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Biology subjects

Segura, E.

Publications and source records attributed to Segura, E..

7 recordsLinked to original sources

Characterizing reward sensitivity to natural singing: an individual differences approach

Singing is an innate human behaviour present across cultures and the lifespan. Despite lacking direct biological advantages, its ubiquity suggests that it is intrinsically rewarding. This research aimed to investigate the underlying factors that explain variability in sensitivity to deriving reward and enjoyment from natural singing in the general population. In Study 1 (n = 606), an initial pool of items describing daily, non-professional singing behaviours were administered to an international adult sample. Exploratory factor analysis revealed a unidimensional structure of 20 items with acceptable model fit, organized into five facets representing distinct domains of singing-related rewards: 1) pleasure and emotional evocation, 2) social singing reward, 3) singing frequency, 4) mood regulation through singing, and 5) inattentional singing during routine tasks. In Study 2 (n = 430), confirmatory factor analysis in a new sample supported this structure. When both samples were combined (n = 1036), the unidimensional model defined by these five facets showed acceptable to excellent goodness-of-fit indices, supporting the conceptualization of singing reward as a multidimensional construct with differentiated facets. This led to the Barcelona-Aarhus Natural Singing Engagement Questionnaire (BANSEQ), which demonstrated excellent reliability ( = .94) and population-level stability. Study 3 (n = 1036) tested the convergent validity of BANSEQ with measures of music reward and engagement and identified sociodemographic and psychological correlates across the five facets of singing reward. Overall, these findings characterize the sources of individual differences in the hedonic experience of natural singing and propose BANSEQ as a robust psychometric tool for its assessment in the general population.

neuroscience↗

Comprehensive annotation of olfactory and gustatory receptor genes and transposable elements revealed their evolutionary dynamics in aphids

Understanding the molecular evolution of genes involved in parasite adaptation and the role of transposable elements (TEs) in driving their diversification is key to unraveling how populations adapt to their environments. In phytophagous insects like aphids, olfactory (OR) and gustatory receptor (GR) genes are crucial for host recognition, yet their post-duplication evolution remains insufficiently explored. Here, we analyzed 521 OR and 399 GR genes, alongside TEs, across 12 aphid genomes with varying host ranges. Aphid lineages with broader host ranges exhibited higher evolutionary rates, driven by gene family expansions linked to host interaction, including lipid metabolism, immune function, and transposase activity. The evolution of OR and GR genes post-duplication was shaped by diversifying selection, with bursts of positive selection followed by long periods of purifying selection, consistent with adaptation to new hosts. OR and GR genes originated from proximal and tandem duplications, with younger TE activity enriched near these genes compared to other genomic regions, suggesting a role for TEs in catalyzing tandem duplications and fueling diversification. The star-like topology of the OR phylogenetic tree, low synteny, and recent TE activity around OR genes support a faster evolutionary rate for ORs than GRs - a trend observed in other insect taxa. This study provides insights into molecular mechanisms underlying host adaptation in aphids and presents the first high-quality genome assembly of Dysaphis plantaginea, a major apple pest, with a comprehensive annotation of chemosensory genes and TEs. These resources offer a foundation for research on aphid genome evolution, insect-plant interactions.

molecular biology↗

Homeostatic activation of Aryl Hydrocarbon Receptor by dietary ligands dampens cutaneous allergic responses by controlling Langerhans cells migration

Dietary compounds can affect the development of inflammatory responses at distant sites. However, mechanisms involved remain incompletely understood. Here we addressed the influence on allergic responses of dietary agonists of Aryl Hydrocarbon Receptor (AhR). In cutaneous papain-induced allergy, we found that lack of dietary AhR ligands exacerbates allergic responses. This phenomenon was tissue-specific, as airway allergy was unaffected by the diet. In addition, lack of dietary AhR ligands worsened asthma-like allergy in a model of atopic march. Mice deprived of dietary AhR ligands displayed impaired Langerhans cell migration, leading to exaggerated T cell responses. Mechanistically, dietary AhR ligands regulated the inflammatory profile of epidermal cells, without affecting barrier function. In particular, we evidenced TGF-{beta} hyperproduction in the skin of mice deprived of dietary AhR ligands, explaining Langerhans cell retention. Our work identifies an essential role for homeostatic activation of AhR by dietary ligands in the dampening of cutaneous allergic responses and uncovers the importance of the gutskin axis in the development of allergic diseases.

immunology↗

Monocyte intrinsic NOD2 signalling inhibits pathogenic macrophage differentiation and its loss in inflammatory macrophages improves intestinal inflammation.

