1. Cleavage-mediated regulation of Myd88 signaling by inflammasome-activated caspase-1Monika Avbelj, Iva Hafner Bratkovič, Duško Lainšček, Mateja Manček Keber, Tina Tinkara Peternelj, Gabriela Panter, Steven P. Treon, Boris Gole, Uroš Potočnik, Roman Jerala, 2022, original scientific article Abstract: Coordination among multiple signaling pathways ensures an appropriate immune response, where a signaling pathway may impair or augment another signaling pathway. Here, we report a negative feedback regulation of signaling through the key innate immune mediator MyD88 by inflammasome-activated caspase-1. NLRP3 inflammasome activation impaired agonist- or infection-induced TLR signaling and cytokine production through the proteolytic cleavage of MyD88 by caspase-1. Site-specific mutagenesis was used to identify caspase-1 cleavage site within MyD88 intermediary segment. Different cleavage site location within MyD88 defined the functional consequences of MyD88 cleavage between mouse and human cells. LPS/monosodium urate–induced mouse inflammation model corroborated the physiological role of this mechanism of regulation, that could be reversed by chemical inhibition of NLRP3. While Toll/interleukin-1 receptor (TIR) domain released by MyD88 cleavage additionally contributed to the inhibition of signaling, Waldenström’s macroglobulinemia associated MyD88L265P mutation is able to evade the caspase-1-mediated inhibition of MyD88 signaling through the ability of its TIRL265P domain to recruit full length MyD88 and facilitate signaling. The characterization of this mechanism reveals an additional layer of innate immunity regulation.
Keywords: Myeloid differentiation factor 88, Myd88, caspase-1, inflammasomes, regulation, innate immunity, inflammation
Published in DKUM: 16.08.2023; Views: 561; Downloads: 35
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2. The function of Zagreb as a factor of the transformation of the greater Zagreb girdle : with a separate commentary on daily migrationPetar Feletar, 2009, review article Abstract: With an almost monocentric development, the most powerful central functions in Croatia are concentrated in Zagreb. These functions have a powerful influence on the transformation of the area towards which they gravitate. This influence is greatest on the geographic area of the Greater Zagreb girdle area, i.e. Zagreb County. The processes of the transformation of the Greater Zagreb girdle relate above all to the urbanisation and suburbanisation of the area. These processes extend to rural areas in a very spatially differentiated way, depending primarily on the level of development and the spatial distribution of the transport network. Spatial differentiation and the level of urbanisation and suburbanisation in the Zagreb environs are illustrated through an analysis of the intensity and distribution of daily migration in Zagreb and through expressed changes in the spatial distribution of inhabitation. These processes were considered to be in parallel in the period from 1948 to 2001, the period of the most intensive change.
Keywords: greater Zagreb girdle, spatial distribution of inhabitation, daily migration, suburbanisation, spatial differentiation
Published in DKUM: 20.03.2018; Views: 1414; Downloads: 100
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3. New trends of development of beer industry in Lithuania : diversification and social responsibilityVladislavas Petraškevičius, Zlatko Nedelko, 2017, original scientific article Abstract: The main purpose of this article is to outline the current challenges of beer industry in Lithuania and provide suggestions for future development of organizations in this industry, by focusing on diversification strategy and social responsibility. The main challenges of Lithuanian beer industry are related to finding ways of future development in a constantly contracting market, as well as to find a competitive strategy of market penetration. In connection of these challenges, product differentiation creates new benefits for the consumers. However this strategy proves itself not being sufficient to reach the desired goals. Diversification of portfolio, being more risky, gives opportunity to target new customer groups and increase market presence. However, both strategies are less effective without changing the culture of drinking and consumer perceptions of beer. These issues will be addressed through the lenses of social responsibility, by emphasizing the promotion of responsible alcohol consumption and responsible behaviour of beer industry. As a result, the customers have to be ready to pay higher price for new products and develop a more responsible culture of beer consumption. To overcome outlined challenges, organizations in Lithuanian beer industry, must rethink their existing strategies and operations. Based on proposed future directions, the paper provides suggestions for business practices, how to implement differentiation strategy and actions in order to increase the level of social responsibility of various stakeholders.
Keywords: beer industry, Lithuania, differentiation, diversification, social responsibility, beer consumption, responsible drinking, entrepreneurship, development
Published in DKUM: 09.08.2017; Views: 1885; Downloads: 181
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4. Developmental differentiation and binding of mental processes with g through the life-spanAndreas Demetriou, George Spanoudis, Smaragda Kazi, Antigoni Mougi, Mislav Stjepan Žebec, Elena Kazali, Hudson Golino, Karin Bakračevič, Michael Shayer, 2017, original scientific article Abstract: Integration/differentiation of mental processes is major mechanism of development. Developmental theories ascribe intellectual development to it. In psychometric theory, Spearman’s law of diminishing returns postulates that increasing g allows increasing differentiation of cognitive abilities, because increased mental power allows variable investment in domain-specific learning. Empirical evidence has been inconsistent so far, with some studies supporting and others contradicting this mechanism. This state of affairs is due to a developmental phenomenon: Both differentiation and strengthening of relations between specific processes and g may happen but these changes are phase-specific and ability-specific, depending upon the developmental priorities in the formation of g in each phase. We present eight studies covering the age span from 4 to 85 years in support of this phenomenon. Using new powerful modeling methods we showed that differentiation and binding of mental processes in g occurs in cycles. Specific processes intertwine with g at the beginning of cycles when they are integrated into it; when well established, these processes may vary with increasing g, reflecting its higher flexibility. Representational knowledge, inductive inference and awareness of it, and grasp of logical constraints framing inference are the major markers of g, first intertwining with in their respective cycles and differentiating later during the periods of 2–6, 7–11, and 11–20 years, respectively. The implications of these findings for an overarching cognitive developmental/differential theory of human mind are discussed.
Keywords: intelligence, cognitive development, individual differences, integration, differentiation, awareness
Published in DKUM: 21.06.2017; Views: 1094; Downloads: 388
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5. Forms of social and spatial differentiation in towns (based on the case of Maribor)Vladimir Drozg, 2012, original scientific article Abstract: This contribution discusses forms of spatial differentiation of the town, occurring while human needs are being fulfilled (social connections, supply, culture, education and recreation). Social and spatial differentiation is most noticeable in the area of social connections, clothing stores and culture. The most important social characteristics, responsible for spatial differentiation are age and material situation. Also, the size of the town proved to be crucial for social and spatial differentiation.
Keywords: social differentiation, spatial differentiation, Maribor
Published in DKUM: 21.12.2015; Views: 955; Downloads: 111
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6. Dyslexia and Foreign Language Learning in Primary SchoolsDijana Šmon, 2014, undergraduate thesis Abstract: The thesis Dyslexia and Learning a Foreign Language in Primary Schools deals with the general difficulties in foreign language learning which are caused by a very specific disorder called dyslexia. The problems that come with the disorder are in most cases transferred across languages and the aim of this thesis was to find out how dyslexia influences on the learning of the foreign language (English) in the primary school, which is becoming an issue and an open question nowadays between scientists and teachers who have a direct contact with the pupils.
The main goals of the thesis are to connect the general characteristics of dyslexia and its influence on English as a foreign language and to identify the main language learning areas and skills in which dyslectics need special support and need to be taken under further investigation. The emphasis is also on providing some solutions, strategies and methods that would help teachers to support their learners with dyslexia.
In the empirical part, I discuss the results. I also provide interpretations of one questionnaire, which was filled in by teachers of foreign language and one test that Slovene learners who have been learning English as their foreign language took. To obtain more additional data, five interviews with English language teachers were transcribed and analysed about their knowledge of dyslexia and the methods that they use to help dyslectics to benefit as much as possible from the foreign language lessons.
Keywords: dyslexia, English as a foreign language, early identification, language awareness transfer, differentiation, teachers’ knowledge, developing language skills
Published in DKUM: 07.03.2014; Views: 3590; Downloads: 299
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7. Multivariate data analysis of erythrocyte membrane phospholipid fatty acid profiles in the discrimination between normal blood tissue and various disease statesZdenka Cencič-Kodba, Darinka Brodnjak-Vončina, Marjana Novič, Uroš Potočnik, 2010, original scientific article Abstract: The investigation presented here aims to compare the fatty acid composition of red blood cells of patients with different disease states and to test the hypothesis that the changes in fatty acid profiles derived from erythrocyte phospholipids might be relevant to various diseases. The study sample consisted of 342 blood donors, among them 135 with inflammatory bowel disease, 53 with uterine leiomyoma, 14 with verified absence of uterine leiomyoma, 52 with asthma, 18 with colon adenomas, and 70 blood samples without any of mentioned diseases that was used as a control group. After the isolation of erythrocytes from blood samples, total extracted lipids were separated by solid-phase extraction (SPE) into non polar lipids and polar phospholipids. After the saponification of phospholipid fraction, the esterification process followed with boron trifluoride-methanol reagent. The fatty acid methyl ester (FAME) composition of the total red blood cell phospholipid fraction was analyzed by gas chromatography (GC) with flame ionization detector (FID). Additionally two fatty aldehyde dimethyl acetals (hexadecanal and octadecanal dimethyl acetals; 16:0 DMA and 18:0 DMA) derived from erythrocyte membrane plasmalogen phospholipids were also determined. The resulting fatty acid and plasmalogen linked fatty acid composition was evaluated by the principal component analysis (PCA). We demonstrated decreased levels of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in red blood cell membrane of patients with colon adenomas. Also, a large negative correlation was observed among all samples between the quantity of saturated acids and arachidonic (20:4n6) acid as well as saturated acids and adrenic (22:4n6) acid. In PCA score plot a group of female donors is distinguished mainly by the content of linoleic (18:2n6) acid; a small subgroup shows its concentration highly above the average value. At the same time, the same subgroup has both dimethyl acetals below the average concentrations. The study demonstrates feasibility of multivariate data analysis in discrimination of patients with different diseases according to fatty acid profile and suggests considerable differences in membrane fatty acid profiles in patients with various disease states.
Keywords: erythrocyte phospholipids, cell membrane, fatty acid profiles, differentiation, disease state, gas chromatography, principal component analysis
Published in DKUM: 31.05.2012; Views: 3112; Downloads: 95
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