Creation of the global of Slovenia

The most realistic way to represent the topography of the Earth is by using a globe; this fact was known as early as in ancient Greece. The biggest contribution to the making of these reduced models of our planet was made by Gerardus Mercator, who split the surface of the globe into zones in the 16th century This gave rise to a revolution in the development of cartography, which also sparked the beginning of the mass production of globes. The principle for the production of this instrument has remained the same to this day; the only difference is that the major part of the process is now automated. However, globes of individual countries are still quite unusual and rare; this is why we decided to take on the project of designing the globe of Slovenia, which was performed within the Cartography III study course at the Faculty of Civil and Geodetic Engineering. The making of the globe of Slovenia includes the production of a general map of the country at the scale of I: 1,000,000, the projection of a flat map on the globe and the pasting of printed zones on the supporting medium, in our case a table lamp

An oomycete NLP cytolysin forms transient small pores in lipid membranes

Microbial plant pathogens secrete a range of effector proteins that damage host plants and consequently constrain global food production. Necrosis and ethylene-inducing peptide 1-like proteins (NLPs) are produced by numerous phytopathogenic microbes that cause important crop diseases. Many NLPs are cytolytic, causing cell death and tissue necrosis by disrupting the plant plasma membrane. Here, we reveal the unique molecular mechanism underlying the membrane damage induced by the cytotoxic model NLP. This membrane disruption is a multistep process that includes electrostatic-driven, plant-specific lipid recognition, shallow membrane binding, protein aggregation, and transient pore formation. The NLP-induced damage is not caused by membrane reorganization or large-scale defects but by small membrane ruptures. This distinct mechanism of lipid membrane disruption is highly adapted to effectively damage plant cells.Peer reviewe

How Can We Advance Integrative Biology Research in Animal Science in 21st Century?:Experience at University of Ljubljana from 2002 to 2022

In this perspective analysis, we strive to answer the following question: how can we advance integrative biology research in the 21st century with lessons from animal science? At the University of Ljubljana, Biotechnical Faculty, Department of Animal Science, we share here our three lessons learned in the two decades from 2002 to 2022 that we believe could inform integrative biology, systems science, and animal science scholarship in other countries and geographies. Cultivating multiomics knowledge through a conceptual lens of integrative biology is crucial for life sciences research that can stand the test of diverse biological, clinical, and ecological contexts. Moreover, in an era of the current COVID-19 pandemic, animal nutrition and animal science, and the study of their interactions with human health (and vice versa) through integrative biology approaches hold enormous prospects and significance for systems medicine and ecosystem health

Smernice za diagnostiko, zdravljenje in sledenje bolnikov s sarkomi mehkih tkiv in kosti

no abstractni abstrakt

EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

Funding Information: The authors would like to thank everybody who contributed to the HBM4EU Aligned Studies: the participating children, teenagers, adults and their families, the fieldworkers that collected the samples and database managers that made the information available to HBM4EU, the HBM4EU project partners, especially those from WP7 for developing all materials supporting the fieldwork, WP9 for organizing the QA/QC scheme under HBM4EU and all laboratories who performed the analytical measurements. We would like to acknowledge Sun Kyoung Jung from the National Institute of Environmental Research of South-Korea for providing the KoNEHS Cycle III results (crt adjusted). HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032). The authors thank all principal investigators of the contributing studies for their participation and contribution to the HBM4EU Aligned Studies and the national program owners for their financial support. Further details on funding for all the participating studies can be found in the Supplemental Material, Table S12.As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants of three age groups: (i) 3,576 children aged 6–12 years, (ii) 3,117 teenagers aged 12–18 years and (iii) 4,102 young adults aged 20–39 years. The participants were recruited between 2014 and 2021 in 11–12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability and will give leverage to national policy makers for the implementation of targeted measures.publishersversionpublishe

Harmonized human biomonitoring in European children, teenagers and adults: EU-wide exposure data of 11 chemical substance groups from the HBM4EU Aligned Studies (2014–2021)

HBM4EU is co-financed under Horizon 2020 (grant agreement No 733032).As one of the core elements of the European Human Biomonitoring Initiative (HBM4EU) a human biomonitoring (HBM) survey was conducted in 23 countries to generate EU-wide comparable HBM data. This survey has built on existing HBM capacity in Europe by aligning national or regional HBM studies, referred to as the HBM4EU Aligned Studies. The HBM4EU Aligned Studies included a total of 10,795 participants from three age groups: (i) 3,576 children aged 6-12 years, (ii) 3,117 teenagers aged 12-18 years, and (iii) 4,102 young adults aged 20-39 years. The participants were recruited between 2014 and 2021 in 11-12 countries per age group, geographically distributed across Europe. Depending on the age group, internal exposure to phthalates and the substitute DINCH, halogenated and organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFASs), cadmium, bisphenols, polycyclic aromatic hydrocarbons (PAHs), arsenic species, acrylamide, mycotoxins (deoxynivalenol (total DON)), benzophenones and selected pesticides was assessed by measuring substance specific biomarkers subjected to stringent quality control programs for chemical analysis. For substance groups analyzed in different age groups higher average exposure levels were observed in the youngest age group, i.e., phthalates/DINCH in children versus teenagers, acrylamide and pesticides in children versus adults, and benzophenones in teenagers versus adults. Many biomarkers in teenagers and adults varied significantly according to educational attainment, with higher exposure levels of bisphenols, phthalates, benzophenones, PAHs, and acrylamide in participants (from households) with lower educational attainment, while teenagers from households with higher educational attainment have higher exposure levels for PFASs and arsenic. In children, a social gradient was only observed for the non-specific pyrethroid metabolite 3-PBA and di-isodecyl phthalate (DiDP), with higher levels in children from households with higher educational attainment. Geographical variations were seen for all exposure biomarkers. For 15 biomarkers, the available health-based HBM guidance values were exceeded with the highest exceedance rates for toxicologically relevant arsenic in teenagers (40%), 3-PBA in children (36%), and between 11 and 14% for total DON, Σ (PFOA + PFNA + PFHxS + PFOS), bisphenol S and cadmium. The infrastructure and harmonized approach succeeded in obtaining comparable European-wide internal exposure data for a prioritized set of 11 chemical groups. These data serve as a reference for comparison at the global level, provide a baseline to compare the efficacy of the European Commission's chemical strategy for sustainability, and will give leverage to national policymakers for the implementation of targeted measures.info:eu-repo/semantics/publishedVersio

From science to policy: How European HBM indicators help to answer policy questions related to phthalates and DINCH exposure

Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined

Use of solvatic model for retention times prediction in reversed-phase liquid cromatography

Obstajajo različni pristopi za razvoj kromatografskih metod pri reverznofazni tekočinski kromatografiji. Poleg tradicionalnega pristopa »poskus-napaka« lahko uporabljamo tudi različno programsko opremo za razvoj in optimizacijo kromatografskih metod, ki deluje na podlagi različnih retencijskih modelov. Glavni namen mojega doktorskega dela je bil uporaba solvatnega modela za napovedovanje retencijskih časov pri reverznofazni tekočinski kromatografiji z gradientno elucijo na različnih stacionarnih fazah (C18, C8 in fenil-heksil) in z različnimi mobilnimi faza mi (klasične vodne mobilne faze – fosforna kislina, amonijev acetat ter modernejše vodne mobilne faze – ionske tekočine) za zdravilno učinkovino aripiprazol in njegove nečistote, opisane v Evropski farmakopeji. Ker imajo te spojine izjemno podobne kemijske strukture, predstavlja njihova ločba zahteven izziv. Napoved zadrževanja je bila ustrezna na vseh testiranih stacionarnih fazah v kombinaciji z 0,1 % fosforno kislino oz. 10 mM amonijevim acetatom oz. 1 mM ionsko tekočino [BMIM][BF4] kot vodno mobilno fazo ter acetonitrilom oz. metanolom kot organskim modifikatorjem. Za napoved zadrževanja pri ničelni aproksimaciji upoštevamo strukturno formulo analitov ter značilnosti stacionarne in mobilne faze. Pri uporabi klasičnih mobilnih faz je bila povprečna razlika v rezultatih med eksperimentalnimi in napovedanimi retencijskimi časi -14 – -17 % v primeru uporabe stacionarne faze fenil-heksil, na kateri je bilo ujemanje največje. Po uporabi solvatnega retencijskega modela skupaj s podatki enega eksperimenta se je povprečna razlika retencijskih časov zmanjšala na največ -7 %, po uporabi podatkov dveh eksperimentov pa se je povprečna razlika zmanjšala na največ -2 % na vseh preiskovanih stacionarnih fazah (za večinopreiskovanih spojin je bila razlika med napovedanimi retencijskimi in eksperimentalno dobljenimi retencijskimi časi manjša od -3 %). Ovrednotila sem tudi vpliv klasičnih mobilnih faz in modernejših vodnih mobilnih faz na ločbo posameznih spojin in na faktor simetrije. Pri eksperimentalnem delu sem uporabila tri različne ionske tekočine. Kot najbolj primerna in najbolj uporabna se je izkazala ionska tekočina [BMIM][BF4]. Po uporabi solvatnega retencijskega modela pri mobilni fazi s to ionsko tekočino skupaj s podatki enega eksperimenta je bila povprečna razlika retencijskih časov največ -5 %, po uporabi podatkov dveh eksperimentov pa se je povprečna razlika zmanjšala na največ -1 %. Pri uporabi ionske tekočine [BMIM][BF4] so bili v primerjavi z uporabo pufra amonijevega acetata kromatografski vrhovi bolj simetrični. Preučevala sem tudi stabilnost aripiprazola po stresnem testiranju pri povišani temperaturi in pri oksidacijskih pogojih. Razgradne produkte sem identificirala z masno spektrometrijo sklopljeno s tekočinsko kromatografijo. Poleg farmakopejske nečistote sem identificirala še dva dodatna razgradna produkta.There are several different approaches for high performance liquid chromatography method development. Beside traditional approach »trial and error«, different software programs for method development and optimization are available, which are based on different retention models. Main goal of my PhD work was application of solvatic model for prediction of retention at gradient elution in reversed-phase liquid chromatography with different type of stationary phases (C18, C8 and phenyl-hexyl) and with different type of mobile phases (classical aqueous mobile phases – phosphoric acid/ammonium acetate and more modern aqueous mobile phases – ionic liquids) for active pharmaceutical ingredient aripiprazole and its related substances, described in European Pharmacopoeia. As this compounds have very similar chemical structure, their separation is challenging. Retention prediction was suitable on all examined stationary phases with 0.1 % phosphoric acid / 10 mM ammonium acetate/ 1 mM ionic liquid [BMIM][BF4] as aqueous mobile phases and acetonitrile / methanol as organic modifiers. Predicted retention take into account structural formulae of compounds and properties of stationary and mobile phases. In the case of classical mobile phases the average differencebetween experimental and predicted retention times was -14 – -17 % on phenyl-hexyl stationary phase, where the highest matching was obtained. After utilisation of the solvation retention model with data from one experimental run, the average difference decreased to maximal -7 %and after contribution of data from two experimental runs, to maximal -2 % on all examined stationary phases (for majority of studied compounds difference between predicted and experimental values is lower than -3 %). The influence of classical and modern aqueous mobile phases on resolution of individual components and simmetry factor was evaluated. At experimental work three different ionic liquids were examined. Ionic liquid [BMIM][BF4] was the most appropriate and the most useful. In the case of usage of modern mobile phases (ionic liquids) and after utilisation of the solvation retention models with data from one experimental run, the average difference decreased to maximal -5 % and after contribution of data from two experimental runs, to maximal -1 %. In the case of ionic liquid [BMIM][BF4] in comparison with buffer ammonium acetate, chromatographic peaks were more symmetrical. The stability of aripiprazole at higher temperatures and at oxidation conditions was studied. Degradation products of aripiprazole were identified with mass spectrometry coupled to liquid chromatography. Beside pharmacopoeia impurity two additional degradation products were identified