69 research outputs found

    Protein Arginine Methylation and Citrullination in Epigenetic Regulation

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    The post-translational modification of arginine residues represents a key mechanism for the epigenetic control of gene expression. Aberrant levels of histone arginine modifications have been linked to the development of several diseases including cancer. In recent years, great progress has been made in understanding the physiological role of individual arginine modifications and their effects on chromatin function. The present review aims to summarize the structural and functional aspects of histone arginine modifying enzymes and their impact on gene transcription. We will discuss the potential for targeting these proteins with small molecules in a variety of disease states

    Chemical Biology of Protein Arginine Modifications in Epigenetic Regulation

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    Review article on histone citrullination (arginine deimination), histone arginine methylation, and noncanonical histone arginine modifications

    Complex THz and DC inverse spin Hall effect in YIG/Cu1−x_{1-x}Irx_{x} bilayers across a wide concentration range

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    We measure the inverse spin Hall effect of Cu1−x_{1-x}Irx_{x} thin films on yttrium iron garnet over a wide range of Ir concentrations (0.05⩽x⩽0.70.05 \leqslant x \leqslant 0.7). Spin currents are triggered through the spin Seebeck effect, either by a DC temperature gradient or by ultrafast optical heating of the metal layer. The spin Hall current is detected by, respectively, electrical contacts or measurement of the emitted THz radiation. With both approaches, we reveal the same Ir concentration dependence that follows a novel complex, non-monotonous behavior as compared to previous studies. For small Ir concentrations a signal minimum is observed, while a pronounced maximum appears near the equiatomic composition. We identify this behavior as originating from the interplay of different spin Hall mechanisms as well as a concentration-dependent variation of the integrated spin current density in Cu1−x_{1-x}Irx_{x}. The coinciding results obtained for DC and ultrafast stimuli show that the studied material allows for efficient spin-to-charge conversion even on ultrafast timescales, thus enabling a transfer of established spintronic measurement schemes into the terahertz regime.Comment: 12 pages, 4 figure

    Temperature dependent study of the spin dynamics of coupled Y3_3Fe5_5O12_{12}/Gd3_3Fe5_5O12_{12}/Pt trilayers

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    In this study, we investigate the dynamic response of a Y3_3Fe5_5O12_{12} (YIG)/ Gd3_3Fe5_5O12_{12} (GdIG)/ Pt trilayer system by measurements of the ferromagnetic resonance (FMR) and the pumped spin current detected by the inverse spin Hall effect. This trilayer system offers the unique opportunity to investigate the spin dynamics of the ferrimagnetic GdIG, close to its compensation temperature. We show that our trilayer acts as a highly tunable spin current source. Our experimental results are supported by micro-magnetic simulations. As the detected spin current in the top Pt layer is distinctly dominated by the GdIG layer, this gives the unique opportunity to investigate the excitation and dynamic properties of GdIG while comparing it to the broadband FMR absorption spectrum of the heterostructure

    Anisotropic magnetotransport realized in doped hematite

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    Conventional antiferromagnetic materials have long been recognized for their time-reversal symmetry, resulting in a zero anomalous Hall coefficient. However, a paradigm shift occurs when examining easy-axis antiferromagnets and their spin-flop transition. This transition introduces a magnetic canted moment, leading to the emergence of a non-zero anomalous Hall signal and the generation of a non-dissipative transversal current. While high symmetry systems typically manifest an isotropic Hall effect, our study unveils the extraordinary behavior exhibited by hematite that becomes conductive due to small Ti doping. We investigate the magnetotransport in Titanium-doped hematite, uncovering a highly pronounced and unconventional symmetry. Notably, this effect displays a remarkable dependence on the crystal orientation of the material. We establish a compelling correlation between our experimental observations and the predicted anomalous Hall effect in altermagnets through symmetry analysis. This study expands our understanding of the Hall effect in antiferromagnetic materials and sheds light on the intricate interplay between crystal orientation and unconventional Hall phenomena

    National and subnational short-term forecasting of COVID-19 in Germany and Poland during early 2021

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    We compare forecasts of weekly case and death numbers for COVID-19 in Germany and Poland based on 15 different modelling approaches. These cover the period from January to April 2021 and address numbers of cases and deaths one and two weeks into the future, along with the respective uncertainties. We find that combining different forecasts into one forecast can enable better predictions. However, case numbers over longer periods were challenging to predict. Additional data sources, such as information about different versions of the SARS-CoV-2 virus present in the population, might improve forecasts in the future

    Multi-dimensional modeling and simulation of semiconductor nanophotonic devices

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    Self-consistent modeling and multi-dimensional simulation of semiconductor nanophotonic devices is an important tool in the development of future integrated light sources and quantum devices. Simulations can guide important technological decisions by revealing performance bottlenecks in new device concepts, contribute to their understanding and help to theoretically explore their optimization potential. The efficient implementation of multi-dimensional numerical simulations for computer-aided design tasks requires sophisticated numerical methods and modeling techniques. We review recent advances in device-scale modeling of quantum dot based single-photon sources and laser diodes by self-consistently coupling the optical Maxwell equations with semiclassical carrier transport models using semi-classical and fully quantum mechanical descriptions of the optically active region, respectively. For the simulation of realistic devices with complex, multi-dimensional geometries, we have developed a novel hp-adaptive finite element approach for the optical Maxwell equations, using mixed meshes adapted to the multi-scale properties of the photonic structures. For electrically driven devices, we introduced novel discretization and parameter-embedding techniques to solve the drift-diffusion system for strongly degenerate semiconductors at cryogenic temperature. Our methodical advances are demonstrated on various applications, including vertical-cavity surface-emitting lasers, grating couplers and single-photon sources

    CernVM-FS: delivering scientific software to globally distributed computing resources

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    The computing facilities used to process data for the experiments at the Large Hadron Collider at CERN are scattered around the world. The embarrassingly parallel workload allows for use of various computing resources, such as Grid sites of the Worldwide LHC Computing Grid, commercial and institutional cloud resources, as well as individual home PCs in "volunteer clouds". Unlike data, the experiment software cannot be easily split into small work units. Efficient delivery of the complex and frequently changing experiment software is a crucial step to harness heterogeneous resources. Here we present an approach to deliver software on demand using a scalable hierarchy of standard HTTP caches. We show how to tackle this problem by pre-processing software into content-addressable storage. On the worker nodes, we use a specially crafted file system that ensures data integrity and provides fault-tolerance. We show performance figures from large-scale deployment. For the most common case of computing clusters with 10 to 1000 worker nodes, we present a novel state dissemination protocol to support a fully decentralized and distributed memory cache

    Protein arginine methyltransferase 5 catalyzes substrate dimethylation in a distributive fashion.

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    Protein arginine methyltransferase 5 (PRMT5) is a histone-modifying enzyme whose activity is aberrantly upregulated in various cancers and thereby contributes to a progrowth phenotype. Indeed, knockdown of PRMT5 leads to growth arrest and apoptosis, suggesting that inhibitors targeting this enzyme may have therapeutic utility in oncology. To aid the development of inhibitors targeting PRMT5, we initiated mechanistic studies geared to understand how PRMT5 selectively catalyzes the symmetric dimethylation of its substrates. Toward that end, we characterized the regiospecificity and processivity of bacterially expressed Caenorhabditis elegans PRMT5 (cPRMT5), insect cell-expressed human PRMT5 (hPRMT5), and human PRMT5 complexed with methylosome protein 50 (MEP50), i.e., the PRMT5.MEP50 complex. Our studies confirm that arginine 3 is the only site of methylation in both histone H4 and H4 tail peptide analogues and that sites distal to the site of methylation promote the efficient symmetric dimethylation of PRMT5 substrates by increasing the affinity of the monomethylated substrate for the enzyme. Additionally, we show for the first time that both cPRMT5 and the hPRMT5.MEP50 complex catalyze substrate dimethylation in a distributive manner, which is assisted by long-range interactions. Finally, our data confirm that MEP50 plays a key role in substrate recognition and activates PRMT5 activity by increasing its affinity for protein substrates. In total, our results suggest that it may be possible to allosterically inhibit PRMT5 by targeting binding pockets outside the active site

    Targeting the arginine phosphatase YwlE with a catalytic redox-based inhibitor.

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    Protein phosphatases are critical regulators of cellular signaling in both eukaryotes and prokaryotes. The majority of protein phosphatases dephosphorylate phosphoserine/phosphothreonine or phosphotyrosine residues. Recently, however, YwlE, a member of the low-molecular weight protein tyrosine phosphatase (LMW-PTP) family, was shown to efficiently target phosphoarginine. YwlE shares several sequence motifs with this family including the C(X)4 CR(S/T) motif that is crucial for catalysis and redox regulation of the enzyme. Herein we confirm that Cys9 and Cys14 play important roles in YwlE catalysis and regulation. On the basis of these observations, we designed and synthesized a YwlE inhibitor, denoted cyc-SeCN-amidine, that irreversibly inhibits YwlE (kinact/KI = 310 M(-1) min(-1)) by inducing disulfide bond formation between the two active site cysteine residues. Interestingly, inactivation appears to be catalytic, since the compound is neither destroyed nor altered after enzyme inhibition. Although the exact mechanism of disulfide induction remains elusive, we propose several potential mechanisms accounting for the cyc-SeCN-amidine mediated inhibition of YwlE. These findings could stimulate the design of similar selenium-based compounds targeting other redox-sensitive enzymes
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