Biology subjects

Moreno, E.

Publications and source records attributed to Moreno, E..

At least 19 recordsLinked to original sources

bioRxiv2026

Expanding gmx_MMPBSA capabilities for end-state binding free energy calculations with GROMACS and AMBER

gmx_MMPBSA is an end-to-end tool for performing end-state binding free energy calculations. Here, we present advances in the gmx_MMPBSA suite that simplify preparation, expand the calculation options, and improve the analysis of results. The new features include the GBNSR6 and nonlinear PB models, second-order cumulant (C2) entropy estimation, inclusion of explicit structural waters, and multiple alanine/glycine mutations. We also introduce amber_MMPBSA, a new entry point that accepts native AMBER input files and extends the calculation and analysis capabilities of gmx_MMPBSA to AMBER users. The redesigned graphical analyzer, gmx_MMPBSA_ana, and modernized Python API facilitate exploration of large datasets and comparisons across multiple systems. We illustrate the new gmx_MMPBSA capabilities using a diverse set of biomolecular complexes (protein-protein, protein-RNA, protein-small molecule, DNA-small molecule) and show how the calculated binding energies vary across systems depending on the methodological choices. The source code is available at https://github.com/Valdes-Tresanco-MS/gmx_MMPBSA.

bioinformatics↗

bioRxiv2026

A whole-genome screen identifies a bilateral Flower-Grindelwald/TNFR-Veli/LIN-7 communication module in cell competition

Viable yet suboptimal ("loser") cells can be recognized and selectively eliminated when in the presence of neighboring fitter ("winner") cells through cell competition, thereby promoting optimal tissue fitness and homeostasis. One mechanism through which cells compare their relative fitness levels relies on isoforms of the conserved transmembrane protein Flower (Fwe). Despite the role of Fwe-dependent cell selection in several pathophysiological processes, little is known about downstream components of this pathway. In this study, we develop a versatile clonal interaction assay in Drosophila, the Easy Win Assay. By overexpressing human FWE1 Lose isoform to trigger cell competition, we perform an unbiased whole-genome RNAi screen and identify new pathway modulators. We show that the receptor Grindelwald/TNFR is necessary in either winner or loser cells to drive Eiger/TNF--independent elimination of losers, whereas the scaffolding protein Veli/LIN-7 is simultaneously required in both cell populations. We further demonstrate that Fwe, Grindelwald and Veli redistribute to establish a previously undescribed bilateral communication module at winner-loser interfaces, promoting intercellular communication and elimination of loser cells. These findings show that distinct cell elimination pathways converge on a common execution module while remaining independently regulated upstream, enabling flexible recognition and elimination of diverse damaged or dangerous cells.

cell biology↗

bioRxiv2026

Loss of NudE-mediated dynein activation at synaptic terminals causes progressive axon length-dependent neurodegeneration

Progressive, axon length-dependent degeneration of nerve terminals is a defining feature of dying-back neuropathies; yet, whether defects in axonal transport initiate or are a consequence of this process remains unresolved. Here, we show that NudE, a scaffold for dynein motor activation, is required for the initiation of retrograde axonal transport at Drosophila motoneuron synapses in vivo. Loss of NudE impairs dynein activation at the synaptic terminal, severely reducing the proportion of cargo entering retrograde transport and decreasing retrograde motor velocity. Live imaging and temporal analysis establish that this transport initiation defect is the earliest event in a degenerative cascade, followed by progressive microtubule destabilization, impaired synaptic transmission, and structural degeneration in a distal-to-proximal gradient that recapitulates dying-back neuropathies. Structure-function analysis validates the biochemically defined NudE-dynein binding domains in vivo, with graded disruption producing correspondingly graded phenotypes. Genetic two-hit experiments uncover a reciprocal dependence between transport initiation and microtubule maintenance: perturbations in either process that are individually tolerated synergistically trigger degeneration when combined, while increasing microtubule levels alone cannot compensate for failed dynein activation. These findings reveal retrograde transport initiation as a critical vulnerability point in motoneurons and provide a mechanistic basis for how defects in dynein activation produce progressive neurodegeneration.

neuroscience↗

bioRxiv2025

Cell-to-cell transmission of Brucella abortus

Brucella abortus is a persistent intracellular pathogen capable of evading early immune responses. To explore the mechanism of exit of this bacterium, we monitored Brucella infection by live cell imaging for up to 100 hours. This approach uncovered various modes of bacterial spreading, including individual organisms, bacteria-containing vacuoles, and direct transmission between cells (called cell-to-cell transmission), each fueling new infections. This dissemination occurred regardless of antibiotic presence in the extracellular milieu. While receptor blockade using heparin suppressed free bacterial infections, it promoted cell-to-cell transmission, dependent on cell density. Cells participating in intercellular transmission survived longer than their non-infected counterparts. These observations underscore the adaptability of Brucella for propagating across diverse conditions. ImportanceThe intracellular life cycle of pathogenic bacteria encompasses adhesion, invasion, intracellular replication, and eventual exit from host cells. The exit phase is a critical step for pathogen persistence and dissemination to new hosts. Despite its relevance, the egress mechanisms of Brucella spp. remain largely unexplored. In this study, we describe three distinct modes of Brucella abortus exit: individual bacteria, bacterial clumps, and through direct cell-to-cell transmission. The latter may facilitate immune evasion by bypassing extracellular exposure, thereby contributing to the stealthy survival strategy of Brucella. The presence of multiple egress mechanisms suggests that B. abortus tailors its exit strategies according to its intracellular biogenesis and environmental cues.These findings not only advance our understanding of Brucella pathogenesis but also highlight potential avenues for targeting bacterial dissemination and persistence.

microbiology↗

bioRxiv2025

Brucella abortus egresses from host cells in infective clumps through an actin-dependent mechanism

Brucella abortus is an intracellular pathogen whose cell cycle encompasses attachment, internalization, trafficking, replication, and egress from cells. While the intracellular life of Brucella has been extensively studied, the mechanisms underlying its exit from host cells are still unclear. In this work, we observed a significant increase in the formation of B. abortus containing vacuoles intracellular clumps (BCVIC) and abundant B. abortus containing vacuoles-derived extracellular clumps (BCVEC) after 72 h of infection. Membrane extensions protruding through the polymerization of actin filaments were evident in cells at later stages of infection. Purified BCVIC and BCVEC were of similar sizes and predominantly acidic. These vacuoles exhibited a compact arrangement of well-ordered bacteria, comprised of a heterogeneous population of dead and live bacteria and host components LAMP-1 and actin filaments. A proportion of BCVEC were naked, while others were enclosed within an impermeable host membrane. The actin cytoskeleton was implicated in the protrusion of BCVEC since the modulation of Rho GTPases affected the egress of BCVEC. The BCVEC protruding from cells were capable of invading non-infected cells, initiating a new cycle of infection. The topological structure and function of BCVEC underscore their significance in the Brucella life cycle as vehicles for bacterial dissemination to host cells and organs. ImportanceB. abortus is an intracellular pathogen that traffics to the endoplasmic reticulum, where it replicates. However, the mechanisms by which Brucella exits host cells and infects new ones are not fully understood. We found that protruding acidic autophagic-like vesicles containing compact, well-organized Brucella clusters are shed from cells via GTPase and actin filament recruitment. Through this process, the vesicles are impermeable to antibodies and other substances, like antibiotics, and are highly infectious to neighboring cells. This previously unreported mechanism enhances understanding of the well-known Brucella stealth strategy to evade the immune system and establish harmful, long-lasting infections.

microbiology↗

bioRxiv2025

Hbs and Rst adhesion molecules provide a regional code that regulates cell elimination during epithelial remodelling

Cell-cell interactions and mechanical forces are fundamental in shaping epithelial tissue architecture. For example, tissue compression promotes cell elimination by downregulating compaction-sensitive EGFR/ERK signalling. However, a subgroup of cells that are eliminated do not show EGFR/ERK downregulation, suggesting the involvement of additional mechanisms. Here, we conducted a multi-step RNAi screen in the Drosophila notum and identified 47 diverse regulators of epithelial remodelling. Among them, we focused on two membrane proteins, Hibris (Hbs) and Roughest (Rst), which mediate heterophilic cell adhesion. We show that Hbs and Rst exhibit region-specific expression patterns in the developing notum, showing elevated protein levels in zones of cell survival and reduced expression in regions undergoing cell pruning. Uniform knock-down of hbs and rst or homogenous overexpression of hbs, disrupts normal cell elimination during morphogenesis and results in adult tissue malformations. Remarkably, local suppression of Hbs and Rst in Hbshigh /Rsthigh territories triggers ectopic cell elimination, indicating that a surface code defined by Hbs/Rst can instruct cell removal. We further demonstrate that Hbs, but not Rst, is regulated by compaction-sensitive EGFR signalling, positioning Hbs as a potential integrator of mechanical cues and cell property signals, possibly via its interaction with Rst. These findings uncover a novel adhesive code that shapes the thorax midline and potentially other organs.

cell biology↗

bioRxiv2025

Remodeling Activity of ChAHP Restricts Transcription Factor Access to Chromatin

Transcription in eukaryotes is regulated by chromatin-based mechanisms that control nucleosome occupancy, chromatin modifications, and transcription factor binding. We have previously shown that the transcription factor ADNP forms the ChAHP complex with the chromatin remodeler CHD4 and HP1 proteins, acting as a site-specific regulator of transcription and antagonist of CTCF binding. However, the molecular basis of these functions remained unclear. Here, we demonstrate that the CHD4 subunit is essential to antagonize CTCF and silence transcription of transposons, while HP1 proteins are dispensable. Although the remodeling activity of CHD4 is not required for ChAHP chromatin association, it is critical for both transposon repression and CTCF antagonism. Our findings support a model wherein ADNP recruits chromatin remodeling activity in a sequence-specific manner, enabling transcriptional control and local modulation of chromatin architecture.

molecular biology↗

bioRxiv2025

Dietary Interventions Modulate Cell Competition and Locomotor Decline in an Alzheimer's Disease Drosophila Model

Alzheimers Disease (AD) is a neurodegenerative disorder characterised by the accumulation of Amyloid-beta 42 (A{beta}42) plaques and cognitive decline. Using Drosophila models, we investigated the impact of diet on cell competition, a process that eliminates unfit cells and is involved in AD progression. Cell competition is present in AD flies, where unfit neurons express fweLoseB and azot, leading to their elimination and motor improvements. In this study, we fed AD and control (healthy) flies with either a yeast-based diet (YBD) or a synthetic diet (SAA) for up to 28 days and evaluated cell competition at the cellular level and locomotion as behavioural output. AD flies fed with YBD exhibited a peak of cell competition at day 14 of feeding, being cyclical over time and followed by a progressive locomotion decline. In contrast, the SAA diet delayed the activation of cell competition until day 21, coinciding with locomotion restoration. Moreover, the synthetic diet postponed A{beta} formation, suggesting a slower progression of AD. Overexpression of the human Flower (hFWE) isoforms in Drosophila photoreceptors revealed their conserved function in regulating cell competition, with hFWE1 identified as the sole loser isoform in neuronal context. Conversely, hFWE2, a winner isoform, induced higher levels of cell competition in a diet-dependent manner. hFWE3 and hFWE4 induced a milder effect on cell competition but also have a winner-like function. In YBD-fed AD flies, hFWE2 failed to promote efficient elimination of unfit cells over time, as these flies exhibited even worse locomotion decline than control flies without hFWE2. In contrast with SAA, expression of hFWE2 induced better locomotion outcomes. Our data seems to indicate that diet may regulate AD progression through cell competition regulation, highlighting the complex interplay between diet, cell competition, and AD progression and providing insights into potential therapeutic strategies.

