Biology subjects

Vidal, J.

Publications and source records attributed to Vidal, J..

7 recordsLinked to original sources

bioRxiv2026

Sodium tungstate promotes vascularization to support beta bell replacement in diabetes

Insufficient vascularization remains a major obstacle to the success of cell-based therapies for diabetes. Building on prior findings that loss of the phosphatase PTP1B enhances VEGFA production and improves graft vascularization, we investigated sodium tungstate (NaW), a pharmacological phosphatase inhibitor, as a strategy to improve transplantation outcomes. Using human fibroblast-derived insulin-producing cells and human stem cell-derived islets transplanted into the anterior chamber of the eye in immunodeficient mice, we show that NaW treatment significantly increases both vascularized area and insulin-positive tissue area, while reducing apoptosis within transplanted cells. Mechanistically, NaW upregulates VEGFA expression in transplanted cells and amplifies VEGFA-induced endothelial cell proliferation, migration, and tubulogenesis via MAPK/ERK signalling. These dual effects, which encompass stimulating both endocrine and endothelial compartments, lead to enhanced integration and function of transplanted cells. Importantly, the pro-angiogenic effects of NaW occur independently of exogenous endothelial cell supplementation, relying solely on the hosts endogenous endothelial cells. These findings position NaW, and potentially other phosphatase inhibitors, as promising adjuncts to improve vascularization, survival, and therapeutic efficacy in clinical cell-based transplantation protocols for diabetes. One-sentence summaryProangiogenic role of sodium tungstate in transplantation

physiology↗

bioRxiv2026

Uncovering the function of Wisp1 in whole-body glucose homeostasis: insights from Wisp1 knockout mice

WNT1-inducible signaling pathway protein 1 (Wisp1/CCN4) is a matricellular protein implicated in inflammation and metabolic dysfunction in obesity, yet its role in whole-body glucose metabolism remains unclear. In this study, Wisp1 knockout (KO) mice were analysed under physiological and high-fat (HF) diet conditions to define its impact on metabolic regulation. Neither physiological nor HF diet conditions revealed an effect of Wisp1 deficiency on whole-body glucose tolerance. However, male KO mice on a HF diet exhibited enhanced insulin sensitivity, lower insulin levels, and a marked reduction in adipose tissue inflammation, as evidenced by diminished macrophage infiltration and decreased pro-inflammatory cytokine expression in visceral fat. Additionally, beta cell mass expansion was attenuated in KO mice under HF diet, aligning with lower macrophage infiltration in islets. These findings suggest that improved insulin sensitivity in KO mice occurs independently of changes in glucose tolerance, likely due to mitigated adipose tissue inflammation. Thus, Wisp1 primarily modulates local adipose inflammatory responses, indirectly affecting islet adaptation to metabolic stress, rather than serving as a direct regulator of systemic glucose homeostasis.

physiology↗

bioRxiv2025

Multiple task-demands flexibly optimize neural geometry in human ventral temporal cortex

A hallmark of human intelligence is the ability to perform multiple tasks immediately upon instruction. Yet, the neural processes that implement such flexibility remain unclear. Using intracranial electrophysiology in epilepsy patients, we examined how representational geometries evolve as participants switched among three tasks - individuation, categorization, and conceptualization - on a trial-by-trial basis. Although tasks differed in the required representational geometries, neural representations across cortex were not immediately optimized following task cues. Instead, task-tailored geometries emerged gradually over successive stimulus repetitions within a trial. Ventral temporal cortex was the only region to exhibit task-specific adjustments for all three tasks, dynamically transforming within- and between-category distances in line with task demands. Importantly, these gradual representational changes were behaviorally relevant, predicting trial-level performance. Our results show that behavioral flexibility is supported by incremental, task-dependent refinement of representational geometry already within sensory cortex - far earlier in the processing hierarchy than previously thought.

neuroscience↗

bioRxiv2025

Reading about sensations recruits the posterior insula: An intracranial EEG study

When we read, how do words and sentences become concepts? Contrary to theoretical perspectives that conceptualize meaning and concepts as symbolic and abstract, embodied approaches propose that semantic access relies on mental simulations of bodily experiences□associated with the word’s meaning (e.g., simulating the act of running when we read the word ‘run’ or feeling pain when reading the word ‘burn’). If this view of cognition underpins conceptual processing, then sensory and motor cortices should play an early role during language comprehension. To test this idea, we recorded intracranial neural activity (High-Frequency Activity, 50–150 Hz) in epileptic patients while they read short sentences from different semantic categories: abstract-, action- and sensation-related. We hypothesized that reading sensation-related sentences (e.g., “he burns me”) would preferentially involve the posterior insula — a key region for processing affective and painful sensations. Our results, revealed an early functional dissociation between the anterior and posterior insula: the anterior insula showed a non-selective response across all semantic categories, whereas the posterior insula presented an early selective response (around 170 ms) for the sensation-related ones. Furthermore, the intensity of this selective neural response in the posterior insula correlated with the intensity of subjective perceived pain. These results provide direct intracranial evidence suggesting that language is deeply rooted in body-environment interactions.

neuroscience↗

bioRxiv2024

Odor-induced persistent neural activity in associativeencoding in humans

This study explored the impact of brief exposure to odor cues on sustained neural activity during a 6-second delay period before memory encoding of a picture image. Combining univariate and multivariate ERP analytical approaches, our results align with nonhuman data, indicating that odor cues induced sustained neural activity in humans, persisting beyond the odor exposure throughout the nearly 6-second delay period. We observed higher amplitude of sustained ERPs for unpleasant compared to pleasant odor cues. Additionally, participants exhibited more confident memory recall for pictures preceded by unpleasant rather than pleasant odor cues during encoding, underscoring the influence of brief odor cues on memory formation for temporally distant events. In conclusion, this study revealed that brief exposure to odor cues induced sustained neural activity in humans, with distinct effects on memory formation along the pleasantness dimension, emphasizing the lasting impact of olfactory stimuli on cognitive processes.

neuroscience↗

bioRxiv2022

A novel mechanism for left-right asymmetry establishment involving tissue remodeling and MyoID

Left-right asymmetries have repeatedly evolved in diverse animals and affect the position, shape or size of specific organs. How novel left-right asymmetries arise remains unknown. Here, we examined Drosophila pachea, where males have evolved unique asymmetric genitalia lobes and a right-sided copulation posture in the past 3-6 million years. We found that male asymmetric lobes grow in pupae during a 360{degrees} clockwise genitalia rotation, a conserved and widespread developmental process in flies. Using two complementary approaches, drug application and a CRISPR-induced MyoID mutant, we altered genitalia rotation and found that asymmetric lobe sizes depend on genitalia rotation completion, while the sidedness of lobe asymmetry is determined by the rotation direction. We then investigated the impact of genital asymmetry on copulation posture. Males with reversed genital asymmetry still mate in the typical right-sided posture, indicating that right-sided behavior is not determined by asymmetric male genitalia. Our study reveals that a novel genitalia asymmetry has evolved through the co-option of a pre-existing tissue remodeling process. Tissue rotation represents a new mechanism, through which a bilateral organ can acquire a left-right size asymmetry. Summary statementHow asymmetric shapes evolve from symmetry is an important question in developmental biology. Using a juvenile hormone derivative, transgenics and CRISPR mutants in the non model species Drosophila pachea, we uncover that the developmental process of male genitalia rotation got co-opted during evolution of D. pachea to determine the extent and direction of a novel genital left-right asymmetry.

evolutionary biology↗

bioRxiv2021

Direct reprogramming of human fibroblasts into insulin-producing cells by transcription factors

Direct lineage reprogramming of one somatic cell into another bypassing an intermediate pluripotent state has emerged as an alternative to embryonic or induced pluripotent stem cell differentiation to generate clinically relevant cell types. One cell type of clinical interest is the pancreatic {beta} cell that secretes insulin and whose loss and/or dysfunction leads to diabetes. Generation of functional {beta}-like cells from developmentally related somatic cell types (pancreas, liver, gut) has been achieved via enforced expression of defined sets of transcription factors. However, clinical applicability of these findings is challenging because the starting cell types are not easily obtainable. Skin fibroblasts are accessible and easily manipulated cells that could be a better option, but available studies indicate that their competence to give rise to {beta} cells through similar direct reprogramming approaches is limited. Here, using human skin fibroblasts and a protocol that ensures high and consistent expression of adenovirus-encoded reprogramming factors, we show that the transcription factor cocktail consisting of Pdx1, Ngn3, MafA, Pax4 and Nkx2-2 activates key {beta} cell genes and down-regulates the fibroblast transcriptional program. The converted cells produce insulin and exhibit intracellular calcium responses to glucose and/or membrane depolarization. Furthermore, they secrete insulin in response to glucose in vitro and after transplantation in vivo. These findings demonstrate that transcription factor-mediated direct reprogramming of human fibroblasts is a feasible strategy to generate insulin-producing cells.

developmental biology↗