Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. Initial nucleation of a yeast prion by ...transiently overproduced prion-forming protein or its (typically, QN-rich) prion domain is efficient only in the presence of another aggregated (in most cases, QN-rich) protein. Here, we demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non-QN–rich mammalian proteins, associated with amyloid diseases, promotes nucleation of Sup35 prions in the absence of pre-existing aggregates. In contrast, both a fusion of the Sup35 prion domain to a multimeric non-amyloidogenic protein and the expression of a mammalian amyloidogenic protein that is not fused to the Sup35 prion domain failed to promote prion nucleation, further indicating that physical linkage of a mammalian amyloidogenic protein to the prion domain of a yeast protein is required for the nucleation of a yeast prion. Biochemical and cytological approaches confirmed the nucleation of protein aggregates in the yeast cell. Sequence alterations antagonizing or enhancing amyloidogenicity of human amyloid-β (associated with Alzheimer's disease) and mouse prion protein (associated with prion diseases), respectively, antagonized or enhanced nucleation of a yeast prion by these proteins. The yeast-based prion nucleation assay, developed in our work, can be employed for mutational dissection of amyloidogenic proteins. We anticipate that it will aid in the identification of chemicals that influence initial amyloid nucleation and in searching for new amyloidogenic proteins in a variety of proteomes.
Yeast prions are self-perpetuating, QN-rich amyloids that control heritable traits and serve as a model for mammalian amyloidoses. De novo prion formation by overproduced prion protein is facilitated ...by other aggregated QN-rich protein(s) and is influenced by alterations of protein homeostasis. Here we explore the mechanism by which the Las17-binding protein Lsb2 (Pin3) promotes conversion of the translation termination factor Sup35 into its prion form, PSI+. We show that Lsb2 localizes with some Sup35 aggregates and that Lsb2 is a short-lived protein whose levels are controlled via the ubiquitin-proteasome system and are dramatically increased by stress. Loss of Lsb2 decreases stability of PSI+ after brief heat shock. Mutations interfering with Lsb2 ubiquitination increase prion induction, while a mutation eliminating association of Lsb2 with the actin cytoskeleton blocks its aggregation and prion-inducing ability. These findings directly implicate the UPS and actin cytoskeleton in regulating prions via a stress-inducible QN-rich protein.
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► High levels of Lsb2/Pin3 induce formation of both Sup35 and Rnq1 prions ► Lsb2 is a short-lived protein that is dramatically increased by thermal stress ► Loss of Lsb2 decreases the stability of the Sup35 prion after brief heat shock ► Preventing Lsb2 ubiquitination or actin association modulates prion induction
Abstract
The relevance of the chosen topic is due to the need to solve environmental problems that arise when drilling oil and gas wells. The study is aimed at the disposal, neutralization and reuse ...of drilling waste, which will create a reserve of competitive raw materials for the production of bricks. The possibility of recycling a man-made product obtained in the process of drilling oil wells at the facilities of the Morozovskoye deposit (Krasnodar Territory) in the production of ceramic products, namely building bricks, is considered. A physical and chemical study of the drilling waste of the considered deposit was carried out, with the aim of its subsequent use in the raw mix for the production of building bricks. A comparative characteristic of the raw material composition, phase and mineralogical composition, as well as the plasticity number of drilling waste and clay from the Gubskoye deposit (Krasnodar Territory) is presented. On the basis of the data obtained, appropriate conclusions were made about the possibility of using drilling waste as a raw material component.
Summary
Self‐perpetuating amyloid‐based protein isoforms (prions) transmit neurodegenerative diseases in mammals and phenotypic traits in yeast. Although mechanisms that control species specificity ...of prion transmission are poorly understood, studies of closely related orthologues of yeast prion protein Sup35 demonstrate that cross‐species prion transmission is modulated by both genetic (specific sequence elements) and epigenetic (prion variants, or ‘strains’) factors. Depending on the prion variant, the species barrier could be controlled at the level of either heterologous co‐aggregation or conversion of the aggregate‐associated heterologous protein into a prion polymer. Sequence divergence influences cross‐species transmission of different prion variants in opposing ways. The ability of a heterologous prion domain to either faithfully reproduce or irreversibly switch the variant‐specific prion patterns depends on both sequence divergence and the prion variant. Sequence variations within different modules of prion domains contribute to transmission barriers in different cross‐species combinations. Individual amino acid substitutions within short amyloidogenic stretches drastically alter patterns of cross‐species prion conversion, implicating these stretches as major determinants of species specificity.
The investigation is aimed at elaboration of technology for submicron p+-GaAs layer formation on micro/nanotextured n-GaAs substrates by using low-temperature (550°C) diffusion of zinc to take the ...advantage of optical and recombination properties of textured interface for solar cells. Process duration, surface microrelief morphology (dendrite or quasi-grating (grating-like)) and the substrate doping impurity concentration were varied. Optical, photoelectric and electrical properties of p+–n junction were studied to optimize the process conditions. The highest efficiency was obtained in structures with a quasi-grating surface microrelief, substrate doping close to Nd≃1017cm−3 and process duration about 45min.
•Technology of diffused GaAs p+-n junction with microrelief interface was elaborated.•Surface microrelief with different morphology was obtained by anisotropic etching.•Optical, photoelectric and electric characterization to optimize low-temperature diffusion.•Theoretical analysis of doping fluctuation effect was performed.•Low-temperature diffusion conditions were optimized for different relief morphologies.
Аналізується визначення цінностей у науковій літературі, мотиваційна основа становлення цінностей особистості та співвідношення понять “цінність” і “ціннісна орієнтація”; обґрунтовується авторське ...визначення поняття “становлення цінностей особистості”, а також висвітлюються кроскультурні співвідношення становлення цінностей в українській і румунській та українській і македонській вибірках досліджуваних. Подано результати пояснювального (EFA) та підтверджувального (CFA) факторного аналізу за результатами вимірювання становлення особистісних цінностей цих категорій досліджуваних. Здійснено кроскультурне порівняння особливостей становлення цінностей аксіофактору відкритості до змін та аналізуються його результати. Наводяться дані про взаємозв’язок між особистісними цінностями й суб’єктивним благополуччям досліджуваних у кроскультурному розрізі. Теоретичний аналіз провідних наукових підходів до обґрунтування цінностей вимагає усвідомлення того, що вони відбивають культурні й соціальні (ідеологічні і політичні) носії суспільства, соціальної групи та особистості, а емпіричне дослідження частково пітвердило гіпотезу про закономірність зв’язку між суб’єктивним благополуччям і цінностями особистості. Цінності конформності і традицій виявилися значуще пов’язаними із задоволеністю життям для македонської групи дорослих, що підтвердило очікування щодо негативного співвідношення “нездорових” цінностей із суб’єктивним благополуччям. З’ясовано, що молоді люди, цінності яких орієнтовані на володіння речами та їх накопичення на противагу духовним цінностям, виявляються зазвичай менш задоволеними власним життям; молодь із досліджених країн, яка володіє сильними і розвиненими “здоровими” цінностями, відчуває себе в житті краще, і навпаки, носії “нездорових” цінностей найчастіше не задоволені життям і відчувають через це певний неспокій.
Aim
. In vitro evaluation of the inhibitory activity of aqueous extracts and dry ethanol extracts of St John's wort (Hypericum perforatum L.) on the replication of SARS-CoV-2 according to three ...experimental schemes – direct inactivation (neutralisation) of the virus as well as "prevention" and "treatment" of cells.
Materials and Methods
. The laboratory strain SARS-CoV-2/human/RUS/Nsk-FRCFTM-1/2020 was passed on Vero cell culture. Water extracts and dry ethanol extracts of parts of H. perforatum L. collected during the flowering period in the Novosibirsk region were prepared. Dry extracts were dissolved in DMSO. Comparison samples are dry ethanol extracts of chaga, cloves and black tea.
Results
. It is shown that the aqueous extract of grass (a mixture of flowers with leaves) of H. perforatum L. with direct inactivation of the virus it is active in dilution of 1/4096. For the dry ethanol extract of the herb H. perforatum L., 50 % effective concentrations (EC50) were found equal to 2.44±0.87; 8.79±1.91 and 14.65±1.91 μg/ml respectively with direct inactivation as well as according to the "preventive" scheme and with the "treatment" of cells. Taking into account cytotoxicity, as well as in comparison with control samples, the values of selective indices (SI50) of the studied herbal preparations during direct inactivation were higher than with other experimental schemes and were distributed as follows (in descending order): 204.92; 153.68; 115.27; 32.01 and 21.33 for dry ethanol extracts of black tea from India, cloves, herbs, a mixture of flowers with leaves, of H. perforatum, chaga and the stems of H. perforatum respectively. The HPLC method has shown that the ethanol extract of the herb H. perforatum L. contains a greater amount of flavonoids than the extract of stems. Nevertheless, antiviral activity was also detected for the extract of stems of this plant with EC50 equal to 14.65±1.91; 78.13±20.05 and 117.19±15.31 μg/ml (according to three experimental schemes), respectively.
Conclusion
. For the preparation of antiviral drugs the whole plant of H. perforatum L., including stems, can be used as raw materials.
U–Pb dating, Hf-isotope, and trace-element studies on two detrital zircon samples from sandstone interlayers in the Upper Jurassic conglomerates of the Southern coast of the Mountainous Crimea ...provide new information on the primary crystalline complexes from which those conglomerates were sourced. The U–Pb age spectra of studied zircons suggest that they were most likely sourced from the (meta)sedimentary complexes of the Eastern and Western Pontides blocks and the Dobrogea platform. In particular, a close similarity of the Precambrian age spectra with the detrital zircons from Late Neoproterozoic–Late Paleozoic (meta)sedimentary complexes of the Dobrogea block provides strong supporting evidence for the affinity between the Pre-Mesozoic basement of the Crimea and the Dobrogea platform. The zircons in the first sample were recycled through Dobrogea sedimentary complexes and originated from terranes with Amazonia affinities, while zircons in the second sample were recycled through the Taurides and originated from terranes related to northeastern Africa and Arabia. The strong similarity of the Precambrian parts of the age spectra of the Dobrogea complexes and the sample K15-007 suggests a resemblance of the Crimea’s Pre-Mesozoic foundation and the Dobrogea platform. Initial analytical data are provided in Electronic Supplementary Materials A (ESM A). Descriptions of measurement parameters, methodologies, and constants used to process primary analytical data and some processing results are reported in ESM B (Figs. B1–B8). Schemes of locations within Balkans–Anatolia–Black Sea–Caucasus region the crystalline complexes with Jurassic, Triassic, Permian–Carboniferous, as well as Late Neoproterozoic–Cambrian and Ordovician–Devonian ages are in ESM C (Figs. C1, C3–C5).
The effect of single-wall carbon nanotube (SWCNT) nanolayers deposited on Si substrate on optical, photoelectric and electric properties of Au/n-Si structures has been investigated. Highly purified ...SWСNTs were prepared by the arc-discharge method. Significant enhancement of the photocurrent (especially in the long-wave range) and the photoelectric conversion efficiency was found for structures with SWСNT and its mechanism was analyzed taking into account optical and electric characteristics of structures.
► Single-wall carbon nanotube increases the photocurrent in Au/n-Si barrier structures. ► Photocurrent enhancement effect is caused by increased photocarriers collection area. ► Poly(vinyl pyridine) used for nanotube immobilization increases open circuit voltage.
Synthetic silica opals were investigated by infrared and Raman spectroscopies. Vibrational modes associated with molecular groups of opal globules and admixtures were detected. Similarities in Raman ...and infrared spectra of synthetic opal with reference fused and α-quartz indicate the presence of amorphous phase in opal globules. Also some spectral bands designate on modified optical stretching vibrations at 1000-1200 cm−1 and bigger amount of Si-H defects in photonic crystal.
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