Rajput, Ashish

[["dc.bibliographiccitation.artnumber","959"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Molecular systems biology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Hatje, Klas"],["dc.contributor.author","Rahman, Raza-Ur"],["dc.contributor.author","Vidal, Ramon O."],["dc.contributor.author","Simm, Dominic"],["dc.contributor.author","Hammesfahr, Björn"],["dc.contributor.author","Bansal, Vikas"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Mickael, Michel Edwar"],["dc.contributor.author","Sun, Ting"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Kollmar, Martin"],["dc.date.accessioned","2019-07-30T10:25:25Z"],["dc.date.available","2019-07-30T10:25:25Z"],["dc.date.issued","2017"],["dc.description.abstract","Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA-Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi-cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila Finally, MXEs are significantly enriched in pathogenic mutations and their spatio-temporal expression might predict human disease pathology."],["dc.identifier.doi","10.15252/msb.20177728"],["dc.identifier.pmid","29242366"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62194"],["dc.language.iso","en"],["dc.relation.eissn","1744-4292"],["dc.relation.issn","1744-4292"],["dc.relation.issn","1744-4292"],["dc.relation.issn","1744-4292"],["dc.title","The landscape of human mutually exclusive splicing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","D204"],["dc.bibliographiccitation.issue","D1"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","D219"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Rahman, Raza-Ur"],["dc.contributor.author","Liebhoff, Anna-Maria"],["dc.contributor.author","Bansal, Vikas"],["dc.contributor.author","Fiosins, Maksims"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Sattar, Abdul"],["dc.contributor.author","Magruder, Daniel S"],["dc.contributor.author","Madan, Sumit"],["dc.contributor.author","Sun, Ting"],["dc.contributor.author","Gautam, Abhivyakti"],["dc.contributor.author","Heins, Sven"],["dc.contributor.author","Liwinski, Timur"],["dc.contributor.author","Bethune, Jörn"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Fluck, Juliane"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Bonn, Stefan"],["dc.date.accessioned","2020-12-10T18:19:36Z"],["dc.date.available","2020-12-10T18:19:36Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1093/nar/gkz869"],["dc.identifier.eissn","1362-4962"],["dc.identifier.issn","0305-1048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75307"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","SEAweb: the small RNA Expression Atlas web application"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","35"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communication"],["dc.bibliographiccitation.lastpage","20"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Sikorska, Beata"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Fernández-Borges, Natalia"],["dc.contributor.author","Cramm, Maria"],["dc.contributor.author","Gotzmann, Nadine"],["dc.contributor.author","Carmona, Margarita"],["dc.contributor.author","Streichenberger, Nathalie"],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Liberski, Pawel P."],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-01-09T14:57:08Z"],["dc.date.available","2018-01-09T14:57:08Z"],["dc.date.issued","2017-04-27"],["dc.description.abstract","Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrPSc). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca2+) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca2+ responsive genes in sCJD brain tissue, accompanied by two Ca2+-dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrPSc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1186/s40478-017-0431-y"],["dc.identifier.pmid","28449707"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11612"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","2051-5960"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","149"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of general physiology"],["dc.bibliographiccitation.lastpage","170"],["dc.bibliographiccitation.volume","149"],["dc.contributor.author","Wolfes, Anne C."],["dc.contributor.author","Ahmed, Saheeb"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Stahlberg, Markus A."],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Magruder, Daniel S."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Dean, Camin"],["dc.date.accessioned","2019-07-09T11:43:25Z"],["dc.date.available","2019-07-09T11:43:25Z"],["dc.date.issued","2017"],["dc.description.abstract","Interactions between astrocytes and neurons rely on the release and uptake of glial and neuronal molecules. But whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures. This method is superior to other monocultures in terms of astrocyte morphology, mRNA expression profile, protein expression of cell maturity markers, and Ca(2+) fluctuations: In astrocytes transduced with GFAP promoter-driven Lck-GCaMP3, spontaneous Ca(2+) events in distinct domains (somata, branchlets, and microdomains) are similar to those in astrocytes co-cultured with other glia and neurons but unlike Ca(2+) events in astrocytes prepared using the McCarthy and de Vellis (MD) method and immunopanned (IP) astrocytes. We identify two distinct populations of constitutively recycling vesicles (harboring either VAMP2 or SYT7) specifically in branchlets of cultured stellate astrocytes. SYT7 is developmentally regulated in these astrocytes, and we observe significantly fewer synapses in wild-type mouse neurons grown on Syt7(-/-) astrocytes. SYT7 may thus be involved in trafficking or releasing synaptogenic factors. In summary, our novel method yields stellate astrocyte monocultures that can be used to study Ca(2+) signaling and vesicle recycling and dynamics in astrocytic processes."],["dc.description.abstract","whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures. This method is superior to other monocultures in terms of astrocyte morphology, mRNA expression profile, protein expression of cell maturity markers, and Ca2+ fluctuations: In astrocytes transduced with GFAP promoter–driven Lck-GCaMP3, spontaneous Ca2+ events in distinct domains (somata, branchlets, and microdomains) are similar to those in astrocytes co-cultured with other glia and neurons but unlike Ca2+ events in astrocytes prepared using the McCarthy and de Vellis (MD) method and immunopanned (IP) astrocytes. We identify two distinct populations of constitutively recycling vesicles (harboring either VAMP2 or SYT7) specifically in branchlets of cultured stellate astrocytes. SYT7 is developmentally regulated in these astrocytes, and we observe significantly fewer synapses in wild-type mouse neurons grown on Syt7−/− astrocytes. SYT7 may thus be involved in trafficking or releasing synaptogenic factors. In summary, our novel method yields stellate astrocyte monocultures that can be used to study Ca2+ signaling and vesicle recycling and dynamics in astrocytic processes."],["dc.identifier.doi","10.1085/jgp.201611607"],["dc.identifier.pmid","27908976"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14524"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58885"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/260916/EU//SYT ACTIVITY"],["dc.relation.issn","1540-7748"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject.ddc","612"],["dc.title","A novel method for culturing stellate astrocytes reveals spatially distinct Ca2+ signaling and vesicle recycling in astrocytic processes."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2231"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","2246"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Paiva, Isabel"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Pavlou, Maria Angeliki"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Schütz, Anna-Lena"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Szegő, Éva M."],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Rego, Ana Cristina"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2018-04-23T11:47:17Z"],["dc.date.available","2018-04-23T11:47:17Z"],["dc.date.issued","2017"],["dc.description.abstract","Alpha-synuclein (aSyn) is considered a major culprit in Parkinson’s disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed at evaluating the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms underlying aSyn-mediated transcriptional deregulation. We performed gene expression analysis using RNA-sequencing in Lund Human Mesencephalic (LUHMES) cells expressing endogenous (control) or increased levels of WT or A30P aSyn. Compared to control cells, cells expressing both aSyn variants exhibited robust changes in the expression of several genes, including downregulation of major genes involved in DNA repair. WT aSyn, unlike A30P aSyn, promoted DNA damage and increased levels of phosphorylated p53. In dopaminergic neuronal cells, increased aSyn expression led to reduced levels of acetylated histone 3. Importantly, treatment with sodium butyrate, a histone deacetylase inhibitor (HDACi), rescued WT aSyn-induced DNA damage, possibly via upregulation of genes involved in DNA repair. Overall, our findings provide novel and compelling insight into the mechanisms associated with aSyn neurotoxicity in dopaminergic cells, which could be ameliorated with an HDACi. Future studies will be crucial to further validate these findings and to define novel possible targets for intervention in PD."],["dc.identifier.doi","10.1093/hmg/ddx114"],["dc.identifier.gro","3142201"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13321"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0964-6906"],["dc.title","Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","102"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","110"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Halder, Rashi"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Vidal, Ramon O."],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Rahman, Raza-Ur"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Centeno, Tonatiuh Pena"],["dc.contributor.author","van Bebber, Frauke"],["dc.contributor.author","Capece, Vincenzo"],["dc.contributor.author","Garcia Vizcaino, Julio C."],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Burkhardt, Susanne"],["dc.contributor.author","Benito, Eva"],["dc.contributor.author","Navarro Sala, Magdalena"],["dc.contributor.author","Bahari Javan, Sanaz"],["dc.contributor.author","Haass, Christian"],["dc.contributor.author","Schmid, Bettina"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Bonn, Stefan"],["dc.date.accessioned","2018-05-30T15:01:05Z"],["dc.date.available","2018-05-30T15:01:05Z"],["dc.date.issued","2016"],["dc.description.abstract","The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring."],["dc.identifier.doi","10.1038/nn.4194"],["dc.identifier.pmid","26656643"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/14808"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1546-1726"],["dc.title","DNA methylation changes in plasticity genes accompany the formation and maintenance of memory"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]