ObjectiveIt is believed that intestinal recruitment of monocytes from Crohns Disease (CD) patients who carry NOD2 risk alleles may repeatedly give rise to recruitment of pathogenic macrophages. We investigated an alternative possibility that NOD2 may rather inhibit their differentiation from intravasating monocytes. DesignThe monocyte fate decision was examined by using germ-free mice, mixed bone marrow chimeras and a culture system yielding macrophages and monocyte-derived dendritic cells (mo-DCs). We next asked whether Nod2 in either monocytes or tissue macrophages have distinct resolving properties in colitis. ResultsDespite a similar abundance of monocytes, the intestinal frequency of mo-DCs from Nod2-deficient mice was lowered independently of the changes in the gut microbiota that are caused by Nod2 deficiency. Similarly, the pool of mo-DCs was poorly reconstituted with mobilized bone marrow Nod2-deficient cells. The use of pharmacological inhibitors revealed that activated NOD2 at an early stage of development dominantly inhibits mTOR-mediated macrophage differentiation in a TNFalpha-dependent manner. These observations were supported by the identification of a TNFalpha-dependent response to MDP that is specifically lost in CD14-expressing blood cells bearing the frameshift mutation in NOD2. Accordingly, loss of NOD2 in monocytes lowers glycolytic reserve, CD115 expression and pro-resolving features. Dietary intake of aryl hydrocarbon receptor (AHR) agonists that promotes mo-DCs generation improves colitis in Nod2-deficient mice to the same extent as what is observed upon macrophage ablation of Nod2. ConclusionNOD2 negatively regulates a macrophage developmental program through a feed-forward loop that could be exploited for overcoming resistance to anti-TNF therapy in CD. Significance of this studyO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LILoss of NOD2 function is predisposing to Crohns disease. C_LIO_LIRapamycin, a serine/THR kinase inhibitor of mammalian target (mTOR) has been reported as potentially effective treatment in discrete subset of CD patients with refractory colitis. C_LIO_LIThe NOD2 protein promotes the chemokine CCL2-dependent recruitment of inflammatory monocytes in response to tissue injury. C_LIO_LIAn accumulation of CCR2-expressing monocytes and inflammatory macrophages is observed within the intestinal mucosa of CD patients including those resistant to anti-TNF therapy. C_LIO_LIActivated NOD2 enhances proinflammatory activity of CX3CR1intLy6Chi effector monocytes. C_LIO_LIThe monocyte fate toward mo-DCs is orchestrated by the aryl hydrocarbon receptor. C_LI What are the new findings?O_LINOD2 has a hierarchically dominant negative role on the mTORC-driven monocyte conversion to inflammatory macrophages independently of the changes in the gut microbiota that are caused by Nod2 deficiency. C_LIO_LIA defect in monocytes fate at the early stage allow the expansion of pathogenic macrophages in Nod2-deficient mice at the expense of mo-DC. C_LIO_LIAdoptive transfer of Nod2-deficient monocytes into wild-type mice was sufficient to exacerbate DSS-induced intestinal damage. C_LIO_LIThe glycolytic reserve of monocytes and their ability to respond to M-CSF is lowered upon loss of NOD2 signalling. C_LIO_LIDeletion of NOD2 in macrophage improves colitis to the same extent as dietary supplementation of AHR agonist in mice. C_LIO_LIThe recognition of the gut microbiota by NOD2 is required for de novo reconstitution of mo-DCs in the lamina propria of the murine intestine, while having minimal effect on the mobilization of their precursors to the intestinal mucosa. C_LI How might it impact on clinical practice in the foreseeable future?This study might contribute to the development of novel mTORC-based therapeutic strategies for improving the response to biologics by restoring the ability of circulating monocytes to reconstitute the pool of mo-DCs during homeostatic turnover and upon tissue injury. It may thereby prevent the accumulation of pathogenic macrophages in patients with loss-of-function NOD2 alleles, which fail to respond to anti-TNF and are at greater risk of developing stricturing disease.

immunology↗

High efficacy of therapeutic equine hyperimmune antibodies against SARS CoV-2 variants of concern

SARS-CoV-2 variants of concern (VoC) show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies. We tested therapeutic equine polyclonal antibodies (pAbs) against four VoC (alpha, beta, epsilon and gamma). We show that equine pAbs efficiently neutralize VoC, suggesting they are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

microbiology↗

Development and pre-clinical characterization of two therapeutic equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.

microbiology↗

Surface LSP1 is a phenotypic marker distinguishing human classical versus monocyte-derived dendritic cells

Human mononuclear phagocytes comprise several subsets of dendritic cells (DCs), monocytes and macrophages. Distinguishing one population from another is challenging, especially in inflammed tissues, due to the promiscuous expression of phenotypic markers. Using a synthetic library of humanized llama single domain antibodies, we identified a novel surface marker for human naturally-occuring monocyte-derived DCs. Our antibody targets an extra-cellular domain of LSP-1, specifically on monocyte-derived DCs, but not on monocytes, macrophages or classical DCs. Using this antibody, we provide evidence that the recently described blood DC3 population does not correspond to circulating monocyte-derived DCs. Our findings will pave the way for a better characterization of human mononuclear phagocytes in pathological settings.

immunology↗