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Henry E.,Rennes Institute of Physics | Henry E.,CNRS Laboratory of Biology and Applied Pharmacology | Dif A.,CNRS Chemistry Institute of Rennes | Schmutz M.,Charles Sadron Institute | And 4 more authors.
Nano Letters | Year: 2011

Biological molecules and molecular self-assemblies are promising templates to organize well-defined inorganic nanostructures. We demonstrate the ability of a self-assembled three-dimensional crystal template of helical actin protein filaments and lipids bilayers to generate a hierarchical self-assembly of quantum dots. Functionnalized tricystein peptidic quantum dots (QDs) are incorporated during the dynamical self-assembly of this actin/lipid template resulting in the formation of crystalline fibers. The crystal parameters, 26.5 × 18.9 × 35.5 nm 3, are imposed by the membrane thickness, the diameter, and the pitch of the actin self-assembly. This process ensures the high quality of the crystal and results in unexpected fluorescence properties. This method of preparation offers opportunities to generate crystals with new symmetries and a large range of distance parameters. © 2011 American Chemical Society.


Tovey M.G.,CNRS Laboratory of Biology and Applied Pharmacology | Legrand J.,CNRS Laboratory of Biology and Applied Pharmacology | Lallemand C.,CNRS Laboratory of Biology and Applied Pharmacology
Expert Review of Clinical Pharmacology | Year: 2011

The safety and efficacy of biopharmaceuticals can be severely impaired by their immunogenicity. A risk-based strategy should be used to assess immunogenicity on a case-by-case basis using standardized methods to correlate anti-drug antibody levels with clinical outcome. In silico and in vitro techniques allow putative T-cell epitopes to be identified and eliminated in candidate molecules while maintaining structure and function. Putative T-cell epitopes can be studied in the context of the HLA allotypes representative of the target population in vitro and in transgenic mice that express human HLA genes. Mice immune tolerant to human proteins allow the study of the effect of factors such as aggregation on the loss of immune tolerance. However, significant challenges remain in order to be able predict the immunogenicity of a therapeutic protein in a particular individual. © 2011 Expert Reviews Ltd.


Tovey M.G.,CNRS Laboratory of Biology and Applied Pharmacology | Lallemand C.,CNRS Laboratory of Biology and Applied Pharmacology
Bioanalysis | Year: 2012

Biopharmaceuticals are used extensively for the treatment of a number of chronic debilitating and fatal diseases such as cancer and inflammatory or autoimmune diseases. Although biopharmaceuticals are in general well tolerated, the development of anti-drug antibodies can impair their safety and efficacy. Assessment of immunogenicity is essential for a more effective and rational use of biopharmaceuticals, and is dependent upon the establishment of efficient standardized assays that allow direct comparison of immunogenicity data with clinical outcome. Although regulatory authorities recommend the use of cell-based assays that reflect the mechanism of action of the drug for the detection of neutralizing anti-drug antibodies, conventional cell-based assays are difficult to standardize and often give variable results. A number of strategies have been adopted to improve the performance of cell-based assays, including quantification of drug-induced proteins using either real-time RT-PCR or branched DNA to detect mRNA, or ELISAs to detect protein, bridging assays using immobilized cells and the use of reporter gene assays. The relative merits and limitations of each of these methods is reviewed herein. © 2012 Future Science Ltd.


Olliver A.,CNRS Laboratory of Biology and Applied Pharmacology | Saggioro C.,CNRS Laboratory of Biology and Applied Pharmacology | Herrick J.,CNRS Laboratory of Biology and Applied Pharmacology | Sclavi B.,CNRS Laboratory of Biology and Applied Pharmacology
Molecular Microbiology | Year: 2010

Summary Ribonucleotide reductase (RNR) is the bottleneck enzyme in the synthesis of dNTPs required for DNA replication. In order to avoid the mutagenic effects of imbalances in dNTPs the amount and activity of RNR enzyme in the cell is tightly regulated. RNR expression from the nrdAB operon is thus coupled to coincide with the initiation of DNA replication. However, the mechanism for the co-ordination of gene transcription and DNA replication remains to be elucidated. The timing and synchrony of DNA replication initiation in Escherichia coli is controlled in part by the binding of the DnaA protein to the origin of replication. DnaA is also a transcription factor of the nrdAB operon and could thus be the link between these two processes. Here we show that RNA polymerase can form a stable transcription initiation complex at the nrdAB promoter by direct interaction with the far upstream sites required for the timing of expression as a function of DNA replication. In addition, we show that the binding of DnaA on the promoter can either activate or repress transcription as a function of its concentration and its nucleotide-bound state. However, transcription regulation by DnaA does not significantly affect the timing of expression of RNR from the nrdAB operon. © 2010 Blackwell Publishing Ltd.


