Search Results (10)

Breast cancer, a complex disease with a significant prevalence to form metastases, necessitates novel therapeutic strategies to improve treatment outcomes. Here, we present the results of a comparative molecular study of primary breast tumours, their metastases, and the corresponding primary cell lines using Desorption Electrospray Ionisation (DESI) and Laser-Assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) imaging. Our results show that ambient ionisation mass spectrometry technology is suitable for rapid characterisation of samples, providing a lipid- and metabolite-rich spectrum within seconds. Our study demonstrates that the lipidomic fingerprint of the primary tumour is not significantly distinguishable from that of its metastasis, in parallel with the similarity observed between their respective primary cell lines. While significant differences were observed between tumours and the corresponding cell lines, distinct lipidomic signatures and several phospholipids such as PA(36:2), PE(36:1), and PE(P-38:4)/PE(O-38:5) for LA-REIMS imaging and PE(P-38:4)/PE(O-38:5), PS(36:1), and PI(38:4) for DESI-MSI were identified in both tumours and cells. We show that the tumours’ characteristics can be found in the corresponding primary cell lines, offering a promising avenue for assessing tumour responsiveness to therapeutic interventions. A comparative analysis by DESI-MSI and LA-REIMS imaging revealed complementary information, demonstrating the utility of LA-REIMS in the molecular imaging of cancer. Full article

Porous butterfly wings with hierarchically organized structures from nanometer to centimeter scales were tested as substrates for carrying plasmonic Au and Ag/Au nanoparticles with potential application in photocatalysis. Wings exhibiting structural color generated by chitin-air nanocomposites were used. Hundreds of butterfly species possess these types of color-generating photonic nanoarchitectures, producing color by a similar mechanism to manmade photonic crystals. Artificial photonic crystals are known to enhance photocatalytic processes through the slow light effect. The impact of pure water, water-based sodium citrate solution, and Au and Ag/Au alloy nanoparticles on the optical properties of the natural photonic structures were separated. While water and aqueous sodium citrate solutions change the wing reflectance by the alteration of the wing scale position with respect to the wing plane, Au and Ag/Au alloy nanoparticles form a new, hybrid nanostructure with the chitin nanoarchitecture modifying the structural color of the butterfly wings. The optical properties of the new types of hybrid photonic nanoarchitectures (consisting of butterfly wings and plasmonic nanoparticles) are different from those of the components. Full article

Investigation of drug-induced liver injuries requires appropriate in vivo and in vitro toxicological model systems. In our study, an attempt was made to compare the hepatocarcinoma HepG2 and the stem cell-derived HepaRG cell lines both in two- and three-dimensional culture conditions to find the most suitable model. Comparison of the liver-specific characteristics of these models was performed via the extent and mechanism of acetaminophen (APAP)-induced hepatotoxicity. Investigating the detailed mechanism of APAP-induced hepatotoxicity, different specific cell death inhibitors were used: the pan-caspase inhibitor zVAD-fmk and dabrafenib significantly protected both cell lines from APAP-induced cell death. However, the known specific inhibitors of necroptosis (necrostatin-1 and MDIVI) were only effective in differentiated HepaRG, which suggest a differential execution of activated pathways in the two models. By applying 3D culture methods, CYP2E1 mRNA levels could be elevated, but we failed to achieve a significant increase in hepatocyte function; hence, the 3D cultivation especially in APAP toxicity studies is not necessarily worth the complicated maintenance. Based on our findings, the hepatocyte functions of HepaRG may stand between the properties of HepG2 cells and primary hepatocytes (PHHs). However, it should be noted that in contrast to PHHs having many limitations, HepaRG cells are relatively immortal, having a stable phenotype and CYP450 expression. Full article

Introduction: Magnesium (Mg²⁺) deficiency is a common finding in the early phase after kidney transplantation (KT) and has been linked to immune dysfunction and infections. Data on the association of hypomagnesemia and the rate of infections in kidney transplant recipients (KTRs) are sparse. Methods: We conducted a single-center retrospective cohort study of KTRs transplanted between 2005 and 2015. Laboratory data, including serum Mg²⁺ (median time of the Mg²⁺ measurement from KT: 29 days), rate of infections including mainly urinary tract infections (UTI), and common transplant-related viral infections (CMV, polyoma, EBV) in the early phase after KT were recorded. The primary outcome was the incidence of infections within one year after KT, while secondary outcomes were hospitalization due to infection, incidence rates of long-term (up to two years) infections, and all-cause mortality. Results: We enrolled 376 KTRs of whom 229 patients (60.9%) suffered from Mg²⁺ deficiency defined as a serum Mg²⁺ < 0.7 mmol/L. A significantly higher incidence rate of UTIs and viral infections was observed in patients with versus without Mg²⁺ deficiency during the first year after KT (58.5% vs. 47.6%, p = 0.039 and 69.9% vs. 51.7%, p < 0.001). After adjustment for potential confounders, serum Mg²⁺ deficiency remained an independent predictor of both UTIs and viral infections (odds ratio (OR): 1.73, 95% CI: 1.04–2.86, p = 0.035 and OR: 2.05, 95% CI: 1.23–3.41, p = 0.006). No group differences according to Mg²⁺ status in hospitalizations due to infections and infection incidence rates in the 12–24 months post-transplant were observed. In the Cox regression analysis, Mg²⁺ deficiency was not significantly associated with all-cause mortality (HR: 1.15, 95% CI: 0.70–1.89, p = 0.577). Conclusions: KTRs suffering from Mg²⁺ deficiency are at increased risk of UTIs and viral infections in the first year after KT. Interventional studies investigating the effect of Mg²⁺ supplementation on Mg²⁺ deficiency and viral infections in KTRs are needed. Full article

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients. We studied the nationwide impact of COVID-19 on kidney transplantation in Austria during the first six months of 2020. Concurrent with general lockdown measures, all kidney transplant activity was suspended from 13 March to 9 April. Nevertheless, between January and June, total transplant (p = 0.48) and procured donor organ numbers (p = 0.6) did not differ significantly from earlier years. Ten (0.18%) of 5512 prevalent Austrian kidney transplant recipients were diagnosed with SARS-CoV-2. The case fatality rate (one death; 10%) in renal transplant patients was less than in other countries but higher than in Austria’s general population (2.4%). We conclude that early and strict general lockdown measures imposed by the government allowed an early, however cautious, re-opening of Austrian transplant programs and played a crucial role for the favorable outcomes of SARS-CoV-2 in Austrian kidney transplant patients. Even though it may be uncertain whether similar results may be obtainable in other countries, the findings may support early intervention strategies during similar episodes in the future. Full article

Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic resistance often reduces fitness, but compensatory mutations may counteract this tendency. The appearance of new antibiotic resistance is frequently accompanied by a collateral sensitivity to other resistances. Organisms with an expanding open pan-genome, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, can withstand an increased number of resistances by exploiting their evolutionary plasticity and disseminating clonally or poly-clonally. Multidrug-resistant pathogen clones can become predominant under antibiotic stress conditions but, under the influence of negative frequency-dependent selection, are prevented from rising to dominance in a population in a commensal niche. Antimicrobial peptides have a great potential to combat multidrug resistance, since antibiotic-resistant bacteria have shown a high frequency of collateral sensitivity to antimicrobial peptides. In addition, the mobility patterns of antibiotic resistance, and antimicrobial peptide resistance, genes are completely different. The integron trade in commensal niches is fortunately limited by the species-specificity of resistance genes. Hence, we theorize that the suggested post-antibiotic era has not yet come, and indeed might never come. Full article

A gold-coated array of flow-through inverse pyramids applicable as substrate for entrapment and immobilization of micro-objects and for surface enhanced Raman spectroscopic measurements was fabricated using bulk micromachining techniques from silicon. Surface morphology, optical reflectance, immobilization properties, and surface enhanced Raman amplification of the array were modelled and characterized. It was found that the special perforated periodic 3D structure can be used for parallel particle and cell trapping and highly sensitive molecular analysis of the immobilized objects. Full article

Cameleons are sophisticated genetically encoded fluorescent probes that allow quantifying cellular Ca²⁺ signals. The probes are based on Förster resonance energy transfer (FRET) between terminally located fluorescent proteins (FPs), which move together upon binding of Ca²⁺ to the central calmodulin myosin light chain kinase M13 domain. Most of the available cameleons consist of cyan and yellow FPs (CFP and YFP) as the FRET pair. However, red-shifted versions with green and orange or red FPs (GFP, OFP, RFP) have some advantages such as less phototoxicity and minimal spectral overlay with autofluorescence of cells and fura-2, a prominent chemical Ca²⁺ indicator. While GFP/OFP- or GFP/RFP-based cameleons have been successfully used to study cytosolic and mitochondrial Ca²⁺ signals, red-shifted cameleons to visualize Ca²⁺ dynamics of the endoplasmic reticulum (ER) have not been developed so far. In this study, we generated and tested several ER targeted red-shifted cameleons. Our results show that GFP/OFP-based cameleons due to miss-targeting and their high Ca²⁺ binding affinity are inappropriate to record ER Ca²⁺ signals. However, ER targeted GFP/RFP-based probes were suitable to sense ER Ca²⁺ in a reliable manner. With this study we increased the palette of cameleons for visualizing Ca²⁺ dynamics within the main intracellular Ca²⁺ store. Full article

Natura 2000 Habitat Conservation Status is currently evaluated based on fieldwork. However, this is proving to be unfeasible over large areas. The use of remote sensing is increasingly encouraged but covering the full range of ecological variables by such datasets and ensuring compatibility with the traditional assessment methodology has not been achieved yet. We aimed to test Airborne Laser Scanning (ALS) as a source for mapping all variables required by the local official conservation status assessment scheme and to develop an automated method that calculates Natura 2000 conservation status at 0.5 m raster resolution for 24 km² of Pannonic Salt Steppe habitat (code 1530). We used multi-temporal (summer and winter) ALS point clouds with full-waveform recording and a density of 10 pt/m². Some required variables were derived from ALS product rasters; others involved vegetation classification layers calculated by machine learning and fuzzy categorization. Thresholds separating favorable and unfavorable values of each variable required by the national assessment scheme were manually calibrated from 10 plots where field-based assessment was carried out. Rasters representing positive and negative scores for each input variable were integrated in a ruleset that exactly follows the Hungarian Natura 2000 assessment scheme for grasslands. Accuracy of each parameter and the final conservation status score and category was evaluated by 10 independent assessment plots. We conclude that ALS is a suitable data source for Natura 2000 assessments in grasslands, and that the national grassland assessment scheme can successfully be used as a GIS processing model for conservation status, ensuring that the output is directly comparable with traditional field based assessments. Full article

There is increasing demand for reliable, high-resolution vegetation maps covering large areas. Airborne laser scanning data is available for large areas with high resolution and supports automatic processing, therefore, it is well suited for habitat mapping. Lowland hay meadows are widespread habitat types in European grasslands, and also have one of the highest species richness. The objective of this study was to test the applicability of airborne laser scanning for vegetation mapping of different grasslands, including the Natura 2000 habitat type lowland hay meadows. Full waveform leaf-on and leaf-off point clouds were collected from a Natura 2000 site in Sopron, Hungary, covering several grasslands. The LIDAR data were processed to a set of rasters representing point attributes including reflectance, echo width, vegetation height, canopy openness, and surface roughness measures, and these were fused to a multi-band pseudo-image. Random forest machine learning was used for classifying this dataset. Habitat type, dominant plant species and other features of interest were noted in a set of 140 field plots. Two sets of categories were used: five classes focusing on meadow identification and the location of lowland hay meadows, and 10 classes, including eight different grassland vegetation categories. For five classes, an overall accuracy of 75% was reached, for 10 classes, this was 68%. The method delivers unprecedented fine resolution vegetation maps for management and ecological research. We conclude that high-resolution full-waveform LIDAR data can be used to detect grassland vegetation classes relevant for Natura 2000. Full article