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Results can be viewed by uploading data to http://crosslinkviewer.org/ or by downloading the software from http://github.com/colin-combe/ crosslink-viewer and running it locally. ... What follows describes the process of producing the interactive figure while keeping the cross-link data confidential 1 Download the xiNET project from https://github.com/ colin-combe/crosslink-viewer/ ...doi:10.1074/mcp.o114.042259 pmid:25648531 pmcid:PMC4390258 fatcat:a64p4mcdhjaijjh5psvqxw6nry
ComplexViewer is derived from xiNET (Combe et al., 2015) , which already contained functionality for displaying pairs of linked residues but could not display binding regions nor support n-ary interactions ...doi:10.1093/bioinformatics/btx497 pmid:29036573 pmcid:PMC5870653 fatcat:kpee5g2y4zcy5c5vpcjjuz6doq
Amyloid precursor protein (APP) plays a pivotal role in Alzheimer's disease (AD) pathogenesis, but its normal physiological functions are less clear. Combined deletion of the APP and APP-like protein 2 (APLP2) genes in mice results in post-natal lethality, suggesting that APP performs an essential, if redundant, function during embryogenesis. We previously showed that injection of antisense morpholino to reduce APP levels in zebrafish embryos caused convergent-extension defects. Here we reportdoi:10.1371/journal.pone.0034209 pmid:22545081 pmcid:PMC3335837 fatcat:z4b2j2kolvbsjfnksnlha5jxii
more »... hat a reduction in APP levels causes defective axonal outgrowth of facial branchiomotor and spinal motor neurons, which involves disorganized axonal cytoskeletal elements. The defective outgrowth is caused in a cell-autonomous manner and both extracellular and intracellular domains of human APP are required to rescue the defective phenotype. Interestingly, wild-type human APP rescues the defective phenotype but APPswe mutation, which causes familial AD, does not. Our results show that the zebrafish model provides a powerful system to delineate APP functions in vivo and to study the biological effects of APP mutations.
ratio (w/w) of 1:100 and incubated ON at 37°C. ... Crosslinker was added to a 1:1 (w/w) protein to crosslinker ratio and samples incubated for 2 h on ice. ...doi:10.1101/355396 fatcat:pmuw363tcvaonds3qjr3sy53y4
While numerous studies have documented evidence for plasticity of the human brain there is little evidence that the human spinal cord can change after injury. Here, we employ a novel spinal fMRI design where we stimulate normal and abnormal sensory dermatomes in persons with traumatic spinal cord injury and perform a connectivity analysis to understand how spinal networks process information. Methods: Spinal fMRI data was collected at 3 Tesla at two institutions from 38 individuals using thedoi:10.1371/journal.pone.0045560 pmid:23029097 pmcid:PMC3446947 fatcat:vxl3psc45bcgnjsms64f6ctwdu
more »... ndard SEEP functional MR imaging techniques. Thermal stimulation was applied to four dermatomes in an interleaved timing pattern during each fMRI acquisition. SCI patients were stimulated in dermatomes both above (normal sensation) and below the level of their injury. Sub-group analysis was performed on healthy controls (n = 20), complete SCI (n = 3), incomplete SCI (n = 9) and SCI patients who recovered full function (n = 6). Results: Patients with chronic incomplete SCI, when stimulated in a dermatome of normal sensation, showed an increased number of active voxels relative to controls (p = 0.025). There was an inverse relationship between the degree of sensory impairment and the number of active voxels in the region of the spinal cord corresponding to that dermatome of abnormal sensation (R 2 = 0.93, p,0.001). Lastly, a connectivity analysis demonstrated a significantly increased number of intraspinal connections in incomplete SCI patients relative to controls suggesting altered processing of afferent sensory signals. Conclusions: In this work we demonstrate the use of spinal fMRI to investigate changes in spinal processing of somatosensory information in the human spinal cord. We provide evidence for plasticity of the human spinal cord after traumatic injury based on an increase in the average number of active voxels in dermatomes of normal sensation in chronic SCI patients and an increased number of intraspinal connections in incomplete SCI patients relative to healthy controls.
