Biology subjects

Bosch, E.

Publications and source records attributed to Bosch, E..

9 recordsLinked to original sources

bioRxiv2026

Denisovan introgression left differential selection regimes in Humans and Neanderthals on the SLC30A9 gene

Signals of positive selection around the SLC30A9 gene have been reported in human populations outside Africa. Selection likely acted on a highly differentiated single-nucleotide polymorphism, rs1047626, leading to a non-synonymous substitution in the encoded zinc transporter. Because of the striking similarity between the putatively selected SLC30A9 haplotype observed in several current human populations and the Denisovan individual, previous work has proposed adaptive introgression. Yet alternative explanations, including ancient human variation, and the precise archaic source -Neanderthal or Denisovan- remained unresolved. Considering the potentially complex evolution of SLC30A9, we applied Approximate Bayesian Computation (ABC) algorithms coupled to machine learning to investigate the most plausible evolutionary origin of this substitution. After modelling different evolutionary scenarios with forward-in-time simulations, our results highlight that the most probable scenario is a Denisovan origin of the rs1047626 polymorphism. However, the allele likely introgressed into Neanderthals first and was then passed into non-African modern humans. Moreover, the derived allele frequency for rs1047626 across several African populations is consistent with back-to-Africa migrations. Finally, our ABC analyses indicate strong positive selection in East Asian populations and other out-of-Africa populations, whereas in Neanderthal populations, the selection coefficient was probably neutral or slightly deleterious.

evolutionary biology↗

bioRxiv2025

Comparative microbiome analyses reveal differences between wild populations and captive groups of the Montseny Brook Newt (Calotriton arnoldi)

The Montseny brook newt, Calotriton arnoldi, is a Critically Endangered amphibian species endemic to the Montseny Massif in Catalonia, Northeastern Spain. Due to population declines and threats to its natural habitat, an ex-situ breeding program was initiated in 2007. A key goal of the program is to ensure the survival of captive-bred individuals after reintroduction, which in amphibians heavily relies on the specimens microbiome being capable of protecting them from environmental microorganisms, especially considering the global Chytridiomycosis pandemic caused by the fungi Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). This study aims to characterize the microbiome of wild and captive specimens of Calotriton arnoldi, to identify differences in microbiome composition, and to determine their potential impact on captive-bred individuals upon reintroduction. Up to 7,438 ASVs (Amplicon Sequence Variants) were identified from 138 samples from 21 and 61 wild and captive-bred individuals, respectively. Results indicate that wild populations from different subspecies have significantly different microbiome composition, as do wild and captive-bred groups from the same subspecies. Additionally, dissimilarities in microbiome variability were only found within each subspecies, between wild and captive-bred groups. In terms of composition, certain bacteria were identified as potential markers for both wild and captive environments. Enhancing microbiome variability might improve the survival prospects of reintroduced specimens. Thus, exposing captive specimens to a more natural environment while in captivity or a soft-release procedure could potentially mitigate the absence of exposure to other bacteria and potential pathogens from their native environment.

microbiology↗

bioRxiv2025

Novel insights into the genetic architecture and mechanisms of host/microbiome interactions from a multi-cohort analysis of outbred laboratory rats

The intestinal microbiome influences health and disease. Its composition is affected by host genetics and environmental exposures. Understanding host genetic effects is critical but challenging in humans, due to the difficulty of detecting, mapping and interpreting them. To address this, we analysed host genetic effects in four cohorts of outbred laboratory rats exposed to distinct but controlled environments. We found that polygenic host genetic effects were consistent across environments. We identified three replicated microbiome-associated loci, one of which involved a sialyltransferase gene and Paraprevotella. We found a similar association in a human cohort, between ST6GAL1 and Paraprevotella, both of which have been linked with immune and infectious diseases. Moreover, we found evidence of indirect genetic effects on microbiome phenotypes, which substantially increased their total genetic variance. Finally, we identified a novel mechanism whereby indirect genetic effects can contribute to "missing heritability".

genetics↗

bioRxiv2023

Typical neural adaptation for familiar images in autistic adolescents

It has been proposed that autistic perception may be marked by a reduced influence of temporal context. Under this hypothesis, prior exposure to a stimulus should lead to a weaker or absent alteration of the behavioral and neural response to the stimulus in autism, compared to a typical population. To examine this hypothesis, we recruited two samples of human volunteers: a student sample (N=26), which we used to establish our analysis pipeline, and an adolescent sample (N=36), which consisted of a group of autistic (N=18) and a group of non-autistic (N=18) participants. All participants were presented with visual stimulus streams consisting of novel and familiar image pairs, while they attentively monitored each stream. We recorded task performance and used magnetoencephalography (MEG) to measure neural responses, and to compare the responses to familiar and novel images. We found behavioral facilitation as well as a reduction of event-related field (ERF) amplitude for familiar, compared to novel, images in both samples. Crucially, we found statistical evidence against between-group effects of familiarity on both behavioral and neural responses in the adolescent sample, suggesting that the influence of familiarity is comparable between autistic and non-autistic adolescents. These findings challenge the notion that perception in autism is marked by a reduced influence of prior exposure.

neuroscience↗

bioRxiv2022

Lysosomal calcium loading promotes arrhythmias by potentiating ryanodine receptor release

Spontaneous calcium release by ryanodine receptors (RyRs) due to intracellular calcium overload results in delayed afterdepolarisations, closely associated with life-threatening arrhythmias. In this regard, inhibiting lysosomal calcium release by two-pore channel 2 (TPC2) knockout has been shown to reduce the incidence of ventricular arrhythmias under {beta}-adrenergic stimulation. However, mechanistic investigations into the role of lysosomal function on RyR spontaneous release remain missing. We investigate the calcium handling mechanisms by which lysosome function modulates RyR spontaneous release, and determine how lysosomes are able to mediate arrhythmias by its influence on calcium loading. Mechanistic studies were conducted using a population of biophysically-detailed mouse ventricular models including for the first time modelling of lysosomal function, and calibrated by experimental calcium transients modulated by TPC2. We demonstrate that lysosomal calcium uptake and release can synergistically provide a buffering pathway of fast calcium transport, by which lysosomal calcium release primarily modulates sarcoplasmic reticulum (SR) calcium reuptake and RyR release. Enhancement of this lysosomal transport pathway promoted RyR spontaneous release by elevating the SR-junction calcium gradient. In contrast, blocking either lysosomal calcium uptake or release revealed an antiarrhythmic impact. Under conditions of calcium overload, our results indicate that these responses are strongly modulated by intercellular variability in L-type calcium current, RyR release, and SERCA reuptake. Altogether, our investigations identify that lysosomal calcium handling directly influences RyR spontaneous release by regulating the SR-junction calcium gradient, suggesting antiarrhythmic strategies and identifying key modulators of lysosomal proarrhythmic action. Statement of SignificanceDelayed afterdepolarisations arising from spontaneous RyR calcium release are an important risk factor for arrhythmogenesis. Inhibiting lysosomal calcium release by TPC2-KO reduces the propensity for ventricular arrhythmias. However, understanding downstream effects of lysosomal calcium release on spontaneous RyR release is lacking. Understanding lysosomes as arrhythmia sources requires alternative approaches to controlled laboratory techniques: these restrain variability experimentally and statistically. Our study presents two methodological novelties by focusing on calibration with experimental findings using a population of biophysically-detailed models and incorporating lysosomal mechanisms. Lysosomal calcium handling promotes RyR spontaneous release by elevating the SR-junction calcium gradient. Blocking lysosomal function uncovers an antiarrhythmic strategy. Lysosome-release proarrhythmic risk is determined by synergistic enhancements of lysosomal uptake with RyR release or L-type calcium current.

biophysics↗

bioRxiv2022

Multi-scale spatial modeling of immune cell distributions enables survival prediction in primary central nervous system lymphoma

To understand the clinical significance of the tumor microenvironment (TME), it is essential to study the interactions between malignant and non-malignant cells in clinical specimens. Here, we established a computational framework for a multiplex imaging system to comprehensively characterize spatial contexts of the TME at multiple scales, including close and long-distance spatial interactions between cell type pairs. We applied this framework to a total of 1,393 multiplex imaging data newly generated from 88 primary central nervous system lymphomas with complete follow-up data and identified significant prognostic subgroups mainly shaped by the spatial context. A supervised analysis confirmed a significant contribution of spatial context in predicting patient survival. In particular, we found an opposite prognostic value of macrophage infiltration depending on its proximity to specific cell types. Altogether, we provide a comprehensive framework to analyze spatial cellular interaction that can be broadly applied to other technologies and tumor contexts.

systems biology↗

bioRxiv2022

Functional characterization of the Met50Val substitution in SLC30A9 as a novel case of adaptive introgression in humans

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans. Author SummaryContrasting continental signatures of positive natural selection have been previously found in the human SLC30A9 gene encoding the protein ZnT9, which transports zinc across cell membranes. Here we investigate the genetic variants that have been targeted by natural selection in the surrounding region of this gene and which molecular and whole-body changes may have brought about. We found that two major SLC30A9 variant combinations (haplotypes) that are extremely frequent in Africa and East Asia, respectively, are expressed differentially. These two haplotypes also differ at one site that creates an amino acid difference at ZnT9; the version most often found outside Africa avoiding zinc overload in the endoplasmic reticulum and mitochondria and directly influencing mitochondrial activity. Moreover, we found that this substitution, which is known to be associated with greater susceptibility to several neuropsychiatric disorders, is present in the Denisova and displays accompanying patterns of variation that could be suggestive of adaptive introgression. Since mitochondria play an important role in skeletal muscle energy metabolism, we speculate that adaptation to cold may have driven this selection event outside Africa, while also impacting predisposition to neuropsychiatric disorders in modern humans.

evolutionary biology↗

bioRxiv2021

Adaptation and serial choice bias are unaltered in autism

Autism Spectrum Disorder (ASD) or autism is characterized by social and non-social symptoms, including sensory hyper- and hyposensitivities. A suggestion has been put forward that some of these symptoms could be explained by differences in how sensory information is integrated with its context, including a lower tendency to leverage the past in the processing of new perceptual input. At least two history-dependent effects of opposite directions have been described in the visual perception literature: a repulsive adaptation effect, where perception of a stimulus is biased away from an adaptor stimulus, and an attractive serial choice bias, where perceptual choices are biased towards the previous choice. In this study, we investigated whether autistic participants differed in either bias from typically developing controls (TD). Sixty-four adolescent participants (31 with ASD, 33 TD) were asked to categorize oriented line stimuli in two tasks which were designed so that we would induce either adaptation or serial choice bias. Although our tasks successfully induced both biases, in comparing the two groups, we found no differences in the magnitude of adaptation nor in the modulation of perceptual choices by the previous choice. In conclusion, we find no evidence of a decreased integration of the past in visual perception of autistic individuals.

neuroscience↗

bioRxiv2020

Opposite effects of choice history and stimulus history resolve a paradox of sequential choice bias

Perceptual decisions are biased towards previous decisions. Previous research suggests that this choice repetition bias is increased after previous decisions of high confidence, as inferred from response time measures (Urai et al., 2017), but also when previous decisions were based on weak sensory evidence (Akaishi et al., 2014). As weak sensory evidence is typically associated with low confidence, these previous findings appear conflicting. To resolve this conflict, we set out to investigate the effect of decision confidence on choice repetition more directly by measuring explicit confidence ratings in a motion coherence discrimination task. Moreover, we explored how choice and stimulus history jointly affect subsequent perceptual choices. We found that participants were more likely to repeat previous choices of high subjective confidence, as well as previous fast choices, confirming the boost of choice repetition with decision confidence. Furthermore, we discovered that current choices were biased away from the previous evidence direction, not previous choice, and that this effect grew with previous evidence strength. These findings point towards simultaneous biases of choice repetition, modulated by decision confidence, and adaptation, modulated by the strength of evidence, which bias current perceptual decisions in opposite directions.

neuroscience↗