Genetically modified macrophages accelerate myelin repair

[EN] Preventing neurodegeneration-associated disability progression in patients with multiple sclerosis (MS) remains an unmet therapeutic need. As remyelination prevents axonal degeneration, promoting this process in patients might enhance neuroprotection. In demyelinating mouse lesions, local overexpression of semaphorin 3F (Sema3F), an oligodendrocyte progenitor cell (OPC) attractant, increases remyelination. However, molecular targeting to MS lesions is a challenge. A clinically relevant paradigm for delivering Sema3F to demyelinating lesions could be to use blood-derived macrophages as vehicles. Thus, we chose transplantation of genetically modified hematopoietic stem cells (HSCs) as means of obtaining chimeric mice with circulating Sema3F-overexpressing monocytes. We demonstrated that Sema3F-transduced HSCs stimulate OPC migration in a neuropilin 2 (Nrp2, Sema3F receptor)-dependent fashion, which was conserved in middle-aged OPCs. While demyelinating lesions induced in mice with Sema3F-expressing blood cells showed no changes in inflammation and OPC survival, OPC recruitment was enhanced which accelerated the onset of remyelination. Our results provide a proof of concept that blood cells, particularly monocytes/macrophages, can be used to deliver pro-remyelinating agents "at the right time and place," suggesting novel means for remyelination-promoting strategies in MS.This work was supported by the French National Institute of Health and Medical Research (INSERM), French National Research Agency (ANR, project Stemimus ANR-12-BSV4-0002-02), the European Leukodystrophy Association (ELA, project 2016-004C5B), NeurATRIS, the program "Investissements d'avenir" (ANR-10-IAIHU-06), CIBERNED (CB06/0005/0076), and Gobierno Vasco (IT1203-19). VT was a recipient of the Spanish Ministry of Economy Young Investigator Grant (SAF2015-74332-JIN)

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells

Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6Chi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Urban Seismomorphoses Seismic Vulnerabilities, an Embarrassing Legacy

Seismic vulnerability challenges sustainable urbanism. Antioch, Manosque and Oran, three Mediterranean cities destroyed by earthquakes, demonstrate how preservation of urban patrimony protects populations. The methodological pattern “urban seismic patrimonial strategies” cross investment and patrimonial care demonstrate natural hazards mitigation as a factor of urban policy. Urban patrimonial managers are unaware of seismic threat which obliges them to explain liabilities. Buildings evolution observation indicates urban phases. According urban policy reshape urban morphology and amplify social vulnerability

Seismic and air monitoring observatory for greater Beirut : a citizen observatory of the "urban health" of Beirut

International audienceAlready sensitive because of its geology (seismic-tsunamic risk) and its interface between arid and temperate ecosystems, the Mediterranean Basin is being transformed by climate change and major urban pressure on resources and spaces. Lebanon concentrates on a small territory the environmental, climatic, health, social and political crises of the Middle East: shortages and degradation of surface and groundwater quality, air pollution, landscape fragmentation, destruction of ecosystems, erosion of biodiversity, telluric risks and very few mechanisms of information, prevention and protection against these vulnerabilities. Further, Lebanon is sorely lacking in environmental data at sufficient temporal and spatial scales to cover the range of key phenomena and to allow the integration of environmental issues for the country's development. This absence was sadly illustrated during the August 4th, 2020, explosion at the port of Beirut, which hindered the effective management of induced threats to protect the inhabitants. In this degraded context combined with a systemic crisis situation in Lebanon, frugal innovation is more than an option, it is a necessity. Initiated in 2021 within the framework of the O-LIFE lebanese-french research consortium (www.o-life.org), the « Seismic and air monitoring observatory for greater Beirut » (SMOAG) project aims at setting up a citizen observatory of the urban health of Beirut by deploying innovative, connected, low-cost, energy-efficient and robust environmental and seismological instruments. Through co-constructed web services and mobile applications with various stakeholders (citizens, NGOs, decision makers and scientists), the SMOAG citizen observatory will contribute to the information and mobilization of Lebanese citizens and managers by sharing the monitoring of key indicators associated with air quality, heat islands and building stability, essential issues for a sustainable Beirut.The first phase of the project was dedicated to the development of a low-cost environmental sensor enabling pollution and urban weather measurements (particle matters, SO2, CO, O3, N02, solar radiation, wind speed, temperature, humidity, rainfall) and to the development of all the software infrastructure, from data acquisition to the synoptic indicators accessible via web and mobile application, while following the standards of the Sensor Web Enablement and Sensor Observation System of the OGC and to the FAIR principles (Easy to find, Accessible, Interoperable, Reusable). A website and Android/IOS applications for the restitution of data and indicators and a dashboard allowing real time access to data have been developed. Environmental and low-cost seismological stations (Raspberry Shake) have been already deployed in Beirut, most of them hosted by Lebanese citizens. These instrumental and open data access efforts were completed by participatory workshops with various stakeholders to improve the ergonomy of the web and application interfaces and to define roadmap for the implantation of future stations, consistently with most vulnerable populations identified by NGOs and the current knowledge on the air pollution and heat islands in Beirut

Seismic and air monitoring observatory for greater Beirut : a citizen observatory of the "urban health" of Beirut

International audienceAlready sensitive because of its geology (seismic-tsunamic risk) and its interface between arid and temperate ecosystems, the Mediterranean Basin is being transformed by climate change and major urban pressure on resources and spaces. Lebanon concentrates on a small territory the environmental, climatic, health, social and political crises of the Middle East: shortages and degradation of surface and groundwater quality, air pollution, landscape fragmentation, destruction of ecosystems, erosion of biodiversity, telluric risks and very few mechanisms of information, prevention and protection against these vulnerabilities. Further, Lebanon is sorely lacking in environmental data at sufficient temporal and spatial scales to cover the range of key phenomena and to allow the integration of environmental issues for the country's development. This absence was sadly illustrated during the August 4th, 2020, explosion at the port of Beirut, which hindered the effective management of induced threats to protect the inhabitants. In this degraded context combined with a systemic crisis situation in Lebanon, frugal innovation is more than an option, it is a necessity. Initiated in 2021 within the framework of the O-LIFE lebanese-french research consortium (www.o-life.org), the « Seismic and air monitoring observatory for greater Beirut » (SMOAG) project aims at setting up a citizen observatory of the urban health of Beirut by deploying innovative, connected, low-cost, energy-efficient and robust environmental and seismological instruments. Through co-constructed web services and mobile applications with various stakeholders (citizens, NGOs, decision makers and scientists), the SMOAG citizen observatory will contribute to the information and mobilization of Lebanese citizens and managers by sharing the monitoring of key indicators associated with air quality, heat islands and building stability, essential issues for a sustainable Beirut.The first phase of the project was dedicated to the development of a low-cost environmental sensor enabling pollution and urban weather measurements (particle matters, SO2, CO, O3, N02, solar radiation, wind speed, temperature, humidity, rainfall) and to the development of all the software infrastructure, from data acquisition to the synoptic indicators accessible via web and mobile application, while following the standards of the Sensor Web Enablement and Sensor Observation System of the OGC and to the FAIR principles (Easy to find, Accessible, Interoperable, Reusable). A website and Android/IOS applications for the restitution of data and indicators and a dashboard allowing real time access to data have been developed. Environmental and low-cost seismological stations (Raspberry Shake) have been already deployed in Beirut, most of them hosted by Lebanese citizens. These instrumental and open data access efforts were completed by participatory workshops with various stakeholders to improve the ergonomy of the web and application interfaces and to define roadmap for the implantation of future stations, consistently with most vulnerable populations identified by NGOs and the current knowledge on the air pollution and heat islands in Beirut

Chromogranin A preferential interaction with Golgi phosphatidic acid induces membrane deformation and contributes to secretory granule biogenesis

International audienceChromogranin A (CgA) is a key luminal actor of secretory granule biogenesis at the trans‐Golgi network (TGN) level but the molecular mechanisms involved remain obscure. Here, we investigated the possibility that CgA acts synergistically with specific membrane lipids to trigger secretory granule formation. We show that CgA preferentially interacts with the anionic glycerophospholipid phosphatidic acid (PA). In accordance, bioinformatic analysis predicted a PA‐binding domain (PABD) in CgA sequence that effectively bound PA (36:1) or PA (40:6) in membrane models. We identified PA (36:1) and PA (40:6) as predominant species in Golgi and granule membranes of secretory cells, and we found that CgA interaction with these PA species promotes artificial membrane deformation and remodeling. Furthermore, we demonstrated that disruption of either CgA PABD or phospholipase D (PLD) activity significantly alters secretory granule formation in secretory cells. Our findings show for the first time the ability of CgA to interact with PLD‐generated PA, which allows membrane remodeling and curvature, key processes necessary to initiate secretory granule budding

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6C<sup>hi</sup> monocytes and differentiation to pro-angiogenic myeloid cells.

Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6Chi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer

Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells.

Funder: Association pour la recherche sur le cancerFunder: Ligue Contre le CancerCancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6Chi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer