Retinoic Acid Controls the Bilateral Symmetry of Somite Formation in the Mouse Embryo

A striking characteristic of vertebrate embryos is their bilaterally symmetric body plan, which is particularly obvious at the level of the somites and their derivatives such as the vertebral column. Segmentation of the presomitic mesoderm must therefore be tightly coordinated along the left and right embryonic sides. We show that mutant mice defective for retinoic acid synthesis exhibit delayed somite formation on the right side. Asymmetric somite formation correlates with a left-right desynchronization of the segmentation clock oscillations. These data implicate retinoic acid as an endogenous signal that maintains the bilateral synchrony of mesoderm segmentation, and therefore controls bilateral symmetry, in vertebrate embryos

Inkjet printing of ceramic colloidal suspensions: Filament growth and breakup

Filament growth and breakup are investigated in the context of ceramic inkjet printing. Several inks were formulated and ejected on a printer dedicated to ceramic materials. They consisted of six colloidal inks, four simple fluids and two graphic inks. For each, stroboscopic snapshots were acquired and the filament shape was extracted and analysed, for different nozzle actuation pulses. The filament length and the thread minimum radius were measured during the ejection process. A scaling of the breakup time with the Rayleigh number was obtained, as well as a general behaviour for the filament growth rate during the ejection process

Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells

Caveolin-3 is the major structural protein of caveolae in muscle. Mutations in the CAV3 gene cause different types of myopathies with altered membrane integrity and repair, expression of muscle proteins, and regulation of signaling pathways. We show here that myotubes from patients bearing the CAV3P28L and R26Q mutations present a dramatic decrease of caveolae at the plasma membrane, resulting in abnormal response to mechanical stress. Mutant myotubes are unable to buffer the increase in membrane tension induced by mechanical stress. This results in impaired regulation of the IL6/STAT3 signaling pathway leading to its constitutive hyperactivation and increased expression of muscle genes. These defects are fully reversed by reassembling functional caveolae through expression ofcaveolin-3. Our study reveals that under mechanical stress the regulation of mechan-oprotection by caveolae is directly coupled with the regulation of IL6/STAT3 signaling inmuscle cells and that this regulation is absent in Cav3-associated dystrophic patients

The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP

When an essential amino acid is limited, a signaling cascade is triggered that leads to increased translation of the ‘master regulator’, activating transcription factor 4 (ATF4), and resulting in the induction of specific target genes. Binding of ATF4 to the amino acid response element (AARE) is an essential step in the transcriptional activation of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation. We set out to identify proteins that interact with ATF4 and that play a role in the transcriptional activation of CHOP. Using a tandem affinity purification (TAP) tag approach, we identified p300/CBP-associated factor (PCAF) as a novel interaction partner of ATF4 in leucine-starved cells. We show that the N-terminal region of ATF4 is required for a direct interaction with PCAF and demonstrate that PCAF is involved in the full transcriptional response of CHOP by amino acid starvation. Chromatin immunoprecipitation analysis revealed that PCAF is engaged on the CHOP AARE in response to amino acid starvation and that ATF4 is essential for its recruitment. We also show that PCAF stimulates ATF4-driven transcription via its histone acetyltransferase domain. Thus PCAF acts as a coactivator of ATF4 and is involved in the enhancement of CHOP transcription following amino acid starvation

EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription

Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is rapidly released from caveolae, SUMOylated, and translocated to the nucleus, where it regulates the transcription of several genes including those coding for caveolae constituents. We also found that EHD2 is required to maintain the caveolae reservoir at the plasma membrane during the variations of membrane tension induced by mechanical stress. Metal-replica electron microscopy of breast cancer cells lacking EHD2 revealed a complete absence of caveolae and a lack of gene regulation under mechanical stress. Expressing EHD2 was sufficient to restore both functions in these cells. Our findings therefore define EHD2 as a central player in mechanotransduction connecting the disassembly of the caveolae reservoir with the regulation of gene transcription under mechanical stress

Biodiversity conservation as a new rationale for localized and sustainable agro-food systems. The case of two French PDO mountain cheeses.

International audienceOur paper is based on the first results of a twofold interdisciplinary research project financed by the French Ministry of the Environment (DIVA2 programme) which purpose was to analyse the emergence of biodiversity conservation as a new goal set to geographical indications and to study its effects on the strategies of the various stakeholders, and their impacts on the farming practices and the..

