Influence of age on retinochoroidal healing processes after argon photocoagulation in C57bl/6j mice.

PURPOSE: To analyze the influence of age on retinochoroidal wound healing processes and on glial growth factor and cytokine mRNA expression profiles observed after argon laser photocoagulation. METHODS: A cellular and morphometric study was performed that used 44 C57Bl/6J mice: 4-week-old mice (group I, n=8), 6-week-old mice (group II, n=8), 10-12-week-old mice (group III, n=14), and 1-year-old mice (group IV, n=14). All mice in these groups underwent a standard argon laser photocoagulation (50 microm, 400 mW, 0.05 s). Two separated lesions were created in each retina using a slit lamp delivery system. At 1, 3, 7, 14, 60 days, and 4 months after photocoagulation, mice from each of the four groups were sacrificed by carbon dioxide inhalation. Groups III and IV were also studied at 6, 7, and 8 months after photocoagulation. At each time point the enucleated eyes were either mounted in Tissue Tek (OCT), snap frozen and processed for immunohistochemistry or either flat mounted (left eyes of groups III and IV). To determine, by RT-PCR, the time course of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and monocyte chemotactic protein-1 (MCP-1) gene expression, we delivered ten laser burns (50 microm, 400 mW, 0.05 s) to each retina in 10-12-week-old mice (group III', n=10) and 1-year-old mice (group IV', n=10). Animals from Groups III' and IV' had the same age than those from Groups III and IV, but they received ten laser impacts in each eye and served for the molecular analysis. Mice from Groups III and IV received only two laser impacts per eye and served for the cellular and morphologic study. Retinal and choroidal tissues from these treated mice were collected at 16 h, and 1, 2, 3, and 7 days after photocoagulation. Two mice of each group did not receive photocoagulation and were used as controls. RESULTS: In the cellular and morphologic study, the resultant retinal pigment epithelium interruption expanse was significantly different between the four groups. It was more concise and smaller in the oldest group IV (112.1 microm+/-11.4 versus 219.1 microm+/-12.2 in group III) p<0.0001 between groups III and IV. By contrast, while choroidal neovascularization (CNV) was mild and not readily identifiable in group I, at all time points studied, CNV was more prominent in the (1-year-old mice) Group IV than in the other groups. For instance, up to 14 days after photocoagulation, CNV reaction was statistically larger in group IV than in group III ((p=0.0049 between groups III and IV on slide sections and p<0.0001 between the same groups on flat mounts). Moreover, four months after photocoagulation, the CNV area (on slide sections) was 1,282 microm(2)+/-90 for group III and 2,999 microm(2)+/-115 for group IV (p<0.0001 between groups III and IV). Accordingly, GFAP, VEGF, and MCP-1 mRNA expression profiles, determined by RT-PCR at 16 h, 1, 2, 3, and 7 days postphotocoagulation, were modified with aging. In 1-year-old mice (group IV), GFAP mRNA expression was already significantly higher than in the younger (10-12 week) group III before photocoagulation. After laser burns, GFAP mRNA expression peaked at 16-24 h and on day 7, decreasing thereafter. VEGF mRNA expression was markedly increased after photocoagulation in old mice eyes, reaching 2.7 times its basal level at day 3, while it was only slightly increased in young mice (1.3 times its level in untreated young mice 3 days postphotocoagulation). At all time points after photocoagulation, MCP-1 mRNA expression was elevated in old mice, reaching high levels of expression at 16 h and day 3 respectively. CONCLUSIONS: Our results were based on the study of four different age groups and included not only data from morphological observations but also from a molecular analysis of the various alterations of cytokine signaling and expression. One-year-old mice demonstrated more extensive CNV formation and a slower pace of regression after laser photocoagulation than younger mice. These were accompanied by differences in growth factors and cytokine expression profiles indicate that aging is a factor that aggravates CNV. The above results may provide some insight into possible therapeutic strategies in the future.

Theory for correlation functions of processes driven by external colored noise

We study steady-state correlation functions of nonlinear stochastic processes driven by external colored noise. We present a methodology that provides explicit expressions of correlation functions approximating simultaneously short- and long-time regimes. The non-Markov nature is reduced to an effective Markovian formulation, and the nonlinearities are treated systematically by means of double expansions in high and low frequencies. We also derive some exact expressions for the coefficients of these expansions for arbitrary noise by means of a generalization of projection-operator techniques.

