Determination of the sources of indoor PM2.5 in Amsterdam and Helsinki

Daily PM2.5 samples were repeatedly collected (1-8 times) in the homes of elderly nonsmoking individuals with coronary heart disease in Amsterdam, The Netherlands (33 individuals) and Helsinki, Finland (44 individuals). Sources of indoor PM2.5 were evaluated using a two-way multilinear engine model. Because the indoor elemental data lacked a traffic marker, separation of traffic related PM was attempted by combining the indoor data with fixed site outdoor data that also contained NO. Six outdoor sources, including long-range transport (LRT), urban mixture, oil combustion, traffic, sea-salt, and soil were identified, and three indoor sources were resolved: resuspension, potassium-rich and copper-rich sources. The average contribution of the indoor factors was 6% (1.1 microg m(-3)) and 22% (2.4 microg m(-3)) in Amsterdam and Helsinki, respectively. The highest longitudinal correlations between source-specific outdoor and indoor PM2.5 concentrations were found for LRT and urban mixture; the median R was above 0.6 for most sources. The longitudinal correlations were lower in Helsinki than in Amsterdam. Indoor-generated PM2.5 was not related to ambient concentrations. We conclude that using outdoor and indoor data together improved the source apportionment of indoor PM2.5. The results support the use of fixed site outdoor measurements in epidemiological time-series studies on outdoor air pollution.     

In vitro kinetic analysis of carbohydrate and aromatic amino acid metabolism of different members of the human colon

The carbohydrate and aromatic amino acid metabolism of several species related to the human colon was investigated into more detail. Therefore, in vitro fermentations were performed, with different carbohydrate sources, during which several aromatic amino acids were added to the fermentation medium. Shifts in end-product formation in response to the available nutrients were observed for all strains tested. The major part of amino acid degradation occurred after depletion of the carbohydrates. Moreover, it was shown that Bifidobacterium strains are capable of degrading aromatic amino acids in the absence of carbohydrates. The excretion of certain intermediates of the aromatic amino acid metabolism was observed for a strain of Clostridium clostridioforme, after which they were metabolized again during a later stage of fermentation. This implies that cross-feeding on degradation products of aromatic amino acids, albeit within the same species, can occur in the human colon.     

Method for determining liquid water flow in wood during drying using a fluorescent dye tracer

A novel procedure for the evaluation of liquid water flow during the drying of wood is described. The method is based on the movement of a fluorescent dye solution in liquid water. The addition of the dye solution produced a clear trace inside the wood, the length and direction of which were directly related to the flow of liquid water. A comparison of the results obtained with image analysis using UV illumination and measurement of the reflectance spectrum of wood showed that image analysis is appropriate and accurate enough for the determination of the trace of the dye solution. The trace of the dye solution can be determined from the images of the cross sectional samples of wood in all three main directions.     

Polyphenol and vitamin C contents in European commercial blackcurrant juice products

Vitamin C and polyphenol contents (anthocyanins, proanthocyanidins, phenolic acids and flavonols) were analysed in commercial blackcurrant juice products purchased from various European countries (Finland, Poland, Germany, United Kingdom) using HPLC methods. The aim was to study variation between countries, as well as evaluate the intake of polyphenols from commercial juices. There was significant variation in the contents of polyphenols and vitamin C between countries. Expressed as the ready-to-drink beverages, German, Polish, Finnish and British products averaged anthocyanin contents of 38, 32, 12 and 7.5 mg/2.5 dl, proanthocyanidin contents of 27, 24, 10 and 1.2 mg/2.5 dl, flavonol contents of 16, 15, 5.2 & 1.9 mg/2.5 dl and phenolic acid contents of 12, 8.9, 3.7 and 1.5 mg/2.5 dl, respectively. The mean vitamin C content was highest in British (70 mg/2.5 dl) and lowest in Finnish products (15 mg/2.5 dl). The intake of polyphenols from German and Polish ready-to-drink beverages was clearly higher than that from Finnish, and especially, British beverages.     

Glycolaldehyde‐modified β‐lactoglobulin AGEs are unable to stimulate inflammatory signaling pathways in RAGE‐expressing human cell lines

Scope: Advanced glycation endproducts (AGEs) are suspected to stimulate inflammatory signaling pathways in target tissues via activation of the receptor for AGEs. Endotoxins are generally recognized as potential contamination of AGE preparations and stimulate biological actions that are very similar as or identical to those induced by AGEs. Methods and results: In our study, we used glycolaldehyde‐modified β‐lactoglobulin preparations as model AGEs and employed two methods to remove endotoxin using either affinity columns or extraction with Triton X‐114 (TX‐114). Affinity column‐purified AGEs retained their ability to stimulate inflammatory signaling as measured by mRNA expression of inflammatory cytokines in the human lung epithelial cell line Beas2b. However, glycolaldehyde‐modified AGEs purified by extraction with TX‐114 did not show any stimulation of mRNA expression of inflammatory cytokines. The presence of a cell stimulating endotoxin‐like activity was demonstrated in the detergent phase after extraction with TX‐114, thus indicating that not AGEs but a lipophilic contamination was responsible for the stimulation of inflammatory signaling. Conclusion: Our results demonstrate that glycolaldehyde‐modified AGEs are unable to induce inflammatory signaling in receptor for AGE‐expressing cells. The observed cell‐activating activity can be ascribed to an endotoxin‐like lipophilic contamination present in AGE preparations and affinity column purification was insufficient to remove this contamination.     

Novel BQCA- and TBPB-Derived M1 Receptor Hybrid Ligands: Orthosteric Carbachol Differentially Regulates Partial Agonism

Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M₁-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M₁ positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy.     

Efficient Enzymatic Cyclization of Disulfide-Rich Peptides by Using Peptide Ligases

Disulfide-rich macrocyclic peptides—cyclotides, for example—represent a promising class of molecules with potential therapeutic use. Despite their potential their efficient synthesis at large scale still represents a major challenge. Here we report new chemoenzymatic strategies using peptide ligase variants—inter alia, omniligase-1—for the efficient and scalable one-pot cyclization and folding of the native cyclotides MCoTI-II, kalata B1 and variants thereof, as well as of the θ-defensin RTD-1. The synthesis of the kB1 variant T20K was successfully demonstrated at multi-gram scale. The existence of several ligation sites for each macrocycle makes this approach highly flexible and facilitates both the larger-scale manufacture and the engineering of bioactive, grafted cyclotide variants, therefore clearly offering a valuable and powerful extension of the existing toolbox of enzymes for peptide head-to-tail cyclization.     

搭载人类自体干细胞的纤维支架及其在软组织再生中的应用

文章介绍了搭载人类自体干细胞的纤维支架技术及其在软组织再生中的应用优势。选用藻酸盐材料结合人体干细胞搭载关键技术制成的纤维支架,同时具有促进血管再生和触发成脂分化的能力。