frequency of hypertension, its cause in the majority of adults is unknown.
Hypertension is complex, with no single mechanism—sodium re- tention, renin release, and increased vascular tone—entirely explain- ing the blood pressure (BP) rise. The past 50 years have seen growing evidence implicating the immune system. 3 Recent data suggest that macrophages (M/) contribute to, and protect from, hypertension. Early studies in the spontaneously hypertensive rat 4 found a correl- ation between the distribution of sub-endothelial M/ and endothelial function, and that treatment with an angiotensin convertingenzyme inhibitor improved endothelial function and reduced the number of vascular M/. Furthermore, many models of hypertension—angioten- sin II (ANG II), high salt—are associated with renal accumulation of M/. 5 , 6 Despite these and many other observational studies, few have attempted to modify M/ phenotype/number to examine their role in hypertension. 7 – 10
cathepsin G , have chymotrypsin-like activity and generate the 31 amino acid intermediate in this particular cell model.
Finally, similarly to pulmonary tissue investigated previously [14,16], soluble extracts of human aortic biopsies were found to generate ET-1 (1–31) with no further conversion to ET-1 in a TY- 51469-sensitive fashion. In contrast to experiments with LUVA cells, conversion of Big ET-1 to ET-1 (1–31) by human aortic homogenates was fully inhibited by TY-51469 at 10 µM, in agreement with our results from the murine system and when using human recombinant CMA1. Thus, the present study suggests for the first time that the production of ET-1 (1–31) requires a chymase-like activity in human blood vessels. Interestingly, Mawatari and colleagues  reported ET-1 (1–31) reactivity in all vascular layers in the hamster aortic arch, which is increased in the intimal lesions of hypercholesterolemic animals. However, chymase-dependent generation of ET-1 (1–31) remains to be confirmed as a relevant factor in human atherosclerosis. The present study did not address the ECE/chymase conversion ratio in murine and human tissue extracts. However, it is of interest to note that no ECE-dependent synthesis of ET-1 from exogenous Big ET-1 was detected by the LC–MS/MS approach. This could perhaps be due to the experimental conditions imposed throughout the present study, such as the removal of non- soluble proteins. It is possible that the ECE-dependent production of ET-1 would have been measurable in intact tissues or organs, particularly in conditions where the vascular endothelium would have been maintained intact. We suggest that, similarly to the angiotensin convertingenzyme/chymase paradigm in the production of angiotensin-II from angiotensin-I , the ECE plays an important role in the production of the circulating levels of ET-1 whereas chymase-like activity may be predominantly involved in perivascular and tissue-derived genesis of the latter vasoactive peptide.
Solid reconstruction from engineering drawings is one of the effi- cient technologies to product solid models. The B-rep oriented ap- proach provides a practical way for reconstructing a wide range of objects. However, its major limitation is the computational com- plexity involved in the search for all valid faces from the inter- mediate wire-frame, especially for objects with complicated face topologies. In previous work, we presented a hint-based algorithm to recognize quadric surfaces from orthographic views and generate a hybrid wire-frame as the intermediate model of our B-rep oriented method. As a key stage in the process of solid reconstructing, we propose an algorithm to convert the hybrid wire-frame to the final B-rep model by extracting all the rest faces of planes based on graph theory. The entities lying on the same planar surface are first col- lected in a plane graph. After all the cycles are traced in a simplified edge-adjacency matrix of the graph, the face loops of the plane are formed by testing loop containment and assigning loop directions. Finally, the B-rep model is constructed by sewing all the plane faces based on the M¨obius rule. The method can efficiently construct 2- manifold objects with a variety of face topologies, which is illus- trated by results of implementation.
des causes des maladies cardiovascu- laires en augmentation. L’obésité est ainsi associée à une augmentation de l’activité enzymatique d’IDO avec, pour conséquence, une utilisation accrue du Trp pour générer la kynurénine au détri- ment des dérivés indoles et de l’IL-22. Cette étude permet donc d’envisager l’utilisation thérapeutique d’inhibiteurs d’IDO afin de lutter contre l’obésité. Un inhibiteur spécifique de cette enzyme a été testé jusqu’en phase 3. Il n’a pas montré de bénéfice dans les traitements du cancer. Mais cette molécule pourrait être proposée pour le traitement des maladies cardio-métaboliques. ‡
Figure 1. Contractile response of the human uterine artery to ET-1 and effect of ET receptor antagonists. (A) Upper panel: Dose-response curves obtained by cumulative increases in the concentration of ET-1 (0.1 nM–0.1 mM) on basal tone (CTL, ), after pre-incubation for 10 minutes with either an ET A receptor antagonist (BQ-123, 1 mM, N ) or an ET B receptor antagonist (BQ-788, 1 mM, ), or a mixture of both antagonists (BQ-
123+788, 1 mM,&). Lower panel: Average contraction of uterine artery induced by 10 nM ET-1 with or without a 10 minutes pre-incubation period with either BQ-123, BQ-788 or BQ123+788 each at 1 mM concentration. Data are expressed as a percentage of the contraction induced by Phe (10 mM). (B) Effects of ET receptor antagonists when arteries were contracted with ET-1 (0.1 mM). When maximal contraction was established, ET receptor antagonists were added at the same concentrations used in panel A as illustrated on typical recordings of variations of isometric tension (upper panels). Bar graph represents the average tension after the addition of the drugs, expressed as a percentage of the contraction induced by ET-1 (lower panel). In all experiments, values indicate the means 6 S.E.M. of 10 different arteries with experiments performed in triplicate.
A biphasic calcium phosphate has been chosen as a mate- rial for implantology to improve dissolution characteristics imparted by the addition of b-tricalcium phosphate. The b- TCP phase undergoes faster resorption than FAp, allowing the precipitation of apatites. The choice of uorapatite is reasonable due to more thermally stable and higher crystal- linity than hydroxyapatite, what is also signicant in cement production for implantology. The Ca 10 (PO 4 ) 6 F 2 and Ca 3 (PO 4 ) 2 materials from diﬀerent stable phases and the bioactivity as well as biodegradation of a biphasic phosphate containing both phases depends strongly on the variation of the ratio of FAp/b-TCP.
colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.
Nat Med 2016 ; 22 : 598-605.
9. Zelante T, Iannitti RG, Cunha C, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 2013 ; 39 : 372-85. 10. Lamas B, Richard ML, Sokob H. Card9 et colyte : un
Two examples are shown in Table 4. In the case of wheat, when expressing the nitrogen content as crude protein (Nx6.25), the chemical score is 0.50, exactly as it is when using nitrogen. When resorting to Jones' factor, the use of 5.83 as a conversion factor decreases the estimate of protein and accordingly increases the chemical score, or quality index. The use of a real specific conversion factor (Nx5.49) further decreases the estimate of protein content (as it is more accurate with respect to amino acids) and increases the quality index (“protein”-amino acids being, of course, richer in lysine). A similar impact on estimates of protein quantity and quality are shown for navy bean (Table 4). Interestingly, in this latter example, if the real conversion factor is used rather than the standard method of converting nitrogen to “protein”, the real protein content is 15% lower and the chemical score is no longer below the unit. The final conclusion is thus that if protein per se is considered, navy bean protein is not deficient in sulfur amino acids. Please note that for sake of clarity in these examples, we set the lysine reference at 51 mg/g_protein although when resorting to real specific conversion factors, the average conversion factor of 5.6 is preferable to 6.25 when expressing the reference pattern as protein and therefore calculating a chemical score based on protein in both the foodstuff (Nx5.4 in the example) and the reference (Nx5.6). If this system is applied, the reference for lysine (320mg/g_N) would be better set at 51x6.25/5.6 = 57 rather than 51 mg/g_protein, which would result in the most accurate estimate of protein quality. This slightly differs from the chemical score based on nitrogen or Nx6.25, depending on whether the specific foodstuff factor is distant from 5.6.
This article treats the rapid-equilibrium kinetics of the forward and reverse reactions of the enzyme-catalyzed A + B ) P + Q together and emphasizes the importance of reporting the values of the full set of equilibrium constants. A computer is used to derive rate equations for three mechanisms and to estimate the kinetic parameters with the minimum number of velocity measurements. The concept that N kinetic parameters can be calculated from N velocity measurements was introduced by Duggleby 1 in connection with his discussion of the statistics of
Figure 1: Effect of pH on lipase activity
Thermal stability: The immobilization of lipases onto
solid support contributes to increase their thermostability and to extend their biotechnology potential, since running bioprocesses at elevated temperature is advantageous (Hasan et al., 2006). Both of the thermal stability of the free and the immobilized lipase was determined by measuring the residual conversion of oleic acid at 37°C after the enzyme exposed to temperatures ranging from 37 to 60°C in phosphate buffer (0.1 M, pH 7.5) for 30 min
Examination of the structure of the b-wing (Figure 3) suggests an explanation for this eﬀect. The wing from vZa E3L is positioned parallel to the DNA, aligning the two prolines nearest to the backbone, while the wing from yabZa E3L extends toward the backbone, providing DNA interactions not only with the prolines but also with the Asn at P-1. It is possible that both P-1 and P-2 amino acid residues can make DNA contacts, possibly with DNA in an intermediate state between B and Z. These residues would then play a larger role in the conversion of DNA from the B to the Z-form than in binding to pre-stabilized Z-DNA. If this is true, positively charged and polar residues at positions P-1 and P-2 should eﬀect the B to Z-DNA transition better non-polar amino acids and much better than negatively charged amino acids. The yabZa E3L mutants described above both satisfy this prediction. In the case of vZa E3L , the negatively charged Asp at P-2 could decrease binding to DNA, and the neutral Ile at P-1 cannot form hydrogen binds. The mutations D60T and I61T, vZa E3L DI6061TT, remove one negative charge and oﬀer the possibility of hydrogen bonds at both sites. Effect of changes in P-1 and P-2 in other viral Zas
Figure 4. Implication de la protéine kinase CK2 dans la survie cellulaire. Lors d’une réponse inflammatoire, la protéine inhibitrice I κ B, qui maintient normalement dans le cytoplasme le facteur de transcription NF- κ B sous une forme inac- tive, est dégradée. La CK2 fait partie des kinases qui règlent la dégradation de I κ B et stimulent l’activité transcrip- tionnelle de NF- κ B. La voie de signalisation dépendante du ligand Wnt-1 contribue à l’augmentation de la survie cel- lulaire en bloquant l’apoptose  . La CK2, présente dans un complexe contenant, entre autres, la protéine Dsh et la β -caténine, participe à la transduction du signal Wnt-1. La phosphorylation de la β -caténine par CK2 stimule sa translocation nucléaire et règle l’expression de gènes dont les produits protéiques sont impliqués dans la survie cel- lulaire  . Lors de l’activation du récepteur Fas, la protéine pro-apoptotique Bid doit être clivée par la caspase-8 pour permettre la libération du cytochrome C  . La phosphorylation de Bid par la CK2 sur un site proche du site de coupure de la caspase-8 la rend résistante à cette protéolyse activatrice  . La phosphorylation par CK2 de la pro- téine ARC, protéine inhibitrice de la caspase-8, cible cette protéine dans la mitochondrie et permet ainsi son interac- tion avec la caspase  . De façon similaire, l’activation du récepteur Fas déclenche la protéolyse du facteur de transcription Max par la caspase 5. Là encore, la phosphorylation de Max par la CK2 rend ce facteur de transcription résistant à cette protéolyse  . La PI3K est nécessaire et suffisante pour protéger les cellules de l’apoptose. Le pro- duit du gène suppresseur de tumeur PTEN antagonise l’action anti-apoptotique de la PI3K  . La phosphorylation de PTEN par CK2 entraîne une inhibition de son activité phosphatase  . TNF α : tumor necrosis factor α ; FRZ: récep- teur frizzled; Dsh: dishevelled; GSK3 β : glycogen synthase kinase 3 β ; Fas L: Fas ligand; Fas R: récépteur de Fas L; PI3K: phosphatidylinositol 3-kinase; Cyt C: cytochrome C; PKB: protéine kinase B, IKK: I κ B-kinase.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. The cells were isolated from human articular cartilage obtained at surgery and were cultured in the absence or presence of ET-1 with or without inhibitors of protein kinase or LY83583 (an inhibitor of soluble guanylate cyclase and of cGMP). MMP-1, MMP-13 and NO levels were then measured by ELISA and Griess reaction, respectively. Additionally, inducible nitric oxide synthase (iNOS) and phosphorylated forms of p38 mitogen-activated protein kinase, p44/42, stress-activated protein kinase/Jun-N-terminal kinase and serine-threonine Akt kinase were determined by western blot. Results show that ET-1 greatly increased MMP-1
Figure 1: Synthesis of a caged isoproterenol analog. N-(2-nitrobenzyl)-L-isoproterenol (ZCS- 1-67) was synthesized as described in Methods.
