64 research outputs found

    Seiteneinsteiger:innen im Schuldienst aus Sicht ihrer Kolleg:innen

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    Überall in Deutschland wird für die Deckung des Lehrkräftebedarfs auf Seiteneinsteiger:innen zurückgegriffen. Über die Ausgestaltung des Seiteneinstiegs in den Schulen und seine Auswirkungen auf das vorhandene Personal ist bislang wenig bekannt. Der vorliegende Beitrag gibt aus einer repräsentativen Befragung sächsischer Lehrkräfte erste Einblicke in die Einstellungen grundständig qualifizierter Lehrkräfte zum Seiteneinstieg: Einer verbreiteten grundsätzlichen Skepsis gegenüber dem Seiteneinstieg stehen tendenziell positive Erfahrungen mit Seiteneinsteiger:innen im eigenen Kollegium gegenüber. Deren Einsatz wird allerdings nicht als unmittelbare Entlastung in Situationen des Personalmangels wahrgenommen, sondern stellt für die grundständig qualifizierten Lehrkräfte eine zusätzliche Belastung dar. Eine Herausforderung für die Gestaltung des Seiteneinstiegs besteht darin, eine kollegiale Begleitung und Unterstützung der Seiteneinsteiger:innen bereitzustellen, die auf eine berufsbegleitende Professionalisierung der Seiteneinsteiger:innen zielt und die vorhandenen Kollegien zugleich nicht überfordert. (DIPF/Orig.

    Die Studiensituation im Lehramt. Lehramtsstudierendenbefragung 2021

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    Im Sommersemester 2021 führte das Zentrum für Lehrerbildung, Schul- und Berufsbildungsforschung (ZLSB) der TU Dresden eine Online-Befragung der Lehramtsstudierenden der Universität durch. Befragt wurde u. a. zu den Themen Kohärenz der Lehramtsstudiengänge, Lehrangebot, Schulpraktika und zu studienorganisatorischen Aspekten, um die Zufriedenheit der Studierenden in einem breiten Umfang zu erfassen. Aufgrund der Corona-Pandemie stellte auch die Umstellung auf die digitale Lehre ein wichtiges Thema dar. Die in der Broschüre vorgestellten Befunde geben einen differenzierten Einblick in die aktuelle Studiensituation im Lehramt an der TU Dresden. Obwohl sich die Befragten tendenziell mit ihrem Studium zufrieden zeigen, wird an manchen Stellen eine Unzufriedenheit mit der TU Dresden deutlich. U. a. fühlen sich die Studierenden hinsichtlich mancher Aspekte des Studiums nicht ausreichend informiert. Ein großes Problem stellt für sie zudem die Überschneidung von Lehrveranstaltungen dar, welchem die TU Dresden mittlerweile mit der Einführung eines Zeitfenstermodells entgegenwirkt. (DIPF/Orig.)In the summer semester of 2021, the Center for Teacher Education and Educational Research (ZLSB) at TU Dresden conducted an online survey of the university\u27s student teachers. The survey covered topics such as the coherence of the teaching degree programs, the range of courses offered, school internships and aspects of study organization in order to capture student satisfaction on a broad scale. Due to the Corona pandemic, the transition to digital teaching also represented an important topic. The findings presented in the booklet provide a differentiated insight into the current study situation in the teaching profession at the TU Dresden. Although the respondents tend to be satisfied with their studies, dissatisfaction with the TU Dresden is evident in some places. Among other things, the students feel that they are not sufficiently informed about some aspects of their studies. Another major problem for them is the overlapping of courses, which the TU Dresden counteracts by implementing a time slot model

    Influence of ground-state structure and Mg2+ binding on folding kinetics of the guanine-sensing riboswitch aptamer domain

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    Riboswitch RNAs fold into complex tertiary structures upon binding to their cognate ligand. Ligand recognition is accomplished by key residues in the binding pocket. In addition, it often crucially depends on the stability of peripheral structural elements. The ligand-bound complex of the guanine-sensing riboswitch from Bacillus subtilis, for example, is stabilized by extensive interactions between apical loop regions of the aptamer domain. Previously, we have shown that destabilization of this tertiary loop–loop interaction abrogates ligand binding of the G37A/C61U-mutant aptamer domain (Gswloop) in the absence of Mg2+. However, if Mg2+ is available, ligand-binding capability is restored by a population shift of the ground-state RNA ensemble toward RNA conformations with pre-formed loop–loop interactions. Here, we characterize the striking influence of long-range tertiary structure on RNA folding kinetics and on ligand-bound complex structure, both by X-ray crystallography and time-resolved NMR. The X-ray structure of the ligand-bound complex reveals that the global architecture is almost identical to the wild-type aptamer domain. The population of ligand-binding competent conformations in the ground-state ensemble of Gswloop is tunable through variation of the Mg2+ concentration. We quantitatively describe the influence of distinct Mg2+ concentrations on ligand-induced folding trajectories both by equilibrium and time-resolved NMR spectroscopy at single-residue resolution

    13C-direct detected NMR experiments for the sequential J-based resonance assignment of RNA oligonucleotides

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    We present here a set of 13C-direct detected NMR experiments to facilitate the resonance assignment of RNA oligonucleotides. Three experiments have been developed: (1) the (H)CC-TOCSY-experiment utilizing a virtual decoupling scheme to assign the intraresidual ribose 13C-spins, (2) the (H)CPC-experiment that correlates each phosphorus with the C4′ nuclei of adjacent nucleotides via J(C,P) couplings and (3) the (H)CPC-CCH-TOCSY-experiment that correlates the phosphorus nuclei with the respective C1′,H1′ ribose signals. The experiments were applied to two RNA hairpin structures. The current set of 13C-direct detected experiments allows direct and unambiguous assignment of the majority of the hetero nuclei and the identification of the individual ribose moieties following their sequential assignment. Thus, 13C-direct detected NMR methods constitute useful complements to the conventional 1H-detected approach for the resonance assignment of oligonucleotides that is often hindered by the limited chemical shift dispersion. The developed methods can also be applied to large deuterated RNAs

