Teaching Qualitative Research Methods in Media and Communication: The Benefits and Limitations of Digital Learning Objects

Teaching qualitative research is often hampered by student uncertainties around how to apply methodological knowledge in practice. Digital learning objects (DLOs) may offer a solution to this problem, although they also come with limitations. This study assessed the student perspective on the strengths and limitations of six qualitative analysis DLOs in the field of media and communication. Drawing from a thematic analysis of 527 written student reflections on the use of these DLOs in learning practices, this paper found that DLOs were helpful in clearing doubts and cementing knowledge. Furthermore, they motivated students by increasing self-regulation and by providing a new learning environment that was perceived as showcasing “learning how to learn.” However, the DLOs also introduced new anxieties, destabilized the relationship between lecture and tutorial, and were not successful at fostering student reflexivity in relation to the research process. These findings provide practitioners with pedagogical insight into using DLOs to improve the learning experience of qualitative research

Molecular Mechanism of Thymidylate Synthase Inhibition by N 4 Hydroxy dCMP in View of Spectrophotometric and Crystallographic Studies

Novel evidence is presented allowing further clarification of the mechanism of the slow binding thymidylate synthase TS inhibition by N4 hydroxy dCMP N4 OH dCMP . Spectrophotometric monitoring documented time and temperature , and N4 OH dCMP dependent TS catalyzed dihydrofolate production, accompanying the mouse enzyme incubation with N4 OH dCMP and N5,10 methylenetetrahydrofolate, known to inactivate the enzyme by the covalent binding of the inhibitor, suggesting the demonstrated reaction to be uncoupled from the pyrimidine C 5 methylation. The latter was in accord with the hypothesis based on the previously presented structure of mouse TS cf. PDB ID 4EZ8 , and with conclusions based on the present structure of the parasitic nematode Trichinella spiralis, both co crystallized with N4 OH dCMP and N5,10 methylenetetrahdrofolate. The crystal structure of the mouse TS N4 OH dCMP complex soaked with N5,10 methylenetetrahydrofolate revealed the reaction to run via a unique imidazolidine ring opening, leaving the one carbon group bound to the N 10 atom, thus too distant from the pyrimidine C 5 atom to enable the electrophilic attack and methylene group transfe

2,4-Dithiouracil: the reproducible H-bonded structural motifs in the complexes with 18-membered crown ethers

[[abstract]]2,4-Dithiouracil (DTU) forms in the crystals the H-bonded monohydrates of a 1 : 1 : 1 ratio with 18-crown-6 (18C6) 1, cis,syn,cis-isomer of dicyclohexano-18-crown-6 (DCH6A) 2, and benzo-18-crown-6 (B18C6) 3, while the anhydrous adduct with cis,anti,cis-isomer of dicyclohexano-18-crown-6 (DCH6B) 4 is of a 2 : 1 ratio. In 1–3 the components reproducibly alternate in the chains, while in 4 the chains are built of the alternative centrosymmetric dimers of 2,4-dithiouracil and the molecules of the cis,anti,cis-isomer of dicyclohexano-18-crown-6.[[journaltype]]國外[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子版[[countrycodes]]GB

The dUTPase Enzyme Is Essential in Mycobacterium smegmatis

Thymidine biosynthesis is essential in all cells. Inhibitors of the enzymes involved in this pathway (e.g. methotrexate) are thus frequently used as cytostatics. Due to its pivotal role in mycobacterial thymidylate synthesis dUTPase, which hydrolyzes dUTP into the dTTP precursor dUMP, has been suggested as a target for new antitubercular agents. All mycobacterial genomes encode dUTPase with a mycobacteria-specific surface loop absent in the human dUTPase. Using Mycobacterium smegmatis as a fast growing model for Mycobacterium tuberculosis, we demonstrate that dUTPase knock-out results in lethality that can be reverted by complementation with wild-type dUTPase. Interestingly, a mutant dUTPase gene lacking the genus-specific loop was unable to complement the knock-out phenotype. We also show that deletion of the mycobacteria-specific loop has no major effect on dUTPase enzymatic properties in vitro and thus a yet to be identified loop-specific function seems to be essential within the bacterial cell context. In addition, here we demonstrated that Mycobacterium tuberculosis dUTPase is fully functional in Mycobacterium smegmatis as it rescues the lethal knock-out phenotype. Our results indicate the potential of dUTPase as a target for antitubercular drugs and identify a genus-specific surface loop on the enzyme as a selective target

Teaching Qualitative Research Methods in Media and Communication: The Benefits and Limitations of Digital Learning Objects

