Expanding the Toolbox of R-Selective Amine Transaminases by Identification and Characterization of New Members

Amine transaminases (ATAs) are used to synthesize enantiomerically pure amines, which are building blocks for pharmaceuticals and agrochemicals. R-selective ATAs belong to the fold type IV PLP-dependent enzymes, and different sequence-, structure- and substrate scope-based features have been identified in the past decade. However, our knowledge is still restricted due to the limited number of characterized (R)-ATAs, with additional bias towards fungal origin. We aimed to expand the toolbox of (R)-ATAs and contribute to the understanding of this enzyme subfamily. We identified and characterized four new (R)-ATAs. The ATA from Exophiala sideris contains a motif characteristic for d -ATAs, which was previously believed to be a disqualifying factor for (R)-ATA activity. The crystal structure of the ATA from Shinella is the first from a Gram-negative bacterium. The ATAs from Pseudonocardia acaciae and Tetrasphaera japonica are the first characterized (R)-ATAs with a shortened/missing N-terminal helix. The active-site charges vary significantly between the new and known ATAs, correlating with their diverging substrate scope.     

Cross-Sectional Associations of Food Consumption with Plasma Fatty Acid Composition and Estimated Desaturase Activities in Finnish Children

Plasma fatty acid (FA) composition is known to be an indicator of dietary fat quality, but the associations of other dietary factors with plasma FA composition remain unknown in children. We investigated the cross-sectional associations of food consumption with the proportions of FA and estimated desaturase activities in plasma cholesteryl esters (CE) and phospholipids (PL) among children. The subjects were a population sample of 423 children aged 6–8 years examined at baseline of The Physical Activity and Nutrition in Children (PANIC) Study. We assessed food consumption by food records and plasma FA composition by gas chromatography. We used linear regression models adjusted for age, sex, physical activity and total energy intake to analyze the associations. A higher consumption of vegetable oil-based margarine (fat 60–80 %) was associated with a higher proportion of linoleic and α-linolenic acids in plasma CE and PL. A higher consumption of high-fiber grain products was related to a lower proportion of oleic acid in CE and PL. The consumption of candy was directly associated with the proportion of palmitoleic and oleic acid in plasma CE. The consumption of vegetable oil-based margarine was inversely associated with estimated stearoyl-CoA-desaturase activity in plasma CE and PL and the consumption of candy was directly related to it in plasma CE. The results of our study suggest that plasma FA composition is not only a biomarker for dietary fat quality but also reflects the consumption of high-fiber grain products and foods high in sugar among children.     

Enhancing the efficiency of alternating current driven organic light-emitting devices by optimizing the operation frequency

We report efficient and bright organic light-emitting devices operated by capacitive energy coupling. In this approach, the organic layers are enclosed between sputter-deposited hafnium dioxide layers to prevent charge carrier injection. When a sinusoidal voltage signal is applied to the electrodes, the devices emit bright green light whereas no detectable emission is generated upon application of a constant voltage. The efficiency of the process depends heavily on the frequency of the applied voltage signal. By optimizing the driving scheme, a record luminous efficacy for AC driven OLEDs of 2.7 lm/W at 500 cd/m² is achieved.     

Interplay between Endothelin and Erythropoietin in Astroglia: The Role in Protection against Hypoxia

We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48–72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested.     

中央通过《关于设立知识产权法院的方案》

6月6日，中央全面深化改革领导小组第三次会议召开，会议审议通过了“关于设立知识产权法院的方案》等方案。     

Etablierung einer nationalen Rohstoffbuchhaltung und dafür notwendige Informationen und Informationsgüte

The influence of anthropogenic processes on global material flow systems increasingly dominates the influence of natural processes. In this context, the provision of detailed knowledge on material flow systems is relevant for decision makers in resource policy. This information can be provided in the form of one-year material balances or, if repeated over a period of consecutive years, in the form of national resource budgets. In national resource budgets, all relevant flows of a material through a national economy are balanced and displayed in neatly arranged diagrams. By updating these material balances over a series of years, the development of material stocks can be estimated. Upcoming challenges both regarding supply and disposal of materials can be identified. Comprehensive balances are useful for decision makers in resource policy and, moreover, as an information basis for future exploitation of anthropogenic resources. However, both availability of data and possibilities for assessing the reliability of data are very limited. In this work, a methodology for investigating and evaluating the information basis of national resource budgets is presented. The methodology includes procedures for systematic characterization of resource budget data and formal procedures for evaluating their reliability. From a scientific perspective, the methodology contributes to understanding material flow systems better. It also enables implementing procedures towards national resource budgets in an administrative context.     

Assessment of Bioaerosol Generation and Sampling Efficiency Based on Pantoea agglomerans

This study was conducted to evaluate the effect of aerosol generation, relative humidity, and method of sampling on the culturability of the vegetative bacteria Pantoea agglomerans (P. agglomerans) formerly known as Erwinia herbicola. This research has relevance both for the use of this organism as a biowarfare simulant and for bioaerosol exposure assessment and public health. The culturability of P. agglomerans was tested using a test chamber against two generating systems (Collison and Bubble nebulizers), two sampling systems (the all-glass impinger (AGI-30), and the BioSampler), three collection media (water, TSB, and PBS) and across a range of humidities. Results indicated that the Bubble nebulizer was 15% more efficient in generating viable P. agglomerans counts (p ≤ 0.05). No difference was observed in overall efficiency between sampling methods (p > 0.05). However, as a collection media, PBS was observed to yield higher (p ≤ 0.01) viable counts compared to sterile deionized water. Relative humidity was found to strongly influence airborne P. agglomerans culturability. Culturable P. agglomerans was below the limit of detection for RH < 15% and then increased in a log-linear fashion to humidities of 75%. This research will help identify optimal means for evaluation of environmentally sensitive airborne bacteria for purposes of exposure assessment and public health as well as homeland security.     

The crystal structure of human procathepsin K

Cathepsin K is a cysteine protease present in human osteoclasts that plays an important role in bone resorption. Cathepsin K is synthesized as an inactive proenzyme and activated under conditions of low pH. Autoproteolytic processing of the N-terminal 99 amino acid propeptide produces the active, mature form of cathepsin K. It is presumed that the activation of procathepsin K in vivo occurs in the bone resorption pit, which has a low-pH environment. We have determined the structure of human procathepsin K at 2.8 A resolution. The structure of the mature enzyme domain within procathepsin K is virtually identical to that of mature cathepsin K. The fold of the propeptide of procathepsin K is similar to that observed in procathepsins B and L despite differences in length and sequence. A portion of the propeptide occupies the active site cleft of cathepsin K. Hydrophobic interactions, salt bridges, and hydrogen-bonding interactions are observed in the structure of the propeptide and between the propeptide and the mature enzyme of procathepsin K. These interactions suggest an explanation for the stability of the proenzyme. The structure of procathepsin K contributes to an understanding of the molecular basis of inhibition by the propeptide portion of the molecule and activation of this important member of the cysteine protease family.