Common origin of the gelsolin gene variant in 62 Finnish AGel amyloidosis families

Finnish gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominantly inherited systemic disorder with ophthalmologic, neurologic and dermatologic symptoms. Only the gelsolin (GSN) c.640G>A variant has been found in the Finnish patients thus far. The purpose of this study was to examine whether the Finnish patients have a common ancestor or whether multiple mutation events have occurred at c.640G, which is a known mutational hot spot. A total of 79 Finnish AGel amyloidosis families including 707 patients were first discovered by means of patient interviews, genealogic studies and civil and parish registers. From each family 1-2 index patients were chosen. Blood samples were available from 71 index patients representing 64 families. After quality control, SNP array genotype data were available from 68 patients from 62 nuclear families. All the index patients had the same c.640G>A variant (rs121909715). Genotyping was performed using the Illumina CoreExome SNP array. The homozygosity haplotype method was used to analyse shared haplotypes. Haplotype analysis identified a shared haplotype, common to all studied patients. This shared haplotype included 17 markers and was 361 kb in length (GRCh37 coordinates 9:124003326–124364349) and this level of haplotype sharing was found to occur highly unlikely by chance. This GSN haplotype ranked as the largest shared haplotype in the 68 patients in a genome-wide analysis of haplotype block lengths. These results provide strong evidence that although there is a known mutational hot spot at GSN c.640G, all of the studied 62 Finnish AGel amyloidosis families are genetically linked to a common ancestor.Peer reviewe

Second-generation antipsychotic use during pregnancy and risk of congenital malformations

Purpose To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM). Methods A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models. Results Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results. Conclusions Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.Peer reviewe

Synthesis and Cytotoxicity Evaluation of Spirocyclic Bromotyrosine Clavatadine C Analogs

Marine-originated spirocyclic bromotyrosines are considered as promising scaffolds for new anticancer drugs. In a continuation of our research to develop potent and more selective anticancer compounds, we synthesized a library of 32 spirocyclic clavatadine analogs by replacing the agmatine, i.e., 4-(aminobutyl)guanidine, side chain with different substituents. These compounds were tested for cytotoxicity against skin cancer using the human melanoma cell line (A-375) and normal human skin fibroblast cell line (Hs27). The highest cytotoxicity against the A-375 cell line was observed for dichloro compound 18 (CC50 0.4 ± 0.3 µM, selectivity index (SI) 2). The variation of selectivity ranged from SI 0.4 to reach 2.4 for the pyridin-2-yl derivative 29 and hydrazide analog of 2-picoline 37. The structure–activity relationships of the compounds in respect to cytotoxicity and selectivity toward cancer cell lines are discussed

Educational achievement of children with selected major congenital anomalies and associated factors: a Finnish registry-based study

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association. BACKGROUND: Children with major congenital anomalies may be at risk of poor educational outcomes. We aimed to evaluate the educational achievement of children born with major congenital anomalies compared with children without major congenital anomalies in relation to sociodemographic factors. METHODS: We performed a registry-based study including 401 544 children in Finland, graduates of the compulsory school who applied to secondary education. We used health data from the Finnish Register of Congenital Malformations for children born from 1995 to 2002 linked with education data from the Finnish Ministry of Education and Culture. We used generalized linear regression to compare the mean grade differences of children with specific major congenital anomalies and \u27All anomalies\u27 subgroup (major congenital anomalies, chromosomal syndromes, and multiple anomalies) with reference children. RESULTS: Children with major congenital anomalies were less likely to apply for further education than reference children (88.0% vs. 96.8%; odds ratio = 4.13; 95% confidence interval, 3.92-4.36). For most non-chromosomal congenital anomalies, children born with congenital anomalies had similar educational achievement to the reference children. For the \u27All anomalies\u27 subgroup, children with congenital anomalies had lower educational achievement than reference children. Among children with congenital anomalies, male sex, lower maternal educational levels and younger maternal age were associated with lower educational achievement. CONCLUSIONS: For children applying to further education, most non-chromosomal congenital anomalies were not associated with lower educational achievement. Nevertheless, efforts are needed to improve educational achievement in children with major congenital anomalies associated with maternal sociodemographic background

Media Communication Product as a Key to the Cultural and Historical Code of Urban Space

В статье рассматривается роль медиакоммуникационного продукта (докудрамы «Братья Елькины» режиссера Светланы Поповой) в декодировании культурно-исторического кода городского пространства. Докудрама — это жанр игрового кино, целью которого является реконструкция исторических событий через актерскую игру. Через вербальные, визуальные и аудиальные знаки медиакоммуникационный продукт помогает целевой аудитории правильно интерпретировать реалии городского пространства.The article examines the role of a media communication product (docudrama “The Yelkin Brothers” directed by Svetlana Popova) in decoding the cultural and historical code of urban space. Docudrama 267 is a genre of feature films, the purpose of which is to reconstruct historical events through acting. Through verbal, visual and auditory signs, the media communication product helps the target audience to correctly interpret the realities of urban space.Исследование выполнено при поддержке Фонда перспективных научных исследований ЧелГУ.The research was carried out with the support of the ChelSU Foundation for Advanced Scientific Research

Communication and Media Communication Product in the Discourses of Creative Industries: to the Question of Typology

Статья поступила в редакцию 04.06.2023 г.В настоящее время формируются дискурсы креативных индустрий, в которых функционируют новые типы медиакоммуникационных продуктов. Статья посвящена рассмотрению типов коммуникационных и медиакоммуникационных продуктов в дискурсах таких креативных индустрий, как мода и кинематограф. Авторы вводят в научный оборот понятия «модный дискурс» и «кинодискурс», сформулированные с позиций медиакоммуникаций и медиапроизводства в креативных индустриях.Currently, discourses of creative industries are being formed, in which new types of media communication products are functioning. The article is devoted to the types of communication and media communication products in the discourses of such creative industries as fashion and cinema. The authors introduce into scientific circulation the concepts of “fashion discourse” and “cinema discourse”, formulated from the standpoint of media communications and media production in creative industries.Работа выполнена при поддержке Фонда перспективных научных исследований Челябинского государственного университета.The study was conducted with the support of the Foundation for Advanced Scientific Research of Chelyabinsk State University

The Role of Academic Buoyancy and Emotions in Students’ Learning-Related Expectations and Behaviours in Primary School

Background. Academic buoyancy refers to students’ ability to come through ordinary challenges they face in the academic context, and it can positively contribute to students’ beliefs and behaviours in learning situations. Although buoyancy has been found to be related to positive academic outcomes, previous studies have not examined how buoyancy influences academic emotions in learning situations and how these emotions further affect students’ learning-related expectations and behaviours. Aims. This study investigated to what extent academic buoyancy predicts students’ failure expectations, avoidance behaviour, and task-oriented planning in learning situations, and to what extent academic emotions mediate the effect of academic buoyancy on these expectations and behaviours. Sample. A total of 845 Finnish students in the sixth grade of primary school. Methods. Self-report data for academic buoyancy and academic emotions in the autumn semester and learning-related expectations and behaviours in the spring semester were analysed using structural equation modelling, controlling for gender, grade point average, and previous levels of learning-related expectations and behaviours. Results. The findings showed that high academic buoyancy indirectly predicted lower avoidance behaviour, fewer failure expectations, and higher task-oriented planning via academic emotions. High academic buoyancy was related to high enjoyment and hope as well as low boredom and hopelessness, which further predicted low failure expectations. High hope and low boredom also predicted low avoidance behaviour and high hope was associated with high task-oriented planning. Conclusions. The findings suggest that academic buoyancy supports positive expectations and adaptive behaviours in learning situations through the regulation of emotions

FILM LANGUAGE AS A MEANS OF EMOTIONAL IMPACT IN AN AUDIOVISUAL PRODUCT

Объектом исследования в статье являются средства моделирования эмоциогенности в коммуникационном продукте. Предметом – киноязык (сюжет) как средство эмоционального воздействия в аудиовизуальном коммуникационном продукте. На примере анализа рекламного ролика «Другое небо» с помощью авторского алгоритма создания медиакоммуникационного продукта, включающего в себя драматургический дизайн, нарративный дизайн и визуальный сторителлинг, делается вывод о том, что построение сюжета в рекламном ролике способствует формированию эмоциональных реакций потребителя, влияющих на отношение к объекту рекламирования.The object of research in the article is the means of modeling emotionality in a communication product. The subject is the film language (plot) as a means of emotional impact in an audiovisual communication product. Using the example of the analysis of the commercial “Another Sky” using the author’s algorithm for creating a media communication product, including dramatic design, narrative design and visual storytelling, it is concluded that plotting in an advertising video contributes to the formation of emotional reactions of the consumer, affecting the attitude towards the advertised object

Asymmetry in catalysis by Thermotoga maritima membrane-bound pyrophosphatase demonstrated by a nonphosphorus allosteric inhibitor

Membrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyze pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and parasitic protists, but no homologous proteins exist in vertebrates, making them a promising drug target. Here, we report the first nonphosphorus allosteric inhibitor of the thermophilic bacterium Thermotoga maritima membrane-bound pyrophosphatase and its bound structure together with the substrate analog imidodiphosphate. The unit cell contains two protein homodimers, each binding a single inhibitor dimer near the exit channel, creating a hydrophobic clamp that inhibits the movement of β-strand 1–2 during pumping, and thus prevents the hydrophobic gate from opening. This asymmetry of inhibitor binding with respect to each homodimer provides the first clear structural demonstration of asymmetry in the catalytic cycle of membrane-bound pyrophosphatases