showing 31 related works from this author
Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study
2018
AbstractThreat detection is essential for protecting individuals from adverse situations, in which a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) regions are involved in fear processing. Excitability regulation in the dmPFC might be crucial for fear processing, while abnormal patterns could lead to mental illness. Notwithstanding, non-invasive paradigms to measure excitability regulation during fear processing in humans are missing. To address this challenge we adapted an approach for excitability characterization, combining electroencephalography (EEG) and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed fear paradigm, to dynamica…
Profiling of lipid species by normal-phase liquid chromatography, nanoelectrospray ionization, and ion trap–orbitrap mass spectrometry
2013
Detailed analysis of lipid species can be challenging due to their structural diversity and wide concentration range in cells, tissues, and biofluids. To address these analytical challenges, we devised a reproducible, sensitive, and integrated lipidomics workflow based on normal-phase liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) and LC-ITMS(2) (ion trap tandem mass spectrometry) for profiling and structural analysis of lipid species. The workflow uses a normal-phase LC system for efficient separation of apolar and polar lipid species combined with sensitive and specific analysis powered by a chip-based nanoelectrospray ion source and a hybrid ion trap-orbitrap mass sp…
(γ,2N) reaction inC12
1995
The $^{12}$C(\ensuremath{\gamma},pn) and $^{12}$C(\ensuremath{\gamma},pp) reactions have been measured for photon energies between 80 and 157 MeV using a photon tagging spectrometer and plastic scintillator detectors. The overall energy resolution was \ensuremath{\sim}7 MeV, sufficient to determine the initial shells of the emitted nucleons. Corrections were made for solid angle and threshold effects by means of Monte Carlo simulations. For the (\ensuremath{\gamma},pn) reaction both the missing energy and recoil momentum distributions are largely consistent with a two-nucleon absorption process on p-shell an sp nucleon pairs. For the much smaller $^{12}$C(\ensuremath{\gamma},pp) cross secti…
Community driven dynamics of oscillatory network responses to threat
2019
AbstractPhysiological responses to threat stimuli involve neural synchronized oscillations in cerebral networks with distinct organization properties. Community architecture within these networks and its dynamic adaptation could play a critical role in achieving optimal physiological responses.Here we applied dynamic network analyses to address the early phases of threat processing at the millisecond level, describing multi-frequency (theta and alpha) integration and basic reorganization properties (flexibility and clustering) that drive physiological responses. We quantified cortical and subcortical network interactions and captured illustrative reconfigurations using community allegiance …
Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation.
2018
Ongoing axonal degeneration is thought to underlie disability in chronic neuroinflammation, such as multiple sclerosis (MS), especially during its progressive phase. Upon inflammatory attack, axons undergo pathological swelling, which can be reversible. Because we had evidence for beneficial effects of T helper 2 lymphocytes in experimental neurotrauma and discovered interleukin-4 receptor (IL-4R) expressed on axons in MS lesions, we aimed at unraveling the effects of IL-4 on neuroinflammatory axon injury. We demonstrate that intrathecal IL-4 treatment during the chronic phase of several experimental autoimmune encephalomyelitis models reversed disease progression without affecting inflamma…
NT-3 protein levels are enhanced in the hippocampus of PRG1-deficient mice but remain unchanged in PRG1/LPA2 double mutants
2015
The plasticity-related gene 1 (PRG1) modulates bioactive lipids at the postsynaptic density and is a novel player in neuronal plasticity and regulation of glutamatergic transmission at principal neurons. PRG1, a neuronal molecule, is highly expressed during development and regeneration processes at the postsynaptic density, modulates synaptic lysophosphatidic acid (LPA) levels and is related to epilepsy and brain injury. In the present study, we analyzed the interaction between the synaptic molecules PRG1 and LPA2R with other plasticity-related molecules the neurotrophins. The protein levels of NGF, BDNF and NT-3 were measured using ELISA in hippocampal tissue of homozygous (PRG(-/-)) and h…
Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study
2018