Transmission electron microscopy Samples were fixed 2 h at 0u-4uC adding to sperm suspensions (PBS) equal volume of fixative solution consisting of 4% paraformaldehide (w/v), 4% glutaraldehyde (w/v) and ... Then sperm cells were centrifuged -equal time and force-and sperm pellets were post-fixed adding 30 ml of 1% OsO4 (w/v) overnight at 4uC. ...doi:10.1371/journal.pone.0013457 pmid:20976152 pmcid:PMC2956674 fatcat:tbt7klxix5bmhevrcxarllxv7m
The amyloid precursor protein (APP) is a type-I transmembrane glycoprotein widely studied for its role as the source of β-amyloid peptide, accumulation of which is causal in at least some cases of Alzheimer's disease (AD). APP is expressed ubiquitously and is involved in diverse biological processes. Growing bodies of evidence indicate connections between AD and somatic metabolic disorders related to type-2 diabetes, and App-/- mice show alterations in glycemic regulation. We find that App-/-doi:10.1152/ajpendo.00279.2018 pmid:30422705 pmcid:PMC6417684 fatcat:aokolkenovchjdztmwyllhbhfy
more »... ve higher levels of insulin-degrading enzyme (IDE) mRNA, protein, and activity compared to wild-type controls. This regulation of IDE by APP was widespread across numerous tissues including liver, skeletal muscle, and brain as well as cell types within neural tissue including neurons, astrocytes, and microglia. RNAi-mediated knockdown of APP in the SIM-A9 microglia cell line elevated IDE levels. Fasting levels of blood insulin were lower in App-/- than App+/+ mice, but the former showed a larger increase in response to glucose. These low basal levels may enhance peripheral insulin sensitivity, as App-/- mice failed to develop impairment of glucose tolerance on a high-fat, high-sucrose ("western") diet. Insulin levels and insulin signaling were also lower in App-/- brain; synaptosomes prepared from App-/- hippocampus showed diminished insulin receptor phosphorylation compared to App+/+ mice when stimulated ex vivo. These findings represent a new molecular link connecting APP to metabolic homeostasis and demonstrate a novel role for APP as an upstream regulator of IDE in vivo.
W. Bennett for their assistance in collection of animal tissues and A. Measham for his technical assistance with atomic absorption spectroscopy. Author Contributions ...doi:10.1371/journal.pone.0031185 pmid:22363575 pmcid:PMC3281953 fatcat:46i56aae3jdc3j7yjai2ke24pa
Sections were stained with 0.1% (w/v) Cresyl violet for 5 min, dehydrated through graded concentrations of ethanol, and cleared in xylene. ...doi:10.1371/journal.pone.0034504 pmid:22485176 pmcid:PMC3317633 fatcat:qffgadq4yfaqdkuwov53nh4xei
ratio (w/w) of 1:100 and incubated ON at 37°C. ... Crosslinker was added to a 1:1 (w/w) protein to crosslinker ratio and samples incubated for 2 h on ice. ...doi:10.15252/msb.20198994 pmid:31556486 pmcid:PMC6753376 fatcat:3nydwujmxrcjroena3zb7oajzq
An important neuropathological feature of neuroinflammatory processes that occur during e.g. Multiple Sclerosis (MS) is the formation of an astroglial scar. Astroglial scar formation is facilitated by the interaction between astrocytes and extracellular matrix proteins (ECM) such as fibronectin. Since there is evidence indicating that glial scars strongly inhibit both axon growth and (re)myelination in brain lesions, it is important to understand the factors that contribute to the interactiondoi:10.1371/journal.pone.0025037 pmid:21949843 pmcid:PMC3174992 fatcat:6g2iedjnxnam5mhnvotwsmgo5a
more »... tween astrocytes and ECM proteins. Tissue Transglutaminase (TG2) is a multifunctional enzyme with an ubiquitous tissue distribution, being clearly present within the brain. It has been shown that inflammatory cytokines can enhance TG2 activity. In addition, TG2 can mediate cell adhesion and migration and it binds fibronectin with high affinity. We therefore hypothesized that TG2 is involved in astrocyte-fibronectin interactions. Our studies using primary rat astrocytes show that intracellular and cell surface expression and activity of TG2 is increased after treatment with pro-inflammatory cytokines. Astrocyte-derived TG2 interacts with fibronectin and is involved in astrocyte adhesion onto and migration across fibronectin. TG2 is involved in stimulating focal adhesion formation which is necessary for the interaction of astrocytes with ECM proteins. We conclude that astrocyte-derived TG2 contributes to the interaction between astrocytes and fibronectin. It might thereby regulate ECM remodeling and possibly glial scarring.
Correspondence: Colin K. ...doi:10.1016/j.envpol.2018.05.047 pmid:29843010 pmcid:PMC6082156 fatcat:idxt2ko2gvgppob53edvhy6v4a
Exposure to air pollutants, including particulate matter, results in activation of the brain inflammatory response and Alzheimer disease (AD)-like pathology in dogs and humans. However, the length of time required for inhalation of ambient particulate matter to influence brain inflammation and AD pathology is less clear. Here, we studied the effect of 3 and 9 months of air particulate matter (<2.5 μm diameter, PM 2.5 ) exposure on brain inflammatory phenotype and pathological hallmarks of AD indoi:10.1371/journal.pone.0127102 pmid:25992783 pmcid:PMC4439054 fatcat:qtbk6gstwzbaxgsyzwkknq2mdq
more »... C57BL/6 mice. Using western blot, ELISA, and cytokine array analysis we quantified brain APP, beta-site APP cleaving enzyme (BACE), oligomeric protein, total Aβ 1-40 and Aβ 1-42 levels, inducible nitric oxide synthase (iNOS), nitrotyrosine-modified proteins, HNE-Michael adducts, vascular cell adhesion molecule 1 (VCAM-1), glial markers (GFAP, Iba-1), pre-and post-synaptic markers (synaptophysin and PSD-95), cyclooxygenase (COX-1, COX-2) levels, and the cytokine profile in PM 2.5 exposed and filtered air control mice. Only 9 month PM 2.5 exposure increased BACE protein levels, APP processing, and Aβ 1-40 levels. This correlated with a concomitant increase in COX-1 and COX-2 protein levels and a modest alteration in the cytokine profile. These data support the hypothesis that prolonged exposure to airborne particulate matter has the potential to alter brain inflammatory phenotype and promote development of early AD-like pathology. Primary antibodies (Ab) against actin (sc-1616), α-tubulin (sc-8304), COX-2 (sc-1745), tau (sc-1995), and VCAM-1 (sc-8035) were purchased from Santa Cruz Biotechnology Inc. (Dallas, TX). Antibodies against BACE (5606), GFAP (3670), and PSD-95 (3450 XP) were obtained from Cell Signaling Technology Inc. (Danvers, MA). HNE-adducts Ab (393207) and synaptophysin Ab (MAB5258) were from EMD Millipore (Billerica MA). Antibodies for inducible-NOS (ALX-210-504-R100) and nitrotyrosine (ALX-804-204-C050) were from Enzo Life Sciences Inc. (Farmingdale, NY).
The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenicdoi:10.1371/journal.pone.0037742 pmid:22675489 pmcid:PMC3366988 fatcat:6xvargzucfhzfh2x4qw6lou5xy
more »... ubventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5-6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments.
Visualisation tools should have low entry barriers such as being browser-based (Combe et al., 2015; Deutsch et al., 2015; Graham et al.; Kolbowski et al., 2018; Riffle et al., 2016; Trnka et al., 2014 ... Tools increase in value through integration, for example node-link diagrams that classically display protein interaction data (Combe et al., 2015) can be supplemented by a display of the residue-level ...arXiv:2007.00383v1 fatcat:cchlu3nykjcobhydrmfjrwyrqi
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