Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement

Background: The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in TTC7A have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. Objectives: This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/phosphatidylinositol 4 kinase type III α pathway in the control of leukocyte migration and actin dynamics. Methods: Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single-cell level. Results: We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the phosphoinositide 3-kinase/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage, and increased cell death in dense 3-dimensional gels in the presence of chemokines. Conclusions: These results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients.</p

West Africa in the British Atlantic: trade, violence, and empire in the 1640s

The importance of Africa and African agency in the formation of the Atlantic world is now widely acknowledged by historians, but Africa has drawn less attention than other regions in analyses of the British Atlantic. Drawing upon the nascent methodology of global microhistory, this article contributes to a scholarly rebalancing by examining two maritime lawsuits from the 1640s concerning British voyages to Senegambia and Sierra Leone, both of which resulted in conflict between British seafarers and with their African trading partners. A close study of the documents surviving from these lawsuits provides an unusually detailed glimpse of these particular moments of contact and violence across cultures. More fundamentally, such an approach illuminates the ocean-spanning networks within which these ventures took place, and reveals the ways in which British traders and sailors perceived trade in Africa within their own legal frameworks. This article argues that by the middle of the seventeenth century, as merchants and politicians in Britain began to imagine an Atlantic empire, trade in West Africa was an important part of their vision of the Atlantic world

Le Refuge , roman

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La Folle du logis, roman / Michèle Saint-Lô

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Bulletin de l'Association pomologique de l'Ouest

19081908 (A26,FASC1).Appartient à l’ensemble documentaire : Bretagn1Appartient à l’ensemble documentaire : BNormand1Appartient à l’ensemble documentaire : HNormand1Appartient à l’ensemble documentaire : PaysLoir

Bulletin de l'Association pomologique de l'Ouest

10 octobre 19011901/10/10 (A19,FASC1)-1901/10/13.Appartient à l’ensemble documentaire : Bretagn1Appartient à l’ensemble documentaire : BNormand1Appartient à l’ensemble documentaire : HNormand1Appartient à l’ensemble documentaire : PaysLoir

Bulletin de l'Association pomologique de l'Ouest

19221922 (A41).Appartient à l’ensemble documentaire : Bretagn1Appartient à l’ensemble documentaire : BNormand1Appartient à l’ensemble documentaire : HNormand1Appartient à l’ensemble documentaire : PaysLoir

Bulletin de l'Association pomologique de l'Ouest

avril 19311931/04 (A49,N2)-1931/06.Appartient à l’ensemble documentaire : Bretagn1Appartient à l’ensemble documentaire : BNormand1Appartient à l’ensemble documentaire : HNormand1Appartient à l’ensemble documentaire : PaysLoir

Bulletin de l'Association pomologique de l'Ouest

19131913 (A31,FASC1).Appartient à l’ensemble documentaire : Bretagn1Appartient à l’ensemble documentaire : BNormand1Appartient à l’ensemble documentaire : HNormand1Appartient à l’ensemble documentaire : PaysLoir

[Monnaie. Guénar, Saint-Lô, Charles VI]

Appartient à l’ensemble documentaire : MonnFrRo