Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors

BACKGROUND: The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate. RESULTS: Ethanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid. CONCLUSION: The reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation

Folding and Self-Assembly of the TatA Translocation Pore Based on a Charge Zipper Mechanism

SummaryWe propose a concept for the folding and self-assembly of the pore-forming TatA complex from the Twin-arginine translocase and of other membrane proteins based on electrostatic “charge zippers.” Each subunit of TatA consists of a transmembrane segment, an amphiphilic helix (APH), and a C-terminal densely charged region (DCR). The sequence of charges in the DCR is complementary to the charge pattern on the APH, suggesting that the protein can be “zipped up” by a ladder of seven salt bridges. The length of the resulting hairpin matches the lipid bilayer thickness, hence a transmembrane pore could self-assemble via intra- and intermolecular salt bridges. The steric feasibility was rationalized by molecular dynamics simulations, and experimental evidence was obtained by monitoring the monomer-oligomer equilibrium of specific charge mutants. Similar “charge zippers” are proposed for other membrane-associated proteins, e.g., the biofilm-inducing peptide TisB, the human antimicrobial peptide dermcidin, and the pestiviral ERNS protein

A Survey of Methods for Volumetric Scene Reconstruction from Photographs

Scene reconstruction, the task of generating a 3D model of a scene given multiple 2D photographs taken of the scene, is an old and difficult problem in computer vision. Since its introduction, scene reconstruction has found application in many fields, including robotics, virtual reality, and entertainment. Volumetric models are a natural choice for scene reconstruction. Three broad classes of volumetric reconstruction techniques have been developed based on geometric intersections, color consistency, and pair-wise matching. Some of these techniques have spawned a number of variations and undergone considerable refinement. This paper is a survey of techniques for volumetric scene reconstruction

"Das ist ja wie bei den Heinzelmännchen!" - Unterstützung der Digitalisierung der medizinischen Lehre durch ein interdisziplinäres E-Tutor*innen-Team

Background: The forced and time-critical changeover to digital teaching and learning formats in the summer semester 2020 brought about numerous new challenges for the teaching staff of the Faculty of Medicine at the University of Regensburg. Didactic and personnel support of clinical lecturers for the preparation, creation, and supervision of digital teaching materials became necessary.Project description: Since interdisciplinary teams seem to be superior in finding creative solutions, an interdisciplinary student e-tutor team was established at the Faculty of Medicine to support the digitalization of the range of courses. After their initial basic training the e-tutors had regular team meetings and internal mini-training sessions to ensure their continuous professional development. The e-tutors could be "requested" by clinical teaching staff and then accompanied the respective course preparation and implementation as required. Results and discussion: Both clinical teachers and students perceived the student e-tutors' support to be very positive. The e-tutors described the interdisciplinarity of the team as an important learning resource and their work as an exciting and instructive task. Conclusion and outlook: Due to the positive experiences with the e-tutors, the faculty is striving to establish sustainable digital teaching and learning services in the coming semesters.Hintergrund: Die erzwungene und zeitkritische Umstellung auf digitale Lehr-Lernformate im Sommersemester 2020 brachte für die Lehrenden der Fakultät für Medizin an der Universität Regensburg zahlreiche neue Herausforderungen mit sich. Didaktische und personelle Unterstützung der Lehrenden zur Vorbereitung, Erstellung und Betreuung digitaler Angebote wurde notwendig.Projektbeschreibung: Da interdisziplinäre Teams in der kreativen Lösungsfindung überlegen scheinen, wurde ein interdisziplinäres studentisches E-Tutor*innen-Team an der Fakultät für Medizin etabliert, um die Digitalisierung des Lehrangebots zu unterstützen. Nach einem initialen Basistraining der E-Tutor*innen erfolgten zur kontinuierlichen Weiterentwicklung regelmäßige Teamtreffen und interne Mini-Schulungen. Die E-Tutor*innen konnten von den Lehrenden "angefordert" werden und begleiteten dann bedarfsorientiert die jeweiligen Kursvorbereitungen und -durchführungen. Ergebnisse und Diskussion: Die Unterstützung durch die studentischen E-Tutor*innen wurde von Lehrenden und Studierenden sehr positiv wahrgenommen. Die E-Tutor*innen beschreiben die Interdisziplinarität des Teams als wichtige Lernressource und ihre Tätigkeit als spannende und lehrreiche Aufgabe. Fazit und Ausblick: Aufgrund der positiven Erfahrungen mit den E-Tutor*innen wird zur nachhaltigen Verankerung digitaler Lehr-Lernangebote an der Fakultät für die kommenden Semester eine Verstetigung dieser Unterstützungsleistung angestrebt

Magnetic-Fe/Fe3O4-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages

The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell Fe/Fe[subscript]3O[subscript]4 magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells. They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system

Stabilisation effects of phosphane ligands in the homogeneous approach of sunlight induced hydrogen production

Most of the systems for photochemical hydrogen production are not stable and suffer from decomposition. With bis(bidentate) tetraphosphane ligands the stability increases enormously, up to more than 1000 h. This stability was achieved with a system containing osmium(ii) as a light harvesting antenna and palladium(ii) as a water reduction catalyst connected with a bis(bidentate) phosphane ligand in one molecule with the chemical formula [Os(bpy)2(dppcb)Pd(dppm)](PF6)4. With the help of electrochemical measurements as well as photophysical data and its single crystal X-ray structure, the electron transfer between the two active metal centres (light harvesting antenna, water reduction catalyst) was analysed. The distance between the two active metal centres was determined to be 7.396(1) \uc5. In a noble metal free combination of a copper based photosensitiser and a cobalt diimine-dioxime complex as water reduction catalyst a further stabilisation effect by the phosphane ligands is observed. With the help of triethylamine as a sacrificial donor in the presence of different monophosphane ligands it was possible to produce hydrogen with a turnover number of 1176. This completely novel combination is also able to produce hydrogen in a wide pH-range from pH = 7.0 to 12.5 with the maximum production at pH = 11.0. The influence of monophosphane ligands with different Tolman cone angles was investigated. Monophosphane ligands with a large Tolman cone angle (>160\ub0) could not stabilise the intermediate of the cobalt based water reduction catalyst and so the turnover number is lower than for systems with an addition of monophosphane ligands with a Tolman cone angle smaller than 160\ub0. The role of the monophosphane ligand during sunlight-induced hydrogen production was analysed and these results were confirmed with DFT calculations. Furthermore the crystal structures of two important Co(i) intermediates, which are the catalytic active species during the catalytic pathway, were obtained. The exchange of PPh3 with other tertiary phosphane ligands can have a major impact on the activity, depending on the coordination properties. By an exchange of monophosphane ligands with functionalised phosphane ligands (hybrid ligands) the hydrogen production was raised 2.17 times