The role of oxidative stress during inflammatory processes.

Abstract The production of various reactive oxidant species in excess of endogenous antioxidant defense mechanisms promotes the development of a state of oxidative stress, with significant biological consequences. In recent years, evidence has emerged that oxidative stress plays a crucial role in the development and perpetuation of inflammation, and thus contributes to the pathophysiology of a number of debilitating illnesses, such as cardiovascular diseases, diabetes, cancer, or neurodegenerative processes. Oxidants affect all stages of the inflammatory response, including the release by damaged tissues of molecules acting as endogenous danger signals, their sensing by innate immune receptors from the Toll-like (TLRs) and the NOD-like (NLRs) families, and the activation of signaling pathways initiating the adaptive cellular response to such signals. In this article, after summarizing the basic aspects of redox biology and inflammation, we review in detail the current knowledge on the fundamental connections between oxidative stress and inflammatory processes, with a special emphasis on the danger molecule high-mobility group box-1, the TLRs, the NLRP-3 receptor, and the inflammasome, as well as the transcription factor nuclear factor-κB.

Mineralization of the recalcitrant oxalic and oxamic acids by electrochemical advanced oxidation processes using a boron-doped diamond anode

Oxalic and oxamic acids are the ultimate and more persistent by-products of the degradation of N-aromatics by electrochemical advanced oxidation processes (EAOPs). In this paper, the kinetics and oxidative paths of these acids have been studied for several EAOPs using a boron-doped diamond (BDD) anode and a stainless steel or an air-diffusion cathode. Anodic oxidation (AO-BDD) in the presence of Fe2+ (AO-BDD-Fe2+) and under UVA irradiation (AO-BDD-Fe2+-UVA), along with electro-Fenton (EF-BDD), was tested. The oxidation of both acids and their iron complexes on BDD was clarified by cyclic voltammetry. AO-BDD allowed the overall mineralization of oxalic acid, but oxamic acid was removed much more slowly. Each acid underwent a similar decay in AO-BDD-Fe2+ and EFBDD, as expected if its iron complexes were not attacked by hydroxyl radicals in the bulk. The faster and total mineralization of both acids was achieved in AO-BDD-Fe2+-UVA due to the high photoactivity of their Fe(III) complexes that were continuously regenerated by oxidation of their Fe(II) complexes. Oxamic acid always released a larger proportion of NH4 + than NO3- ion, as well as volatile NOx species. Both acids were independently oxidized at the anode in AO-BDD, but in AO-BDD-Fe2+-UVA oxamic acid was more slowlydegraded as its content decreased, without significant effect on oxalic acid decay. The increase in current density enhanced the oxidation power of the latter method, with loss of efficiency. High Fe2+ contents inhibited the oxidation of Fe(II) complexes by the competitive oxidation of Fe2+ to Fe3+. Low current densities and Fe2+ contents are preferable to remove more efficiently these acids by the most potent AO-BDD-Fe2+-UVA method.

Unravelling the interaction between tectonic and sedimentary processes during lithospheric thinning in the Alpine Tethys margins

The discovery of exhumed continental mantle and hyper-extended crust in present-day magma-poor rifted margins is at the origin of a paradigm shift within the research field of deep-water rifted margins. It opened new questions about the strain history of rifted margins and the nature and composition of sedimentary, crustal and mantle rocks in rifted margins. Thanks to the benefit of more than one century of work in the Alps and access to world-class outcrops preserving the primary relationships between sediments and crustal and mantle rocks from the fossil Alpine Tethys margins, it is possible to link the subsidence history and syn-rift sedimentary evolution with the strain distribution observed in the crust and mantle rocks exposed in the distal rifted margins. In this paper, we will focus on the transition from early to late rifting that is associated with considerable crustal thinning and a reorganization of the rift system. Crustal thinning is at the origin of a major change in the style of deformation from high-angle to low-angle normal faulting which controls basin-architecture, sedimentary sources and processes and the nature of basement rocks exhumed along the detachment faults in the distal margin. Stratigraphic and isotopic ages indicate that this major change occurred in late Sinemurian time, involving a shift of the syn-rift sedimentation toward the distal domain associated with a major reorganization of the crustal structure with exhumation of lower and middle crust. These changes may be triggered by mantle processes, as indicated by the infiltration of MOR-type magmas in the lithospheric mantle, and the uplift of the Brianconnais domain. Thinning and exhumation of the crust and lithosphere also resulted in the creation of new paleogeographic domains, the Proto Valais and Liguria-Piemonte domains. These basins show a complex, 3D temporal and spatial evolution that might have evolved, at least in the case of the Liguria-Piemonte basin, in the formation of an embryonic oceanic crust. The re-interpretation of the rift evolution and the architecture of the distal rifted margins in the Alps have important implications for the understanding of rifted margins worldwide, but also for the paleogeographic reconstruction of the Alpine domain and its subsequent Alpine compressional overprint.

