Magainin 2 and PGLa are cationic, amphipathic antimicrobial peptides which when added as equimolar mixture exhibit a pronounced synergism in both their antibacterial and pore-forming activities. Here we show for the first time that the peptides assemble into defined supramolecular structures along the membrane interface. The resulting mesophases are quantitatively described by state-of-the art fluorescence self-quenching and correlation spectroscopies. Notably, the synergistic behavior of magainin 2 and PGLa correlates with the formation of hetero-domains and an order-of-magnitude increased membrane affinity of both peptides. Enhanced membrane association of the peptide mixture is only observed in the presence of phophatidylethanolamines but not of phosphatidylcholines, lipids that dominate bacterial and eukaryotic membranes, respectively. Thereby the increased membrane-affinity of the peptide mixtures not only explains their synergistic antimicrobial activity, but at the same time provides a new concept to increase the therapeutic window of combinatorial drugs.

• MeSH
• antibakteriální látky chemie   izolace a purifikace   farmakologie   MeSH
• buněčná membrána chemie   účinky léků   MeSH
• ethanolaminy chemie   MeSH
• fixní kombinace léků MeSH
• fluorescenční barviva chemie   MeSH
• fluorescenční spektrometrie MeSH
• fosfatidylcholiny chemie   MeSH
• fosfatidylethanolaminy chemie   MeSH
• fosfatidylglyceroly chemie   MeSH
• kationické antimikrobiální peptidy chemie   izolace a purifikace   farmakologie   MeSH
• kůže chemie   MeSH
• lipidové dvojvrstvy chemie   MeSH
• magaininy chemie   izolace a purifikace   farmakologie   MeSH
• proteiny Xenopus chemie   izolace a purifikace   farmakologie   MeSH
• sloučeniny boru chemie   MeSH
• synergismus léků MeSH
• vazba proteinů MeSH
• Xenopus laevis MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Within streptophyte green algae Zygnematophyceae are the sister group to the land plants that inherited several traits conferring stress protection. Zygnema sp., a mat-forming alga thriving in extreme habitats, was collected from a field site in Svalbard, where the bottom layers are protected by the top layers. The two layers were investigated by a metatranscriptomic approach and GC-MS-based metabolite profiling. In the top layer, 6569 genes were significantly upregulated and 149 were downregulated. Upregulated genes coded for components of the photosynthetic apparatus, chlorophyll synthesis, early light-inducible proteins, cell wall and carbohydrate metabolism, including starch-degrading enzymes. An increase in maltose in the top layer and degraded starch grains at the ultrastructural levels corroborated these findings. Genes involved in amino acid, redox metabolism and DNA repair were upregulated. A total of 29 differentially accumulated metabolites (out of 173 identified ones) confirmed higher metabolic turnover in the top layer. For several of these metabolites, differential accumulation matched the transcriptional changes of enzymes involved in associated pathways. In summary, the findings support the hypothesis that in a Zygnema mat the top layer shields the bottom layers from abiotic stress factors such as excessive irradiation.

• MeSH
• Chlorophyta genetika   metabolismus   MeSH
• ekosystém MeSH
• fotosyntéza genetika   MeSH
• fyziologický stres MeSH
• metabolom MeSH
• Streptophyta genetika   metabolismus   MeSH
• transkriptom MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Arktida MeSH
• Svalbard MeSH

• Publikační typ
• novinové články MeSH
• rozhovory MeSH

BACKGROUND: Neurodegeneration with brain iron accumulation constitutes a group of rare progressive movement disorders sharing intellectual disability and neuroimaging findings as common denominators. Beta-propeller protein-associated neurodegeneration (BPAN) represents approximately 7% of the cases, and its first signs are typically epilepsy and developmental delay. We aimed to describe in detail the phenotype of BPAN with a special focus on iron metabolism. MATERIAL AND METHODS: We present a cohort of paediatric patients with pathogenic variants of WD-Repeat Domain 45 gene (WDR45). The diagnosis was established by targeted panel sequencing of genes associated with epileptic encephalopathies (n = 9) or by Sanger sequencing of WDR45 (n = 1). Data on clinical characteristics, molecular-genetic findings and other performed investigations were gathered from all participating centres. Markers of iron metabolism were analysed in 6 patients. RESULTS: Ten children (3 males, 7 females, median age 8.4 years) from five centres (Prague, Berlin, Vogtareuth, Tubingen and Cologne) were enrolled in the study. All patients manifested first symptoms (e.g. epilepsy, developmental delay) between 2 and 31 months (median 16 months). Seven patients were seizure-free (6 on antiepileptic medication, one drug-free) at the time of data collection. Neurological findings were non-specific with deep tendon hyperreflexia (n = 4) and orofacial dystonia (n = 3) being the most common. Soluble transferrin receptor/log ferritin ratio was elevated in 5/6 examined subjects; other parameters of iron metabolism were normal. CONCLUSION: Severity of epilepsy often gradually decreases in BPAN patients. Elevation of soluble transferrin receptor/log ferritin ratio could be another biochemical marker of the disease and should be explored by further studies.

