Converse Flexoelectricity in van der Waals (vdW) Three-Dimensional Topological Insulator Nanoflakes.

Low-dimensional van der Waals (vdW) three-dimensional (3D) topological insulators (TIs) have been overlooked, regarding their electromechanical properties. In this study, we experimentally investigate the electromechanical coupling of low-dimensional 3D TIs with a centrosymmetric crystal structure, where a binary compound, bismuth selenide (BiSe), is taken as an example. Piezoresponse force microscopy (PFM) results of BiSe nanoflakes show that the material exhibits both out-of-plane and in-plane electromechanical responses.

A computational map of the human-SARS-CoV-2 protein-RNA interactome predicted at single-nucleotide resolution.

RNA-binding proteins (RBPs) are critical host factors for viral infection, however, large scale experimental investigation of the binding landscape of human RBPs to viral RNAs is costly and further complicated due to sequence variation between viral strains. To fill this gap, we investigated the role of RBPs in the context of SARS-CoV-2 by constructing the first map of human RBP-viral RNA interactions at nucleotide-resolution using two deep learning methods (pysster and DeepRiPe) trained on data from CLIP-seq experiments on more than 100 human RBPs. We evaluated conservation of RBP binding between six other human pathogenic coronaviruses and identified sites of conserved and differential binding in the UTRs of SARS-CoV-1, SARS-CoV-2 and MERS.

Network Embedding Across Multiple Tissues and Data Modalities Elucidates the Context of Host Factors Important for COVID-19 Infection.

COVID-19 is a heterogeneous disease caused by SARS-CoV-2. Aside from infections of the lungs, the disease can spread throughout the body and damage many other tissues, leading to multiorgan failure in severe cases. The highly variable symptom severity is influenced by genetic predispositions and preexisting diseases which have not been investigated in a large-scale multimodal manner.

Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects.

Classical xanthinuria is a rare autosomal recessive metabolic disorder caused by variants in the (type I) or (type II) genes. Thirteen Israeli kindred (five Jewish and eight Arab) and two isolated cases from Germany were studied between the years 1997 and 2013. Four and a branch of a fifth of these families were previously described.

Publisher Correction: Non-cuttable material created through local resonance and strain rate effects.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Non-cuttable material created through local resonance and strain rate effects.

We have created a new architected material, which is both highly deformable and ultra-resistant to dynamic point loads. The bio-inspired metallic cellular structure (with an internal grid of large ceramic segments) is non-cuttable by an angle grinder and a power drill, and it has only 15% steel density. Our architecture derives its extreme hardness from the local resonance between the embedded ceramics in a flexible cellular matrix and the attacking tool, which produces high-frequency vibrations at the interface.

Crystal structure of human mARC1 reveals its exceptional position among eukaryotic molybdenum enzymes.

Biotransformation enzymes ensure a viable homeostasis by regulating reversible cycles of oxidative and reductive reactions. The metabolism of nitrogen-containing compounds is of high pharmaceutical and toxicological relevance because N-oxygenated metabolites derived from reactions mediated by cytochrome P450 enzymes or flavin-dependent monooxygenases are in some cases highly toxic or mutagenic. The molybdenum-dependent mitochondrial amidoxime-reducing component (mARC) was found to be an extremely efficient counterpart, which is able to reduce the full range of N-oxygenated compounds and thereby mediates detoxification reactions.

T4 lysozyme-facilitated crystallization of the human molybdenum cofactor-dependent enzyme mARC.

The human mitochondrial amidoxime reducing component (hmARC) is a molybdenum cofactor-dependent enzyme that is involved in the reduction of a diverse range of N-hydroxylated compounds of either physiological or xenobiotic origin. In this study, the use of a fusion-protein approach with T4 lysozyme (T4L) to determine the structure of this hitherto noncrystallizable enzyme by X-ray crystallography is described. A set of four different hmARC-T4L fusion proteins were designed.

Detoxification of Trimethylamine N-Oxide by the Mitochondrial Amidoxime Reducing Component mARC.

Although known for years, the toxic effects of trimethylamine N-oxide (TMAO), a physiological metabolite, were just recently discovered and are currently under investigation. It is known that elevated TMAO plasma levels correlate with an elevated risk for cardiovascular disease (CVD). Even though there is a general consensus about the existence of a causal relationship between TMAO and CVD, the underlying mechanisms are not fully understood.

Scale-Up of the Electrodeposition of ZnO/Eosin Y Hybrid Thin Films for the Fabrication of Flexible Dye-Sensitized Solar Cell Modules.

The low-temperature fabrication of flexible ZnO photo-anodes for dye-sensitized solar cells (DSSCs) by templated electrochemical deposition of films was performed in an enlarged and technical simplified deposition setup to demonstrate the feasibility of the scale-up of the deposition process. After extraction of eosin Y (EY) from the initially deposited ZnO/EY hybrid films, mesoporous ZnO films with an area of about 40 cm² were reproducibly obtained on fluorine doped tin oxide (FTO)-glass as well as flexible indium tin oxide (ITO)-polyethylenterephthalate (PET) substrates. With a film thickness of up to 9 µm and a high specific surface area of up to about 77 m²·cm the ZnO films on the flexible substrates show suitable properties for DSSCs.

Cloning and Characterization of Cheilanthifoline and Stylopine Synthase Genes from Chelidonium majus.

The most prominent alkaloid of Chelidonium majus is dihydrocoptisine, revealing the characteristic benzophenanthridine skeleton. To date, any informationon on the enzymes responsible for its biosynthesis and the related genes in C. majus is lacking.

Defining the Role of the NADH-Cytochrome-b5 Reductase 3 in the Mitochondrial Amidoxime Reducing Component Enzyme System.

The importance of the mitochondrial amidoxime reducing component (mARC)-containing enzyme system in N-reductive metabolism has been studied extensively. It catalyzes the reduction of various N-hydroxylated compounds and therefore acts as the counterpart of cytochrome P450- and flavin-containing monooxygenase-catalyzed oxidations at nitrogen centers. This enzyme system was found to be responsible for the activation of amidoxime and N-hydroxyguanidine prodrugs in drug metabolism.

Dual and Opposing Roles of Xanthine Dehydrogenase in Defense-Associated Reactive Oxygen Species Metabolism in Arabidopsis.

While plants produce reactive oxygen species (ROS) for stress signaling and pathogen defense, they need to remove excessive ROS induced during stress responses in order to minimize oxidative damage. How can plants fine-tune this balance and meet such conflicting needs? Here, we show that XANTHINE DEHYDROGENASE1 (XDH1) in Arabidopsis thaliana appears to play spatially opposite roles to serve this purpose. Through a large-scale genetic screen, we identified three missense mutations in XDH1 that impair XDH1's enzymatic functions and consequently affect the powdery mildew resistance mediated by RESISTANCE TO POWDERY MILDEW8 (RPW8) in epidermal cells and formation of xanthine-enriched autofluorescent objects in mesophyll cells.

Oxyl and hydroxyl radical transfer in mitochondrial amidoxime reducing component-catalyzed nitrite reduction.

A combination of electron paramagnetic resonance (EPR) spectroscopy and computational approaches has provided insight into the nature of the reaction coordinate for the one-electron reduction of nitrite by the mitochondrial amidoxime reducing component (mARC) enzyme. The results show that a paramagnetic Mo(V) species is generated when reduced enzyme is exposed to nitrite, and an analysis of the resulting EPR hyperfine parameters confirms that mARC is remarkably similar to the low-pH form of sulfite oxidase. Two mechanisms for nitrite reduction have been considered.

Sulphur shuttling across a chaperone during molybdenum cofactor maturation.

Formate dehydrogenases (FDHs) are of interest as they are natural catalysts that sequester atmospheric CO2, generating reduced carbon compounds with possible uses as fuel. FDHs activity in Escherichia coli strictly requires the sulphurtransferase EcFdhD, which likely transfers sulphur from IscS to the molybdenum cofactor (Mo-bisPGD) of FDHs. Here we show that EcFdhD binds Mo-bisPGD in vivo and has submicromolar affinity for GDP-used as a surrogate of the molybdenum cofactor's nucleotide moieties.

Electrochemical and mARC-catalyzed enzymatic reduction of para-substituted benzamidoximes: consequences for the prodrug concept "amidoximes instead of amidines".

The mitochondrial amidoxime reducing component (mARC) activates amidoxime prodrugs by reduction to the corresponding amidine drugs. This study analyzes relationships between the chemical structure of the prodrug and its metabolic activation and compares its enzyme-mediated vs. electrochemical reduction.

Reduction of sulfamethoxazole hydroxylamine (SMX-HA) by the mitochondrial amidoxime reducing component (mARC).