Weakening processes in thrust faults: insights from the Monte Perdido thrust fault (southern Pyrenees, Spain)

The Monte Perdido thrust fault (southern Pyrenees) consists of a 6-m-thick interval of intensely deformed clay-bearing rocks. The fault zone is affected by a pervasive pressure solution seam and numerous shear surfaces. Calcite extensional-shear veins are present along the shear surfaces. The angular relationships between the two structures indicate that shear surfaces developed at a high angle (70°) to the local principal maximum stress axis r1. Two main stages of deformation are present. The first stage corresponds to the development of calcite shear veins by a combination of shear surface reactivation and extensional mode I rupture. The second stage of deformation corresponds to chlorite precipitation along the previously reactivated shear surfaces. The pore fluid factor k computed for the two deformation episodes indicates high fluid pressures during the Monte Perdido thrust activity. During the first stage of deformation, the reactivation of the shear surface was facilitated by a suprahydrostatic fluid pressure with a pore fluid factor kv equal to 0.89. For the second stage, the fluid pressure remained still high (with a k value ranging between 0.77 and 0.84) even with the presence of weak chlorite along the shear surfaces. Furthermore, evidence of hydrostatic fluid pressure during calcite cement precipitation supports that incremental shear surface reactivations are correlated with cyclic fluid pressure fluctuations consis- tent with a fault-valve model.

Multiple processes regulate long-term population dynamics of sea urchins on Mediterranean rocky reefs

We annually monitored the abundance and size structure of herbivorous sea urchin populations (Paracentrotus lividus and Arbacia lixula) inside and outside a marine reserve in the Northwestern Mediterranean on two distinct habitats (boulders and vertical walls) over a period of 20 years, with the aim of analyzing changes at different temporal scales in relation to biotic and abiotic drivers. P. lividus exhibited significant variability in density over time on boulder bottoms but not on vertical walls, and temporal trends were not significantly different between the protection levels. Differences in densities were caused primarily by variance in recruitment, which was less pronounced inside the MPA and was correlated with adult density, indicating density-dependent recruitment under high predation pressure, as well as some positive feedback mechanisms that may facilitate higher urchin abundances despite higher predator abundance. Populations within the reserve were less variable in abundance and did not exhibit the hyper-abundances observed outside the reserve, suggesting that predation effects maybe more subtle than simply lowering the numbers of urchins in reserves. A. lixula densities were an order of magnitude lower than P. lividus densities and varied within sites and over time on boulder bottoms but did not differ between protection levels. In December 2008, an exceptionally violent storm reduced sea urchin densities drastically (by 50% to 80%) on boulder substrates, resulting in the lowest values observed over the entire study period, which remained at that level for at least two years (up to the present). Our results also showed great variability in the biological and physical processes acting at different temporal scales. This study highlights the need for appropriate temporal scales for studies to fully understand ecosystem functioning, the concepts of which are fundamental to successful conservation and management.

Early clarification processes in clients presenting with borderline personality disorder: Relations with symptom level and change

Clarification-Oriented Psychotherapy (COP), an integrative treatment form with a basis in process-experiential psychotherapy, is particularly relevant for clients with Personality Disorders (PDs). We argue here that two related core therapeutic COP principles, "dual action regulation" and "interactional games" have consequences for symptom severity and therapeutic outcome for clients with PDs. A high quality COP clarification process requires that client's interactional games may be quickly assessed and treated in all (preferably early) therapy sessions. These processes can be observed and measured using the observer-rated Bochum Process and Relationship Rating Scales (BPRRS) which measure both clients' and therapists' contributions to the quality of the clarification processes engaged in therapy. This measure has been successfully applied to COP-therapies, but not, as yet, to therapies other than experiential, nor to specific client populations such as borderline personality disorder. The present study is a first attempt to evaluate the application of COP processes to other therapies and populations. We measured action regulation and interactional games using the BPRRS during intake sessions of a 10-session psychodynamic treatment of borderline personality disorder for a total of N = 30 clients and N = 8 therapists. Significant relationships were found between the client's degree of interactional games and both pretherapy symptom level and symptom change across therapy. These results are discussed in the context of Clarification-Oriented Psychotherapy, and more generally Person-Centered and Process-Experiential Psychotherapies. The potential relevance of the findings for psychodynamic psychotherapists are explored as well as the potential usefulness of taking into account a detailed analysis of interactional games for the training of psychotherapists working with any model of therapy working with clients presenting with BPD.

Characterization of a MexAB-OprM efflux system necessary for productive metabolism of Pseudomonas azelaica HBP1 on 2-hydroxybiphenyl.

Pseudomonas azelaica HBP1 is one of the few bacteria known to completely mineralize the biocide and toxic compound 2-hydroxybiphenyl (2-HBP), but the mechanisms of its tolerance to the toxicity are unknown. By transposon mutant analysis and screening for absence of growth on water saturating concentrations of 2-HBP (2.7 mM) we preferentially found insertions in three genes with high homology to the mexA, mexB, and oprM efflux system. Mutants could grow at 2-HBP concentrations below 100 μM but at lower growth rates than the wild-type. Exposure of the wild-type to increasing 2-HBP concentrations resulted in acute cell growth arrest and loss of membrane potential, to which the cells adapt after a few hours. By using ethidium bromide (EB) as proxy we could show that the mutants are unable to expel EB effectively. Inclusion of a 2-HBP reporter plasmid revealed that the wild-type combines efflux with metabolism at all 2-HBP concentrations, whereas the mutants cannot remove the compound and arrest metabolism at concentrations above 24 μM. The analysis thus showed the importance of the MexAB-OprM system for productive metabolism of 2-HBP.

The biogenic origin of needle fibre calcite

Needle fibre calcite is one of the most ubiquitous habits of calcite in vadose environments (caves deposits, soil pores, etc.). Its origin, either through inorganic, indirect or direct biological processes, has long been debated. In this study, investigations at 11 sites in Europe, Africa and Central America support arguments for its biogenic origin. The wide range of needle morphologies is the result of a gradual evolution of the simplest type, a rod. This rod is the elementary brick which, by aggregation and welding, builds more complex needles. The absence of cross-welded needles implies that they are welded in a mould, or under a longitudinal and unidirectional constraint, before being released inside the soil pores. The difference between the lengthening of the needles and the c axis can be explained by the existence of needles observed under a scanning electron microscope in organic sleeves, which can act as a mould during rod growth. Complex morphologies with epitaxial outgrowths on straight rods cannot have grown entirely inside organic microtubes; they must result from soil diagenesis after the release of straight rods in a soil-free medium. Whisker crystals are interpreted as the result of growth and coalescence of euhedral crystals on a rod. Rhomb chains are considered to be the consequence of successive epitaxial growth steps on a needle during variations in growth conditions. Isotopic signatures for needle fibre calcite vary from -16.63[per mille] to +1.10[per mille] and from -8.63[per mille] to -2.25[per mille] for Delta13C and Delta18O, respectively. The absence of high Delta18O values for needle fibre calcite precludes a purely physicochemical origin (evaporative) for this particular habit of calcite. As epitaxial growth cannot precipitate in the same conditions as initial needles, needle fibre calcite stable isotopic signatures should be used with caution as a proxy for palaeoenvironmental reconstructions. In addition, it is suggested that the term needle fibre calcite should be kept for the original biogenic form. The other habit should be referred to as epitaxial forms of needle fibre calcite.

EuroPhenome: a repository for high-throughput mouse phenotyping data.

