Although paraoxonase-1 (PON1) activity has been demonstrated to be a reliable biomarker of various diseases, clinical studies have been based only on relative comparison of specific enzyme activities, which capture differences mainly due to (usually unknown) PON1 concentration. Hence, the aim of this report is to present for the first time the simple evaluation method for determining autonomous kinetic parameter of PON1 that could be also associated with polymorphic forms and diseases; i.e. the Michaelis constant which is enzyme concentration independent quantity. This alternative approach significantly reduces the number of experiments needed, and it yields the results with great accuracy.
COBISS.SI-ID: 34576857
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.
COBISS.SI-ID: 34039769
The neurotropic and extremophilic black yeast Exophiala dermatitidis (Herpotrichellaceae) inhabits diverse indoor environments, in particular bathrooms, steam baths, and dishwashers. Here, we show that the selected strain, EXF-10123, is polymorphic, can grow at 37 °C, is able to assimilate aromatic hydrocarbons (toluene, mineral oil, n-hexadecane), and shows abundant growth with selected neurotransmitters (acetylcholine, gamma-aminobutyric acid, glycine, glutamate, and dopamine) as sole carbon sources. We have for the first time demonstrated the effect of E. dermatitidis on neuroblastoma cell model SH-SY5Y. Aqueous and organic extracts of E. dermatitidis biomass reduced SH-SY5Y viability by 51% and 37%, respectively. Melanized extracellular vesicles (EVs) prepared from this strain reduced viability of the SH-SY5Y to 21%, while non-melanized EVs were considerably less neurotoxic (79% viability). We also demonstrated direct interactions of E. dermatitidis with SH-SY5Y by scanning electron and confocal fluorescence microscopy. The observed invasion and penetration of neuroblastoma cells by E. dermatitidis hyphae presumably causes the degradation of most neuroblastoma cells in only three days. This may represent a so far unknown indirect or direct cause for the development of some neurodegenerative diseases such as Alzheimer's.
COBISS.SI-ID: 34781401
Inflammation and oxidative stress are recognized as important contributors to Parkinson's disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson's disease susceptibility and the occurrence of adverse events of dopaminergic treatment. In total, 224 patients were enrolled, and their demographic and clinical data on the disease course were collected. Furthermore, a control group of 146 healthy Slovenian blood donors were included for Parkinson's disease' risk evaluation. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1[beta] rs16944, IL1[beta] rs1143623, IL6 rs1800795, CAT rs1001179, CAT rs10836235, SOD2 rs4880, NOS1 rs2293054, NOS1 rs2682826, TNF-[alpha] rs1800629, and GPX1 rs1050450. Logistic regression was used for analysis of possible associations. We observed a nominally significant association of the IL1ß rs1143623 C allele with the risk for Parkinson’s disease (OR=0.59; 95%CI=0.38-0.92, p=0.021). CAT rs1001179 A allele was significantly associated with peripheral edema (OR=0.32; 95%CI= 0.15-0.68; p=0.003). Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR=1.75; 95%CI= 1.00-3.06, p=0.048), SOD2 rs4880 T allele and nausea/vomiting (OR=0.49, 95%CI=0.25-0.94; p=0.031), IL1ß rs1143623 C allele and orthostatic hypotension (OR=0.57, 95%CI=0.32-1.00, p=0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR=2.59; 95%CI=1.09-6.19; p=0.032). We did not find any associations between selected polymorphisms and motor adverse events. Apart from some nominally significant associations also one significant association between CAT genetic variability and peripheral edema was observed. Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment. However, the investigated polymorphisms do not play a major role in the occurrence of the disease and the adverse events of dopaminergic treatment.
COBISS.SI-ID: 34211545
The most common psychiatric complications due to dopaminergic treatment in Parkinson’s disease (PD) are visual hallucinations (VH) and impulse control disorders (ICD). Their development depends on clinical and genetic factors. We evaluated the simultaneous effect of 16 clinical and 34 genetic variables on the occurrence of VH and ICD. Altogether, 214 PD patients were enrolled. Their demographic, clinical, and genotype data were obtained. Clinical and clinical-pharmacogenetic models were built by The Least Absolute Shrinkage and Selection Operator penalized logistic regression. The predictive capacity was evaluated with the cross-validated area under the receiver operating characteristic curve (AUC). The clinical-pharmacogenetic index for prediction of VH encompassed age at diagnosis (OR=0.99), REM sleep behaviour disorder (OR=2.27), depression (OR=1.0002), IL6 rs1800795 (OR=0.99), GPX1 s1050450 (OR=1.07), COMT rs165815 (OR=0.69), MAOB rs1799836 (OR=0.97), DRD3 rs6280 (OR=1.32), and BIRC5 rs8073069 (OR=0.94). The clinical-pharmacogenetic index for prediction of ICD encompassed age at diagnosis (OR=0.95), depression (OR=1.75), beta-blockers (OR=0.99), coffee consumption (OR=0.97), NOS1 rs2682826 (OR=1.15), SLC6A3 rs393795 (OR=1.27), SLC22A1 rs628031 (OR=1.19), DRD2 rs1799732 (OR=0.88), DRD3 rs6280 (OR=0.88), NRG1 rs3924999 (OR=0.96). The cross-validated AUCs of clinical and clinical-pharmacogenetic models for VH were 0.60 and 0.59, respectively. The AUCs of clinical and clinical-pharmacogenetic models for ICD were 0.72 and 0.71, respectively. The AUCs show that the addition of selected genetic variables to the analysis does not contribute to better prediction of VH and ICD. Models could be improved by a larger cohort and by addition of other types of PD biomarkers to the analysis.
COBISS.SI-ID: 12969219