A Simple Self-Maintaining Metabolic System: Robustness, Autocatalysis, Bistability

International audienceA living organism must not only organize itself from within; it must also maintain its organization in the face of changes in its environment and degradation of its components. We show here that a simple (M,R)-system consisting of three interlocking catalytic cycles, with every catalyst produced by the system itself, can both establish a non-trivial steady state and maintain this despite continuous loss of the catalysts by irreversible degradation. As long as at least one catalyst is present at a sufficient concentration in the initial state, the others can be produced and maintained. The system shows bistability, because if the amount of catalyst in the initial state is insufficient to reach the non-trivial steady state the system collapses to a trivial steady state in which all fluxes are zero. It is also robust, because if one catalyst is catastrophically lost when the system is in steady state it can recreate the same state. There are three elementary flux modes, but none of them is an enzyme-maintaining mode, the entire network being necessary to maintain the two catalysts

Considering the role of cognitive control in expert performance

© 2014, Springer Science+Business Media Dordrecht. Dreyfus and Dreyfus’ (1986) influential phenomenological analysis of skill acquisition proposes that expert performance is guided by non-cognitive responses which are fast, effortless and apparently intuitive in nature. Although this model has been criticised (e.g., by Breivik Journal of Philosophy of Sport, 34, 116–134 2007, Journal of the Philosophy of Sport, 40, 85–106 2013; Eriksen 2010; Montero Inquiry:An interdisciplinary Journal of Philosophy, 53, 105–122 2010; Montero and Evans 2011) for over-emphasising the role that intuition plays in facilitating skilled performance, it does recognise that on occasions (e.g., when performance goes awry for some reason) a form of ‘detached deliberative rationality’ may be used by experts to improve their performance. However, Dreyfus and Dreyfus (1986) see no role for calculative problem solving or deliberation (i.e., drawing on rules or mental representations) when performance is going well. In the current paper, we draw on empirical evidence, insights from athletes, and phenomenological description to argue that ‘continuous improvement’ (i.e., the phenomenon whereby certain skilled performers appear to be capable of increasing their proficiency even though they are already experts; Toner and Moran 2014) among experts is mediated by cognitive (or executive) control in three distinct sporting situations (i.e., in training, during pre-performance routines, and while engaged in on-line skill execution). We conclude by arguing that Sutton et al. Journal of the British Society for Phenomenology, 42, 78–103 (2011) ‘applying intelligence to the reflexes’ (AIR) approach may help to elucidate the process by which expert performers achieve continuous improvement through analytical/mindful behaviour during training and competition

Genome-Wide Screening of Genes Whose Enhanced Expression Affects Glycogen Accumulation in Escherichia coli

Using a systematic and comprehensive gene expression library (the ASKA library), we have carried out a genome-wide screening of the genes whose increased plasmid-directed expression affected glycogen metabolism in Escherichia coli. Of the 4123 clones of the collection, 28 displayed a glycogen-excess phenotype, whereas 58 displayed a glycogen-deficient phenotype. The genes whose enhanced expression affected glycogen accumulation were classified into various functional categories including carbon sensing, transport and metabolism, general stress and stringent responses, factors determining intercellular communication, aggregative and social behaviour, nitrogen metabolism and energy status. Noteworthy, one-third of them were genes about which little or nothing is known. We propose an integrated metabolic model wherein E. coli glycogen metabolism is highly interconnected with a wide variety of cellular processes and is tightly adjusted to the nutritional and energetic status of the cell. Furthermore, we provide clues about possible biological roles of genes of still unknown functions

The [OIII] emission line luminosity function of optically selected type-2 AGN from zCOSMOS

We present a catalog of 213 type-2 AGN selected from the zCOSMOS survey. The selected sample covers a wide redshift range (0.15<z<0.92) and is deeper than any other previous study, encompassing the luminosity range 10^{5.5} < Lsun< L[OIII] < 10^{9.1} Lsun. We explore the intrinsic properties of these AGN and the relation to their X-ray emission (derived from the XMM-COSMOS observations). We study their evolution by computing the [OIII]5007A line luminosity function (LF) and we constrain the fraction of obscured AGN as a function of luminosity and redshift. The sample was selected on the basis of the optical emission line ratios, after applying a cut to the signal-to-noise ratio (S/N) of the relevant lines. We used the standard diagnostic diagrams [OIII]/Hbeta versus [NII]/Halpha and ([OIII]/Hbeta versus [SII]/Halpha) to isolate AGN in the redshift range 0.15<z<0.45 and the diagnostic diagram [OIII]/Hbeta versus [OII]/Hbeta to extend the selection to higher redshift (0.5<z<0.92). Combining our sample with one drawn from SDSS, we found that the best description of the evolution of type-2 AGN is a luminosity-dependent density evolution model. Moreover, using the type-1 AGN LF we were able to constrain the fraction of type-2 AGN to the total (type-1 + type-2) AGN population. We found that the type-2 fraction decreases with luminosity, in agreement with the most recent results, and shows signs of a slight increase with redshift. However, the trend with luminosity is visible only after combining the SDSS+zCOSMOS samples. From the COSMOS data points alone, the type-2 fraction seems to be quite constant with luminosity.Comment: 20 pages, 11 figures, accepted for publication in Astronomy and Astrophysic

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb/V and dialysis in Spanish clinical practice – preliminary data Vie-KinD study

Poster presentatio

Rab18 Dynamics in Adipocytes in Relation to Lipogenesis, Lipolysis and Obesity

Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed

High spatial resolution mid-infrared spectroscopy of the starburst galaxies NGC 3256, IIZw40 and Henize 2-10

In order to show the importance of high spatial resolution observations of extra-galactic sources when compared to observations obtained with larger apertures such as ISO, we present N-band spectra (8-13 um) of some locations in three starburst galaxies. In particular, the two galactic nuclei of the spiral galaxy NGC3256, the compact IR supernebula in the dwarf galaxy IIZw40 and the two brightest IR knots in the central starburst of the WR galaxy He2-10. The spectra have been obtained with TIMMI2 on the ESO 3.6m telescope. An inventory of the spectra in terms of atomic fine-structure lines and molecular bands is presented. We show the great value of these high spatial resolution data at constraining properties such as the extinction in the mid-IR, metallicity or stellar content (age, IMF, etc.). Regarding this, we have constrained the stellar content of the IR compact knot in IIZw40 by using the mid-IR fine-structure lines and setting restrictions on the nebular geometry. Considering the PAH bands, we have constructed a new mid-/far-IR diagnostic diagram based on the 11.2 um PAH and continuum, accessible to ground-based observations. Finally, we find a dependence between the presence or non-presence of PAHs and the hardness of the radiation field as measured by the [SIV]/[NeII] ratio. In particular, sources with PAH emission have in general a [SIV]/[NeII] ratio < 0.35. We investigate possible origins for this relation and conclude that it does not necessarily imply PAH destruction, but could also be explained by the PAH-dust competition for FUV photons.Comment: 22 pages, 10 figures, accepted for publication in A&

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe