501 research outputs found

    Stimulation of Na<sup>+</sup>/H<sup>+</sup> Exchanger Isoform 1 Promotes Microglial Migration

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    Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

    Carbon foams from emulsion-templated reduced graphene oxide polymer composites: electrodes for supercapacitor devices

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    Amphiphilic reduced graphene oxide (rGO) is an efficient emulsifier for water-in-divinylbenzene (DVB) high internal phase emulsions. The polymerisation of the continuous DVB phase of the emulsion template and removal of water results in macroporous poly(divinylbenzene) (polyDVB). Subsequent pyrolysis of the poly(DVB) macroporous polymers yields ‘all-carbon’ foams containing micropores alongside emulsion templated-macropores, resulting in hierarchical porosity. The synthesis of carbon foams, or ‘carboHIPEs’, from poly(DVB) produced by polymerisation of rGO stabilised HIPEs provides both exceptionally high surface areas (up to 1820 m2 g−1) and excellent electrical conductivities (up to 285 S m−1), competing with the highest figures reported for carboHIPEs. The use of a 2D carbon emulsifier results in the elimination of post-carbonisation treatments to remove standard inorganic particulate emulsifiers, such as silica particles. It is demonstrated that rGO containing carboHIPEs are good candidates for supercapacitor electrodes where carboHIPEs derived from more conventional polymerised silica-stabilised HIPEs perform poorly. Supercapacitor devices featured a room-temperature ionic liquid electrolyte and electrodes derived from either rGO- or silica-containing poly(DVB)HIPEs demonstrated a maximum specific capacitance of 26 F g−1, an energy density of 5.2 W h kg−1 and a power density of 280 W kg−1

    Drought rewires the cores of food webs

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    Droughts are intensifying across the globe, with potentially devastating implications for freshwater ecosystems. We used new network science approaches to investigate drought impacts on stream food webs and explored potential consequences for web robustness to future perturbations. The substructure of the webs was characterized by a core of richly connected species surrounded by poorly connected peripheral species. Although drought caused the partial collapse of the food webs, the loss of the most extinction-prone peripheral species triggered a substantial rewiring of interactions within the networks’ cores. These shifts in species interactions in the core conserved the underlying core/periphery substructure and stability of the drought-impacted webs. When we subsequently perturbed the webs by simulating species loss in silico, the rewired drought webs were as robust as the larger, undisturbed webs. Our research unearths previously unknown compensatory dynamics arising from within the core that could underpin food web stability in the face of environmental perturbations

    Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

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    Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, VerĂłnica. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Santa Fe. Instituto Nacional de LimnologĂ­a. Universidad Nacional del Litoral. Instituto Nacional de LimnologĂ­a; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Santa Fe. Instituto Nacional de LimnologĂ­a. Universidad Nacional del Litoral. Instituto Nacional de LimnologĂ­a; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Santa Fe. Instituto Nacional de LimnologĂ­a. Universidad Nacional del Litoral. Instituto Nacional de LimnologĂ­a; Argentina. Universidad Nacional del Litoral. Facultad de BioquĂ­mica y Ciencias BiolĂłgicas; Argentin

    Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

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    Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

    Does a PBL-based medical curriculum predispose training in specific career paths? A systematic review of the literature

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    Background North American medical schools have used problem-based learning (PBL) structured medical education for more than 60 years. However, it has only recently been introduced in other medical schools outside of North America. Since its inception, there has been the debate on whether the PBL learning process predisposes students to select certain career paths. Objectives To review available evidence to determine the predisposition of specific career paths when undertaking a PBL-based medical curriculum. The career path trajectory was determined as measured by official Matching Programs, self-reported questionnaires and surveys, and formally defined career development milestones. Methods A systematic literature review was performed. PubMed, Medline, Cochrane and ERIC databases were analysed in addition to reference lists for appropriate inclusion. Results Eleven studies fitting the inclusion criteria were identified. The majority of studies showed that PBL did not predispose a student to a career in a specific speciality (n = 7 out of 11 studies, 64%). However, three studies reported a significantly increased number of PBL graduates working in primary care compared to those from a non-PBL curriculum. Conclusions PBL has been shown not to predispose medical students to a career in General Practice or any other speciality. Furthermore, a greater number of similar studies are required before a definitive conclusion can be made in the future

    In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells

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    INTRODUCTION: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells. METHODS: Human MCF-7 breast cancer cells were treated with up to 100 ÎŒM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation. RESULTS: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 ÎŒM and 20 ÎŒM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis. CONCLUSION: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma

    NMR-based metabolic characterization of chicken tissues and biofluids: a model for avian research

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    Introduction Poultry is one of the most consumed meat in the world and its related industry is always looking for ways to improve animal welfare and productivity. It is therefore essential to understand the metabolic response of the chicken to new feed formulas, various supplements, infections and treatments. Objectives As a basis for future research investigating the impact of diet and infections on chicken’s metabolism, we established a high-resolution proton nuclear magnetic resonance (NMR)-based metabolic atlas of the healthy chicken (Gallus gallus). Methods Metabolic extractions were performed prior to 1H-NMR and 2D NMR spectra acquisition on twelve biological matrices: liver, kidney, spleen, plasma, egg yolk and white, colon, caecum, faecal water, ileum, pectoral muscle and brain of 6 chickens. Metabolic profiles were then exhaustively characterized. Results Nearly 80 metabolites were identified. A cross-comparison of these matrices was performed to determine metabolic variations between and within each section and highlighted that only eight core metabolites were systematically found in every matrice. Conclusion This work constitutes a database for future NMR-based metabolomic investigations in relation to avian production and health
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