Biology subjects

Bertani, I.

Publications and source records attributed to Bertani, I..

10 recordsLinked to original sources

bioRxiv2026

A switch-rheostat circuit governs quorum sensing homeostasis in a phytopathogen

Pseudomonas fuscovaginae, a wide-host-range plant pathogen of several cereal and grass species, possesses two canonical N-acyl homoserine (AHL)-based quorum sensing (QS) systems called PfsI/R and PfvI/R, both of which are inactive under laboratory conditions but active in planta. The pfsI-pfsR intergenic region encodes for RsaM, a putative protein that has since been hypothesized to act as a repressor switch of this QS circuit. In the present study, we demonstrate that the stringent repression exerted on the PfsI/R system depends entirely on the divergent promoter/intergenic pfsR-rsaM region rather than RsaM itself. Remarkably, this regulatory switch element stringently represses the expression of both the pfsR and rsaM genes. We further show for the first time that RsaM is endogenously expressed and functions as a negative regulator modulating the PfsI/R circuit instead of preventing its activation. Taken together, our results evidence a unique two-tiered/hierarchical repression of a QS system, provided by a master repressor switch and a repressor modulator. ImportancePseudomonas fuscovaginae is a globally occurring plant pathogen that employs AHL QS to regulate virulence. In this bacterium, QS signaling circuits display a rather unusual feature: the lack of activation at high cell densities under standard laboratory conditions. A hypothetical regulator named RsaM was previously linked to this phenomenon as a repressor switch acting on the PfsI/R AHL QS system in the absence of an unknown signal or stimulus. In this study, we show that a regulatory element within the pfsR-rsaM intergenic region acts as the primary switch of the PfsI/R QS system, independently of RsaM. Conversely, RsaM functions as a post-activation modulator that fine-tunes the QS response. This study advances our understanding of the regulatory configurations of unconventional QS systems by revealing a two-tier control mechanism in which a master regulatory switch governs circuit activation, while the previously uncharacterized protein RsaM controls signaling output once the system is engaged.

microbiology↗

bioRxiv2026

Lysergic acid diethylamide reverses aging- and neurodegeneration-associated brain transcriptional programs

Psychedelic compounds such as lysergic acid diethylamide (LSD) are increasingly studied for their neuroplastic effects and potential relevance to brain aging and neurodegeneration. However, the molecular mechanisms linking psychedelic-induced plasticity to age-associated cognitive decline remain unclear. Brain aging and dementia are characterized by coordinated transcriptional programs that underlie synaptic dysfunction and altered neuron-glia interactions. If psychedelic-induced plasticity engages opposing molecular programs, it could counteract these conserved trajectories. In computational drug discovery, this concept has been formalized as the principle of transcriptional signature reversal, whereby compounds inducing gene expression states opposite to disease-associated programs may exert a therapeutic effect by counteracting disease-associated phenotypes. Here, we combine cross-species transcriptomic analyses with experimental validation to test whether LSD opposes conserved signatures of brain aging and dementia. By comparing transcriptional profiles induced by chronic LSD treatment in rodents with age- and dementia-associated gene expression changes in the human prefrontal cortex, we show that LSD induces gene expression patterns strongly anti-correlated with aging and neurodegeneration programs. This reversal is specific compared to other pharmacological perturbations and is reproducible across datasets and species. Moreover, LSD counteracts amyloid-{beta}-induced structural and molecular alterations in primary cortical neurons, linking transcriptomic opposition to functional rescue under neurodegenerative stress. Together, our findings suggest that LSD modulates molecular and cellular pathways associated with brain aging and neurodegeneration, linking systems-level gene expression changes to structural and functional resilience in neurodegeneration-relevant contexts.

neuroscience↗

bioRxiv2026

Human basal radial glia morphotypes are transcriptionally distinct and exhibit different cell fate determination

Basal radial glia (bRG) are key neural progenitors driving human neocortical expansion. They exhibit remarkable morphological heterogeneity, yet the stability and functional significance of their distinct morphotypes remains unclear. Using human cortical brain organoids combined with long-term live imaging and morphology-resolved spatial transcriptomics (CellShape-seq), we show that bRG morphotypes display distinct morphodynamic behaviors, proliferative capacities and transcriptional profiles. While bifurcated bRG remodel extensively during mitosis to produce morphologically diverse progeny, multipolar cells are most morphologically flexible during interphase. Multipolar bRG further show the greatest proliferative capacity and the transcriptional signature related to progenitor state. Bifurcated bRG are least proliferative and are enriched for the multifunctional gene expression regulator YBX1. Pharmacological inhibition of YBX1 depletes bifurcated bRG, reduces neurogenesis, and promotes glial commitment. Our findings link progenitor morphology, gene expression and fate, providing a framework for understanding the cellular logic of human cortical development.

neuroscience↗

bioRxiv2026

RsaM is not a switch but a built-in modulator of quorum sensing in Pseudomonas fuscovaginae

Pseudomonas fuscovaginae, a wide host-range plant pathogen of several cereal and grass species, possesses two canonical N-acyl homoserine (AHL)-based quorum sensing (QS) systems called PfsI/R and PfvI/R, both of which are inactive under laboratory conditions but active in planta. A Tn5 mutant insertion in the pfsI and pfsR intergenic region was previously reported to trigger the PfsI/R system. This region contains coding sequences for RsaM, a putative protein that has since been hypothesized to play a central role in imposing repression on the PfsI/R system. Putative rsaM genes/RsaM proteins negatively controlling AHL QS systems have also been reported in several other bacterial species. In the present study, we report for the first time the endogenous expression of an RsaM family protein and determine its position within the PfsI/R regulatory circuit. We found that RsaM is not produced in the wild-type P. fuscovaginae and does not play a role in keeping the PfsI/R system in a quiescent state. The expression of RsaM is instead triggered upon targeted mutations in the pfsR-rsaM intergenic region, which concomitantly activate the transcription of both the pfsI and pfsR genes. Moreover, we demonstrated that RsaM attenuates the PfsI/R circuit upon its activation. Taken together, our results evidenced that RsaM does not function as a repressor switch of the PfsI/R system, but behaves as a built-in modulator that prevents overactivation of this circuit once it is triggered. ImportancePseudomonas fuscovaginae is a globally occurring plant pathogen that employs AHL QS to regulate virulence. In this bacterium, QS signalling circuits display a rather unusual feature; the lack of activation at high cell densities under standard laboratory conditions. A hypothetical regulator named RsaM was previously linked to this phenomenon as a possible repressor switch acting on the PfsI/R AHL QS system in the absence of an unknown signal or stimulus. In this study, we demonstrated that the expression of RsaM and activation of the PfsI/R system both depend on the disruption of the rsaM and pfsR divergent intergenic region, and that RsaM functions as a negative modulator of this circuit, rather than as its master repressor. This study unveils the functional position of a novel protein regulator and broadens our understanding of regulatory configurations governing QS circuits.

microbiology↗

bioRxiv2024

Adducins regulate morphology and fate of neural progenitors during neocortical neurogenesis

The evolutionary expansion of the mammalian neocortex is mediated by an increase in the proliferative capacity of neural progenitor cells. However, the molecular machinery controlling the proliferation of apical and basal progenitors during neocortical development is still poorly understood. Here we show that the three actin-associated morpho-regulatory adducins (ADD1-3), underlie abundance of basal progenitors in developing mouse and ferret neocortex in vivo and in human cortical organoids. Over expression of adducins in embryonic mouse neocortex increases the number of protrusions of basal progenitors, leading to an increase in their proliferative capacity and neuronal output. Conversely, knock-out of ADD1 in human cortical organoids, which also leads to down-regulation of other adducins, results in reduced proliferation of progenitors and aberrant neurogenesis. Hence, we show that adducins underlie proliferation and fate of neural progenitors, which are key cellular features underlying progression of mammalian neurogenesis.

neuroscience↗

bioRxiv2024

Morphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections

Glioblastoma is a major unmet clinical need characterized by striking inter- and intra-tumoral heterogeneity and a population of glioblastoma stem cells (GSCs), conferring aggressiveness and therapy resistance. GSCs communicate through a network of tumor-tumor connections (TTCs), including nanotubes and microtubes, promoting tumor progression. However, very little is known about the mechanisms underlying TTC formation and overall GSC morphology. As GSCs closely resemble neural progenitor cells during neurodevelopment, we hypothesised that GSCs morphological features affect tumour progression. We identified GSC morphology as a new layer of tumoral heterogeneity with important consequences on GSC proliferation. Strikingly, we showed that the neurodevelopmental morphoregulator ADD3, is sufficient and necessary for maintaining proper GSC morphology, TTC abundance and cell cycle progression as well as required for cell survival. Remarkably, both the effects on cell morphology and proliferation depend on the stability of actin cytoskeleton. Hence, cell morphology and its regulators play a key role in tumor progression by mediating cell-cell communication. We thus propose that GSC morphological heterogeneity holds the potential to identify new therapeutic targets and diagnostic markers.

cell biology↗

bioRxiv2022

DOT1L activity affects cell lineage progression in the developing brain by controlling metabolic programs

Cortical neurogenesis depends on the tight balance between self-renewal and differentiation of apical progenitors (APs), the key progenitor type generating all other neural cells including neocortical neurons. We here report the activity of the histone methyltransferase DOT1L as a gatekeeper for AP cell identity. Combining lineage tracing with single-cell RNA sequencing of clonally related cells, we explore consequences of DOT1L inhibition on AP lineage progression during neurogenesis in the embryonic mouse neocortex. At the cellular level, DOT1L inhibition led to increased neurogenesis driven by a shift from asymmetric self-renewing to symmetric neurogenic divisions of APs. At the molecular level, we show that DOT1L activity preserved AP identity by promoting transcription of a gene set involved in AP metabolism. On a mechanistic level, DOT1L inhibition increased expression of metabolic genes, including microcephaly-associated Asparagine synthetase (Asns) and overexpression of ASNS in APs resulted in increased neuronal differentiation. Asns expression was predicted to be controlled through EZH2 and we show that DOT1L activity allows PRC2-mediated repression of Asns expression. Importantly, inhibition of ASNS activity rescued increased AP differentiation upon DOT1L inhibition. Our data show that DOT1L activity/PRC2 crosstalk controls AP lineage progression by regulating AP metabolism, and they provide a mechanistic view on how DOT1L activity might affect neocortical neurogenesis.

developmental biology↗

bioRxiv2020

Isolation and characterization of Pseudomonas chlororaphis strain ST9 and its potential as a bioinoculant for agriculture

The development of biotechnologies based on beneficial microorganisms for improving soil fertility and crop yields could help addressing many current agriculture challenges, such as food security, climate change, pests control, soil depletion while decreasing the use of chemical fertilizers and pesticides. Plant Growth Promoting (PGP) microbes can be used as probiotics in order to increase plant tolerance/resistance to abiotic/biotic stresses and in this context strains belonging to the Pseudomonas chlororaphis group have shown to have potential as PGP candidates. In this work a new P. chlororaphis isolate is reported and tested for (i) in vitro PGP features, (ii) whole genome sequence analysis, and (iii) its effects on root microbiome, plant growth and on the expression of different plant genes in greenhouse experiments. The potential use of this P. chlororaphis strain as a plant probiotic is discussed.

microbiology↗

bioRxiv2020

Integrating large-scale neuroimaging research datasets: harmonisation of white matter hyperintensity measurements across Whitehall and UK Biobank datasets

Large scale neuroimaging datasets present the possibility of providing normative distributions for a wide variety of neuroimaging markers, which would vastly improve the clinical utility of these measures. However, a major challenge is our current poor ability to integrate measures across different large-scale datasets, due to inconsistencies in imaging and non-imaging measures across the different protocols and populations. Here we explore the harmonisation of white matter hyperintensity (WMH) measures across two major studies of healthy elderly populations, the Whitehall II imaging sub-study and the UK Biobank. We identify pre-processing strategies that maximise the consistency across datasets and utilise multivariate regression to characterise sample differences contributing to study-level differences in WMH variations. We also present a parser to harmonise WMH-relevant non-imaging variables across the two datasets. We show that we can provide highly calibrated WMH measures from these datasets with: (1) the inclusion of a number of specific standardised processing steps; and (2) appropriate modelling of sample differences through the alignment of demographic, cognitive and physiological variables. These results open up a wide range of applications for the study of WMHs and other neuroimaging markers across extensive databases of clinical data. HIGHLIGHTSO_LIWe harmonised measures of WMHs across two studies on healthy ageing C_LIO_LISpecific pre-processing strategies can increase comparability across studies C_LIO_LIModelling of biological differences is crucial to provide calibrated measures C_LI

neuroscience↗

bioRxiv2020

Role of misfolded tau in the onset and progression of brain toxicity after trauma

Traumatic brain injury (TBI) is associated with widespread tau pathology in about one third of patients. We previously found that TBI induces a transmissible tau pathology (tauTBI), with late cognitive decline and synaptic dysfunction. To understand whether tauTBI is a marker of ongoing neurodegeneration or a driver of functional decline, we employed C. elegans. Brain homogenates from chronic TBI mice, or from mice in which tauTBI had been transmitted by intracerebral inoculation, impaired C. elegans motility and neuromuscular synaptic transmission. Brain homogenates from tau P301L transgenic mice, or pre-aggregated recombinant tau, induced a similar toxic response. Protease digestion or pre-incubation of homogenates with anti-tau antibodies abolished toxicity, and TBI brain homogenates from tau knock-out mice had no toxic effect. These results support a vital role of abnormal tau species in chronic neurodegeneration after TBI and set the groundwork for the development of a C. elegans-based platform for screening anti-tau compounds.

neuroscience↗