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Lacasa, L.

Publications and source records attributed to Lacasa, L..

4 recordsLinked to original sources

Activation of IL-17+ ILC subsets in IL-18R-deficient mice during fungal allergen exposure

Group 2 innate lymphoid cells (ILC2s) are critical players during type 2 inflammation present in most forms of asthma. ILC2s are tissue-resident cells that produce cytokines IL-5 and IL-13 critical to eosinophilic airway inflammation, mucus production, remodeling, and hyperresponsiveness. Though each ILC subset (ILC1s, ILC2s, ILC3s) is identified by specific transcription factors, cell surface receptors and cytokine profiles, functional plasticity between ILC subtypes occurs in various contexts. IL-18/IL-18R loci SNPs are linked to asthma in multiple genome-wide association studies and IL-18 has been shown to promote plasticity in ILC2s. Despite this, little is known about the in vivo role of IL-18/IL-18R on ILC2 responses in the lung. Within hours after mice were exposed to the fungal allergy Alternaria alternata, airway levels of IL-18 and IL-18 receptor expression increased on ST2+ ILCs. Single-cell RNA sequencing of lung cells from Alternaria-challenged mice showed that Il18 was largely expressed by alveolar macrophages, while IL-18R was highly expressed in IL-13+ILC2s. Utilizing IL-18 receptor knock-out mice (IL- 18R-/-), we observed increases in IL-17A production from both ST2+ and ST2-negative ILCs compared to control mice. We further observed an early increase in dual production of IL-5 and IL-17A in ST2+ ILCs followed by enhanced lung eosinophilia in the absence of IL-18R. Together, our findings suggest that IL-18 signaling prevents IL-17A production from ILC2s and subsequent eosinophilia in vivo. A further understanding of the regulation of ILC plasticity may lead to novel therapeutic targets in the treatment of ILC-driven asthma.

immunology↗

NAc-DBS selectively enhances memory updating without effect on retrieval

Deep brain stimulation (DBS) has emerged as a widely used therapeutic option when pharmacological treatments prove ineffective or refractory for psychiatric patients. The nucleus accumbens (NAc) represents a frequently targeted site in DBS interventions due to its demonstrated safety profile and therapeutic efficacy in obsessive-compulsive disorder, major depression, and anorexia nervosa. However, limited mechanistic understanding hampers its broader clinical applicability. This study sought to delineate the distinct behavioural dimensions modulated by NAc-DBS, its impact on distinct facets of memory, and to elucidate the underlying brain-network mechanism of action. We developed a novel spatial navigation task for rats and employed a high-dimensional behavioural analysis complemented by fMRI to dissect the cognitive, behavioural and neurobiological effects of NAc-DBS. Active NAc-DBS produced a selective enhancement of long-term memory encoding without affecting memory recall or working memory. We found no effect of NAc-DBS on motor, appetitive or stress-related behaviours. Sustained neuronal activation in the NAc, septum, entorhinal and insular cortex demonstrated no desensitization to chronic NAc-DBS, which triggered a functional reorganization among dopaminergic-related structures. These findings suggest that NAc-DBS induces a functional reorganization in the mesocorticolimbic system, potentially mimicking a dopaminergic novelty signal to enhance memory updating. This provides a mechanistic basis for the therapeutic use of NAc-DBS, particularly in improving cognitive flexibility in psychiatric disorders.

neuroscience↗

The architecture of multifunctional ecological networks

Understanding how biotic interactions affect ecosystem functioning has been a research priority in natural sciences due to their critical role in bolstering ecological resilience1-3. Yet, traditional assessment of ecological complexity typically focus on species-species effective interactions that mediate a particular function (e.g. pollination4 or seed dispersal5), overlooking the synergistic effect of multiple functions that further underpin species-function and function-function interactions in multifunctional ecosystems. At the same time, while ecological network theory holds a potential to quantify the relationship between biodiversity and ecosystem multifunctionality6, 7, its connection has been done mainly conceptually, due to challenges measuring different interactions and establishing their relevance across multiple niche dimensions8, 9. Such lack of quantitative studies therefore limits our ability to determine which species and interactions are important to maintain the multiple functions of ecosystems10. Here we develop a framework -derived from a resource-consumer-function tensor analysis-that bridges these gaps by framing biodiversity-ecosystem multifunctionality in terms of multilayer ecological network theory. Its application to recently collected ecological data -- reporting weighted interactions between plants, animals and fungi across multiple function types--allows to (i) unveil and quantify the existence of both (multi-functional) keystone species and a dual function keystoneness pattern, and (ii) project plants and functions into a similarity space where clear clusters emerge and the importance of weak links is manifested. This dual insight from species and functional perspectives will better guide conservation efforts to reduce biodiversity loss.

ecology↗

Visibility graphs for fMRI data: multiplex temporal graphs and their modulations across resting state networks

Visibility graphs have proved a convenient tool to describe the dynamics of time series, finding applications across several disciplines. Recently an approach has been proposed to extend this framework to multivariate time series, allowing a novel way to describe collective dynamics. Here we test their application to fMRI time series and give some explanation on why we think that its an interesting thing to do.

neuroscience↗