Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders

Changes in genetic and/or environmental factors to developing neural circuits and subsequent synaptic functions are known to be a causative underlying the varied socio-emotional behavioural patterns associated with autism spectrum disorders (ASD). Seven transmembrane G protein-coupled receptors (GPCRs) comprising the largest family of cell-surface receptors, mediate the transfer of extracellular signals to downstream cellular responses. Disruption of GPCR and their signalling have been implicated as a convergent pathologic mechanism of ASD. Here, we aim to review the literature about the 23 GPCRs that are genetically associated to ASD pathology according to Simons Foundation Autism Research Initiative (SFARI) database such as oxytocin (OXTR) and vasopressin (V1A, V1B) receptors, metabotropic glutamate (mGlu5, mGlu7) and gamma-aminobutyric acid (GABAB) receptors, dopamine (D1, D2), serotoninergic (5-HT1B and additionally included the 5-HT2A, 5-HT7 receptors for their strong relevance to ASD), adrenergic ($\beta$2) and cholinergic (M3) receptors, adenosine (A2A, A3) receptors, angiotensin (AT2) receptors, cannabinoid (CB1) receptors, chemokine (CX3CR1) receptors, orphan (GPR37, GPR85) and olfactory (OR1C1, OR2M4, OR2T10, OR52M1) receptors. We discussed the genetic variants, relation to core ASD behavioural deficits and update on pharmacological compounds targeting these 23 GPCRs. Of these OTR, V1A, mGlu5, D2, 5-HT2A, CB1, and GPR37 serve as the best therapeutic targets and have potential towards core domains of ASD pathology. With a functional crosstalk between different GPCRs and converging pharmacological responses, there is an urge to develop novel therapeutic strategies based on multiple GPCRs to reduce the socioeconomic burden associated with ASD and we strongly emphasize the need to prioritize the increased clinical trials targeting the multiple GPCRs

Hybrid Regional Aircraft: A Comparative Review of New Potentials Enabled by Electric Power

This article assesses the benefits of hybridization within the regional aircraft scale using a conventional twin-turbo propeller aircraft as reference. For a fair comparison, this reference aircraft was designed assuming a 2035 technology level. The propulsion system of the reference aircraft is analyzed along the mission and the phases of flight with low efficiencies are highlighted. Then the potential benefits of new power management through the use of secondary power generation systems but also through the variation of the size of prime movers are presented and discussed. In particular, the effect of the gas turbine size on its efficiency is studied. Finally, the article focuses on aerodynamic improvements enabled by new propeller or fan integrations and the associated concepts such as differential thrust, blown wing and boundary layer ingestion. For each topic, simplified analyses provide estimated potential of energy saving. These results can be used as indicators for selecting the most promising hybrid architecture concepts for a regional aircraft

Hybrid Propulsion for Regional Aircraft: a Comparative Analysis based on Energy Efficiency

This article assesses the potential benefits of transient energy storage for a hybrid regional aircraft. The mission profile of a reference aircraft is analyzed according to energetic intermittence and the results are compared to typical figures for cars, trains, and ships. Also, the opportunity of recovering energy in descent and during landing is studied. This article shows that energy saving potential brought by transient energy storage is much smaller than for ground-based transportation. In addition, energy recovering does not bring benefit on a hybrid aircraft in normal operation. Nevertheless, the best energy management strategies in descent are highlighted and the use of a hybrid propulsion system in this phase shows significant potential energy savings. Finally, the article addresses other strategies enabled by hybrid propulsion to improve the aircraft energy efficiency

Hybrid Regional Aircraft: A Comparative Review of New Potentials Enabled by Electric Power

International audienceThis article assesses the benefits of hybridization within the regional aircraft scale using a conventional twin-turbo propeller aircraft as reference. For a fair comparison, this reference aircraft was designed assuming a 2035 technology level. The propulsion system of the reference aircraft is analyzed along the mission and the phases of flight with low efficiencies are highlighted. Then the potential benefits of new power management through the use of secondary power generation systems but also through the variation of the size of prime movers are presented and discussed. In particular, the effect of the gas turbine size on its efficiency is studied. Finally, the article focuses on aerodynamic improvements enabled by new propeller or fan integrations and the associated concepts such as differential thrust, blown wing and boundary layer ingestion. For each topic, simplified analyses provide estimated potential of energy saving. These results can be used as indicators for selecting the most promising hybrid architecture concepts for a regional aircraft

Hybrid Regional Aircraft: A Comparative Review of New Potentials Enabled by Electric Power

International audienceThis article assesses the benefits of hybridization within the regional aircraft scale using a conventional twin-turbo propeller aircraft as reference. For a fair comparison, this reference aircraft was designed assuming a 2035 technology level. The propulsion system of the reference aircraft is analyzed along the mission and the phases of flight with low efficiencies are highlighted. Then the potential benefits of new power management through the use of secondary power generation systems but also through the variation of the size of prime movers are presented and discussed. In particular, the effect of the gas turbine size on its efficiency is studied. Finally, the article focuses on aerodynamic improvements enabled by new propeller or fan integrations and the associated concepts such as differential thrust, blown wing and boundary layer ingestion. For each topic, simplified analyses provide estimated potential of energy saving. These results can be used as indicators for selecting the most promising hybrid architecture concepts for a regional aircraft

Risk of relapse after COVID-19 vaccine among patients with multiple sclerosis in France: a self-controlled case series

International audienc

Risk of relapse after COVID-19 vaccine among patients with multiple sclerosis in France: a self-controlled case series

International audienc

Towards the convergent therapeutic potential of G protein‐coupled receptors in autism spectrum disorders

International audienceAutism spectrum disorders (ASDs) are diagnosed in 1/100 children worldwide, based on two core symptoms: deficits in social interaction and communication, and stereotyped behaviours. G protein-coupled receptors (GPCRs) are the largest family of cellsurface receptors that transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR; vasopressin V 1A and V 1B ; metabotropic glutamate mGlu 5 and mGlu 7 ; GABA B2 ; dopamine D 1 , D 2 and D 3 ; serotoninergic 5-HT 1B ; β 2-adrenoceptor; cholinergic M 3 ; adenosine A 2A and A 3 ; angiotensin AT 2 ; cannabinoid CB 1 ; chemokine CX 3 CR1; orphan GPR37 and GPR85; and olfactory OR1C1, OR2M4, OR2T10 and OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, as well as 5-HT 2A and 5-HT 7 , for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopoeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight D 2 , 5-HT 2A , CB 1 , OTR and V 1A as the more promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD

Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders

Changes in genetic and/or environmental factors to developing neural circuits and subsequent synaptic functions are known to be a causative underlying the varied socio-emotional behavioural patterns associated with autism spectrum disorders (ASD). Seven transmembrane G protein-coupled receptors (GPCRs) comprising the largest family of cell-surface receptors, mediate the transfer of extracellular signals to downstream cellular responses. Disruption of GPCR and their signalling have been implicated as a convergent pathologic mechanism of ASD. Here, we aim to review the literature about the 23 GPCRs that are genetically associated to ASD pathology according to Simons Foundation Autism Research Initiative (SFARI) database such as oxytocin (OXTR) and vasopressin (V1A, V1B) receptors, metabotropic glutamate (mGlu5, mGlu7) and gamma-aminobutyric acid (GABAB) receptors, dopamine (D1, D2), serotoninergic (5-HT1B and additionally included the 5-HT2A, 5-HT7 receptors for their strong relevance to ASD), adrenergic (β2) and cholinergic (M3) receptors, adenosine (A2A, A3) receptors, angiotensin (AT2) receptors, cannabinoid (CB1) receptors, chemokine (CX3CR1) receptors, orphan (GPR37, GPR85) and olfactory (OR1C1, OR2M4, OR2T10, OR52M1) receptors. We discussed the genetic variants, relation to core ASD behavioural deficits and update on pharmacological compounds targeting these 23 GPCRs. Of these OTR, V1A, mGlu5, D2, 5-HT2A, CB1, and GPR37 serve as the best therapeutic targets and have potential towards core domains of ASD pathology. With a functional crosstalk between different GPCRs and converging pharmacological responses, there is an urge to develop novel therapeutic strategies based on multiple GPCRs to reduce the socioeconomic burden associated with ASD and we strongly emphasize the need to prioritize the increased clinical trials targeting the multiple GPCRs