Biology subjects

Ricci, M.

Publications and source records attributed to Ricci, M..

9 recordsLinked to original sources

bioRxiv2026

Non-syndromic autism-associated SCN2A variants selectively exert dominant-negative effects on NaV1.2 channels.

The voltage-gated Na+ channel Nav1.2 has a key role for the initiation and propagation of action potentials and therefore in neuronal excitability in brain development and function. Genetic variants of the encoding gene SCN2A cause various neurodevelopmental phenotypes with infantile-childhood onset. Here, we investigated the functional impact on hNav1.2 function of 15 variants associated with pure non-syndromic ASD (nsASD), ASD with epileptic activity, developmental and epileptic encephalopathy or schizophrenia. Only nsASD variants caused a complete loss of function hNav1.2 channels when expressed alone in tsA-201 cells and cultured neocortical neurons. Co-expression of the WT and mutant channels mimicking heterozygosis revealed that ASD mutants induce a dominant negative effect. Using different strategies to impair the domains of the channels that have been suggested to be implicated in the interaction of two Nav subunits, we reversed the dominant negative effect of ASD mutants on WT channels. These findings identify in heterologous systems a mechanistically distinct class of SCN2A variants implicated in nsASD, defined by dominant-negative loss of Nav1.2 function, with potential utility as a biomarker for genetic counseling, patient stratification, and the development of precision therapeutic strategies.

neuroscience↗

bioRxiv2025

Ecology and temporal dynamics of urban Drosophila species communities as potential indicators of biodiversity decline

Understanding the impact of ecological factors on biodiversity is central in the context of accelerating climate change and biodiversity loss. Urban areas, as landscapes under particularly strong anthropogenic influence, are undergoing rapid ecological change, yet the consequences for urban biodiversity and ecosystem functioning remain poorly understood. In this study, we focused on fruit flies of the genus Drosophila - a diverse group of dipterans with variable ecological niches and degrees of synanthropy - to investigate species composition and community ecology in the metropolitan area of Vienna, Austria. With the help of numerous citizen scientists, we have collected approximately 18,000 specimens through dense spatio-temporal sampling both indoors and outdoors of human dwellings. A total of 13 Drosophila species were identified, with communities dominated by widespread cosmopolitan synanthropic species. Among these, D. mercatorum and D. virilis represent novel records for Austria. Comparisons to a previous study from more than 30 years ago revealed that the species richness in Vienna was more than 50% lower than before and showed that formerly common species were potentially replaced by neobiots. We further assessed ecological niches by intersecting species abundance data with high-dimensional, high-resolution earth observation datasets, which revealed distinct ecological preferences among species. In particular, the neozoan D. mercatorum emerged as a highly synanthropic species, tightly confined to urban areas with high levels of imperviousness. In summary, our study underpins the versatility of the Drosophila system as indicators of biodiversity loss in a rapidly changing world.

ecology↗

bioRxiv2022

A cadherin mutation in Celsr3 linked to Tourette Disorder affects dendritic patterning and excitability of cholinergic interneurons

CELSR3 encodes an atypical protocadherin cell adhesion receptor that was recently identified as a high-risk gene for Tourette disorder. A putative damaging de novo variant was inserted into the mouse genome to generate an amino acid substitution within the fifth cadherin repeat. By contrast to Celsr3 constitutive null animals, mice homozygous for the R774H amino acid substitution are viable and have grossly normal forebrain development. The density of cortical and striatal interneuron subpopulations is normal, but 3D geometric analysis of cortical pyramidal neurons and striatal cholinergic interneurons revealed changes to dendritic patterning and types and distributions of spines. Furthermore, patch clamp recordings in cholinergic interneurons located within the sensorimotor striatum uncovered mild intrinsic hyperexcitability. Despite these changes, Celsr3R774H homozygous mice do not show obvious tic-like stereotypies at baseline nor motor learning impairments, but females exhibited perseverative digging behavior. Our findings show that a human mutation in CELSR3 linked to Tourette disorder is sufficient to alter dendritic patterning in the cortex and striatum and also the intrinsic excitability of cholinergic interneurons.

neuroscience↗

bioRxiv2021

Involvement of non-LTR retrotransposons in the cancer incidence and lifespan of mammals

The presence in nature of closely related species showing drastic differences in lifespan and cancer incidence has recently increased the interest of the scientific community on these topics. In particular, the adaptations and genomic characteristics underlying the evolution of cancer-resistant and long-lived species have recently focused on the presence of alterations in the number of non-coding RNAs, on epigenetic regulation and, finally, on the activity of transposable elements (TEs). In this study, we compared the content and dynamics of TE activity in the genomes of four rodent and six bat species exhibiting different lifespans and cancer susceptibility. Mouse, rat and guinea pig (short-lived and cancer-prone organisms) were compared with the naked mole rat (Heterocephalus glaber) which is the rodent with the longest lifespan. The long-lived and cancer-resistant bats of the genera Myotis, Rhinolophus, Pteropus and Rousettus were instead compared with the Molossus, which is instead a short-lived and cancer-resistant organism. Analyzing the patterns of recent accumulations of TEs in the genome in these species, we found a strong suppression or negative selection to accumulation, of non-LTR retrotransposons in long-lived and cancer-resistant organisms. On the other hand, all short-lived and cancer-prone species have shown recent accumulation of this class of TEs. Among bats, the Molossus molossus turned out to be a very particular species and, at the same time, an important model because, despite being susceptible to rapid ageing, it is resistant to cancer. In particular, we found that its genome has the highest density of SINE (non-LTR retrotransposons), but, on the other hand, a total lack of active LINE retrotransposons. Our hypothesis is that the lack of LINEs presumably makes the Molossus cancer resistant due to lack of retrotransposition but, at the same time, the high presence of SINE, may be related to their short life span due to "sterile inflammation" and high mutation load. We suggest that research on ageing and cancer evolution should put particular attention to the involvement of non-LTR retrotransposons in these phenomena.

evolutionary biology↗

bioRxiv2021

Behavioral and nociceptor states of inflammatory painacross timescales in 2D and 3D

Ongoing pain is often driven by direct activation of pain-sensing neurons and neuroimmune mediated sensitization. These heightened states of pain alter physiology, reduce motor function, and alter motivation to engage in normal behaviors. The complexity of the pain state has evaded a comprehensive definition, especially in nonverbal animals. Here in mice, we capture the physiological state of sensitized pain neurons at different time points post-inflammation and used computational tools to automatically map behavioral signatures of evoked and spontaneous displays of pain. First, retrograde labeling coupled with electrophysiology of neurons innervating the site of localized inflammation defined critical time points of pain sensitization. Next, we used high-speed videography combined with supervised and unsupervised machine learning tools and uncovered sensory-evoked defensive coping postures to pain. Using 3D pose analytics inspired by natural language processing, we identify movement sequences that correspond to robust representations of ongoing pain states. Surprisingly, with this analytical framework, we find that a commonly used anti-inflammatory painkiller does not return an animals behavior back to a pre-injury state. Together, these findings reveal the previously unidentified signatures of pain and analgesia at timescales when inflammation induces heightened pain states.

neuroscience↗

bioRxiv2020

Quantitative properties of the creation and activation of a cell-intrinsic engram

The conditional pause in the spontaneous firing of the cerebellar Purkinje, which determines the timing of the conditional eyeblink response, is mediated by a cell-intrinsic engram (Johansson, et al. 2014) that encodes the interstimulus interval. Our trial-by-trial analysis of the pause parameters reveals that it consists of a single unusually long interspike interval, whose onset and offset latencies are stochastically independent scalar functions of the interstimulus interval. The coefficients of variation are comparable to those observed in the timing of the overt conditional eyeblink. The onsets of the long interspike interval are step changes; there is no prior build-up of inhibition. A single spike volley in the parallel fiber input triggers the read-out of the engram into the long interspike interval; subsequent volleys have no effect on the pause. The high spontaneous firing rate on which the one-interval firing pause supervenes is markedly non-stationary (Fano factors >> 1).

bioinformatics↗

bioRxiv2019

Differential involvement of EEG oscillatory components in sameness vs. spatial-relation visual reasoning tasks

The development of deep convolutional networks (DCNs) has recently led to great successes in computer vision and have become de facto computational models of vision. However, a growing body of work suggests that they exhibit critical limitations beyond image categorization. Here, we study a fundamental limitation of DCNs for judging whether two items are the same or different (SD) compared to a baseline assessment of their spatial relationship (SR). We test the prediction that SD tasks recruit additional cortical mechanisms which underlie critical aspects of visual cognition that are not explained by current computational models. We thus recorded EEG signals from 14 participants engaged in the same tasks as the computational models. Importantly, the two tasks were matched in terms of difficulty by an adaptive psychometric procedure: yet, on top of a modulation of evoked potentials, our results revealed higher activity in the low beta (13-20Hz) band in the SD compared to the SR conditions, which we surmise as reflecting the crucial involvement of recurrent mechanisms sustaining working memory and attention. Author SummaryDespite the impressive progress of deep convolutional networks (DCNs) in object recognition, recent studies demonstrated that state-of-the-art vision algorithms encounter severe limitations when performing certain visual reasoning tasks: for instance, convolutional networks can easily solve problems involving spatial relations, but fail in identifying whether two items are identical or different (same-different task). This conclusion led us to test the hypothesis that different computational mechanisms are needed to successfully perform these tasks also in the visual system. First, we confirmed in our simulations that DCNs can successfully perform spatial relationship tasks but struggle with same-different ones. Then, we tested 14 participants on the same experimental design while recording their EEG signals. Remarkably, our results revealed a significant difference between the tasks in the occipital brain regions both in evoked potentials and in the oscillatory dynamics. Specifically, an increase of activity was found when performing the SD over the SR condition. We interpret these results as reflecting the fundamental involvement of recurrent mechanisms implementing cognitive functions such as working memory and attention.

neuroscience↗

bioRxiv2017

Impact of non-LTR retrotransposons in the differentiation and evolution of Anatomically Modern Humans

Transposable Elements are biologically important components of eukaryote genomes. In particular, non-LTR retrotransposons (N-LTRrs) extensively shaped the human genome throughout evolution. In this study, we compared retrotransposon insertions differentially present in the genomes of Anatomically Modern Humans, Neanderthals, Denisovans and Chimpanzees, in order to assess the possible impact of retrotransposition in the differentiation of the human lineage. Briefly, we first identified species-specific N-LTRrs and established their distribution in present day human populations. These analyses shortlisted a group of N-LTRr insertions that were found exclusively in Anatomically Modern Humans. Notably, these insertions targeted genes more frequently than randomly expected and are associated with an increase in the number of transcriptional/splicing variants of those genes they inserted in. The analysis of the functionality of genes targeted by human-specific N-LTRr insertions seems to reflect phenotypic changes that occurred during human evolution. Furthermore, the expression of genes containing the most recent N-LTRr insertions is enriched in the brain, especially in undifferentiated neurons, and these genes associate in networks related to neuron maturation and migration. Additionally, we also identified candidate N-LTRr insertions that have likely produced new functional variants exclusive to modern humans, which show traces of positive selection and are now fixed in all present-day human populations. In sum, our results strongly suggest that N-LTRr impacted our differentiation as a species and have been a constant source of genomic variability all throughout the evolution of the human lineage.

genomics↗

bioRxiv2016

Transposable elements reveals punctuated patterns of evolution in Mammals

Transposable elements (TEs) play an essential role in shaping eukaryotic genomes and generating variability. Our \"Cold Genome\" hypothesis postulates that speciation and TEs activity are strongly related in mammals. In order to test this hypothesis, we created two new parameters: the Density of Insertion (DI) and the Relative Rate of Speciation (RRS). The DI is the ratio between the number of TE insertions in a genome and its size, whereas the RRS is a conditional parameter designed to identify potential speciation bursts. Thus, by analyzing TEs insertions in mammals, we defined the genomes as \"hot\" (low DI) and \"cold\" (high DI). Then, comparing TEs activity among 16 intra-order pairs of mammalian species, 4 superorders of Eutheria and 29 taxonomical families of the whole Mammalia class, we showed that taxa with positive RRS correlate with \"hot\" genomes, whereas taxa with negative RRS correlate with \"cold\" genomes. In addition, our study supports the \"Punctuated Equilibria\" theory in mammals for both adaptive radiation and stasis.

evolutionary biology↗