Teaching qualitative research is often hampered by student uncertainties around how to apply methodological knowledge in practice. Digital learning objects (DLOs) may offer a solution to this problem, although they also come with limitations. This study assessed the student perspective on the strengths and limitations of six qualitative analysis DLOs in the field of media and communication. Drawing from a thematic analysis of 527 written student reflections on the use of these DLOs in learning practices, this paper found that DLOs were helpful in clearing doubts and cementing knowledge. Furthermore, they motivated students by increasing self-regulation and by providing a new learning environment that was perceived as showcasing "learning how to learn." However, the DLOs also introduced new anxieties, destabilized the relationship between lecture and tutorial, and were not successful at fostering student reflexivity in relation to the research process. These findings provide practitioners with pedagogical insight into using DLOs to improve the learning experience of qualitative research

Increasing sequence diversity in protein design by combining Rosetta with molecular dynamics

Protein design is a procedure for computing natural-like sequences that will fold into a specifiedstructure. It has already been demonstrated that considering the backbone flexibility during thedesign process positively influences the diversity of the resulting sequences [1]. Rosetta Design, acommonly used software for protein design, allows for the effective exploration of the sequencespace, while the molecular dynamics (MD) simulations can thoroughly sample the protein nativestate conformational space. By combining these two approaches, we developed an iterative designprocedure, in which backbone conformational ensembles obtained by clustering of MD trajectoriesare used as templates for the design. We show that such a combined approach can generatesignificantly more diverse sequences than currently used procedures. The observed increase in thediversity is achieved without a loss in the quality of sequences, measured as overall resemblance ofthe designed sequences to natural sequences. In addition, we implemented a MD-based protocol [2]that can be used for assessing the stability of designed models and selecting the best candidates forexperimental validation or generating the structural ensembles that can be used as an input forfurther design simulations. In sum, our results demonstrate that the MD ensemble-based flexiblebackbone design significantly outperforms the current state-of-the-art methods and thus should be amethod of choice for the design of virtually all protein classes, including coiled coils. Finally, tomake the procedure accessible for the community we provide a set of easy-to-use scripts forperforming the simulations and visualizing the results

Crystal structures of complexes of mouse thymidylate synthase crystallized with N 4 OH dCMP alone or in the presence of N 5,N 10 methylenetetrahydrofolate

Abstract To solve the inhibition mechanism of thymidylate synthase (TS) by N4-hydroxy-dCMP (N4-OH-dCMP), crystallographic studies were undertaken. Structures of three mouse TS (mTS) complexes with the inhibitor were solved, based on crystals formed by the enzyme protein in the presence of either only N4-OH-dCMP [crystal A, belonging to the space group C 1 2 1, with two monomers in asymmetric unit (ASU), measured to 1.75 Å resolution] or both N4-OH-dCMP and N5,10 -methylenetetrahydrofolate (mTHF) (crystals B and C, both belonging to the space group C 2 2 21, each with a single monomer in ASU, measured to resolution of 1.35 Å and 1.17 Å, respectively). Whereas crystal A-based structure revealed the mTS-N4-OH-dCMP binary complex, as expected, crystals B- and C-based structures showed the enzyme to be involved in a ternary complex with N4-OH-dCMP and noncovalently bound dihydrofolate (DHF), instead of expected mTHF, suggesting the inhibition to be a consequence of an abortive enzyme-catalyzed reaction, involving a transfer of the one-carbon group to a hitherto unknown site and oxidation of THF to DHF. Moreover, both C(5) and C(6) inhibitor atoms showed sp3 hybridization, suggesting C(5) reduction, with no apparent indication of C(5) proton release. In accordance with our previous results, in all subunits of these structures the inhibitor molecule was identified as the anti rotamer of imino tautomer, forming, similar to deoxyuridine monophosphate, two hydrogen bonds with a conservative asparagine (mouse Asn220) side chain.</jats:p

The Current State of Visualization Techniques in Endoscopic Skull Base Surgery

Skull base surgery has undergone significant progress following key technological developments. From early candle-lit devices to the modern endoscope, refinements in visualization techniques have made endoscopic skull base surgery (ESBS) a standard practice for treating a variety of conditions. The endoscope has also been integrated with other technologies to enhance visualization, including fluorescence agents, intraoperative neuronavigation with augmented reality, and the exoscope. Endoscopic approaches have allowed neurosurgeons to reevaluate skull base neuroanatomy from new perspectives. These advances now serve as the foundation for future developments in ESBS. In this narrative review, we discuss the history and development of ESBS, current visualization techniques, and future innovations