Bistability of mitochondrial respiration underlies paradoxical reactive oxygen species generation induced by anoxia

Increased production of reactive oxygen species (ROS) in mitochondria underlies major systemic diseases, and this clinical problem stimulates a great scientific interest in the mechanism of ROS generation. However, the mechanism of hypoxia-induced change in ROS production is not fully understood. To mathematically analyze this mechanism in details, taking into consideration all the possible redox states formed in the process of electron transport, even for respiratory complex III, a system of hundreds of differential equations must be constructed. Aimed to facilitate such tasks, we developed a new methodology of modeling, which resides in the automated construction of large sets of differential equations. The detailed modeling of electron transport in mitochondria allowed for the identification of two steady state modes of operation (bistability) of respiratory complex III at the same microenvironmental conditions. Various perturbations could induce the transition of respiratory chain from one steady state to another. While normally complex III is in a low ROS producing mode, temporal anoxia could switch it to a high ROS producing state, which persists after the return to normal oxygen supply. This prediction, which we qualitatively validated experimentally, explains the mechanism of anoxia-induced cell damage. Recognition of bistability of complex III operation may enable novel therapeutic strategies for oxidative stress and our method of modeling could be widely used in systems biology studies.

Precipitacion de plata en efluentes electroliticos

La recuperación de plata contenida en efluentes electrolíticos es atractiva por su alto valor económico. Estos efluentes son catalogados como residuos tóxicos y no pueden ser evacuados a cauces públicos sin un tratamiento previo de detoxificación. Una de las vías propuestas para recuperar plata de este tipo de efluentes es la precipitación química utilizando ditionito de sodio, borohidruro de sodio o monohidrato de hidracina. En este trabajo, se discuten los aspectos más signifícativos de la utilización de estos reactivos para el citado objetivo. Se presentan resultados de la precipitación de plata con ditionito de sodio en efluentes base tiosulfato, sin eliminación de otras especies presentes. Se pone de maniflesto la capacidad de este reactivo de cumplir los objetivos de alcanzar una precipitación, prácticamente total, de la plata, dejando el metal en el efluente a niveles de menos de 1 ppm, sin introducir substancias extrañas al sistema.

Variacion del modulo de 'Young' con el tratamiento termico en aceros al carbono hipoeutectoides

En trabajos anteriores se ha constatado que varios aceros al carbono hipoeutectoides, en estado de temple, presentan valores del módulo de Young inferiores a los correspondientes en estado de revenido. En todos los casos la determinación se ha realizado mediante ultrasonidos. En concreto, para el acero C22E (EN 10083), el módulo se incrementa ligeramente desde 209 GPa (material templado) hasta 211 GPa (revenido a 650 °C), para el acero C45E el módulo aumenta desde 199 GPa hasta 211 GPa (revenido a 500 °C) y para el acero C55E el módulo varía desde 202 GPa hasta 209 GPa para el acero revenido a 650 °C. El presente trabajo se centra en la caracterización estructural de los tres aceros mencionados a los distintos estados de tratamiento térmico, utilizando las técnicas de microscopía óptica de reflexión y microscopía electrónica de barrido, y se propone una explicación de la variación del módulo a partir del comportamiento de las dislocaciones y su interacción con átomos de soluto y con otras dislocaciones.

Filamin depletion blocks endoplasmic spreading and destabilizes force-bearing adhesions

Cell motility is an essential process that depends on a coherent, cross-linked actin cytoskeleton that physically coordinates the actions of numerous structural and signaling molecules. The actin cross-linking protein, filamin (Fln), has been implicated in the support of three-dimensional cortical actin networks capable of both maintaining cellular integrity and withstanding large forces. Although numerous studies have examined cells lacking one of the multiple Fln isoforms, compensatory mechanisms can mask novel phenotypes only observable by further Fln depletion. Indeed, shRNA-mediated knockdown of FlnA in FlnB¿/¿ mouse embryonic fibroblasts (MEFs) causes a novel endoplasmic spreading deficiency as detected by endoplasmic reticulum markers. Microtubule (MT) extension rates are also decreased but not by peripheral actin flow, because this is also decreased in the Fln-depleted system. Additionally, Fln-depleted MEFs exhibit decreased adhesion stability that appears in increased ruffling of the cell edge, reduced adhesion size, transient traction forces, and decreased stress fibers. FlnA¿/¿ MEFs, but not FlnB¿/¿ MEFs, also show a moderate defect in endoplasm spreading, characterized by initial extension followed by abrupt retractions and stress fiber fracture. FlnA localizes to actin linkages surrounding the endoplasm, adhesions, and stress fibers. Thus we suggest that Flns have a major role in the maintenance of actin-based mechanical linkages that enable endoplasmic spreading and MT extension as well as sustained traction forces and mature focal adhesions.

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.

Mapping cell-matrix stresses during stretch reveals inelastic reorganization of the cytoskeleton.

The mechanical properties of the living cell are intimately related to cell signaling biology through cytoskeletal tension. The tension borne by the cytoskeleton (CSK) is in part generated internally by the actomyosin machinery and externally by stretch. Here we studied how cytoskeletal tension is modified during stretch and the tensional changes undergone by the sites of cell-matrix interaction. To this end we developed a novel technique to map cell-matrix stresses during application of stretch. We found that cell-matrix stresses increased with imposition of stretch but dropped below baseline levels on stretch release. Inhibition of the actomyosin machinery resulted in a larger relative increase in CSK tension with stretch and in a smaller drop in tension after stretch release. Cell-matrix stress maps showed that the loci of cell adhesion initially bearing greater stress also exhibited larger drops in traction forces after stretch removal. Our results suggest that stretch partially disrupts the actin-myosin apparatus and the cytoskeletal structures that support the largest CSK tension. These findings indicate that cells use the mechanical energy injected by stretch to rapidly reorganize their structure and redistribute tension.

Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy

Contractile tension of alveolar epithelial cells plays a major role in the force balance that regulates the structural integrity of the alveolar barrier. The aim of this work was to study thrombin-induced contractile forces of alveolar epithelial cells. A549 alveolar epithelial cells were challenged with thrombin, and time course of contractile forces was measured by traction microscopy. The cells exhibited basal contraction with total force magnitude 55.0 ± 12.0 nN (mean ± SE, n = 12). Traction forces were exerted predominantly at the cell periphery and pointed to the cell center. Thrombin (1 U/ml) induced a fast and sustained 2.5-fold increase in traction forces, which maintained peripheral and centripetal distribution. Actin fluorescent staining revealed F-actin polymerization and enhancement of peripheral actin rim. Disruption of actin cytoskeleton with cytochalasin D (5 µM, 30 min) and inhibition of myosin light chain kinase with ML-7 (10 µM, 30 min) and Rho kinase with Y-27632 (10 µM, 30 min) markedly depressed basal contractile tone and abolished thrombin-induced cell contraction. Therefore, the contractile response of alveolar epithelial cells to the inflammatory agonist thrombin was mediated by actin cytoskeleton remodeling and actomyosin activation through myosin light chain kinase and Rho kinase signaling pathways. Thrombin-induced contractile tension might further impair alveolar epithelial barrier integrity in the injured lung.

L'herència insolvent

La insolvència de l'herència o del causant ha estat afrontada amb tècniques diverses en tots els ordenaments jurídics. La Llei concursal (Llei 22/2003, de 9 de juliol, a partir d'ara, LCon) es refereix en alguns articles al que s'ha anomenat concurs de l'herència, la qual cosa no vol dir que solucioni, ni de bon tros, els problemes que sorgeixen de la insolvència. En aquest treball només intento identificar alguns dels problemes que la Llei concursal deixa sense resoldre i el que succeeix quan es posen en relació les normes concursals amb el Codi de successions i molt especialment, amb la institució del benefici d¿inventari, així com les regles de la LEC, ja complexes per elles mateixes. Aquest treball, per tant, s¿ha de considerar un working paper en sentit estricte: sempre resulta molt difícil iniciar una matèria en la qual la bibliografia és pràcticament inexistent.

Citizens' control and the efficiency of local public services

Està àmpliament acceptat que la descentralització fiscal incrementa el control dels ciutadans sobre els polítics, fomenta el rendiment de comptes i augmenta l¿eficiència. Aquest treball té per objectiu identificar les característiques socio-econòmiques dels ciutadans (votants potencials) que generen un major control sobre els responsables polítics locals provocant, així, un major nivell d'eficiència en un context descentralitzat.També s'analitzen les característiques fiscals dels governs locals que fomenten aquest control i eficiència. L'estudi s'ha aplicat a una mostra de municipis catalans seguint la metodologia convencional basada en l'estimació en dues etapes. A la primera etapa s'estima l'eficiència en que operen els municipis mitjançant la tècnica DEA. La novetat rau en el càlcul d'una nova versió d'indicador global d¿output municipal. En la segona etapa, a través d¿una estimació tipus Tobit (models censurats) i de mètodes bootstrap, es mostra com els factors abans comentats poden influir sobre l¿eficiència. Els resultats suggereixen que la forta presencia de comerciants, jubilats i persones amb dret a vot afavoreixen el control dels ciutadans, el rendiment de comptes i l¿eficiència. Un factor que facilita aquest control, i per tant una major eficiència, és la presència de baixos costos d'oportunitat d'obtenir informació sobre la gestió local dels serveis públics.

Measuring the efficiency in Spanish municipal refuse collection services

The objective of this study is to analyse the technical or productive efficiency ofthe refuse collection services in 75 municipalities located in the Spanish regionof Catalonia. The analysis has been carried out using various techniques. Firstly we have calculated a deterministic parametric frontier, then a stochastic parametric frontier, and finally, various non-parametric approaches (DEA and FDH). Concerning the results, these naturally differ according to the technique used to approach the frontier. Nevertheless, they have an appearance of solidity, at least with regard to the ordinal concordance among the indices of efficiency obtained by the different approaches, as is demonstrated by the statistical tests used. Finally, we have attempted to search for any relation existing between efficiency and the method (public or private) of managing the services. No significant relation was found between the type of management and efficiencyindices