Publications by authors named "Francoise Bleicher"

Hox genes encode Homeodomain-containing transcription factors, which specify segmental identities along the anterior-posterior axis. Functional changes in Hox genes have been directly implicated in the evolution of body plans across the metazoan lineage. The Hox protein Ultrabithorax (Ubx) is expressed and required in developing third thoracic (T3) segments in holometabolous insects studied so far, particularly, of the order Coleoptera, Lepidoptera and Diptera.

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Biological pathways rely on the formation of intricate protein interaction networks called interactomes. Getting a comprehensive map of interactomes implies the development of tools that allow one to capture transient and low-affinity protein-protein interactions (PPIs) in live conditions. Here we presented an experimental strategy: the Cell-PCA (cell-based protein complementation assay), which was based on bimolecular fluorescence complementation (BiFC) for ORFeome-wide screening of proteins that interact with different bait proteins in the same live cell context, by combining high-throughput sequencing method.

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Deciphering protein-protein interactions (PPIs) in vivo is crucial to understand protein function. Bimolecular fluorescence complementation (BiFC) makes applicable the analysis of PPIs in many different native contexts, including human live cells. It relies on the property of monomeric fluorescent proteins to be reconstituted from two separate subfragments upon spatial proximity.

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  • Juvenile idiopathic arthritis (JIA) is the most prevalent chronic rheumatic disease in children, and the underlying causes are still not well understood, particularly in cases with genetic factors like LACC1 mutations.
  • This study investigated four families with early-onset arthritis and identified that mutations in LACC1 lead to deficiencies in macrophage autophagy, a crucial cellular process.
  • The findings suggest that LACC1 plays a significant role in macrophage energy metabolism and could be linked to a new genetic type of juvenile arthritis due to its impact on autophagy functions.
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  • HOX proteins interact with TALE-class cofactors PBX and MEIS, which helps them regulate gene expression through unique binding motifs.
  • The interaction of HOX-PBX complexes usually requires a specific hexapeptide motif, but the presence of MEIS can change this requirement for many HOX proteins.
  • The study focused on the human HOXA9 protein's interactions with PBX1 and MEIS1, demonstrating that the binding depends on both a conserved HX motif and specific residues of HOXA9, highlighting the complexity of these protein interactions.
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  • HOX and TALE genes are significant transcription factors involved in managing cell development and structure during embryonic growth, forming diverse protein complexes on DNA.
  • Research reveals that mutations in these genes are linked to several cancers, yet their combined impact on cancer development has not been thoroughly investigated.
  • This study utilizes extensive RNA-sequencing data from cancer and normal tissues to analyze the expression profiles of HOX and TALE genes, offering insights into their potential collaborative roles in promoting or inhibiting cancer.
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  • HOX proteins interact with PBX and MEIS cofactors, crucial in development and disease, but the exact nature of these interactions is still not fully understood.
  • This study systematically analyzes the interaction properties of HOX, PBX, and MEIS proteins using human and mouse samples, revealing that a key HOX motif is less important when MEIS is present, except for two specific paralog groups.
