Dynamics of learning motives and barriers in the context of changing human life roles

This paper promotes a theoretical discussion that focuses on the motives and barriers that make impact on adults learning as well as on their dynamics related to the change of social roles. The adult learning motives and barriers change and vary according to the prevailing social roles at different periods of one’s life. This dynamics of adult learning motives and barriers is mostly influenced by the importance and compatibility of acquired social roles, responsibility areas and spaces of a person and other factors. The qualitative data was gathered in March – April 2016 in Kaunas, Lithuania. The sample consisted of 30 narratives, written by informants, aged 35 to 65 years that were participating in professional training courses. There has been prepared 30 self-reflections that were analysed using content analysis. The analysis of empirical data shows that external learning motives and barriers prevail in the period when an individual is active in the labour market while the personal motives remain overshadowed. However, personal barriers prevail in the expression of learning barriers. This is influenced by the society’s attitude towards the performance of pupil and student roles and the value attitudes of surrounding people that partially control it

Understanding the Mechanism of Atovaquone Drug Resistance in <i>Plasmodium falciparum</i> Cytochrome b Mutation Y268S Using Computational Methods

<div><p>The rapid appearance of resistant malarial parasites after introduction of atovaquone (ATQ) drug has prompted the search for new drugs as even single point mutations in the active site of Cytochrome b protein can rapidly render ATQ ineffective. The presence of Y268 mutations in the Cytochrome b (Cyt b) protein is previously suggested to be responsible for the ATQ resistance in <i>Plasmodium falciparum</i> (<i>P. falciparum</i>). In this study, we examined the resistance mechanism against ATQ in <i>P. falciparum</i> through computational methods. Here, we reported a reliable protein model of Cyt bc1 complex containing Cyt b and the Iron-Sulphur Protein (ISP) of <i>P. falciparum</i> using composite modeling method by combining threading, <i>ab initio</i> modeling and atomic-level structure refinement approaches. The molecular dynamics simulations suggest that Y268S mutation causes ATQ resistance by reducing hydrophobic interactions between Cyt bc1 protein complex and ATQ. Moreover, the important histidine contact of ATQ with the ISP chain is also lost due to Y268S mutation. We noticed the induced mutation alters the arrangement of active site residues in a fashion that enforces ATQ to find its new stable binding site far away from the wild-type binding pocket. The MM-PBSA calculations also shows that the binding affinity of ATQ with Cyt bc1 complex is enough to hold it at this new site that ultimately leads to the ATQ resistance.</p></div

Molecular dynamics simulation graph of wild (Y268) and mutant (Y268S) Cyt bc1 complexes of <i>P. falciparum</i> in solution.

<p>(A) Root mean square deviation (RMSD) of backbone atoms with respect to their initial complexes over a period of 90 ns simulation time. (B) Radius of gyration (Rg) graph and (C) Distance of ATQ from the Qo site over the whole simulation in wild as well as mutant type.</p

Two dimensional contact plots of amino acid residues from the wild and all screened mutant models of Cyt bc1 complex from P. falciparum in the vicinity of 5 Å radius around ATQ.

<p>It may be noted that in the mutant models the position 268 shifted away from the 5 Å radius of ATQ Binding site. Whereas green color indicates that the particular amino acid residue is present in the wild as well as in all mutant models in the observed area; yellow, red, blue, cyan color shows amino acid residues present only in wild type, Y268S, Y268N and Y268C mutant models respectively.</p

Structural overlay of the homology model of Cyt b protein of <i>P. falciparum</i> (blue) with the Cyt b unit of <i>S. cerevisiae</i> (golden) (PDB ID: 3CX5).

<p>A total of 4 amino acid residues deletion in cd2 helix (red) of <i>P. falciparum</i> resulted in structural displacement when compared with the same domain of <i>S. cerevisiae</i> (green). Also the structural changes in ‘PEWY’ motif of ef helix are shown.</p

MM/PBSA binding free energies (kJ/mol) of wild-type and mutant Cyt bc1/ATQ complexes.

1<p>: coulombic term;</p>2<p>: van der Waals term;</p>3<p>: polar solvation term;</p>4<p>: nonpolar solvation term;</p>5<p>: polar term (sum of coulombic and polar solvation terms);</p>6<p>: nonpolar term (sum of van der Waals and nonpolar solvation terms);</p>7<p>: computational binding free energy.</p><p>MM/PBSA binding free energies (kJ/mol) of wild-type and mutant Cyt bc1/ATQ complexes.</p

ATQ binding site in the wild and mutant (Y268S) Cyt bc1 complex of <i>P. falciparum</i>.

<p>The figure indicates that ATQ binds to a new site in the mutant model which is around 12 Å distant from the Qo site. The structure was captured from the average structure of the Cyt bc1 complex of <i>P. falciparum</i> over 70–90 ns (converged part of the trajectory).</p

Sequence alignment of Cyt b protein and ISP chain of <i>P. falciparum</i> and <i>S. cerevisiae</i>.

<p>Amino acid residues involved in the formation of Qo site are highlighted in yellow tinted color.</p

Expression patterns of differentially expressed TFs and TF regulatory networks for primary and metastatic prostate cancer.

<p>Heat map of differentially expressed TFs having significant correlations with differentially expressed target genes in primary (A) and metastatic tumors (B). Each row represents a TF and each column represents a different sample. Color bars above the columns represent groups of samples: light blue, red and magenta for primary, metastatic and normal samples, respectively. Cells represent z-scores of TF expression values ranging from blue for low expression to red for highly expressed TFs. TF regulatory interactions with corresponding genes have been represented for primary (C) and metastatic (D) tumors. TFs and target genes are shown as triangular and oval nodes. The node color represent log fold changes (blue: down-regulation; red: up-regulation). The edge color indicates the type of regulation (green for activation and red for repression) and the edge width is proportional to the absolute correlation coefficient for the expression values of the connected pair.</p

Integrative regulatory network analysis results based on two network structure parameters (degree and betweenness centrality).

<p>Integrative regulatory network analysis results based on two network structure parameters (degree and betweenness centrality).</p