24 / 03 / 2022
Clocks & Sleep
Direct Effects of Light on Sleep under Ultradian Light-Dark Cycles Depend on Circadian Time and Pulses Duration
Fanny Fuchs, Ludivine Robin-Choteau, Laurence Hugueny, Dominique Ciocca, Patrice Bourgin
Ultradian light-dark cycles in rodents are a precious tool to study the direct effects of repeated light exposures on sleep, in order to better understand the underlying mechanisms. This study aims to precisely evaluate the effects of light and dark exposures, according to circadian time, on sleep and waking distribution and quality, and to determine if these effects depend on the duration of light and dark pulses...
17 / 03 / 2022
EMBO molecular medicine
CD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype
Antoine de Zélicourt, Abdallah Fayssoil, Mbarka Dakouane-Giudicelli, Isley De Jesus,..., Mathias Mericskay, Eduardo N Chini, Ana Maria Gomez, José-Manuel Cancela, Sabine de la Porte
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca2+ dysregulation linked to Ca2+ influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD+ ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD+ glycohydrolase-producing modulators of Ca2+ signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers.
24 / 02 / 2022
Nature Immunology
Long-term culture-expanded alveolar macrophages restore their full epigenetic identity after transfer in vivo
Sethuraman Subramanian, Clara Jana-Lui Busch, Kaaweh Molawi, Laufey Geirsdottir, Julien Maurizio,..., Sandrine Sarrazin, Lena Alexopoulou, Michael H Sieweke
Alveolar macrophages (AMs) are lung tissue-resident macrophages that can be expanded in culture, but it is unknown to what extent culture affects their in vivo identity. Here we show that mouse long-term ex vivo expanded AMs (exAMs) maintained a core AM gene expression program, but showed culture adaptations related to adhesion, metabolism and proliferation. Upon transplantation into the lung, exAMs reacquired full transcriptional and epigenetic AM identity, even after several months in culture and could self-maintain long-term in the alveolar niche.
08 / 02 / 2022
Frontiers in Immunology
The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?
Raefa Abou Khouzam, Rania Faouzi Zaarour, Klaudia Brodaczewska, Bilal Azakir, Goutham Hassan Venkatesh, Jerome Thiery, Stéphane Terry, Salem Chouaib
Hypoxia is an environmental stressor that is instigated by low oxygen availability. It fuels the progression of solid tumors by driving tumor plasticity, heterogeneity, stemness and genomic instability. Hypoxia metabolically reprograms the tumor microenvironment (TME), adding insult to injury to the acidic, nutrient deprived and poorly vascularized conditions that act to dampen immune cell function. Through its impact on key cancer hallmarks and by creating a physical barrier conducive to tumor survival, hypoxia modulates tumor cell escape from the mounted immune response.
04 / 02 / 2022
Oncoimmunology
Immune sunrise: from the immunome to the cancer immune landscape
Gabriela Bindea, Bernhard Mlecnik, Jérôme Galon
The complex dynamics of the tumor-immune interaction during tumor progression have been characterized by integrating genomic and proteomic experiments. The Immunome, a reference compendium of markers for the majority of immune cell subpopulations was used to describe the immune landscape in cancer. The immune contexture is at the cornerstone in the success of cancer immunotherapies.
25 / 01 / 2022
Bone research
Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia
Ludovic Martin, Nabil Kaci, Catherine Benoist-Lasselin, ..., Antonio Segura-Carretero, Emilie Dambroise, Laurence Legeai-Mallet
A gain-of-function mutation in the fibroblast growth factor receptor 3 gene (FGFR3) results in achondroplasia (ACH), the most frequent form of dwarfism. Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways. Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH, and natural plant compounds are prime drug candidate sources. Here, we found that the phenolic compound (-)-epicatechin, isolated from Theobroma cacao, effectively inhibited FGFR3's downstream signaling pathways...