Influence of Magnetic Sublattice Ordering on Skyrmion Bubble Stability in 2D Magnet FeGeTe.

The realization of above room-temperature ferromagnetism in the two-dimensional (2D) magnet FeGeTe represents a major advance for the use of van der Waals (vdW) materials in practical spintronic applications. In particular, observations of magnetic skyrmions and related states within exfoliated flakes of this material provide a pathway to the fine-tuning of topological spin textures via 2D material heterostructure engineering. However, there are conflicting reports as to the nature of the magnetic structures in FeGeTe.

Genetic variation of the 5-HT1A rs6295, 5-HT2A rs6311, and CNR1 rs1049353 and an altered endocannabinoid system in depressed patients.

Background: The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention.

Method: In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5-HT2A rs6311, and 5-HT1A rs6295 by high-resolution melting genotyping.

Direct Observation of Propagating Spin Waves in the 2D van der Waals Ferromagnet FeGeTe.

Magnetism in reduced dimensionalities is of great fundamental interest while also providing perspectives for applications of materials with novel functionalities. In particular, spin dynamics in two dimensions (2D) have become a focus of recent research. Here, we report the observation of coherent propagating spin-wave dynamics in a ∼30 nm thick flake of 2D van der Waals ferromagnet FeGeTe using X-ray microscopy.

Arabidopsis nicotianamine synthases comprise a common core-NAS domain fused to a variable autoinhibitory C terminus.

Nicotianamine synthase (NAS) catalyzes the biosynthesis of the low-molecular-mass metal chelator nicotianamine (NA) from the 2-aminobutyrate moieties of three SAM molecules. NA has central roles in metal nutrition and metal homeostasis of flowering plants. The enzymatic function of NAS remains poorly understood.

Seeding and Emergence of Composite Skyrmions in a van der Waals Magnet.

Topological charge plays a significant role in a range of physical systems. In particular, observations of real-space topological objects in magnetic materials have been largely limited to skyrmions - states with a unitary topological charge. Recently, more exotic states with varying topology, such as antiskyrmions, merons, or bimerons and 3D states such as skyrmion strings, chiral bobbers, and hopfions, have been experimentally reported.

Single Skyrmion Generation via a Vertical Nanocontact in a 2D Magnet-Based Heterostructure.

Skyrmions have been well studied in chiral magnets and magnetic thin films due to their potential application in practical devices. Recently, monochiral skyrmions have been observed in two-dimensional van der Waals magnets. Their atomically flat surfaces and capability to be stacked into heterostructures offer new prospects for skyrmion applications.

A high frequency builder software for arbitrary radio frequency signals.

While the frequencies accessible by signal generators steadily rise, the synthesization of complex and arbitrary waveforms with high frequency components remains challenging, especially when restricted by an external reference clock. In this article, we present a comprehensive software package combined with state-of-the-art hardware as a solution for the generation of highly sampled, arbitrary radio frequency waveforms. The software can be used to conduct both synchronous and heterodyne pump-probe experiments due to a variety of different synchronization modules.

[COVID-19 in obstetric anesthesia : Prospective surveillance of peripartum infections with SARS-CoV-2 and peripartum course of disease in affected women].

Background: In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected.

Objective: This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV‑2 positive pregnant women hospitalized for childbirth.

Rational prioritization strategy allows the design of macrolide derivatives that overcome antibiotic resistance.

Antibiotic resistance is a major threat to global health; this problem can be addressed by the development of new antibacterial agents to keep pace with the evolutionary adaptation of pathogens. Computational approaches are essential tools to this end since their application enables fast and early strategical decisions in the drug development process. We present a rational design approach, in which acylide antibiotics were screened based on computational predictions of solubility, membrane permeability, and binding affinity toward the ribosome.

Polyether Cyclization Cascade Alterations in Response to Monensin Polyketide Synthase Mutations.

The targeted manipulation of polyketide synthases has in recent years led to numerous new-to-nature polyketides. For type I polyketide synthases the response of post-polyketide synthases (PKS) processing enzymes onto the most frequently polyketide backbone manipulations is so far insufficiently studied. In particular, complex processes such as the polyether cyclisation in the biosynthesis of ionophores such as monensin pose interesting objects of research.

[Intranasal lidocaine atomization as novel and noninvasive treatment option for postdural puncture headache : Two case reports from obstetric anesthesiology].

Background: Postdural puncture headache (PDPH) occurs in up to 11% of patients after spinal anesthesia and in more than 80% after dural perforation upon epidural anesthesia. It represents a severe anesthesiological complication in obstetric patients. If conservative medication measures do not result in a timely relief of symptoms, the current guidelines recommend the early implementation of an epidural blood patch; however, although performing an epidural blood patch is effective to treat PDPH, potential side effects include neurological complications, spinal hematoma and infections.

Sensitivity of VCD spectroscopy for small structural and stereochemical changes of macrolide antibiotics.

We report the application of VCD spectroscopy for the characterization of clarithromycin and erythromycin. We show that the VCD spectra of these large macrolides are distinctly different and that spectra calculations reproduce the experimentally observed VCD signatures. In addition, computed VCD spectra of different epimers indicate that they should also be distinguishable from the correct structure of clarithromycin.

Identification of crucial bottlenecks in engineered polyketide biosynthesis.

The concept of combinatorial biosynthesis promises access to compound libraries based on privileged natural scaffolds. Ever since the elucidation of the biosynthetic pathway towards the antibiotic erythromycin A in 1990, the predictable manipulation of type I polyketide synthase megaenzymes was investigated. However, this goal was rarely reached beyond simplified model systems.

Exploring the Promiscuous Enzymatic Activation of Unnatural Polyketide Extender Units in Vitro and in Vivo for Monensin Biosynthesis.

The incorporation of new-to-nature extender units into polyketide synthesis is an important source for diversity yet is restricted by limited availability of suitably activated building blocks in vivo. We here describe a straightforward workflow for the biogenic activation of commercially available new-to-nature extender units. Firstly, the substrate scope of a highly flexible malonyl co-enzyme A synthetase from Streptomyces cinnamonensis was characterized.

An in Vitro Biosynthesis of Sesquiterpenes Starting from Acetic Acid.

The enzymatic synthesis of terpenes was investigated by using a cascade based on the mevalonic acid pathway. Suitable enzymes from all kingdoms of life were identified and combined to give rise to geosmin and patchoulol as representative compounds. The pathway was studied in three separate segments, which were subsequently combined in a ten-step cascade plus added cofactor regeneration systems.

A Multiperspective Approach to Solvent Regulation of Enzymatic Activity: HMG-CoA Reductase.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase was investigated in different organic cosolvents by means of kinetic and calorimetric measurements, molecular dynamics simulations, and small-angle X-ray scattering. The combined experimental and theoretical techniques were essential to complement each other's limitations in the investigation of the complex interaction pattern between the enzyme, different solvent types, and concentrations. In this way, the underlying mechanisms for the loss of enzyme activity in different water-miscible solvents could be elucidated.

Elucidation of the Catalytic Mechanism of a Miniature Zinc Finger Hydrolase.

To improve our mechanistic understanding of zinc metalloenzymes, we report a joint computational and experimental study of a minimal carbonic anhydrase (CA) mimic, a 22-residue Zn-finger hydrolase. We combine classical molecular dynamics (MD) simulations, quantum mechanics/molecular mechanics (QM/MM) geometry optimizations, and QM/MM free energy simulations with ambient and high-pressure kinetic measurements to investigate the mechanism of the hydrolysis of the substrate p-nitrophenylacetate (pNPA). The zinc center of the hydrolase prefers a pentacoordinated geometry, as found in most naturally occurring CAs and CA-like enzymes.

Stereochemical assignment of fusiccocadiene from NMR shielding constants and vibrational circular dichroism spectroscopy.

The absolute configuration (AC) of the common precursor of the fusicoccane family of terpenoids, fusicocca-2,10(14)-diene (FCdiene), had only been deduced by a lengthy total synthesis, or indirectly from crystal structures of fusicoccin A. However, in particular the AC determinations based on downstream products of the terpene synthase intrinsically overlook potential epimerization reactions. In this contribution, we confirm the relative stereochemistry of FCdiene by comparison of experimental and predicted C-NMR chemical shifts, and finally determine the absolute configuration from an analysis of its infrared and vibrational circular dichroism spectra.

Data in support of substrate flexibility of a mutated acyltransferase domain and implications for polyketide biosynthesis.

Enzyme-directed mutasynthesis is an emerging strategy for the targeted derivatization of natural products. Here, data on the synthesis of malonic acid derivatives for feeding studies in Saccharopolyspora erythraea , the mutagenesis of DEBS and bioanalytical data on the experimental investigation of studies on the biosynthetic pathway towards erythromycin are presented.

Substrate Flexibility of a Mutated Acyltransferase Domain and Implications for Polyketide Biosynthesis.

Polyketides are natural products frequently used for the treatment of various diseases, but their structural complexity hinders efficient derivatization. In this context, we recently introduced enzyme-directed mutasynthesis to incorporate non-native extender units into the biosynthesis of erythromycin. Modeling and mutagenesis studies led to the discovery of a variant of an acyltransferase domain in the erythromycin polyketide synthase capable of accepting a propargylated substrate.

Heterologous fermentation of a diterpene from .

A variety of different applications render terpenes and terpenoids attractive research targets. A promising but so far insufficiently explored family of terpenoids are the fusicoccanes that comprise a characteristic 5-8-5 fused tricyclic ring system. Besides herbicidal effects, these compounds also show apoptotic and anti-tumour effects on mammalian cells.

Predicted incorporation of non-native substrates by a polyketide synthase yields bioactive natural product derivatives.

The polyether ionophore monensin is biosynthesized by a polyketide synthase that delivers a mixture of monensins A and B by the incorporation of ethyl- or methyl-malonyl-CoA at its fifth module. Here we present the first computational model of the fifth acyltransferase domain (AT5mon ) of this polyketide synthase, thus affording an investigation of the basis of the relaxed specificity in AT5mon , insights into the activation for the nucleophilic attack on the substrate, and prediction of the incorporation of synthetic malonic acid building blocks by this enzyme. Our predictions are supported by experimental studies, including the isolation of a predicted derivative of the monensin precursor premonensin.

Biosynthesis with fluorine.

No longer in-F-able: fluorine building blocks can be used in polyketide biosynthesis. This represents a more flexible approach to organofluorines than the traditional use of fluorinated starter units in multistep organic syntheses, and will hopefully increase the number of compounds available for drug development.

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis.

Polyketides are biosynthesized through consecutive decarboxylative Claisen condensations between a carboxylic acid and differently substituted malonic acid thioesters, both tethered to the giant polyketide synthase enzymes. Individual malonic acid derivatives are typically required to be activated as coenzyme A-thioesters prior to their enzyme-catalyzed transfer onto the polyketide synthase. Control over the selection of malonic acid building blocks promises great potential for the experimental alteration of polyketide structure and bioactivity.