Coarsegrained modeling and electrostatics of phospholipid monolayers

Vangaveti, Sweta

doi:10.31274/etd-180810-3813

Cited by 2 publications

(2 citation statements)

References 126 publications

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“…Few studies on G2A effects on pain were also performed in patients. Thus, patients with neck pain or chronic widespread pain showed increased plasma levels of 9-HODE were found and in diabetes patients G2A was upregulated in activated monocytes [109,110]. Similar results were observed in patients with primary Sjögren's syndrome, who suffered from widespread pain [111].…”

Section: G2a and Neuropathic Painsupporting

confidence: 61%

Oxidized lipids and signaling pathways of G2A receptor involved in nerve injury induced neuropathic pain

Osthues¹

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Neuropathic pain, a form of chronic pain, is a steadily rising health problem due to health costs and increasing numbers of patients. Neuropathic pain conditions arise upon metabolic disorders, infections, chemotherapeutic treatment, trauma or nerve injury. Especially nerve injury induced neuropathic pain is characterized by spontaneous or ongoing pain due to neuroimmune interactions. Thereby, inflammatory mediators, released by the injured nerve, recruit to and activate immune cells at the site of injury. Those mediators further activate transient receptor potential vanilloid 1 (TRPV1), a known channel involved in pain perception, or bind to G-protein coupled receptors (GPCR) in peripheral nerve endings. The following activated second messenger signaling pathways lead to sensitization of TRPV1. One of those GPCRs is G2A. The overall aim of this thesis was to investigate the role of G2A in nerve-injury induced neuropathic pain. For this, the common mouse model of nerve-injury induced neuropathic pain, the spared-nerve injury, was used. As measurements with dynamic plantar aesthesiometer showed, G2A-deficiency leads to reduced mechanical hypersensitivity. Upon analysis with FACS, ELISA and Luminex a reduced number of macrophages and neutrophils at the injured nerve, as well as less inflammatory mediators (TNFα, IL-6, VEGF) in G2A-deficient animals was observed. In dorsal root ganglia (DRGs) there was only a reduced number of macrophages and less IL-12 observed in G2A-deficient animals. Additionally, in wild-type mice, G2A agonist 9-HODE was elevated at the injured nerve, as a LC-MS/MS analysis showed. To investigate the underlying pathways of G2A-9-HODE signaling, a proteom screen was performed. This screen revealed upregulation of multiple proteins involved in migration in wild-type macrophages. Additionally, Ca-Imaging and transwell migration assays showed that the G2A antagonist G2A11, had desensitizing effects on DRG neurons and inhibited macrophage migration. Overall, the results suggest that loss of G2A has dual effects. On the one hand loss of G2A is antinociceptive. On the other hand, G2A-deficiency leads to reduced inflammation, suggesting G2A as promising target in treatment of neuropathic pain. Here, an antagonist had inhibitory effects on the migration and the sensitization.

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Section: G2a and Neuropathic Painsupporting

confidence: 61%

Oxidized lipids and signaling pathways of G2A receptor involved in nerve injury induced neuropathic pain

Osthues¹

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“…13 Even more difficult are studies of dynamic complexes such as nucleic acids or intrinsically unstructured proteins, where the CCS must be calculated as an ensemble average over many different structures generated from molecular dynamic simulations, further increasing the computational complexity. [14][15][16] To this end, the work presented here introduces a novel collision engine that calculates trajectory method CCSs of both small and large molecules, applies common molecular mechanic algorithms when appropriate to save computational time, and is designed for both single and multi-threaded computer systems. A summary of the most common CCS calculation methods used in practice will be covered in section 2, while the details of the algorithm used in our proposed Collision Simulator for Ion Mobility Spectrometry (CoSIMS) will be described in section 3.…”

Section: Introductionmentioning

confidence: 99%

CoSIMS: An Optimized Trajectory-Based Collision Simulator for Ion Mobility Spectrometry

et al. 2019

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A new, multi-threaded, trajectory method based software platform, CoSIMS, is revealed and compared to reference MOBCAL collision cross sections (CCS). CoSIMS employs various molecular mechanics algorithms to lessen the computational resources required to simulate thousands of buffer gas-ion collisions, including the neglect of London dispersion interactions at long distances and the removal of trajectories that insignificantly contribute to the total CCS via an ellipsoidal projection approximation. The showcased program is used to calculate the collision cross sections of carbon fullerenes, proteins, and DNA strands of various lengths, sizes, and molecular weights, and compared against the the CCSs calculated by MOBCAL. Through this analysis, it is shown that the application the aforementioned algorithms enables for both faster and more reasonable CCS calculations than MOBCAL for highly elongated molecules such as nucleic acids; for all other molecules, CoSIMS is able to reproduce the CCSs generated by MOBCAL's trajectory method within a few percent. Overall, CoSIMS is able to calculate nearly identical CCSs as MOBCAL in nearly two orders of magnitude less CPU time due to the various numerical methods implemented into the software, even when run on a single CPU core.

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Coarsegrained modeling and electrostatics of phospholipid monolayers

Cited by 2 publications

References 126 publications

Oxidized lipids and signaling pathways of G2A receptor involved in nerve injury induced neuropathic pain

Oxidized lipids and signaling pathways of G2A receptor involved in nerve injury induced neuropathic pain

CoSIMS: An Optimized Trajectory-Based Collision Simulator for Ion Mobility Spectrometry

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