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies.

Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 5580 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function.We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.1511.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.0100.316) and 0.294 (0.0550.534), respectively];walnuts with working memory [1.191 (0.0612.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.0060.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.2362.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.

Real-time monitoring of the silicidation process of tungsten filaments at high temperature used as catalysers for silane decomposition

The scope of this work is the systematic study of the silicidation process affecting tungsten filaments at high temperature (1900ºC) used for silane decomposition in the hot-wire chemical vapour deposition technique (HWCVD). The correlation between the electrical resistance evolution of the filaments, Rfil(t), and the different stages of the their silicidation process is exposed. Said stages correspond to: the rapid formation of two WSi2 fronts at the cold ends of the filaments and their further propagation towards the middle of the filaments; and, regarding the hot central portion of the filaments: a initial stage of silicon dissolution into the tungsten bulk, with a random duration for as-manufactured filaments, followed by the inhomogeneous nucleation of W5Si3 (which is later replaced by WSi2) and its further growth towards the filaments core. An electrical model is used to obtain real-time information about the current status of the filaments silicidation process by simply monitoring their Rfil(t) evolution during the HWCVD process. It is shown that implementing an annealing pre-treatment to the filaments leads to a clearly repetitive trend in the monitored Rfil(t) signatures. The influence of hydrogen dilution of silane on the filaments silicidation process is also discussed.

Selection processes in a citrus hybrid population using RAPD markers

The objective of this work was to evaluate the processes of selection in a citrus hybrid population using segregation analysis of RAPD markers. The segregation of 123 RAPD markers between 'Cravo' mandarin (Citrus reticulata Blanco) and 'Pêra' sweet orange (C. sinensis (L.) Osbeck) was analysed in a F1 progeny of 94 hybrids. Genetic composition, diversity, heterozygosity, differences in chromosomal structure and the presence of deleterious recessive genes are discussed based on the segregation ratios obtained. A high percentage of markers had a skeweness of the 1:1 expected segregation ratio in the F1 population. Many markers showed a 3:1 segregation ratio in both varieties and 1:3 in 'Pêra' sweet orange, probably due to directional selection processes. The distribution analysis of the frequencies of the segregant markers in a hybrid population is a simple method which allows a better understanding of the genetics of citrus group.

External forcings, oceanographic processes and particle flux dynamics in Cap de Creus submarine canyon, NW Mediterranean Sea

Particle fluxes (including major components and grain size), and oceanographic parameters (near-bottom water temperature, current speed and suspended sediment concentration) were measured along the Cap de Creus submarine canyon in the Gulf of Lions (GoL; NW Mediterranean Sea) during two consecutive winter-spring periods (2009 2010 and 2010 2011). The comparison of data obtained with the measurements of meteorological and hydrological parameters (wind speed, turbulent heat flux, river discharge) have shown the important role of atmospheric forcings in transporting particulate matter through the submarine canyon and towards the deep sea. Indeed, atmospheric forcing during 2009 2010 and 2010 2011 winter months showed differences in both intensity and persistence that led to distinct oceanographic responses. Persistent dry northern winds caused strong heat losses (14.2 × 103 W m−2) in winter 2009 2010 that triggered a pronounced sea surface cooling compared to winter 2010 2011 (1.6 × 103 W m−2 lower). As a consequence, a large volume of dense shelf water formed in winter 2009 2010, which cascaded at high speed (up to ∼1 m s−1) down Cap de Creus Canyon as measured by a current-meter in the head of the canyon. The lower heat losses recorded in winter 2010 2011, together with an increased river discharge, resulted in lowered density waters over the shelf, thus preventing the formation and downslope transport of dense shelf water. High total mass fluxes (up to 84.9 g m−2 d−1) recorded in winter-spring 2009 2010 indicate that dense shelf water cascading resuspended and transported sediments at least down to the middle canyon. Sediment fluxes were lower (28.9 g m−2 d−1) under the quieter conditions of winter 2010 2011. The dominance of the lithogenic fraction in mass fluxes during the two winter-spring periods points to a resuspension origin for most of the particles transported down canyon. The variability in organic matter and opal contents relates to seasonally controlled inputs associated with the plankton spring bloom during March and April of both years.