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1.
The changing world dynamics of research performance
Marko Marhl, Rene Markovič, Vladimir Grubelnik, Matjaž Perc, 2025, izvirni znanstveni članek

Opis: In recent years, a notable diversification in the geographical representation of the World's top universities could be observed. Chinese universities play an increasingly prominent role in these rankings, thus indicating that we might be in the midst of a regional shift in academic performance. To explore this dynamics, we analyze seven years' worth of data used for university rankings by academic subjects from the Academic Ranking of World Universities (ARWU). We focus on China, Europe, the USA, and other global regions of the world. We find that China has indeed seen an unprecedented growth in Engineering and Life Sciences research, positioning itself rather firmly as a leader in these fields. Conversely, the USA leads in the Social Sciences, while Europe excels in Geography, Ecology, Public and Business Administration, and Pharmacy. Other regions worldwide stand out in Transportation Science, Nursing, and Hospitality & Tourism Management. These results reveal the evolving landscape of global academic research, highlighting regional strengths and emerging world trends in subject-specifc excellence.
Ključne besede: research dynamics, academic excellence, geographical diversifcation, University rankings
Objavljeno v DKUM: 11.02.2025; Ogledov: 0; Prenosov: 8
.pdf Celotno besedilo (3,19 MB)
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2.
From isles of Königsberg to islets of Langerhans: examining the function of the endocrine pancreas through network science
Andraž Stožer, Marko Šterk, Eva Paradiž, Rene Markovič, Maša Skelin, Cara E. Ellis, Lidija Križančić Bombek, Jurij Dolenšek, Patrick E. MacDonald, Marko Gosak, 2022, pregledni znanstveni članek

Opis: Islets of Langerhans are multicellular microorgans located in the pancreas that play a central role in whole-body energy homeostasis. Through secretion of insulin and other hormones they regulate postprandial storage and interprandial usage of energy-rich nutrients. In these clusters of hormone-secreting endocrine cells, intricate cell-cell communication is essential for proper function. Electrical coupling between the insulin-secreting beta cells through gap junctions composed of connexin36 is particularly important, as it provides the required, most important, basis for coordinated responses of the beta cell population. The increasing evidence that gap-junctional communication and its modulation are vital to well-regulated secretion of insulin has stimulated immense interest in how subpopulations of heterogeneous beta cells are functionally arranged throughout the islets and how they mediate intercellular signals. In the last decade, several novel techniques have been proposed to assess cooperation between cells in islets, including the prosperous combination of multicellular imaging and network science. In the present contribution, we review recent advances related to the application of complex network approaches to uncover the functional connectivity patterns among cells within the islets. We first provide an accessible introduction to the basic principles of network theory, enumerating the measures characterizing the intercellular interactions and quantifying the functional integration and segregation of a multicellular system. Then we describe methodological approaches to construct functional beta cell networks, point out possible pitfalls, and specify the functional implications of beta cell network examinations. We continue by highlighting the recent findings obtained through advanced multicellular imaging techniques supported by network-based analyses, giving special emphasis to the current developments in both mouse and human islets, as well as outlining challenges offered by the multilayer network formalism in exploring the collective activity of islet cell populations. Finally, we emphasize that the combination of these imaging techniques and network-based analyses does not only represent an innovative concept that can be used to describe and interpret the physiology of islets, but also provides fertile ground for delineating normal from pathological function and for quantifying the changes in islet communication networks associated with the development of diabetes mellitus.
Ključne besede: pancreatic islets, beta cells, calcium imaging, intercellular communication, functional networks, multilayer networks
Objavljeno v DKUM: 20.12.2024; Ogledov: 0; Prenosov: 79
.pdf Celotno besedilo (14,78 MB)
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3.
Socio-demographic and health factors drive the epidemic progression and should guide vaccination strategies for best COVID-19 containment
Rene Markovič, Marko Šterk, Marko Marhl, Matjaž Perc, Marko Gosak, 2021, izvirni znanstveni članek

Opis: We propose and study an epidemiological model on a social network that takes into account heterogeneity of the population and different vaccination strategies. In particular, we study how the COVID-19 epidemics evolves and how it is contained by different vaccination scenarios by taking into account data showing that older people, as well as individuals with comorbidities and poor metabolic health, and people coming from economically depressed areas with lower quality of life in general, are more likely to develop severe COVID-19 symptoms, and quicker loss of immunity and are therefore more prone to reinfection. Our results reveal that the structure and the spatial arrangement of subpopulations are important epidemiological determinants. In a healthier society the disease spreads more rapidly but the consequences are less disastrous as in a society with more prevalent chronic comorbidities. If individuals with poor health are segregated within one community, the epidemic outcome is less favorable. Moreover, we show that, contrary to currently widely adopted vaccination policies, prioritizing elderly and other higher-risk groups is beneficial only if the supply of vaccine is high. If, however, the vaccination availability is limited, and if the demographic distribution across the social network is homogeneous, better epidemic outcomes are achieved if healthy people are vaccinated first. Only when higher-risk groups are segregated, like in elderly homes, their prioritization will lead to lower COVID-19 related deaths. Accordingly, young and healthy individuals should view vaccine uptake as not only protecting them, but perhaps even more so protecting the more vulnerable socio-demographic groups.
Ključne besede: epidemic model, COVID-19, vaccination strategy, vaccination strategy, population heterogeneity, socio-demographic structure, metabolic disease, social network
Objavljeno v DKUM: 14.11.2024; Ogledov: 0; Prenosov: 12
.pdf Celotno besedilo (7,09 MB)
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4.
Psychosocial and moral factors of bystanders in peer bullying
Sonja Pečjak, Tina Pirc, Rene Markovič, Tanja Špes, Katja Košir, 2024, izvirni znanstveni članek

Opis: The aim of our study was to explore students’ bystander roles in peer bullying considering the interaction between their individual and contextual characteristics. We included social status goals (popularity, social preference and social insecurity), moral disengagement and peer support as key variables for differentiating bystander behaviour. Our sample comprised 5148 students from the 8th and 9th grades across 118 primary schools in Slovenia. Bystander roles (active and passive reinforcers, ignorants and defenders) were determined by peer nominations. Other characteristics were measured with self-report questionnaires. For each variable, we normalized students’ results with regard to their classroom to define classroom norms as the context of peer bullying resulting in “low”, “average” and “high” group. Students with similar individual and contextual characteristics were grouped into four clusters. The results showed that students from all clusters were present in all bystander roles, which indicates a highly complex interaction of various factors in bystander behaviour. Some educational implications are discussed.
Ključne besede: medvrstniško nasilje, opazovalci, vrstniška podpora, moralnost, osnovnošolci, bullying, bystanders, peer support, morality, elementary school students
Objavljeno v DKUM: 17.10.2024; Ogledov: 0; Prenosov: 4
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5.
Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic ▫$\alpha$▫-cells
Vladimir Grubelnik, Rene Markovič, Saška Lipovšek Delakorda, Gerd Leitinger, Marko Gosak, Jurij Dolenšek, Ismael Valladolid-Acebes, Per-Olof Berggren, Andraž Stožer, Matjaž Perc, Marko Marhl, 2020, izvirni znanstveni članek

Opis: Type 2 diabetes mellitus (T2DM) has been associated with insulin resistance and the failure of β-cells to produce and secrete enough insulin as the disease progresses. However, clinical treatments based solely on insulin secretion and action have had limited success. The focus is therefore shifting towards α-cells, in particular to the dysregulated secretion of glucagon. Our qualitative electron-microscopy-based observations gave an indication that mitochondria in α-cells are altered in Western-diet-induced T2DM. In particular, α-cells extracted from mouse pancreatic tissue showed a lower density of mitochondria, a less expressed matrix and a lower number of cristae. These deformities in mitochondrial ultrastructure imply a decreased efficiency in mitochondrial ATP production, which prompted us to theoretically explore and clarify one of the most challenging problems associated with T2DM, namely the lack of glucagon secretion in hypoglycaemia and its oversecretion at high blood glucose concentrations. To this purpose, we constructed a novel computational model that links α-cell metabolism with their electrical activity and glucagon secretion. Our results show that defective mitochondrial metabolism in α-cells can account for dysregulated glucagon secretion in T2DM, thus improving our understanding of T2DM pathophysiology and indicating possibilities for new clinical treatments.
Ključne besede: diabetes, pancreatic alpha cells, glucagon, mitochondrial dysfunction, free fatty acid
Objavljeno v DKUM: 03.09.2024; Ogledov: 49; Prenosov: 6
.pdf Celotno besedilo (1,60 MB)
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6.
Mitochondrial dysfunction in pancreatic alpha and beta cells associated with type 2 diabetes mellitus
Vladimir Grubelnik, Jan Zmazek, Rene Markovič, Marko Gosak, Marko Marhl, 2020, izvirni znanstveni članek

Opis: Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30-40% reduction in alpha cells' mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases.
Ključne besede: pancreatic endocrine cells, mathematical model, mitochondrial dysfunction, cellular bioenergetics, diabetes, glucagon, insulin
Objavljeno v DKUM: 03.09.2024; Ogledov: 47; Prenosov: 16
.pdf Celotno besedilo (1,63 MB)
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7.
Cardiovascular comorbidities in COVID-19 : comprehensive analysis of key topics
Rene Markovič, Luka Ternar, Tim Trstenjak, Marko Marhl, Vladimir Grubelnik, 2024, izvirni znanstveni članek

Ključne besede: hypertension, hyperglycemia, embolism, thrombosis, heart failure, vascular disease
Objavljeno v DKUM: 22.08.2024; Ogledov: 53; Prenosov: 10
.pdf Celotno besedilo (1,12 MB)
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8.
Assessing different temporal scales of calcium dynamics in networks of beta cell populations
Jan Zmazek, Maša Skelin, Rene Markovič, Jurij Dolenšek, Marko Marhl, Andraž Stožer, Marko Gosak, 2021, izvirni znanstveni članek

