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Ibanez, C.

Publications and source records attributed to Ibanez, C..

7 recordsLinked to original sources

Involvement of the medial prefrontal cortex in food addiction: new insights from in vivo calcium Imaging

Food addiction is a multifactorial disorder characterized by a loss of control over food intake, contributing to the development of obesity. To investigate the involvement of the prelimbic (PL) medial prefrontal cortex (mPFC) in the transition to food addiction, we examined PL calcium dynamics in mice exhibiting addicted versus non-addicted behavioral phenotypes. Our behavioral results allowed the identification of two distinct subpopulations of addicted and non-addicted mice, enabling direct comparison of their neural activity profiles. Addicted and non-addicted mice showed significant differences across several PL calcium activity parameters. These findings demonstrate a strong association between PL mPFC calcium activity dynamics and key addiction criteria, highlighting a critical role of this brain region in the development of food addiction. Understanding these neurobiological differences enhances our insight into brain mechanisms underlying loss of eating control and may inform more targeted approaches for studying and ultimately treating food addiction.

neuroscience↗

Coronavirus protein interaction mapping in bat and human cells identifies molecular and genetic switches for immune evasion and replication

Coronaviruses, including SARS-CoV-2, can cause severe disease in humans, whereas reservoir hosts like Rhinolophus bats remain asymptomatic. To investigate how host-specific protein-protein interactions (PPIs) influence infection, we generated comparative PPI maps for SARS-CoV-2 and its bat-origin relative RaTG13 using affinity purification-mass spectrometry (AP-MS) in human and Rhinolophus ferrumequinum (RFe) bat cells. This approach identified both conserved and virus- and host-specific interactions that regulate infection dynamics. Notably, SARS-CoV-2 required a non-synonymous mutation in nucleocapsid to replicate in bat cells expressing human ACE2 and TMPRSS2. Analysis of the viral protein Orf9b revealed differential interactions with mitochondrial proteins Tom70 and MTARC2. A single residue difference in Orf9b between SARS-CoV-2 and RaTG13 functions as a molecular switch, weakening Tom70 binding and immune evasion in human cells while enhancing interaction with the bat-specific restriction factor MTARC2. These findings demonstrate how a single-residue substitution can reshape virus-host interactions and contribute to immune evasion and host adaptation.

systems biology↗

Applying genomic approaches to identify historic population declines in European forest bats

O_LIAnthropogenically-driven environmental changes over the past two centuries have led to severe biodiversity loss, most prominently in the form of loss of populations and individuals. Better tools are needed to assess the magnitude of these wildlife population declines. Anecdotal evidence suggests European bat populations have suffered substantial declines in the past few centuries. However, there is little empirical evidence of these declines that can be used to put more recent population changes into historic context and set appropriate targets for species recovery. C_LIO_LIThis study is a collaboration between academics and conservation practitioners to develop molecular approaches capable of providing quantitative evidence of historic population changes and their drivers that can inform the assessment of conservation status and conservation management. We generated a genomic dataset for the Western barbastelle, Barbastella barbastellus, a globally Near Threatened and regionally Vulnerable bat species, including colonies from across the species British and Iberian ranges. We used a combination of landscape genetics and approximate Bayesian computation model-based inference of demographic history to identify both evidence of population size changes and possible drivers of these changes. C_LIO_LIWe found that levels of genetic diversity increased and inbreeding decreased with increasing broadleaf woodland cover around the colony location. Genetic connectivity was impeded by artificial lights and facilitated by the combination of rivers and broadleaf woodland cover. C_LIO_LIThe demographic history analysis showed that both the northern and southern British barbastelle populations have declined by 99% over the past 330-548 years. These declines may have been triggered by loss of large oak trees and native woodlands due to shipbuilding during the early colonial period. C_LIO_LISynthesis and applications. Genomic approaches can be applied to provide a better understanding of the conservation status of threatened species, within historic and contemporary context, and inform their conservation management. This study shows how we can bridge the implementation gap and promote the application of genomics in conservation management through co-designing studies with conservation practitioners and co-developing applied management targets and recommendations. C_LI

genomics↗

Bat pluripotent stem cells reveal unique entanglement between host and viruses

Bats have evolved features unique amongst mammals, including flight, laryngeal echolocation, and certain species have been shown to have a unique immune response that may enable them to tolerate viruses such as SARS-CoVs, MERS-CoVs, Nipah, and Marburg viruses. Robust cellular models have yet to be developed for bats, hindering our ability to further understand their special biology and handling of viral pathogens. To establish bats as new model study species, we generated induced pluripotent stem cells (iPSCs) from a wild greater horseshoe bat (Rhinolophus ferrumequinum) using a modified Yamanaka protocol. Rhinolophids are amongst the longest living bat species and are asymptomatic carriers of coronaviruses, including one of the viruses most closely related to SARS-CoV-2. Bat induced pluripotent stem (BiPS) cells were stable in culture, readily differentiated into all three germ layers, and formed complex embryoid bodies, including organoids. The BiPS cells were found to have a core pluripotency gene expression program similar to that of other species, but it also resembled that of cells attacked by viruses. The BiPS cells produced a rich set of diverse endogenized viral sequences and in particular retroviruses. We further validated our protocol by developing iPS cells from an evolutionary distant bat species Myotis myotis (greater mouse-eared bat) non-lethally sampled in the wild, which exhibited similar attributes to the greater horseshoe bat iPS cells, suggesting that this unique pluripotent state evolved in the ancestral bat lineage. Although previous studies have suggested that bats have developed powerful strategies to tame their inflammatory response, our results argue that they have also evolved mechanisms to accommodate a substantial load of endogenous viral sequences and suggest that the natural history of bats and viruses is more profoundly intertwined than previously thought. Further study of bat iPS cells and their differentiated progeny should advance our understanding of the role bats play as virus hosts, provide a novel method of disease surveillance, and enable the functional studies required to ascertain the molecular basis of bats unique traits.

developmental biology↗

Adult medial habenula neurons require GDNF receptor GFRalpha1 for synaptic stability and function

The medial habenula (mHb) is an understudied small brain nucleus linking forebrain and midbrain structures controlling anxiety and fear behaviors. The mechanisms that maintain the structural and functional integrity of mHb neurons and their synapses remain unknown. Using spatio-temporally controlled Cre-mediated recombination in adult mice, we found that the GDNF receptor alpha 1 (GFR1) is required in adult mHb neurons for synaptic stability and function. mHb neurons express some of the highest levels of GFR1 in the mouse brain, and acute ablation of GFR1 results in loss of septo-habenular and habenulo-interpeduncular glutamatergic synapses, with the remaining synapses displaying reduced numbers of presynaptic vesicles. Chemo- and opto-genetic studies in mice lacking GFR1 revealed impaired circuit connectivity, reduced AMPA receptor postsynaptic currents, and abnormally low rectification index of AMPARs, suggesting reduced Ca2+-permeability. Further biochemical and proximity ligation assay studies defined the presence of GluA1/GluA2 (Ca2+-impermeable) as well as GluA1/GluA4 (Ca2+-permeable) AMPAR complexes in mHb neurons, as well as clear differences in the levels and association of AMPAR subunits in mHb neurons lacking GFR1. Finally, acute loss of GFR1 in adult mHb neurons reduced anxiety-like behavior and potentiated context-based fear responses, phenocopying the effects of lesions to septal projections to the mHb. These results uncover an unexpected function for GFR1 in the maintenance and function of adult glutamatergic synapses, and reveal a potential new mechanism for regulating synaptic plasticity in the septo-habenulo-interpeduncular pathway and attuning of anxiety and fear behaviors.

neuroscience↗

Diet diversification shapes broad-scale distribution patterns in European bats

Large-scale species distributions have been traditionally attributed to physiological traits related to abiotic factors, while behavioural features linked to biotic interactions have received little attention. We tested the relationship between trophic and spatial niche breadths through combining species distribution modelling with dietary DNA metabarcoding of over 400 bats sampled across Europe belonging to seven species. Our results point to a causality cascade between hunting plasticity, trophic niche breadth and spatial niche breadth, and thus indicate that behavioral plasticity and dietary diversification can contribute to shaping broad-scale species distributions.

ecology↗

Understanding social behaviour in mammals: Kin structure and roost fidelity in greater noctule bats

Roost fidelity is an important aspect of mammalian biology. Studying the mechanisms underlying philopatry can help us understand a species energetic requirements, ecological constraints and social organisation. Temperate bat species notably exhibit a comparatively high degree of female philopatry, resulting in maternity colonies segregated at the mitochondrial level. We focus on the greater noctule, Nyctalus lasiopterus, to study this behaviour in more depth. We make use of microsatellite data for 11 markers across 84 individuals residing in Maria Luisa Park in Seville, Spain. At the time of sampling, this urban park boasted the highest number of registered bats of this species, among which three social groups were observed to segregate spatially. We studied the distribution of pairs of individuals across filial relationship categories and relatedness estimates relative to the social group of each individual. This analysis was complemented by information on roost-use frequency among a subset of genotyped bats. We found no significant relationship between roost use and genetic distance, but there was evidence of higher group-sharing with increased levels of relatedness. Mother-daughter pairs shared the same group more often than expected, as did pairs of individuals of relatedness above 0.36. We discuss the implications of these results in terms of the behavioural ecology of temperate bats and for conservation efforts aimed at preserving them.

ecology↗