal setting for the patients. Thus, in later stages of treatment, single infusions of TMs with an increased half-life might play an important role in long-term surveillance and eradication of residual tumor cells. Given this, we aimed to develop and characterize a novel TM with extended half-life targeting the tumor-associated carbohydrate sialyl-Tn (STn). Methods: The extended half-life TM is composed of the STn-specific single-chain variable fragment (scFv) and the UniCAR epitope, fused to the hinge region and Fc domain of a human immunoglobulin 4 (IgG4) antibody. Specific binding and functionality of the αSTn-IgG4 TM as well as pharmacokinetic features were assessed using in vitro and in vivo assays and compared to the already established small-sized αSTn TM. Results: The novel αSTn-IgG4 TM efficiently activates and redirects UniCAR T-cells to STn-expressing tumors in a target-specific and TM-dependent manner, thereby promoting the secretion of proinflammatory cytokines and tumor cell lysis in vitro and in experimental mice. Moreover, PET-imaging results demonstrate the specific enrichment of the αSTn-IgG4 TM at the tumor site, while presenting a prolonged serum half-life compared to the short-lived αSTn TM. Conclusion: In a clinical setting, the combination of TMs with different formats and pharmacokinetics may represent a promising strategy for retargeting of UniCAR T-cells in a flexible, individualized and safe manner at particular stages of therapy. Furthermore, as these molecules can be used for in vivo imaging, they pose as attractive candidates for theranostic approaches.publishersversionpublishe

Resistive Switching Mechanisms on TaOx and SrRuO3 Thin-Film Surfaces Probed by Scanning Tunneling Microscopy

The local electronic properties of tantalum oxide (TaO[subscript x], 2 ≤ x ≤ 2.5) and strontium ruthenate (SrRuO[subscript 3]) thin-film surfaces were studied under the influence of electric fields induced by a scanning tunneling microscope (STM) tip. The switching between different redox states in both oxides is achieved without the need for physical electrical contact by controlling the magnitude and polarity of the applied voltage between the STM tip and the sample surface. We demonstrate for TaO[subscript x] films that two switching mechanisms operate. Reduced tantalum oxide shows resistive switching due to the formation of metallic Ta, but partial oxidation of the samples changes the switching mechanism to one mediated mainly by oxygen vacancies. For SrRuO[subscript 3], we found that the switching mechanism depends on the polarity of the applied voltage and involves formation, annihilation, and migration of oxygen vacancies. Although TaO[subscript x] and SrRuO[subscript 3] differ significantly in their electronic and structural properties, the resistive switching mechanisms could be elaborated based on STM measurements, proving the general capability of this method for studying resistive switching phenomena in different classes of transition metal oxides.National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Grant DMR-1419807