The role of c-Myc in phagocytosis of mycobacteria in human macrophages

Poster Presentation (Doctor’s Session)This journal issue contain proceedings of the CongressMycobacterium tuberculosis is an intracellular pathogen and the causative agent of the disease tuberculosis. Macrophages are the major immunocytes to initiate host immunity against mycobacteria. Among the multiple strategies employ by macrophages to defence against mycobacteria, phagocytosis is the first step. Throughphagocytosis, macrophages could not only clear the pathogens from infection sites, but also present antigens derived from the engulfed bacteria to lymphoid cells. c-Myc is a transcription factor that regulates a variety of target genes. It can form a complex with Max and bind to the enhancer box sequences of the promoter to mediate the transcription. Recently, our group revealed that c-Myc has a potential role in regulating the antimicrobial responses in macrophages. Here, we further revealed that c-Myc may play a positive role in phagocytosis and contribute to host defense to mycobacteria. Pretreatment of c-Myc inhibitor, 10058-F4, could significantly reduce the amount of mycobacteria internalised by macrophages. The acidification of phagolysosome in mycobacteria infected macrophages was also inhibited by 10058-F4. Further investigation showed that macrophages phagocytose mycobacteria in a PI3K/Akt independent pathway. And the action of c-Myc inhibitor does not affect the expression levels of Rho family GTPases. However, we found that 10058-F4 could significantly inhibit phorsphorylation of ERK1/2 kinase, which has been indicated to play a role in FcR mediated phagocytosis in macrophage. In conclusion, c-Myc may play a role in phagocytosis of mycobacteria through regulating phorsphorylation of ERK1/2.published_or_final_versio

Dual-specificity protein phosphatase-1 positively regulates the anti-mycobacterial responses

Posters: abstract no. 214Tuberculosis is still prevalent around world. It is caused by Mycobacterium tuberculosis (Mtb). This microbe stimulates monocytes/macrophages leading to the production of specific cytokines for initiating immune responses. Of these cytokines, tumour necrosis factor-alpha (TNF-α) is crucial for inducing the granuloma formation for restricting Mtb dissemination. Using Bacillus Calmette Guerin (BCG) as a model, we showed ...postprintThe 1st Lorne Infection and Immunity Conference, Lorne, Australia, February 2011. In Abstract Book of the 1st Lorne Infection and Immunity Conference, 2011, p. 111, abstract no. 21

Inhibitory effect of Panax Notoginseng (PNG) extracts on the TNF-α-induced MMP-9 activity in cardiomyoblasts

Poster Presentation 10Cardiac remodeling is a compensatory physiologic response to myocardial infarction. The progression of cardiac remodeling may lead to congestive heart failure which has high mortality rate. In this progression, matrix metalloproteinases (MMPs) plays an important role in the degradation of extracellular matrix (ECM) and subsequent ventricular dilation. Therefore, new treatments targeting MMPs are suggested to ...published_or_final_versio

Theory of disk accretion onto supermassive black holes

Accretion onto supermassive black holes produces both the dramatic phenomena associated with active galactic nuclei and the underwhelming displays seen in the Galactic Center and most other nearby galaxies. I review selected aspects of the current theoretical understanding of black hole accretion, emphasizing the role of magnetohydrodynamic turbulence and gravitational instabilities in driving the actual accretion and the importance of the efficacy of cooling in determining the structure and observational appearance of the accretion flow. Ongoing investigations into the dynamics of the plunging region, the origin of variability in the accretion process, and the evolution of warped, twisted, or eccentric disks are summarized.Comment: Mostly introductory review, to appear in "Supermassive black holes in the distant Universe", ed. A.J. Barger, Kluwer Academic Publishers, in pres

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-

Dynamical Evolution of Planetary Systems

Planetary systems can evolve dynamically even after the full growth of the planets themselves. There is actually circumstantial evidence that most planetary systems become unstable after the disappearance of gas from the protoplanetary disk. These instabilities can be due to the original system being too crowded and too closely packed or to external perturbations such as tides, planetesimal scattering, or torques from distant stellar companions. The Solar System was not exceptional in this sense. In its inner part, a crowded system of planetary embryos became unstable, leading to a series of mutual impacts that built the terrestrial planets on a timescale of ~100 My. In its outer part, the giant planets became temporarily unstable and their orbital configuration expanded under the effect of mutual encounters. A planet might have been ejected in this phase. Thus, the orbital distributions of planetary systems that we observe today, both solar and extrasolar ones, can be different from the those emerging from the formation process and it is important to consider possible long-term evolutionary effects to connect the two.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Black hole spin: theory and observation

In the standard paradigm, astrophysical black holes can be described solely by their mass and angular momentum - commonly referred to as `spin' - resulting from the process of their birth and subsequent growth via accretion. Whilst the mass has a standard Newtonian interpretation, the spin does not, with the effect of non-zero spin leaving an indelible imprint on the space-time closest to the black hole. As a consequence of relativistic frame-dragging, particle orbits are affected both in terms of stability and precession, which impacts on the emission characteristics of accreting black holes both stellar mass in black hole binaries (BHBs) and supermassive in active galactic nuclei (AGN). Over the last 30 years, techniques have been developed that take into account these changes to estimate the spin which can then be used to understand the birth and growth of black holes and potentially the powering of powerful jets. In this chapter we provide a broad overview of both the theoretical effects of spin, the means by which it can be estimated and the results of ongoing campaigns.Comment: 55 pages, 5 figures. Published in: "Astrophysics of Black Holes - From fundamental aspects to latest developments", Ed. Cosimo Bambi, Springer: Astrophysics and Space Science Library. Additional corrections mad

Dynamics of Disks and Warps

This chapter reviews theoretical work on the stellar dynamics of galaxy disks. All the known collective global instabilities are identified, and their mechanisms described in terms of local wave mechanics. A detailed discussion of warps and other bending waves is also given. The structure of bars in galaxies, and their effect on galaxy evolution, is now reasonably well understood, but there is still no convincing explanation for their origin and frequency. Spiral patterns have long presented a special challenge, and ideas and recent developments are reviewed. Other topics include scattering of disk stars and the survival of thin disks.Comment: Chapter accepted to appear in Planets, Stars and Stellar Systems, vol 5, ed G. Gilmore. 32 pages, 17 figures. Includes minor corrections made in proofs. Uses emulateapj.st

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700