Analysis of Multi-Element Blended Course Teaching and Learning Mode Based on Student-Centered Concept under the Perspective of “Internet+”

The integration of Internet and education has changed students’ learning environment and affected their learning behavior, which poses a greater challenge to the traditional teaching mode. Through the SWOT analysis of the “student centered” multi-element blended teaching mode in the era of “Internet + education”, it is concluded that the adaptability of learners themselves and the mismatch between teachers’ educational ideas and this teaching model delay the development of education to a certain extent. Some suggestions are put forward, such as strengthening the supervision and guidance, implementing the teaching and learning model scientifically, improving teachers’ ideology and comprehensive quality, and making full use of the characteristics of Internet opening, sharing and collaboration to construct the public service system and platform of national educational resources

Identification of a sub-micromolar, non-peptide inhibitor of β-secretase with low neural cytotoxicity through in silico screening

Nowadays identification of novel non-peptide β-secretase (BACE-1, hereinafter) inhibitors with low cytotoxicity and good blood–brain barrier (BBB) property holds common interest of drug discovery for Alzheimer’s disease. Twenty SPECS compounds were tested in BACE-1 FRET assays and methylthiazoletetrazolium (MTT) cytotoxicity experiment. Two compounds: 2 and 15 demonstrated IC50 values of 0.53 and 9.4 μM. In addition, 2 showed least toxic effect to the neuroblastoma cells. The results from both in silico and in vitro studies provided new pharmacophoric entities for chemical synthesis and optimization on the current discovered BACE-1 small molecule inhibitors

Molecular docking and structure-activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors

A similarity search on the structural analogs of an inhibitor of BACE-1 with IC50 2.8 μM, which contained a P1 benzothiazole group together with a triazine ring linked by a secondary amine group, was described in this Letter and some more potent inhibitors against BACE-1 were identified. The most potent compound 5 (IC50 = 0.12 μM) increases the inhibitory potency by 24 folds. Our results suggest that a pyrrolidinyl side group at the P3′ and P4′ of the inhibitors are favored for strong inhibition and a small aromatic group at the P4 position is also essential to the potency

Sequence and structural evolution of the KsgA/Dim1 methyltransferase family

<p>Abstract</p> <p>Background</p> <p>One of the 60 or so genes conserved in all domains of life is the <it>ksgA/dim1 </it>orthologous group. Enzymes from this family perform the same post-transcriptional nucleotide modification in ribosome biogenesis, irrespective of organism. Despite this common function, divergence has enabled some family members to adopt new and sometimes radically different functions. For example, in <it>S. cerevisiae </it>Dim1 performs two distinct functions in ribosome biogenesis, while human mtTFB is not only an rRNA methyltransferase in the mitochondria but also a mitochondrial transcription factor. Thus, these proteins offer an unprecedented opportunity to study evolutionary aspects of structure/function relationships, especially with respect to our recently published work on the binding mode of a KsgA family member to its 30S subunit substrate. Here we compare and contrast KsgA orthologs from bacteria, eukaryotes, and mitochondria as well as the paralogous ErmC enzyme.</p> <p>Results</p> <p>By using structure and sequence comparisons in concert with a unified ribosome binding model, we have identified regions of the orthologs that are likely related to gains of function beyond the common methyltransferase function. There are core regions common to the entire enzyme class that are associated with ribosome binding, an event required in rRNA methylation activity, and regions that are conserved in subgroups that are presumably related to non-methyltransferase functions.</p> <p>Conclusion</p> <p>The ancient protein KsgA/Dim1 has adapted to cellular roles beyond that of merely an rRNA methyltransferase. These results provide a structural foundation for analysis of multiple aspects of ribosome biogenesis and mitochondrial transcription.</p