Untersuchungen zur Regulation der seneszenzabhängig exprimierten Gene hpd und HvS40 der Gerste (Hordeum vulgare L.) und subzelluläre Lokalisierung des HvS40 Proteins

In der vorliegenden Arbeit wurde die Regulation der Genexpression während der Blattseneszenz der Gerste am Beispiel der Gene hpd und HvS40 untersucht. Im hpd Promotor konnte in Gelretardierungsexperimenten ein Abscisinsäure-Element identifiziert werden, dass an der Transkription des hpd Gens während der Blattseneszenz beteiligt sein könnte. Im HvS40 Promotors konnten zwei Bereiche identifiziert werden, die die Transkription des HvS40 Gens während der Blattseneszenz steuern könnten. Beide Motive beinhalten jeweils einen Teil des ERE-Elements sowie eine W-Box. Mit Hilfe einer DNA-Affinitätschromatographie konnte ein Protein, das nur im Fall junger Primärblätter an das eine Motiv bindet, isoliert werden. Es handelt sich hierbei um den Transkriptionsfaktor p24, der als Repressor die Transkription des HvS40 Gens vor Beginn der Seneszenz unterdrücken könnte. Mit Hilfe von immunelektronenmikroskopischen Untersuchungen konnte das HvS40 Protein im Zellkern von Mesophyllzellen seneszierender Primärblätter nachgewiesen werden, in denen das HvS40 Protein nicht mit DNA kolokalisiert

Comparison of the immediate effects of gaseous ozone and chlorhexidine gel on bacteria in cavitated carious lesions in children in vivo

Clinical application of ozone gas has been shown to arrest the progression of dentinal caries in children. In this study, we compare the immediate effects of gaseous ozone and chlorhexidine gel on bacteria in cavitated carious lesions in children. Forty children, each with at least two open occlusal carious lesions, were enrolled in the study. Two teeth were chosen randomly. In one lesion, overlying soft biological material was removed, whilst the other lesion was not excavated. Cavities were rinsed with sterile water and dried with air. A standardised sample was taken from the mesial part of each lesion. Then, gaseous ozone (HealOzone) or 1% chlorhexidine gel (Corsodyl) was applied for 30s on both lesions of 20 children each, and a second sample was taken from the distal part of each lesion. The anaerobic microbiota was cultivated; the number of colony forming units was calculated per milligram sample. The two-sided paired t test showed no significant (P > 0.05) differences in the reduction of total bacterial counts per milligram comparing samples before and after ozone or chlorhexidine application. The tests also showed no statistically significant difference whether the superficial decayed dentine had been removed before ozone or with chlorhexidine treatment or not. It can be concluded that gaseous ozone or chlorhexidine gel application for 30s to deep occlusal carious cavities had no significant immediate antimicrobial effects whether the superficial decayed layers dentine were removed or no

Echinacea purpurea-derived alkylamides exhibit potent anti-inflammatory effects and alleviate clinical symptoms of atopic eczema

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Synthesis and in vitro evaluation of cyclodextrin hyaluronic acid conjugates as a new candidate for intestinal drug carrier for steroid hormones

Steroid hormones became increasingly interesting as active pharmaceutical ingredients for the treatment of endocrine disorders. However, medical applications of many steroidal drugs are inhibited by their very low aqueous solubilities giving rise to low bioavailabilities. Therefore, the prioritized oral administration of steroidal drugs remains problematic. Cyclodextrins are promising candidates for the development of drug delivery systems for oral route applications, since they solubilize hydrophobic steroids and increase their rate of transport in aqueous environments. In this study, the synthesis and characterization of polymeric β-cyclodextrin derivates is described, which result from the attachment of a hydrophilic β-CD-thioether to hyaluronic acid. Host-guest complexes of the synthesized β-cyclodextrin hyaluronic acid conjugates were formed with two poorly soluble model steroids (β-estradiol, dexamethasone) and compared to monomeric β-cyclodextrin derivates regarding solubilization and complexation efficiency. The β-cyclodextrin-drug (host-guest) complexes were evaluated in vitro for their suitability (cytotoxicity and transport rate) as intestinal drug carriers for steroid hormones. In case of β-estradiol, higher solubilities could be achieved by complexation with both synthesized β-cyclodextrin derivates, leading to significantly higher intestinal transport rates in vitro. However, this success could not be shown for dexamethasone, which namely solubilized better, but could not enhance the transport rate significantly. Thus, this study demonstrates the biocompatibility of the synthesized and characterized β-cyclodextrin derivates and shows their potential as new candidate for intestinal drug carrier for steroid hormones like β-estradiol

Influence of Physicochemical Characteristics and Stability of Gold and Silver Nanoparticles on Biological Effects and Translocation across an Intestinal Barrier—A Case Study from In Vitro to In Silico

A better understanding of their interaction with cell-based tissue is a fundamental prerequisite towards the safe production and application of engineered nanomaterials. Quantitative experimental data on the correlation between physicochemical characteristics and the interaction and transport of engineered nanomaterials across biological barriers, in particular, is still scarce, thus hampering the development of effective predictive non-testing strategies. Against this background, the presented study investigated the translocation of gold and silver nanoparticles across the gastrointestinal barrier along with related biological effects using an in vitro 3D-triple co-culture cell model. Standardized in vitro assays and quantitative polymerase chain reaction showed no significant influence of the applied nanoparticles on both cell viability and generation of reactive oxygen species. Transmission electron microscopy indicated an intact cell barrier during the translocation study. Single particle ICP-MS revealed a time-dependent increase of translocated nanoparticles independent of their size, shape, surface charge, and stability in cell culture medium. This quantitative data provided the experimental basis for the successful mathematical description of the nanoparticle transport kinetics using a non-linear mixed effects modeling approach. The results of this study may serve as a basis for the development of predictive tools for improved risk assessment of engineered nanomaterials in the future

Lignite planning, structural change and coal phase-out in Germany

Lignite planning in the Rhineland, central German and Lusatian coalfields is a core spatial development planning task at the federal state and regional levels. The Lignite Planning Information Group and Initiative (Informations- und Initiativkreis Braunkohlenplanung) was founded in 1994 at the ARL - Academy for Territorial Development in the Leibniz Association to provide a platform for expert discussion. Starting from experiences with the Rhineland and the structural upheavals in the new federal states in the early 1990s, it has since continuously addressed new technical and legal requirements involving resettlement, water balance issues, environmental assessments, the energy transition and the common good. Against the backdrop of rapid change and geopolitical events, the combination of structural change and the politically initiated phase-out of lignite-based power generation in a time frame between 'ideally 2030' and no later than the end of 2038 constitutes a challenge that will have to be met by the active players from the perspective of both federal state and regional planning and of regional development. This position paper takes stock of the situation across federal states and across coalfields and describes the required actions for lignite planning as a basis for reaching conclusions about a process with far-reaching national consequences. The various aspects of this process are subject to constant change and call for proactive strategies to exploit opportunities, tap potential, and effectively identify and avoid negative developments

A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the <i>LPA</i> and 1 SNP in the <i>APOE</i> gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the <i>LPA</i> , 1 in the <i>APOE</i> gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio = 1.73, <i>P</i> = 3.35 × 10 <sup>-30</sup> ). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the <i>APOE2</i> -determining allele of rs7412 to be significantly associated with Lp(a) concentrations ( <i>P</i> = 3.47 × 10 <sup>-10</sup> ). Each <i>APOE2</i> allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the population's mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the <i>TLR2</i> gene with Lp(a) ( <i>P</i> = 3.4 × 10 <sup>-4</sup> ). In summary, we identified a large number of independent SNPs in the <i>LPA</i> gene region, as well as the <i>APOE2</i> allele, to be significantly associated with Lp(a) concentrations

A genome-wide association meta-analysis on apolipoprotein A-IV concentrations.

Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 (-)  (44)), rs5104 in APOA4 (P = 1.79 × 10(-)(24)) and rs4241819 in KLKB1 (P = 5.6 × 10(-)(14)). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 (-)  (07)). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10(-)(05)). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations

Plasma Concentrations of Afamin Are Associated With Prevalent and Incident Type 2 Diabetes: A Pooled Analysis in More Than 20,000 Individuals.

The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). Individual-level baseline ( javax.xml.bind.JAXBElement@f254025 = 20,136) and follow-up data ( javax.xml.bind.JAXBElement@30ded076 = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12-1.26], javax.xml.bind.JAXBElement@300447f6 = 5.96 × 10 javax.xml.bind.JAXBElement@7b7e80f0 ). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089-0.132], javax.xml.bind.JAXBElement@5e7fd3d2 = 1.37 × 10 javax.xml.bind.JAXBElement@18e4f50b ). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], javax.xml.bind.JAXBElement@a4d3a16 = 3.53 × 10 javax.xml.bind.JAXBElement@53b52af ) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes