Biology subjects

Ferrer, E.

Publications and source records attributed to Ferrer, E..

5 recordsLinked to original sources

bioRxiv2026

Brain Kappa Opioid Receptor Availability Across Stress and Social Buffering Conditions: A Positron Emission Tomography Study in Coppery Titi Monkeys

Social connectedness strongly influences health and longevity, and adult pair bonds provide psychological benefits distinct from other social relationships. Oxytocin (OT), corticotropin-releasing hormone (CRH), and opioids, play an important role in the formation and maintenance of pair bonds. Evidence suggests that OT modulates the stress response via the hypothalamic-pituitary-adrenal (HPA) axis, while the kappa ({kappa}) opioid system interacts with and may modulate OT signaling in contexts of stress and separation. In this study 20 coppery titi monkeys were exposed to a physical stressor under three social conditions: baseline (no stressor, partner present), stress (stressor, no partner present) and buffering (stressor, partner present). We predicted stress-induced dynorphin release would reduce {kappa}-opioid receptor availability measured via [{superscript 1}{superscript 1}C]GR103545 Positron Emission Tomography (PET) and lower cerebrospinal fluid (CSF) OT, whereas partner presence would mitigate dynorphin release and increase CSF OT, with reduced dynorphin inferred from higher {kappa}-opioid receptor radioligand binding. Our results show condition-dependent differences in [{superscript 1}{superscript 1}C]GR103545 binding in several brain regions, including the amygdala and hippocampus, with altered binding in both the stress and social buffering conditions. Cortisol levels were elevated in the stress condition compared to baseline. Females exhibited lower CSF OT levels during stress than at baseline, whereas plasma OT levels did not differ across conditions or between sexes. Spearman correlations revealed no significant associations between plasma and CSF OT. Together, these findings highlight the complex interaction between {kappa}-opioid signaling, OT, and HPA axis activity in the context of social relationships and highlight neuroendocrine mechanisms underlying stress regulation in pair-bonded species.

neuroscience↗

bioRxiv2025

TL1A-activated T cells remodel the rectal mucosa in Crohn's disease patients with perianal fistulizing disease

BackgroundPerianal fistulizing disease (PFD) is a complication that affects about 20% of Crohns disease (CD) patients whose etiology remains unknown. ObjectivesTo identify predisposing events driving fistula formation. DesignRectal biopsies from CD patients with or without PFD (CD+PFD and CD, respectively; n=31) were collected and subjected to single-cell RNA sequencing (scRNA-seq). Functional analyses were conducted using peripheral CD3+ T cells, intestinal tissue explants, primary fibroblasts and 2D-epithelial monolayer cell cultures. ResultsThe rectal mucosa of CD+PFD patients is imprinted with cellular and transcriptomic alterations specific to PFD and independent of luminal inflammation, potentially driven by TL1A activation in CD4+ T cells. We identified lymphotoxin beta (LTB or its functional heterotrimer LT1{beta}2) as a novel mediator downstream of TL1A that, along with IL-22, induces a PFD-associated signature in rectal fibroblast and epithelial cells, respectively. This signature includes an increased abundance of fibroblasts, an induction of matrix-degrading enzymes, transcriptomic rewiring of the lamina propria S1 fibroblasts, and an anti-bacterial and immune responses in epithelial cells. Notably, the induction of LT1{beta}2 and IL-22 occurs independently of TNF signaling, revealing a new TL1A-LT1{beta}2/IL-22 axis that remains active under anti-TNF therapy. ConclusionOur findings revealed unique cellular alterations in the rectum of CD patients with PFD, highlighting the previously unrecognized involvement of TL1A in mediating this signature and supporting the need for exploring the role of TL1A inhibition as a therapeutic approach for PFD.

immunology↗

bioRxiv2022

Development of human lateral prefrontal sulcal morphology and its relation to reasoning performance