    Structure and dynamics of the deoxyguanosine-sensing riboswitch studied by NMR-spectroscopy

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    The mfl-riboswitch regulates expression of ribonucleotide reductase subunit in Mesoplasma florum by binding to 2′-deoxyguanosine and thereby promoting transcription termination. We characterized the structure of the ligand-bound aptamer domain by NMR spectroscopy and compared the mfl-aptamer to the aptamer domain of the closely related purine-sensing riboswitches. We show that the mfl-aptamer accommodates the extra 2′-deoxyribose unit of the ligand by forming a more relaxed binding pocket than these found in the purine-sensing riboswitches. Tertiary structures of the xpt-aptamer bound to guanine and of the mfl-aptamer bound to 2′-deoxyguanosine exhibit very similar features, although the sequence of the mfl-aptamer contains several alterations compared to the purine-aptamer consensus sequence. These alterations include the truncation of a hairpin loop which is crucial for complex formation in all purine-sensing riboswitches characterized to date. We further defined structural features and ligand binding requirements of the free mfl-aptamer and found that the presence of Mg2+ is not essential for complex formation, but facilitates ligand binding by promoting pre-organization of key structural motifs in the free aptamer

    In vitro models of medulloblastoma: choosing the right tool for the job

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    The recently-defined four molecular subgroups of medulloblastoma have required updating of our understanding of in vitro models to include molecular classification and risk stratification features from clinical practice. This review seeks to build a more comprehensive picture of the in vitro systems available for modelling medulloblastoma. The subtype classification and molecular characterisation for over 40 medulloblastoma cell-lines has been compiled, making it possible to identify the strengths and weaknesses in current model systems. Less than half (18/44) of established medulloblastoma cell-lines have been subgrouped. The majority of the subgrouped cell-lines (11/18) are Group 3 with MYC-amplification. SHH cell-lines are the next most common (4/18), half of which exhibit TP53 mutation. WNT and Group 4 subgroups, accounting for 50% of patients, remain underrepresented with 1 and 2 cell-lines respectively. In vitro modelling relies not only on incorporating appropriate tumour cells, but also on using systems with the relevant tissue architecture and phenotype as well as normal tissues. Novel ways of improving the clinical relevance of in vitro models are reviewed, focusing on 3D cell culture, extracellular matrix, co-cultures with normal cells and organotypic slices. This paper champions the establishment of a collaborative online-database and linked cell-bank to catalyse preclinical medulloblastoma research

    Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development

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    12 pags., 4 figs., 3 tabs.SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.Work at BMRZ is supported by the state of Hesse. Work in Covid19-NMR was supported by the Goethe Corona Funds, by the IWBEFRE-program 20007375 of state of Hesse, the DFG through CRC902: “Molecular Principles of RNA-based regulation.” and through infrastructure funds (project numbers: 277478796, 277479031, 392682309, 452632086, 70653611) and by European Union’s Horizon 2020 research and innovation program iNEXT-discovery under grant agreement No 871037. BY-COVID receives funding from the European Union’s Horizon Europe Research and Innovation Programme under grant agreement number 101046203. “INSPIRED” (MIS 5002550) project, implemented under the Action “Reinforcement of the Research and Innovation Infrastructure,” funded by the Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the EU (European Regional Development Fund) and the FP7 REGPOT CT-2011-285950—“SEE-DRUG” project (purchase of UPAT’s 700 MHz NMR equipment). The support of the CERM/CIRMMP center of Instruct-ERIC is gratefully acknowledged. This work has been funded in part by a grant of the Italian Ministry of University and Research (FISR2020IP_02112, ID-COVID) and by Fondazione CR Firenze. A.S. is supported by the Deutsche Forschungsgemeinschaft [SFB902/B16, SCHL2062/2-1] and the Johanna Quandt Young Academy at Goethe [2019/AS01]. M.H. and C.F. thank SFB902 and the Stiftung Polytechnische Gesellschaft for the Scholarship. L.L. work was supported by the French National Research Agency (ANR, NMR-SCoV2-ORF8), the Fondation de la Recherche Médicale (FRM, NMR-SCoV2-ORF8), FINOVI and the IR-RMN-THC Fr3050 CNRS. Work at UConn Health was supported by grants from the US National Institutes of Health (R01 GM135592 to B.H., P41 GM111135 and R01 GM123249 to J.C.H.) and the US National Science Foundation (DBI 2030601 to J.C.H.). Latvian Council of Science Grant No. VPP-COVID-2020/1-0014. National Science Foundation EAGER MCB-2031269. This work was supported by the grant Krebsliga KFS-4903-08-2019 and SNF-311030_192646 to J.O. P.G. (ITMP) The EOSC Future project is co-funded by the European Union Horizon Programme call INFRAEOSC-03-2020—Grant Agreement Number 101017536. Open Access funding enabled and organized by Projekt DEALPeer reviewe

    Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

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    The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form

    International cooperation and health. Part 2: making a difference.

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    The world is increasingly shaped by powerful global forces, many of which have consequences for human health and the social, economic, and environmental factors that influence health are increasingly determined at a supranational level. As a result, local or national level efforts to influence health determinants can have only a limited impact and it is all too easy for the individual public health practitioner to feel powerless. Yet while public health practitioners, on their own, may indeed be relatively powerless, together they can achieve a great deal. Part 2 of this glossary explores some of the strategies that they can use as they seek to make a difference
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