639 research outputs found
K(+)-Dependent Na(+)/Ca(2+) Exchanger Isoform 2, Nckx2, Takes Part in the Neuroprotection Elicited by Ischemic Preconditioning in Brain Ischemia
No full textSodium/Calcium exchangers are neuronal plasma membrane antiporters which, by coupling Ca(2+) and Na(+) fluxes across neuronal membranes, play a relevant role in brain ischemia. The most brain-expressed isoform among the members of the K(+)-dependent Na(+)/Ca(2+) exchanger family, NCKX2, is involved in the progression of the ischemic lesion, since both its knocking-down and its knocking-out worsens ischemic damage. The aim of this study was to elucidate whether NCKX2 functions as an effector in the neuroprotection evoked by ischemic preconditioning. For this purpose, we investigated: (1) brain NCKX2 expression after preconditioning and preconditioning + ischemia; (2) the contribution of AKT and calpain to modulating NCKX2 expression during preconditioning; and (3) the effect of NCKX2 knocking-out on the neuroprotection mediated by ischemic preconditioning. Our results showed that NCKX2 expression increased in those brain regions protected by ischemic preconditioning. These changes were p-AKT-mediated since its inhibition prevented NCKX2 up-regulation. More interestingly, NCKX2 knocking-out significantly prevented the protection exerted by ischemic preconditioning. Overall, our results suggest that NCKX2 plays a fundamental role in the neuroprotective effect mediated by ischemic preconditioning and support the idea that the enhancement of its expression and activity might represent a reasonable strategy to reduce infarct extension after stroke
Online resources for mathematics in the scientific virtual reference desk
No full textThe present work briefly describes the Virtual Reference Desk for mathematics elaborated during the time I worked at the CERN Library (European Laboratory for Particle Physics or Laboratoire européen pour la physique des particules) in Geneva. This instrument is dedicated to the CERN librarians, with whom I have shared important moments of my professional career. In particular, I would like to gratefully acknowledge their valuable co-operation and assistance during our time spent working together. The Web metasource is comprised of three directories, annotated and interrelated with dual application: The first is intended as a work tool for librarians working in mathematics libraries, but above all for librarians of high energy physics, who more often than not must turn to mathematics and the use of mathematical applications and models for the physical sciences and in particular particle physics. The second is an on-line resource for mathematics; that is, a Virtual Reference Desk for the community of mathematicians, with whom I have been collaborating for some twenty years at the University of Padova. The bibliographical instrument is born from the need to have at our disposal a scientific Virtual Reference Desk created according to the needs of those working in physics and mathematics libraries – a tool which is comprised of materials collected during years of work as much as material available on-line through the use of new technologies
Ncx3 gene ablation impairs oligodendrocyte precursor response and increases susceptibility to experimental autoimmune encephalomyelitis
No full textThe Na(+) /Ca(2+) exchanger NCX3, recently identified as a myelin membrane component, is involved in the regulation of [Ca(2+) ]i during oligodendrocyte maturation. Here NCX3 involvement was studied in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Western blotting and quantitative colocalization studies performed in wild-type ncx3(+/+) mice at different stages of EAE disease showed that NCX3 protein was intensely upregulated during the chronic stage, where it was intensely coexpressed with the oligodendrocyte precursor cells (OPC) marker NG2 and the premyelinating marker CNPase. Moreover, MOG35-55 -immunized mice lacking the ncx3 gene displayed not only a reduced diameter of axons and an intact myelin ring number but also a dramatic decrease in OPC and pre-myelinating cells in the white matter of the spinal cord when compared with ncx3(+/+) . Accordingly, ncx3(-/-) and ncx3(+/-) mutants developed early onset of EAE and more severe clinical symptoms. Interestingly, cytofluorimetric analysis revealed that during the peak stage of the disease, the number of immune T-cell subsets in ncx3(-/-) mice, was not statistically different from that measured in ncx3(+/+) . Our findings demonstrate that knocking-out NCX3 impairs oligodendrocyte response and worsens clinical symptoms in EAE without altering the immune T-cell population
Glial Na(+) -dependent ion transporters in pathophysiological conditions
