We studied interactions between integrins and Flk-1 in transducing the mechanical shear stress due to flow. This application of a step shear stress caused Flk-1 ⅐ Casitas B-lineage lymphoma (Cbl) activation (Flk-1 ⅐ Cbl association, tyrosine phosphorylation of the Cbl-bound Flk-1, and tyrosine phosphorylation of Cbl) in bovine aortic endothelial cells (BAECs). The activation of integrins by plating BAECs on vitronectin or fibronectin also induced this Flk-1 ⅐ Cbl activation. The shear-induced Flk-1 ⅐ Cbl activation was blocked by inhibitory antibodies for ␣ v␤3-or ␤1-integrin, suggesting that it is mediated by integrins. Inhibition of Flk-1 by SU1498 also abolished this shear-induced Flk-1 ⅐ Cbl activation. In contrast to the requirement of integrins for Flk-1 ⅐ Cbl activation, the Flk-1 blocker SU1498 had no detectable effect on the shear-induced integrin activation, suggesting that integrins and Flk-1 play sequential roles in the signal transduction hierarchy induced by shear stress. Integrins are essential for the mechanical activation of Flk-1 by shear stress but not for the chemical activation of Flk-1 by VEGF. mechanotransduction; vascular endothelial growth factor; Casitas B-lineage lymphoma MECHANICAL FORCES ARE KNOWN TO PLAY A KEY ROLE in many physiological processes, but how cells perceive mechanical stimuli and convert them into biochemical signaling pathways is not yet well understood. Shear stress, the tangential component of hemodynamic forces acting on the vessel wall, is an important modulator of vascular cell functions in normal and pathophysiological conditions, e.g., endothelial wound healing, atherosclerosis, and reperfusion injury (14,36,37,43). In vitro experiments using endothelial cells (ECs) cultured in flow channels have shown that the structure and function of ECs are modulated by shear stress (6). Recent studies indicate that the mechanochemical transduction in response to shear stress involves different types of receptors and multiple intracellular signaling pathways. Studies from several laboratories, including our own, have demonstrated that shear stress can activate integrins, VEGF receptor-2 (Flk-1), G protein-coupled receptors (GPCR), and ion channels and subsequently regulate mitogen-activated protein kinases and the NF-B pathway through Ras and Rho family GTPases (5,26,33,40). The available evidence indicates that the shear stress-induced signaling from different sensing elements can coordinate downstream signaling through convergent and divergent pathways. However, the possible interaction of these sensing elements in ECs in response to shear stress remains to be investigated.Most intracellular signals are not transduced along a simple linear path involving the interaction of only one molecule with the next. Proteins associate into networks, which are subject to control by many interdependent processes. Many different types of receptors exert mutual influences on each other (9,16,23,30). There is considerable evidence for the synergistic regulation of signals by integrins and...

Decisional impulsivity represents an important phenotype and a therapeutic target in Internet gaming disorder (IGD). Reality therapy and mindfulness meditation were two approaches to reduce impulsivity. This study aimed to evaluate the efficacy of a group behavioral intervention combining reality therapy and mindfulness meditation in reducing decisional impulsivity and IGD severity. Twenty-five IGD and 21 healthy comparison (HC) young adults participated in baseline tests on the delay discounting and balloon analog risk tasks to measure intertemporal and risky decision-making respectively. Among them, 18 IGD subjects participated in the intervention and were tested again at the end of intervention, and 19 HC subjects without intervention were also tested twice within a similar time period. Results indicate that: (1) at baseline, IGD subjects showed greater intertemporal and risky decisional impulsivity than HC subjects; (2) After intervention, IGD subjects were decreased in delay discounting rate and IGD severity, but did not perform differently on decisional impulsivity in risky choices, as compared with baseline. These findings suggest that decisional impulsivity is a multifaceted behavioral construct and may serve as a possible therapeutic target for IGD. In addition, these results highlight the need for further research into the roles of different forms of decisional impulsivity in the shaping, maintenance, and remission of IGD.

