Real time noise and wavelength correlations in octave-spanning supercontinuum generation

We use dispersive Fourier transformation to measure shot-to-shot spectral instabilities in femtosecond supercontinuum generation. We study both the onset phase of supercontinuum generation with distinct dispersive wave generation, as well as a highly-unstable supercontinuum regime spanning an octave in bandwidth. Wavelength correlation maps allow interactions between separated spectral components to be identified, even when such interactions are not apparent in shot-to-shot or average measurements. Experimental results are interpreted using numerical simulations. Our results show the clear advantages of dispersive Fourier transformation for studying spectral noise during supercontinuum generation.Comment: 14 pages, 5 figure

Simulation de l'effet des surcharges sur le comportement mécanique des P.T.H à couples de matériaux différents

International audienceThe reliability of total hip arthroplasties (THA) is not any more to show. It is allowed by all. Indeed, the retreat of such interventions exceeds now fifteen years and the hopes which the first clinicians formulated are now realities. Nevertheless, the deformation and the wear of cup components remain an inevitable mechanism and loosening appear in long-term. Prevention of loosening passes by the reduction of this wear. This study deals with a simulation of the effect of overloads on THA with different materials. Three materials are analyzed in order to choose the couple which has better bio functionality.La fiabilité des arthroplasties totales de hanche n'est plus à démontrer. Elle est admise par tous. En effet, le recul de telles interventions dépasse maintenant quinze ans et les espérances que les premiers cliniciens ont formulées à leur égard sont maintenant des réalités. Néanmoins, la déformation et l'usure des composants acétabulaires restent un mécanisme inévitable et des descellements asceptiques apparaissent à long terme. La prévention du descellement passe donc par la réduction de cette usure. Cette étude porte sur une simulation de l'effet de certains paramètres mécaniques, entre autres « les surcharges » sur le comportement des PTH hybrides à couples de matériaux différents. Trois couples de matériaux sont analysés, en vue de choisir celui qui offre une meilleure biofonctionnalité

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders.

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders

Oat–buckwheat breads – technological quality, staling and sensory properties

peer reviewedThe technological and sensory properties and the staling of breads made from oat flour (OF) and buckwheat flour (BF) were analysed. Significant differences in protein and ash content were found in the experimental breads due to significant differences in the composition of the BF and OF used. As the proportion of BF in the recipe increased, a deterioration in the technological properties of the dough and bread as well as an increase in the crumb hardness were observed. The presence of OF in the recipe increased the bread volume, significantly enhanced the lightness of the crust and crumb and improved the overall sensory quality. The OF used in the recipe decreased the starch retrogradation enthalpy value, which is strongly related to a delay in bread staling. The proposed bakery products can be attractive to consumers who are looking for new food products

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

Purpose Although haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants. Methods We collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants through in silico analyses and cell-based experiments. Results We identified 20 unique, mostly de novo, ANKRD11 missense variants in 29 individuals, presenting with syndromic neurodevelopmental disorders similar to KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in repression domain 2 at the ANKRD11 C-terminus. Of the 10 functionally studied missense variants, 6 reduced ANKRD11 stability. One variant caused decreased proteasome degradation and loss of ANKRD11 transcriptional activity. Conclusion Our study indicates that pathogenic heterozygous ANKRD11 missense variants cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges because the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome