Two Subtle Amino Acid Changes in a Transaminase Substantially Enhance or Invert Enantiopreference in Cascade Syntheses

Amine transaminases (ATAs) are powerful enzymes for the stereospecific production of chiral amines. However, the synthesis of amines incorporating more than one stereocenter is still a challenge. We developed a cascade synthesis to access optically active 3‐alkyl‐substituted chiral amines by combining two asymmetric synthesis steps catalyzed by an enoate reductase and ATAs. The ATA wild type from Vibrio fluvialis showed only modest enantioselectivity (14 % de) in the amination of (S)‐3‐methylcyclohexanone, the product of the enoate‐reductase‐catalyzed reaction step. However, by protein engineering we created two variants with substantially improved diastereoselectivities: variant Leu56Val exhibited a higher R selectivity (66 % de) whereas the Leu56Ile substitution caused a switch in enantiopreference to furnish the S‐configured diastereomer (70 % de). Addition of 30 % DMSO further improved the selectivity and facilitated the synthesis of (1R,3S)‐1‐amino‐3‐methylcyclohexane with 89 % de at 87 % conversion.     

Pima Indian males have lower beta-adrenergic sensitivity than Caucasian males

The sympathetic nervous system controls cardiovascular homeostasis and regulates energy metabolism. Pima Indians, a population with a low prevalence of hypertension and a high prevalence of obesity, have low sympathetic nervous activity, compared with Caucasians. Preliminary findings suggest that they may also have a low beta-adrenergic sensitivity. We studied beta-adrenergic sensitivity in 87 nondiabetic normotensive individuals [52 Pima Indians (35 males/17 females) and 35 Caucasians (24 males/11 females)], matched for age and body weight. Chronotropic sensitivity to beta-adrenergic stimulation was assessed by the dose of isoproterenol necessary to increase heart rate by 25 beats per minute [chronotropic dose-25 (CD25)]. Despite a similar basal heart rate and arterial blood pressure, Pimas tended to have lower beta-adrenergic sensitivity than Caucasians (CD25 = 2.37 +/- 2.27 vs. 1.57 +/- 1.38 microg, P = 0.07; mean +/- SD). This difference was significant in males (CD25 = 3.03 +/- 2.39 vs. 1.85 +/- 1.56 microg, P = 0.02) but not in females (CD25 = 1.01 +/- 1.17 vs. 0.96 +/- 0.61 microg, P = 0.99). In males only, CD25 was positively correlated to percent body fat (r = 0.36, P < 0.01). After adjustment for percent body fat, beta-adrenergic sensitivity was still significantly lower in Pima than in Caucasian males (CD25 = 3.44 +/- 2.24 vs. 2.57 +/- 1.60 microg, P = 0.05). In conclusion, our data suggest that increased adiposity is accompanied by decreased beta-adrenergic sensitivity in males only. However, at each level of adiposity, Pima Indian males have lower beta-adrenergic sensitivity than Caucasian males. In combination with a low sympathetic nervous system activity, a reduced beta-adrenergic sensitivity may contribute to the low prevalence of hypertension and the high prevalence of obesity observed in Pima Indians.     

Carotenoids and chlorophylls in processed xanthophyll-rich food

Processing of food modifies nutrient contents and food matrices. The present analyses provide information about the effects of heat steam sterilization (HSS), high pressure processing (HPP) and common household cooking on the stability of carotenoids and chlorophylls in spinach, parsley, dill and kale. For HSS, samples were heated in an autoclave for 5, 10, 15 and 20 min at 121 °C. Additionally, one sample was treated via HPP at 200, 400 and 600 MPa for 5, 10 and 40 min at room temperature. Carotenoid and chlorophyll contents were determined by reversed-phase HPLC. Lutein was the most abundant carotenoid in all samples. Furthermore, violaxanthin, zeaxanthin, β-carotene, chlorophylls a and b were quantified. Thermal treatment via HSS led to a significant decline of contents of lutein, chlorophylls a and b. HPP did not reduce the amounts of xanthophylls and chlorophylls. Conclusively, HPP seems to be a good alternative to HSS for the preservation of xanthophyll-rich food.     

Design,Synthesis and Biological Evaluation of Highly Potent Simplified Archazolids

The archazolids are potent antiproliferative compounds that have recently emerged as a novel class of promising anticancer agents. Their complex macrolide structures and scarce natural supply make the development of more readily available analogues highly important. Herein, we report the design, synthesis and biological evaluation of four simplified and partially saturated archazolid derivatives. We also reveal important structure-activity relationship data as well as insights into the pharmacophore of these complex polyketides.     

Herausforderungen und Chancen für die Arbeit der Akademie für Ethik in der Medizin angesichts der COVID-19-Pandemie

Ethik in der Medizin -     

Evaluating semantometrics from computer science publications

Scientometrics - Identification of important works and assessment of importance of publications in vast scientific corpora are challenging yet common tasks subjected by many research projects....     

Thermal,fire, and mechanical properties of solvent‐free processed BN/boehmite‐filled prepregs

Within the scope of this research, platelet‐shaped hexagonal Boron Nitride (h‐BN) with a size of 2 and 12 μm, and oval‐shaped Boehmite (BT) with a size of 2 μm were incorporated in a glass fiber‐reinforced epoxy novolac matrix cured with a diamine‐based hardener. The effects of the platelet size (BN 2 and 12 μm) and filler nature (BT vs. BN) were correlated with the final thermal and fire‐related properties. The incorporation of the fillers shows that not only the thermal conductivity (σ) was increased from approximately 0.2 up to 1.04 W/mK (through‐plane) but also the flame retardancy was improved by using a hybrid combination. The time to ignition (t_ig) was increased by 48 s and the FIGRA value was decreased from 6.5 to 3.3 indicating a much lower fire hazard for the material. scanning electron microscopic micrographs of the laminate cross sections show that the fillers are distributed and oriented randomly in the fiber‐reinforced matrix, and also highlight the fiber wetting. Furthermore, the results show that the resulting 3D filler network and infiltration of the intratow regions is strongly dependent on lateral filler size and filler combination. With increasing the filler aspect ratio, the effect on thermal properties and filtration is more evident. Moreover, the hybrid combination of BN and Boehmite fillers has a strong effect on the network formation during processing, resulting in enhanced thermal and mechanical properties. A synergy was observed when using BN 12 μm in combination with Boehmite 2 μm as the larger platelets tend to assemble themselves in the intertow region (resin‐rich region) and the smaller particles infiltrate into the intratow regions. This leads to a formation of a thermal pathway throughout the glass fabric barrier. Considering the cost factor, the through‐plane (z‐direction) heat dissipation and the flame retardancy can be tailored by optimizing the size, aspect ratio/geometry, and nature of the fillers. POLYM. ENG. SCI., 59:1840–1852, 2019. © 2019 The Authors. Polymer Engineering & Science published by Wiley Periodicals, Inc. on behalf of Society of Plastics Engineers.     

Novel Old Yellow Enzyme Subclasses

Many drug candidate molecules contain at least one chiral centre, and consequently, the development of biocatalytic strategies to complement existing metal- and organocatalytic approaches is of high interest. However, time is a critical factor in chemical process development, and thus, the introduction of biocatalytic steps, even if more suitable, is often prevented by the limited availability of off-the-shelf enzyme libraries. To expand the biocatalytic toolbox with additional ene reductases, we screened 19 bacterial strains for double bond reduction activity by using the model substrates cyclohexanone and carvone. Overall, we identified 47 genes coding for putative ene reductases. Remarkably, bioinformatic analysis of all genes and the biochemical characterization of four representative novel ene reductases led us to propose the existence of two new Old Yellow Enzyme subclasses, which we named OYE class III and class IV. Our results demonstrate that although, on a DNA level, each new OYE subclass features a distinct combination of sequence motifs previously known from the classical and the thermophilic-like group, their substrate scope more closely resembles the latter subclass.     

uSafe: A privacy-aware and participative mobile application for citizen safety in urban environments

Recent mobile applications empower citizens to monitor noise pollution or report on features of their urban environment. One important aspect of urban life has, however, not been sufficiently addressed, namely the safety of citizens. We present a privacy-aware application called uSafe, in which users indicate how safe they feel in geographical locations. These feelings are then consolidated into summary maps accessible by other users and urban planners. We evaluate our concept with a questionnaire-based study involving 183 participants. The results confirm the utility of uSafe and show that privacy protection is a decisive factor in their decision to contribute to it.