AlphaFold and the amyloid landscape

Protein aggregation is a widespread phenomenon with important implications in many scientific areas. Although amyloid formation is typically considered as detrimental, functional amyloids that perform physiological roles have been identified in all kingdoms of life. Despite their functional and pathological relevance, the structural details of the majority of molecular species involved in the amyloidogenic process remains elusive. Here, we explore the application of AlphaFold, a highly accurate protein structure predictor, in the field of protein aggregation. While we envision a straightforward application of AlphaFold in assisting the design of globular proteins with improved solubility for biomedical and industrial purposes, the use of this algorithm for predicting the structure of aggregated species seems far from trivial. First, in amyloid diseases, the presence of multiple amyloid polymorphs and the heterogeneity of aggregation intermediates challenges the “one sequence, one structure” paradigm, inherent to sequence-based predictions. Second, aberrant aggregation is not the subject of positive selective pressure, precluding the use of evolutionary-based approaches, which are the core of the AlphaFold pipeline. Instead, amyloid polymorphism seems to be constrained by the need for a defined structure-activity relationship in functional amyloids. They may thus provide a starting point for the application of AlphaFold in the amyloid landscape.     

A Cysteine Endopeptidase (“Dionain”) Is Involved in the Digestive Fluid of Dionaea muscipula (Venus’s Fly-trap)

The carnivorous plant Dionaea muscipula (Venus’s flytrap) secretes proteinases into the digestive fluid to digest prey proteins. In this study, we obtained evidence that the digestive fluid contains a cysteine endopeptidase, presumably belonging to the papain family, through inhibitor studies and partial amino acid sequencing of the major SDS–PAGE band protein. The name “dionain” is proposed for the enzyme.     

Effects of Methoxsalen from Poncirus trifoliata on Acetylcholinesterase and Trimethyltin-Induced Learning and Memory Impairment

Previously, we identified methoxsalen (8-methoxy-2′,3′,6,7-furocoumarin) as the bioactive compound probably responsible for acetylcholinesterase (AchE) inhibition achieved by feeding crude extract of Poncirus trifoliate. To confirm the activity of methoxsalen, Institute of Cancer Research (ICR) mice were fed a control or a methoxsalen-supplemented diet for 4 weeks, and then learning and memory enhancing effects with respect to trimethyltin (TMT)-induced neurotoxicity were evaluated. The brain tissues of ICR mice were dissected after completion of the behavioral tests for biochemical analysis. Methoxsalen effectively reversed TMT-induced memory impairment on both Y-maze and passive avoidance tests. Brain AchE activity was inhibited by the oral consumption of all concentrations of methoxsalen. Moreover, the level of oxidative stress was significantly ameliorated in the groups on methodsalen containing diets. This is the first in vivo study conducted with methoxsalen in the field of AD research, and it indicates that further investigation of methoxsalen is warranted.     

Structure of the Maturing 90S Pre-ribosome in Association with the RNA Exosome

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Synthesis,characterization, and molecular docking analysis of novel benzimidazole derivatives as cholinesterase inhibitors

Two series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure were synthesized by a four-step reaction pathway starting from 4-fluoro-3-nitrobenzoic acid as the basic compound. The structure of the novel benzimidazoles was characterized and confirmed by the elemental and mass spectral analyses as well as ¹H NMR spectroscopic data. Of the 34 novel synthesized compounds, three benzimidazoles revealed AChE inhibition with IC₅₀ < 10 μM. The highest inhibitory activity (IC₅₀ = 5.12 μM for AChE and IC₅₀ = 8.63 μM for BChE) corresponds to the compound 5IIc (ethyl 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate). The relationship between lipophilicity and the chemical structures as well as their limited structure–activity relationship was discussed.     

Early human dispersal at the western edge of the Eastern European plain: Data from Ukraine

The current state of research on Lower Palaeolithic sites in Ukraine within its 1991 borders is the focus of this paper. Over the last 10–15 years, many new sites have been discovered in different parts of the eastern European area of the country, reassessed some old materials. In the central European region of the country, in the Ukrainian Transcarpathia, important new stratified Lower Palaeolithic sites have also been found. The current Ukrainian Lower Palaeolithic records demonstrate hominin presence in mountainous areas (Carpathians, Crimea) and the valleys of all major rivers, namely the Dniester, Southern Buh, Dnieper and Severskiy Donets. The article presents a brief review of the main currently known Lower Palaeolithic assemblages. Available geological, geomorphological, biostratigraphical data and ESR dates allow defining their age between 1.2 and 0.4 Myг; sites correlate with few warm phases between MIS 35 and MIS 11. Earlier sites, very tentatively dated at around 2 Myг, gravitate towards the seashore and mountainous areas. Later sites witness steady, though not continuous, colonisation of East European plain fringe areas. The main regularities of geographical setting, chronology, morphological and technological characteristics of assemblages of the Lower Palaeolithic sites of the Western segment of the East European plain are characterised. Typologically, industries are mainly characterised as belonging to Mode I. Core-and-flake industries survives to the Holsteinian. Essential difficulties in lithic raw materials supply could probably be a reason for the rise of a peculiar pattern of technological behaviour that involved mainly bipolar knapping and widely applied trimming technique of shaping the working edges of tools. Some signals of probable population movements penetrated the territory of Ukraine by the Asia Minor “western” trajectory and by Caucasian “eastern” way are revealed.     

A simple device to measure root growth rates

The construction and use of a simple auxanometer is described. With this instrument students can readily and accurately measure root growth rates of intact seedlings. Typical time course data are presented for the effect of ethylene and indole acetic acid on pea root growth.     

Out-of-school experience categories influencing interest in biology of secondary school students by gender: exploration on an Abu Dhabi sample

This study employed the international Relevance of Science Education questionnaire to survey the interest in biology and the out-of-school experiences of Abu Dhabi secondary school students (median age 17, mean age 17.53 and mode age of 16) in the third semester of 2014. It included 3100 participants. An exploratory factor analysis was used to categorise the items for both interest in biology and out-of-school experience. Ten interest in biology and 12 out-of-school experience factors were extracted. The summated means for each factor indicated that ‘health and fitness’ and ‘disease control’ enjoyed highest interests among students. For out-of-school experiences, the two factors of ‘digital applications’ and ‘medical treatment’ received the highest scores. Multivariate analysis of variance revealed that all factors for both interest in biology and out-of-school experience exhibited significant differences between boys and girls. More girls than boys were interested in disease control, reproduction (human biology), alternative science, health and fitness, zoology, and applied cosmetic biology. No significant differences were observed for the remaining five other categories. Furthermore, analysis of variance revealed significant differences between boys and girls with regard to individual items comprising each of the factors. The highest correlations were between the two factors of out-of-school experiences of ‘the natural world’ and ‘learning through observation’ and the interest in biology factor related to ‘plant and animal farming and agriculture’. Results suggested that more emphasis must be placed on students’ out-of-school experience and their engagement in informal learning in contextual outdoor environments to enhance their interest in learning more about biology and the living environment in general.