cell biology↗

bioRxiv2025

Imaging Cell Competition in Ex-Vivo Drosophila Adult Brains

Live imaging has been instrumental in understanding cellular dynamics in Drosophila tissues, but technical limitations have prevented long-term visualization of cell competition in adult brains. Here, we describe a simple ex-vivo protocol that enables extended live imaging of adult Drosophila brains for up to 32 hours. The method relies on non-supplemented Schneiders Drosophila medium and hydrophobic interactions to maintain brain stability during imaging, eliminating the need for complex culture conditions or embedding procedures. We validate this approach by studying cell competition in the optic lobes following traumatic brain injury, where cell competition is expected to occur with a peak at 48 hours after damage. We demonstrate the utility of this method by visualizing the expression of the fitness checkpoint Azot in a loser cell and its subsequent elimination. This protocol offers a versatile platform for studying cell competition and other cellular processes requiring extended observation of the adult Drosophila brain.

cell biology↗

bioRxiv2024

Heterotypic competition between cancer cells and hepatocytes generates heterogeneous context-dependent phenotypes

Competitive interactions between tumor cells and surrounding healthy cells are constantly present during the progression of a solid tumor, and their outcome has been proposed to affect the clinical behavior. Previous studies have described various mechanistic and molecular aspects that characterize this process, overall indicating that cancer cells behave as supercompetitors, which eliminate neighboring healthy cells to gain vital space for growth and infiltration of the tissue. Nevertheless, there is a lack of systematic characterization of these competitive interactions, particularly in the context of cancer in mammals. Furthermore, previous studies in the field of cell competition have primarily focused on homotypic cell competition, involving different clones of the same cell or cells deriving from the same tissue. Data are scarce regarding heterotypic cell competition between two unrelated cell types, which is particularly critical for the understanding of metastatic tumors. In this research, we study cell competition in the context of liver metastases, providing a broad characterization of this process in different relevant scenarios, including cells growing in vitro in 2D and 3D, and in vivo. Results show that in vitro, only a subset of cancer cell lines are coherently strong or moderate competitors against hepatocytes, while the remaining demonstrate poor competitiveness. The competitive proficiency can vary depending on the experimental growth system that is employed, and often predicts the phenotype of liver metastases in terms of aggressiveness and morphology. Finally, our data point towards an involvement of mechanical competition in determining the supercompetitor trait of cancer cells. Altogether, our research provides the first comprehensive characterization of heterotypic cell competition, and indicates that cancer cells possess heterogeneous competitive proficiency towards hepatocytes which can be affected by the growth conditions.

cancer biology↗

bioRxiv2024

Characterising the Modulatory Role of Ikebana in Flower-Dependent Cell Competition

Tissues encompass a quality control mechanism that promotes their optimal state. This mechanism, designated cell competition, is characterised by the elimination of suboptimal yet viable cells when they are near healthier cells within the same tissue compartment. This study explores Flower-dependent cell competition and introduces Ikebana as a novel player. The differential expression of the flower isoforms labels cells as winners or losers, influencing their fate in diverse contexts, including eye development, traumatic brain injury, and Alzheimers disease. Ikebana, ubiquitously produced in wing imaginal discs and adult brains, modulates loser cell elimination. Reduction of ikebana expression correlates with an increased number of loser cells, while its overexpression in the Alzheimers disease model reduces the number of Flower LoseB-positive cells. We suggest that Ikebana protects loser cell elimination, particularly when excessive elimination of loser cells can compromise tissue function. Thus, Ikebana might be a potential therapeutic target for modulating Flower LoseB expression.

cell biology↗

bioRxiv2024

Longitudinal analysis of Flower-dependent cell competition fitness markers in Drosophila melanogaster

Cell competition is a conserved phenomenon spanning from arthropods to humans. It involves the elimination of viable yet suboptimal "loser" cells when juxtaposed with their fitter "winner" counterparts. This process has received increased attention for its implications in cancer initiation and progression, neurodegeneration, and ageing. This study investigates the presence of the loser fitness fingerprint Flower LoseB (Fwe LB) and the fitness checkpoint Azot in the optic lobes over a period of 28 days. Notably, the absence of Azot is conventionally linked to the accumulation of loser cells over time. However, our investigation reveals that this accumulation is not perpetual and, intriguingly, Azot is not required for loser cell elimination in this context. Furthermore, we estimate that fewer than 50% of Fwe LB-expressing cells also express Azot and undergo apoptosis. Remarkably, our calculations also demonstrate that over 50% of cells undergoing apoptosis at any given time point are positive for the loser markers Fwe LB and Azot. This comprehensive analysis of fitness marker dynamics over a 28-day timeframe sheds new light on the intricate mechanisms governing Flower-dependent cell competition.

cell biology↗

bioRxiv2023

Foraging task specialization in honey bees (Apis mellifera): the contribution of floral rewards on the learning performance of pollen and nectar foragers

Social insects live in communities where cooperative actions heavily rely on the individual cognitive abilities of their members. In the honey bee (Apis mellifera), the specialization in nectar or pollen collection is associated with variations in gustatory sensitivity, affecting both associative and non-associative learning. Gustatory sensitivity fluctuates as a function of changes in motivation for the specific floral resource throughout the foraging cycle, yet differences in learning abilities between nectar and pollen foragers at the onset of recollection remains unexplored. Here, we examined nectar and pollen foragers captured upon arrival at food sources. We subjected them to an olfactory PER conditioning using a 10% sucrose solution paired (S10%+P) or unpaired (S10%) with pollen as a co-reinforcement. For non-associative learning, we habituated foragers with a 10% sucrose solution paired (S10%+P) or unpaired (S10%) with pollen, followed by dishabituation tests with either S50% or S10%+P. Our results indicate that pollen foragers show lower performance than nectar foragers when conditioned with S10%. Interestingly, performance improves to levels similar to those of nectar foragers when pollen is included as rewarding stimulus (S10%+P). In non-associative learning, pollen foragers tested with S10%+P displayed a lower degree of habituation than nectar foragers and a higher degree of dishabituation when pollen was used as the dishabituating stimulus (S10%+P). Altogether, our results support the idea that pollen and nectar honey bee foragers differ in their perception of rewards, leading to inter-individual differences in learning that contribute to foraging specialization.

animal behavior and cognition↗

bioRxiv2023

The CB1 receptor interacts with cereblon and drives cereblon deficiency-associated memory shortfalls

Cereblon/CRBN is a substrate-recognition component of the Cullin4A-DDB1-Roc1 E3 ubiquitin ligase complex. Destabilizing mutations in the human CRBN gene cause a form of autosomal recessive non-syndromic intellectual disability (ARNSID) that is modelled by knocking-out the mouse Crbn gene. A reduction in excitatory neurotransmission has been proposed as an underlying mechanism of the disease, but the intimate factors eliciting this impairment remain mostly unknown. Here we report that CRBN molecules selectively located on glutamatergic neurons are necessary for proper memory function. Combining various in vivo approaches, we show that the cannabinoid CB1 receptor (CB1R), a key suppressor of synaptic transmission, is overactivated in CRBN deficiency-linked ARNSID mouse models, and that the memory deficits observed in these animals can be rescued by acute CB1R-selective pharmacological antagonism. Molecular studies demonstrated that CRBN interacts physically with CB1R and impairs the CB1R-Gi/o-cAMP-PKA pathway in a ubiquitin ligase-independent manner. Taken together, these findings unveil that CB1R overactivation is a driving mechanism of CRBN deficiency-linked ARNSID and anticipate that the blockade of CB1R could constitute a new therapy for this orphan disease.

