1001. Image reconstruction using small-voxel size improves small lesion detection for positron emission tomographySebastijan Rep, Petra Tomše, Luka Jensterle, Leon Jarabek, Katja Zaletel, Luka Ležaič, 2022, izvirni znanstveni članek Povzetek: Background. PET/CT imaging is widely used in oncology and provides both metabolic and anatomic information. Because of the relatively poor spatial resolution of PET, the detection of small lesions is limited. The low spatial resolution introduces the partial-volume effect (PVE) which negatively affects images both qualitatively and quantitatively. The aim of the study was to investigate the effect of small-voxel (2 mm in-line pixel size) vs. standard-voxel (4 mm in-line pixel size) reconstruction on lesion detection and image quality in a range of activity ratios. Materials and methods. The National Electrical Manufacturers Association (NEMA) body phantom and the Micro Hollow-Sphere phantom spheres were filled with a solution of [18F]fluorodeoxyglucose ([18F]FDG) in sphere-to-background ratios of 2:1, 3:1, 4:1 and 8:1. In all images reconstructed with 2 mm and 4 mm in-line pixel size the visual lesion delineation, contrast recovery coefficient (CRC) and contrast-to-noise ratio (CNR) were evaluated. Results. For smaller (≤ 13 mm) phantom spheres, significantly higher CRC and CNR using small-voxel reconstructions were found, also improving visual lesion delineation. CRC did not differ significantly for larger (≥ 17 mm) spheres using 2 mm and 4 mm in-line pixel size, but CNR was significantly lower; however, lower CNR did not affect visual lesion delineation. Conclusions. Small-voxel reconstruction consistently improves precise small lesion delineation, lesion contrast and image quality.
Ključne besede: PET/CT, voxel size, contrast recovery coefficient, contrast-to-noise ratio
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1004. Spatial and temporal recruitment of the neurovascular unit during development of the mouse blood-retinal barrierAnne-Eva van der Wijk, Ilse M.C. Vogels, Henk A. van Veen, Cornelis J. F. van Noorden, Reinier O. Schlingemann, Ingeborg Klaassen, 2018, izvirni znanstveni članek Povzetek: The inner blood-retinal barrier (BRB) is made up by the neurovascular unit, consisting of endothelial cells, pericytes and glial cells. The BRB maintains homeostasis of the neural retina, but in pathological eye conditions the neurovascular unit is often disrupted, causing BRB loss. Here, we investigated in detail temporal and spatial recruitment of the neurovascular unit in the neonatal mouse retina from postnatal day (P)3 to P25 employing immunohistochemical staining of vascular endothelium (isolectin B4), pericytes (α-SMA and NG2) and astrocytes (GFAP). In addition, we investigated gene expression of polarized astrocytic end-feet markers aquaporin-4 and laminin α2 chain with qPCR. We observed GFAP-positive cells migrating ahead of the retinal vasculature during the first postnatal week, suggesting that the retinal vasculature follows an astrocytic meshwork. From P9 onwards, astrocytes acquired a mature phenotype, with a more stellate shape and increased expression of aquaporin-4. NG2-positive cells and tip cells co-localized at P5 and invaded the retina together as a vascular sprouting front. In summary, these data suggest that recruitment of the cell types of the neurovascular unit is a prerequisite for proper retinal vascularization and BRB formation.
Ključne besede: endothelial cells, astrocytes, pericytes, retinal development
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1005. IDH1-mutant cancer cells are sensitive to cisplatin and an IDH1-mutant inhibitor counteracts this sensitivityMohammed Khurshed, Niels Aarnoudse, Renske Hulsbos, Vashendriya V. V. Hira, Hanneke WM van Laarhoven, Johanna W Wilmink, Remco J. Molenaar, Cornelis J. F. van Noorden, 2018, izvirni znanstveni članek Povzetek: Isocitrate dehydrogenase (IDH1)-1 is mutated in various types of human cancer, and the presence of this mutation is associated with improved responses to irradiation and chemotherapy in solid tumor cells. Mutated IDH1 (IDH1MUT) enzymes consume NADPH to produce D-2-hydroxyglutarate (D-2HG) resulting in the decreased re ducing power needed for detoxification of reactive oxygen species (ROS), for example. The objective of the current study was to investigate the mechanism behind the chemosensitivity of the widely used anticancer agent cisplatin in IDH1MUT cancer cells. Oxidative stress, DNA damage, and mitochondrial dysfunction caused by cisplatin treatment were monitored in IDH1MUT HCT116 colorectal cancer cells and U251 glioma cells. We found that exposure to cisplatin induced higher levels of ROS, DNA double-strand breaks (DSBS), and cell death in IDH1MUT cancer cells, as compared with IDH1 wild-type (IDH1WT) cells. Mechanistic investigations revealed that cisplatin treatment dose dependently reduced oxidative respiration in IDH1MUT cells, which was accompanied by disturbed mitochondrial proteostasis, indicative of impaired mitochondrial activity. These effects were abolished by the IDH1MUT inhibitor AGI-5198 and were restored by treatment with D-2HG. Thus, our study shows that altered oxidative stress responses and a vulnerable oxidative metabolism underlie the sensitivity of IDH1MUT cancer cells to cisplatin.—Khurshed, M., Aarnoudse, N., Hulsbos, R., Hira, V. V. V., van Laarhoven, H. W. M., Wilmink, J. W., Molenaar, R. J., van Noorden, C. J. F. IDH1-mutant cancer cells are sensitive to cisplatin and an IDH1-mutant inhibitor counteracts this sensitivity. 32, 6344–6352 (2018). www.fasebj.org
Ključne besede: isocitrate dehydrogenase, chemosensitivity, cis-diamminedichloroplatinum, 2-hydroxyglutarate
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1006. IGF2 and IGF1R identified as novel tip cell genes in primary microvascular endothelial cell monolayersMarchien G. Dallinga, Bahar Yetkin-Arik, Richelle P. Kayser, Ilse M.C. Vogels, Patrycja Nowak-Sliwinska, Arjan W. Griffioen, Cornelis J. F. van Noorden, Ingeborg Klaassen, Reinier O. Schlingemann, 2018, izvirni znanstveni članek Povzetek: Tip cells, the leading cells of angiogenic sprouts, were identified in cultures of human umbilical vein endothelial cells (HUVECs) by using CD34 as a marker. Here, we show that tip cells are also present in primary human microvascular endothelial cells (hMVECs), a more relevant endothelial cell type for angiogenesis. By means of flow cytometry, immunocytochemistry, and qPCR, it is shown that endothelial cell cultures contain a dynamic population of CD34+ cells with many hallmarks of tip cells, including filopodia-like extensions, elevated mRNA levels of known tip cell genes, and responsiveness to stimulation with VEGF and inhibition by DLL4. Furthermore, we demonstrate that our in vitro tip cell model can be exploited to investigate cellular and molecular mechanisms in tip cells and to discover novel targets for anti-angiogenesis therapy in patients. Small interfering RNA (siRNA) was used to knockdown gene expression of the known tip cell genes angiopoietin 2 (ANGPT2) and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1), which resulted in similar effects on tip cells and sprouting as compared to inhibition of tip cells in vivo. Finally, we identified two novel tip cell-specific genes in CD34+ tip cells in vitro: insulin-like growth factor 2 (IGF2) and IGF-1-receptor (IGF1R). Knockdown of these genes resulted in a significant decrease in the fraction of tip cells and in the extent of sprouting in vitro and in vivo. In conclusion, this study shows that by using our in vitro tip cell model, two novel essential tip cells genes are identified.
Ključne besede: Angiogenesis, tip cells, CD34, IGF2, endothelial cells, cultured cells, endothelial growth factors
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1007. Fungi between extremotolerance and opportunistic pathogenicity on humansCene Gostinčar, Janja Zajc, Metka Lenassi, Ana Plemenitaš, Sybren de Hoog, Abdullah M. S. Al-Hatmi, Nina Gunde-Cimerman, 2018, izvirni znanstveni članek Povzetek: Numerous agents of infections in humans and other mammals are found among fungi that are able to survive extreme environmental conditions and to quickly adapt to novel habitats. Nevertheless, the relationship between opportunistic potential and polyextremotolerance was not yet studied systematically in fungi. Here, the link between polyextremotol- erance and opportunistic pathogenicity is shown in a kingdom-wide phylogenetic analysis as a statistically significant co- occurrence of extremotolerance (e.g. osmotolerance and psychrotolerance) and opportunism at the level of fungal orders. In addition to extremotolerance, fungal opportunists share another characteristic%an apparent lack of specialised virulence traits. This is illustrated by a comparative genomic analysis of 20 dothideomycetous and eurotiomycetous black fungi. While the genomes of specialised fungal plant pathogens were significantly enriched in known virulence-associated genes that encode secreted proteases, carbohydrate active enzyme families, polyketide synthases, and non-ribosomal peptide synthetases, no such signatures were observed in human opportunists. Together the presented results have several implications. If infection of human hosts is a side effect of fungal stress tolerance and adaptability, the human body is most likely neither the preferred habitat of such species, nor important for their evolutionary success. This defines opportunism as opposed to pathogenicity, where infection is advantageous for the species% fitness. Since opportunists are generally incapable of the host-to-host transmission, any host-specific adaptations are likely to be lost with the resolution of the infection, explaining the observed lack of specialised virulence traits. In this scenario opportunistic infections should be seen as an evolutionary dead end and unlikely to lead to true pathogenicity.
Ključne besede: fungi, pathogenicity, infections in humans
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1008. Effects of oils and solid fats on blood lipids : a systematic review and network meta-analysisLukas Schwingshackl, Berit Bogensberger, Aleksander Benčič, Sven Knüppel, Heiner Boeing, Georg Hofmann, 2018, izvirni znanstveni članek Povzetek: The aim of this network meta-analysis (NMA) is to compare the effects of different oils/solid fats on blood lipids. Literature searches were performed until March 2018. Inclusion criteria were as follows: i) randomized trial (≥3 weeks study length) comparing at least two of the following oils/solid fats: safflower, sunflower, rapeseed, hempseed, flaxseed, corn, olive, soybean, palm, and coconut oil, and lard, beef-fat, and butter; ii) outcomes LDL-cholesterol (LDL-C), total cholesterol (TC), HDL-cholesterol (HDL-C), and triacylglycerols (TGs). A random dose-response (per 10% isocaloric exchange) NMA was performed and surface under the cumulative ranking curve (SUCRA) was estimated. Fifty-four trials were included in the NMA. Safflower oil had the highest SUCRA value for LDL-C (82%) and TC (90%), followed by rapeseed oil (76% for LDL-C, 85% for TC); whereas, palm oil (74%) had the highest SUCRA value for TG, and coconut oil (88%) for HDL-C. Safflower, sunflower, rapeseed, flaxseed, corn, olive, soybean, palm, and coconut oil as well beef fat were more effective in reducing LDL-C (−0.42 to −0.23 mmol/l) as compared with butter. Despite limitations in these data, our NMA findings are in line with existing evidence on the metabolic effects of fat and support current recommendations to replace high saturated-fat food with unsaturated oils.
Ključne besede: cardiovascular disease, evidence synthesis, fatty acids
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1009. Diversity and flight activity of aphid species as potential vectors of oilseed pumpkin viruses in SerbiaAna Vučurović, Olivera Petrović-Obradović, Anđa Radonjić, Dušan Nikolić, Katarina Zečević, Ivana Stanković, Branka Krstić, 2018, izvirni znanstveni članek Povzetek: The fauna of aphids appearing on cucurbits, including oilseed pumpkin have been poorly investigated in Serbia. Yellow water traps were used to determine the diversity of aphid species visiting cucurbits in Serbia and to monitor their flight activity. During the years 2009 to 2011, a total of 1,447 specimens were collected and a total of 57 different aphid taxa were identified. In 2009, the highest total number of aphids were caught (755), followed by 203 and 489 aphids in 2010 and 2011, respectively. The most abundant species were Aphis fabae (15%), Myizus persicae (13.4%) and Acyrthosiphon pisum (11.7%), followed by Anoecia corni (6.4%)and Aphis gossypii(5.6%). All of them, except A. corni,are reported as efficient vectors of cucurbit viruses. These five species represent 52.1% of all aphid species collected within this study. Out of 57 taxa found in oilseed pumpkin crops, 17 are known as vectors of ZYMV, 18 of WMV and 15 of CMV. Generally, 25 out of a total of 57 taxa are known as vectors of at least one of three viruses present in Serbia. From total of 1,447 specimens collected during three years of investigation, 917 (63.4%) are vectors of at least one of three viruses. Individual oilseed pumpkin plants were frequently colonized by A. gossypiiduring all three years of investigation. Results of this study showed that Serbian oilseed pumpkin growing localities are grouped among medium to reach in aphidofauna, according to total Shannon-Weaver index values which varied from 1.8 to 2.8. The highest value of Shannon-Weaver (2.8) was recorded in the Bački Petrovac I locality in 2009, while the lowest Shannon-Weaver (1.8) was recorded in Kisač locality in 2010. The maximum values of Shanon-Weaver diversity index in almost all crops were recorded in the second week of investigation or in early stages of oilseed pumpkin growth when plants had 5-6 true leaves or were in flowering stage, when potential virus infection could lead to significant yield losses.
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