169 research outputs found
Tris(methylthio)methane produced by Mortierella hyalina affects sulfur homeostasis in Arabidopsis
Incommensurate magnetic ordering in Cu2Te2O5X2 (X=Cl, Br) studied by single crystal neutron diffraction
Polarized and unpolarized neutron diffraction studies have been carried out
on single crystals of the coupled spin tetrahedra systems Cu2Te2O5X2 (X=Cl,
Br). A model of the magnetic structure associated with the propagation vectors
k'Cl ~ -0.150,0.422,1/2 and k'Br ~ -0.172,0.356,1/2 and stable below TN=18 K
for X=Cl and TN=11 K for X=Br is proposed. A feature of the model, common to
both the bromide and chloride, is a canted coplanar motif for the 4 Cu2+ spins
on each tetrahedron which rotates on a helix from cell to cell following the
propagation vector. The Cu2+magnetic moment determined for X=Br, 0.395(5)muB,
is significantly less than for X=Cl, 0.88(1)muB at 2K. The magnetic structure
of the chloride associated with the wave-vector k' differs from that determined
previously for the wave vector k~0.150,0.422,1/2 [O. Zaharko et.al. Phys. Rev.
Lett. 93, 217206 (2004)]
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A fixed-target platform for serial femtosecond crystallography in a hydrated environment.
For serial femtosecond crystallography at X-ray free-electron lasers, which entails collection of single-pulse diffraction patterns from a constantly refreshed supply of microcrystalline sample, delivery of the sample into the X-ray beam path while maintaining low background remains a technical challenge for some experiments, especially where this methodology is applied to relatively low-ordered samples or those difficult to purify and crystallize in large quantities. This work demonstrates a scheme to encapsulate biological samples using polymer thin films and graphene to maintain sample hydration in vacuum conditions. The encapsulated sample is delivered into the X-ray beam on fixed targets for rapid scanning using the Roadrunner fixed-target system towards a long-term goal of low-background measurements on weakly diffracting samples. As a proof of principle, we used microcrystals of the 24 kDa rapid encystment protein (REP24) to provide a benchmark for polymer/graphene sandwich performance. The REP24 microcrystal unit cell obtained from our sandwiched in-vacuum sample was consistent with previously established unit-cell parameters and with those measured by us without encapsulation in humidified helium, indicating that the platform is robust against evaporative losses. While significant scattering from water was observed because of the sample-deposition method, the polymer/graphene sandwich itself was shown to contribute minimally to background scattering
Dataset of electrophysiological patch-clamp recordings of the effect of the compounds deltamethrin, ATx-II and β4-peptide on human cardiac Nav1.5 sodium channel gating properties.
This article describes the effect of the pyrethroid insecticide deltamethrin on the cardiac voltage-gated sodium channel Nav1.5. Two concentrations of deltamethrin were used and the effects were compared with those of the sea anemone toxin ATx-II and β4-peptide, which is the C-terminus of the Nav channel β-subunit. Activation, fast inactivation, deactivation, persistent currents and resurgent currents of Nav1.5 channels were assessed in the presence of these compounds. The data display not only the effect of separately applied compounds on Nav1.5 channels but also investigates how combinations of these substances affect Nav1.5 channel gating properties. The dataset presented in this article is related to the research article "Mechanism underlying hooked resurgent-like tail currents induced by an insecticide in human cardiac Nav1.5″ (Sarah Thull, Cristian Neacsu, Andrias O. O'Reilly, Stefanie Bothe, Ralf Hausmann, Tobias Huth, Jannis Meents, Angelika Lampert, doi: 10.1016/j.taap.2020.11501), that investigates the effect of the pyrethroid insecticide deltamethrin on Nav channel gating properties and explains the mechanism underlying hooked, resurgent-like tail currents induced by deltamethrin in Nav1.5 channels
Resonance Raman Spectroscopy For In-Situ Monitoring Of Radiation Damage
Radiation induced damage of metal centres in proteins is a severe problem in X-ray structure determination. Photoreduction can lead to erroneous structural implications, and in the worst cases cause structure solution to fail. Resonance Raman (RR) spectroscopy is well suited in-situ monitoring of X-ray induced photoreduction. However the laser excitation needed for RR can itself cause photoreduction of the metal centres. In the present study myoglobin and rubredoxin crystals were used as model systems to assess the feasibility of using RR for this application. It is shown that at least 10-15 RR spectra per crystal can be recorded at low laser power before severe photoreduction occurs.Furthermore it is possible to collect good quality RR spectra from cryocooled protein crystals with exposure times of only a few seconds. Following extended laser illumination photoreduction is observed through the formation and decay of spectral bands as a function of dose. The experimental setup planned for integration into the SLS protein crystallography beamlines is also described. This setup should also prove to be very useful for other experimental techniques at synchrotrons where X-ray photoreduction is a problem e.g. X-ray absorption spectroscopy.Fil: Meents, A.. Swiss Light Source; SuizaFil: Owen, R. L.. Swiss Light Source; SuizaFil: Murgida, Daniel Horacio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Ciudad Universitaria. Instituto de QuĂmica, FĂsica de los Materiales, Medioambiente y EnergĂa. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de QuĂmica, FĂsica de los Materiales, Medioambiente y EnergĂa; ArgentinaFil: Hildebrandt, P.. Swiss Light Source; SuizaFil: Schneider, R.. Swiss Light Source; SuizaFil: Pradervand, C.. Swiss Light Source; SuizaFil: Bohler, P.. Swiss Light Source; SuizaFil: Schulze Briese, C.. Swiss Light Source; Suiz
Hard X-ray stereographic microscopy for single-shot differential phase imaging
The characterisation of fast phenomena at the microscopic scale is required for the understanding of catastrophic responses of materials to loads and shocks, the processing of materials by optical or mechanical means, the processes involved in many key technologies such as additive manufacturing and microfluidics, and the mixing of fuels in combustion. Such processes are usually stochastic in nature and occur within the opaque interior volumes of materials or samples, with complex dynamics that evolve in all three dimensions at speeds exceeding many meters per second. There is therefore a need for the ability to record three-dimensional X-ray movies of irreversible processes with resolutions of micrometers and frame rates of microseconds. Here we demonstrate a method to achieve this by recording a stereo phase-contrast image pair in a single exposure. The two images are combined computationally to reconstruct a 3D model of the object. The method is extendable to more than two simultaneous views. When combined with megahertz pulse trains of X-ray free-electron lasers (XFELs) it will be possible to create movies able to resolve 3D trajectories with velocities of kilometers per second
Mechanism underlying hooked resurgent-like tail currents induced by an insecticide in human cardiac Nav1.5.
Voltage-gated sodium channels are responsible not only for the fast upstroke of the action potential, but they also modify cellular excitability via persistent and resurgent currents. Insecticides act via permanently opening sodium channels to immobilize the animals. Cellular recordings performed decades ago revealed distinctly hooked tail currents induced by these compounds. Here, we applied the classical type-II pyrethroid deltamethrin on human cardiac Nav1.5 and observed resurgent-like currents at very negative potentials in the absence of any pore-blocker, which resemble those hooked tail currents. We show that deltamethrin dramatically slows both fast inactivation and deactivation of Nav1.5 and thereby induces large persistent currents. Using the sea anemone toxin ATx-II as a tool to prevent all inactivation-related processes, resurgent-like currents were eliminated while persistent currents were preserved. Our experiments suggest that, in deltamethrin-modified channels, recovery from inactivation occurs faster than delayed deactivation, opening a brief window for sodium influx and leading to hooked, resurgent-like currents, in the absence of an open channel blocker. Thus, we now explain with pharmacological methods the biophysical gating changes underlying the deltamethrin induced hooked tail currents. SUMMARY: The pyrethroid deltamethrin induces hooked resurgent-like tail currents in human cardiac voltage-gated Nav1.5 channels. Using deltamethrin and ATx-II, we identify additional conducting channel states caused by a faster recovery from inactivation compared to the deltamethrin-induced delayed deactivation
Multimodal X-ray imaging of nanocontainer-treated macrophages and calcium distribution in the perilacunar bone matrix
Studies of biological systems typically require the application of several complementary methods able to yield statistically-relevant results at a unique level of sensitivity. Combined X-ray fluorescence and ptychography offer excellent elemental and structural imaging contrasts at the nanoscale. They enable a robust correlation of elemental distributions with respect to the cellular morphology. Here we extend the applicability of the two modalities to higher X-ray excitation energies, permitting iron mapping. Using a long-range scanning setup, we applied the method to two vital biomedical cases. We quantified the iron distributions in a population of macrophages treated with Mycobacterium-tuberculosis-targeting iron-oxide nanocontainers. Our work allowed to visualize the internalization of the nanocontainer agglomerates in the cytosol. From the iron areal mass maps, we obtained a distribution of antibiotic load per agglomerate and an average areal concentration of nanocontainers in the agglomerates. In the second application we mapped the calcium content in a human bone matrix in close proximity to osteocyte lacunae (perilacunar matrix). A concurrently acquired ptychographic image was used to remove the mass-thickness effect from the raw calcium map. The resulting ptychography-enhanced calcium distribution allowed then to observe a locally lower degree of mineralization of the perilacunar matrix
Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease
The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site
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