Traceable surface sources by functionalization for initial mapping of nuclear facilities

International audienceDuring decommissioning and dismantling, the initial cartography of all the surfaces is a key step that will enable in the classification of potential future wastes as a function of their radioactivity level. Using relevant surface sources, contamination detectors must be calibrated in terms of emitted flux, or Bq.cm-2. Current standard surface sources are made of thick aluminum with limited surface areas complying with ISO 8769 standard (Reference Sources-Calibration of Surface Contamination Monitors). These sources lack representativeness. This research intends to produce flexible, traceable surface sources with limited radiation self-absorption (for alpha and beta emitters). In this study, we propose a novel approach that will allow us to produce non-contaminating sources, due to the strong chemical bonds between the substrate and radioactive molecule. Using this method, unlike the commercial ones, a protective layer on the surface is not needed. We will then be able to manufacture more representative and non-contaminating sources to be used on-site to check the stability of the measurement devices. Two substrates, aluminium foils and polymeric surfaces, were selected to create sources that are both thin and flexible, curved or rough. Primarily, three molecules were selected to bind to the substrate at one end, and show a high affinity for the radionuclides at the other end. Due to the flexibility of aluminium foils, these sources can also be used to assess the performance of the detector in front of a curved surface. The experimental study includes cleaning, etching, grafting, and radionuclide binding steps. The substrates are cleaned in order to eliminate any organic residues. Afterwards, hydroxide functions were released by etching. Finally, in the grafting step, etched samples are immersed to graft the selected molecule on the substrate. These functionalization methods and their parameters such as concentration, reaction time, temperature, and drying conditions are optimized. In addition to these methods, sulfonation was found to be efficient for radionuclide attachment on polymeric surfaces. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was used to assess the functionalization success before and after grafting and to identify the functions on the surface. The topography was observed using scanning electron microscopy (SEM). The FTIR spectra results indicated that all of the selected chemicals were grafted onto the aluminum substrate. The SEM images also demonstrate that the surface morphology has changed significantly after grafting. Eventually, radionuclide binding experiments were carried out with 152Eu, used as a chemical surrogate for 241Am. We will present the radionuclide's binding yield obtained as a function of the functionalization as well as the associated surface uniformity of the samples, using respectively liquid scintillation counting and autoradiography

Novel production method for traceable surface sources by aluminium functionalisation

International audienceAccurate detection of low-level radioactivity is critical in decommissioning. However, commercial sources used for calibration lack representativeness due to their flat surface. The objective of this work is to produce flexible and large area surface sources for alpha and beta emitters by functionalising aluminium foil. Functionalisation strategies were developed to provide these sources. The manganese oxide coated sample shows the highest fixation yield for $^{241}$Am: (70.0 ± 2.6)% and conforms to ISO 8769 for uniformity (92%)

Development of alpha-emitting large area radioactive surface sources tailored for decommissioning

International audienceThe reliability of contamination measurements during decommissioning and dismantling of used nuclear facilities is of the utmost importance for the rest of the process and an efficient waste management. Therefore, the surface contamination monitors used have to be calibrated on-site, regularly, with the use of reference sources. There is a need for new reference sources that could compare to real contaminated surfaces in term of size, level of contamination, but also shape and roughness, while being traceable to national standards and without labile contamination. The approach described herein is the encapsulation of radionuclides in the matrix of an epoxy resin. Surface sources are obtained by pouring the liquid resin in molds of desired size and geometry. Any radionuclide can be scavenged, even volatile ones, as long as they can be processed in aqueous form. The activity used to spike the resin is traceable and was compared with the emission rate of particles measured using a primary method of standardization, the coincidence technique. For alpha emitting radionuclides, the source efficiency is low, around 1 %, but the relation between activity and surface emission rate has proven robust at different activity levels and source thickness. The uniformity of the sources is below 90 %, for sources larger than 100 cm², however large area modular pixelated sources with uniformity of around 90 % could be obtained by assembling several smaller sources. Additionally, the sources prepared have shown no or very low labile contamination, using dry and wet smear tests. This allows their use without any cover layer, and is very beneficial for their use in harsh on-site environments. The sources prepared do not comply with most of the standard ISO 8769 requirements, which regulates the characteristics of metrological reference sources. However, they can be applied to the specific needs of the decommissioning and dismantling process