2D numerical modelling of tracer transport and dilution in the Loire river

Water Qualit

About quantitative EBSD analysis of deformation and recovery substructures in pure Tantalum

International audienceThe aim of this work is to present a quantitative analysis of features involved in recovery during annealing of deformed Tantalum. In pure metals where crystalline defects usually have high mobility, dislocation annihilation and rearrangement occur to a great extent prior to recrystallization. Therefore a complete understanding of recrystallization cannot be accomplished without an advanced knowledge of the recovery phenomenon. Depending on whether dislocations induce a measurable curvature in the crystal lattice or not, they are called Geometrically Necessary Dislocations (GNDs) or Statistically Stored Dislocations (SSDs) respectively. In the present work only GNDs are considered. For this purpose electron backscatter diffraction (EBSD) is an advantageous technique to obtain statistically representative results when compared to Transmission Electron Microscopy (TEM). However, a quantitative analysis of GNDs from EBSD data is not straightforward. Since local misorientations are induced by the curvature of the crystal lattice caused by GNDs, GNDs analysis can be done using local misorientations. However the values obtained from this analysis are step size dependent and influenced by the measurement noise. Reasoning on the basis that when the step size tends to zero, local misorientation should also tend to zero, measurement noise can be estimated [1]. The measurement noise appears to notably be very much dependent on the amplitude of local misorientations, which must be considered in the perspective of GND density calculatio

Substitution of the α-lactalbumin transcription unit by a CAT cDNA within a BAC clone silenced the locus in transgenic mice without affecting the physically linked Cyclin T1 gene

We recently reported that a goat bacterial artificial chromosome (BAC) clone conferred site-independent expression in transgenic mice of the two loci present within its insert, the ubiquitously expressed Cyclin T1 and the mammary specific β-lactalbumin (αlac) genes. To assess if this vector could target mammary-restricted expression of cDNA, the CAT ORF was introduced by homologous recombination in Escherichia coli in place of the αlac transcription unit. The insert of this modified BAC was injected into mice and three transgenic lines were derived. None of these lines expressed the CAT gene suggesting that the use of long genomic inserts is not sufficient to support the expression of intron-less transgenes. The physically linked goat Cyclin T1 locus was found to be active in all three lines. This observation reinforced the hypothesis that the two loci are localised in two separate chromatin domains

Substitution of the ?-lactalbumin transcription unit by a CAT cDNA within a BAC clone silenced the locus in transgenic mice without affecting the physically linked Cyclin T1 gene

We recently reported that a goat bacterial artificial chromosome (BAC) clone conferred site-independent expression in transgenic mice of the two loci present within its insert, the ubiquitously expressed Cyclin T1 and the mammary specific $\alpha$-lactalbumin ($\alpha$lac) genes. To assess if this vector could target mammary-restricted expression of cDNA, the CAT ORF was introduced by homologous recombination in Escherichia coli in place of the $\alpha$lac transcription unit. The insert of this modified BAC was injected into mice and three transgenic lines were derived. None of these lines expressed the CAT gene suggesting that the use of long genomic inserts is not sufficient to support the expression of intron-less transgenes. The physically linked goat Cyclin T1 locus was found to be active in all three lines. This observation reinforced the hypothesis that the two loci are localised in two separate chromatin domains

Full field modeling of recrystallization and grain growth thanks to a level set approach: towards modeling by industry

International audienceMetal forming modeling can be predictive only if the strain rate, strain and temperature dependency of the flow behaviour are correctly described. The mechanical properties and behaviour of metallic materials mainly depends on the content and structure of dislocation network, this points out the need to incorporate microstructure concepts into the numerical models. The goal is to correctly describe the main physical mechanisms occurring in metals during thermomechanical processes i.e. work-hardening, recovery, grain boundary migration, nucleation and grain growth related to dynamic, static or metadynamic recrystallization. Macroscopic and homogenized models are widely used in the industry, mainly due to their low computational cost. If this mean field framework is quite convenient, it can be synonymous, for a given material, with a large amount of experiments with advanced laboratory devices. Moreover, the homogenization of the microstructure does not permit to capture some very local phenomena

Distal element(s) is(are) required for position-independent expression of the goat α-lactalbumin gene in transgenic mice. Potential relationship with the location of the cyclin T1 locus

We recently reported the site-independent and copy-number-related expression in mice of a goat α-lactalbumin gene with 150 kb and 10 kb of 5'- and 3'-flanking sequences, respectively. In the present study, we observed that the resection of the 5'-flanking region, leaving only 70 kb, resulted in a site-dependent expression of this milk protein-encoding transgene. This suggests that important cis-regulatory elements are located within the distal-deleted sequence. Within this region, we localised the promoter of the cyclin T1 gene, an ubiquitously expressed gene. So far, no other gene has been located between these two loci. Since these two genes are differentially expressed, our data suggest the potential location of an insulator within the deleted region that allows the two genes to be independently regulated

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity

ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized. International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing. We identified 13 individuals with heterozygous likely pathogenic variants in ARFGEF1. These individuals displayed congruent clinical features of developmental delay, behavioral problems, abnormal findings on brain magnetic resonance image (MRI), and epilepsy for almost half of them. While nearly half of the cohort carried de novo variants, at least 40% of variants were inherited from mildly affected parents who were clinically re-evaluated by reverse phenotyping. Our in silico predictions and in vitro assays support the contention that ARFGEF1-related conditions are caused by haploinsufficiency, and are transmitted in an autosomal dominant fashion with variable expressivity. We provide evidence that loss-of-function variants in ARFGEF1 are implicated in sporadic and familial cases of developmental delay with or without epilepsy

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder