Verbal Formulas in the Magical Ritual: Aspects of Interaction

The article traces the origins of the Eastern and Western Slavic charms intended to cast worms out of the wounds. Magical folklore of the Eastern and Western Slavs, as well as of the German peoples, counts short verbal charms recited when the wound festers and has fly larvae, or even worms, inside. Often, such charms are cast over farm animals (horses, cows, sheep, and pigs), but sometimes, though less frequently, are employed to cure people. Such Eastern and Western Slavic charms have methodological interest since they show that the symbolism of charms, their motives and language develop at the intersection of ritual, folklore imagery, and dialect speech. In the typological sense, the ritual of “breaking off” the worms can be regarded as an individual case of a broader threatening strategy in relation to plants which fits into a wider context of magical rituals

Рус. дубоглот в заговорах и диалектной лексике (к изучению мифопоэтической мотивации слов)

The article considers the word duboglot, which functions in the Russian dialects (mainly South Russian) in the meanings of ‘strong dry cough, usually accompanied by a sore throat,’ ‘angina.’ Semantic and motivational reconstruction of this word is carried out based on its role in the text. The authors conclude that the word got into the dialect system from the folklore (mainly from the charms), where it refers to diseases related to inflammation of the oral cavity, pharynx and lower respiratory tract, and accompanied by a strong cough, pain. It is established that most often the word appeared in the texts as a part of the formula “X (a tree), take your Y (duboglot), otherwise I will eat you / swallow you,” which is initially addressed to an oak tree as a convenient “recipient” of diseases that are expelled from the speaker’s space. The authors suggest that the word duboglot is “induced” by the logic of unfolding the text: this is “the oak glot” (glot is the ability to swallow – from the Russian verb glotat’ ‘to swallow’), which should belong to an oak, not a sick person. The word creation within the framework of a spoken construction is supported by the capabilities that are inherent in the language system. Firstly, it is the image of an oak “mouth” (throat), which is formed on the basis of the natural properties and features of oak. This image could be fixed in the internal form of the word itself, which is a controversial issue, but it certainly is seen in the stable compatibility of dub ‘oak’ ↔ duplo ‘hollow’, and at the synchronous level is also supported by the phonetic proximity of these words. The image of a tree, secondly, has another facet: the image of roots of a tree and its crown is projected on the idea of the growth of a tumour (including one in the throat); roots and crown of a tree simultaneously seem to be a “tool” for clearing the throat. Yet another facet of the image is related to how the native speaker sees the properties of a bark: there is a productive model for the Russian language that fixates the connection between the designations of wood (oak) bark and tumours on the human body (including throat tumours); oak bark itself is generally an “archetype” of a bark, hard, rough, stripped from the surface of a tree (which corresponds to “tearing” sensations with a sore throat). © 2020. All Rights Reserved.Работа Е. Л. Березович выполнена при поддержке гранта РНФ № 20-18-00223 «Этимологизация и семантическая реконструкция русской диалектной лексики». Авторы благодарят Т. В. Володину и С. М. Толстую за ценные замечания, высказанные при подготовке статьи

Рус. «дубоглот» в заговорах и диалектной лексике (к изучению мифопоэтической мотивации слов)

The article considers the word duboglot, which functions in the Russian dialects (mainly South Russian) in the meanings of ‘strong dry cough, usually accompanied by a sore throat,’ ‘angina.’ Semantic and motivational reconstruction of this word is carried out based on its role in the text. The authors conclude that the word got into the dialect system from the folklore (mainly from the charms), where it refers to diseases related to inflammation of the oral cavity, pharynx and lower respiratory tract, and accompanied by a strong cough, pain. It is established that most often the word appeared in the texts as a part of the formula “X (a tree), take your Y (duboglot), otherwise I will eat you / swallow you,” which is initially addressed to an oak tree as a convenient “recipient” of diseases that are expelled from the speaker’s space. The authors suggest that the word duboglot is “induced” by the logic of unfolding the text: this is “the oak glot” (glot is the ability to swallow – from the Russian verb glotat’ ‘to swallow’), which should belong to an oak, not a sick person. The word creation within the framework of a spoken construction is supported by the capabilities that are inherent in the language system. Firstly, it is the image of an oak “mouth” (throat), which is formed on the basis of the natural properties and features of oak. This image could be fixed in the internal form of the word itself, which is a controversial issue, but it certainly is seen in the stable compatibility of dub ‘oak’ ↔ duplo ‘hollow’, and at the synchronous level is also supported by the phonetic proximity of these words. The image of a tree, secondly, has another facet: the image of roots of a tree and its crown is projected on the idea of the growth of a tumour (including one in the throat); roots and crown of a tree simultaneously seem to be a “tool” for clearing the throat. Yet another facet of the image is related to how the native speaker sees the properties of a bark: there is a productive model for the Russian language that fixates the connection between the designations of wood (oak) bark and tumours on the human body (including throat tumours); oak bark itself is generally an “archetype” of a bark, hard, rough, stripped from the surface of a tree (which corresponds to “tearing” sensations with a sore throat). DOI: 10.31168/2305-6754.2020.9.2.14В статье рассматривается слово дубоглот, которое функционирует в русских говорах (преимущественно южнорусских) в значениях ʻсильный сухой кашель, обычно сопровождающийся болью в горлеʼ, ʻангинаʼ. Осуществляется семантико-мотивационная реконструкция этого слова с опорой на его роль в тексте. Авторы приходят к выводу, что слово попало в диалектную систему из фольклорных произведений (преимущественно заговорных), где оно обозначает заболевания, касающиеся воспаления ротовой полости, глотки и нижних дыхательных путей и сопровождаемые сильным кашлем, болевыми ощущениями. Устанавливается, что чаще всего слово выступало в текстах в составе формулы «X (дерево), возьми свой Y (дубоглот), иначе я тебя съем / проглочу», которая обращена изначально к дубу как к удобному «восприемнику» болезней, изгоняемых из пространства говорящего. Авторы высказывают предположение, что слово дубоглот «наведено» логикой разворачивания текста: это тот «дубовый глот» (глот — способность собственно глотать), который должен принадлежать дубу, а не больному человеку. Творение слова в рамках заговорной конструкции поддерживается теми возможностями, которые заложены в системе языка. Во-первых, это образ дубовой «пасти» (глотки), который формируется на основе естественных свойств и особенностей дуба и закрепляется если не во внутренней форме слова (это спорный вопрос), то в устойчивой сочетаемости дуб ↔ дупло, а также поддерживается на синхронном уровне фонетической близостью этих слов. Образ дерева, во-вторых, имеет еще одну грань: образ корней дерева и его кроны проецируется на представление о разрастании опухоли (в т. ч. в горле); корни и крона дерева одновременно как бы являются и «инструментом» для прочистки горла. Еще одна грань образа связана с тем, как видятся носителю языка свойства коры: есть продуктивная для русского языка модель, закрепляющая связь обозначений древесной (дубовой) коры и опухолей на теле человека (в т. ч. опухолей горла); сама же дубовая кора — вообще «архетип» коры, жесткой, шершавой, обдираемой с поверхности дерева (что соответствует «дерущим» ощущениям при боли в горле).  DOI: 10.31168/2305-6754.2020.9.2.1

Cellular immune response induced by dna immunization of mice with drug resistant integrases of hiv-1 clade a offers partial protection against growth and metastatic activity of integrase-expressing adenocarcinoma cells

