Unique Structure and Stability of HmuY, a Novel Heme-Binding Protein of Porphyromonas gingivalis

Infection, survival, and proliferation of pathogenic bacteria in humans depend on their capacity to impair host responses and acquire nutrients in a hostile environment. Among such nutrients is heme, a co-factor for oxygen storage, electron transport, photosynthesis, and redox biochemistry, which is indispensable for life. Porphyromonas gingivalis is the major human bacterial pathogen responsible for severe periodontitis. It recruits heme through HmuY, which sequesters heme from host carriers and delivers it to its cognate outer-membrane transporter, the TonB-dependent receptor HmuR. Here we report that heme binding does not significantly affect the secondary structure of HmuY. The crystal structure of heme-bound HmuY reveals a new all-β fold mimicking a right hand. The thumb and fingers pinch heme iron through two apical histidine residues, giving rise to highly symmetric octahedral iron co-ordination. The tetrameric quaternary arrangement of the protein found in the crystal structure is consistent with experiments in solution. It shows that thumbs and fingertips, and, by extension, the bound heme groups, are shielded from competing heme-binding proteins from the host. This may also facilitate heme transport to HmuR for internalization. HmuY, both in its apo- and in its heme-bound forms, is resistant to proteolytic digestion by trypsin and the major secreted proteases of P. gingivalis, gingipains K and R. It is also stable against thermal and chemical denaturation. In conclusion, these studies reveal novel molecular properties of HmuY that are consistent with its role as a putative virulence factor during bacterial infection

Fundamental Rights in Europe after Opinion 2/13: The Hidden Promise of Mutual Trust

This chapter takes a closer look at the productive partnership between the Court of Justice of the European Union (CJEU) and the European Court of Human Rights (ECtHR) and asks whether the existing legal framework guarantees the endurance of the cooperative dialogue between both courts. First, it summarizes the ground rules of their symbiosis, going over the status of the European Convention on Human Rights in EU law and the ECtHR’s recognition of the EU’s legal personality. Then, it briefly addresses the impact of the CJEU's Opinion 2/13 on the EU’s accession to the Convention before exploring, in section 3, the many forms that the judicial dialogue between the CJEU and the ECtHR has taken over the years and discussing the influence of the jurisprudence of one over the other. A final part asks whether it is possible to move beyond labels of comity and identify a legal duty for both courts to cooperate. </p

Surface temperature measurement of a copper anode submitted to a non-stationary electric arc in air

This work concerns the assessment of the surface temperature of copper anodes submitted to an electric arc in a non-stationary regime in air at atmospheric pressure. An infrared camera is used to measure the decrease of the surface temperature just after a very fast controlled arc extinction. Results are presented for different mean values of the arc current intensity (30, 70 and 130 A) with an electric arc duration in the range of 2–5 ms. The temperature decrease after the arc extinction allows an assessment of the surface temperature just at the moment of the arc switching off. In the present experimental conditions the mean temperatures reached for copper anodes are in the range of 750–1200 °C according to the arc current intensity values. Comparison between experimental results and a numerical modeling of the electrode heating allowed one to assess the surface power balance. The values for the volt equivalent are found about 12 V and the values for the surface power density are found to be near 2 × 109 W/m2

Temperature Measurement of Copper Contact Surfaces

LGEP 2010 ID = 656International audienc

MIP-3α expression in macrophages is NOD dependent

Background: The first identified susceptibility gene for Crohn's disease, NOD2, acts as a sensor for the bacterial-wall peptidoglycan fragment muramyl dipeptide (MDP) and activates the transcription factor nuclear factor-κB (NF-κB). Upon NF-κB activation, intestinal macrophages (IMACs) induce expression of macrophage inflammatory protein (MIP)-3α to attract memory T lymphocytes. We therefore investigated the influence of NOD2 ligation of IMAC differentiation and functional MIP-3α induction. Methods: Human embryonal kidney HEK293 cells were transfected with NOD2 wild-type (NOD2(WT)) and the NOD2 SNP13 variant (NOD2(L1007fsinsC)) and stimulated with MDP. Recruitment of CD45R0(+) and Th17 cells was determined by immunohistochemistry. Results: Endogenous NOD2 stimulation was followed by a dose-dependent increase in MIP-3α secretion in MONO-MAC-6 (MM6) cells. MIP-3α mRNA was also significantly (* p < 0.05) induced in HEK293 transfected with NOD2(WT) via MDP ligation. In vivo cell-cell contacts between IMACs and CD45R0(+) memory T cells as well as recruitment of Th17 cells in patients of NOD2 variants were unchanged as compared to wild-type patients. Conclusion: Our data demonstrate a dose-dependent increase in MIP-3α secretion in the human myeloid cell line MM6 upon MDP. However, MIP-3α-driven recruitment of Th17 cells or CD45R0(+) memory T lymphocytes is not affected in patients carrying heterozygous NOD2 variants