253 research outputs found
Comparison of LMA Unique, Ambu laryngeal mask and Soft Seal laryngeal mask during routine surgical procedures
A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex
Myosin Va (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but the role of MyoVa in synaptic development and function is largely unknown. Here, in studies using the dominantnegative MyoVa neurological mutant mouse Flailer, we find that MyoVa plays an essential role in activity-dependent delivery of PSD-95 and other critical PSD molecules to synapses and in endocytosis of AMPA-type glutamate receptors (AMPAR) in the dendrites of CNS neurons. MyoVa is known to carry a complex containing the major scaffolding proteins of the mature PSD, PSD-95, SAPAP1/GKAP, Shank, and Homer to dendritic spine synapses. In Flailer, neurons show abnormal dendritic shaft localization of PSD-95, stargazin, dynamin3, AMPARs and abnormal spine morphology. Flailer neurons also have abnormally highAMPARminiature current frequencies and spontaneous AMPAR currents that are more frequent and larger than in wild-type while numbers of NMDAR containing synapses remain normal. The AMPAR abnormalities are consistent with a severely disrupted developmental regulation of long-term depression that we find in cortical Flailer neurons. Thus MyoVa plays a fundamentally important role both in localizing mature glutamate synapses to spines and in organizing the synapse for normal function. For this reason Flailer mice will be valuable in further dissecting the role of MyoVa in normal synaptic and circuit refinement and also in studies of neurological and neuropsychiatric diseases where disruptions of normal glutamate synapses are frequently observed.National Institutes of Health (U.S.) (Grant R01-EY014074–17)National Institutes of Health (U.S.) (Grant EY014420
ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers
Indexación: Web of Science; Scopus.Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM) components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα), Tcf4 and α-smooth muscle actin (α-SMA) levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs), which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF) signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases. © 2017 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.017764
Protein kinase B (AKT) upregulation and Thy-1-α<sub>v</sub>β<sub>3</sub> integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.
In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including α <sub>v</sub> β <sub>3</sub> integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined.
Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1 <sup>G93A</sup> transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi).
The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1 <sup>G93A</sup> transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation.
Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis
Radiofrequency Treatment of Facet-related Pain: Evidence and Controversies
Pain originating from the lumbar facet joints is estimated to represent about 15% of all low back pain complaints. The diagnostic block is considered to be a valuable tool for confirming facetogenic pain. It was demonstrated that a block of the ramus medialis of the ramus dorsalis is preferred over an intra-articular injection. The outcome of the consequent radiofrequency treatment is not different in patients reporting over 80% pain relief after the diagnostic block than in those who have between 50% and 79% pain relief. There is one well-conducted comparative trial assessing the value of one or two controlled diagnostic blocks to none. The results of the seven randomized trials on the use of radiofrequency treatment of facet joint pain demonstrate that good patient selection is imperative for good clinical outcome. Therefore, we suggest one block of the ramus medialis of the ramus dorsalis before radiofrequency treatment
Epigenetic control of the bone-master Runx2 gene during Osteoblast-lineage commitment by the Histone Demethylase JARID1B/KDM5B
Q2Q128329-28342Transcription factor Runx2 controls bone development and osteoblast differentiation by regulating expression of a significant number of bone-related target genes. Here, we report that transcriptional activation and repression of the Runx2 gene via its osteoblast-specific P1 promoter (encoding mRNA for the Runx2/p57 isoform) is accompanied by selective deposition and elimination of histone marks during differentiation of mesenchymal cells to the osteogenic and myoblastic lineages. These epigenetic profiles are mediated by key components of the Trithorax/COMPASS-like and Polycomb group complexes together with histone arginine methylases like PRMT5 and lysine demethylases like JARID1B/KDM5B. Importantly, knockdown of the H3K4me2/:3 demethylase JARID1B, but not of the demethylases UTX and N066, prevents repression of the Runx2 P1 promoter during myogenic differentiation of mesenchymal cells. The epigenetically forced expression of Runx2/p57 and osteocalcin, a classical bone-related target gene, under myoblastic-differentiation is accompanied by enrichment of the H3K/Ime3 and H3K27ac marks at the Runx2 P1 promoter region. Our results identify JARID1B as a key component of a potent epigenetic switch that controls mesenchymal cell fate into myogenic and osteogenic lineages
Pulsed radiofrequency or anterior neurectomy for anterior cutaneous nerve entrapment syndrome (ACNES) (the PULSE trial): study protocol of a randomized controlled trial
INDIGO-DataCloud: a Platform to Facilitate Seamless Access to E-Infrastructures
[EN] This paper describes the achievements of the H2020 project INDIGO-DataCloud. The project has provided e-infrastructures with tools, applications and cloud framework enhancements to manage the demanding requirements of scientific communities, either locally or through enhanced interfaces. The middleware developed allows to federate hybrid resources, to easily write, port and run scientific applications to the cloud. In particular, we have extended existing PaaS (Platform as a Service) solutions, allowing public and private e-infrastructures, including those provided by EGI, EUDAT, and Helix Nebula, to integrate their existing services and make them available through AAI services compliant with GEANT interfederation policies, thus guaranteeing transparency and trust in the provisioning of such services. Our middleware facilitates the execution of applications using containers on Cloud and Grid based infrastructures, as well as on HPC clusters. Our developments are freely downloadable as open source components, and are already being integrated into many scientific applications.INDIGO-Datacloud has been funded by the European Commision H2020 research and innovation program under grant agreement RIA 653549.Salomoni, D.; Campos, I.; Gaido, L.; Marco, J.; Solagna, P.; Gomes, J.; Matyska, L.... (2018). INDIGO-DataCloud: a Platform to Facilitate Seamless Access to E-Infrastructures. Journal of Grid Computing. 16(3):381-408. https://doi.org/10.1007/s10723-018-9453-3S381408163García, A.L., Castillo, E.F.-d., Puel, M.: Identity federation with VOMS in cloud infrastructures. In: 2013 IEEE 5Th International Conference on Cloud Computing Technology and Science, pp 42–48 (2013)Chadwick, D.W., Siu, K., Lee, C., Fouillat, Y., Germonville, D.: Adding federated identity management to OpenStack. Journal of Grid Computing 12(1), 3–27 (2014)Craig, A.L.: A design space review for general federation management using keystone. In: Proceedings of the 2014 IEEE/ACM 7th International Conference on Utility and Cloud Computing, pp 720–725. IEEE Computer Society (2014)Pustchi, N., Krishnan, R., Sandhu, R.: Authorization federation in iaas multi cloud. In: Proceedings of the 3rd International Workshop on Security in Cloud Computing, pp 63–71. ACM (2015)Lee, C.A., Desai, N., Brethorst, A.: A Keystone-Based Virtual Organization Management System. In: 2014 IEEE 6Th International Conference On Cloud Computing Technology and Science (Cloudcom), pp 727–730. IEEE (2014)Castillo, E.F.-d., Scardaci, D., García, A.L.: The EGI Federated Cloud e-Infrastructure. Procedia Computer Science 68, 196–205 (2015)AARC project: AARC Blueprint Architecture, see https://aarc-project.eu/architecture . Technical report (2016)Oesterle, F., Ostermann, S., Prodan, R., Mayr, G.J.: Experiences with distributed computing for meteorological applications: grid computing and cloud computing. Geosci. Model Dev. 8(7), 2067–2078 (2015)Plasencia, I.C., Castillo, E.F.-d., Heinemeyer, S., García, A.L., Pahlen, F., Borges, G.: Phenomenology tools on cloud infrastructures using OpenStack. The European Physical Journal C 73(4), 2375 (2013)Boettiger, C.: An introduction to docker for reproducible research. ACM SIGOPS Operating Systems Review 49(1), 71–79 (2015)Docker: http://www.docker.com (2013)Gomes, J., Campos, I., Bagnaschi, E., David, M., Alves, L., Martins, J., Pina, J., Alvaro, L.-G., Orviz, P.: Enabling rootless linux containers in multi-user environments: the udocker tool. Computing Physics Communications. https://doi.org/10.1016/j.cpc.2018.05.021 (2018)Zhang, Z., Chuan, W., Cheung, D.W.L.: A survey on cloud interoperability taxonomies, standards, and practice. SIGMETRICS perform. Eval. Rev. 40(4), 13–22 (2013)Lorido-Botran, T., Miguel-Alonso, J., Lozano, J.A.: A Review of Auto-scaling Techniques for Elastic Applications in Cloud Environments. Journal of Grid Computing 12(4), 559–592 (2014)Nyrén, R., Metsch, T., Edmonds, A., Papaspyrou, A.: Open Cloud Computing Interface–Core. Technical report, Open Grid Forum (2010)Metsch, T., Edmonds, A.: Open Cloud Computing Interface-Infrastructure. Technical report, Open Grid Forum (2010)Metsch, T., Edmonds, A.: Open Cloud Computing Interface-RESTful HTTP Rendering. Technical report, Open Grid Forum (2011)(Ca Technologies) Lipton, P., (Ibm) Moser, S., (Vnomic) Palma, D., (Ibm) Spatzier, T.: Topology and Orchestration Specification for Cloud Applications. Technical report, OASIS Standard (2013)Teckelmann, R., Reich, C., Sulistio, A.: Mapping of cloud standards to the taxonomy of interoperability in IaaS. In: Proceedings - 2011 3rd IEEE International Conference on Cloud Computing Technology and Science, CloudCom 2011, pp 522–526 (2011)García, A.L., Castillo, E.F.-d., Fernández, P.O.: Standards for enabling heterogeneous IaaS cloud federations. Computer Standards & Interfaces 47, 19–23 (2016)Caballer, M., Zala, S., García, A.L., Montó, G., Fernández, P.O., Velten, M.: Orchestrating complex application architectures in heterogeneous clouds. Journal of Grid Computing 16 (1), 3–18 (2018)Hardt, M., Jejkal, T., Plasencia, I.C., Castillo, E.F.-d., Jackson, A., Weiland, M., Palak, B., Plociennik, M., Nielsson, D.: Transparent Access to Scientific and Commercial Clouds from the Kepler Workflow Engine. Computing and Informatics 31(1), 119 (2012)Fakhfakh, F., Kacem, H.H., Kacem, A.H.: Workflow Scheduling in Cloud Computing a Survey. In: IEEE 18Th International Enterprise Distributed Object Computing Conference Workshops and Demonstrations (EDOCW), 2014, Vol. 71, pp. 372–378. Springer, New York (2014)Stockton, D.B., Santamaria, F.: Automating NEURON simulation deployment in cloud resources. Neuroinformatics 15(1), 51–70 (2017)Plóciennik, M., Fiore, S., Donvito, G., Owsiak, M., Fargetta, M., Barbera, R., Bruno, R., Giorgio, E., Williams, D.N., Aloisio, G.: Two-level Dynamic Workflow Orchestration in the INDIGO DataCloud for Large-scale, Climate Change Data Analytics Experiments. Procedia Computer Science 80, 722–733 (2016)Moreno-Vozmediano, R., Montero, R.S., Llorente, I.M.: Multicloud deployment of computing clusters for loosely coupled mtc applications. IEEE transactions on parallel and distributed systems 22(6), 924–930 (2011)Katsaros, G., Menzel, M., Lenk, A.: Cloud Service Orchestration with TOSCA, Chef and Openstack. In: Ic2e (2014)Garcia, A.L., Zangrando, L., Sgaravatto, M., Llorens, V., Vallero, S., Zaccolo, V., Bagnasco, S., Taneja, S., Dal Pra, S., Salomoni, D., Donvito, G.: Improved Cloud resource allocation: how INDIGO-DataCloud is overcoming the current limitations in Cloud schedulers. J. Phys. Conf. Ser. 898(9), 92010 (2017)Singh, S., Chana, I.: A survey on resource scheduling in cloud computing issues and challenges. Journal of Grid Computing, pp. 1–48 (2016)García, A.L., Castillo, E.F.