  • The research also uncovers unique, paralog-specific binding sites that vary in their usage and highlight one site's significance in the growth of HOXA7 in breast cancer cells, showcasing the flexible interaction dynamics of HOX proteins with their cofactors.
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  • This study investigates the expression of the putative tumor suppressor gene exostosin 1 (EXT-1) in human odontoblasts, which are cells responsible for forming dentin and maintaining tooth vitality.
  • Using techniques like DNA microarray, PCR, and immunohistochemistry, researchers found that EXT-1 is significantly more expressed in mature odontoblasts compared to pulp tissue, indicating its potential role in tooth health and development.
  • The presence of EXT-1 in both mature and developing teeth suggests it plays a crucial role in dentin formation and overall tooth development.
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  • The study investigates the role of odontoblasts, the cells responsible for dentin formation, in the immune response to cariogenic bacteria during tooth decay.
  • Researchers stimulated odontoblast-like cells with a TLR2 agonist and found that this activation significantly increased the expression of the NOS2 gene, which is linked to the production of nitric oxide (NO), a compound with antibacterial properties.
  • The findings suggest that odontoblasts contribute to the antimicrobial response against harmful bacteria in the dental pulp and may play a crucial role in the healing and regeneration processes of pulp tissue after carious damage.
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  • Odontoblasts are specialized cells located between dental pulp and dentin, crucial for forming primary and secondary dentins.
  • They create an organic matrix of type I collagen and help in its mineralization, producing proteins necessary for dentin growth and maintenance.
  • Besides forming dentin, odontoblasts may also act as sensors for bacterial invasion, triggering immune responses and mediating tooth pain through their ion channels.
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  • Previous studies indicate that odontoblasts can detect components from gram-positive bacteria via Toll-like receptor 2 (TLR2), leading to an immune response in the dental pulp through the production of proinflammatory cytokines.
  • This study investigates how lipopolysaccharide-binding protein (LBP) influences the TLR2 response in human odontoblast-like cells, using various stimulation combinations and assessing gene expression and signaling pathways.
  • Results show that LBP significantly reduces the expression of inflammatory cytokines CXCL8 and IL-6 in stimulated cells, suggesting that LBP may play a role in modulating immune responses in dental pulp during inflammation.
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  • The study investigates a protein called SMILE (TMTC3) that is over-expressed in the blood of renal transplant patients who have achieved operational tolerance without immunosuppressive drugs.
  • Researchers confirmed that SMILE is linked to endoplasmic reticulum (ER) stress responses and affects proteasome activity, which is crucial for protein degradation within cells.
  • The findings suggest that understanding SMILE's role could lead to new insights in regulating immune responses in transplantation, potentially improving long-term acceptance of grafts.
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Dental pain arises from exposed dentin following bacterial, chemical, or mechanical erosion of enamel and/or recession of gingiva. Thus, dentin tissue and more specifically patent dentinal tubules represent the first structure involved in dentin sensitivity. Interestingly, the architecture of dentin could allow for the transfer of information to the underlying dental pulp via odontoblasts (dentin-forming cells), via their apical extension bathed in the dentinal fluid running in the tubules, or via a dense network of trigeminal sensory axons intimately related to odontoblasts.

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Recent studies have suggested that odontoblasts are involved in the dental pulp immune response to oral pathogens that invade human dentin during the caries process. How odontoblasts regulate the early inflammatory and immune pulp response to Gram-positive bacteria, which predominate in shallow and moderate dentin caries, is still poorly understood. In this study, we investigated the production of pro- and anti-inflammatory cytokines by odontoblast-like cells upon engagement of Toll-like receptor (TLR) 2, a pattern recognition molecule activated by Gram-positive bacteria components.

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  • Human odontoblasts play a crucial role in triggering immune responses to bacteria that invade dental tissues during tooth decay (caries).
  • This study focused on the NOD2 receptor's expression in healthy and inflamed dental pulp, revealing that its expression increases significantly during inflammation caused by Gram-positive bacteria.
  • The research found that stimulating odontoblast-like cells with a specific bacterial component (LTA) boosts NOD2 gene expression, indicating that NOD2 is important for the immune response in protecting dental pulp from harmful bacteria.
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  • - MAP-1B is a microtubule-associated protein crucial for stabilizing microtubules during the development of nerve cells, particularly in odontoblasts involved in tooth formation, and its expression is regulated by FMRP.
  • - The study employed various methods like real-time PCR and immunochemistry to analyze MAP-1B expression, discovering it in adult and embryonic human dentin-forming cells, especially in response to differentiation states.
  • - Findings suggest that MAP-1B plays a significant role in the terminal differentiation of odontoblasts, alongside other proteins like MAP2 and tau, indicating its importance in both healthy development and dental conditions.
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  • - KLF4 and KLF5 are transcription factors that influence tooth development, and their expression patterns during this process in mice were studied from embryonic day E12.5 to postnatal day PN3.
  • - KLF4 was found to be specifically expressed in polarizing odontoblasts and ameloblasts during later stages of tooth development, while KLF5 was primarily expressed in secretory ameloblasts and odontoblasts, as well as in proliferating epithelial cells at earlier stages.
  • - The findings suggest KLF4 is linked to the differentiation of odontoblasts and ameloblasts, while KLF5 may play roles in both early cell proliferation and later mineralization of tooth structures.
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  • Odontoblasts, dental pulp fibroblasts, and immature dendritic cells (DCs) play a role in the immune response of human dental pulp to oral pathogens, especially during tooth decay.
  • The study focused on how these cells produce pro-inflammatory cytokines in response to lipoteichoic acid (LTA), a component from Gram-positive bacteria, activating the Toll-like receptor 2 (TLR2).
  • Results showed that while all cell types increased CXCL8 production upon stimulation, only immature DCs significantly produced TNF-alpha and IL-1beta, indicating differing roles in the inflammatory response to bacteria.
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Odontoblasts are organized as a single layer of specialized cells responsible for dentine formation and presumably for playing a role in tooth pain transmission. Each cell has an extension running into a dentinal tubule and bathing in the dentinal fluid. A dense network of sensory unmyelinated nerve fibers surrounds the cell bodies and processes.

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  • Recent research shows that human dental pulp cells can detect pathogens and initiate immune responses, particularly through specialized cells called odontoblasts, which defend against harmful bacteria that can enter the tooth.
  • These odontoblasts use Toll-like receptors (TLRs) to sense bacteria and produce various chemokines that help lead to the migration of immune cells to the site of infection.
  • The study identifies many specific chemokine genes and receptors active in the healthy dental pulp, suggesting that these components could be potential targets for creating treatments aimed at lessening inflammation and promoting healing in response to dental infections.
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  • Odontoblasts are essential for creating dentin through the production of organic matrix and mineralization, and new techniques have been developed to study both mature and newly formed odontoblasts.
  • A comparison of gene expression profiles between native and cultured odontoblasts revealed notable similarities, particularly in the expression levels of genes related to neuronal proteins.
  • Findings indicated that cultured odontoblasts closely mimic the gene expression patterns of native ones, highlighting their potential for in vitro research and supporting the idea that odontoblasts may function as sensory cells.
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  • * A study using cDNA gene arrays on human dental pulp cells revealed that EVI1, a transcription factor that inhibits TGF-beta/BMP signaling, is under-expressed in odontoblast-like cells compared to pulp fibroblast-like cells.
  • * EVI1 levels were confirmed through PCR and immunohistochemistry, showing that its expression varies in the dental pulp, potentially impacting odontoblast differentiation and the overall healing process in dental therapeutics.
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  • Odontoblasts are cells that create dentin in teeth and may also play a role in tooth pain, but this function has not been definitively proven before.
  • New research shows that human odontoblasts can generate electrical signals and action potentials, indicating they have excitability similar to nerve cells.
  • The study finds that odontoblasts have specific sodium channel subunits which cluster with nerve fibers, suggesting they could act as sensor cells involved in transmitting tooth pain signals.
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  • Gram-positive bacteria entering the dental tissue can affect the immune response in the dental pulp, with odontoblasts being the first cells to encounter these bacteria.
  • The study found that odontoblasts expressed certain pattern recognition receptors and showed a strong response to lipoteichoic acid (LTA), a component of Gram-positive bacterial walls, enhancing the release of specific chemokines like CCL2 and CXCL10.
  • Interestingly, while LTA triggered an immune response and chemokine production to recruit immune cells, it also decreased the expression of genes related to dentin matrix synthesis, highlighting a trade-off between immune activation and odontoblast function.
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