43 research outputs found

    Keratinocyte and Fibroblast Wound Healing In Vitro Is Repressed by Non-Optimal Conditions but the Reparative Potential Can Be Improved by Water-Filtered Infrared A

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    It is a general goal to improve wound healing, especially of chronic wounds. As light therapy has gained increasing attention, the positive influence on healing progression of water-filtered infrared A (wIRA), a special form of thermal radiation, has been investigated and compared to the detrimental effects of UV-B irradiation on wound closure in vitro. Models of keratinocyte and fibroblast scratches help to elucidate effects on epithelial and dermal healing. This study further used the simulation of non-optimal settings such as S. aureus infection, chronic inflammation, and anti-inflammatory conditions to determine how these affect scratch wound progression and whether wIRA treatment can improve healing. Gene expression analysis for cytokines ( IL1A , IL6 , CXCL8 ), growth ( TGFB1 , PDGFC ) and transcription factors ( NFKB1 , TP53 ), heat shock proteins ( HSP90AA1 , HSPA1A , HSPD1 ), keratinocyte desmogleins ( DSG1 , DSG3 ), and fibroblast collagen ( COL1A1 , COL3A1 ) was performed. Keratinocyte and fibroblast wound healing under non-optimal conditions was found to be distinctly reduced in vitro. wIRA treatment could counteract the inflammatory response in infected keratinocytes as well as under chronic inflammatory conditions by decreasing pro-inflammatory cytokine gene expression and improve wound healing. In contrast, in the anti-inflammatory setting, wIRA radiation could re-initiate the acute inflammatory response necessary after injury to stimulate the regenerative processes and advance scratch closure

    Biophysical Characterization of Pro-apoptotic BimBH3 Peptides Reveals an Unexpected Capacity for Self-Association

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    Bcl-2 proteins orchestrate the mitochondrial pathway of apoptosis, pivotal for cell death. Yet, the structural details of the conformational changes of pro- and antiapoptotic proteins and their interactions remain unclear. Pulse dipolar spectroscopy (double electron-electron resonance [DEER], also known as PELDOR) in combination with spin-labeled apoptotic Bcl-2 proteins unveils conformational changes and interactions of each protein player via detection of intra- and inter-protein distances. Here, we present the synthesis and characterization of pro-apoptotic BimBH3 peptides of different lengths carrying cysteines for labeling with nitroxide or gadolinium spin probes. We show by DEER that the length of the peptides modulates their homo-interactions in the absence of other Bcl-2 proteins and solve by X-ray crystallography the structure of a BimBH3 tetramer, revealing the molecular details of the inter-peptide interactions. Finally, we prove that using orthogonal labels and three-channel DEER we can disentangle the Bim-Bim, Bcl-xL-Bcl-xL, and Bim-Bcl-xL interactions in a simplified interactome.This work was funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2033—Projektnummer 390677874, the DFG Priority Program SPP1601 “New Frontiers in Sensitivity in EPR Spectroscopy” (to E.B.), DFG BO 3000/5-1 (to E.B.), SFB958 – Z04 (to E.B.), DFG grant INST 130/972-1 FUGG (to E.B.). P.E.C. is supported by an Australian NHMRC fellowship (1079700

    Hurricanes and Climate: the U.S. CLIVAR Working Group on Hurricanes

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    While a quantitative climate theory of tropical cyclone formation remains elusive, considerable progress has been made recently in our ability to simulate tropical cyclone climatologies and understand the relationship between climate and tropical cyclone formation. Climate models are now able to simulate a realistic rate of global tropical cyclone formation, although simulation of the Atlantic tropical cyclone climatology remains challenging unless horizontal resolutions finer than 50 km are employed. The idealized experiments of the Hurricane Working Group of U.S. CLIVAR, combined with results from other model simulations, have suggested relationships between tropical cyclone formation rates and climate variables such as mid-tropospheric vertical velocity. Systematic differences are shown between experiments in which only sea surface temperature is increases versus experiments where only atmospheric carbon dioxide is increased, with the carbon dioxide experiments more likely to demonstrate a decrease in numbers. Further experiments are proposed that may improve our understanding of the relationship between climate and tropical cyclone formation, including experiments with two-way interaction between the ocean and the atmosphere and variations in atmospheric aerosols

    The Imaging X-ray Polarimetry Explorer (IXPE): Technical Overview

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    The Imaging X-ray Polarimetry Explorer (IXPE) will expand the information space for study of cosmic sources, by adding linear polarization to the properties (time, energy, and position) observed in x-ray astronomy. Selected in 2017 January as a NASA Astrophysics Small Explorer (SMEX) mission, IXPE will be launched into an equatorial orbit in 2021. The IXPE mission will provide scientifically meaningful measurements of the x-ray polarization of a few dozen sources in the 2-8 keV band, including polarization maps of several x-ray-bright extended sources and phase-resolved polarimetry of many bright pulsating x-ray sources

    In Vitro Lipophilic Antioxidant Capacity, Antidiabetic and Antibacterial Activity of Citrus Fruits Extracts from Aceh, Indonesia

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    This study reports in vitro lipophilic antioxidant, inhibition of α-amylase and antibacterial activities of extracts of peel and pulp of citrus samples from Aceh, Indonesia. HPLC (high-performance liquid chromatography), phytochemical, and FTIR (fourier transform infrared) analysis detected carotenoids, flavonoids, phenolic acids and terpenoids, contributing to the biological potencies. Most peel and pulp extracts contained lutein and lower concentrations of zeaxanthin, α-carotene, ÎČ-carotene and ÎČ-cryptoxanthin. The extracts also contained flavanone glycosides (hesperidin, naringin and neohesperidin), flavonol (quercetin) and polymethoxylated flavones (sinensetin, tangeretin). L-TEAC (lipophilic trolox equivalent antioxidant capacity) test determined for peel extracts higher antioxidant capacity compared to pulp extracts. All extracts presented α-amylase inhibitory activity, pulp extracts showing stronger inhibitory activity compared to peel extracts. All extracts inhibited the growth of both gram (+) and gram (−) bacteria, with peel and pulp extracts of makin showing the strongest inhibitory activity. Therefore, local citrus species from Aceh are potential sources of beneficial compounds with possible health preventive effects

    ÎŽ<sup>13</sup>C and ÎŽ<sup>37</sup>Cl Isotope Fractionation To Characterize Aerobic vs Anaerobic Degradation of Trichloroethylene

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    Trichloroethylene (TCE) is a carcinogenic organic chemical impacting water resources worldwide. Its breakdown by reductive vs oxidative degradation involves different types of chemical bonds. Hence, if distinct isotope effects are reflected in dual element (carbon and chlorine) isotope values, such trends could help distinguishing both processes in the environment. This work explored dual element isotope trends associated with TCE oxidation by two pure bacterial cultures: Pseudomonas putida F1 and Methylosinus trichosporium OB3b, where the latter expresses either soluble methane-monooxygenase (sMMO) or particulate methane-monooxygenase (pMMO). Carbon and chlorine isotope enrichment factors of TCE (Δ<sup>13</sup>C = −11.5, −2.4, and −4.2‰; Δ<sup>37</sup>Cl = 0.3, −1.3, and −2.4‰, respectively) differed strongly between the strains. The dual element isotope trend for strain F1 (Δ<sup>13</sup>C/Δ<sup>37</sup>Cl = −38) reflected, as expected, primary carbon and negligible chlorine isotope effects, whereas unexpectedly large chlorine isotope effects became apparent in the trend obtained with strain OB3b (Δ<sup>13</sup>C/Δ<sup>37</sup>Cl = +1.7 for sMMO and pMMO). Therefore, although dual element isotope analysis partly reflects predicted differences in oxidative vs reductive (Δ<sup>13</sup>C/Δ<sup>37</sup>Cl = 3.4–5.7) degradation, the unexpected OB3b fractionation data may challenge field interpretation

    gem‐Diethyl Pyrroline Nitroxide Spin Labels: Synthesis, EPR Characterization, Rotamer Libraries and Biocompatibility

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    The availability of bioresistant spin labels is crucial for the optimization of site‐directed spin labeling protocols for EPR structural studies of biomolecules in a cellular context. As labeling can affect proteins’ fold and/or function, having the possibility to choose between different spin labels will increase the probability to produce spin‐labeled functional proteins. Here, we report the synthesis and characterization of iodoacetamide‐ and maleimide‐functionalized spin labels based on the gem‐diethyl pyrroline structure. The two nitroxide labels are compared to conventional gem‐dimethyl analogs by site‐directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy, using two water soluble proteins: T4 lysozyme and Bid. To foster their use for structural studies, we also present rotamer libraries for these labels, compatible with the MMM software. Finally, we investigate the “true” biocompatibility of the gem‐diethyl probes comparing the resistance towards chemical reduction of the NO group in ascorbate solutions and E. coli cytosol at different spin concentrations
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