636 research outputs found
Phosphorylation in intrinsically disordered regions regulates the activity of Neurogenin2.
BACKGROUND: Neuronal differentiation is largely under the control of basic Helix-Loop-Helix (bHLH) proneural transcription factors that play key roles during development of the embryonic nervous system. In addition to well-characterised regulation of their expression, increasing evidence is emerging for additional post-translational regulation of proneural protein activity. Of particular interest is the bHLH proneural factor Neurogenin2 (Ngn2), which orchestrates progression from neural progenitor to differentiated neuron in several regions of the central nervous system. Previous studies have demonstrated a key role for cell cycle-dependent multi-site phosphorylation of Ngn2 protein at Serine-Proline (SP) sites for regulation of its neuronal differentiation activity, although the potential structural and functional consequences of phosphorylation at different regions of the protein are unclear. RESULTS: Here we characterise the role of phosphorylation of specific regions of Ngn2 on the stability of Ngn2 protein and on its neuronal differentiation activity in vivo in the developing embryo, demonstrating clearly that the location of SP sites is less important than the number of SP sites available for control of Ngn2 activity in vivo. We also provide structural evidence that Ngn2 contains large, intrinsically disordered regions that undergo phosphorylation by cyclin-dependent kinases (cdks). CONCLUSIONS: Phosphorylation of Ngn2 occurs in both the N- and C-terminal regions, either side of the conserved basic Helix-Loop-Helix domain. While these phosphorylation events do not change the intrinsic stability of Ngn2, phosphorylation on multiple sites acts to limit its ability to drive neuronal differentiation in vivo. Phosphorylated regions of Ngn2 are predicted to be intrinsically disordered and cdk-dependent phosphorylation of these intrinsically disordered regions contributes to Ngn2 regulation.This work was
supported by MRC Research Grant G0700758 (AP), a Cancer Research UK Studentship (CH) and an
MRC DTA Studentship (GM). Support was also received (IL) from the TGE RMN THC (FR-3050,
France). We acknowledge support for international collaboration by a BQR fellowship from Lille
North of France University. The NMR facilities were funded by the Région Nord, CNRS, Pasteur
Institute of Lille, European Community (FEDER), French Research Ministry and the University of
Sciences and Technologies of Lille 1.This is the final version. It was first published by BioMed Central at http://www.biomedcentral.com/1471-2091/15/2
Cosmetische rostrale neusreconstructie na plaveiselcelcarninoomresectie bij twee honden
Two male Golden retrievers, each one about ten years old, were presented with a visible mass in the nose, showing symptoms of sneezing and epistaxis. The histopathological examination of biopsies indicated that both dogs were affected by a squamous cell carcinoma. Further staging did not reveal any indications for metastases. Surgical removal of the tumor through a planectomy or nosectomy was proposed. Since the classical removal of the nose was cosmetically unacceptable for the owners of both dogs, a rostral nose reconstruction was opted for in both cases. As the tumor in the first dog was rather superficial, resection of the cartilaginous part of the nose (planectomy) turned out to be sufficient. In the second dog however, there was also evidence of bony involvement. Therefore, not only the nose but also the os incisiva was removed (nosectomy). In both cases, remission of the tumor was obtained after a 35 and 29 months follow-up, respectively, accompanied by an excellent cosmetic result
Evolution of the electronic structure with size in II-VI semiconductor nanocrystals
In order to provide a quantitatively accurate description of the band gap
variation with sizes in various II-VI semiconductor nanocrystals, we make use
of the recently reported tight-binding parametrization of the corresponding
bulk systems. Using the same tight-binding scheme and parameters, we calculate
the electronic structure of II-VI nanocrystals in real space with sizes ranging
between 5 and 80 {\AA} in diameter. A comparison with available experimental
results from the literature shows an excellent agreement over the entire range
of sizes.Comment: 17 pages, 4 figures, accepted in Phys. Rev.
Tight-binding g-Factor Calculations of CdSe Nanostructures
The Lande g-factors for CdSe quantum dots and rods are investigated within
the framework of the semiempirical tight-binding method. We describe methods
for treating both the n-doped and neutral nanostructures, and then apply these
to a selection of nanocrystals of variable size and shape, focusing on
approximately spherical dots and rods of differing aspect ratio. For the
negatively charged n-doped systems, we observe that the g-factors for
near-spherical CdSe dots are approximately independent of size, but show strong
shape dependence as one axis of the quantum dot is extended to form rod-like
structures. In particular, there is a discontinuity in the magnitude of
g-factor and a transition from anisotropic to isotropic g-factor tensor at
aspect ratio ~1.3. For the neutral systems, we analyze the electron g-factor of
both the conduction and valence band electrons. We find that the behavior of
the electron g-factor in the neutral nanocrystals is generally similar to that
in the n-doped case, showing the same strong shape dependence and discontinuity
in magnitude and anisotropy. In smaller systems the g-factor value is dependent
on the details of the surface model. Comparison with recent measurements of
g-factors for CdSe nanocrystals suggests that the shape dependent transition
may be responsible for the observations of anomalous numbers of g-factors at
certain nanocrystal sizes.Comment: 15 pages, 6 figures. Fixed typos to match published versio
Bone regeneration via novel macroporous CPC scaffolds in critical-sized cranial defects in rats
