Modulation of the glutamate-evoked release of arachidonic acid from mouse cortical neurons: involvement of a pH-sensitive membrane phospholipase A2

Excitatory synaptic transmission is associated with changes in both extracellular and intracellular pH. Using mouse cortical neurons in primary cultures, we studied the sensitivity of glutamate-evoked release of 3H-arachidonic acid (3H-AA) to changes in extracellular pH (pHo) and related intracellular pH (pHi). As pHo was shifted from 7.2 to 7.8, the glutamate-evoked release of 3H-AA was enhanced by approximately threefold. The effect of alkaline pHo on the glutamate response was rapid, becoming significant within 2 min. 3H-AA release, evoked by both NMDA and kainate, was also enhanced by pHo alkalinization. NMDA- and kainate-induced increase in free intracellular Ca2+ was unaffected by changing pHo from 7.2 to 7.8, indicating that the receptor-induced Ca2+ influx is not responsible for the pHo sensitivity of the glutamate-evoked release of 3H-AA. Alkalinization of pHi obtained by incubating neurons in the presence of HCO3- or NH4 enhanced the glutamate-evoked release of 3H-AA, while pHi acidification obtained by blockade of Na+/H+ and Cl-/HCO3- exchangers decreased the glutamate response. Membrane-bound phospholipase A2 (mPLA2) activity was stimulated by Ca2+ in a pH-dependent manner, increasing its activity as pH was shifted from 7.2 to 7.8. This pH profile corresponds to the pH profile of the glutamate-, NMDA- and kainate-evoked release of 3H-AA. Taken together, these results indicate that the glutamate-evoked release of 3H-AA may be mediated by the pH-sensitive mPLA2. Since excitatory neurotransmission mediated by glutamate results in both pHo and pHi changes and since AA enhances glutamatergic neurotransmission at both pre- and postsynaptic levels, the data reported here reveals a possible molecular mechanism whereby glutamate can modulate its own signalling efficacy in a pH-dependent manner by regulating the release of AA

Constraining Stellar Feedback: Shock-ionized Gas in Nearby Starburst Galaxies

(abridged) We investigate the properties of feedback-driven shocks in 8 nearby starburst galaxies using narrow-band imaging data from the Hubble Space Telescope (HST). We identify the shock--ionized component via the line diagnostic diagram \oiii/\hb vs. \sii (or \nii)/\ha, applied to resolved regions 3--15 pc in size. We divide our sample into three sub-samples: sub-solar (Holmberg II, NGC 1569, NGC 4214, NGC 4449, and NGC 5253), solar (He 2-10, NGC 3077) and super-solar (NGC 5236) for consistent shock measurements. For the sub-solar sub-sample, we derive three scaling relations: (1) $L_{shock} \propto {SFR}^{~0.62}$, (2) $L_{shock} \propto {\Sigma_{SFR,HL}}^{~0.92}$, and (3) $L_{shock}/L_{tot} \propto {(L_H/L_{\odot,H})}^{-0.65}$, where $L_{shock}$ is the \ha luminosity from shock--ionized gas, ${\Sigma_{SFR,HL}}$ the SFR per unit half-light area, $L_{tot}$ the total \ha luminosity, and $L_H/L_{\odot,H}$ the absolute H-band luminosity from 2MASS normalized to solar luminosity. The other two sub--samples do not have enough number statistics, but appear to follow the first scaling relation. The energy recovered indicates that the shocks from stellar feedback in our sample galaxies are fully radiative. If the scaling relations are applicable in general to stellar feedback, our results are similar to those by Hopkins et al. (2012) for galactic super winds. This similarity should, however, be taken with caution at this point, as the underlying physics that enables the transition from radiative shocks to gas outflows in galaxies is still poorly understood.Comment: 29 pages, 14 figures, accepted for publication in the Ap

Caveolin expression changes in the neurovascular unit after juvenile traumatic brain injury: signs of blood-brain barrier healing?

Traumatic brain injury (TBI) is one of the major causes of death and disability in pediatrics, and results in a complex cascade of events including the disruption of the blood-brain barrier (BBB). A controlled-cortical impact on post-natal 17-day-old rats induced BBB disruption by IgG extravasation from 1 to 3 days after injury and returned to normal at day 7. In parallel, we characterized the expression of three caveolin isoforms, caveolin 1 (cav-1), caveolin 2 (cav-2) and caveolin 3 (cav-3). While cav-1 and cav-2 are expressed on endothelial cells, both cav-1 and cav-3 were found to be present on reactive astrocytes, in vivo and in vitro. Following TBI, cav-1 expression was increased in blood vessels at 1 and 7 days in the perilesional cortex. An increase of vascular cav-2 expression was observed 7 days after TBI. In contrast, astrocytic cav-3 expression decreased 3 and 7 days after TBI. Activation of endothelial nitric oxide synthase (eNOS) (via its phosphorylation) was detected 1 day after TBI and phospho-eNOS was detected both in association with blood vessels and with astrocytes. The molecular changes involving caveolins occurring in endothelial cells following juvenile-TBI might participate, independently of eNOS activation, to a mechanism of BBB repair while, they might subserve other undefined roles in astrocytes

Structure and dynamics of Oxide Melts and Glasses : a view from multinuclear and high temperature NMR

Solid State Nuclear Magnetic Resonance (NMR) experiments allow characterizing the local structure and dynamics of oxide glasses and melts. Thanks to the development of new experiments, it now becomes possible to evidence not only the details of the coordination state of the network formers of glasses but also to characterize the nature of polyatomic molecular motifs extending over several chemical bonds. We present results involving 31P homonuclear experiments that allow description of groups of up to three phosphate units and 27Al/17O heteronuclear that allows evidencing μ3 oxygen bridges in aluminate glasses and rediscussion of the structure of high temperature melts.Comment: Journal of Non-Crystalline Solids (2007) in press; Also available online at: http://crmht.cnrs-orleans.fr/Intranet/Publications/?id=207

Percutaneous pulmonary valve implantation in humans - Results in 59 consecutive patients

Background - Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life.Methods and Results - Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n = 36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n = 8). The right ventricular (RV) pressure (64.4 +/- 17.2 to 50.4 +/- 14 mm Hg, P < 0.001), RVOT gradient (33 +/- 24.6 to 19.5 +/- 15.3, P < 0.001), and pulmonary regurgitation ( PR) (grade 2 of greater before, none greater than grade 2 after, P < 0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21 +/- 13% versus 3 +/- 4%, P < 0.001) and in RV end-diastolic volume (EDV) (94 +/- 28 versus 82 +/- 24 mL (.) beat(-1) (.) m(-2), P < 0.001) and a significant increase in left ventricular EDV ( 64 +/- 12 versus 71 +/- 13 mL (.) beat(-1.) m(-2), P = 0.005) and effective RV stroke volume ( 37 +/- 7 versus 42 +/- 9 mL (.) beat(-1) (.) m(-2), P = 0.006) in 28 patients (age 19 +/- 8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in V(O2)max (26 +/- 7 versus 29 +/- 6 mL (.) kg(-1) (.) min(-1), P < 0.001). There was no mortality.Conclusions - PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity

Monocarboxylate transporters in the brain and in cancer.

Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou

Tapping Environmental History to Recreate America’s Colonial Hydrology

To properly remediate, improve, or predict how hydrological systems behave, it is vital to establish their histories. However, modern-style records, assembled from instrumental data and remote sensing platforms, hardly exist back more than a few decades. As centuries of data is preferable given multidecadal fluxes of both meteorology/climatology and demographics, building such a history requires resources traditionally considered only useful in the social sciences and humanities. In this Feature, Pastore et al. discuss how they have undertaken the synthesis of historical records and modern techniques to understand the hydrology of the Northeastern U.S. from Colonial times to modern day. Such approaches could aid studies in other regions that may require heavier reliance on qualitative narratives. Further, a better insight as to how historical changes unfolded could provide a “past is prologue” methodology to increase the accuracy of predictive environmental models

Alteration of glucose metabolism in cultured astrocytes after AQP9-small interference RNA application.

Aquaglyceroporin-9 (AQP9) facilitates diffusion of water and energy substrates such as glycerol and monocarboxylates. AQP9 is present in plasma membrane and mitochondria of astrocytes and catecholaminergic neurons, suggesting that it plays a role in the energetic status of these cells. Using specific small interference RNA directed against AQP9 in astrocyte cultures, we showed that glycerol uptake is decreased which is associated with an increase in glucose uptake and oxidative metabolism. Our results not only confirm the presence of AQP9 in astrocytes but also suggest that changes in AQP9 expression alter glial energy metabolism

Theory of extraordinary optical transmission through subwavelength hole arrays

We present a fully three-dimensional theoretical study of the extraordinary transmission of light through subwavelength hole arrays in optically thick metal films. Good agreement is obtained with experimental data. An analytical minimal model is also developed, which conclusively shows that the enhancement of transmission is due to tunneling through surface plasmons formed on each metal-dielectric interfaces. Different regimes of tunneling (resonant through a ''surface plasmon molecule", or sequential through two isolated surface plasmons) are found depending on the geometrical parameters defining the system.Comment: 4 pages, 4 figure

Diffuse far-infrared and ultraviolet emission in the NGC4435/4438 system: tidal stream or Galactic cirrus?

We report the discovery of diffuse far-infrared and far-ultraviolet emission projected near the interacting pair NGC4435/4438, in the Virgo cluster. This feature spatially coincides with a well known low surface-brightness optical plume, usually interpreted as tidal debris. If extragalactic, this stream would represent not only one of the clearest examples of intracluster dust, but also a rare case of intracluster molecular hydrogen and large-scale intracluster star formation. However, the ultraviolet, far-infrared, HI and CO emission as well as the dynamics of this feature are extremely unusual for tidal streams but are typical of Galactic cirrus clouds. In support to the cirrus scenario, we show that a strong spatial correlation between far-infrared and far-ultraviolet cirrus emission is observed across the center of the Virgo cluster, over a scale of several degrees. This study demonstrates how dramatic Galactic cirrus contamination can be, even at optical and ultraviolet wavelengths and at high galactic latitudes. If ignored, the presence of diffuse light scattered by Galactic dust clouds could significantly bias our interpretation of low surface-brightness features and diffuse light observed around galaxies and in clusters of galaxies.Comment: 6 pages, 4 figures. Accepted for publication in MNRAS Letter