Sustained Na⁺/H⁺ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation

Hypoxia ischemia (HI)-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na +/H+ exchanger isoform 1 (NHE1) protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX). 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na+ and Ca2+ overload. The latter was mediated by reversal of Na+/Ca2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα) during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H + homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na+ and Ca2+ homeostasis, which reduces Na+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI. © 2014 Cengiz et al

Synthesis of Ag@Silica Nanoparticles by Assisted Laser Ablation

This paper reports the synthesis of silver nanoparticles coated with porous silica (Ag@Silica NPs) using an assisted laser ablation method. This method is a chemical synthesis where one of the reagents (the reducer agent) is introduced in nanometer form by laser ablation of a solid target submerged in an aqueous solution. In a first step, a silicon wafer immersed in water solution was laser ablated for several minutes. Subsequently, an AgNO(3) aliquot was added to the aqueous solution. The redox reaction between the silver ions and ablation products leads to a colloidal suspension of core-shell Ag@Silica NPs. The influence of the laser pulse energy, laser wavelength, ablation time, and Ag(+) concentration on the size and optical properties of the Ag@Silica NPs was investigated. Furthermore, the colloidal suspensions were studied by UV–VIS-NIR spectroscopy, X-Ray diffraction, and high-resolution transmission electron microscopy (HRTEM)

Ecological Implications of Extreme Events: Footprints of the 2010 Earthquake along the Chilean Coast

Deciphering ecological effects of major catastrophic events such as earthquakes, tsunamis, volcanic eruptions, storms and fires, requires rapid interdisciplinary efforts often hampered by a lack of pre-event data. Using results of intertidal surveys conducted shortly before and immediately after Chile's 2010 Mw 8.8 earthquake along the entire rupture zone (ca. 34–38°S), we provide the first quantification of earthquake and tsunami effects on sandy beach ecosystems. Our study incorporated anthropogenic coastal development as a key design factor. Ecological responses of beach ecosystems were strongly affected by the magnitude of land-level change. Subsidence along the northern rupture segment combined with tsunami-associated disturbance and drowned beaches. In contrast, along the co-seismically uplifted southern rupture, beaches widened and flattened increasing habitat availability. Post-event changes in abundance and distribution of mobile intertidal invertebrates were not uniform, varying with land-level change, tsunami height and coastal development. On beaches where subsidence occurred, intertidal zones and their associated species disappeared. On some beaches, uplift of rocky sub-tidal substrate eliminated low intertidal sand beach habitat for ecologically important species. On others, unexpected interactions of uplift with man-made coastal armouring included restoration of upper and mid-intertidal habitat seaward of armouring followed by rapid colonization of mobile crustaceans typical of these zones formerly excluded by constraints imposed by the armouring structures. Responses of coastal ecosystems to major earthquakes appear to vary strongly with land-level change, the mobility of the biota and shore type. Our results show that interactions of extreme events with human-altered shorelines can produce surprising ecological outcomes, and suggest these complex responses to landscape alteration can leave lasting footprints in coastal ecosystems

Podocyte-Specific Overexpression of Wild Type or Mutant Trpc6 in Mice Is Sufficient to Cause Glomerular Disease

Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6) gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS) affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K) previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2–3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated) in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease

First-Borns Carry a Higher Metabolic Risk in Early Adulthood: Evidence from a Prospective Cohort Study

Birth order has been associated with early growth variability and subsequent increased adiposity, but the consequent effects of increased fat mass on metabolic risk during adulthood have not been assessed. We aimed to quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently.Body composition and metabolic risk were assessed in 2,249 men, aged 17-19 years, from a birth cohort in southern Brazil. Metabolic risk was assessed using a composite z-score integrating standardized measurements of blood pressure, total cholesterol, high density lipoprotein, triglycerides and fat mass. First-borns had lower birth weight z-score (Δ = -0.25, 95%CI -0.35, -0.15,p<0.001) but showed greater weight gain during infancy (change in weight z-score from birth to 20 months: Δ = 0.39, 95%CI 0.28-0.50, p<0.0001) and had greater mean height (Δ = 1.2 cm, 95%CI: 0.7-1.6, p<0.0001) and weight (Δ = 0.34 kg, 95%CI: 0.13-0.55, p<0.002) at 43 months. This greater weight and height tracked into early adulthood, with first-borns being significantly taller, heavier and with significantly higher fat mass than later-borns. The metabolic risk z-score was significantly higher in first-borns.First-born status is associated with significantly elevated adiposity and metabolic risk in young adult men in Brazil. Our results, linking cardiovascular risk with life history variables, suggest that metabolic risk may be associated with the worldwide trend to smaller family size and it may interact with changes in behavioural or environmental risk factors

Wind speed variability over the Canary Islands, 1948-2014: focusing on trend differences at the land-ocean interface and below-above the trade-wind inversion layer

This study simultaneously examines wind speed trends at the land?ocean interface, and below?above the trade-wind inversion layer in the Canary Islands and the surrounding Eastern North Atlantic Ocean: a key region for quantifying the variability of trade-winds and its response to large-scale atmospheric circulation changes. Two homogenized data sources are used: (1) observed wind speed from nine land-based stations (1981?2014), including one mountain weather station (Izaña) located above the trade-wind inversion layer; and (2) simulated wind speed from two atmospheric hindcasts over ocean (i.e., SeaWind I at 30 km for 1948?2014; and SeaWind II at 15 km for 1989?2014). The results revealed a widespread significant negative trend of trade-winds over ocean for 1948?2014, whereas no significant trends were detected for 1989?2014. For this recent period wind speed over land and ocean displayed the same multi-decadal variability and a distinct seasonal trend pattern with a strengthening (late spring and summer; significant in May and August) and weakening (winter?spring?autumn; significant in April and September) of trade-winds. Above the inversion layer at Izaña, we found a predominance of significant positive trends, indicating a decoupled variability and opposite wind speed trends when compared to those reported in boundary layer. The analysis of the Trade Wind Index (TWI), the North Atlantic Oscillation Index (NAOI) and the Eastern Atlantic Index (EAI) demonstrated significant correlations with the wind speed variability, revealing that the correlation patterns of the three indices showed a spatio-temporal complementarity in shaping wind speed trends across the Eastern North Atlantic.C. A. -M. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 703733 (STILLING project). This research was also supported by the Research Projects: Swedish BECC, MERGE, VR (2014–5320), PCIN-2015-220, CGL2014-52135-C03-01 and Red de variabilidad y cambio climático RECLIM (CGL2014-517221-REDT). M.M is indebted to the Spanish Government for funding through the “Ramón y Cajal” program and supported by Grant PORTIO (BIA2015-70644-R