Gordel M.,Wroclaw University of Technology | Gordel M.,CNRS Laboratory of Biology and Applied Pharmacology | Olesiak-Banska J.,Wroclaw University of Technology | Matczyszyn K.,Wroclaw University of Technology | And 3 more authors.
Physical Chemistry Chemical Physics | Year: 2014

This work describes the interaction between femtosecond laser pulses (∼130 fs, 800 nm) and gold nanorods (NRs) leading to reshaping of the NRs. We focus on the investigation of structural changes of the NRs and the parameters influencing the reshaping, like surface modification using sodium sulphide, laser power and the position of the longitudinal surface plasmon resonance band (l-SPR) with respect to the laser wavelength. A thermogravimetric analysis experiment is performed to examine changes in the composition of NRs upon heating. A new type of banana-shaped NPs is described and the conditions of their appearance are discussed. © 2014 the Owner Societies.


Arock M.,CNRS Laboratory of Biology and Applied Pharmacology | Valent P.,Medical University of Vienna
Expert Review of Hematology | Year: 2010

Mastocytosis is a myeloid neoplasm characterized by abnormal accumulation and frequent activation of mast cells (MCs) in various organs. Organ systems typically involved are the bone marrow, skin, liver and gastrointestinal tract. In most adult patients, the systemic form of mastocytosis (SM) is diagnosed, which includes an indolent subvariant, an aggressive subvariant and a leukemic subvariant, also termed MC leukemia. Whereas in pediatric mastocytosis, which is usually confined to the skin, a number of different KIT mutations and other defects may be detected, the KIT mutation D816V is detectable in most (adult) patients with SM. In a subset of these patients, additional oncogenic factors may lead to enhanced survival and growth of MCs and, thus, to advanced SM. Other factors may lead to MC activation, with consecutive anaphylactic reactions that can be severe or even fatal. Treatment of SM usually focuses on symptom relief by histamine receptor antagonists and other supportive therapy. However, in aggressive and leukemic variants, cytoreductive and targeted drugs must be applied. Unfortunately, the prognosis in these patients remains poor, even when treated with novel KIT-targeting agents, polychemotherapy or stem cell transplantation. This article provides a summary of our knowledge on the pathogenesis and on treatment options in SM. © 2010 Expert Reviews Ltd.


Amson R.,CNRS Laboratory of Biology and Applied Pharmacology | Karp J.E.,Johns Hopkins Sidney Kimmel Comprehensive Cancer Center | Telerman A.,CNRS Laboratory of Biology and Applied Pharmacology
Current Opinion in Oncology | Year: 2013

PURPOSE OF REVIEW: Tumor reversion is the biological process by which highly tumorigenic cells lose at great extent or entirely their malignant phenotype. The purpose of our research is to understand the molecular program of tumor reversion and its clinical application. We first established biological models of reversion, which was done by deriving revertant cells from different tumors. Secondly, the molecular program that could override the malignant phenotype was assessed. Differential gene-expression profiling showed that at least 300 genes are implicated in this reversion process such as SIAH-1, PS1, TSAP6, and, most importantly, translationally controlled tumor protein (TPT1/TCTP). Decreasing TPT1/TCTP is key in reprogramming malignant cells, including cancer stem cells. RECENT FINDINGS: Recent findings indicate that TPT1/TCTP regulates the P53-MDM2-Numb axis. Notably, TPT1/TCTP and p53 are implicated in a reciprocal negative-feedback loop. TPT1/TCTP is a highly significant prognostic factor in breast cancer. Sertraline and thioridazine interfere with this repressive feedback by targeting directly TPT1/TCTP and inhibiting its binding to MDM2, restoring wildtype p53 function. Combining sertraline with classical drugs such as Ara-C in acute myeloid leukemia may be also beneficial. SUMMARY: In this review, we discuss some of these reversion pathways and how this approach could open a new route to cancer treatment. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Amson R.,CNRS Laboratory of Biology and Applied Pharmacology | Pece S.,Instituto Firc Of Oncologia Molecolare | Pece S.,Instituto Europeo Of Oncologia | Pece S.,Catholic University of Leuven | And 6 more authors.
Trends in Cell Biology | Year: 2013

Evolutionary conserved and pleiotropic, the TPT1/TCTP gene (translationally controlled tumor protein, also called HRF, fortilin), encodes a highly structured mRNA shielded by ribonucleoproteins and closely resembling viral particles. This mRNA activates, as do viruses, protein kinase R (PKR). The TPT1/TCTP protein is structurally similar to mRNA-helicases and MSS4. TPT1/TCTP has recently been identified as a prognostic factor in breast cancer and a critical regulator of the tumor suppressor p53 and of the cancer stem cell (SC) compartment. Emerging evidence indicates that TPT1/TCTP is key to phenotypic reprogramming, as shown in the process of tumor reversion and possibly in pluripotency. We provide here an overview of these diverse functions of TPT1/TCTP. © 2012 Elsevier Ltd.


Brambilla E.,CNRS Laboratory of Biology and Applied Pharmacology | Brambilla E.,Jacobs University Bremen | Sclavi B.,CNRS Laboratory of Biology and Applied Pharmacology
G3: Genes, Genomes, Genetics | Year: 2015

Cellular adaptation to changing environmental conditions requires the coordinated regulation of expression of large sets of genes by global regulatory factors such as nucleoid associated proteins. Although in eukaryotic cells genomic position is known to play an important role in regulation of gene expression, it remains to be established whether in bacterial cells there is an influence of chromosomal position on the efficiency of these global regulators. Here we show for the first time that genome position can affect transcription activity of a promoter regulated by the histone-like nucleoid-structuring protein (H-NS), a global regulator of bacterial transcription and genome organization. We have used as a local reporter of H-NS activity the level of expression of a fluorescent reporter protein under control of an H-NS2regulated promoter (Phns) at different sites along the genome. Our results show that the activity of the Phns promoter depends on whether it is placed within the AT-rich regions of the genome that are known to be bound preferentially by H-NS. This modulation of gene expression moreover depends on the growth phase and the growth rate of the cells, reflecting the changes taking place in the relative abundance of different nucleoid proteins and the inherent heterogeneous organization of the nucleoid. Genomic position can thus play a significant role in the adaptation of the cells to environmental changes, providing a fitness advantage that can explain the selection of a gene's position during evolution. © 2015 Brambilla and Sclavi.


Bayart E.,CNRS Laboratory of Biology and Applied Pharmacology | Cohen-Haguenauer O.,CNRS Laboratory of Biology and Applied Pharmacology | Cohen-Haguenauer O.,University Paris Diderot
Current Gene Therapy | Year: 2013

The unlimited proliferation capacity of embryonic stem cells (ESCs) combined with their pluripotent differentiation potential in various lineages raised great interest in both the scientific community and the public at large with hope for future prospects of regenerative medicine. However, since ESCs are derived from human embryos, their use is associated with significant ethical issues preventing broad studies and therapeutic applications. To get around this bottleneck, Takahashi and Yamanaka have recently achieved the conversion of adult somatic cells into ES-like cells via the forced expression of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. This first demonstration attracted public attention and opened a new field of stem cells research with both cognitive - such as disease modeling - and therapeutic prospects. This pioneer work just received the 2012 Nobel Prize in Physiology or Medicine. Many methods have been reported since 2006, for the generation of induced pluripotent stem (iPS) cells. Most strategies currently under use are based on gene delivery via gamma-retroviral or lentiviral vectors; some experiments have also been successful using plasmids or transposons- based systems and few with adenovirus. However, most experiments involve integration in the host cell genome with an identified risk for insertional mutagenesis and oncogenic transformation. To circumvent such risks which are deemed incompatible with therapeutic prospects, significant progress has been made with transgene-free reprogramming methods based on e.g.: sendaï virus or direct mRNA or protein delivery to achieve conversion of adult cells into iPS. In this review we aim to cover current knowledge relating to both delivery systems and combinations of inducing factors including chemicals which are used to generate human iPS cells. Finally, genetic instability resulting from the reprogramming process is also being considered as a safety bottleneck for future clinical translation and stem cell-therapy prospects based on iPS. © 2013 Bentham Science Publishers.

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