Biology subjects

Favre, C.

Publications and source records attributed to Favre, C..

5 recordsLinked to original sources

bioRxiv2026

Multiscale alterations and cortex-wide organizational trends in focal cortical dysplasia

BACKGROUND AND OBJECTIVESFocal cortical dysplasia (FCD) is a leading cause of surgically remediable pharmaco-resistant epilepsy. Previous research has used various MRI sequences to profile FCD lesions, but multi-site studies using personalized features derived from sequences routinely used in the clinic are sparse. This study aimed to quantify changes in cortical morphology, myeloarchitecture, and function within FCD lesions, compare MRI signatures between lesion subtypes and outcomes, and investigate links to macroscale brain organization. METHODSThis cross-sectional study included patients with FCD-related epilepsy aggregated across 3 datasets from Canada and Germany. The 3T MRI acquisitions included T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, with the addition of a resting-state functional sequence for two datasets. We derived cortex-wide maps of patient-specific variations in morphology, myeloarchitecture, and function. Variations were quantified in lesions, ipsilateral cortex, and homotopic regions using age- and sex-adjusted normative models. Subgroup analyses explored the role of histological subtype and surgical outcome. Variations were also related to anterior-posterior and sensory-association organizational gradients. RESULTSWe included 159 patients with epilepsy and FCD (47 % female) and 183 healthy control participants (50 % female). Lesions exhibited changes in morphology (cortical thickness; FLAIR blurring) and in specific measures of depth-dependent intracortical myelin (variance and kurtosis of intracortical myelin profiles across depths), but not in local function (regional homogeneity; node strength). Spatial contextualization indicated more pronounced thickness changes in transmodal association cortices, while increased blurring of the gray-white matter interface co-localized with posterior cortical regions. FCD Type IIb lesions contained more marked changes in blurring and depth-dependent intracortical myelin (kurtosis of intracortical myelin profiles across depths) than Type IIa lesions. DISCUSSIONOur findings provide robust evidence that multiscale MRI profiling can identify FCD signatures and contribute to in-vivo subtyping. Furthermore, the novel use of myeloarchitecture profiling and contextualization with macro-scale brain gradients provides new avenues to understand intracortical alterations and the embedding of FCD lesions into broader organizational patterns.

neuroscience↗

bioRxiv2026

PKA/CIP4 SIGNALING REGULATES CIP4 RELOCATION IN ACTIVATED NATURAL KILLER CELLS

Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system that eliminate virus-infected and transformed cells through the formation of a specialized immune synapse. Effective target cell killing requires coordinated plasma membrane remodeling and dynamic reorganization of the actin and microtubule cytoskeletons, enabling centrosome polarization and directed secretion of lytic granules. The scaffold protein CIP4 has emerged as an important regulator of cytoskeletal coordination in NK cells, yet how its subcellular localization is controlled during NK cell activation is unknown. CIP4 contains a unique protein kinase A (PKA) phosphorylation site (threonine 225, T225) within its F-BAR domain, a domain that mediates interactions with microtubules and the plasma membrane. We hypothesized that localized PKA signaling controls CIP4 redistribution during immune synapse assembly. To test this hypothesis, we analyzed CIP4 localization and phosphorylation in NK cells engaged with sensitive target cells using biochemical and imaging approaches. We show that NK-target cell interaction enhances PKA activity and promotes phosphorylation of CIP4, coinciding with its delocalization from microtubules and accumulation at the immune synapse. Importantly, this relocalization process requires the PKA-anchoring protein AKAP350, which positions PKA and CIP4 within the same protein complex, thereby facilitating CIP4 phosphorylation. Consistently, pharmacological inhibition of PKA prevented CIP4 delocalization from microtubules and reduced its accumulation at the immune synapse. The non-phosphorylatable CIP4 mutant T225A displayed increased association with microtubules compared with a phosphomimetic mutant, identifying phosphorylation at T225 as a key determinant of CIP4 spatial regulation. Together, these findings identify a signaling mechanism that links compartmentalized PKA activity to the spatial control of CIP4 during immune synapse formation, providing new insight into the molecular mechanisms governing immune synapse maturation.

immunology↗

bioRxiv2026

Hierarchical Signatures of Language in the Human Brain

Language relies on a hierarchy of sensory and cognitive processes, yet how different levels of this hierarchy are supported by distinct neural architectures remains unclear. Here we show that semantic processing, compared with phonological processing, is associated with higher-level brain networks, as characterized by resting-state fMRI connectivity, in vivo measures of cortical myelin, and cortical types derived from a cytoarchitecture-defined reference atlas. These relationships were established using individualized ultra-high field fMRI in both English and French speakers leveraging a multi-session, multi-modal 7T MRI protocol including a language localizer. For comparison, we developed an artificial neural network, in which a representational hierarchy spontaneously emerged where phonological information was captured in earlier layers and semantic information in later layers. By integrating individualized functional mapping, neuroanatomical characterization and artificial intelligence, this study advances understanding of the neural basis of language and provides a framework for linking biological and artificial systems of communication. Significance StatementLanguage is widely described as hierarchical, yet how this functional organization is implemented in the brains biological architecture remains unclear. By combining ultra-high field, individualized neuroimaging with in vivo measures of cortical microstructure and large-scale connectivity, this study establishes a framework for linking distinct levels of linguistic computation to the brains structural and functional organization. Integrating these findings with artificial neural network modeling further reveals shared principles between biological and machine systems. Together, this work advances a biologically grounded account of language, bridges cognitive neuroscience and artificial intelligence, and provides a roadmap for understanding how complex cognition emerges from structured brain architecture.

neuroscience↗

bioRxiv2025

CLASP1/2 REGULATE IMMUNE SYNAPSE MATURATION IN NATURAL KILLER CELLS

Natural killer (NK) cells are the first line of defense against viral infections and tumors. Their cytotoxic activity relies on the formation of an immune synapse (IS) with target cells. The lymphocyte function-associated antigen (LFA)-1 plays a central role in NK cell cytotoxicity by modulating NK-IS assembly and maturation. LFA-1 organization at the IS involves a Golgi-dependent mechanism, which has not been completely elucidated. CLIP-associating proteins (CLASP) 1/2 are microtubule plus-tip interacting proteins that control the dynamics of Golgi derived microtubules (GDMTs). In the present study, we found that CLASP1/2 depletion impaired LFA-1 organization at the IS and inhibited the polarization of the centrosome and the lytic granules towards the target cell. Our results also revealed the role of the Golgi apparatus as a microtubule organizing center (MTOC) in these cells. Furthermore, we found that, similarly to what was described in other cell types, NK cells require CLASP1/2 and AKAP350 for efficient nucleation of microtubules at the Golgi. Overall, this study uncovers the role of CLASP1/2 in the maturation of the lytic IS in NK cells, and presents evidence supporting the contribution of GDMTs in this process. Summary sentenceThe Golgi apparatus (GA) functions as a microtubule-organizing center (MTOC) in NK cells. During the recognition of tumoral cells by NK cells, CLASP1/2-mediated stabilization of GA-derived microtubules (GDMTs) facilitates vesicular LFA-1 (LFA-1v) trafficking toward the interaction surface, thereby promoting the immune synapse (IS) maturation.

immunology↗

bioRxiv2020

AKAP350 REGULATES CYTOSKELETON REMODELLING AND LFA-1 ORGANIZATION DURING NK CYTOLYTIC RESPONSE

The elimination of transformed and viral infected cells by natural killer (NK) cells requires the formation of a specialized junction between NK and target cells, generally denominated immunological synapse (IS). After initial recognition, the IS enables the directed secretion of lytic granules content into the susceptible target cell. The lymphocyte function-associated antigen (LFA)-1 regulates NK effector function by enabling NK-IS assembly and maturation. The pathways underlying LFA-1 accumulation at the IS in NK cells have not been elucidated so far. A kinase anchoring protein 350 (AKAP350) is a centrosome/Golgi associated protein with a central role in the regulation of Golgi organization and microtubule dynamics. In T cells, AKAP350 participates in LFA-1 activation by mechanisms that remain elusive. We first investigated AKAP350 participation in NK cytolytic activity. Our results showed that the decrease in AKAP350 levels by expression of specific shRNAs (AKAP350KD) inhibited NK-YTS cytolytic activity, without affecting NK:target cell conjugate formation. The impairment of NK effector function in AKAP350KD cells correlated with decreased LFA-1 clustering and defective IS maturation. AKAP350KD cells that were exclusively activated via LFA-1 showed impaired LFA-1 organization and deficient lytic granule translocation as well. In NK AKAP350KD cells, activation signaling through Vav1 was preserved up to 10 min of interaction with target cells, but significantly decreased afterwards. Experiments in YTS and in ex vivo NK cells revealed the existence of an intracellular pool of LFA-1 vesicles, which partially associated with the Golgi apparatus. Upon NK cell activation, this LFA-1 pool redistributed to the IS in a Golgi-AKAP350-dependent manner. Disruption of Golgi integrity or alteration of microtubule dynamics impaired LFA-1 localization at the IS. Therefore, this study reveals the existence of a Golgi/AKAP350 dependent trafficking pathway for LFA-1, which is relevant for LFA-1 organization at NK-lytic IS and, concomitantly, for NK cytolytic function.

cell biology↗