Search results for "REGIONS"
showing 10 items of 1521 documents
Determinants of intracellular RNA pharmacokinetics: Implications for RNA-based immunotherapeutics
2011
RNAs with optimized properties are increasingly investigated as a tool to deliver the genetic information of complete antigens into professional antigen-presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. As the dose of the antigen and duration of its presentation are critical factors for generating strong and sustained antigen-specific immune responses, improvement of the immunobioavailability of RNA-based vaccines has been a recurrent subject of research. Substantial increase of the amount of antigen produced from RNA can be achieved by optimizing RNA stability and translational efficiency. Both features are determined by cis-acting elemen…
EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-κB Activation
2005
Abstract The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of the cytokine IL-27 that controls Th cell development. However, its regulated expression in DCs is poorly understood. In the present study we demonstrate that EBI3 is expressed in splenic CD8−, CD8+, and plasmacytoid DC subsets and is induced upon TLR signaling. Cloning and functional analysis of the EBI3 promoter using in vivo footprinting and mutagenesis showed that stimulation via TLR2, TLR4, and TLR9 transactivated the promoter in primary DCs via NF-κB and Ets binding sites at −90 and −73 bp upstream of the transcriptional start site, respectively. Furthermore, we observed that NF-κB p50/p65 and PU.1…
Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids
2005
Dietary vegetable oils and fish oils rich in PUFA (polyunsaturated fatty acids) exert hypocholesterolaemic and hypotriglyceridaemic effects in rodents. The plasma cholesterol-lowering properties of PUFA are due partly to a diminution of cholesterol synthesis and of the activity of the rate-limiting enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase). To better understand the mechanisms involved, we examined how tuna fish oil and individual n−3 and n−6 PUFA affect the expression of hepatic FPP synthase (farnesyl diphosphate synthase), a SREBP (sterol regulatory element-binding protein) target enzyme that is subject to negative-feedback regulation by sterols, in co-ordination …
APOBEC4 Enhances the Replication of HIV-1
2016
APOBEC4 (A4) is a member of the AID/APOBEC family of cytidine deaminases. In this study we found a high mRNA expression of A4 in human testis. In contrast, there were only low levels of A4 mRNA detectable in 293T, HeLa, Jurkat or A3.01 cells. Ectopic expression of A4 in HeLa cells resulted in mostly cytoplasmic localization of the protein. To test whether A4 has antiviral activity similar to that of proteins of the APOBEC3 (A3) subfamily, A4 was co-expressed in 293T cells with wild type HIV-1 and HIV-1 luciferase reporter viruses. We found that A4 did not inhibit the replication of HIV-1 but instead enhanced the production of HIV-1 in a dose-dependent manner and seemed to act on the viral L…
Electron beam induced polymerisation of MMA in the presence of rubber: a novel process to produce tough materials
2002
Abstract PMMA-rubber blends are formed through electron beam induced in situ polymerisation. The influence of rubber nature and irradiation dose has been investigated through mechanical tensile tests, solubility analysis and the results were related to material structure investigated through atomic force microscopy. Some blend formulations present a significant increase of ductility with respect to pure PMMA, without a dramatic decrease of modulus, yield stress and stress at break values. The results are interpreted on the basis of the criterion of the critical inter-particle thickness.
Recent evolution of the multi-isotopic radioactive content in ice of Livingston Island, Antarctica.
1999
The temporal arrangement of the ice layers that are produced in ecosystems with perpetual snows form situations that greatly favour the study of the temporal evolution of the radioactive fallout that occurs in the said zones, whether this fallout is natural or artificial in origin. This allows one to investigate the causes of the fallout and the mechanisms transporting the radionuclides involved from their source point to the study zone, as well as their subsequent behaviour in that zone. There are special difficulties involved in this type of study in Antarctica. Some are of a general character deriving from the conditions of extreme climate and isolation which complicate the processes of …
Posterior subtalar dislocation.
2009
A subtalar dislocation of the foot is an uncommon injury, and cases of posterior subtalar dislocation are even rarer. This injury is characterized by a simultaneous dislocation of talocalcaneal and talonavicular joints while tibiotalar and calcaneocuboid articulations remain intact. Subtalar dislocation is commonly accompanied by fractures of the malleoli, talus, or fifth metatarsal and by a rotational component of the subtalar joint. Subtalar dislocation can occur in any direction and produces significant deformity. This article presents a case of pure posterior subtalar dislocation in an 80-year-old man who presented with pain and deformity in his left ankle following a motorcycle acciden…
Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development
2003
Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by regulating gene expression in subsynaptic nuclei. To analyze the function of Erbb2 in this process, we have inactivated the Erbb2 gene in developing muscle fibers by Cre/Lox-mediated gene ablation. Neuromuscular synapses form in the mutant mice, but the synapses are less efficient and contain reduced levels of acetylcholine receptors. Surprisingly, the mutant mice also show proprioceptive defects caused by abnormal muscle spindle development. Sensory Ia afferent neurons establish initial contact with Erbb2-deficient myotubes. However, functional spindles never develop. Taken together, our data su…
Human leucocyte antigen-A2 restricted and Mycobacterium tuberculosis 19-kDa antigen-specific CD8+ T-cell responses are oligoclonal and exhibit a T-ce…
2001
CD8+ T cells can be grouped into two different types of secretory T lymphocytes, based on the cytokine-secretion pattern upon antigen exposure: those with a T-cell cytotoxic type 1 response (Tc1), which secrete interferon-gamma (IFN-gamma), or those with a T-cell cytotoxic type 2 response, which secrete interleukin (IL)-4 and IL-10. We examined the CD8+ T-cell response directed against an immunodominant human leucocyte antigen (HLA)-A2-presented peptide derived from a 19-kDa Mycobacterium tuberculosis-associated antigen. T cells were examined by functional analysis and by T-cell receptor (TCR) complementarity-determining region 3 (CDR3)-spectratyping, which defines the complexity of a T-cel…
The unique complexity of the CYP3A4 upstream region suggests a nongenetic explanation of its expression variability.
2010
The individually variable and unpredictable expression of CYP3A4 compromises therapies with 50% of contemporary drugs. Gene variants explain only a fraction of this variability.We investigated the evolution of CYP3A4 transcriptional regulation by nuclear receptors such as the xenobiotics sensors PXR and CAR.The combination of a proximal ER6 element with XREM and CLEM represents the original scheme of CYP3A regulation by nuclear receptors in placental mammals. Among human CYP3A genes, this scheme is retained only in CYP3A4, whereas non-CYP3A4 genes lost these elements to a variable extent during primate evolution. In parallel, the number of elements outside XREM and CLEM potentially responsi…