Under high dose treatment with sulfamethoxazole (SMX)/trimethoprim (TMP), hypersensitivity reactions occur with a high incidence. The mechanism of this adverse drug reaction is not fully understood. Several steps in the toxification pathway of SMX were investigated.

Molybdenum site structure of MOSC family proteins.

Mo K-edge X-ray absorption spectroscopy has been used to probe as-isolated structures of the MOSC family proteins pmARC-1 and HMCS-CT. The Mo K-edge near-edge spectrum of HMCS-CT is shifted ~2.5 eV to lower energy compared to the pmARC-1 spectrum, which indicates that as-isolated HMCS-CT is in a more reduced state than pmARC-1.

The mitochondrial amidoxime reducing component (mARC): involvement in metabolic reduction of N-oxides, oximes and N-hydroxyamidinohydrazones.

The mitochondrial amidoxime reducing component (mARC) is a molybdenum-containing enzyme and capable of reducing N-hydroxylated structures such as amidoxime prodrugs. In this study, we tested the involvement of mARC in the reduction of N-oxides (amitriptyline-N-oxide, nicotinamide-N-oxide), oximes ((E)-/(Z)-2,4,6-trimethylacetophenonoxime) and a N-hydroxyamidinohydrazone (guanoxabenz). All groups are reduced by mARC proteins, and the enzymes are therefore involved in the interconversion of N-oxygenated metabolites originating from cytochrome P450s and flavin-containing monooxygenases.

Molybdenum metabolism in plants and crosstalk to iron.

In the form of molybdate the transition metal molybdenum is essential for plants as it is required by a number of enzymes that catalyze key reactions in nitrogen assimilation, purine degradation, phytohormone synthesis, and sulfite detoxification. However, molybdate itself is biologically inactive and needs to be complexed by a specific organic pterin in order to serve as a permanently bound prosthetic group, the molybdenum cofactor, for the socalled molybdo-enyzmes. While the synthesis of molybdenum cofactor has been intensively studied, only little is known about the uptake of molybdate by the roots, its transport to the shoot and its allocation and storage within the cell.

Functional characterization of protein variants encoded by nonsynonymous single nucleotide polymorphisms in MARC1 and MARC2 in healthy Caucasians.

Human molybdenum-containing enzyme mitochondrial amidoxime reducing component (mARC), cytochrome b5 type B, and NADH cytochrome b5 reductase form an N-reductive enzyme system that is capable of reducing N-hydroxylated compounds. Genetic variations are known, but their functional relevance is unclear. Our study aimed to investigate the incidence of nonsynonymous single nucleotide polymorphisms (SNPs) in the mARC genes in healthy Caucasian volunteers, to determine saturation of the protein variants with molybdenum cofactor (Moco), and to characterize the kinetic behavior of the protein variants by in vitro biotransformation studies.

The involvement of mitochondrial amidoxime reducing components 1 and 2 and mitochondrial cytochrome b5 in N-reductive metabolism in human cells.

The mitochondrial amidoxime reducing component mARC is a recently discovered molybdenum enzyme in mammals. mARC is not active as a standalone protein, but together with the electron transport proteins NADH-cytochrome b5 reductase (CYB5R) and cytochrome b5 (CYB5), it catalyzes the reduction of N-hydroxylated compounds such as amidoximes. The mARC-containing enzyme system is therefore considered to be responsible for the activation of amidoxime prodrugs.

Activation of the anti-cancer agent upamostat by the mARC enzyme system.

Upamostat (Mesupron®) is a new small molecule serine protease inhibitor. The drug candidate was developed to inhibit the urokinase-type plasminogen activator (uPA) system, which plays a major role in tumor invasion and metastasis. Upamostat is currently in clinical development as an anti-metastatic and non-cytotoxic agent against pancreatic and breast cancer.

The stomatal response to reduced relative humidity requires guard cell-autonomous ABA synthesis.

Stomata are pores on the leaf surface, bounded by two guard cells, which control the uptake of CO(2) for photosynthesis and the concomitant loss of water vapor. In 1898, Francis Darwin showed that stomata close in response to reduced atmospheric relative humidity (rh); however, our understanding of the signaling pathway responsible for coupling changes in rh to alterations in stomatal aperture is fragmentary. The results presented here highlight the primacy of abscisic acid (ABA) in the stomatal response to drying air.