Search results for " maps"
showing 10 items of 198 documents
Identification of novel drug resistance mechanisms by genomic and transcriptomic profiling of glioblastoma cells with mutation-activated EGFR.
2021
Abstract Aims Epidermal growth factor receptor (EGFR) is not only involved in carcinogenesis, but also in chemoresistance. We characterized U87.MGΔEGFR glioblastoma cells with constitutively active EGFR due to deletion at the ligand binding domain in terms of gene expression profiling and chromosomal aberrations. Wild-type U87.MG cells served as control. Materials and methods RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed to identify novel drug resistance mechanisms related to expression of mutation activated EGFR. Chromosomal aberrations were characterized by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (…
Virus-host interactome: Putting the accent on how it changes
2017
[EN] Viral infections are extremely complex processes that could only be well understood by precisely characterizing the interaction networks between the virus and the host components. In recent years, much effort has gone in this directionwith the aimof unveiling themolecular basis of viral pathology. These networks are mostly formed by viral and host proteins, and are expected to be dynamic bothwith time and space (i.e., with the progression of infection, as well as with the virus and host genotypes; what we call plastodynamic). This largely overlooked spatio-temporal evolution urgently calls for a change both in the conceptual paradigms and experimental techniques used so far to characte…
HIPPIE v2.0: Enhancing meaningfulness and reliability of protein-protein interaction networks
2016
The increasing number of experimentally detected interactions between proteins makes it difficult for researchers to extract the interactions relevant for specific biological processes or diseases. This makes it necessary to accompany the large-scale detection of protein-protein interactions (PPIs) with strategies and tools to generate meaningful PPI subnetworks. To this end, we generated the Human Integrated Protein-Protein Interaction rEference or HIPPIE (http://cbdm.uni-mainz.de/hippie/). HIPPIE is a one-stop resource for the generation and interpretation of PPI networks relevant to a specific research question. We provide means to generate highly reliable, context-specific PPI networks …
TLR4 participates in the transmission of ethanol-induced neuroinflammation via astrocyte-derived extracellular vesicles
2019
Background Current evidence indicates that extracellular vesicles (EVs) participate in intercellular signaling, and in the regulation and amplification of neuroinflammation. We have previously shown that ethanol activates glial cells through Toll-like receptor 4 (TLR4) by triggering neuroinflammation. Here, we evaluate if ethanol and the TLR4 response change the release and inflammatory content of astrocyte-derived EVs, and whether these vesicles are capable of communicating with neurons by spreading neuroinflammation. Methods Cortical neurons and astrocytes in culture were used. EVs were isolated from the extracellular medium of the primary culture of the WT and TLR4-KO astrocytes treated …
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
2017
International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…
Cell Type-Specific Tandem Affinity Purification of the Mouse Hippocampal CB1 Receptor-Associated Proteome
2016
G protein coupled receptors (GPCRs) exert their effects through multiprotein signaling complexes. The cannabinoid receptor type 1 (CB1) is among the most abundant GPCRs in the mammalian brain and involved in a plethora of physiological functions. We used a combination of viral-mediated cell type-specific expression of a tagged CB1 fusion protein (CB1-SF), tandem affinity purification (TAP) and proteomics on hippocampal mouse tissue to analyze the composition and differences of CB1 protein complexes in glutamatergic neurons and in GABAergic interneurons. Purified proteins underwent tryptic digestion and were identified using deep-coverage data-independent acquisition with ion mobility separa…
Human R1441C LRRK2 regulates the synaptic vesicle proteome and phosphoproteome in a Drosophila model of Parkinson's disease
2016
International audience; Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinsons disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model. To explore the function of LRRK2 variants in vivo, we …
The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model
2017
Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC) loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP), followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced b…
The latent geometry of the human protein interaction network
2017
Abstract Motivation A series of recently introduced algorithms and models advocates for the existence of a hyperbolic geometry underlying the network representation of complex systems. Since the human protein interaction network (hPIN) has a complex architecture, we hypothesized that uncovering its latent geometry could ease challenging problems in systems biology, translating them into measuring distances between proteins. Results We embedded the hPIN to hyperbolic space and found that the inferred coordinates of nodes capture biologically relevant features, like protein age, function and cellular localization. This means that the representation of the hPIN in the two-dimensional hyperboli…
Exploring the Human-Nipah Virus Protein-Protein Interactome
2017
ABSTRACT Nipah virus is an emerging, highly pathogenic, zoonotic virus of the Paramyxoviridae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified 101 human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel. This data set provides a comprehensive view of the host complexes that are manip…