Search results for " Targeting"
showing 10 items of 146 documents
Profilin 1 is required for abscission during late cytokinesis of chondrocytes
2009
Profilins are key factors for dynamic rearrangements of the actin cytoskeleton. However, the functions of profilins in differentiated mammalian cells are uncertain because profilin deficiency is early embryonic lethal for higher eukaryotes. To examine profilin function in chondrocytes, we disrupted the profilin 1 gene in cartilage (Col2pfn1). Homozygous Col2pfn1 mice develop progressive chondrodysplasia caused by disorganization of the growth plate and defective chondrocyte cytokinesis, indicated by the appearance of binucleated cells. Surprisingly, Col2pfn1 chondrocytes assemble and contract actomyosin rings normally during cell division; however, they display defects during late cytokines…
Charting the Drosophila neuropile: a strategy for the standardised characterisation of genetically amenable neurites
2003
Insect neurons are individually identifiable and have been used successfully to study principles of the formation and function of neuronal circuits. In the fruitfly Drosophila, studies on identifiable neurons can be combined with efficient genetic approaches. However, to capitalise on this potential for studies of circuit formation in the CNS of Drosophila embryos or larvae, we need to identify pre- and postsynaptic elements of such circuits and describe the neuropilar territories they occupy. Here, we present a strategy for neurite mapping, using a set of evenly distributed landmarks labelled by commercially available anti-Fasciclin2 antibodies which remain comparatively constant between s…
Lipid nanocarriers containing esters prodrugs of Flurbiprofen. Preparation, physical-chemical characterization and biological studies.
2013
In this paper, the preparation, chemical-physical, technological and in vitro characterization of nanostructured lipid carriers (NLC) carrying R-flurbiprofen ester prodrugs, were analyzed for a potential pharmaceutical application. R-flurbiprofen was chosen as a model drug because it has been found to play an effective role in counteracting secretases involved in neurodegenerative diseases, although it does not cross the Blood Brain Barrier (BBB). In this study, two R-flurbiprofen ester prodrugs (ethyl and hexyl) were successfully synthesized and entrapped into non-pegylated and pegylated NLC. The obtained systems showed average diameters in the colloidal size range, negative zeta potential…
Rapid, reproducible transduction of select forebrain regions by targeted recombinant virus injection into the neonatal mouse brain
2009
Viral vectors can mediate long-term gene expression in different regions of the brain. Recombinant adeno-associated virus (rAAV) and Lenti virus (LV) have both gained prominence due to their ability to achieve specific transduction of various neuronal populations. Whilst widespread gene delivery has been obtained by targeted injection of rAAV in various brain structures, LV has also been utilized for infection of stem cell populations for cell lineage tracing. Both viral vector systems are most commonly used for gene delivery in mature brains, but the great potential of somatic gene delivery into the neonate brain has not been systematically exploited. Here we provide a systematic guideline…
Fluorinated and pegylated polyaspartamide derivatives to increase solubility and efficacy of Flutamide
2012
New fluorinated amphiphilic copolymers based on a biocompatible polyaspartamide have been prepared in order to obtain polymeric micelles useful for delivering anticancer drugs. In particular, α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) has been derivatized with polyethylene glycol (PEG(2000)) and ethylendiamine (EDA). Both these portions form the hydrophilic part of the copolymer, while the hydrophobic moiety is given by 1,2,4-oxadiazoles: 5-pentafluorophenyl-3-perfluoroheptyl-1,2,4-oxadiazole (PPOX) or 3-carboxyethyl-5-pentadecafluoroheptyl-1,2,4-oxadiazole (CPOX). Copolymers named PHEA-PEG(2000)-EDA-PPOX and PHEA-PEG(2000)-EDA-CPOX have been prepared with various degrees of derivati…
Deficit sustainability and inflation in EMU: An analysis from the Fiscal Theory of the Price Level
2007
Price determination theory typically focuses on the role of monetary policy, while the role of fiscal policy is usually neglected. From a different point of view, the Fiscal Theory of the Price Level takes into account monetary and fiscal policy interactions and assumes that fiscal policy may determine the price level, even if monetary authorities pursue an inflation targeting strategy. In this paper we try to test empirically whether the time path of the government budget in EMU countries would have affected price level determination. Our results point to the sustainability of fiscal policy in all the EMU countries but Finland, although no firm conclusions can be drawn about the prevalence…
A T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis.
2017
Multiple sclerosis (MS) is a human neurodegenerative disease characterized by the invasion of autoreactive T cells from the periphery into the CNS. Application of pan-histone deacetylase inhibitors (HDACi) ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model for MS, suggesting that HDACi might be a potential therapeutic strategy for MS. However, the function of individual HDAC members in the pathogenesis of EAE is not known. In this study we report that mice with a T cell-specific deletion of HDAC1 (using the Cd4-Cre deleter strain; HDAC1-cKO) were completely resistant to EAE despite the ability of HDAC1cKO CD4+ T cells to differentiate into Th17 cells. RNA sequencin…
Phosphorylation of CENP-A on serine 7 does not control centromere function.
2019
CENP-A is the histone H3 variant necessary to specify the location of all eukaryotic centromeres via its CENP-A targeting domain and either one of its terminal regions. In humans, several post-translational modifications occur on CENP-A, but their role in centromere function remains controversial. One of these modifications of CENP-A, phosphorylation on serine 7, has been proposed to control centromere assembly and function. Here, using gene targeting at both endogenous CENP-A alleles and gene replacement in human cells, we demonstrate that a CENP-A variant that cannot be phosphorylated at serine 7 maintains correct CENP-C recruitment, faithful chromosome segregation and long-term cell viab…
Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.
2011
SummaryImmunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defe…
Folate targeted coated SPIONs as efficient tool for MRI
2017
The development of more sensitive diagnostic tools allowing an early-stage and highly efficient medical imaging of tumors remains a challenge. Magnetic nanoparticles seem to be the contrast agents with the highest potential, if properly constructed. Therefore, in this study, hybrid magnetic nanoarchitectures were developed using a new amphiphilic inulin-based graft copolymer (INU-LAPEG-FA) as coating material for 10-nm spinel iron oxide (magnetite, Fe3O4) superparamagnetic nanoparticles (SPION). Folic acid (FA) covalently linked to the coating copolymer in order to be exposed onto the nanoparticle surface was chosen as the targeting agent because folate receptors are upregulated in many can…