neuroscience↗

bioRxiv2022

The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters

A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supports further testing and optimization of NTZ-based therapy for SARS-CoV-2 infection alone and in combination with antiviral drugs.

immunology↗

bioRxiv2022

Discovery of a SARS-CoV-2 Broadly-Acting Neutralizing Antibody with Activity against Omicron and Omicron + R346K Variants

The continual emergence of SARS-CoV-2 variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant, has rendered ineffective a number of previously EUA approved SARS-CoV-2 neutralizing antibody therapies. Furthermore, even those approved antibodies with neutralizing activity against Omicron are reportedly ineffective against the subset of Omicron variants that contain a R346K substitution, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. Following a campaign of antibody discovery based on the vaccination of Harbour H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of Spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against the Omicron and Omicron + R346K variants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for use in human clinical trials.

microbiology↗

bioRxiv2021

Metabolic snapshot of plasma samples reveals new pathways implicated in SARS-CoV-2 pathogenesis

Despite of the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways related to SARS-CoV-2 susceptibility and COVID-19 clinical severity using capillary electrophoresis coupled to a time-of-flight mass spectrometer (CE-TOF-MS) in plasma samples. We included 27 patients with confirmed COVID-19 early after symptom onset who were prospectively followed and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection ( nonsusceptible). We found that the metabolite profile was predictive of the study group. We identified a total of 55 metabolites as biomarkers of SARS-CoV-2 susceptibility or COVID-19 clinical severity. We report the discovery of new plasma biomarkers for COVID-19 that provide mechanistic explanations for the clinical consequences of SARS-CoV-2, including mitochondrial and liver dysfunction as a consequence of hypoxemia (citrulline, citrate, and BAIBA), energy production and amino acid catabolism (L-glycine, L-alanine, L-serine, L-proline, L-aspartic acid and L-histidine), endothelial dysfunction and thrombosis (citrulline, L-ADMA, 2-AB, and Neu5Ac), and we found interconnections between these pathways. In summary, in this first report of the metabolomic profile of individuals with severe COVID-19 and SARS-CoV-2 susceptibility by CE-MS, we define several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression that could be developed as biomarkers of COVID-19.

biochemistry↗

bioRxiv2021

A low repeated dose of Δ9-tetrahydrocannabinol affects memory performance through serotonergic signalling in mice

Cannabis is the most widely used illicit drug worldwide. Its principal psychoactive component, {Delta}9-tetrahydrocannabinol (THC), acts as a partial agonist of the main cannabinoid receptor in the brain, the cannabinoid type-1 receptor (CB1R), that is responsible for the central effects of THC including memory impairment. CB1Rs may form heterodimers with the serotonin 5-HT2A receptor (5-HT2AR) which were found responsible for the memory impairment produced by acute high dose of THC in mice. In this study we investigated whether a repeated low dose of THC (1 mg/kg), with no acute consequence on memory performance, could eventually have deleterious cognitive effects. We found that this dose of THC impaired novel object-recognition memory and fear conditioning memory 24 h after the last of 7 consecutive daily treatments. At that time, a general enhancement of c-Fos expression was also observed in several brain regions of THC-exposed animals, as well as a decreased dendritic spine density on hippocampal CA1 pyramidal neurons that was accompanied by reduced long-term potentiation (LTP) at Schaffer collateral-CA1 synapses. Interestingly, an up-regulation in the expression of CB1R/5-HT2AR heterodimers was observed in the hippocampus after THC exposure and pre-treatment with the 5-HT2AR antagonist MDL 100,907 (0.01 mg/kg) prevented the enhanced heterodimerization and the THC-associated memory impairment. Together, these results reveal the significance of serotonergic signalling through 5-HT2ARs in the memory-impairing effects of repeated low doses of THC.

neuroscience↗