20 research outputs found

    Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

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    Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-ÎČ or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior

    16S rRNA gene metabarcoding and TEM reveals different ecological strategies within the genus Neogloboquadrina (planktonic foraminifer)

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    CB was supported on a Daphne Jackson Fellowship sponsored by Natural Environmental Research Council (www.nerc.ac.uk) and the University of Edinburgh via the Daphne Jackson Trust. Field collections were supported by the National Science Foundation (www.nsf.gov) grant number OCE-1261519 to ADR and JSF.Uncovering the complexities of trophic and metabolic interactions among microorganisms is essential for the understanding of marine biogeochemical cycling and modelling climate-driven ecosystem shifts. High-throughput DNA sequencing methods provide valuable tools for examining these complex interactions, although this remains challenging, as many microorganisms are difficult to isolate, identify and culture. We use two species of planktonic foraminifera from the climatically susceptible, palaeoceanographically important genus Neogloboquadrina, as ideal test microorganisms for the application of 16S rRNA gene metabarcoding. Neogloboquadrina dutertrei and Neogloboquadrina incompta were collected from the California Current and subjected to either 16S rRNA gene metabarcoding, fluorescence microscopy, or transmission electron microscopy (TEM) to investigate their species-specific trophic interactions and potential symbiotic associations. 53–99% of 16S rRNA gene sequences recovered from two specimens of N. dutertrei were assigned to a single operational taxonomic unit (OTU) from a chloroplast of the phylum Stramenopile. TEM observations confirmed the presence of numerous intact coccoid algae within the host cell, consistent with algal symbionts. Based on sequence data and observed ultrastructure, we taxonomically assign the putative algal symbionts to Pelagophyceae and not Chrysophyceae, as previously reported in this species. In addition, our data shows that N. dutertrei feeds on protists within particulate organic matter (POM), but not on bacteria as a major food source. In total contrast, of OTUs recovered from three N. incompta specimens, 83–95% were assigned to bacterial classes Alteromonadales and Vibrionales of the order Gammaproteobacteria. TEM demonstrates that these bacteria are a food source, not putative symbionts. Contrary to the current view that non-spinose foraminifera are predominantly herbivorous, neither N. dutertrei nor N. incompta contained significant numbers of phytoplankton OTUs. We present an alternative view of their trophic interactions and discuss these results within the context of modelling global planktonic foraminiferal abundances in response to high-latitude climate change.Publisher PDFPeer reviewe

    Witty Celebrity-Endorsed Ads: Share and Share Alike

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    Actor George Clooney’s ‘What else?’ slogan is arguably the most memorable piece of Nespresso Coffee’s online advertising campaign. Like Clooney, an incredible number of celebrities now endorse a product or brand image. Viewers of the U.S.A.’s Super Bowl can attest to the public’s fondness for humorous ads. This research is a preliminary investigation of how consumers react to a celebrity endorsement in an online humorous ad. The objective of this study is to highlight how humor influences consumer attitude, how it affects the likelihood of an ad going viral, and whether it encourages the consumer to share the ad on social media. Exploratory research provides answers to these questions

    Genetic Liability to Schizophrenia Measured by P300 in Concordant and Discordant Monozygotic Twins

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    Background: Differential effects of genes and environment can contribute to etiological heterogeneity in schizophrenia. Twins concordant and discordant for schizophrenia may differ in genetic predisposition to schizophrenia with concordant twins having a higher genetic liability and discordant twins having a lower genetic liability to schizophrenia. We aimed to investigate whether P300 amplitude (which has been postulated as a genetic marker for schizophrenia) reflected this heterogeneity. Sampling and Methods: We compared P300 amplitudes across 36 monozygotic twin pairs (6 concordant for schizophrenia/schizoaffective disorder, 11 discordant and 19 healthy control pairs) performing an auditory oddball task, using multiple regression (age, gender, birth order, premorbid IQ as covariates). We further looked at the correlation between the Brief Psychiatric Rating Scale (BPRS) and P300 amplitude in affected twins, and compared concordant and discordant affected twins on the Global Assessment Scale (GAS). Results: Multiple regression yielded a highly significant model (p = 0.004) though the explained variance was limited (21%). The main effect of the group on P300 amplitude was significant (p = 0.0001): affected concordant twins showed a significantly lower P300 amplitude as compared to affected discordant (p = 0.005, Cohen's d = 1.08) and control twins (p = 0.000, d = 1.16). Discordant affected and unaffected twins did not differ significantly from each other or from control twins. P300 did not correlate significantly with the BPRS and the affected groups did not differ across the GAS. Conclusions: Our results provide evidence for etiological heterogeneity within schizophrenia pointing to different pathophysiological mechanisms that may underlie more and less genetically determined forms of schizophrenia. They also indicate that P300 correlates with a differing degree of genetic liability to schizophrenia independently of the psychopathological status and even in the presence of similar functional profiles. Copyright © 2011 S. Karger AG, Basel

    Ocean acidification compromises a planktic calcifier with implications for global carbon cycling

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    Anthropogenically-forced changes in ocean chemistry at both the global and regional scale have the potential to negatively impact calcifying plankton, which play a key role in ecosystem functioning and marine carbon cycling. We cultured a globally important calcifying marine plankter (the foraminifer, Globigerina bulloides) under an ecologically relevant range of seawater pH (7.5 to 8.3 total scale). Multiple metrics of calcification and physiological performance varied with pH. At pH > 8.0, increased calcification occurred without a concomitant rise in respiration rates. However, as pH declined from 8.0 to 7.5, calcification and oxygen consumption both decreased, suggesting a reduced ability to precipitate shell material accompanied by metabolic depression. Repair of spines, important for both buoyancy and feeding, was also reduced at pH < 7.7. The dependence of calcification, respiration, and spine repair on seawater pH suggests that foraminifera will likely be challenged by future ocean conditions. Furthermore, the nature of these effects has the potential to actuate changes in vertical transport of organic and inorganic carbon, perturbing feedbacks to regional and global marine carbon cycling. The biological impacts of seawater pH have additional, important implications for the use of foraminifera as paleoceanographic indicators

    Regional Climate Shifts Caused by Gradual Global Cooling in the Pliocene Epoch

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    The Earth\u27s climate has undergone a global transition over the past four million years, from warm conditions with global surface temperatures about 3 °C warmer than today, smaller ice sheets and higher sea levels to the current cooler conditions. Tectonic changes and their influence on ocean heat transport have been suggested as forcing factors for that transition, including the onset of significant Northern Hemisphere glaciation 2.75 million years ago, but the ultimate causes for the climatic changes are still under debate. Here we compare climate records from high latitudes, subtropical regions and the tropics, indicating that the onset of large glacial/interglacial cycles did not coincide with a specific climate reorganization event at lower latitudes. The regional differences in the timing of cooling imply that global cooling was a gradual process, rather than the response to a single threshold or episodic event as previously suggested. We also find that high-latitude climate sensitivity to variations in solar heating increased gradually, culminating after cool tropical and subtropical upwelling conditions were established two million years ago. Our results suggest that mean low-latitude climate conditions can significantly influence global climate feedbacks
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