Surface plasmon resonance approach to study drug interactions with SARS-CoV-2 RNA-dependent RNA polymerase highlights treatment potential of suramin

The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is essential for virus replication, therefore it is a promising drug target. Here we present a surface plasmon resonance approach to study the interaction of RdRp with drugs in real time. We monitored the effect of favipiravir, ribavirin, sofosbuvir triphosphate PSI-7409 and suramin on RdRp binding to RNA immobilized on the chip. Suramin precluded interaction of RdRp with RNA and even displaced RdRp from RNA

School grade: how much of it can be explained with the adolescent's individual characteristics and how much with the variables of the family environment

Our paper presents results of a research of factors of the academic achievement of the ninth-grade elementary school students. Four hundred twenty-seven adolescents participated, among them 225 girls and 202 boys. We attempted to determine the extent in which the academic achievement (evaluated by means of national examinations and teachers' marks) in Slovene, mathematics and biology can be predicted by students' individual characteristics (language competence, intellectual abilities and personality dimensions) and some variables related to the family environment (parents' educational level, parental pressure on adolescent's learning, number of books at home, parents' wishes concerning the continuation of adolescent's education). By means of hierarchical linear modeling (HLM) we found rather small across-schools differences in average students' achievement; the proportion of the school-level variance ranged between 0% and 9%. On the other hand, variation between students within schools was larger; the proportion of the student-level variance in achievement ranged between 91% and 100%. The variables related to the student and the family environment explained between 37% and 63% of the variance in achievement evaluated by means of national examinations, and between 56% and 62% of the variance in achievement evaluated by means of teachers' marks, respectively. The most important predictors of the achievement were language competence, intellectual abilities, personality dimensions conscientiousness and openness/intellect, two components of parental influence to the school work, namely parental pressure and help with the school work, and the parents' educational level. We further tried to determine the extent in which schools differ with regard to the evaluated individual characteristics of adolescents and to the family environment variables. We found out that the across-school variation of adolescents' intellectual abilities, parents' educational level and certain components of parental influence on the student's school work is larger than the across-school variation of students' achievement, with the exception of the national examination in biology

The effect of psychological factors and parental education on adolescents' academic achievement

The aim of our research was to check the assumed path model of causal relationships between adolescent's psychological characteristics (language competence, intellectual ability, and personality dimensions), parental education, and adolescent's academic achievement. Adolescents (N = 427; among them 225 girls and 202 boys), who were attending the ninth grade of elementary school in the school year 2005/2006, and their parents participated in the study. Adolescent's academic achievement was assessed by the results of national examinations in Slovene and mathematics, teachers' marks in Slovene and mathematics, and adolescent's general school success. The results of structural equation modelling showed a good fit of the assumed path model if it included the direct effect of adolescent's psychological characteristics and parental education on adolescent's academic achievement and also the indirect effect of parental education and three personality dimensions (Conscientiousness, Extraversion, and Openness/Intellect) through the adolescent's language competence and general intelligence. The fit of the adopted path model was acceptable regardless of the way in which academic achievement was assessed and regardless of the sex of the participants. The most important predictors of the academic achievement were language competence, general intelligence, and personality dimensions Conscientiousness and Openness/Intellect. With the assumed path model of casual relationships we could explain between 53% and 63% of differences in adolescents' academic achievement

Specificity of Escherichia coli heat-Labile enterotoxin investigated by single-site mutagenesis and crystallography

Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a close homologue of the cholera toxin. The toxins bind to carbohydrate receptors in the gastrointestinal tract, leading to toxin uptake and, ultimately, to severe diarrhea. Previously, LT from human- and porcine-infecting ETEC (hLT and pLT, respectively) were shown to have different carbohydrate-binding specificities, in particular with respect to N-acetyllactosamine-terminating glycosphingolipids. Here, we probed 11 single-residue variants of the heat-labile enterotoxin with surface plasmon resonance spectroscopy and compared the data to the parent toxins. In addition we present a 1.45 Å crystal structure of pLTB in complex with branched lacto-N-neohexaose (Galβ4GlcNAcβ6[Galβ4GlcNAcβ3]Galβ4Glc). The largest difference in binding specificity is caused by mutation of residue 94, which links the primary and secondary binding sites of the toxins. Residue 95 (and to a smaller extent also residues 7 and 18) also contribute, whereas residue 4 shows no effect on monovalent binding of the ligand and may rather be important for multivalent binding and avidity

Identification of forest reproductive material origin of European beech using molecular methods

Od kakovosti in izvora gozdnega reprodukcijskega materiala (GRM) bodo odvisni genetska pestrost, struktura, preživetje in uspevanje sadik ter končno uspevanje in odpornost bodočega gozda. Zato mora Gozdarski inštitut Slovenije (GIS) na podlagi javnega pooblastila po Zakonu o gozdovih in zahtev zakonodaje o GRM preveriti njegov izvor pred izdajo glavnega spričevala ali na zahtevo inšpektorata kadarkoli v času trženja in uporabe. Uporaba molekularnih metod pripomore k vedenju o izvoru in genetski kakovosti GRM. GIS kontinuirano razvija znanje, infrastrukturo, gensko banko in molekularne baze podatkov za izvajanje opisanih testov. Zaradi suma o (načrtno) napačni navedbi izvora GRM, nabranega jeseni 2016 iz vsaj enega semenskega objekta, smo v predstavljeni študiji analizirali izvor in genetsko pestrost GRM iz štirih semenskih objektov bukve (Fagus sylvatica L.), v katerih je bilo seme nabrano v istem letu, ter drugih vzorcev iz Slovenske gozdne genske banke, skupaj petnajst. Za analize smo uporabili jedrne mikrosatelite, šestnajst lokusov, ki jih na GIS uporabljamo rutinsko. S tehničnega vidika so se izbrani markerji izkazali za primerne za identifikacijo posameznikov, oceno genetske pestrosti in identifikacijo domnevnega izvora. Zaradi možnosti mešanja vzorcev, pridobljenih s tal, in tehničnih potreb bomo v prihodnosti za potrebe rekonstrukcije genotipa semenskega drevesa analizirali vsaj dvanajst semen na drevo. Genetska pestrost manjših vzorcev je bila značilno manjša od tiste v velikih vzorcih. Opozarjamo, da je GRM nujno treba nabirati najmanj z v odobritvi semenskega objekta predpisanega števila dreves, da zagotovimo ustrezno veliko genetsko pestrost GRM, ki ga sadimo v gozdove. Metode razvrščanja posameznikov na podlagi Bayesove verjetnosti in filogenetska drevesa so pravilno določili izvor referenčnih vzorcev, medtem ko je bila resolucija analize glavnih komponent manjša. Vse metode, uporabljene za identifikacijo domnevnega izvora vzorcev semena, so nedvoumno pokazale, da vzorec TURs ni bil nabran v sestoju TUR, različen je tudi od preostalega analiziranega genofonda bukve v Sloveniji.Quality and origin of forest reproductive material (FRM) define the possible genetic diversity, structure, survival and development of seedlings and resilience of the future forest to stress and disturbances. The Slovenian Forestry Institute (SFI) must, based on the public authorization, in accordance to the Forest Act, The Act on Forest Reproductive Material and other legislation requirements concerning FRM, check its origin before issuing the master certificate or, on demand of the inspectorate, at any time during its marketing and use. Application of molecular methods contributes to the determination of FRM origin and its genetic quality. SFI continually develops know-how, infrastructure, gene bank, and molecular databases for performing such tests. In this study, the origin (provenance) and genetic diversity of FRM collected from four beech (Fagus sylvatica L.) seed stands in 2016 were analysed, resulting on the suspicion of (intentional) mislabelling of the origin of the FRM, and compared to samples stored in the Slovenian Forest Gene Bank. In total 15 samples were analysed using 16 nuclear microsatellite loci. From the technical point of view, the selected markers proved to be appropriate for individual tree identification, evaluation of genetic diversity, and identification of the alleged origin. Due to the possible mixing of samples, for which seed was collected from the ground, and technical needs, we will analyze in the future at least 12 seeds per tree for the needs of the seed tree genotype reconstruction. Genetic diversity of smaller samples (seed collected from less seed trees) was significantly lower than that of large ones. We would like to emphasize that FRM should be collected at least from the number of trees prescribed in the decree on approval of the seed object in order to safeguard genetic diversity of FRM. Methods of clustering using Bayesian methods and phylogenetic trees correctly determined the origin of reference samples, while the resolution of the principle component analysis was lower. All methods used for identification of the alleged origin of seed samples, unambiguously proved that TURs sample was not collected in TUR seed stand, and it also differed from the rest of the analysed beech gene pool in Slovenia. In the presented case study, the applied methods for the molecular identification of FRM origin proved to be necessary and prevented introduction of the inappropriate FRM into Slovenian forests