-d., Fernández, P.O., Plasencia, I.C., de Lucas, J.M.: Resource provisioning in Science Clouds: Requirements and challenges. Software: Practice and Experience 48(3), 486–498 (2018)Chauhan, M.A., Babar, M.A., Benatallah, B.: Architecting cloud-enabled systems: a systematic survey of challenges and solutions. Software - Practice and Experience 47(4), 599–644 (2017)Somasundaram, T.S., Govindarajan, K.: CLOUDRB A Framework for scheduling and managing High-Performance Computing (HPC) applications in science cloud. Futur. Gener. Comput. Syst. 34, 47–65 (2014)Sotomayor, B., Keahey, K., Foster, I.: Overhead Matters: A Model for Virtual Resource Management. In: Proceedings of the 2nd International Workshop on Virtualization Technology in Distributed Computing SE - VTDC ’06, p 5. IEEE Computer Society, Washington (2006)SS, S.S., Shyam, G.K., Shyam, G.K.: Resource management for Infrastructure as a Service (IaaS) in cloud computing SS Manvi A survey. J. Netw. Comput. Appl. 41, 424–440 (2014)INDIGO-DataCloud consortium: Initial requirements from research communities - d2.1, see https://www.indigo-datacloud.eu/documents/initial-requirements-research-communities-d21 https://www.indigo-datacloud.eu/documents/initial-requirements-research-communities-d21 https://www.indigo-datacloud.eu/documents/initial-requirements-research-communities-d21 . Technical report (2015)Europen open science cloud: https://ec.europa.eu/research/openscience (2015)Proot: https://proot-me.github.io/ (2014)Runc: https://github.com/opencontainers/runc (2016)Fakechroot: https://github.com/dex4er/fakechroot (2015)Pérez, A., Moltó, G., Caballer, M., Calatrava, A.: Serverless computing for container-based architectures Future Generation Computer Systems (2018)de Vries, K.J.: Global fits of supersymmetric models after LHC run 1. Phd thesis Imperial College London (2015)Openstack: https://www.openstack.org/ (2015)See http://argus-documentation.readthedocs.io/en/stable/argus_introduction.html (2017)See https://en.wikipedia.org/wiki/xacml (2013)See http://www.simplecloud.info (2014)Opennebula: http://opennebula.org/ (2018)Redhat openshift: http://www.opencityplatform.eu (2011)The cloud foundry foundation: https://www.cloudfoundry.org/ (2015)Caballer, M., Blanquer, I., Moltó, G., de Alfonso, C.: Dynamic management of virtual infrastructures. Journal of Grid Computing 13(1), 53–70 (2015)See http://www.infoq.com/articles/scaling-docker-with-kubernetes http://www.infoq.com/articles/scaling-docker-with-kubernetes (2014)Prisma project: http://www.ponsmartcities-prisma.it/ (2010)Opencitiy platform: http://www.opencityplatform.eu (2014)Onedata: https://onedata.org/ (2018)Dynafed: http://lcgdm.web.cern.ch/dynafed-dynamic-federation-project http://lcgdm.web.cern.ch/dynafed-dynamic-federation-project (2011)Fts3: https://svnweb.cern.ch/trac/fts3 (2011)Fernández, P.O., García, A.L., Duma, D.C., Donvito, G., David, M., Gomes, J.: A set of common software quality assurance baseline criteria for research projects, see http://hdl.handle.net/10261/160086 . Technical reportHttermann, M.: Devops for developers Apress (2012)EOSC-Hub: ”Integrating and managing services for the European Open Science Cloud” Funded by H2020 research and innovation pr ogramme under grant agreement No. 777536. See http://eosc-hub.eu (2018)Apache License: author = https://www.apache.org/licenses/LICENSE-2.0 (2004)INDIGO Package Repo: http://repo.indigo-datacloud.eu/ (2017)INDIGO DockerHub: https://hub.docker.com/u/indigodatacloud/ https://hub.docker.com/u/indigodatacloud/ (2015)Indigo gitbook: https://indigo-dc.gitbooks.io/indigo-datacloud-releases https://indigo-dc.gitbooks.io/indigo-datacloud-releases (2017)Van Zundert, G.C., Bonvin, A.M.: Disvis: quantifying and visualizing the accessible interaction space of distance restrained biomolecular complexes. Bioinformatics 31(19), 3222–3224 (2015)Van Zundert, G.C., Bonvin, A.M.: Fast and sensitive rigid–body fitting into cryo–em density maps with powerfit. AIMS Biophys. 2(0273), 73–87 (2015
- …