Endothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxia.

Hypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated, drug-/gene-targeting approach. Thus, EPC lines were established from aorta-gonad-mesonephros (AGM) of murine 10.

Sensitive Trimodal Magnetic Resonance Imaging-Surface-Enhanced Resonance Raman Scattering-Fluorescence Detection of Cancer Cells with Stable Magneto-Plasmonic Nanoprobes.

Novel magneto-plasmonic nanoprobes were designed for multimodal diagnosis of cancer by combination of magnetic resonance imaging (MRI), surface-enhanced resonance Raman scattering (SERRS), and fluorescence emission in the very near infrared (VNIR). A controlled electrostatic assembly of silver nanoparticles (AgNPs), superparamagnetic iron oxide nanoparticles (SPIONs), VNIR dye Nile Blue (NB), and biopolymer chitosan (Chi) was used to formulate the AgIONs-Chi nanoprobes. The formulation protocol did not involve organic solvents and was rapid and efficient as confirmed by magnetic sorting.

Metabolite localization in living drosophila using High Resolution Magic Angle Spinning NMR.

We have developed new methods enabling in vivo localization and identification of metabolites through their (1)H NMR signatures, in a drosophila. Metabolic profiles in localized regions were obtained using HR-MAS Slice Localized Spectroscopy and Chemical Shift Imaging at high magnetic fields. These methods enabled measurement of metabolite contents in anatomic regions of the fly, demonstrated by a decrease in β-alanine signals in the thorax of flies showing muscle degeneration.

Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: implications for Down syndrome.

PCP4/PEP19 is a modulator of Ca(2+)-CaM signaling. In the brain, it is expressed in a very specific pattern in postmitotic neurons. In particular, Pcp4 is highly expressed in the Purkinje cell, the sole output neuron of the cerebellum.

Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage Plasmodium berghei ANKA.

Cerebral malaria is a severe complication of Plasmodium falciparum infection. Although T-cell activation and type II IFN-γ are required for Plasmodium berghei ANKA (PbA)-induced murine experimental cerebral malaria (ECM), the role of type I IFN-α/β in ECM development remains unclear. Here, we address the role of the IFN-α/β pathway in ECM devel-opment in response to hepatic or blood-stage PbA infection, using mice deficient for types I or II IFN receptors.

Stable tumor vessel normalization with pO₂ increase and endothelial PTEN activation by inositol trispyrophosphate brings novel tumor treatment.

Tumor hypoxia is a characteristic of cancer cell growth and invasion, promoting angiogenesis, which facilitates metastasis. Oxygen delivery remains impaired because tumor vessels are anarchic and leaky, contributing to tumor cell dissemination. Counteracting hypoxia by normalizing tumor vessels in order to improve drug and radio therapy efficacy and avoid cancer stem-like cell selection is a highly challenging issue.

In vivo magnetic resonance microscopy of Drosophilae at 9.4 T.

In preclinical research, genetic studies have made considerable progress as a result of the development of transgenic animal models of human diseases. Consequently, there is now a need for higher resolution MRI to provide finer details for studies of small animals (rats, mice) or very small animals (insects). One way to address this issue is to work with high-magnetic-field spectrometers (dedicated to small animal imaging) with strong magnetic field gradients.

Functionalized single-walled carbon nanotubes containing traces of iron as new negative MRI contrast agents for in vivo imaging.

Single-walled carbon nanotubes (SWCNTs) containing traces of iron oxide were functionalized by noncovalent lipid-PEG or covalent carboxylic acid function to supply new efficient MRI contrast agents for in vitro and in vivo applications. Longitudinal (r(1)) and transversal (r(2)) water proton relaxivities were measured at 300 MHz, showing a stronger T(2) feature as an MRI contrast agent (r(2)/r(1)  = 190 for CO(2) H functionalisation). The r(2) relaxivity was demonstrated to be correlated to the presence of iron oxide in the SWNT-carboxylic function COOH, in comparison to iron-free ones.

Protein kinase C-theta is required for development of experimental cerebral malaria.

Cerebral malaria is the most severe neurologic complication in children and young adults infected with Plasmodium falciparum. T-cell activation is required for development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (CM). To characterize the T-cell activation pathway involved, the role of protein kinase C-theta (PKC-θ) in experimental CM development was examined.

MRI characterization of structural mouse brain changes in response to chronic exposure to the glufosinate ammonium herbicide.

Glufosinate ammonium (GLA) is the active component of herbicides widely used in agriculture, truck farming, or public domains. GLA acts by inhibiting the plant glutamine synthetase (GlnS). It also inhibits mammalian GlnS in vitro and ex vivo.

Simultaneous two-voxel localized (1)H-observed (13)C-edited spectroscopy for in vivo MRS on rat brain at 9.4T: Application to the investigation of excitotoxic lesions.

(13)C spectroscopy combined with the injection of (13)C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of (13)C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references.

Both functional LTbeta receptor and TNF receptor 2 are required for the development of experimental cerebral malaria.

Background: TNF-related lymphotoxin alpha (LTalpha) is essential for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTalpha-signaling essential for ECM development through LTbeta-R, receptor of LTalpha1beta2 heterotrimer.

MRI methodological development of intervertebral disc degeneration: a rabbit in vivo study at 9.4 T.

Intervertebral disc (IVD) degeneration is a complex process characterized by biochemical and structural changes in both the nucleus pulposus and the anulus fibrosus. In this study, we were able to obtain in vivo magnetic resonance (MR) images of the rabbit spine, with several MR imaging (MRI) contrasts (rho, T(1) and T(2)). We quantified several parameters (T(2), apparent diffusion coefficient, disc height and area) to differentiate between healthy and degenerative IVDs and to characterize the degeneration process.

Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice.

Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans.

In vivo MRI assessment of a novel GdIII-based contrast agent designed for high magnetic field applications.

Gd(3)L is a trinuclear Gd(3+) complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H(12)L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine- N,N,N'',N''-tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd(3)L has remarkable proton relaxivities at high magnetic field (r(1) = 10.2 vs 3.

Increased dosage of DYRK1A and brain volumetric alterations in a YAC model of partial trisomy 21.

A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes -- including DYRK1A, which encodes a serine threonine kinase involved in cell cycle control -- has been shown to present an increase in brain weight. We analyzed this new phenotype by measuring total and regional brain volumes at different ages, using a 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed a total volume increase of 13.

Noncovalent functionalization of carbon nanotubes with amphiphilic gd3+ chelates: toward powerful t1 and t2 MRI contrast agents.

An amphiphilic gadolinium (III) chelate (GdL) was synthesized from commercially available stearic acid. Aqueous solutions of the complex at different concentrations (from 1 mM to 1 microM) were prepared and adsorbed on multiwalled carbon nanotubes. The resulting suspensions were stable for several days and have been characterized with regard to magnetic resonance imaging (MRI) contrast agent applications.

KIT is required for hepatic function during mouse post-natal development.

Background: The Kit gene encodes a receptor tyrosine kinase involved in various biological processes including melanogenesis, hematopoiesis and gametogenesis in mice and human. A large number of Kit mutants has been described so far showing the pleiotropic phenotypes associated with partial loss-of-function of the gene. Hypomorphic mutations can induce a light coat color phenotype while complete lack of KIT function interferes with embryogenesis.

In vivo brain edema classification: New insight offered by large b-value diffusion-weighted MR imaging.

Purpose: To assess the role of large b-value diffusion weighted imaging (DWI) in the characterization of the physicochemical properties of the water in brain edema under experimental and clinical conditions.

Materials And Methods: Vasogenic brain edema was induced in mice by means of cold injury. A total of 17 patients with extensive peritumoral brain edema were also investigated.

New self-assembled nanogels based on host-guest interactions: characterization and drug loading.

We show here, for the first time, that two neutral polymers may completely associate together in water to spontaneously form supramolecular nanoassemblies (nanogels) of spherical shape. The cohesion of these stable structures of about 200 nm is based upon a "lock and key" mechanism: inclusion complexes are formed between the hydrophobic alkyl chains grafted on a polysaccharide (dextran) and the molecular cavities contained in a poly-cyclodextrin polymer. Production yields reached 95%.

Magnetic resonance imaging of Klebsiella pneumoniae-induced pneumonia in mice.

In vivo imaging of small animals is a rapidly developing field. However, the potential of global imaging of infectious processes in animal models remains poorly explored. We used magnetic resonance imaging (MRI) to follow the development and regression of inflammatory lesions caused by infection by Klebsiella pneumoniae in mouse lungs.

Preclinical metabolic changes in mouse prion diseases detected by 1H-nuclear magnetic resonance spectroscopy.

Magnetic resonance spectroscopy studies in animal models of prion disease are very few and concern terminal stages of infection. In order to study earlier stages of the disease, we used in-vivo magnetic resonance spectroscopy in a mouse model of scrapie and, for the first time, in mice infected with a bovine spongiform encephalopathy strain. In bovine spongiform encephalopathy-infected mice, we observed an increase in myo-inositol preceding clinical signs by 20 days, followed by a decrease in N-acetylaspartate at advanced stages.

The existence of biexponential signal decay in magnetic resonance diffusion-weighted imaging appears to be independent of compartmentalization.

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion-weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b-values (up to 10,000 mm(-2) s) under intact, global ischemic, and cold-injury conditions.