Farnesol induces the transcriptional accumulation of the Aspergillus nidulans Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase

Farnesol (FOH) is a non-sterol isoprenoid produced by dephosphorylation of farnesyl pyrophosphate, a catabolite of the cholesterol biosynthetic pathway. These isoprenoids inhibit proliferation and induce apoptosis. It has been shown previously that FOH triggers morphological features characteristic of apoptosis in the filamentous fungus Aspergillus nidulans. Here, we investigate which pathways are influenced through FOH by examining the transcriptional profile of A. nidulans exposed to this isoprenoid. We observed decreased mRNA abundance of several genes involved in RNA processing and modification, transcription, translation, ribosomal structure and biogenesis, amino acid transport and metabolism, and ergosterol biosynthesis. We also observed increased mRNA expression of genes encoding a number of mitochondrial proteins and characterized in detail one of them, the aifA, encoding the Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase. The Delta aifA mutant is more sensitive to FOH (about 8.0% and 0% survival when exposed to 10 and 100 mu M FOH respectively) than the wild type (about 97% and 3% survival when exposed to 10 and 100 mu M FOH respectively). These results suggest that AifA is possibly important for decreasing the effects of FOH and reactive oxygen species. Furthermore, we showed an involvement of autophagy and protein kinase C in A. nidulans FOH-induced apoptosis.

The roles played by Aspergillus nidulans apoptosis-inducing factor (AIF)-like mitochondrial oxidoreductase (AifA) and NADH-ubiquinone oxidoreductases (NdeA-B and NdiA) in farnesol resistance

Farnesol (FOH) is a nonsterol isoprenold produced by dephosphorylanon of farnesyl pyrophosphate a catabolite of the cholesterol biosynthetic pathway These isoprenoids inhibit proliferation and induce apoptosis Here we show that Aspergillus nidulans MA encoding the apoptosis-Inducing factor (AIF)-like mitochondrial oxidoreductase plays a role in the function of the mitochondrial Complex I Additionally we demonstrated that ndeA B and ndiA encode external and internal alternative NADH dehydrogenases respectively that have a function in FOH resistance When exposed to FOH the Delta aifA and Delta ndeA strains have increased ROS production while Delta ndeB Delta ndeA Delta ndeB and Andul mutant strains showed the same ROS accumulation than in the absence of FOH We observed several compensatory mechanisms affecting the differential survival of these mutants to FOH (C) 2010 Elsevier Inc All rights reserved

Leukotrienes Are Potent Adjuvant during Fungal Infection: Effects on Memory T Cells

Leukotrienes (LTs) are potent lipid mediators involved in the control of host defense. LTB(4) induces leukocyte accumulation, enhances phagocytosis and bacterial clearance, and increases NO synthesis. LTB(4) is also important in early effector T cell recruitment that is mediated by LTB(4) receptor 1, the high-affinity receptor for LTB(4). The aims of this study were to evaluate whether LTs are involved in the secondary immune response to vaccination in a murine model of Histoplasma capsulatum infection. Our results demonstrate that protection of wild-type mice immunized with cell-free Ags from H. capsulatum against histoplasmosis was associated with increased LTB(4) and IFN-gamma production as well as recruitment of memory T cells into the lungs. In contrast, cell-free Ag-immunized mice lacking 5-lipoxygenase(-/-), a critical enzyme involved in LT synthesis, displayed a marked decrease on recruitment of memory T cells to the lungs associated with increased synthesis of TGF-beta as well as IL-10. Strikingly, these effects were associated with increased mortality to 5-lipoxygenase(-/-)-infected mice. These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis. The Journal of Immunology, 2008,181: 8544-8551.

A Critical Appraisal of Narrative in Sport History: Reading the Surf Lifesaving Debate

All debates in history—who started the Cold War, how successful were the Chartists in achieving their aims, to what extent was the recession of the American frontier culturally significant in American history— are debates between competing narrative interpretations. Moreover, because the historical imagination itself exists intertextually within our own social and political environment, the past is never discovered set aside from everyday life. History is designed and composed in the here and now.

On the relationship between the critical temperature and the London penetration depth in layered organic superconductors

We present an analysis of previously published measurements of the London penetration depth of layered organic superconductors. The predictions of the BCS theory of superconductivity are shown to disagree with the measured zero temperature, in plane, London penetration depth by up to two orders of magnitude. We find that fluctuations in the phase of the superconducting order parameter do not determine the superconducting critical temperature as the critical temperature predicted for a Kosterlitz–Thouless transition is more than an order of magnitude greater than is found experimentally for some materials. This places constraints on theories of superconductivity in these materials.

Least energy solutions of a critical Neumann problem with a weight

We investigate the effect of the coefficient of the critical nonlinearity for the Neumann problem on the existence of least energy solutions. As a by-product we establish a Sobolev inequality with interior norm.

On a semilinear Schrodinger equation with critical Sobolev exponent

We consider the semilinear Schrodinger equation -Deltau+V(x)u= K(x) \u \ (2*-2 u) + g(x; u), u is an element of W-1,W-2 (R-N), where N greater than or equal to4, V, K, g are periodic in x(j) for 1 less than or equal toj less than or equal toN, K>0, g is of subcritical growth and 0 is in a gap of the spectrum of -Delta +V. We show that under suitable hypotheses this equation has a solution u not equal 0. In particular, such a solution exists if K equivalent to 1 and g equivalent to 0.

On the nonlinear Neumann problem with critical and supercritical nonlinearities

We investigate the solvability of the Neumann problem (1.1) involving a critical Sobolev exponent. In the first part of this work it is assumed that the coeffcients Q and h are at least continuous. Moreover Q is positive on overline Omega and lambda > 0 is a parameter. We examine the common effect of the mean curvature and the shape of the graphs of the coeffcients Q and h on the existence of low energy solutions. In the second part of this work we consider the same problem with Q replaced by - Q. In this case the problem can be supercritical and the existence results depend on integrability conditions on Q and h.

Two-body and three-body abrasion: A critical discussion

It is argued that the common classification of abrasive wear into 'two-body abrasion' and 'three-body abrasion' is seriously flawed. No definitions have been agreed upon for these terms, and indeed there are two quite different interpretations, the implications of which are mutually inconsistent. In the dominant interpretation, the primary thrust of the two-body/three-body concept is to describe whether the abrasive particles are constrained (two-body) or free to roll (three-body). In this view, two-body abrasion is generally much more severe than three-body. The alternative interpretation emphasises the presence (three-body) or absence (two-body) of a rigid counterface backing the abrasive. In this view, three-body abrasion is equated to high-stress (or grinding) abrasion and is generally more severe than two-body (low-stress) abrasion. This paper recommends that the 'two-body/three-body' terminology be abandoned, to be replaced by an alternative classification scheme based directly upon the manifest severity of wear. (C) 1998 Elsevier Science S.A.

The critical power function is dependent on the duration of the predictive exercise tests chosen

The linear relationship between work accomplished (W-lim) and time to exhaustion (t(lim)) can be described by the equation: W-lim = a + CP.t(lim). Critical power (CP) is the slope of this line and is thought to represent a maximum rate of ATP synthesis without exhaustion, presumably an inherent characteristic of the aerobic energy system. The present investigation determined whether the choice of predictive tests would elicit significant differences in the estimated CP. Ten female physical education students completed, in random order and on consecutive days, five art-out predictive tests at preselected constant-power outputs. Predictive tests were performed on an electrically-braked cycle ergometer and power loadings were individually chosen so as to induce fatigue within approximately 1-10 mins. CP was derived by fitting the linear W-lim-t(lim) regression and calculated three ways: 1) using the first, third and fifth W-lim-t(lim) coordinates (I-135), 2) using coordinates from the three highest power outputs (I-123; mean t(lim) = 68-193 s) and 3) using coordinates from the lowest power outputs (I-345; mean t(lim) = 193-485 s). Repeated measures ANOVA revealed that CPI123 (201.0 +/- 37.9W) > CPI135 (176.1 +/- 27.6W) > CPI345 (164.0 +/- 22.8W) (P < 0.05). When the three sets of data were used to fit the hyperbolic Power-t(lim) regression, statistically significant differences between each CP were also found (P < 0.05). The shorter the predictive trials, the greater the slope of the W-lim-t(lim) regression; possibly because of the greater influence of 'aerobic inertia' on these trials. This may explain why CP has failed to represent a maximal, sustainable work rate. The present findings suggest that if CP is to represent the highest power output that an individual can maintain for a very long time without fatigue then CP should be calculated over a range of predictive tests in which the influence of aerobic inertia is minimised.

Critical sets for families of Latin squares

In this paper I give details of new constructions for critical sets in latin squares. These latin squares, of order n, are such that they can be partitioned into four subsquares each of which is based on the addition table of the integers module n/2, an isotopism of this or a conjugate.