The metabolism of glutathione by the periodontal pathogen Treponema denticola produces hydrogen sulfide, which may play a role in the host tissue destruction seen in periodontitis. H 2 S production in this organism has been proposed to occur via a three enzyme pathway, ␥-glutamyltransferase, cysteinylglycinase (CGase), and cystalysin. In this study, we describe the purification and characterization of T. denticola CGase. Standard approaches were used to purify a 52-kDa CGase activity from T. denticola, and high pressure liquid chromatography electrospray ionization tandem mass spectrometry analysis of this molecule showed that it matches the amino acid sequence of a predicted 52-kDa protein in the T. denticola genome data base. A recombinant version of this protein was overexpressed in and purified from Escherichia coli and shown to catalyze the hydrolysis of cysteinylglycine (Cys-Gly) with the same kinetics as the native protein. . Importantly, in combination with the two other previously purified T. denticola enzymes, ␥-glutamyltransferase and cystalysin, CGase mediates the in vitro degradation of glutathione into the expected end products, including H 2 S. These results prove that T. denticola contains the entire three-step pathway to produce H 2 S from glutathione, which may be important for pathogenesis.The volatile sulfur compound H 2 S can be produced by the metabolic activity of numerous oral bacteria, including several periodontal pathogens (1-3). This gas, which is malodorous and highly toxic (4 -6), is found in high concentrations in periodontal pockets (7-9) and may play a role in some of the tissue destruction seen in periodontal diseases (7,8,10). H 2 S can be produced from the metabolism of several molecules, but glutathione (L-␥-glutamyl-L-cysteinylglycine) is believed to be the major source for H 2 S production in the oral cavity; human cells, especially polymorphonuclear leucocytes, have high concentrations (up to 4 mM) of glutathione that can be released when host cells are damaged in the periodontal pocket. Although a number of oral bacteria have been tested, only a few of them are able to catabolize glutathione into H 2 S (3, 11, 12). Treponema denticola, which appears to play a significant role in the development of acute and chronic periodontal diseases in humans (13-17), is the only oral pathogen in which the proteins involved in this catabolic pathway have begun to be identified and characterized (18 -22). Glutathione catabolism to H 2 S (and glutamate, glycine, ammonia, and pyruvate) has been proposed to occur via a three-step enzyme pathway in this spirochete (12). In the first step, glutathione is split into glutamate and Cys-Gly. This dipeptide is then hydrolyzed into glycine and L-cysteine followed by the breakdown of L-cysteine into pyruvate, ammonia, and H 2 S. The enzymes involved in the first and third steps have been purified from T. denticola and characterized (19 -30). ␥-Glutamyltransferase (GGT) 2 is a 27-kDa protein that catalyzes the cleavage of glutathione into glutamate ...

BackgroundChinese bayberry (Myrica rubra Sieb. & Zucc.) is an important subtropical evergreen fruit tree in southern China. Generally dioecious, the female plants are cultivated for fruit and have been studied extensively, but male plants have received very little attention. Knowledge of males may have a major impact on conservation and genetic improvement as well as on breeding. Using 84 polymorphic SSRs, we genotyped 213 M. rubra individuals (99 male individuals, 113 female varieties and 1 monoecious) and compared the difference in genetic diversity between the female and the male populations.ResultsNeighbour-joining cluster analysis separated M. rubra from three related species, and the male from female populations within M. rubra. By structure analysis, 178 M. rubra accessions were assigned to two subpopulations: Male dominated (98) and Female dominated (80). The well-known cultivars ‘Biqi’ and ‘Dongkui’, and the landraces ‘Fenhong’ are derived from three different gene pools. Female population had a slightly higher values of genetic diversity parameters (such as number of alleles and heterozygosity) than the male population, but not significantly different. The SSR loci ZJU062 and ZJU130 showed an empirical Fst value of 0.455 and 0.333, respectively, which are significantly above the 95 % confidence level, indicating that they are outlier loci related to sex separation.ConclusionThe male and female populations of Chinese bayberry have similar genetic diversity in terms of average number of alleles and level of heterozygosity, but were clearly separated by genetic structure analysis due to two markers associated with sex type, ZJU062 and ZJU130. Zhejiang Province China could be the centre of diversity of M. rubra in China, with wide genetic diversity coverage; and the two representative cultivars ‘Biqi’ and ‘Dongkui’, and one landrace ‘Fenhong’ in three female subpopulations. This research provides genetic information on male and female Chinese bayberry and will act as a reference for breeding programs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1602-5) contains supplementary material, which is available to authorized users.

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