Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation

Chronic kidney disease is a common problem in the elderly and is associated with increased mortality. We have reported on the role of nitric oxide, which is generated from endothelial nitric oxide synthase (eNOS), in the progression of aged kidneys. To elucidate the role of endothelial dysfunction and the lack of an eNOS-NO pathway in ageing kidneys, we conducted experiments using eNOS and ASC-deficient mice. C57B/6 J mice (wild type (WT)), eNOS knockout (eNOS KO), and ASC knockout (ASC KO) mice were used in the present study. Then, eNOS/ASC double-knockout (eNOS/ASC DKO) mice were generated by crossing eNOS KO and ASC KO mice. These mice were sacrificed at 17−19 months old. The Masson positive area and the KIM-1 positive area tended to increase in eNOS KO mice, compared with WT mice, but not eNOS/ASC DKO mice. The COX-positive area was significantly reduced in eNOS KO mice, compared with WT and eNOS/ASC DKO mice. To determine whether inflammasomes were activated in infiltrating macrophages, the double staining of IL-18 and F4/80 was performed. IL-18 and F4/80 were found to be co-localised in the tubulointerstitial areas. Inflammasomes play a pivotal role in inflammaging in ageing kidneys. Furthermore, inflammasome activation may accelerate cellular senescence via mitochondrial dysfunction. The importance of endothelial function as a regulatory mechanism suggests that protection of endothelial function may be a potential therapeutic target.     

Path integral approach to dissipation in solid-state qubits

We provide a full numerical characterization of non-Markovian quantum decoherence for a two-level (qubit) system coupled to a tailorable reservoir by studying the influence of different factors, such as system–reservoir coupling and temperature. The necessity of a decoherence analysis from short to long time ranges and for a large set of parameters are fundamental requirements for quantum information processing in order to produce a controlled conditional quantum dynamics. We show how the Feynman–Vernon influence functional technique can be used in order to obtain a numerical algorithm that enables a full characterization of non-Markovian processes. This analysis paves the way for modeling the prevention and control of decoherence in solid-state systems with ultrafast dynamics and strong environmental coupling.     

Gap filling strategies for 3-D-FBP reconstructions of High-Resolution Research Tomograph scans

The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography scanner. Currently available iterative reconstruction algorithms show bias due to nonnegativity constraints. Consequently, implementation of 3-D filtered backprojection (3-D-FBP) is of interest. To apply 3-D-FBP all missing data including those due to gaps between detector heads need to be estimated. The aim of this study was to evaluate various gap filling strategies for 3-D-FBP reconstructions of HRRT data, such as linear and bilinear interpolation or constraint Fourier space gap filling (confosp). Furthermore, missing planes were estimated using segment 0 image data only (noniterative) or by using reconstructed images based on all previous segments (iterative method). Use of bilinear interpolation showed worst correspondence between reconstructed and true activity concentration, especially for small structures. Moreover, phantom data indicated that use of linear interpolation resulted in artifacts in planes located near the edge of the field-of-view. Use of confosp did not show these artifacts. Iterative estimations of the missing planes for $vert {hbox {segments}}vert > 0$ improved image quality at the cost of more computation time. Therefore, use of confosp for filling sinogram gaps with both iterative and noniterative estimation of missing planes are recommended for quantitative 3-D-FBP of HRRT studies.      

Virtue-based measurement of ethical leadership: The Leadership Virtues Questionnaire.

Approaching ethical leadership from a characterological perspective, this study reports on the creation of the Leadership Virtues Questionnaire (LVQ). Defining an ethical leader as one who adheres to the four cardinal virtues of prudence, fortitude, temperance, and justice, as discussed in the ancient texts of Aristotle and St. Thomas Aquinas, we developed a rating instrument for assessing leader virtues. A series of studies with managers examined the psychometric properties and correlates of the LVQ. Factor analyses suggested that one factor best captured the construct, not inconsistent with philosophers' notions of the “unity” of the cardinal virtues. The LVQ was shown to be highly positively correlated with transformational leadership, authentic leadership, and another recently developed measure of ethical leadership, and there was evidence of discriminant validity. The LVQ, used with the virtues approach to ethical leadership, should prove to be a valuable tool for the assessment and development of leader virtues and ethics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunopathology of the uveitis in canine leishmaniasis

Particular immunopathological features and their effects on the vascular permeability of different ocular structures were analysed in two dogs naturally infected by Leishmania infantum. The existence of specific anti-Leishmania immunoglobulin G (IgG) in the aqueous humour was confirmed by the ELISA technique. There was no correlation between antibody levels in the aqueous humour and the related serum. The histopathological study of the eyes showed the existence of lesions in various ocular structures. The ciliary processes, ciliary body, sclerocorneal limbus, iris and lacrimal duct showed intense inflammatory zones with lymphocyte infiltrates, plasmatic cells and macrophages with amastigote forms of Leishmania. In addition vasculitis with dilation and thrombi were also detected in both cases, with consequent oedema and hyalinization. The immunohistochemistry analysis revealed the presence of granular and diffuse IgG deposits in the ciliary body, ciliary processes, sclerocorneal limbus and iris. Furthermore, numerous thrombosed vessels were observed in the sclerocorneal zone and iris. Complement 3 (C3) fraction deposits were not present in the ocular structures. The present data suggest that the ocular lesions may have an immunopathological origin.     

Efficient Construction of Minimal Cut Sets from Fault Trees

A formal method and an algorithm are presented to determine minimal cut sets (MCSs) from fault trees. The method is based upon segmenting the tree, constructing MCSs of subtrees and subsequent expanding into the MCS of the original tree. The major advantage of the method is the direct determination of MCSs up to any order required. More particularly, the algorithm DICOMICS allows straightforward analyses for all those cases (large trees, high order cut sets, repeated elements) where present combinatorial and Monte Carlo techniques are not effective. Compared with other structural algorithms now in use, DICOMICS provides a near optimal effective construction of MCSs. Thus, even when there are many redundant cut sets, computer implementations yield a substantial reduction of computing steps and effort. Hand calculation and interactive programming are also possible.     

Increase of Circulating Monocyte–Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte–PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte–PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.