Objectives. Calcium phosphate cement (CPC) is promising for dental and craniofacial applications due to its ability to be injected or filled into complex-shaped bone defects and molded for esthetics, and its resorbability and replacement by new bone. The objective of this study was to investigate bone regeneration via novel macroporous CPC containing absorbable fibers, hydrogel microbeads and growth factors in critical-sized cranial defects in rats. Methods. Mannitol porogen and alginate hydrogel microbeads were incorporated into CPC. Absorbable fibers were used to provide mechanical reinforcement to CPC scaffolds. Six CPC groups were tested in rats: (1) control CPC without macropores and microbeads; (2) macroporous CPC + large fiber; (3) macroporous CPC + large fiber + nanofiber; (4) same as (3), but with rhBMP2 in CPC matrix; (5) same as (3), but with rhBMP2 in CPC matrix + rhTGF-beta 1 in microbeads; (6) same as (3), but with rhBMP2 in CPC matrix + VEGF in microbeads. Rats were sacrificed at 4 and 24 weeks for histological and micro-CT analyses. Results. The macroporous CPC scaffolds containing porogen, absorbable fibers and hydrogel microbeads had mechanical properties similar to cancellous bone. At 4 weeks, the new bone area fraction (mean +/- sd; n = 5) in CPC control group was the lowest at (14.8 +/- 3.3)%, and that of group 6 (rhBMP2 + VEGF) was (31.0 +/- 13.8)% (p < 0.05). At 24 weeks, group 4 (rhBMP2) had the most new bone of (38.8 +/- 15.6)%, higher than (12.7 +/- 5.3)% of CPC control (p < 0.05). Micro-CT revealed nearly complete bridging of the critical-sized defects with new bone for several macroporous CPC groups, compared to much less new bone formation for CPC control. Significance. Macroporous CPC scaffolds containing porogen, fibers and microbeads with growth factors were investigated in rat cranial defects for the first time. Macroporous CPCs had new bone up to 2-fold that of traditional CPC control at 4 weeks, and 3-fold that of traditional CPC at 24 weeks, and hence may be useful for dental, craniofacial and orthopedic applications. (C) 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved
Photonic crystal carpet: Manipulating wave fronts in the near field at 1550 nm
Ground-plane cloaks, which transform a curved mirror into a flat one, and
recently reported at wavelengths ranging from the optical to the visible
spectrum, bring the realm of optical illusion a step closer to reality.
However, all carpet-cloaking experiments have thus far been carried out in the
far-field. Here, we demonstrate numerically and experimentally that a
dielectric photonic crystal (PC) of a complex shape made of a honeycomb array
of air holes can scatter waves in the near field like a PC with a at boundary
at stop band frequencies. This mirage effect relies upon a specific arrangement
of dielectric pillars placed at the nodes of a quasi-conformal grid dressing
the PC. Our carpet is shown to work throughout the range of wavelengths 1500nm
to 1650nm within the stop band extending from 1280 to 1940 nm. The device has
been fabricated using a single- mask advanced nanoelectronics technique on
III-V semiconductors and the near field measurements have been carried out in
order to image the wave fronts's curvatures around the telecommunication
wavelength 1550 nm.Comment: 6 page
Does Pelletizing Catalysts Influence the Efficiency Number of Activity Measurements? Spectrochemical Engineering Considerations for an Accurate Operando Study
International audienc
Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase
Tau neuronal protein has a central role in neurodegeneration and is implicated in Alzheimer disease development. Abnormal phosphorylation of Tau impairs its interaction with other proteins and is associated with its dysregulation in pathological conditions. Molecular mechanisms leading to hyperphosphorylation of Tau in pathological conditions are unknown. Here, we characterize phosphorylation of Tau by extracellular-regulated kinase (ERK2), a mitogen-activated kinase (MAPK) that responds to extracellular signals. Analysis of in vitro phosphorylated Tau by activated recombinant ERK2 with nuclear magnetic resonance spectroscopy (NMR) reveals phosphorylation of 15 Ser/Thr sites. In vitro phosphorylation of Tau using rat brain extract and subsequent NMR analysis identifies the same sites. Phosphorylation with rat brain extract is known to transform Tau into an Alzheimer disease-like state. Our results indicate that phosphorylation of Tau by ERK2 alone is sufficient to produce the same characteristics. We further investigate the mechanism of ERK2 phosphorylation of Tau. Kinases are known to recognize their protein substrates not only by their specificity for a targeted Ser or Thr phosphorylation site but also by binding to linear-peptide motifs called docking sites. We identify two main ERK2 docking sites in Tau sequence using NMR. Our results suggest that ERK2 dysregulation in Alzheimer disease could lead to abnormal phosphorylation of Tau resulting in the pathology of the disease.This work was supported by TGE RMN THC (FR-3050, France) and FRABio (Lille University, CNRS, FR 3688) and also by a grant from the LabEx (Laboratory of Excellence), DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer's disease), and in part by the French government funding agency Agence Nationale de la Recherche TAF. This work was supported by National Institutes of Health Grant R01 GM081578 (to S. P. and J. G.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
Electron-Hole Correlations and Optical Excitonic Gaps in Quantum-Dot Quantum Wells: Tight-Binding Approach
Electron-hole correlation in quantum-dot quantum wells (QDQW's) is
investigated by incorporating Coulomb and exchange interactions into an
empirical tight-binding model. Sufficient electron and hole single-particle
states close to the band edge are included in the configuration to achieve
convergence of the first spin-singlet and triplet excitonic energies within a
few meV. Coulomb shifts of about 100 meV and exchange splittings of about 1 meV
are found for CdS/HgS/CdS QDQW's (4.7 nm CdS core diameter, 0.3 nm HgS well
width and 0.3 nm to 1.5 nm CdS clad thickness) which have been characterized
experimentally by Weller and co-workers [ D. Schooss, A. Mews, A. Eychmuller,
H. Weller, Phys. Rev. B, 49, 17072 (1994)]. The optical excitonic gaps
calculated for those QDQW's are in good agreement with the experiment.Comment: 3 figures, to appear in Phys.Rev.
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