The Tumor Microenvironment-Dependent Transcription Factors AHR and HIF-1α Are Dispensable for Leukemogenesis in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia.

peer reviewedChronic lymphocytic leukemia (CLL) is the most frequent leukemia in the elderly and is characterized by the accumulation of mature B lymphocytes in peripheral blood and primary lymphoid organs. In order to proliferate, leukemic cells are highly dependent on complex interactions with their microenvironment in proliferative niches. Not only soluble factors and BCR stimulation are important for their survival and proliferation, but also the activation of transcription factors through different signaling pathways. The aryl hydrocarbon receptor (AHR) and hypoxia-inducible factor (HIF)-1α are two transcription factors crucial for cancer development, whose activities are dependent on tumor microenvironment conditions, such as the presence of metabolites from the tryptophan pathway and hypoxia, respectively. In this study, we addressed the potential role of AHR and HIF-1α in chronic lymphocytic leukemia (CLL) development in vivo. To this end, we crossed the CLL mouse model Eµ-TCL1 with the corresponding transcription factor-conditional knock-out mice to delete one or both transcription factors in CD19+ B cells only. Despite AHR and HIF-1α being activated in CLL cells, deletion of either or both of them had no impact on CLL progression or survival in vivo, suggesting that these transcription factors are not crucial for leukemogenesis in CLL

Normalizing single-cell RNA sequencing data: challenges and opportunities

Single-cell transcriptomics is becoming an important component of the molecular biologist's toolkit. A critical step when analyzing data generated using this technology is normalization. However, normalization is typically performed using methods developed for bulk RNA sequencing or even microarray data, and the suitability of these methods for single-cell transcriptomics has not been assessed. We here discuss commonly used normalization approaches and illustrate how these can produce misleading results. Finally, we present alternative approaches and provide recommendations for single-cell RNA sequencing users

Laboratory to pilot scale: Microwave extraction for polyphenols lettuce

International audienceMicrowave hydrodiffusion and gravity (MHG) technique has been applied to pilot-scale solvent-free microwave extraction (SFME) of polyphenols from Lettuce sativa. Following the dictates of green extraction and with the aim to save time and energy, the lab-scale knowledge on SFME was exploited for the development of a pilot-scale process. The investigation entailed the optimization of all main parameters (temperature, time, extracted water volume, etc.) and we showed that the polyphenols composition profile under SFME was similar to the classic methods though a bit lower in total content. The energy consumption in the optimized procedure (30 min) was 1W/g of fresh matrix

Innovative Zr-Cu-Ag thin film metallic glass deposed by magnetron PVD sputtering for antibacterial applications

cited By 4International audienceZr-based thin film metallic glasses appear as promising coatings for biomedical applications, due to their microstructural and physicochemical properties. Materials used as medical instruments or devices require antibacterial activity to avoid nosocomial infections. In this paper, an optimized Zr-Cu-Ag thin film metallic glass deposited by PVD magnetron sputtering is evaluated for antibacterial applications. Ternary Zr39Cu39Ag22 TFMG was elaborated by PVD magnetron sputtering using a multi-target reactor. It has been demonstrated that this thin film is amorphous, uniformly thick and chemically homogenous. Mechanical, electrochemical properties and thermal stability were also characterized. These films display high hardness and Young's modulus, as well as an interesting passive behavior. Finally, this TFMG exhibits a strong antibacterial effect against Staphylococcus aureus. © 2016 Elsevier B.V

The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells ex vivo but fails to prevent leukemia development in a murine model

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Clickable C-glycosyl scaffold for the development of a dual fluorescent and [18F]fluorinated cyanine-containing probe and preliminary in vitro/vivo evaluation by fluorescence imaging

International audienceConsidering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable C-glycosyl scaffold to gather the different elements. We describe, for the first time, the synthesis of a cyanine-based dual PET/OI imaging probe based on a versatile synthetic strategy and its direct radiofluorination via [18F]F-C bond formation. The non-radioactive dual imaging probe coupled with two c(RGDfK) peptides was evaluated in vitro and in vivo in fluorescence imaging. The binding on αvβ3 integrin (IC50 = 16 nM) demonstrated the efficiency of the dimeric structure and PEG linkers in maintaining the affinity. In vivo fluorescence imaging of U-87 MG engrafted nude mice showed a high tumor uptake (40- and 100-fold increase for orthotopic and ectopic brain tumors, respectively, compared to healthy brain). In vitro and in vivo evaluations and resection of the ectopic tumor demonstrated the potential of the conjugate in glioblastoma cancer diagnosis and image-guided surgery

Better understand the crystallization dynamics of ZrCu TFMGs: Benefits of combining global and local in situ approaches

International audienceThis work describes crystallization mechanisms in a model ZrCu thin film metallic glass, synthesized through magnetron sputtering. Global-scale characterization techniques, including differential scanning calorimetry and X-ray diffraction, are compared with local-scale characterization obtained through in situ transmission electron microscopy during isothermal heating. This multi-scale approach establishes the crystallization sequence of ZrCu thin film metallic glasses. Furthermore, it highlights the role of oxidation as a nucleation site, initiating the crystallization process. Once initiated, crystallization progresses as a propagating front, scanning and transforming the amorphous matrix. The combination of both global and local approaches yields consistent key thermodynamic values. Additionally, monitoring the advancing crystallization front during in situ high-temperature transmission electron microscopy provides access to crucial kinetic parameters, such as diffusion coefficients

Clickable C-Glycosyl Scaffold for the Development of a Dual Fluorescent and [18F]fluorinated Cyanine-Containing Probe and Preliminary In Vitro/Vivo Evaluation by Fluorescence Imaging

Considering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable C-glycosyl scaffold to gather the different elements. We describe, for the first time, the synthesis of a cyanine-based dual PET/OI imaging probe based on a versatile synthetic strategy and its direct radiofluorination via [18F]F-C bond formation. The non-radioactive dual imaging probe coupled with two c(RGDfK) peptides was evaluated in vitro and in vivo in fluorescence imaging. The binding on αvβ3 integrin (IC50 = 16 nM) demonstrated the efficiency of the dimeric structure and PEG linkers in maintaining the affinity. In vivo fluorescence imaging of U-87 MG engrafted nude mice showed a high tumor uptake (40- and 100-fold increase for orthotopic and ectopic brain tumors, respectively, compared to healthy brain). In vitro and in vivo evaluations and resection of the ectopic tumor demonstrated the potential of the conjugate in glioblastoma cancer diagnosis and image-guided surgery