Chemoenzymatische Synthese von N6-Carbamoyl-D-4-thialysin und N7-Carbamoyl-D-homo-5-thialysin

Chemoenzymatical Synthesis of N⁶-Carbamoyl-D-4-thialysine and N⁷-Carbamoyl-D-homo-5-thialysine The combination of classical chemical and enzymatical methods opens a way to highly functionalized chiral molecules like N⁶-carbamoyl-D-4-thialysine ( 5 ) or N⁷-carbamoyl-D-homo-5-thialysine ( 6 ). The biotransformation of the corresponding hydantoines with Agrobacterium radiobacter is creating the desired D chirality.     

Identification,Isolation, and Characterization of Melanocyte Precursor Cells in the Human Limbal Stroma

Given their vital role in the homeostasis of the limbal stem cell niche, limbal melanocytes have emerged as promising candidates for tissue engineering applications. This study aimed to isolate and characterize a population of melanocyte precursors in the limbal stroma, compared with melanocytes originating from the limbal epithelium, using magnetic-activated cell sorting (MACS) with positive (CD117/c-Kit microbeads) or negative (CD326/EpCAM or anti-fibroblast microbeads) selection approaches. Both approaches enabled fast and easy isolation and cultivation of pure limbal epithelial and stromal melanocyte populations, which differed in phenotype and gene expression, but exhibited similar functional properties regarding proliferative potential, pigmentation, and support of clonal growth of limbal epithelial stem/progenitor cells (LEPCs). In both melanocyte populations, limbus-specific matrix (laminin 511-E8) and soluble factors (LEPC-derived conditioned medium) stimulated melanocyte adhesion, dendrite formation, melanogenesis, and expression of genes involved in UV protection and immune regulation. The findings provided not only a novel protocol for the enrichment of pure melanocyte populations from limbal tissue applying easy-to-use MACS technology, but also identified a population of stromal melanocyte precursors, which may serve as a reservoir for the replacement of damaged epithelial melanocytes and an alternative resource for tissue engineering applications.     

SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.     

Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.     

Influence of priming time and primer’s concentrations on bovine enamel bond strengths

This study investigated the effects of priming time (5, 30 or 60?s), 10-MDP (10-methacryloyloxydecyl dihydrogen phosphate)-containing primer’s concentrations (0.5, 1, 5, 10 and 20% (w/w)) and two neutral primers (5% (w/w) of 10-MDP-Na or EDTA-2Na) on bovine enamel microtensile bond strength (μTBS) using a novel prime-and-rinse approach. After priming, the enamel surfaces were thoroughly water-sprayed and dried before resin composite was placed. There was a significant influence of primer’s concentrations and priming time on bovine enamel μTBS when 10-MDP-containing primers were used (p?<?0.001), revealing the optimal priming time (30?s) and the best combination (priming with 20% of 10-MDP for 30?s). The prime-and-rinse approach might be an innovative supplement to contemporary dental adhesive procedures. The neutral primer (5% of 10-MDP-Na) produced moderate enamel μTBS on highly polished enamel surfaces, while another neutral primer (5% of EDTA-2Na) failed, suggesting that chemical bonding of 10-MDP to enamel hydroxyapatite crystallites could yield detectable bond strengths on smooth enamel surfaces.     

Cobalt-Containing Hyperbranched Poly(silylenearylene)s

A group of hyperbranched poly(silylenearylene)s are synthesized by homopolycyclotrimerizations of A₂-type silylenediynes. The polymers can be readily metallized by complexations of their periphery triple bonds with cobalt octacarbonyls Co₂(CO)₈. Pyrolysis of these organometallic polymers gives magnetic ceramics in good yields. Analyses by SEM, TEM, XPS, EDX, and XRD demonstrate that the ceramics comprise ferromagnetic Co and paramagnetic Co₂Si nanocrystallites wrapped by carboneous shell. The ceramics show high magnetic susceptibilities (M _s up to ~50 emu/g) and near-zero coercivity (H _c down to ~0.14 kOe), suggesting that they are good soft magnetic materials with low hysteresis loss. This article was to be included in the March issue of Volume 19, which was dedicated to Professor Takakazu Yamamoto. The journal editors sincerely apologize for the omission and delay in publication for which the authors and the guest editor bare no responsibility. M. Zeldin and A. S. Abd-El-Aziz, Editors.     

Processing of the quench detection signals in W7-X

The Wendelstein 7-X (W7-X) project uses superconductive coils for generation of the magnetic field to keep the plasma. One of the important safety systems is the protection against quench events. The quench detection system of W7-X protects the superconducting coils, the superconducting bus bar sections and the high temperature superconductor of the current leads against the damage because of a quench and against the high stress by a fast discharge of the magnet system.Therefore, the present design of the quench detection system (QDS) uses a two-stage safety concept for discharging the magnetic system. This paper describes the present design of the system assembly from the quench detection unit (QDU) for the detection of the quench to the quench detection interface (QDI) to implement the two-stage safety concept.     

Critical review of models for H2-permeation through polymers with focus on the differential pressure method

To reduce loss of hydrogen in storage vessels with high energy-to-weight-ratio, new materials, especially polymers, have to be developed as barrier materials. Very established methods for characterization of barrier materials with permeation measurements are the time-lag and flow rate method along with the differential pressure method, which resembles the nature of hydrogen vessel systems very well. Long measurement durations are necessary to gain suitable measurement data for these evaluation methods, and often restrictive conditions have to be fullfilled. For these reasons, common models for hydrogen permeation through single-layer and multi-layer membranes, as well as models for hydrogen gas properties were collected and reviewed. Using current computer power together with these models can reduce measurement time for characterization of the barrier properties of materials, while additional information about the quality of the measurement results is obtained.