The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology

Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer’s disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression in AD, trigger the aggregation and modulate the cellular uptake of amyloid beta (Aβ). Utilizing our previously established syndecan-overexpressing cellular assays, we now explore how the interplay of ApoEs with syndecans contributes to key events, namely uptake and aggregation, in Aβ pathology. The interaction of ApoEs with syndecans indicates isoform-specific characteristics arising beyond the frequently studied ApoE–heparan sulfate interactions. Syndecans, and among them the neuronal syndecan-3, increased the cellular uptake of ApoEs, especially ApoE2 and ApoE3, while ApoEs exerted opposing effects on syndecan-3-mediated Aβ uptake and aggregation. ApoE2 increased the cellular internalization of monomeric Aβ, hence preventing its extracellular aggregation, while ApoE4 decreased it, thus helping the buildup of extracellular plaques. The contrary effects of ApoE2 and ApoE4 remained once Aβ aggregated: while ApoE2 reduced the uptake of Aβ aggregates, ApoE4 facilitated it. Fibrillation studies also revealed ApoE4′s tendency to form fibrillar aggregates. Our results uncover yet unknown details of ApoE cellular biology and deepen our molecular understanding of the ApoE-dependent mechanism of Aβ pathology.     

Utilisation of bipolar electrodialysis for recovery of galacturonic acid

Galacturonic acid is an acidifying agent and can be utilized in the food industry. It can be recovered from the hydrolysate of various pectins by electrodialysis. In this work bipolar electrodialysis was applied to separated and concentrated galacturonic acid and finally a crystallised product was obtained.     

Heterogeneous Asymmetric Hydrogenation of N-Heterocyclic Compounds: Hydrogenation of Tetrahydroisoquinoline Derivatives

The preparation and application of heterogeneous chiral catalysts are described. Heterogeneous Pd, Ir and Ru catalysts were tested in the enantioselective hydrogenations of N-heterocyclic compounds, namely 6,7-dimethoxy-3,4-dihydroisoquinoline and 1-methylene-2-ethoxycarbonyl-6,7-dimetoxy-3,4-dihydroisoquinoline in the presence of optically pure cinchonidine, (S,S)- and (R,R)-Ts-DPEN ligands. Cinchonidine-modified metal catalysts exhibited low ee, whereas catalysts stabilized by triphenylphosphane and modified by (S,S)-Ts-DPEN afforded promising ee values (70–80 %). Immobilized Ru(II)-aminophosphane complexes were found to be active in these hydrogenations producing the corresponding tetrahydroisoquinoline derivatives in high optical purities (up to 97 %). The latter catalysts were characterized by infrared spectroscopy, solid-state MAS NMR spectroscopy and elemental analysis. Recycling of these catalysts showed constant or increasing activities in racemic hydrogenation, whereas the presence of the chiral ligands led to leaching of the active species in the liquid phase.     

Natural Molecules and Neuroprotection: Kynurenic Acid,Pantethine and α-Lipoic Acid

The incidence of neurodegenerative diseases has increased greatly worldwide due to the rise in life expectancy. In spite of notable development in the understanding of these disorders, there has been limited success in the development of neuroprotective agents that can slow the progression of the disease and prevent neuronal death. Some natural products and molecules are very promising neuroprotective agents because of their structural diversity and wide variety of biological activities. In addition to their neuroprotective effect, they are known for their antioxidant, anti-inflammatory and antiapoptotic effects and often serve as a starting point for drug discovery. In this review, the following natural molecules are discussed: firstly, kynurenic acid, the main neuroprotective agent formed via the kynurenine pathway of tryptophan metabolism, as it is known mainly for its role in glutamate excitotoxicity, secondly, the dietary supplement pantethine, that is many sided, well tolerated and safe, and the third molecule, α-lipoic acid is a universal antioxidant. As a conclusion, because of their beneficial properties, these molecules are potential candidates for neuroprotective therapies suitable in managing neurodegenerative diseases.     

Effect of radon measurement methods on dose estimation

Different radon measurement methods were applied in the old and new buildings of the Turkish bath of Eger, Hungary, in order to elaborate a radon measurement protocol. Besides, measurements were also made concerning the radon and thoron short-lived decay products, gamma dose from external sources and water radon. The most accurate results for dose estimation were provided by the application of personal radon meters. Estimated annual effective doses from radon and its short-lived decay products in the old and new buildings, using 0.2 and 0.1 measured equilibrium factors, were 0.83 and 0.17 mSv, respectively. The effective dose from thoron short-lived decay products was only 5 % of these values. The respective external gamma radiation effective doses were 0.19 and 0.12 mSv y(-1). Effective dose from the consumption of tap water containing radon was 0.05 mSv y(-1), while in the case of spring water, it was 0.14 mSv y(-1).     

Stable water-soluble iron oxide nanoparticles using Tiron

Success in biological and nanomaterial applications that rely on magnetic iron oxide nanoparticles (IONPs) often depends on monodispersity, size, and aqueous stability of the synthesized particles. Here we report a simple and efficient strategy to prepare monodisperse, ultrasmall, water dispersible superparamagnetic IONPs. Monodisperse IONPs are initially synthesized in organic solvents using oleic acid as a dispersant. The subsequent ligand exchange of oleic acid for dopamine and Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid disodium salt) allows for superior colloidal stability in aqueous media. Zeta potential measurements confirm the stability of the nanoparticles upon redispersal in water or biologically relevant buffers. The synthesized particles also preserve their general shape, size, and crystallinity after ligand exchange as evidenced by TEM and SAED measurements. Magnetic properties are also maintained after the ligand exchange as verified by magnetometry and magnetic force microscopy (MFM). An analysis of potential issues regarding this and other prior ligand exchanges is also highlighted, which may aid others in future investigations.     

Degradation of ochratoxin A and other mycotoxins by Rhizopus isolates

Several filamentous fungi representing the genera Rhizopus and Mucor were examined for their ability to degrade ochratoxin A (OTA), aflatoxin B1, zearalenone and patulin in a liquid medium. While none of the isolates exhibited aflatoxin degrading activity, ochratoxin A, zearalenone and patulin were decomposed by several isolates. Ochratoxin A was successfully degraded by Rhizopus stolonifer, R. microsporus, R. homothallicus and two R. oryzae isolates, and by four unidentified Rhizopus isolates. Kinetics of ochratoxin A detoxification of selected Rhizopus isolates was also examined. Rhizopus isolates were able to degrade more than 95% of ochratoxin A within 16 days. A R. stolonifer isolate could also effectively decompose ochratoxin A on moistened wheat. Further studies are in progress to identify the enzymes and genes responsible for ochratoxin detoxification and to transfer these genes to other Rhizopus isolates or microbes which could be used safely for decontamination of cereal products.     

Determination of tetracyclines in pig and other meat samples using liquid chromatography coupled with diode array and tandem mass spectrometric detectors

Two high performance liquid chromatographic methods (HPLC–DAD and LC–MS/MS) were developed to analyze tetracycline (TC) residues in pig meat (pork) samples. The method involved a sample preparation using a solid–liquid extraction (SLE) by McIlvaine buffer, followed by a solid-phase extraction (SPE) clean-up using Strata-XL cartridges. The developed sample clean-up resulted in a selective chromatogram in the HPLC–DAD separation and a reduced matrix effect (ME) in LC–MS/MS analysis. Moreover, HPLC columns packed with core–shell particles were tested for separation, which further enhanced the sensitivity and the selectivity of determinations. The validation of the methods for pig samples was carried out according to European Union 2002/657/EC decision. In addition, validation was also performed for bovine, chicken, and turkey meat samples using HPLC–DAD method. The performance characteristics of determinations were evaluated with both spiked and incurred samples, and were systematically compared. LC–MS/MS technique was found to be more accurate for spiked samples; however, HPLC–DAD method resulted in more reliable concentrations for incurred samples.