the landscape of Polish scholarship on education. Its subject is intellectual pursuits consisting in categorizing, typologizing and systematizing concepts relevant to education professionals. The ...epistemic potential of philosophical logic provides the grounds for ordering our knowledge and thus a better handling of academic and educational work, but also discovering new and so far unexplored areas of cognition. Despite Poland’s noteworthy heritage of analytical research, such a sub-discipline is still lacking in the science(s) of education.
W recenzowanej monografii zaprezentowano koncepcję pedagogiki analitycznej jako nowej subdyscypliny w polskiej pedagogice akademickiej. Jej przedmiotem są czynności intelektualne polegające na kategoryzowaniu, typologizowaniu i systematyzowaniu pojęć specjalistycznych. Epistemiczny potencjał logiki filozoficznej sprawia, że czynności te umożliwiają uporządkowanie wiedzy, a przez to lepsze posługiwanie się nią w działalności naukowej i edukacyjnej, jak również odkrywanie nieoznaczonych do tej pory obszarów poznania. Pomimo dziedzictwa przeszłości w zakresie prowadzenia badań analitycznych wciąż brakuje w polskiej pedagogice takiej subdyscypliny.
β‐sheet breakers (BSB) constitute a class of peptide inhibitors of amyloidogenesis, a process which is a hallmark of many diseases called amyloidoses, including Alzheimer's disease (AD); however, the ...molecular details of their action are still not fully understood. Here we describe the results of the computational investigation of the three BSBs, iaβ6 (LPFFFD), iaβ5 (LPFFD), and iaβ6_Gly (LPFGFD), in complex with the fibril model of Aβ42 and propose the kinetically probable mechanism of their action. The mechanism involves the binding of BSB to the central hydrophobic core (CHC) region (LVFFA) of Aβ fibril and the π‐stacking of its Phe rings both internally and with the Aβ fibril. In the process, the Aβ fibril undergoes distortion accumulating on the side of chain A (located on the odd tip of the fibril). In a single replica of extended molecular dynamics run of one of the iaβ6 poses, the distortion concludes in a dissociation of chain A from the fibril model of Aβ42. Altogether, we postulate that including consecutive Phe residues into BSBs docked around Phe 20 in the CHC region of Aβ42 improve their potency for dissolution of fibrils.
Alzheimer's disease is a fatal neurodegenerative malady which up to very recently did not have approved therapy modifying its course. After controversial approval of aducanumab (monoclonal antibody ...clearing β-amyloid plaques) by FDA for use in very early stages of disease, possibly new avenue opened for the treatment of patients. In line with this approach is search for compounds blocking aggregation into amyloid oligomers subsequently forming fibrils or compounds helping in getting rid of plaques formed by β-amyloid fibrils. Here we present in silico work on 627 sixtapeptide β-sheet breakers (BSBs) containing consecutive three aromatic residues. Three of these BSBs caused dissociation of one or two β-amyloid chains from U-shaped β-amyloid protofibril model 2BEG after docking and subsequent molecular dynamics simulations. Thorough analysis of our results let us postulate that the first steps of binding these successful BSBs involve π-π interactions with stacked chains of F19 and later also with F20 (F3 and F4 in 2BEG model of protofibril). The consecutive location of aromatic residues in BSBs makes them more attractive for chains of stacked F3 and F4 within the 2BEG model. Spotted by us, BSBs may be prospective lead compounds for an anti-Alzheimer's therapy.
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