• MeSH
• biologické markery krev   MeSH
• dítě MeSH
• epilepsie krev   genetika   metabolismus   MeSH
• fenotyp MeSH
• lidé MeSH
• mentální retardace krev   genetika   metabolismus   MeSH
• neurodegenerativní nemoci krev   genetika   metabolismus   MeSH
• pohybové poruchy krev   genetika   metabolismus   MeSH
• poruchy metabolismu železa krev   genetika   metabolismus   MeSH
• transportní proteiny genetika   MeSH
• železo krev   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: Variable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far. METHODS: In a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n = 42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.2 ± 3.8 years, for whom ambulatory blood pressure monitoring (ABPM) data were available. RESULTS: In the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM > 1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p = 0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p < 0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p = 0.014) and to 14.3% of control (p = 0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p = 0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change. CONCLUSIONS: Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping.

• MeSH
• alografty imunologie   patofyziologie   MeSH
• ambulantní monitorování krevního tlaku MeSH
• cirkadiánní rytmus fyziologie   MeSH
• cyklosporin aplikace a dávkování   škodlivé účinky   MeSH
• dítě MeSH
• glukokortikoidy aplikace a dávkování   škodlivé účinky   MeSH
• hodnoty glomerulární filtrace fyziologie   MeSH
• homologní transplantace škodlivé účinky   MeSH
• hypertenze chemicky indukované   diagnóza   prevence a kontrola   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   MeSH
• krevní tlak účinky léků   MeSH
• kyselina mykofenolová aplikace a dávkování   škodlivé účinky   MeSH
• ledviny imunologie   patofyziologie   MeSH
• lidé MeSH
• methylprednisolon MeSH
• mladiství MeSH
• nenasazení léčby * MeSH
• prospektivní studie MeSH
• rejekce štěpu imunologie   patofyziologie   prevence a kontrola   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

A novel application of the three-dimensional printing technology for the automation of solid phase extraction procedures in a low-pressure sequential injection analysis system is presented. A 3D printed device was used as a housing for nanofiber membranes in solid phase extraction. The applicability of the device is demonstrated with the extraction of substances of various physical-chemical properties. Pharmaceuticals including non-steroidal anti-inflammatory drugs, antihistaminics, and steroidal structures, as well as emerging pollutants such as bisphenols and pesticide metsulfuron methyl were used as model analytes to study the extraction performance of the nanofibers. Six different nanofiber types comprising polyamide, polyethylene, polyvinylidene fluoride, polycaprolactone combined with polyvinylidene fluoride, and polyacrylonitrile, produced by electrospinning were tested in solid phase extraction. The suitability of specific nanofibers for particular analytes is demonstrated.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

INTRODUCTION: Shiga toxin 2a (Stx2a) induces hemolytic uremic syndrome (STEC HUS) by targeting glomerular endothelial cells (GEC). OBJECTIVES: We investigated in a metabolomic analysis the response of a conditionally immortalized, stable glomerular endothelial cell line (ciGEnC) to Stx2a stimulation as a cell culture model for STEC HUS. METHODS: CiGEnC were treated with tumor necrosis factor-(TNF)α, Stx2a or sequentially with TNFα and Stx2a. We performed a metabolomic high-throughput screening by lipid- or gas chromatography and subsequent mass spectrometry. Metabolite fold changes in stimulated ciGEnC compared to untreated cells were calculated. RESULTS: 320 metabolites were identified and investigated. In response to TNFα + Stx2a, there was a predominant increase in intracellular free fatty acids and amino acids. Furthermore, lipid- and protein derived pro-inflammatory mediators, oxidative stress and an augmented intracellular energy turnover were increased in ciGEnC. Levels of most biochemicals related to carbohydrate metabolism remained unchanged. CONCLUSION: Stimulation of ciGEnC with TNFα + Stx2a is associated with profound metabolic changes indicative of increased inflammation, oxidative stress and energy turnover.

• MeSH
• endoteliální buňky cytologie   účinky léků   metabolismus   MeSH
• glomerulus cytologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lipopolysacharidy MeSH
• metabolomika * MeSH
• multivariační analýza MeSH
• počet buněk MeSH
• shiga toxin 2 metabolismus   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zánět chemicky indukované   metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH