<i>N,N</i>-bis-(dimethylfluorosilylmethyl)amides of <i>N</i>-organosulfonylproline and sarcosine: synthesis, structure, stereodynamic behaviour and <i>in silico</i> studies

(O→Si)-Chelate difluorides R3R2NCH(R1)C(O)N(CH2SiMe2F)2 (9a–c, R1R2 = (CH2)3, R3 = Ms (a), Ts (b); R1 = H, R2 = Me, R3 = Ms (c)), containing one penta- and one tetracoordinate silicon atoms were synthesized by silylmethylation of amides R3R2NCH(R1)C(O)NH2, subsequent hydrolysis of unstable intermediates R3R2NCH(R1)C(O)N(CH2SiMe2Cl)2 (7a–c) into 4-acyl-2,6-disilamorpholines R3R2NCH(R1)C(O)N(CH2SiMe2O)2 (8a–c) and the reaction of the latter compounds with BF3·Et2O. The structures of disilamorpholines 8a,c and difluoride 9a were confirmed by an X-ray diffraction study. According to the IR and NMR data, the O→Si coordination in solutions of these compounds was weaker than that in the solid state due to effective solvation of the Si–F bond. A permutational isomerisation involving an exchange of equatorial Me groups at the pentacoordinate Si atom in complexes 9a–c was detected, and its activational parameters were determined by 1H DNMR. In silico estimation of possible pharmacological effects and acute rat toxicity by PASS Online and GUSAR Online services showed a potential for their further pharmacological study

Solitary vortex couples in viscoelastic Couette flow

We report experimental observation of a localized structure, which is of a new type for dissipative systems. It appears as a solitary vortex couple ("diwhirl") in Couette flow with highly elastic polymer solutions. A unique property of the diwhirls is that they are stationary, in contrast to the usual localized wave structures in both Hamiltonian and dissipative systems which are stabilized by wave dispersion. It is also a new object in fluid dynamics - a couple of vortices that build a single entity somewhat similar to a magnetic dipole. The diwhirls arise as a result of a purely elastic instability through a hysteretic transition at negligible Reynolds numbers. It is suggested that the vortex flow is driven by the same forces that cause the Weissenberg effect. The diwhirls have a striking asymmetry between the inflow and outflow, which is also an essential feature of the suggested elastic instability mechanism.Comment: 9 pages (LaTeX), 5 Postscript figures, submitte

Cryo-EM structure of native human thyroglobulin

The thyroglobulin (TG) protein is essential to thyroid hormone synthesis, plays a vital role in the regulation of metabolism, development and growth and serves as intraglandular iodine storage. Its architecture is conserved among vertebrates. Synthesis of triiodothyronine (T; 3; ) and thyroxine (T; 4; ) hormones depends on the conformation, iodination and post-translational modification of TG. Although structural information is available on recombinant and deglycosylated endogenous human thyroglobulin (hTG) from patients with goiters, the structure of native, fully glycosylated hTG remained unknown. Here, we present the cryo-electron microscopy structure of native and fully glycosylated hTG from healthy thyroid glands to 3.2 Å resolution. The structure provides detailed information on hormonogenic and glycosylation sites. We employ liquid chromatography-mass spectrometry (LC-MS) to validate these findings as well as other post-translational modifications and proteolytic cleavage sites. Our results offer insights into thyroid hormonogenesis of native hTG and provide a fundamental understanding of clinically relevant mutations

X-ray observations of sub-mm LABOCA galaxies in the eCDFS

We explore the X-ray properties of the 126 sub-mm galaxies (SMGs) of the LABOCA survey in the CDFS and the eCDFS regions. SMGs are believed to experience massive episodes of star-formation. Our goal is to examine whether star-formation coexists with AGN activity, determine the fraction of highly obscured AGN and finally to obtain an idea of the dominant power-mechanism in these sources. Using Spitzer and radio arc-second positions for the SMGs, we find 14 sources with significant X-ray detections. For most of these there are only photometric redshifts available, with their median redshift being ~2.3. Taking into account only the CDFS area which has the deepest X-ray observations, we estimate an X-ray AGN fraction of <26+/-9 % among SMGs. The X-ray spectral properties of the majority of the X-ray AGN which are associated with SMGs are consistent with high obscuration, 10^23 cm-2, but there is no unambiguous evidence for the presence of Compton-thick sources. Detailed Spectral Energy Distribution fittings show that the bulk of total IR luminosity originates in star-forming processes, although a torus component is usually present. Finally, stacking analysis of the X-ray undetected SMGs reveals a signal in the soft (0.5-2 keV) and marginally in the hard (2-5 keV) X-ray band. The hardness ratio of the stacked signal is relatively soft (-0.40+/-0.10) corresponding to a photon index of ~1.6. This argues against a high fraction of Compton-thick sources among the X-ray undetected SMGs.Comment: 13 pages, to appear in A&

On the Lx-L6micron ratio as a diagnostic for Compton-thick AGN

As the mid-IR luminosity represents a good isotropic proxy of the AGN power, a low X-ray to mid-IR luminosity ratio is often claimed to be a reliable indicator for selecting Compton-thick (CT) AGN. We assess the efficiency of this diagnostic by examining the 12mu IRAS AGN sample for which high signal-to-noise XMM observations have been recently become available. We find that the vast majority (10/11) of the AGN that have been classified as CT on the basis the X-ray spectroscopy by Brightman & Nandra present a low Lx/L6 luminosity ratio, i.e. lower than a few percent of the average AGN ratio which is typical of reflection-dominated CT sources. At low Lx/L6 ratios we also find a comparable number of AGN, most of which are heavily absorbed but not CT. This implies that although most Compton-thick AGN present low Lx/L6 ratios, at least in the local, Universe, the opposite is not necessarily true. Next, we extend our analysis to higher redshifts. We perform the same analysis in the CDFS where excellent quality chandra (4 Ms) and xmm (3 Ms) X-ray spectra are available. We derive accurate X-ray luminosities for chandra sources using X-ray spectral fits, as well as 6mu luminosities from SED fits. We find 8 AGN with low Lx/L6 ratios in total, after excluding one source where the 6mu emission primarily comes from star-formation. One of these sources has been already demonstrated to host a CT nucleus, while for another one at a redshift of z=1.22 we argue it is most likely CT on the basis of its combined chandra and xmm spectrum. We find a large number of non CT contaminant with low Lx/L6 ratios. The above suggest that a low Lx/L6 ratio alone cannot ascertain the presence of a CT AGN, albeit the majority of low Lx/L6 AGN are heavily obscured. The two most reliable CT AGN in the high redshift Universe have high Lx/L6 ratios, showing that this method cannot provide complete CT AGN samples.Comment: 11 pages, to appear to A&

Exploiting Genetically Modified Dual-Reporter Strains to Monitor Experimental Trypanosoma cruzi Infections and Host-Parasite Interactions.

Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. Despite a global research effort, there have been no significant treatment advances for at least 40 years. Gaps in our knowledge of T. cruzi biology and pathogenesis have been major factors in limiting progress. In addition, the extremely low parasite burden during chronic infections has complicated the monitoring of both disease progression and drug efficacy, even in predictive animal models. To address these problems, we genetically modified T. cruzi to express a red-shifted luciferase. Mice infected with these highly bioluminescent parasites can be monitored by in vivo imaging, with exquisite sensitivity. However, a major drawback of bioluminescence imaging is that it does not allow visualization of host-parasite interactions at a cellular level. To facilitate this, we generated T. cruzi strains that express a chimeric protein that is both bioluminescent and fluorescent. Bioluminescence allows the tissue location of infection foci to be identified, and fluorescence can then be exploited to detect parasites in histological sections derived from excised tissue. In this article, we describe in detail the in vivo imaging and confocal microscopy protocols that we have developed for visualizing T. cruzi parasites expressing these dual-reporter fusion proteins. The approaches make it feasible to locate individual parasites within chronically infected murine tissues, to assess their replicative status, to resolve the nature of host cells, and to characterize their immunological context