BAF(mSWI/SNF) complex regulates mediolateral cortical patterning in the developing forebrain

Early forebrain patterning entails the correct regional designation of the neuroepithelium, and appropriate specification, generation, and distribution of neural cells during brain development. Specific signaling and transcription factors are known to tightly regulate patterning of the dorsal telencephalon to afford proper structural/functional cortical arealization and morphogenesis. Nevertheless, whether and how changes of the chromatin structure link to the transcriptional program(s) that control cortical patterning remains elusive. Here, we report that the BAF chromatin remodeling complex regulates the spatiotemporal patterning of the mouse dorsal telencephalon. To determine whether and how the BAF complex regulates cortical patterning, we conditionally deleted the BAF complex scaffolding subunits BAF155 and BAF170 in the mouse dorsal telencephalic neuroepithelium. Morphological and cellular changes in the BAF mutant forebrain were examined using immunohistochemistry and in situ hybridization. RNA sequencing, Co-immunoprecipitation, and mass spectrometry were used to investigate the molecular basis of BAF complex involvement in forebrain patterning. We found that conditional ablation of BAF complex in the dorsal telencephalon neuroepithelium caused expansion of the cortical hem and medial cortex beyond their developmental boundaries. Consequently, the hippocampal primordium is not specified, the mediolateral cortical patterning is compromised, and the cortical identity is disturbed in the absence of BAF complex. The BAF complex was found to interact with the cortical hem suppressor LHX2. The BAF complex suppresses cortical hem fate to permit proper forebrain patterning. We provide evidence that BAF complex modulates mediolateral cortical patterning possibly by interacting with the transcription factor LHX2 to drive the LHX2-dependent transcriptional program essential for dorsal telencephalon patterning. Our data suggest a putative mechanistic synergy between BAF chromatin remodeling complex and LHX2 in regulating forebrain patterning and ontogeny

Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/- mice

Objective FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. Methods We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. Results Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. Interpretation Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome.Peer reviewe

Pseudoacromegaly

© 2018 Elsevier Inc. Individuals with acromegaloid physical appearance or tall stature may be referred to endocrinologists to exclude growth hormone (GH) excess. While some of these subjects could be healthy individuals with normal variants of growth or physical traits, others will have acromegaly or pituitary gigantism, which are, in general, straightforward diagnoses upon assessment of the GH/IGF-1 axis. However, some patients with physical features resembling acromegaly – usually affecting the face and extremities –, or gigantism – accelerated growth/tall stature – will have no abnormalities in the GH axis. This scenario is termed pseudoacromegaly, and its correct diagnosis can be challenging due to the rarity and variability of these conditions, as well as due to significant overlap in their characteristics. In this review we aim to provide a comprehensive overview of pseudoacromegaly conditions, highlighting their similarities and differences with acromegaly and pituitary gigantism, to aid physicians with the diagnosis of patients with pseudoacromegaly.PM is supported by a clinical fellowship by Barts and the London Charity. Our studies on pituitary adenomas and related conditions received support from the Medical Research Council, Rosetrees Trust and the Wellcome Trust

Design of emergency beacons integrated with maritime safety equipment

Au cours de ces dernières années, les communications sans fil connaissent une croissance vertigineuse, avec le développement de standards de communication de plus en plus nombreux, qui ouvrent la voie à de multiples applications telles que : la téléphonie mobile, le biomédical, le maritime, le civil et le militaire. De nos jours, les communications sans fil se sont diversifiées et multipliées. Cela entraîne la conception d’antennes toujours plus innovantes, performantes et de taille de plus en plus réduite (miniaturisation). Le projet FLEXBEA (FLEXible BEAcon) a pour but le développement d’un nouveau concept de balises de détresse miniatures (AIS et COSPAS-SARSAT), faible coût, intégrées dans des équipements de sécurité maritime tels qu’un radeau de survie et un gilet de sauvetage. Ces équipements sont destinés aux professionnels de la mer et aux plaisanciers. L’atout majeur de ce nouveau concept est l’intégration dans des équipements de sécurité maritime d’une fonction de détresse en cas de problème majeur : homme à la mer (MOB, Man OverBoard) par exemple lors d’un naufrage. Différentes antennes ont été étudiées. Nous présentons des antennes planaires (de type dipôle ou monopôle imprimé) développées dans la bande UHF : une solution de dipôle avec brins repliés est proposée afin de réduire l'encombrement, et deux modes d'alimentation (symétrique / dissymétrique) sont comparés. Des exemples d'antenne monopôle sont ensuite présentés avec une modification de leur géométrie (structures de type Bow-tie ou méandre) pour assurer une miniaturisation optimale. Puis les antennes filaires retenues pour le projet, avec une modélisation de ces antennes par un circuit équivalent (RLC). Des formules analytiques sont proposées afin de déterminer les valeurs de composants RLC qui interviennent dans le modèle circuit. Ensuite, nous sommes passés à la conception de l’antenne de la balise. Deux antennes ont été conçues et mesurées. Un monopôle ruban avec introduction de composants localisés pour la balise AIS et COSPAS-SARSAT, et une antenne hélice fonctionnant dans la bande AIS, intégrée dans la balise "SIMY". De nombreuses réalisations et mesures ont été effectuées pour caractériser ses antennes.Over the last few years, wireless communications have grown dramatically, with the development of more and more communication standards, which open the way to multiple applications such as: mobile telephony, biomedical, maritime, the civilian and the military. Today, wireless communications have diversified and multiplied. This leads to the design of antennas that are always more innovative, more efficient and smaller in size (miniaturization). The FLEXBEA project (FLEXible BEAcon) aims to develop a new concept of low cost miniature distress beacons (AIS and COSPAS-SARSAT) integrated into marine safety equipment such as a life raft and a lifejacket safety. This equipment is intended for professionals of the sea and boaters. The main advantage of this new concept is the integration in maritime safety equipment of a distress function in case of major problem: man overboard (MOB, Man OverBoard) for example during a shipwreck. Different antennas have been studied. We present planar antennas (dipole type or printed monopoly) developed in the UHF band: a dipole solution with folded strands is proposed to reduce the bulk, and two modes of supply (symmetrical / asymmetrical) are compared. Examples of monopole antennas are then presented with a modification of their geometry (Bow-tie or meander type structures) to ensure optimal miniaturization. Then the wired antennas selected for the project, with a modeling of these antennas by an equivalent circuit (RLC). Analytical formulas are proposed to determine the RLC component values ​​involved in the circuit model. Then we went to the design of the beacon antenna. Two antennas were designed and measured. A ribbon monopoly with introduction of localized components for the AIS and COSPAS-SARSAT beacon, and a helix antenna operating in the AIS band, integrated into the "SIMY" beacon. Many achievements and measurements have been made to characterize its antennas

