VEGF(164)-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF(164) increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF(164)-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF(164)-deficient (VEGF(120/188)) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF(+/+)) controls. In contrast, administration of a VEGFk-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF(164) selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined

A New Wood Surface Flame-Retardant Based on Poly-m-Aramid Electrospun Nanofibers

Poly(meta-phenylene isophtalamide) (PMIA) was processed via electrospinning to provide nanofibrous membranes with randomly and aligned fibers. Mechanical performance of such membranes was evaluated, applying a normalization procedure that takes into account the peculiar morphology of such complex substrate where voids can sum up to almost 80% of the sample volume. Random and aligned fibers membranes are applied onto wood panels to test their fire resistance in cone calorimetry when coated in polyaramidic thin nanofiber mats. Tests highlighted that random fibers provide a better fire protection, increasing Time to Ignition and decreasing the Fire Performance Index. Another important parameter affecting the performance is the adhesive system used to apply the nanofibers onto wood that is able to significantly modify the fire performance of the polyaramidic-coated wood panels. POLYM. ENG. SCI., 2019. (c) 2019 Society of Plastics Engineer

Probing Rock Type, Fe Redox State, and Transition Metal Contents with Six-Window VNIR Spectroscopy Under Venus Conditions

VEM-window data are shown to distinguish among key rock types on Venus, and evaluate redox state and transition metal contents of Venus surface rocks

VEGFR1 signaling in retinal angiogenesis and microinflammation

Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, –C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds to VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Müller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research

Infrared absorption from Charge Density Waves in magnetic manganites

The infrared absorption of charge density waves coupled to a magnetic background is first observed in two manganites La{1-x}Ca{x}MnO{3} with x = 0.5 and x = 0.67. In both cases a BCS-like gap 2 Delta (T), which for x=0.5 follows the hysteretic ferro-antiferromagnetic transition, fully opens at a finite T{0} < T{Neel}, with 2 Delta(T{0})/kT{c} close to 5. These results may also explain the unusual coexistence of charge ordering and ferromagnetism in La{0.5}Ca{0.5}MnO{3}.Comment: File revtex + 3 figs. in epsf. To appear on Phys. Rev. Let

L-DOPA preloading increases the uptake of borophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy.

Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on 10B(n,a)7Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of 10B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for 10B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first per- formed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectros- copy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All an- imals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malig- nant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms

The strangeonium spectrum seen in LASS; implications for glueball spectroscopy

The status of strangeonium spectroscopy is re-assessed following our recent high statistics study of K/sup /minus// induced hypercharge exchange reactions. The implications of our results for the status of glueball, or otherwise exotic, candidates observed in the same decay modes but produced by different mechanisms are also discussed. 11 refs., 8 figs