48 research outputs found

    Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway

    Get PDF
    During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog

    Global perspectives on observing ocean boundary current systems

    Get PDF
    Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. Next steps in the development of boundary current observing systems are considered, leading to several specific recommendations

    Cohort Contributions to Race- and Gender-Specific Trends in the Incidence of Hepatocellular Carcinoma in the USA

    No full text
    Introduction: Increasing incidence of lifelong obesity and associated nonalcoholic steatohepatitis in younger birth cohorts may have contributed to growing incidence of hepatocellular carcinoma (HCC) in the USA. Yet, the contribution of cohort effects to trends in HCC incidence is unclear. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program 1973�2013, race- and gender-specific trends in HCC incidence in the USA were decomposed using age-period-cohort (APC) modeling. Results: Among SEER registry sites included in the analysis, there were 25,532 cases of HCC diagnosed including 15,867 (62) White males, 3541 (14) Black males, 5009 (20) White females, and 1115 (4) Black females. HCC incidence increases across periods, especially among men. Underlying this increase, APC models found significant cohort effects among White men, White women, and Black men, with rapid growth in HCC risk among cohorts born after 1940. A similar cohort trend among Black women did not reach statistical significance when compared to an age-period model. Conclusions: Cohort-specific trends have significantly contributed to increasing HCC incidence in recent decades. The rapid increase in HCC risk among younger cohorts suggests that the incidence of HCC will continue increasing in the near future. © 2017, Société Internationale de Chirurgie

    Cohort Contributions to Race- and Gender-Specific Trends in the Incidence of Hepatocellular Carcinoma in the USA

    No full text
    Introduction: Increasing incidence of lifelong obesity and associated nonalcoholic steatohepatitis in younger birth cohorts may have contributed to growing incidence of hepatocellular carcinoma (HCC) in the USA. Yet, the contribution of cohort effects to trends in HCC incidence is unclear. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program 1973�2013, race- and gender-specific trends in HCC incidence in the USA were decomposed using age-period-cohort (APC) modeling. Results: Among SEER registry sites included in the analysis, there were 25,532 cases of HCC diagnosed including 15,867 (62) White males, 3541 (14) Black males, 5009 (20) White females, and 1115 (4) Black females. HCC incidence increases across periods, especially among men. Underlying this increase, APC models found significant cohort effects among White men, White women, and Black men, with rapid growth in HCC risk among cohorts born after 1940. A similar cohort trend among Black women did not reach statistical significance when compared to an age-period model. Conclusions: Cohort-specific trends have significantly contributed to increasing HCC incidence in recent decades. The rapid increase in HCC risk among younger cohorts suggests that the incidence of HCC will continue increasing in the near future. © 2017, Société Internationale de Chirurgie

    Apprendre du passé pour prédire le futur : réponses des poissons migrateurs amphihalins européens au changement climatique

    No full text
    International audienceClimate change can have an effect on species distributions. The 1900 distribution and potential future distribution of diadromous fish in Europe, North Africa, and the Middle East were explored using generalized additive models (GAMs) and selected habitat characteristics of 196 basins. Robust presenceabsence models were built for 20 of the 28 diadromous species in the study area using longitude, annual temperature, drainage surface area, annual precipitation, and source elevation as explanatory variables. Inspection of the relationship between each variable and species presenceabsence revealed that the GAMs were generally interpretable and plausible. Given the predicted rise in annual temperature in climate models ranging between 18C and 78C by 2100, the fish species were classified according to those losing suitable basins, those gaining suitable basins, and those showing little or no change. It was found that the climate envelopes based on temperature and precipitation for diadromous species would, in general, be shifted farther northeastwards by 2100, and these shifting ranges were comparable with those assessed in other studies. The uncertain future of some species was highlighted, and it was concluded that conservation policy and management plans will need to be revised in the face of climate change
    corecore