Funding Information: Funding: Experiments were supported by the grants of the Russian Science Fund 15-15-30039, Russian Fund for Basic Research 20-04-01034, Latvian Science Fund LZP 2018-2-03-08, and EU-ROPARTNER project “Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection of University of Lodz, Poland, for interdisciplinary research and innovation”. Mobility and method acquisition were supported by Swedish institute PI project 19806/2016TP, and Horizon 2020 project VACTRAIN#692293. MI and BW were supported by Horizon 2020 grant EAVI contract N68113. Funding Information: Experiments were supported by the grants of the Russian Science Fund 15-15-30039, Russian Fund for Basic Research 20-04-01034, Latvian Science Fund LZP 2018-2-03-08, and EU-ROPARTNER project ?Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection of University of Lodz, Poland, for interdisciplinary research and innovation?. Mobility and method acquisition were supported by Swedish institute PI project 19806/2016TP, and Horizon 2020 project VACTRAIN#692293. MI and BW were supported by Horizon 2020 grant EAVI contract N68113. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Therapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. INs, overexpressed in mammalian cells from synthetic genes, were assessed for stability, route of proteolytic degradation, and ability to induce oxidative stress. Both were found safe in immunotoxicity tests in mice, with no inherent carcinogenicity: their expression did not enhance tumorigenic or metastatic potential of adenocarcinoma 4T1 cells. DNA-immunization of mice with INs induced potent multicytokine T-cell response mainly against aa 209–239, and moderate IgG response cross-recognizing diverse IN variants. DNA-immunization with IN_in_r1 protected 60% of mice from challenge with 4Tlluc2 cells expressing non-mutated IN, while DNA-immunization with IN_in_r2 protected only 20% of mice, although tumor cells expressed IN matching the immunogen. Tumor size inversely correlated with IN-specific IFN-γ/IL-2 T-cell response. IN-expressing tumors displayed compromised metastatic activity restricted to lungs with reduced metastases size. Protective potential of IN immunogens relied on their immunogenicity for CD8+ T-cells, dependent on proteasomal processing and low level of oxidative stress.publishersversionPeer reviewe

Efficient and Specific Internal Cleavage of a Retroviral Palindromic DNA Sequence by Tetrameric HIV-1 Integrase

BACKGROUND: HIV-1 integrase (IN) catalyses the retroviral integration process, removing two nucleotides from each long terminal repeat and inserting the processed viral DNA into the target DNA. It is widely assumed that the strand transfer step has no sequence specificity. However, recently, it has been reported by several groups that integration sites display a preference for palindromic sequences, suggesting that a symmetry in the target DNA may stabilise the tetrameric organisation of IN in the synaptic complex. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the ability of several palindrome-containing sequences to organise tetrameric IN and investigated the ability of IN to catalyse DNA cleavage at internal positions. Only one palindromic sequence was successfully cleaved by IN. Interestingly, this symmetrical sequence corresponded to the 2-LTR junction of retroviral DNA circles-a palindrome similar but not identical to the consensus sequence found at integration sites. This reaction depended strictly on the cognate retroviral sequence of IN and required a full-length wild-type IN. Furthermore, the oligomeric state of IN responsible for this cleavage differed from that involved in the 3'-processing reaction. Palindromic cleavage strictly required the tetrameric form, whereas 3'-processing was efficiently catalysed by a dimer. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the restriction-like cleavage of palindromic sequences may be a general physiological activity of retroviral INs and that IN tetramerisation is strongly favoured by DNA symmetry, either at the target site for the concerted integration or when the DNA contains the 2-LTR junction in the case of the palindromic internal cleavage

МЕТОДОЛОГИЧЕСКИЙ ПОДХОД К ПЛАНИРОВАНИЮ ЭКСПЕРИМЕНТА ПРИ ВЫБОРЕ КАЧЕСТВЕННЫХ РЕАКЦИЙ ДЛЯ ПОДТВЕРЖДЕНИЯ ПОДЛИННОСТИ КОМПОНЕНТОВ ЛЕКАРСТВЕННОГО СРЕДСТВА (НА ПРИМЕРЕ АСКОРБИНОВОЙ КИСЛОТЫ)

