Stephan Philipp
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View article: Optimization of Structure‐Guided Development of Chemical Probes for the Pseudoknot RNA of the Frameshift Element in SARS‐CoV‐2
Optimization of Structure‐Guided Development of Chemical Probes for the Pseudoknot RNA of the Frameshift Element in SARS‐CoV‐2 Open
Targeting the RNA genome of SARS‐CoV‐2 is a viable option for antiviral drug development. We explored three ligand binding sites of the core pseudoknot RNA of the SARS‐CoV‐2 frameshift element. We iteratively optimized ligands, based on im…
View article: Optimization of Structure‐Guided Development of Chemical Probes for the Pseudoknot RNA of the Frameshift Element in SARS‐CoV‐2
Optimization of Structure‐Guided Development of Chemical Probes for the Pseudoknot RNA of the Frameshift Element in SARS‐CoV‐2 Open
Targeting the RNA genome of SARS‐CoV‐2 is a viable option for antiviral drug development. We explored three ligand binding sites of the core pseudoknot RNA of the SARS‐CoV‐2 frameshift element. We iteratively optimized ligands, based on im…
View article: Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes
Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes Open
A disintegrin and metalloproteinases (ADAMs) are transmembrane proteases that cleave other proteins close to the surface in a process called shedding . The prominent member ADAM10 has been linked to several pathologies such as Alzheimer’s …
View article: Comparison of measurements and simulation results of dose for the flash radiation therapy beamline at PITZ
Comparison of measurements and simulation results of dose for the flash radiation therapy beamline at PITZ Open
The high-brightness electron beam at the Photo Injector Test facility at DESY in Zeuthen (PITZ) is now also used for FLASHlab@PITZ: an R.&D platform for studying radiation biology and the FLASH effect in radiation therapy. The available pa…
View article: Overview of FLASHlab@PITZ: the new R&D platform for FLASH radiation therapy and radiation biology
Overview of FLASHlab@PITZ: the new R&D platform for FLASH radiation therapy and radiation biology Open
An R&D platform for electron FLASH radiation therapy and radiation biology is being prepared at the Photo Injector Test facility at DESY in Zeuthen (FLASH lab @PITZ). This platform is based on the unique beam parameters available at PITZ: …
View article: A beam line setup for flash radiation therapy with focused electron beams at the PITZ facility at desy in zeuthen: Basic concept and dosimetry simulations
A beam line setup for flash radiation therapy with focused electron beams at the PITZ facility at desy in zeuthen: Basic concept and dosimetry simulations Open
The objective of this study is demonstration of the principal possibility to increase the electron beam dose deposition at the certain depth of the sample for radiation therapy purposes. Electron bunches of 22 MeV within train generated at…
View article: Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma
Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma Open
Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivatio…
View article: Control of TRPM3 Ion Channels by Protein Kinase CK2-Mediated Phosphorylation in Pancreatic β-Cells of the Line INS-1
Control of TRPM3 Ion Channels by Protein Kinase CK2-Mediated Phosphorylation in Pancreatic β-Cells of the Line INS-1 Open
In pancreatic β-cells of the line INS-1, glucose uptake and metabolism induce the openings of Ca2+-permeable TRPM3 channels that contribute to the elevation of the intracellular Ca2+ concentration and the fusion of insulin granules with th…
View article: Prolactin-sensitive olfactory sensory neurons regulate male preference in female mice by modulating responses to chemosensory cues
Prolactin-sensitive olfactory sensory neurons regulate male preference in female mice by modulating responses to chemosensory cues Open
Prolactin modulates the detection of olfactory signals in female mice to enhance preference toward males.
View article: Cavβ3 regulates Ca2+-signalling and insulin expression in pancreatic β-cells in a cell-autonomous manner
Cavβ3 regulates Ca2+-signalling and insulin expression in pancreatic β-cells in a cell-autonomous manner Open
Voltage-gated Ca2+ (Cav) channels consist of a pore-forming Cavα1 subunit and auxiliary Cavα2-δ and Cavβ subunits. In fibroblasts, Cavβ3, independent of its role as a Cav subunit, reduces the sensitivity to low concentrations of inositol-1…
View article: Cavβ3 regulates Ca2+-signalling and insulin expression in pancreatic β-cells in a cell-autonomous manner
Cavβ3 regulates Ca2+-signalling and insulin expression in pancreatic β-cells in a cell-autonomous manner Open
Voltage-gated Ca2+ (Cav) channels consist of a pore-forming Cavα1 subunit and auxiliary Cavα2-δ and Cavβ subunits. In fibroblasts, Cavβ3, independent of its role as a Cav subunit, reduces the sensitivity to low concentrations of inositol-1…
View article: Cavβ3 Regulates Ca2+ Signaling and Insulin Expression in Pancreatic β-Cells in a Cell-Autonomous Manner
Cavβ3 Regulates Ca2+ Signaling and Insulin Expression in Pancreatic β-Cells in a Cell-Autonomous Manner Open
Voltage-gated Ca2+ (Cav) channels consist of a pore-forming Cavα1 subunit and auxiliary Cavα2-δ and Cavβ subunits. In fibroblasts, Cavβ3, independent of its role as a Cav subunit, reduces the sensitivity to low concentrations of inositol-1…
View article: CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression
CK2 Activity Mediates the Aggressive Molecular Signature of Glioblastoma Multiforme by Inducing Nerve/Glial Antigen (NG)2 Expression Open
Nerve/glial antigen (NG)2 expression crucially determines the aggressiveness of glioblastoma multiforme (GBM). Recent evidence suggests that protein kinase CK2 regulates NG2 expression. Therefore, we investigated in the present study wheth…
View article: Transient Receptor Potential Vanilloid 6 (TRPV6) Proteins Control the Extracellular Matrix Structure of the Placental Labyrinth
Transient Receptor Potential Vanilloid 6 (TRPV6) Proteins Control the Extracellular Matrix Structure of the Placental Labyrinth Open
Calcium-selective transient receptor potential Vanilloid 6 (TRPV6) channels are expressed in fetal labyrinth trophoblasts as part of the feto–maternal barrier, necessary for sufficient calcium supply, embryo growth, and bone development du…
View article: Control of Insulin Release by Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels
Control of Insulin Release by Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels Open
The present study suggests an important role for TRPM3 channels in the control of glucose-dependent insulin release.
View article: The structural basis for an on–off switch controlling Gβγ-mediated inhibition of TRPM3 channels
The structural basis for an on–off switch controlling Gβγ-mediated inhibition of TRPM3 channels Open
Significance µ-Opioid receptors, activated by endogenous peptides or opioid drugs such as morphine, dampen the activity of nociceptor cells that detect noxious stimuli and thereby reduce pain. These receptors achieve this clinically import…
View article: Pharmacological properties of TRPM3 isoforms are determined by the length of the pore loop
Pharmacological properties of TRPM3 isoforms are determined by the length of the pore loop Open
Background and Purpose Transient receptor potential melastatin 3 (TRPM3) is a non‐selective cation channel that plays a pivotal role in the peripheral nervous system as a transducer of painful heat signals. Alternative splicing gives rise …
View article: Protein Kinase CK2 Controls CaV2.1-Dependent Calcium Currents and Insulin Release in Pancreatic β-cells
Protein Kinase CK2 Controls CaV2.1-Dependent Calcium Currents and Insulin Release in Pancreatic β-cells Open
The regulation of insulin biosynthesis and secretion in pancreatic β-cells is essential for glucose homeostasis in humans. Previous findings point to the highly conserved, ubiquitously expressed serine/threonine kinase CK2 as having a nega…
View article: Crystal structure of a conformational antibody that binds tau oligomers and inhibits pathological seeding by extracts from donors with Alzheimer's disease
Crystal structure of a conformational antibody that binds tau oligomers and inhibits pathological seeding by extracts from donors with Alzheimer's disease Open
Soluble oligomers of aggregated tau accompany the accumulation of insoluble amyloid fibrils, a histological hallmark of Alzheimer disease (AD) and two dozen related neurodegenerative diseases. Both oligomers and fibrils seed the spread of …
View article: Polymer foil windows for gas–vacuum separation in accelerator applications
Polymer foil windows for gas–vacuum separation in accelerator applications Open
Various applications in modern particle accelerators or experiments involving high energy particle beams require a gas atmosphere or involve the production of big amounts of residual gas. Among these are, e.g., gas cells for plasma acceler…
View article: Age-Related Intraneuronal Aggregation of Amyloid-β in Endosomes, Mitochondria, Autophagosomes, and Lysosomes
Age-Related Intraneuronal Aggregation of Amyloid-β in Endosomes, Mitochondria, Autophagosomes, and Lysosomes Open
This work provides new insight into the age-related basis of Alzheimer’s disease (AD), the composition of intraneuronal amyloid (iAβ), and the mechanism of an age-related increase in iAβ in adult AD-model mouse neurons. A new end-specific …
View article: Structure-based inhibitors of amyloid beta core suggest a common interface with tau
Structure-based inhibitors of amyloid beta core suggest a common interface with tau Open
Alzheimer’s disease (AD) pathology is characterized by plaques of amyloid beta (Aβ) and neurofibrillary tangles of tau. Aβ aggregation is thought to occur at early stages of the disease, and ultimately gives way to the formation of tau tan…
View article: Author response: Structure-based inhibitors of amyloid beta core suggest a common interface with tau
Author response: Structure-based inhibitors of amyloid beta core suggest a common interface with tau Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Alzheimer’s disease (AD) pathology is char…
View article: Jitter mitigation in low density discharge plasma cells for wakefield accelerators
Jitter mitigation in low density discharge plasma cells for wakefield accelerators Open
In the field of beam driven acceleration of particles in plasma wakefields (PWFA), the source of the plasma medium is a crucial part of the accelerator setup. Gas discharges have proven to be a reliable and simple type of a plasma source i…
View article: Passive Ballistic Microbunching of Nonultrarelativistic Electron Bunches Using Electromagnetic Wakefields in Dielectric-Lined Waveguides
Passive Ballistic Microbunching of Nonultrarelativistic Electron Bunches Using Electromagnetic Wakefields in Dielectric-Lined Waveguides Open
Temporally modulated electron beams have a wide array of applications ranging from the generation of coherently enhanced electromagnetic radiation to the resonant excitation of electromagnetic wakefields in advanced-accelerator concepts. L…
View article: Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease
Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease Open
Our findings demonstrate that CSF1R signaling, either directly on neurons or mediated by microglia, is crucial for the accumulation of intraneuronal amyloid and formation of neuritic plaques, suggesting that these two events are serially l…
View article: Common fibrillar spines of amyloid-β and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors
Common fibrillar spines of amyloid-β and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors Open
Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with Alzheimer's disease (AD) and type II diabetes (T2D), respectively. Individuals with T2D have an in…
View article: Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels
Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels Open
Opioids, agonists of µ-opioid receptors (µORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, µORs are also found on the periphe…