Figure 2: Effect of various agonists on NO production. Enriched nuclear fractions were preincubated with the fluorescent dye DAF-2 (5 µg/mL), then stimulated with either A) 1 µM isoproterenol or 100 nM ET-1, in the absence or presence of the NOS inhibitor L-NAME (1 mM). B) NO production in response to 1 µM isoproterenol, 100 nM forskolin, 1 µM xamoterol, or 1 µM BRL 37344. C) NO production in response to 1 µM isoproterenol in the presence or absence of 5 nM CGP20712, 10 nM ICI 118,551 or 1 µM SR59230A. NO production was determined as a measure of DAF-2 fluorescence at wavelengths of 485 nm (excitation) and 510 nm (emission). Data represents mean ± S.E. of at least three separate experiments performed in duplicate and are normalized to control. Significant differences (*, p<0.05) were determined by one-way ANOVA for three or more experiments.
fibrose, le stress oxydatif et l’apoptose de nombreux types de cellules du sys- tème cardiovasculaire.
La caractérisation de cette enzyme a donné naissance, au cours des années 1980, à une classe thérapeutique majeure, celle des inhibiteurs de l’en- zyme de conversion, qui a démontré sa grande efficacité dans des maladies aussi diverses que l’hypertension arté- rielle, l’insuffisance cardiaque ou la néphropathie diabétique. Le dévelop- NOUVELLE
All the above results show that CsGeBr 3 with C doping
undergoes topological phase transition through path (a)-(b)- (d), while the CsSnBr 3 with C doping undergoes topological
phase transition through path (a)-(c)-(d) (see Fig. 1 ). Evidently the topological phase transition can be attributed to the lower orbital levels of C 2p states in comparison with Ge 4p or Sn 5p states, and different paths for the topological phase transition originate from the energy difference between the dopant state (i.e., C 2p state) and host state (i.e., Ge 4p or Sn 5p state) around the Fermi level. Larger difference in the orbital levels leads to larger downshift of the CBM, and the band inversion occurs directly when the energy difference is large enough.
rendering of the outside of those beads, after converting the mesh to a 3D image.
Efficient data structure conversions should be a basic requirement in any scientific data processing toolbox. When handling 3D image data the passage from a surface mesh to voxels in a cubic grid may arise, and when the data to process is very large (particularly several gigabytes in the case of tomography), the usability of any data processing depends on reasoned algorithmic choices.
The present study is a part of an ongoing research project which is aimed at developing a thermodynamic database for simulation of copper extraction from sulfide concentrates. The previous one dealt with the Cu–O–S system . The major phases that form during copper smelting and converting are: blister copper (a liquid metal phase rich in Cu), matte (a molten sulfide phase containing mainly Cu, S and Fe), slag (a molten oxide phase) and gas. In principle, all three liquid phases represent just one liquid with miscibility gaps. Liquid metal, matte and slag can be completely miscible over certain ranges of temperature and composition, even though this normally does not happen under industrial conditions. It is desirable to have one general thermodynamic model which can describe all three liquid phases simultaneously, but this is very difficult to achieve because the model must reflect quite different atomic interactions that are intrinsic to metallic, sulfide and oxide phases.