The need for identification  testing of active substances or excipients in multi-component medicinal products,  including the use of qualitative tests, calls for research substantiating the choice of tests and test conditions  with due regard to interference  effects caused by other components  of medicinal products and the amount of the sample used. The aim of the study was to develop a methodological approach to designing experiments while selecting qualitative reactions for identification testing of a medicinal product component based on the results of studies investigating the possibility of using known qualitative tests (as illustrated by ascorbic acid in a multi-component product — 0.4 mg of ascorbic acid per 100 mg of the vial contents)  with due regard to interference on the part of other medicinal product components and the amount of the sample used. Material and methods: the study focused on a multi-component medicinal product — lyophilisate for solution for intravenous and intramuscular  injections containing an antiinflammatory active substance and ascorbic acid as a stabilizing agent (antioxidant). The analysis of literature sources helped to determine qualitative tests that were assessed for potential use for identification testing of ascorbic acid as a component of the analysed medicinal product. The study involved experimental testing of the qualitative reactions based on acidic and reducing properties of ascorbic acid. Results: it was demonstrated that several well-known qualitative tests could be used for identification  testing of ascorbic acid as a component of the analysed medicinal product,  namely, the reaction of ferrous ascorbate formation  and the reaction of silver nitrate reduction to metallic silver after preliminary separation of ascorbic acid from the other medicinal product components, as well as the reaction of Prussian blue formation,  iodine test and reaction with a potassium permanganate solution, which do not require additional sample preparation.  It is not practicable to use the reaction with a methylene blue solution and the Fehling’s reagent reaction for this particular medicinal product,  since their results are feeble. Conclusions: the analysis of the multi-component medicinal product helped to develop a methodological  approach to choosing qualitative reactions for identification testing of one of the medicinal product’s components  (e.g., ascorbic acid). The suggested algorithm includes the choice of reactions, determination of their sensitivity and applicability for a particular medicinal product, analysis of the other components’ effects on the results of the chemical reaction,  and the need for additional sample preparation.  The whole complex of the studies performed helped to determine qualitative reactions and optimal conditions for identification testing of the analysed substance.Необходимость подтверждения подлинности  действующих  или  вспомогательных веществ  многокомпонентных лекарственных средств,  в том числе с использованием качественных  реакций, влечет за собой  необходимость  проведения исследований по выбору реакций  и условий их проведения с учетом мешающего  влияния других компонентов лекарственного средства  и количества  используемого образца.  Цель работы: разработка  методологического подхода к планированию эксперимента при выборе  качественных  реакций  для подтверждения подлинности определяемого компонента лекарственного средства на основании результатов исследований возможности использования известных качественных  реакций  (на примере  аскорбиновой кислоты  в многокомпонентном лекарственном средстве — 0,4 мг аскорбиновой кислоты / 100 мг содержимого  флакона) с учетом мешающего влияния других компонентов лекарственного средства и количества  используемого образца.  Материалы и методы: в качестве  объекта исследования было выбрано  многокомпонентное лекарственное средство  — лиофилизат для приготовления раствора  для внутривенного и внутримышечного введения  с лекарственным веществом,  обладающим  противовоспалительным действием,  в состав которого  входит аскорбиновая кислота  в качестве  стабилизатора (антиоксиданта). В результате анализа  данных литературы  выбраны  качественные реакции  для проведения исследований возможности их использования для подтверждения  подлинности аскорбиновой кислоты  в изучаемом  лекарственном средстве.  Проведена  экспериментальная проверка  реакций, основанных на кислотных  и восстановительных свойствах аскорбиновой кислоты.  Результаты: установлено, что в изучаемом многокомпонентном лекарственном средстве для подтверждения подлинности аскорбиновой кислоты могут быть применимы несколько известных качественных реакций: реакции образования аскорбината железа и восстановления нитрата серебра до металлического серебра после предварительного отделения аскорбиновой кислоты  от других компонентов лекарственного средства,  а также реакция  образования берлинской лазури,  йодная проба и реакция  с раствором  перманганата калия,  не требующие  дополнительной пробоподготовки. Использование реакций  с раствором  метиленового  синего и реактивом  Фелинга  применительно к данному лекарственному средству нецелесообразно, так как результат указанных реакций  слабо выражен. Выводы: на примере многокомпонентного лекарственного средства разработан  методологический подход к выбору качественных  реакций  для подтверждения подлинности одного  из компонентов лекарственного средства  (например, аскорбиновой кислоты).  Алгоритм действий включает в себя выбор реакций, определение их чувствительности и целесообразности применения для конкретного лекарственного средства,  изучение  влияния других его компонентов на результат химической реакции, а также необходимость  или отсутствие дополнительной пробоподготовки. Совокупность проведенных  исследований позволяет сделать выбор качественных  реакций  и оптимальных  условий  их проведения для достижения поставленной цели — подтверждения подлинности определяемого вещества

Specificity of LTR DNA recognition by a peptide mimicking the HIV-1 integrase α4 helix

