180 research outputs found
Identification and functional characterization of bacterial small RNAs associating with the RNA chaperone Hfq
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From Mindless to Mindful Decision Making: Reflecting on Prescriptive Processes
People frequently make judgments and decisions in ways that, in hindsight, they might prefer to have made differently. Their judgments and decisions may be strongly influenced by some attributes that people would prefer receive less weight (e.g. transient emotions, peripheral cues, and social influence), and people may neglect other attributes that they would prefer receive more weight (e.g. factual information, subjective experiences, and personal preference). The central claim in this dissertation is that asking people to reflect on prescriptive decision processes--how decisions should be made--elicits a psychological state of mindfulness where people are increasingly aware of and better able to correct decisional influences. Such mindfulness thus improves the subjective quality of decisions. Six experiments examine how introspection-induced mindfulness changes the weighting of decision attributes and the outcome of decisions in various domains including charitable giving (Studies 1 & 5), dating (Studies 2 & 6), policy evaluations (Study 3), and movie preferences (Study 4). In each experiment, people's decisions are strongly influenced by some attributes while neglecting other attributes, in contrast with people's beliefs about how decisions should be made. By inducing mindfulness of prescriptive decision processes, people weight the decision attributes in closer accordance with how they think decisions should be made in that particular context. Furthermore, mindfulness also promotes increased awareness of decisional influences, which leads to judging the quality of decisions differently: a decision that people perceive to be consistent with their beliefs about how decisions should be made, is evaluated more favorably than a decision that is perceived to be inconsistent with such beliefs (Study 6)
Gene autoregulation by 3' UTR-derived bacterial small RNAs
Negative feedback regulation, that is the ability of a gene to repress its own synthesis, is the most abundant regulatory motif known to biology. Frequently reported for transcriptional regulators, negative feedback control relies on binding of a transcription factor to its own promoter. Here, we report a novel mechanism for gene autoregulation in bacteria relying on small regulatory RNA (sRNA) and the major endoribonuclease, RNase E. TIER-seq analysis (transiently-inactivating-an-endoribonuclease-followed-by-RNA-seq) revealed similar to 25,000 RNase E-dependent cleavage sites in Vibrio cholerae, several of which resulted in the accumulation of stable sRNAs. Focusing on two examples, OppZ and CarZ, we discovered that these sRNAs are processed from the 3' untranslated region (3' UTR) of the oppABCDF and carAB operons, respectively, and basepair with their own transcripts to inhibit translation. For OppZ, this process also triggers Rho-dependent transcription termination. Our data show that sRNAs from 3' UTRs serve as autoregulatory elements allowing negative feedback control at the post-transcriptional level
MUDIL – Musikalisches Distance Learning: Erfahrungen, Auswirkungen, Perspektiven:Ein Forschungsbericht zu ausgewählten Ergebnissen einer Online-Befragung zum Musikunterricht während des ersten Corona-Lockdowns im Frühjahr 2020
Die kooperative Studie MUDIL beforscht die Arbeitsfelder von Musiklehrenden an Schulen und Musikschulen unter den Bedingungen von Distance Learning während der Covid-19-Krise in Österreich. Der vorliegende Forschungsbericht stellt ausgewählte Ergebnisse einer österreichweiten, quantitativen online-Befragung im Sommer 2020 dar, in der Rückmeldungen von 1158 Lehrenden aus Musikschulen und Regelschulen der Sekundarstufe in ganz Österreich und Südtirol ausgewertet werden konnten. Inhalt sind neben einer sozio-demografischen Einordnung der Befragungsergebnisse die technischen und rechtlichen Rahmenbedingungen, die pädagogischen Entwicklungen in Unterricht und Lernen sowie damit verbundene Probleme und Chancen, sowie Ausblicke auf zukünftige Entwicklungen mit Einschätzungen von Potentialen und Risiken
The leader region of Laminin B1 mRNA confers cap-independent translation
Translation initiation of eukaryotic mRNAs generally occurs by cap-dependent ribosome scanning. However, certain mRNAs contain internal ribosome entry sites (IRES) allowing cap-independent translation. Several of these IRES-competent transcripts and their corresponding proteins are involved in tumourigenesis. This study focused on IRES-driven translation control during the epithelial to mesenchymal transition (EMT) of hepatocytes that reflects crucial aspects of carcinoma progression. Expression profiling of EMT revealed Laminin B1 (LamB1) to be translationally upregulated. The 5′-untranslated region (UTR) of LamB1 was potent to direct IRES-dependent mRNA utilization of a bicistronic reporter construct. Stringent assays for cryptic promoter and splice sites showed no aberrantly expressed transcripts, suggesting that the reporter activity provided by the leader region of LamB1 mRNA exclusively depends on IRES. In accordance, LamB1 expression increased upon negative interference with cap-dependent translation by expression of human rhinovirus 2A protease or heat shock of cells. Finally, the enhanced expression of LamB1 during EMT correlated with an elevated IRES activity. Together, these data provide first evidence that the 5′-UTR of LamB1 contains a bona fide IRES that directs translational upregulation of LamB1 during stress conditions and neoplastic progression of hepatocytes
Quantitative Analysis of Surface Contouring with Pulsed Bipolar Radiofrequency on Thin Chondromalacic Cartilage
The purpose of this study was to evaluate the quality of surface contouring of chondromalacic cartilage by bipolar radio frequency energy using different treatment patterns in an animal model, as well as examining the impact of the treatment onto chondrocyte viability by two different methods. Our experiments were conducted on 36 fresh osteochondral sections from the tibia plateau of slaughtered 6-month-old pigs, where the thickness of the cartilage is similar to that of human wrist cartilage. An area of 1 cm(2) was first treated with emery paper to simulate the chondromalacic cartilage. Then, the treatment with RFE followed in 6 different patterns. The osteochondral sections were assessed for cellular viability (live/dead assay, caspase (cell apoptosis marker) staining, and quantitative analysed images obtained by fluorescent microscopy). For a quantitative characterization of none or treated cartilage surfaces, various roughness parameters were measured using confocal laser scanning microscopy (Olympus LEXT OLS 4000 3D). To describe the roughness, the Root-Mean-Square parameter (Sq) was calculated. A smoothing effect of the cartilage surface was detectable upon each pattern of RFE treatment. The Sq for native cartilage was Sq=3.8 +/- 1.1 mu m. The best smoothing pattern was seen for two RFE passes and a 2-second pulsed mode (B2p2) with an Sq=27.3 +/- 4.9 mu m. However, with increased smoothing, an augmentation in chondrocyte death up to 95% was detected. Using bipolar RFE treatment in arthroscopy for small joints like the wrist or MCP joints should be used with caution. In the case of chondroplasty, there is a high chance to destroy the joint cartilage
SiteBinder: an improved approach for comparing multiple protein structural motifs.
There is a paramount need to develop new techniques and tools that will extract as much information as possible from the ever growing repository of protein 3D structures. We report here on the development of a software tool for the multiple superimposition of large sets of protein structural motifs. Our superimposition methodology performs a systematic search for the atom pairing that provides the best fit. During this search, the RMSD values for all chemically relevant pairings are calculated by quaternion algebra. The number of evaluated pairings is markedly decreased by using PDB annotations for atoms. This approach guarantees that the best fit will be found and can be applied even when sequence similarity is low or does not exist at all. We have implemented this methodology in the Web application SiteBinder, which is able to process up to thousands of protein structural motifs in a very short time, and which provides an intuitive and user-friendly interface. Our benchmarking analysis has shown the robustness, efficiency, and versatility of our methodology and its implementation by the successful superimposition of 1000 experimentally determined structures for each of 32 eukaryotic linear motifs. We also demonstrate the applicability of SiteBinder using three case studies. We first compared the structures of 61 PA-IIL sugar binding sites containing nine different sugars, and we found that the sugar binding sites of PA-IIL and its mutants have a conserved structure despite their binding different sugars. We then superimposed over 300 zinc finger central motifs and revealed that the molecular structure in the vicinity of the Zn atom is highly conserved. Finally, we superimposed 12 BH3 domains from pro-apoptotic proteins. Our findings come to support the hypothesis that there is a structural basis for the functional segregation of BH3-only proteins into activators and enablers
Loss of Npn1 from motor neurons causes postnatal deficits independent from Sema3A signaling
AbstractThe correct wiring of neuronal circuits is of crucial importance for the function of the vertebrate nervous system. Guidance cues like the neuropilin receptors (Npn) and their ligands, the semaphorins (Sema) provide a tight spatiotemporal control of sensory and motor axon growth and guidance. Among this family of guidance partners the Sema3A-Npn1 interaction has been shown to be of great importance, since defective signaling leads to wiring deficits and defasciculation. For the embryonic stage these defects have been well described, however, also after birth the organism can adapt to new challenges by compensational mechanisms. Therefore, we used the mouse lines Olig2-Cre;Npn1cond and Npn1Sema− to investigate how postnatal organisms cope with the loss of Npn1 selectively from motor neurons or a systemic dysfunctional Sema3A-Npn1 signaling in the entire organism, respectively. While in Olig2-Cre+;Npn1cond−/− mice clear anatomical deficits in paw posturing, bone structure, as well as muscle and nerve composition became evident, Npn1Sema− mutants appeared anatomically normal. Furthermore, Olig2-Cre+;Npn1cond mutants revealed a dysfunctional extensor muscle innervation after single-train stimulation of the N.radial. Interestingly, these mice did not show obvious deficits in voluntary locomotion, however, skilled motor function was affected. In contrast, Npn1Sema− mutants were less affected in all behavioral tests and able to improve their performance over time. Our data suggest that loss of Sema3A-Npn1 signaling is not the only cause for the observed deficits in Olig2-Cre+;Npn1cond−/− mice and that additional, yet unknown binding partners for Npn1 may be involved that allow Npn1Sema− mutants to compensate for their developmental deficits
The need for tumor surveillance of children and adolescents with cancer predisposition syndromes: a retrospective cohort study in a tertiary-care children’s hospital
Expert recommendations for the management of tumor surveillance in children with a variety of cancer predisposition syndromes (CPS) are available. We aimed (1) at identifying and characterizing children who are affected by a CPS and (2) at comparing current practice and consensus recommendations of the American Association for Cancer Research workshop in 2016. We performed a database search in the hospital information system of the University Children’s Hospital for CPS in children, adolescents, and young adults and complemented this by review of electronic patients’ charts. Between January 1, 2017, and December 3, 2019, 272 patients with 41 different CPS entities were identified in 20 departments (144 [52.9%] male, 128 [47.1%] female, median age 9.1 years, range, 0.4–27.8). Three (1.1%) patients died of non-malignancy-associated complications of the CPS; 49 (18.0%) patients were diagnosed with malignancy and received regular follow-up. For 209 (95.0%) of the remaining 220 patients, surveillance recommendations were available: 30/220 (13.6%) patients received CPS consultations according to existing consensus recommendations, 22/220 (10.0%) institutional surveillance approaches were not complying with recommendations, 84/220 (38.2%) patients were seen for other reasons, and 84/220 (38.2%) were not routinely cared for. Adherence to recommendations differed extensively among CPS entities. Conclusion: The spectrum of CPS patients at our tertiary-care children’s hospital is manifold. For most patients, awareness of cancer risk has to be enhanced and current practice needs to be adapted to consensus recommendations. Offering specialized CPS consultations and establishing education programs for patients, relatives, and physicians may increase adherence to recommendations
SiteBinder – an improved approach for comparing multiple protein structural motifs. Case studies on biologically important motifs
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