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74.
In vitro and in vivo correlation of skin and cellular responses to nucleic acid delivery
Maša Omerzel, Katarina Žnidar, A. Sales Conniff, Tanja Jesenko, Boštjan Markelc, Jared Tur, Nina Semenova, Kristopher Kohena, Simona Kranjc Brezar, Loree C. Heller, Maja Čemažar, 2022, izvirni znanstveni članek

Povzetek: Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immuno- genicity of skin, we correlated the effects of pDNA electrotransfer to fibroblasts and keratinocytes to mouse skin using reverse transcription real-time PCR (RT-qPCR) and several types of protein quantification. After pDNA electrotransfer, the mRNAs of the putative DNA sensors DEAD (AspGlu-Ala-Asp) box polypeptide 60 (Ddx60), absent in melanoma 2 (Aim2), Z-DNA binding protein 1 (Zbp1), interferon activated gene 202 (Ifi202), and interferon-inducible protein 204 (Ifi204) were upregulated in keratinocytes, while Ddx60, Zbp1 and Ifi204 were upregulated in fibroblasts. Increased levels of the mRNAs and proteins of several cytokines and chemokines were detected and varied based on cell type. Mouse skin experiments in vivo confirmed our in vitro results with increased expression of putative DNA sensor mRNAs and of the mRNAs and proteins of several cytokines and chemokines.
Ključne besede: DNA sensors, cytokines, electrotransfer, skin
Objavljeno v DiRROS: 06.09.2022; Ogledov: 540; Prenosov: 285
.pdf Celotno besedilo (7,72 MB)
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75.
Inter-person differences in isometric coactivations of triceps surae and tibialis anterior decrease in young, but not in older adults after 14 days of bed rest
Matjaž Divjak, Gašper Sedej, Nina Murks, Mitja Gerževič, Uroš Marušič, Rado Pišot, Boštjan Šimunič, Aleš Holobar, 2022, izvirni znanstveni članek

Povzetek: We examined activation patterns of the gastrocnemius medialis (GM), gastrocnemius lateralis (GL), soleus (SO), and tibialis anterior (TA) muscles in eight older (58.4 ± 3.3 years) and seven young (23.1 ± 2.9 years) participants, before and after 14 days of horizontal bed rest. Visual feedback on the exerted muscle torque was provided to the participants. The discharge patterns of individual motor units (MUs) were studied in three repetitions of isometric plantar flexion at 30 and 60% of Maximum Voluntary Contraction (MVC), before, and 1 day after the 14-day bed rest, respectively. In the GL and GM muscles, the older participants demonstrated higher MU discharge rates than the young, regardless of the contraction level, both before and after the bed rest. In the TA and SO muscles, the differences between the older and young participants were less consistent. Detailed analysis revealed person-specific changes in the MU discharge rates after the bed rest. To quantify the coactivation patterns we calculated the correlation coefficients between the cumulative spike trains of identified MUs from each muscle, and measured the root mean square difference of the correlation coefficients between the trials of the same session (intra-session variability) and between different sessions (inter-session variability) in each participant (intra-person comparison) and across participants (inter-person comparison). In the intra-person comparison, the inter-session variability was higher than the intra-session variability, either before or after the bed rest. At 60% MVC torque, the young demonstrated higher inter-person variability of coactivation than the older participants, but this variability decreased significantly after the bed rest. In older participants, inter-person variability was consistently lower at 60% than at 30% MVC torque. In young participants, inter-person variability became lower at 60% than at 30% MVC torque only after the bed rest. Precaution is required when analyzing the MU discharge and coactivation patterns, as individual persons demonstrate individual adaptations to aging or bed rest.
Ključne besede: high density electromyography, muscle disuse, motor units, discharge rate, aging
Objavljeno v DiRROS: 05.09.2022; Ogledov: 572; Prenosov: 323
.pdf Celotno besedilo (4,31 MB)
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76.
Terminologies and characteristics of natural mineral and thermal waters in selected European countries
Daniel Elster, Teodóra Szőcs, Nóra Gál, Birgitte Hansen, Denitza D. Voutchkova, Jörg Schullehner, Julie Lions, Lucio Martarelli, Elena Giménez-Forcada, José Angel Díaz-Muñoz, Eline Malcuit, Gerhard Schubert, Gerhard Hobiger, Nina Rman, 2022, pregledni znanstveni članek

Povzetek: This study discusses 1) the national legislative frameworks, terminologies, and criteria for the recognition of natural mineral waters and thermal waters in selected European countries (Austria, Bosnia and Herzegovina, Denmark, France, Hungary, Iceland, Italy, Lithuania, Poland, Portugal, Romania, Serbia, Slovenia, and Spain), and 2) it provides a first extensive multi-national overview of hydrogeological and hydrogeochemical characteristics of numerous water sources from those regions.
Ključne besede: hydrogeology, regulatory framework, hydrogeochemical composition, natural mineral water, thermal water, Europe
Objavljeno v DiRROS: 26.07.2022; Ogledov: 658; Prenosov: 236
.pdf Celotno besedilo (10,31 MB)

77.
Synoptic risk assessment of groundwater contamination from landfills
Sonja Cerar, Luka Serianz, Katja Koren, Joerg Prestor, Nina Mali, 2022, izvirni znanstveni članek

Povzetek: Waste management in Europe has improved in recent years, reducing the amount of waste disposed at landfills. However, there are still many landfills in the countries. It is well known that landfills that do not have measures in place to control leachate entering groundwater can contaminate groundwater long after the landfill is closed. Collecting monitoring results from all landfills allows permitting and management agencies to improve action plans. This relies on a synoptic risk assessment that allows prioritization and milestones to be set for required actions. The developed method of synoptic risk assessment is based on a conceptual model of the landfill and the results of chemical groundwater monitoring tested at 69 landfills in Slovenia. The study confirms that most landfills have a direct or indirect impact on groundwater quality. All landfills were classified into three priority classes on the basis of the synoptic risk assessment. The results show that a total of 24 landfills have a clearly pronounced impact on groundwater. A total of 31 landfills have a less pronounced impact due to the favorable natural attenuation capacity of the soil or the technically appropriate design of the landfill itself. A total of 14 landfills have a less pronounced or negligible impact on groundwater.
Ključne besede: conceptual model, synoptic risk assessment, landfill, groundwater, chemical analysis
Objavljeno v DiRROS: 19.07.2022; Ogledov: 528; Prenosov: 280
.pdf Celotno besedilo (3,09 MB)
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78.
Genska terapija v onkologiji, prvi razvojni koraki v Sloveniji
Maja Čemažar, Tanja Jesenko, Maša Omerzel, Boštjan Markelc, Urška Kamenšek, Simona Kranjc Brezar, Špela Kos, Urša Lampreht Tratar, Katarina Žnidar, Andrej Renčelj, Urška Matkovič, Teja Valant, Kristina Levpušček, Živa Modic, Tilen Komel, Tim Božič, Urša Kešar, Barbara Starešinič, Katja Uršič Valentinuzzi, Monika Savarin, Primož Strojan, Gorana Gašljević, Maja Ota, Aleš Grošelj, Črt Jamšek, Rosana Hudej, Matjaž Peterka, Franc Smrekar, Barbara Hubad, Marjan Hosta, Jaka Kužnik, Alojz Hosta, Damijan Miklavčič, Matej Reberšek, Aleksandra Cvetkoska, Anja Zajc, Janja Dermol-Černe, Nataša Tozon, Nina Milevoj, Alenka Nemec Svete, Gregor Serša, 2022, strokovni članek

Povzetek: Genska terapija postaja čedalje bolj zanimiva tudi v onkologiji. Med aplikacijami je morda najzanimivejša imunostimulacija. Pripravimo lahko plazmidno DNA, ki nosi zapis za različne imunostimulatorne molekule, ki jih vnesemo v celice tumorjev ali normalnih tkiv. Ta tkiva postanejo proizvajalci teh molekul, ki lahko delujejo lokalno ali pa se izločajo tudi sistemsko v krvni obtok. Ker plazmidna DNA ne prehaja celične membrane, so potrebni dostavni sistemi, virusni ali nevirusni. V naših študijah uporabljamo predvsem nevirusni dostavni sistem – elektroporacijo. Interlevkin 12 (IL-12) je eden od zanimivih citokinov, za katerega je znano protitumorsko delovanje s spodbujanjem imunskega odziva in antiangiogenim delovanjem. Namen projekta SmartGene.si je bil pripraviti plazmid z zapisom za interlevkin 12 (plazmid phIL12) in pripraviti vse potrebno za njegovo klinično testiranje za zdravljenje kožnih tumorjev. V konzorciju smo združili moči s partnerji z akademskega in industrijskega področja. Treba je bilo pripraviti plazmid za uporabo v humani onkologiji po zahtevah Evropske agencije za zdravila (EMA). Za prijavo klinične študije na Javno agencijo za zdravila in medicinske pripomočke (JAZMP) smo morali izvesti tudi vse neklinične raziskave o varnosti in učinkovitosti zdravila. Nato je bilo treba razviti postopek priprave zdravila, zagotoviti primerne prostore za pripravo in izvedbo postopka priprave zdravila. V treh letih smo dosegli vse te zastavljene cilje in dobili dovoljenje za izvajanje klinične študije na kožnih tumorjih, ki ga je izdala JAZMP na osnovi pozitivnega mnenja Komisije Republike Slovenije za medicinsko etiko. Zdaj poteka klinična študija faze I preizkušanja plazmida phIL12 na kožnih tumorjih glave in vratu z namenom preveriti varnost in sprejemljivost genskega elektroprenosa plazmida v tumorje. Cilj študije je prav tako določiti primeren odmerek zdravila, ki bi ga v nadaljnji klinični študiji uporabili kot adjuvantno zdravljenje k ablativnim terapijam, kot sta radioterapija ali elektrokemoterapija.
Ključne besede: genska terapija, interlevkin-12, plazmidna DNA, elektroprenos genov, rak kože
Objavljeno v DiRROS: 01.07.2022; Ogledov: 1137; Prenosov: 227
.pdf Celotno besedilo (420,40 KB)

79.
Good survival of broadleaf tree species in a four-year-old plantation in the Slovenian Karst
Nina Škrk, Kristjan Jarni, Robert Brus, 2022, izvirni znanstveni članek

Povzetek: Six broadleaf tree species (Celtis australis L. – Mediterranean hackberry, Quercus petraea (Matt.) Liebl. – sessile oak, Fagus sylvatica L. – European beech, Prunus avium L. – wild cherry, Juglans regia L. – Persian walnut and Acer pseudoplatanus L. – sycamore maple) were planted in 2012 in a trial in the Slovenian Karst on two sites differing in productivity to test their suitability for use in the conversion of old pine stands into ecologically more stable broadleaf forests and to investigate their possible response to the harsher growth conditions predicted in the future. The selected economically interesting tree species have higher timber quality than broadleaves which regenerate naturally (e.g., Ostrya carpinifolia, Fraxinus ornus, Quercus cerris). Measurements were taken in 2017, after four growth seasons. All planted species except Fagus sylvatica had a high survival rate. In total, 70% of all seedlings survived, which shows promising potential. The survival rate was higher at the site on flat terrain than at the site on a slope. Prunus avium was the most successful of all planted species in terms of survival rate, at 83%, and other measured parameters (height, height increment, stem diameter, vitality and quality), and Fagus sylvatica was the least successful, with a survival rate of only 20%. Celtis australis had the highest survival rate, at 87%. Acer pseudoplatanus had the largest differences in measured parameters between the more and less productive sites among all planted species. Quercus petraea showed high resistance to xeric conditions and is expected to be the most successful in conversions. All planted species except Fagus sylvatica show favourable initial potential for the future conversion of Karst pine forests.
Ključne besede: forest conversion, broadleaves, survival rate, seedlings quality, climate change
Objavljeno v DiRROS: 28.06.2022; Ogledov: 2101; Prenosov: 959
.pdf Datoteka (3,13 MB)

80.
Solid cancer patients achieve adequate immunogenicity and low rate of severe adverse events after SARS-CoV-2 vaccination
Urška Janžič, Urška Bidovec, Katja Mohorčič, Loredana Mrak, Nina Fokter Dovnik, Marija Ivanović, Maja Ravnik, Marina Čakš, Erik Škof, Jerneja Debeljak, Peter Korošec, Matija Rijavec, 2022, izvirni znanstveni članek

Povzetek: Background: SARS-CoV-2 vaccination in cancer patients is crucial to prevent severe COVID-19 disease course. Methods: This study assessed immunogenicity of cancer patients on active treatment receiving mRNA-based SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum, before, after the first and second doses and 3 months after a complete primary course of vaccination. Results were compared with healthy controls. Results: Of 112 patients, the seroconversion rate was 96%. A significant reduction in antibody levels was observed 3 months after vaccination in patients receiving immune checkpoint inhibitors versus control participants (p < 0.001). Adverse events were mostly mild. Conclusion: Immunogenicity after mRNA-based vaccine in cancer patients is adequate but influenced by the type of anticancer therapy. Antibody levels decline after 3 months, and thus a third vaccination is warranted.
Ključne besede: onkološko zdravljenje, imunogenost, osnovno cepljenje mRNA, čvrsti tumorji, anticancer treatment, immunogenicity, mRNA-based vaccination, solid cancer
Objavljeno v DiRROS: 24.06.2022; Ogledov: 771; Prenosov: 317
.pdf Celotno besedilo (2,03 MB)

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