HIV-1 integrase integrates retroviral DNA through 3′-processing and strand transfer reactions in the presence of a divalent cation (Mg2+ or Mn2+). The α4 helix exposed at the catalytic core surface is essential to the specific recognition of viral DNA. To define group determinants of recognition, we used a model composed of a peptide analogue of the α4 helix, oligonucleotides mimicking processed and unprocessed U5 LTR end and 5 mM Mg2+. Circular dichroism, fluorescence and NMR experiments confirmed the implication of the α4 helix polar/charged face in specific and non-specific bindings to LTR ends. The specific binding requires unprocessed LTR ends—i.e. an unaltered 3′-processing site CA↓GT3′—and is reinforced by Mg2+ (Kd decreases from 2 to 0.8 nM). The latter likely interacts with the ApG and GpT3′ steps of the 3′-processing site. With deletion of GT3′, only persists non-specific binding (Kd of 100 μM). Proton chemical shift deviations showed that specific binding need conserved amino acids in the α4 helix and conserved nucleotide bases and backbone groups at LTR ends. We suggest a conserved recognition mechanism based on both direct and indirect readout and which is subject to evolutionary pressure

The HIV-1 Integrase α4-Helix Involved in LTR-DNA Recognition Is also a Highly Antigenic Peptide Element

Monoclonal antibodies (MAbas) constitute remarkable tools to analyze the relationship between the structure and the function of a protein. By immunizing a mouse with a 29mer peptide (K159) formed by residues 147 to 175 of the HIV-1 integrase (IN), we obtained a monoclonal antibody (MAba4) recognizing an epitope lying in the N-terminal portion of K159 (residues 147–166 of IN). The boundaries of the epitope were determined in ELISA assays using peptide truncation and amino acid substitutions. The epitope in K159 or as a free peptide (pep-a4) was mostly a random coil in solution, while in the CCD (catalytic core domain) crystal, the homologous segment displayed an amphipathic helix structure (α4-helix) at the protein surface. Despite this conformational difference, a strong antigenic crossreactivity was observed between pep-a4 and the protein segment, as well as K156, a stabilized analogue of pep-a4 constrained into helix by seven helicogenic mutations, most of them involving hydrophobic residues. We concluded that the epitope is freely accessible to the antibody inside the protein and that its recognition by the antibody is not influenced by the conformation of its backbone and the chemistry of amino acids submitted to helicogenic mutations. In contrast, the AA →Glu mutations of the hydrophilic residues Gln148, Lys156 and Lys159, known for their interactions with LTRs (long terminal repeats) and inhibitors (

Unprocessed Viral DNA Could Be the Primary Target of the HIV-1 Integrase Inhibitor Raltegravir

Integration of HIV DNA into host chromosome requires a 3′-processing (3′-P) and a strand transfer (ST) reactions catalyzed by virus integrase (IN). Raltegravir (RAL), commonly used in AIDS therapy, belongs to the family of IN ST inhibitors (INSTIs) acting on IN-viral DNA complexes (intasomes). However, studies show that RAL fails to bind IN alone, but nothing has been reported on the behaviour of RAL toward free viral DNA. Here, we assessed whether free viral DNA could be a primary target for RAL, assuming that the DNA molecule is a receptor for a huge number of pharmacological agents. Optical spectroscopy, molecular dynamics and free energy calculations, showed that RAL is a tight binder of both processed and unprocessed LTR (long terminal repeat) ends. Complex formation involved mainly van der Waals forces and was enthalpy driven. Dissociation constants (Kds) revealed that RAL affinity for unbound LTRs was stronger than for bound LTRs. Moreover, Kd value for binding of RAL to LTRs and IC50 value (half concentration for inhibition) were in same range, suggesting that RAL binding to DNA and ST inhibition are correlated events. Accommodation of RAL into terminal base-pairs of unprocessed LTR is facilitated by an extensive end fraying that lowers the RAL binding energy barrier. The RAL binding entails a weak damping of fraying and correlatively of 3′-P inhibition. Noteworthy, present calculated RAL structures bound to free viral DNA resemble those found in RAL-intasome crystals, especially concerning the contacts between the fluorobenzyl group and the conserved 5′C4pA33′ step. We propose that RAL inhibits IN, in binding first unprocessed DNA. Similarly to anticancer drug poisons acting on topoisomerases, its interaction with DNA does not alter the cut, but blocks the subsequent joining reaction. We also speculate that INSTIs having viral DNA rather IN as main target could induce less resistance