Opis: Beta cells within the pancreatic islets of Langerhans respond to stimulation with coherent oscillations of membrane potential and intracellular calcium concentration that presumably drive the pulsatile exocytosis of insulin. Their rhythmic activity is multimodal, resulting from networked feedback interactions of various oscillatory subsystems, such as the glycolytic, mitochondrial, and electrical/calcium components.How these oscillatory modules interact and affect the collective cellular activity, which is a prerequisite for proper hormone release, is incompletely understood. In the present work, we combined advanced confocal Ca2+ imaging in fresh mouse pancreas tissue slices with time series analysis and network science approaches to unveil the glucosedependent characteristics of different oscillatory components on both the intra- and inter-cellular level. Our results reveal an interrelationship between the metabolically driven low-frequency component and the electrically driven high-frequency component, with the latter exhibiting the highest bursting rates around the peaks of the slow component and the lowest around the nadirs. Moreover, the activity, as well as the average synchronicity of the fast component, considerably increased with increasing stimulatory glucose concentration, whereas the stimulation level did not affect any of these parameters in the slow component domain. Remarkably, in both dynamical components, the average correlation decreased similarly with intercellular distance, which implies that intercellular communication affects the synchronicity of both types of oscillations. To explore the intra-islet synchronization patterns in more detail, we constructed functional connectivity maps. The subsequent comparison of network characteristics of different oscillatory components showed more locally clustered and segregated networks of fast oscillatory activity, while the slow oscillations were more global, resulting in several long-range connections and a more cohesive structure. Besides the structural differences, we found a relatively weak relationship between the fast and slow network layer, which suggests that different synchronization mechanisms shape the collective cellular activity in islets, a finding which has to be kept in mind in future studies employing different oscillations for constructing networks.
Ključne besede: islets of Langerhans, beta cell network, calcium oscillations, multimodal activity analysis, confocal imaging, functional connectivity, multiplex network
Objavljeno v DKUM: 06.06.2024; Ogledov: 171; Prenosov: 6
.pdf Celotno besedilo (9,40 MB)
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9.
Role of cAMP in double switch of glucagon secretion
Jan Zmazek, Vladimir Grubelnik, Rene Markovič, Marko Marhl, 2021, izvirni znanstveni članek

Opis: Glucose metabolism plays a crucial role in modulating glucagon secretion in pancreatic alpha cells. However, the downstream effects of glucose metabolism and the activated signaling pathways influencing glucagon granule exocytosis are still obscure. We developed a computational alpha cell model, implementing metabolic pathways of glucose and free fatty acids (FFA) catabolism and an intrinsically activated cAMP signaling pathway. According to the model predictions, increased catabolic activity is able to suppress the cAMP signaling pathway, reducing exocytosis in a Ca2+ -dependent and Ca2+ independent manner. The effect is synergistic to the pathway involving ATPdependent closure of KATP channels and consequent reduction of Ca2+. We analyze the contribution of each pathway to glucagon secretion and show that both play decisive roles, providing a kind of "secure double switch". The cAMP-driven signaling switch plays a dominant role, while the ATP-driven metabolic switch is less favored. The ratio is approximately 60:40, according to the most recent experimental evidence.
Ključne besede: pancreatic alpha cell, glucagon, cAMP, mathematical model, diabetes, cellular bioenergetics
Objavljeno v DKUM: 06.06.2024; Ogledov: 107; Prenosov: 15
.pdf Celotno besedilo (2,58 MB)
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10.
Modeling the amino acid effect on glucagon secretion from pancreatic alpha cells
Jan Zmazek, Vladimir Grubelnik, Rene Markovič, Marko Marhl, 2022, izvirni znanstveni članek

Opis: Type 2 Diabetes Mellitus (T2DM) is a burdensome problem in modern society, and intensive research is focused on better understanding the underlying cellular mechanisms of hormone secretion for blood glucose regulation. T2DM is a bi-hormonal disease, and in addition to 100 years of increasing knowledge about the importance of insulin, the second hormone glucagon, secreted by pancreatic alpha cells, is becoming increasingly important. We have developed a mathematical model for glucagon secretion that incorporates all major metabolic processes of glucose, fatty acids, and glutamine as the most abundant postprandial amino acid in blood. In addition, we consider cAMP signaling in alpha cells. The model predictions quantitatively estimate the relative importance of specific metabolic and signaling pathways and particularly emphasize the important role of glutamine in promoting glucagon secretion, which is in good agreement with known experimental data.
Ključne besede: diabetes, hormone secretion, glucose, amino acid, cAMP
Objavljeno v DKUM: 21.05.2024; Ogledov: 169; Prenosov: 14
.pdf Celotno besedilo (1,82 MB)
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