No full textSodium dynamics are essential for regulating functional processes in glial cells. Indeed, glial Na(+) signaling influences and regulates important glial activities, and plays a role in neuron-glia interaction under physiological conditions or in response to injury of the central nervous system (CNS). Emerging studies indicate that Na(+) pumps and Na(+) -dependent ion transporters in astrocytes, microglia, and oligodendrocytes regulate Na(+) homeostasis and play a fundamental role in modulating glial activities in neurological diseases. In this review, we first briefly introduced the emerging roles of each glial cell type in the pathophysiology of cerebral ischemia, Alzheimer's disease, epilepsy, Parkinson's disease, Amyotrophic Lateral Sclerosis, and myelin diseases. Then, we discussed the current knowledge on the main roles played by the different glial Na(+) -dependent ion transporters, including Na(+) /K(+) ATPase, Na(+) /Ca(2+) exchangers, Na(+) /H(+) exchangers, Na(+) -K(+) -Cl(-) cotransporters, and Na(+) - HCO3- cotransporter in the pathophysiology of the diverse CNS diseases. We highlighted their contributions in cell survival, synaptic pathology, gliotransmission, pH homeostasis, and their role in glial activation, migration, gliosis, inflammation, and tissue repair processes. Therefore, this review summarizes the foundation work for targeting Na(+) -dependent ion transporters in glia as a novel strategy to control important glial activities associated with Na(+) dynamics in different neurological disorders. GLIA 2016;64:1677-1697
Emerging Role of DREAM in Healthy Brain and Neurological Diseases
No full text: The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca2+-sensitive protein exerting a dual mechanism of action to regulate several Ca2+-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system
The Anemonia sulcata Toxin BDS-I Protects Astrocytes Exposed to Aβ1–42 Oligomers by Restoring [Ca2+]i Transients and ER Ca2+ Signaling
No full textIntracellular calcium concentration ([Ca2+]i) transients in astrocytes represent a highly plastic signaling pathway underlying the communication between neurons and glial cells. However, how this important phenomenon may be compromised in Alzheimer’s disease (AD) remains unexplored. Moreover, the involvement of several K+ channels, including KV3.4 underlying the fast-inactivating currents, has been demonstrated in several AD models. Here, the effect of KV3.4 modulation by the marine toxin blood depressing substance-I (BDS-I) extracted from Anemonia sulcata has been studied on [Ca2+]i transients in rat primary cortical astrocytes exposed to Aβ1–42 oligomers. We showed that: (1) primary cortical astrocytes expressing KV3.4 channels displayed [Ca2+]i transients depending on the occurrence of membrane potential spikes, (2) BDS-I restored, in a dose-dependent way, [Ca2+]i transients in astrocytes exposed to Aβ1–42 oligomers (5 µM/48 h) by inhibiting hyperfunctional KV3.4 channels, (3) BDS-I counteracted Ca2+ overload into the endoplasmic reticulum (ER) induced by Aβ1–42 oligomers, (4) BDS-I prevented the expression of the ER stress markers including active caspase 12 and GRP78/BiP in astrocytes treated with Aβ1–42 oligomers, and (5) BDS-I prevented Aβ1–42-induced reactive oxygen species (ROS) production and cell suffering measured as mitochondrial activity and lactate dehydrogenase (LDH) release. Collectively, we proposed that the marine toxin BDS-I, by inhibiting the hyperfunctional KV3.4 channels and restoring [Ca2+]i oscillation frequency, prevented Aβ1–42-induced ER stress and cell suffering in astrocytes
Intervista con Antonella De Robbio, Responsabile del Settore Progetti e Biblioteca Digitale del Centro d'Ateneo per le Biblioteche CAB dell' Università di Padova e Referente per il diritto d'autore del Sistema Bibliotecario di Ateneo
No full textThe interview with Antonella De Robbio – manager of the “Project Sector and Digital Library” for CAB (Centro di Ateneo per le Biblioteche) of the University of Padua and copyright expert for Sistema Bibliotecario di Ateneo – was published in Pinali news.
Antonella De Robbio answered the following questions:
1) How to deal with the issues of author’s intellectual and economic rights in the context of scientific publishing and digital library?
2) What is the influence of the digital approach on the traditional ways to create and disseminate scientific communication?
3) In your opinion, can the experiences of University Press and the Open Archives represent the path to follow in order to overcome the paradox that a scientific author is also the user of his publisher?
4) Which are the outcomes of the fight between copyright and copyleft?
5) Which of these approaches are more suitable to label the metaphor of the “Society of Knowledge”
Literacy in Neapolitan Women's Convents in the Middle Ages and the Contribution of Digital Archives on Monasterium.Net
No full textAntonella Ambrosio seeks a viable way of carrying out research on this topic: the palaeographic analysis of the few available sources using a multidisciplinary approach that combines diplomatics, archival, and historical research. This approach ensures the appropriate contextualization of the source both historically and culturally. In "Literacy in Neapolitan Women's Convents: An Example of Female Handwriting in a Late Fifteenth-Century Accounts Ledger", Ambrosio provides a case study, analysing a single piece of handwriting evidence. The source is an accounts ledger from the Dominican convent of Santi Pietro e Sebastiano compiled in the second half of the fifteenth century, from 1485 to 1496. Using an analytical approach, the author has identified the handwriting of a particular (anonymous) nun from the convent; Ambrosio studies the script the nun used and formulates hypotheses about her cultural background and how she learned to write. The palaeographic analysis is fully contextualized thanks to the reconstruction of the old convent archive, a reconstruction helped by using digital technologies now accessible online at Monasterium.net. As Ambrosio's work demonstrates, technological advances may aid codicological work but careful palaeographic analysis is necessary to ascertain the participation of female scribes. In this case we witness the scribal development of a nun who began with a basic knowledge of writing and who went on to perform her practical task not well but adequately for the purpose
Knocking out the Na+/Ca2+ exchanger NCX3 impairs oligodendrocyte lineage responses and worsens clinical symptoms in experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice
No full textAbstract
The dysregulation of [Ca2+]i and [Na+]i homeostasis is involved in neuronal and glial response occurring in several neurodegenerative diseases, including Multiple Sclerosis. The Na+/Ca2+ exchanger can be considered a key player in modulating the [Ca2+]i and [Na+]i homeostasis following the injury. Recent evidence point out to the isoform NCX3 of the Na+/Ca2+ exchanger as a new potential therapeutic target for neuroprotection. The aim of the present study was to establish the role played by NCX3 in a murine model of Multiple Sclerosis. The experimental model used in these studies was the Experimental Autoimmune Encephalomyelitis (EAE). Biochemical analysis performed on spinal cord tissue homogenates revealed that NCX3 protein levels were progressively up-regulated during EAE progression; this effect was more significant at EAE chronic stage. In addition, quantitative confocal double immunofluorescence experiments showed that the co-expression of NCX3 with both the myelin marker myelin basic protein (MBP) and the axonal marker neurofilament 200 (NF200) was significantly down-regulated at peak and chronic stages of EAE disease. By contrast, quantification of co-localization studies revealed that the co-expression of NCX3 with the oligodendrocyte lineage markers, the membrane chondroitin sulfate proteoglycan NG2, the Galactocebroside (GalC), and the 2’-3’-cyclic nucleotide-3’-phosphodiesterase (CNPase) was up-regulated during EAE progression. Interestingly, this up-regulation was more significant at EAE chronic stage. These early results suggested that NCX3 isoform might be involved in neuroprotective responses mediated by oligodendrocytes during the EAE recovery phase. The importance of the NCX3 isoform in oligodendroglial responses following EAE insult was supported by several findings: 1) at chronic stage of EAE disease, NCX3 knockout (ncx3-/-) mice displayed a reduced number of NG2 and CNPase positive cells when compared to NCX3 congenic wild type (ncx3+/+) mice; 2) NCX3 knockout (ncx3-/-) mice showed an earlier onset of symptoms and an increased susceptibility to the EAE disease when compared to NCX3 congenic wild type (ncx3+/+) mice. In conclusion, our findings suggested that NCX3 exchanger, by modulating [Na+]i and [Ca2+]i homeostasis might play an important role in controlling oligodendrocyte response after a demyelinating insult
Literacy in Neapolitan Women’s Convents: An Example of Female Handwriting in a Late Fifteenth-Century Accounts Ledger
No full textThis paper is about a research i on the literacy and writing skills of Neapolitan sisters in medieval convents, due to the lack of adequate historical study of such nuns and the extremely complex nature of the documentary sources. Surviving evidence is scattered far and wide, and the old convent archives have been dispersed. Given the state of the survivals, Antonella Ambrosio seeks a viable way of carrying out research on this topic: the palaeographic analysis of the few available sources using a multidisciplinary approach that combines diplomatics, archival, and historical research. This approach ensures the appropriate contextualization of the source both historically and culturally. In ‘Literacy in Neapolitan Women’s Convents: An Example of Female Handwriting in a Late Fifteenth-Century Accounts Ledger’, Ambrosio provides a case study, analysing a single piece of handwriting evidence. The source is an accounts ledger from the Dominican convent of Santi Pietro e Sebastiano compiled in the second half of the fifteenth century, from 1485 to 1496. Using an analytical approach, the author has identified the handwriting of a particular (anonymous) nun from the convent; Ambrosio studies the script the nun used and formulates hypotheses about her cultural background and how she learned to write. The palaeographic analysis is fully contextualized thanks to the reconstruction of the old convent archive, a reconstruction helped by using digital technologies now accessible online at Monasterium.net. As Ambrosio’s work demonstrates, technological advances may aid codicological work but careful palaeographic analysis is necessary to ascertain the participation of female scribes. In this case we witness the scribal development of a nun who began with a basic knowledge of writing and who went on to perform her practical task not well but adequately for the
purpose
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