Conception de balises de détresse intégrées aux équipements de sécurité maritime

Over the last few years, wireless communications have grown dramatically, with the development of more and more communication standards, which open the way to multiple applications such as: mobile telephony, biomedical, maritime, the civilian and the military. Today, wireless communications have diversified and multiplied. This leads to the design of antennas that are always more innovative, more efficient and smaller in size (miniaturization). The FLEXBEA project (FLEXible BEAcon) aims to develop a new concept of low cost miniature distress beacons (AIS and COSPAS-SARSAT) integrated into marine safety equipment such as a life raft and a lifejacket safety. This equipment is intended for professionals of the sea and boaters. The main advantage of this new concept is the integration in maritime safety equipment of a distress function in case of major problem: man overboard (MOB, Man OverBoard) for example during a shipwreck. Different antennas have been studied. We present planar antennas (dipole type or printed monopoly) developed in the UHF band: a dipole solution with folded strands is proposed to reduce the bulk, and two modes of supply (symmetrical / asymmetrical) are compared. Examples of monopole antennas are then presented with a modification of their geometry (Bow-tie or meander type structures) to ensure optimal miniaturization. Then the wired antennas selected for the project, with a modeling of these antennas by an equivalent circuit (RLC). Analytical formulas are proposed to determine the RLC component values ​​involved in the circuit model. Then we went to the design of the beacon antenna. Two antennas were designed and measured. A ribbon monopoly with introduction of localized components for the AIS and COSPAS-SARSAT beacon, and a helix antenna operating in the AIS band, integrated into the "SIMY" beacon. Many achievements and measurements have been made to characterize its antennas.Au cours de ces dernières années, les communications sans fil connaissent une croissance vertigineuse, avec le développement de standards de communication de plus en plus nombreux, qui ouvrent la voie à de multiples applications telles que : la téléphonie mobile, le biomédical, le maritime, le civil et le militaire. De nos jours, les communications sans fil se sont diversifiées et multipliées. Cela entraîne la conception d’antennes toujours plus innovantes, performantes et de taille de plus en plus réduite (miniaturisation). Le projet FLEXBEA (FLEXible BEAcon) a pour but le développement d’un nouveau concept de balises de détresse miniatures (AIS et COSPAS-SARSAT), faible coût, intégrées dans des équipements de sécurité maritime tels qu’un radeau de survie et un gilet de sauvetage. Ces équipements sont destinés aux professionnels de la mer et aux plaisanciers. L’atout majeur de ce nouveau concept est l’intégration dans des équipements de sécurité maritime d’une fonction de détresse en cas de problème majeur : homme à la mer (MOB, Man OverBoard) par exemple lors d’un naufrage. Différentes antennes ont été étudiées. Nous présentons des antennes planaires (de type dipôle ou monopôle imprimé) développées dans la bande UHF : une solution de dipôle avec brins repliés est proposée afin de réduire l'encombrement, et deux modes d'alimentation (symétrique / dissymétrique) sont comparés. Des exemples d'antenne monopôle sont ensuite présentés avec une modification de leur géométrie (structures de type Bow-tie ou méandre) pour assurer une miniaturisation optimale. Puis les antennes filaires retenues pour le projet, avec une modélisation de ces antennes par un circuit équivalent (RLC). Des formules analytiques sont proposées afin de déterminer les valeurs de composants RLC qui interviennent dans le modèle circuit. Ensuite, nous sommes passés à la conception de l’antenne de la balise. Deux antennes ont été conçues et mesurées. Un monopôle ruban avec introduction de composants localisés pour la balise AIS et COSPAS-SARSAT, et une antenne hélice fonctionnant dans la bande AIS, intégrée dans la balise "SIMY". De nombreuses réalisations et mesures ont été effectuées pour caractériser ses antennes

Context-specific chromatin remodeling activity of mSWI/SNF complexes depends on the epigenetic landscape

Atrophic brain changes in acute anorexia nervosa (AN) are often visible to the naked eye on computed tomography or magnetic resonance imaging scans, but it remains unclear what is driving these effects. In neurological diseases, neurofilament light (NF-L) and tau protein have been linked to axonal damage. Glial fibrillary acidic protein (GFAP) has been associated with astroglial injury. In an attempt to shed new light on factors potentially underlying past findings of structural brain alterations in AN, the current study investigated serum NF-L, tau protein, and GFAP levels longitudinally in AN patients undergoing weight restoration. Blood samples were obtained from 54 acutely underweight, predominantly adolescent female AN patients and 54 age-matched healthy control participants. AN patients were studied in the severely underweight state and again after short-term partial weight restoration. Group comparisons revealed higher levels of NF-L, tau protein, and GFAP in acutely underweight patients with AN compared to healthy control participants. Longitudinally, a decrease in NF-L and GFAP but not in tau protein levels was observed in AN patients upon short-term partial weight restoration. These results may be indicative of ongoing neuronal and astroglial injury during the underweight phase of AN. Normalization of NF-L and GFAP but not tau protein levels may indicate an only partial restoration of neuronal and astroglial integrity upon weight gain after initial AN-associated cell damage processes

Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders

The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders