Newly generated cells are increased in hippocampus of adult mice lacking a serine protease inhibitor

Background  

Neurogenesis in the hippocampal dentate gyrus and the subventricular zone occurs throughout the life of mammals and newly generated neurons can integrate functionally into established neuronal circuits. Neurogenesis levels in the dentate gyrus are modulated by changes in the environment (enrichment, exercise), hippocampal-dependent tasks, NMDA receptor (NMDAR) activity, sonic hedgehog (SHH) and/or other factors.     

Liquid Metastable Precursors of Ibuprofen as Aqueous Nucleation Intermediates

The nucleation mechanism of crystals of small organic molecules, postulated based on computer simulations, still lacks experimental evidence. In this study we designed an experimental approach to monitor the early stages of the crystallization of ibuprofen as a model system for small organic molecules. Ibuprofen undergoes liquid–liquid phase separation prior to nucleation. The binodal and spinodal limits of the corresponding liquid–liquid miscibility gap were analyzed and confirmed. An increase in viscosity sustains the kinetic stability of the dense liquid intermediate. Since the distances between ibuprofen molecules within the dense liquid phase are similar to those in the crystal forms, this dense liquid phase is identified as a precursor phase in the nucleation of ibuprofen, in which densification is followed by generation of structural order. This discovery may make it possible to enrich poorly soluble pharmaceuticals beyond classical solubility limitations in aqueous environments.     

On the estimation of the strength of supramolecular complexes of fullerenes

The accurate estimation of the free energy changes in solution for supramolecular complexes is one of the most important challenges for quantum chemistry in this century. In general, there is a good correlation between the association constants determined experimentally and the gas phase binding energies calculated using the most popular density functional methods. However, when the receptors adopt very different structures in the gas and condensed phase, this approach does not work, leading to unreliable predictions. We discuss this problem in detail using three popular fullerene receptors: Aida's dimeric porphyrins, buckycatchers I, and II. We found that it is possible to obtain a reliable order of affinities using gas phase binding energies when a special attention is put on analyzing the structure adopted by the receptor in the gas and condensed phases.     

Synthesis and Upconversion Luminescence in LaF3:Yb3+, Ho3+, GdF3: Yb3+, Tm3+ and YF3:Yb3+, Er3+ obtained from Sulfide Precursors

Rare earth fluorides are mainly obtained from aqueous solutions of oxygen‐containing precursors. Probably, this method is simple and efficient, however, oxygen may partially be retained in the fluoride structure. We offer an alternative method: obtaining fluorides and solid solutions based on them from an oxygen‐free precursor. As starting materials, we choose sulfides of rare‐earth elements and solid solutions based on them. The fluorination is carried out by exposure to hydrofluoric acid of various concentrations. The transmission electron microscopy images revealed the different morphologies of the products, which depend on the concentration of the fluorinating component (HF) and the host element. The solid solution particle size varied from 30–35 nm in the case of GdF₃:Yb³⁺, Tm³⁺ (4 % HF) to larger structures with dimensions exceeding 200 nm, such as that for LaF₃:Yb³⁺, Ho³⁺ (40 % HF). The thermal characteristics, such as the temperatures of the transitions and melting and enthalpies, were determined for the solid solutions and simple fluorides. Applicability of the materials obtained as biological luminescent markers was tested on the example of upconversion luminescence, and good upconversion properties were detected.     

A novel crystal form of metacetamol: the first example of a hydrated form

We report the crystal structure and crystallization conditions of a first hydrated form of metacetamol (a hemihydrate), C₈H₉NO₂·0.5H₂O. It crystallizes from metacetamol‐saturated 1:1 (v/v) water–ethanol solutions in a monoclinic structure (space group P2₁/n) and contains eight metacetamol and four water molecules per unit cell. The conformations of the molecules are the same as in polymorph II of metacetamol, which ensures the formation of hydrogen‐bonded dimers and R₂²(16) ring motifs in its crystal structure similar to those in polymorph II. Unlike in form II, however, these dimers in the hemihydrate are connected through water molecules into infinite hydrogen‐bonded molecular chains. Different chains are linked to each other by metacetamol–water and metacetamol–metacetamol hydrogen bonds, the latter type being also present in polymorph I. The overall noncovalent network of the hemihydrate is well developed and several types of hydrogen bonds are responsible for its formation.     

Optimal Data Acquisition Methods for Single-Pixel Imaging

Single-pixel imaging is an image reconstruction technique, which uses spatially modulated illumination of an object and a single-pixel detector collecting the light scattered by the object. This technique is complementary to the conventional imaging based on multipixel matrices and becomes especially interesting when one needs to go beyond the capabilities of the standard silicon-based sensors, e.g., to perform imaging in the infrared range. One of the factors that limit the resolution of the reconstructed images is the signal-to-noise ratio during the data acquisition. We propose several methods for processing the photodetector signal and develop a universal method to determine the optimal pixel number in light patterns with respect to illuminance of the object. We use these methods to capture the standard test images and discuss their advantages.     

Comparison of Differing Formulations of the PCM Model by their Application to the Simulation of an Auto-igniting H 2/air Jet

Different combustion models such as PCM (Presumed Conditional Moments) or ADF-PCM (Approximated Diffusion Flames Presumed Conditional Moments) can be used for RANS simulations of non premixed or partially premixed turbulent flames. In this paper, the auto-ignition experiment performed by Mastorakos and co-workers at Cambridge University is used as a validation case for comparing these two approaches. Furthermore, the first order PCM model is introduced to analyze the effects of the progress variable segregation and an improved version of ADF-PCM is developed with a pdf of the scalar dissipation rate. Compared to ADF-PCM models, the first and second order PCM models predict very sharp temperature and progress variable increase after ignition for all simulated cases. The segregation factors of the progress variable reach important values during the ignition for ADF-PCM models whereas for PCM, high values are reached at the beginning of the ignition.     

Coupling tabulated chemistry with Large Eddy Simulation of turbulent reactive flows

A new modeling strategy is developed to introduce tabulated chemistry methods in the LES of turbulent premixed combustion. The objective is to recover the correct laminar flame propagation speed of the filtered flame front when the subgrid scale turbulence vanishes. The filtered flame structure is mapped by 1D filtered laminar premixed flames. Closure of the filtered progress variable and the energy balance equations are carefully addressed. The methodology is applied to 1D and 2D filtered laminar flames. These computations show the capability of the model to recover the laminar flame speed and the correct chemical structure when the flame wrinkling is completely resolved. The model is then extended to turbulent combustion regimes by introducing subgrid scale wrinkling effects on the flame front propagation. Finally, the LES of a 3D turbulent premixed flame is performed. To cite this article: R. Vicquelin et al., C. R. Mecanique 337 (2009).     

Progranulin is expressed within motor neurons and promotes neuronal cell survival

Background

Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.

Results

In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.

Conclusion

Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.     

Derivation of Hamaker Dispersion Energy of Amorphous Carbon Surfaces in Contact with Liquids Using Photoelectron Energy-Loss Spectra

Hamaker interaction energies and cutoff distances have been calculated for disordered carbon films, in contact with purely dispersive (diiodomethane) or polar (water) liquids, using their experimental dielectric functions ε (q, ω) obtained over a broad energy range. In contrast with previous works, a q-averaged <ε (q, ω) >  _q is derived from photoelectron energy-loss spectroscopy (XPS-PEELS) where the energy loss function (ELF) < Im[?1/ε (q, ω)] >  _q is a weighted average over allowed transferred wave vector values, q, given by the physics of bulk plasmon excitation. For microcrystalline diamond and amorphous carbon films with a wide range of (sp³/sp² + sp³) hybridization, non-retarded Hamaker energies, A ₁₃₂ (L < 1 nm), were calculated in several configurations, and distance and wavenumber cutoff values were then calculated based on A ₁₃₂ and the dispersive work of adhesion obtained from contact angles. A geometric average approximation, H _0?CVL ?=?(H _0?CVC H _0?LVL )^1/2, holds for the cutoff separation distances obtained for carbon-vacuum-liquid (CVL), carbon-vacuum-carbon (CVC) and liquid-vacuum-liquid (LVL) equilibrium configurations. The linear dependence found for A _CVL, A _CLC and A _CLV values as a function of A _CVC, for each liquid, allows predictive relationships for Hamaker energies (in any configuration) using experimental determination of the dispersive component of the surface tension, \( {\gamma}_{CV}^d \), and a guess value of the cutoff distance H _0?CVC of the solid.

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Graphical Abstract