73 research outputs found
Novel Magnet Production Technique Used for an Elliptically Polarizing Undulator
A common problem for elliptically polarizing undulators EPUs is that the magnetic forces give a mechanical deflection in the magnet holder construction when changing the undulator phase. Gluing horizontally and vertically magnetized blocks together can increase the mechanical stability of the magnet holders. The gluing process of pairs of magnetized magnet blocks is time consuming, expensive and difficult to carry out with high positional precision. A novel magnet production technique has been developed where un magnetized pairs of blocks are glued together before magnetization. The large number of parts, the time for assembly, and the cost of the EPU can be reduced with the novel magnet production technique. The novel magnet production method has been used for a 2.6 m long EPU of APPLE II type, which has been built in house at the MAX IV Laboratory. The frame for the EPU is made of cast iron in order to get a small mechanical deformation when changing phase in the inclined mode. The paper includes detailed descriptions of the novel magnet production technique, including measurements of the magnetization, and the new EP
BMP2-induced chemotaxis requires PI3K p55γ/p110α-dependent phosphatidylinositol (3,4,5)-triphosphate production and LL5β recruitment at the cytocortex
Background: BMP-induced chemotaxis of mesenchymal progenitors is fundamental
for vertebrate development, disease and tissue repair. BMP2 induces Smad and
non-Smad signalling. Whereas signal transduction via Smads lead to
transcriptional responses, non-Smad signalling induces both, transcriptional
and immediate/early non-transcriptional responses. However, the molecular
mechanisms by which BMP2 facilitates planar cell polarity, cortical actin
rearrangements, lamellipodia formation and chemotaxis of mesenchymal
progenitors are poorly understood. Our aim was to uncover the molecular
mechanism by which BMP2 facilitates chemotaxis via the BMP2-dependent
activation of PI3K and spatiotemporal control of PIP3 production important for
actin rearrangements at the mesenchymal cell cytocortex. Results: We unveiled
the molecular mechanism by which BMP2 induces non-Smad signalling by PI3K and
the role of the second messenger PIP3 in BMP2-induced planar cell polarity,
cortical actin reorganisation and lamellipodia formation. By using protein
interaction studies, we identified the class Ia PI3K regulatory subunit p55γ
to act as a specific and non-redundant binding partner for BMP receptor type
II (BMPRII) in concert with the catalytic subunit p110α. We mapped the PI3K
interaction to a region within the BMPRII kinase. Either BMP2 stimulation or
increasing amounts of BMPRI facilitated p55γ association with BMPRII, but
BMPRII kinase activity was not required for the interaction. We visualised
BMP2-dependent PIP3 production via PI3K p55γ/p110α and were able to localise
PIP3 to the leading edge of intact cells during the process of BMP2-induced
planar cell polarity and actin dependent lamellipodia formation. Using mass
spectrometry, we found the highly PIP3-sensitive PH-domain protein LL5β to act
as a novel BMP2 effector in orchestrating cortical actin rearrangements. By
use of live cell imaging we found that knock-down of p55γ or LL5β or
pharmacological inhibition of PI3K impaired BMP2-induced migratory responses.
Conclusions: Our results provide evidence for an important contribution of the
BMP2-PI3K (p55γ/p110α)- PIP3-LL5β signalling axis in mesenchymal progenitor
cell chemotaxis. We demonstrate molecular insights into BMP2-induced PI3K
signalling on the level of actin reorganisation at the leading edge
cytocortex. These findings are important to better understand BMP2–induced
cytoskeletal reorganisation and chemotaxis of mesenchymal progenitors in
different physiological or pathophysiological contexts
Eur J Human Genet
Heterozygous missense mutations in the serine-threonine kinase receptor BMPR1B result typically in brachydactyly type A2 (BDA2), whereas mutations in the corresponding ligand GDF5 cause brachydactyly type C (BDC). Mutations in the GDF inhibitor Noggin (NOG) or activating mutations in GDF5 cause proximal symphalangism (SYM1). Here, we describe a novel mutation in BMPR1B (R486Q) that is associated with either BDA2 or a BDC/SYM1-like phenotype. Functional investigations of the R486Q mutation were performed and compared with the previously reported BDA2-causing mutation R486W and WT BMPR1B. Overexpression of the mutant receptors in chicken micromass cultures resulted in a strong inhibition of chondrogenesis with the R486Q mutant, showing a stronger effect than the R486W mutant. To investigate the consequences of the BMPR1B mutations on the intracellular signal transduction, we used stably transfected C2C12 cells and measured the activity of SMAD-dependent and SMAD-independent pathways. SMAD activation after stimulation with GDF5 was suppressed in both mutants. Alkaline phosphatase induction showed an almost complete loss of activation by both mutants. Our data extend the previously known mutational and phenotypic spectrum associated with mutations in BMPR1B. Disturbances of NOG-GDF5-BMPR1B signaling cascade can result in similar clinical manifestations depending on the quantitative effect and mode of action of the specific mutations within the same functional pathway
Risk factors for mediastinitis after cardiac surgery – a retrospective analysis of 1700 patients
Efficient derivation of dopaminergic neurons from SOX1− floor plate cells under defined culture conditions
Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron
The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning
Spinglasverhalten des verduennten Antiferromagneten EuxSr1-xTe
SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman
Surface immobilization of bone morphogenetic protein 2 via a self-assembled monolayer formation induces cell differentiation
Bone extracellular matrix consists of a network of proteins in which growth factors, like bone morphogenetic protein 2 (BMP-2), are embedded and released upon matrix turnover and degradation. Recombinant human (rh)BMP-2 shows promise in enhancing bone fracture repair, although issues regarding finding a suitable delivery system still limit its extensive clinical use. The aim of this study is to determine which cell activities are triggered by the presentation of immobilized rhBMP-2. For this purpose gold surfaces were first decorated with a self-assembled monolayer consisting of a hetero-bifunctional linker. rhBMP-2 was covalently bound to the surfaces via this linker and used to investigate the cellular responses of C2C12 myoblasts. We show that covalently immobilized rhBMP-2 (iBMP-2) initiates short-term signaling events. Using a BMP-responsive reporter gene assay and western blotting to monitor phosphorylation of Smad1/5/8 we prove that iBMP-2 activates BMP-dependent signal transduction. Furthermore, we demonstrate that iBMP-2 suppresses myotube formation and promotes the osteoblast phenotype in C2C12 cells. The bioactivity of surface-bound rhBMP-2 presented in this study is not due to its release into the medium. As such, our simple approach paves the way for the controlled local presentation of immobilized growth factors, limiting degradation while still maintaining biological activity
TCT-751 Eccentricity Of The Aortic Annulus Is Not Associated With Functional Impairment Of The Transapical JenaValve In An In Vitro Durability Test Model
TCT-680 Influence Of Preoperative Computed Tomography Image Analysis By A Dedicated Software On Outcomes After Transcatheter Aortic Valve Implantation
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