AbstractBackgroundThreat detection is essential for protecting individuals from precarious situations. Early studies suggested a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) involved in fear processing. Excitability regulation in the dmPFC might be crucial for physiological fear processing, while an abnormal excitability pattern could lead to mental illness. Non-invasive paradigms to measure excitability regulation during fear processing in humans are missing.MethodsWe adapted an experimental approach of excitability characterization using electroencephalography (EEG) recordings and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed …
Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling
2016
Summary Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in PRG-2 full knockout (KO) and in thalamus-specific KO mice prematurely entered the cortical plate, eventually innervating non-corresponding barrels. This misrouting relied on lost axonal sensitivity toward lysophosphatidic acid (LPA), which failed to repel PRG-2-deficient thalamocortical fibers. PRG-2 electroporation in the PRG-2−/− thalamus restored the aberrant cortical innervation. We ide…
The 16O(γ, 2N) reaction measured with tagged photons
1991
The results of tagged-photon measurements of the 4He(γ, pn)d, 4He(γ, pn)pn and 4He(γ, pp)nn reactions, carried out with photons of energies 80–131 MeV, are presented. The (γ, pn)d three-body-breakup cross section dominates the four-body-breakup cross section. The three-body-breakup cross section and the corresponding deuteron recoil-momentum spectrum are reasonably accounted for by a mechanism of photon absorption on correlated proton-neutron pairs. In contrast the four-body-breakup mechanism appears to have two components: absorption on correlated proton-neutron pairs and a more complex additional component which has a distribution similar to phase space. The data rule out substantial phot…
The reaction at Eγ = 60 and 80 MeV
1986
Abstract The tagged photon technique has been used to measure the 12C photoproton cross section over the angular range θp = 30°–135° for Eγ = 60 and 80 MeV. Comparison of the results with quasifree knockout and quasideuteron calculations shows that photon interaction with two-nucleon pairs is dominant at least for high excitation energies in the residual nucleus.
Measurement of the p(γ,π^{0}) cross section at threshold
1990
Differential and absolute cross sections for the reaction {ital p}({gamma},{pi}{sup 0}) have been measured with energy-defined photons in the threshold region ({ital E}{sub {gamma}}=131.4--157.2 MeV). The {ital E}{sub 0+} amplitude has been extracted out of the data. The values found are in disagreement with predictions of low-energy theorems.
Differential cross sections for coherent and incoherent neutral-pion photoproduction from calcium
1989
Differential and absolute cross sections for the coherent reaction $^{40}\mathrm{Ca}$(\ensuremath{\gamma},${\ensuremath{\pi}}^{0}$${)}^{40}$Ca g.s., as well as for the incoherent reaction $^{40}\mathrm{Ca}$(\ensuremath{\gamma},${\mathrm{\ensuremath{\pi}}}^{0}$${)}^{40}$Ca(g.s.), have been measured with monochromatic photons in the threshold region (${E}_{\ensuremath{\gamma}}$=157--169 MeV). The differential cross section for the coherent process exhibits a diffraction minimum due to the nuclear mass form factor while the incoherent cross section is rather structureless. The cross sections are in good agreement with recent distorted-wave impulse-approximation calculations.
Quantitative Spatial Analysis of the Mouse Brain Lipidome by Pressurized Liquid Extraction Surface Analysis
2014
Here we describe a novel surface sampling technique termed pressurized liquid extraction surface analysis (PLESA), which in combination with a dedicated high-resolution shotgun lipidomics routine enables both quantification and in-depth structural characterization of molecular lipid species extracted directly from tissue sections. PLESA uses a sealed and pressurized sampling probe that enables the use of chloroform-containing extraction solvents for efficient in situ lipid microextraction with a spatial resolution of 400 μm. Quantification of lipid species is achieved by the inclusion of internal lipid standards in the extraction solvent. The analysis of lipid microextracts by nanoelectrosp…
Response of BGO detectors to photons of 3–50 MeV energy
1993
Abstract The response of an array of 7 hexagonal BGO detectors each 7.5 cm long (6.7 radiation lengths) with 3.6 cm side-to-side distance was measured using monochromatic photons from the tagged-photon facility at the electron accelerator MAMI A at Mainz. The experimental spectra of the deposited energy for a single detector and for the array of seven modules compare very well with the predictions of Monte Carlo shower simulations using the code GEANT3. Significant improvement of the energy resolution is observed for the summed energy spectra compared to the resolution of a single module. This improvement deteriorates at higher photon energies because the length of the detector is not suffi…
Analysis of Lipid Experiments (ALEX): A Software Framework for Analysis of High-Resolution Shotgun Lipidomics Data
2013
Global lipidomics analysis across large sample sizes produces high-content datasets that require dedicated software tools supporting lipid identification and quantification, efficient data management and lipidome visualization. Here we present a novel software-based platform for streamlined data processing, management and visualization of shotgun lipidomics data acquired using high-resolution Orbitrap mass spectrometry. The platform features the ALEX framework designed for automated identification and export of lipid species intensity directly from proprietary mass spectral data files, and an auxiliary workflow using database exploration tools for integration of sample information, computat…
Non-cell autonomous and non-catalytic activities of ATX in the developing brain
2015
The intricate formation of the cerebral cortex requires a well-coordinated series of events, which are regulated at the level of cell-autonomous and non-cell autonomous mechanisms. Whereas cell-autonomous mechanisms that regulate cortical development are well-studied, the non cell-autonomous mechanisms remain poorly understood. A non-biased screen allowed us to identify Autotaxin (ATX) as a non cell-autonomous regulator of neural stem cell proliferation. ATX (also known as ENPP2) is best known to catalyze lysophosphatidic acid (LPA) production. Our results demonstrate that ATX affects the localization and adhesion of neuronal progenitors in a cell autonomous and non-cell autonomous manner, …
Mutant Plasticity Related Gene 1 (PRG1) acts as a potential modifier in SCN1A related epilepsy
2018
ABSTRACTPlasticity related gene 1 encodes a cerebral neuron-specific synaptic transmembrane protein that modulates hippocampal excitatory transmission on glutamatergic neurons. In mice, homozygous Prg1-deficiency results in juvenile epilepsy. Screening a cohort of 18 patients with infantile spasms (West syndrome), we identified one patient with a heterozygous mutation in the highly conserved third extracellular phosphatase domain (p.T299S). The functional relevance of this mutation was verified by in-utero electroporation of a mutant Prg1 construct into neurons of Prg1-knockout embryos, and the subsequent inability of hippocampal neurons to rescue the knockout phenotype on the single cell l…
Altered synaptic phospholipid signaling in PRG-1 deficient mice induces exploratory behavior and motor hyperactivity resembling psychiatric disorders.
2017
Abstract Plasticity related gene 1 (PRG-1) is a neuron specific membrane protein located at the postsynaptic density of glutamatergic synapses. PRG-1 modulates signaling pathways of phosphorylated lipid substrates such as lysophosphatidic acid (LPA). Deletion of PRG-1 increases presynaptic glutamate release probability leading to neuronal over-excitation. However, due to its cortical expression, PRG-1 deficiency leading to increased glutamatergic transmission is supposed to also affect motor pathways. We therefore analyzed the effects of PRG-1 function on exploratory and motor behavior using homozygous PRG-1 knockout (PRG-1−/−) mice and PRG-1/LPA2–receptor double knockout (PRG-1−/−/LPA2−/−)…
Model of Wound Healing for Esophagogastric Anastomoses in Rats
2011
<b><i>Background:</i></b> Anastomotic leakage after esophageal surgery is a significant cause of morbidity and mortality. Postoperative leakage of esophagogastric anastomosis has been reported in 2–30% of surgical patient, resulting in an increased need for reoperation and a high risk of subsequent esophageal stricture formation and fistula. So far, experimental investigations on major factors influencing the healing of esophageal anastomoses, e.g. neovascularization and collagen deposition, have been hindered by the lack of a functional rodent model. <b><i>Methods:</i></b> We developed a novel technique of gastric tube formation followed by e…
The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1
2011
The transcription factor Nkx2-1 belongs to the homeobox-encoding family of proteins that have essential functions in prenatal brain development. Nkx2-1 is required for the specification of cortical interneurons and several neuronal subtypes of the ventral forebrain. Moreover, this transcription factor is involved in migratory processes by regulating the expression of guidance molecules. Interestingly, Nkx2-1 expression was recently detected in the mouse brain at postnatal stages. Using two transgenic mouse lines that allow prenatal or postnatal cell type-specific deletion of Nkx2-1, we show that continuous expression of the transcription factor is essential for the maturation and maintenanc…
Synaptic Phospholipid Signaling Modulates Axon Outgrowth via Glutamate-dependent Ca2+-mediated Molecular Pathways.
2015
Abstract Altered synaptic bioactive lipid signaling has been recently shown to augment neuronal excitation in the hippocampus of adult animals by activation of presynaptic LPA2-receptors leading to increased presynaptic glutamate release. Here, we show that this results in higher postsynaptic Ca2+ levels and in premature onset of spontaneous neuronal activity in the developing entorhinal cortex. Interestingly, increased synchronized neuronal activity led to reduced axon growth velocity of entorhinal neurons which project via the perforant path to the hippocampus. This was due to Ca2+-dependent molecular signaling to the axon affecting stabilization of the actin cytoskeleton. The spontaneous…
In‐depth protein profiling of the postsynaptic density from mouse hippocampus using data‐independent acquisition proteomics
2014
Located at neuronal terminals, the postsynaptic density (PSD) is a highly complex network of cytoskeletal scaffolding and signaling proteins responsible for the transduction and modulation of glutamatergic signaling between neurons. Using ion-mobility enhanced data-independent label-free LC-MS/MS, we established a reference proteome of crude synaptosomes, synaptic junctions, and PSD derived from mouse hippocampus including TOP3-based absolute quantification values for identified proteins. The final dataset across all fractions comprised 49 491 peptides corresponding to 4558 protein groups. Of these, 2102 protein groups were identified in highly purified PSD in at least two biological replic…
Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission
2016
Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical respo…
MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4
2015
A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functi…
Differential cross section for the reaction 2H(γ, p)n from 133 to 158 MeV
1991
The cross section for the reaction 2H(γ, p)n has been measured at laboratory photon energies Eγ = 133−158 MeV and c.m. angles between 30° and 150°. The reaction was induced by a tagged bremsstrahlung photon beam incident on a liquid deuterium target. The uncertainty in the absolute cross sections is ⩽ 5%. There is now reasonable agreement between recent measurements in this energy region and the overall data set now defines the cross section sufficiently well to provide a test of current models of the reaction.
Scaling of the 4He(γ,p)t reaction in the Eγ = 80–160 MeV region
1993
The 4He(γ,p) 3H reaction cross section has been measured with tagged photons of energy 81–158 MeV. Protons were detected over the angular range 55°–125°. The scaling of the data as a function of momentum mismatch has been examined for two reaction models, the modified quasideuteron mechanism and quasifree knockout. Both models show clear scaling behaviour but comparison of the predicted and measured scaling function shapes favours the modified quasideuteron mechanism at momenta up to ≈500 MeV/c.
Plasticity-related gene-1 inhibits lysophosphatidic acid-induced vascular smooth muscle cell migration and proliferation and prevents neointima forma…
2012
International audience; Plasticity-related gene-1 (PRG-1) protects neuronal cells from lysophosphatidic acid (LPA) effects. In vascular smooth muscle cells (VSMCs), LPA was shown to induce phenotypic modulation in vitro and vascular remodeling in vivo. Thus we explored the role of PRG-1 in modulating VSMC response to LPA. PCR, Western blot, and immunofluorescence experiments showed that PRG-1 is expressed in rat and human vascular media. PRG-1 expression was strongly inhibited in proliferating compared with quiescent VSMCs both in vitro and in vivo (medial vs. neointimal VSMCs), suggesting that PRG-1 expression is dependent on the cell phenotype. In vitro, adenovirus-mediated overexpression…
Molecular cause and functional impact of altered synaptic lipid signaling due to a prg‐1 gene SNP
2015
Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/ mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1 +/ mice, which are animal correlates of human PRG-1 +/mut carriers, showed an altered cortical networ…
Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations
2016
Extracellular electrode recording demonstrates acid-triggered electrical activity in glioma cell populations.
Multiple sclerosis – candidate mechanisms underlying CNS atrophy
2009
Recently it has become clear that the neuronal compartment plays a more important role than previously thought in the pathology of multiple sclerosis. Apart from demyelination, neuronal pathology is apparently largely responsible for the brain atrophy that can be observed early on and throughout the course of the disease. The loss of axons and their neurons in the course of chronic neuroinflammation is a major factor determining long-term disability in patients. The actual steps leading from immune attack against the myelin sheath to neuronal damage are not yet fully clear. Here we review key findings about direct axonal damage processes, demyelination-related neuronal pathology and cell-bo…
C12(γ,p)11B cross section from 80 to 157 MeV
1995
The $^{12}\mathrm{C}$(\ensuremath{\gamma},p${)}^{11}$B differential cross section has been measured over proton angles ranging from 58\ifmmode^\circ\else\textdegree\fi{} to 128\ifmmode^\circ\else\textdegree\fi{}, using tagged photons of energy 80--157 MeV, for low-lying regions of residual excitation energy in $^{11}\mathrm{B}$. The data have been compared with four different types of calculation. It is shown that scaling of the cross section with momentum mismatch occurs for both the ground-state and excited-state data.