Previous findings show that the morphology of folds (sulci) of the human cerebral cortex flatten during postnatal development. However, previous studies did not consider the relationship between sulcal morphology and cognitive development in individual participants. Here, we fill this gap in knowledge by leveraging cross-sectional morphological neuroimaging data in the lateral prefrontal cortex (LPFC) from individual human participants (6-36 years old, males and females; N = 108; 3672 sulci), as well as longitudinal morphological and behavioral data from a subset of child and adolescent participants scanned at two timepoints (6-18 years old; N = 44; 2992 sulci). Manually defining thousands of sulci revealed that LPFC sulcal morphology (depth, surface area, gray matter thickness, and local gyrification index) differed between children (6-11 years old)/adolescents (11-18 years old) and young adults (22-36 years old) cross-sectionally, but only cortical thickness showed both cross-sectional differences between children and adolescents and presented longitudinal changes during childhood and adolescence. Furthermore, a data-driven approach relating morphology and cognition identified that longitudinal changes in cortical thickness of four rostral LPFC sulci predicted longitudinal changes in reasoning performance, a higher-level cognitive ability that relies on LPFC. Contrary to previous findings, these results suggest that sulci may flatten either after this time frame or over a longer longitudinal period of time than previously presented. Crucially, these results also suggest that longitudinal changes in the cortex within specific LPFC sulci are behaviorally meaningful--providing targeted structures, and areas of the cortex, for future neuroimaging studies examining the development of cognitive abilities. Significance StatementRecent work has shown that individual differences in neuroanatomical structures (indentations, or sulci) within the lateral prefrontal cortex (LPFC) are behaviorally meaningful during childhood and adolescence. Here, we describe how specific LPFC sulci develop at the level of individual participants for the first time--from both cross-sectional and longitudinal perspectives. Further, we show, also for the first time, that the longitudinal morphological changes in these structures are behaviorally relevant. These findings lay the foundation for a future avenue to precisely study the development of the cortex and highlight the importance of studying the development of sulci in other cortical expanses and charting how these changes relate to the cognitive abilities those areas support at the level of individual participants.

neuroscience↗

bioRxiv2021

Cytogenetic evidence supports Avena insularis being closely related to hexaploid oats.

Cytogenetic observations, phylogenetic studies and genome analysis using high-density genetic markers have suggested a tetraploid Avena species carrying the C and D genomes (formerly C and A) to be the donor of all hexaploid oats (AACCDD). However, controversy surrounds which of the three extant CCDD tetraploid species - A. insularis, A. maroccana and A. murphyi - is most closely related to hexaploid oats. The present work describes a comparative karyotype analysis of these three CCDD tetraploid species and two hexaploid species, A. sativa and A. byzantina. This involved the use of FISH with six simple sequence repeats (SSRs) with the motifs CT, AAC, AAG, ACG, ATC and ACT, two repeated ribosomal sequences, and C genome-specific repetitive DNA. The hybridization pattern of A. insularis with oligonucleotide (AC)10 was also determined and compared with those previously published for A. sativa and A. byzantina. Significant differences in the 5S sites and SSR hybridization patterns of A. murphyi compared to the other CCDD species rule out its being directly involved in the origin of the hexaploids. In contrast, the repetitive and SSR hybridization patterns shown by the D genome chromosomes, and by most of the C genome chromosomes of A. maroccana and A. insularis, can be equated with the corresponding chromosomes of the hexaploids. Several chromosome hybridization signals seen for A. insularis, but not for A. maroccana, were shared with the hexaploid oats species, especially with A. byzantina. These diagnostic signals add weight to the idea that the extant A. insularis, or a direct ancestor of it, is the most closely related progenitor of hexaploid oats. The similarity of the chromosome hybridization patterns of the hexaploids and CCDD tetraploids was taken as being indicative of homology. A common chromosome nomenclature for CCDD species based on that of the hexaploid species is proposed.

plant biology↗

bioRxiv2020

Clonal expansion of personalized anti-tumor T cells from circulation using tumor organoid-immune co-cultures

Tumor-specific cytotoxic T cells are effective tools for cancer immunotherapy, but the ability to generate them continues to be a challenge. Furthermore, there are no compelling approaches to empirically identify tumor-targeting T cells and T cell receptors by exploiting the multitude of antigens on tumor cell surfaces. Here, we use patients peripheral blood and autologous tumor organoids to enrich tumor-specific cytotoxic T cells with patient-specific killing mechanisms and a tissue-resident memory phenotype. We further demonstrate that these organoid-primed T (opT) cells undergo several orders of magnitude of clonal expansion and express T cells receptors and check-point proteins unique to each patient. Importantly, transferring the TCRs to heterologous T cells was sufficient to confer tumor recognition in a patient-specific manner. Thus, we report a patient-specific and antigen-agnostic platform for expansion of tumor-targeting T cells and identification of cancer-targeting TCRs from the peripheral blood of pancreatic cancer patients that can be exploited for immunotherapy applications.

cancer biology↗