Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization. STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne® 800 µg/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability. RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 ± 27 vs. 11 ± 2 (mean ± SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 ± 21 vs. 14 ± 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment. CONCLUSION: Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.

Fictions cartographiques

Considering normal maps that geographers do, it is possible to discuss strange maps in confrontation with the status of real maps. It is by using a precise epistemological model inspired by S. Lupasco that we will examine four relevant examples of fictuous maps. We will refer explicitly to a ternary epistemological model to confront extravagant situations furnished by litterature in regard to our normal maps. By using an explicite ternary language in relation here to the structure of the map, we will refer to the two fundamental concepts of scale and legend to show how those four fictions are emblematic and help us to understand the real maps. The ternary model scale/legend/mapmaking will be the reference model to illustrate how the Captain's map in L. Carroll, the Utopia Island of T. More, the Map of China of J.-L. Borgès and the Tender Map of M. de Scudéry are referenced in our model in regard of the real map, tertium datur, the mediator in the interaction of scale and legend.

Integration of ground-penetrating radar and microgravimetric methods to map shallow caves

Ground-penetrating radar (GPR) and microgravimetric surveys have been conducted in the southern Jura mountains of western Switzerland in order to map subsurface karstic features. The study site, La Grande Rolaz cave, is an extensive system in which many portions have been mapped. By using small station spacing and careful processing for the geophysical data, and by modeling these data with topographic information from within the cave, accurate interpretations have been achieved. The constraints on the interpreted geologic models are better when combining the geophysical methods than when using only one of the methods, despite the general limitations of two-dimensional (2D) profiling. For example, microgravimetry can complement GPR methods for accurately delineating a shallow cave section approximately 10 X 10 mt in size. Conversely, GPR methods can be complementary in determining cavity depths and in verifying the presence of off-line features and numerous areas of small cavities and fractures, which may be difficult to resolve in microgravimetric data.

Nouveaux traitements de l'hépatite C: aspects pharmacologiques et potentiel d'interaction [New hepatitis C treatments: pharmacological considerations and potential for drug interactions].

Progress in the understanding of the hepatitis C virus life cycle allowed the development of new, very promising antiviral therapies. Although these new drugs have a favourable profile in terms of efficacy, tolerance and interaction potential, their prescription in the setting of comedication and impaired renal or hepatic function remains a challenge. Here, we provide a summary of pharmacological considerations, focusing on sofosbuvir, simeprevir and daclatasvir. A better understanding of their metabolic pathways and transporters may help the prescriber to identify and manage drug interactions especially in patients under immunosuppressive or anti-HIV therapy. Recommendations for the prescription of these drugs in specific situations are also discussed.

DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.

Detection of viral nucleic acids is central to antiviral immunity. Recently, DAI/ZBP1 (DNA-dependent activator of IRFs/Z-DNA binding protein 1) was identified as a cytoplasmic DNA sensor and shown to activate the interferon regulatory factor (IRF) and nuclear factor-kappa B (NF-kappaB) transcription factors, leading to type-I interferon production. DAI-induced IRF activation depends on TANK-binding kinase 1 (TBK1), whereas signalling pathways and molecular components involved in NF-kappaB activation remain elusive. Here, we report the identification of two receptor-interacting protein (RIP) homotypic interaction motifs (RHIMs) in the DAI protein sequence, and show that these domains relay DAI-induced NF-kappaB signals through the recruitment of the RHIM-containing kinases RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI-induced NF-kappaB activation. Importantly, RIP recruitment to DAI is inhibited by the RHIM-containing murine cytomegalovirus (MCMV) protein M45. These findings delineate the DAI signalling pathway to NF-kappaB and suggest a possible new immune modulation strategy of the MCMV.

User cost of capital with delayed investment grants

The usual assumption when considering investment grants is that grant payments are automatic when investments are undertaken. However, evidence from case studies shows that there can exist some time lag until funds are received by granted firms. In this paper the effects of delays in grant payments on the optimal investment policy of the firm are analyzed. It is shown how these delays lead not only to a higher financing cost but to an effective reduction in the investment grant rate, and in some cases, how benefits from investment grants could be canceled due to interactions with tax effects.

Interaction of prechilling, temperature, osmotic stress, and light in Picea abies seed germination

Summary

Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity : a role for microglia

The neuroprotective effect of neuropeptide Y (NPY) receptor activation was investigated in organotypic mouse hippocampal slice cultures exposed to the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Exposure of 2-week-old slice cultures, derived from 7-day-old C57BL/6 mice, to 8 microm AMPA, for 24 h, induced degeneration of CA1 and CA3 pyramidal cells, as measured by cellular uptake of propidium iodide (PI). A significant neuroprotection, with a reduction of PI uptake in CA1 and CA3 pyramidal cell layers, was observed after incubation with a Y(2) receptor agonist [NPY(13-36), 300 nm]. This effect was sensitive to the presence of the selective Y(2) receptor antagonist (BIIE0246, 1 microm), but was not affected by addition of TrkB-Fc or by a neutralizing antibody against brain-derived neurotrophic factor (BDNF). Moreover, addition of a Y(1) receptor antagonist (BIBP3226, 1 microm) or a NPY-neutralizing antibody helped to disclose a neuroprotective role of endogenous NPY in CA1 region. Cultures exposed to 8 microm AMPA for 24 h, displayed, as measured by an enzyme-linked immunosorbent assay, a significant increase in BDNF. In such cultures there was an up-regulation of neuronal TrkB immunoreactivity, as well as the presence of BDNF-immunoreactive microglial cells at sites of injury. Thus, an increase of AMPA-receptor mediated neurodegeneration, in the mouse hippocampus, was prevented by neuroprotective pathways activated by NPY receptors (Y(1) and Y(2)), which can be affected by BDNF released by microglia and neurons.

First-generation linkage map for the European tree frog (Hyla arborea) with utility in congeneric species.

BACKGROUND: Western Palearctic tree frogs (Hyla arborea group) represent a strong potential for evolutionary and conservation genetic research, so far underexploited due to limited molecular resources. New microsatellite markers have recently been developed for Hyla arborea, with high cross-species utility across the entire circum-Mediterranean radiation. Here we conduct sibship analyses to map available markers for use in future population genetic applications. FINDINGS: We characterized eight linkage groups, including one sex-linked, all showing drastically reduced recombination in males compared to females, as previously documented in this species. Mapping of the new 15 markers to the ~200 My diverged Xenopus tropicalis genome suggests a generally conserved synteny with only one confirmed major chromosome rearrangement. CONCLUSIONS: The new microsatellites are representative of several chromosomes of H. arborea that are likely to be conserved across closely-related species. Our linkage map provides an important resource for genetic research in European Hylids, notably for studies of speciation, genome evolution and conservation.

Interaction analysis and psychology: A dialogical perspective

Interaction analysis is not a prerogative of any discipline in social sciences. It has its own history within each disciplinary field and is related to specific research objects. From the standpoint of psychology, this article first draws upon a distinction between factorial and dialogical conceptions of interaction. It then briefly presents the basis of a dialogical approach in psychology and focuses upon four basic assumptions. Each of them is examined on a theoretical and on a methodological level with a leading question: to what extent is it possible to develop analytical tools that are fully coherent with dialogical assumptions? The conclusion stresses the difficulty of developing methodological tools that are fully consistent with dialogical assumptions and argues that there is an unavoidable tension between accounting for the complexity of an interaction and using methodological tools which necessarily "monologise" this complexity.

Ferromagnetic instabilities in neutron matter at finite temperature with the Skyrme interaction

The properties of spin-polarized neutron matter are studied at both zero and finite temperature using Skyrme-type interactions. It is shown that the critical density at which ferromagnetism takes place decreases with temperature. This unexpected behavior is associated to an anomalous behavior of the entropy that becomes larger for the polarized phase than for the unpolarized one above a certain critical density. This fact is a consequence of the dependence of the entropy on the effective mass of the neutrons with different third spin component. A new constraint on the parameters of the effective Skyrme force is derived if this behavior is to be avoided.

Transition to parenthood: The role of social interaction and endogenous networks

Empirical studies indicate that the transition to parenthood is influenced by an individual's peer group. To study the mechanisms creating interdepen- dencies across individuals' transition to parenthood and its timing we apply an agent-based simulation model. We build a one-sex model and provide agents with three different characteristics regarding age, intended education and parity. Agents endogenously form their network based on social closeness. Network members then may influence the agents' transition to higher parity levels. Our numerical simulations indicate that accounting for social inter- actions can explain the shift of first-birth probabilities in Austria over the period 1984 to 2004. Moreover, we apply our model to forecast age-specific fertility rates up to 2016.

Double folding with a density-dependent effective interaction and it s analytical approximation

The real part of the optical potential for heavy ion elastic scattering is obtained by double folding of the nuclear densities with a density-dependent nucleon-nucleon effective interaction which was successful in describing the binding, size, and nucleon separation energies in spherical nuclei. A simple analytical form is found to differ from the resulting potential considerably less than 1% all through the important region. This analytical potential is used so that only few points of the folding need to be computed. With an imaginary part of the Woods-Saxon type, this potential predicts the elastic scattering angular distribution in very good agreement with experimental data, and little renormalization (unity in most cases) is needed.