Biology subjects

Serra, L.

Publications and source records attributed to Serra, L..

15 recordsLinked to original sources

bioRxiv2026

Cell Geometry and Junction Arrangement Define the Mechanical Robustness of Plant Tissues

Plant tissues are composed of immobile, pressurised cells that must maintain structural integrity under diverse environmental loads. Unlike animal tissues, which adapt through cellular rearrangement, plants must achieve mechanical robustness through the geometric configuration of their cellular networks. In this study, we establish a mechanistic link between cell geometry and mechanical resilience by integrating multilayer 3D mechanical simulations with cellular-resolution image analysis across a phylogenetically diverse panel of plant species, including Zea mays, Tradescantia zebrina, and Arabidopsis thaliana. We identify three-way junctions as fundamental mechanical elements that function as flexible hinges enabling mechanical strain accommodation in plant tissues. In contrast, four-way junctions are significantly stiffer and lack this strain-absorbing mechanism, providing a mechanical rationale for their biological avoidance. We also find that tissue material properties and strain response depend on edge lengths, cell layer, the degree of hexagonal shape, and turgor pressure response. These findings reveal the mechanism by which cell division patterns can actively tune tissue resilience to mechanical stress. This work provides new insights into the evolution of different cell shapes and offers clear principles for bio-inspired material science and tissue engineering.

plant biology↗

bioRxiv2026

Inhibition of RNA splicing is a novel therapeutic strategy for disruption of nuclear replicating viruses

RNA splicing is a fundamental feature of eukaryotic gene expression that is co-opted by many nuclear-replicating viruses to produce viral transcripts. Recent clinical development of spliceosome-targeting therapeutics has demonstrated that splicing can be safely modulated in vivo, raising the possibility that viral dependence on host RNA processing may represent an exploitable antiviral vulnerability. Here, we show that pharmacologic inhibition of cellular RNA splicing preferentially suppresses the expression of spliced viral transcripts and profoundly impairs replication of multiple splicing-dependent viruses. In human adenovirus, low-dose inhibition of the spliceosome using mechanistically distinct chemical inhibitors, or genetic depletion of SF3B1, disrupted splicing of complex late viral transcripts while largely sparing simple early transcripts. This resulted in impaired viral DNA replication, reduced late protein accumulation, and multi-log decreases in infectious progeny production. Splicing inhibitors similarly impaired RNA splicing and viral replication of DNA virus Herpes Simplex virus 1 and RNA virus influenza A, which both rely on host-dependent RNA processing strategies. In contrast, cytoplasmic RNA viruses lacking spliceosome dependence were unaffected, supporting an on-target mechanism. Together, these findings identify viral RNA processing complexity as a determinant of antiviral sensitivity and establish host spliceosome dependence as a shared and targetable vulnerability across diverse viral families.

microbiology↗

bioRxiv2025

Cerebrovascular response dynamics to hypercapnia in healthy aging

Cerebrovascular dysfunction is an early and underrecognized contributor to cognitive decline. Standard measures such as cerebrovascular reactivity (CVR) during hypercapnia capture only the amplitude of flow responses, providing limited insight into the timing of vascular adaptation. Temporal features, such as delay (onset latency) and time constant (rate of adjustment), together with gain (response amplitude) may serve as more sensitive indicators of vascular health, but cannot be directly obtained from conventional imaging. Here, we investigated cerebral blood flow (CBF), cerebral blood volume (CBV), and blood oxygenation level dependent (BOLD) signal dynamics during hypercapnic challenge in healthy aging. Using a physiologically validated computational model, we estimated delay, time constant, and gain by optimizing the mapping of end-tidal gases to their arterial counterparts in a region-of-interest framework. Once parametrized using CBF, the model successfully predicted CBV and BOLD responses in independent experimental sessions. Across subjects, aging was associated with widespread heterogeneous region-specific changes in delay and substantial reductions in gain and time constant, indicating that cerebrovascular responses become weaker and less adaptable with age. These results demonstrate that calibrated simulations have the ability to track vascular aging, allowing the extraction of parameters that may represent novel biomarkers of cerebrovascular dysfunction. Unlike conventional CVR, temporal hemodynamic parameters capture the dynamics of vascular adaptation, providing a complementary dimension for early detection and therapeutic monitoring in aging and disease.

neuroscience↗

bioRxiv2025

Non-neuronal signal fluctuations in Alzheimer's disease and in mild cognitive impairment

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) permits the investigation neural activity thanks to the neurovascular coupling mechanism. However, neural activity accounts for only a portion of the observed BOLD signal fluctuations, as the vasculature integrates multiple physiological inputs that contribute to the response. Research focusing on isolating the vascular components of the BOLD signal revealed that markers of cerebrovascular health, such as cerebrovascular reactivity (CVR), serve as valuable biomarkers for neurodegenerative diseases. This study examines the relationship between vascular metrics and noise in a cohort comprising individuals with Alzheimers disease (AD), mild cognitive impairment (MCI), and healthy controls (HC). Vascular responses were assessed using three functional contrasts during a hypercapnic challenge: arterial spin labeling (ASL) to measure cerebral blood flow (CBF) reactivity, vascular space occupancy (VASO) to quantify cerebral blood volume (CBV) reactivity, and BOLD imaging. Noise metrics were derived from multi-echo BOLD resting-state data by isolating the TE-independent components of the signal. Mean correlation coefficients for noise vs ASL-CVR are: (-0.12 {+/-} 0.06) for HC, (-0.14 {+/-} 0.08) for MCI, (-0.11 {+/-} 0.05) for AD. Mean correlation coefficients for noise vs BOLD-CVR are: (0.25 {+/-} 0.11) for HC, (0.24 {+/-} 0.07) for MCI, (0.23 {+/-} 0.11) for AD. Mean correlation coefficients for noise vs VASO-CVR are: (0.13 {+/-} 0.10) for HC, (0.13 {+/-} 0.07) for MCI, (0.12 {+/-} 0.12) for AD. These results suggest that TE-independent noise relates to the three vascular contrasts to varying extents and directions, with no significant differences across groups. Further analysis within specific functional networks revealed group differences in specific networks. The observed cortical correlations between noise and vascular features provide important insights into brain function and the progression of neurodegenerative diseases, offering a potential avenue to disentangle vascular and neural contributions in brain network and connectivity studies.

neuroscience↗

bioRxiv2025

Gradual ontogenetic shifts in the mobility and space use of long-lived migratory greater flamingos

O_LIHow early-life exploration shapes the adult annual cycle routines of migratory animals remains challenging to study, especially in long-lived species. Delayed recruitment often observed in long-lived migratory birds suggests that the first breeding attempt may be constrained by a protracted learning process in which individuals develop their annual itinerary, which may involve extensive exploration of the winter and breeding sites, potentially causing inexperienced young to wander beyond traditional population areas. C_LIO_LIUsing greater flamingo Phoenicopterus roseus GPS tracking data from 83 individuals tagged as nestlings in the Mediterranean, we analyzed ontogenetic changes in mobility and space use for up to 8 years of age. We segmented autumn-winter and spring-summer tracks (n = 223 device-bird-year combinations) into staging events (n = 1914). We then computed seasonal staging metrics and analysed how they changed with age. We map the traditional congregation sites of flamingos to investigate age-related changes in space use between males and females. C_LIO_LIFlamingos were more exploratory during their early years, gradually transitioning to a more sedentary lifestyle as they grew older. With each additional year of age, the number of staging events decreased by 16%, while the average duration of staging events increased by 8 days. C_LIO_LIBirds remained faithful to the non-breeding staging sites where they spent most of their time during the first year of life. Over time, they returned progressively closer to their natal sites, even after years of exploration at non-traditional locations. Breeding was rare (8%) and occurred at a relatively late age ([≥]5 years), highlighting an extended exploratory phase, a pattern observed in other long-lived species. C_LIO_LIOlder birds were more likely to use traditional sites and spent more time at these sites, particularly after age 5. Our study reveals the individual exploration process underlying natal and non-breeding dispersal patterns previously laid bare by ring-resighting studies and shows that flamingos retain long-term memory of sites learned in early life. C_LI

ecology↗

bioRxiv2024

Mechanical stress orients stomata division to form tissue scale alignments.

The last stomatal division aligns with the leafs main axis in many species [1]. Understanding how cellular events such as these are coordinated across organ scales remains a challenge in developmental biology. In Arabidopsis, polarised proteins guide the asymmetric divisions in the early stomatal lineage. These proteins show organ scale alignment and may be sensitive to mechanical stress [2]. In contrast, what determines the orientation and alignment of the critical final division is unknown [3]. Here we use an artificial system where every cell adopts the fate of a stomata pore [4] making it easy to visualise their alignment. Combining this system with simultaneous time-lapse imaging on both sides of the cotyledon we are able to compare the stomatal orientation relative to the organ axis, the cell major axis, and the principal directions of growth. Using finite element modelling on a realistic template enabled us to identify differential growth-derived stress patterns as a factor coordinating stomata division at the organ scale. Mechanical perturbation confirmed the influence of tensile stress on stomata division orientation. Through this study, we have identified a mechanism that can explain this nearly century-old observation.

plant biology↗

bioRxiv2024

m6A landscape is more pervasive when Trypanosoma brucei exits the cell cycle

N6-methyladenosine (m6A) is a mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how m6A landscape varies across the life cycle remains poorly defined. Using full-length, non-fragmented RNA, we immunoprecipitated and sequenced m6A-modified transcripts across three life cycle stages of Trypanosoma brucei - slender (proliferative), stumpy (quiescent), and procyclic forms (proliferative). We found that 1037 transcripts are methylated in at least one of these three life cycle stages. While 21% of methylated transcripts are common in the three stages of the life cycle, globally each stage has a distinct methylome. Interestingly, 47% of methylated transcripts are detected in the quiescent stumpy form only, suggesting a critical role for m6A when parasites exit the cell cycle and prepare for transmission by the Tsetse fly. In this stage, we found that a significant proportion of methylated transcripts encodes for proteins involved in RNA metabolism, which is consistent with their reduced transcription and translation. Moreover, we found that not all major surface proteins are regulated by m6A, as procyclins are not methylated, and that, within the VSG repertoire, not all VSG transcripts are demethylated upon parasite differentiation to procyclic form. This study reveals that the m6A regulatory landscape is specific to each life cycle stage, becoming more pervasive as T. brucei exits the cell cycle. SummaryAfrican trypanosome parasites adapt to mammalian and insect hosts by adjusting gene expression, morphology, and metabolism. In this study, we focus on how N6-methyladenosine (m6A), a post-transcriptional modification, affects the parasites transcriptome throughout its differentiation from the mammalian host to the fly. We found that methylation is differentially regulated as the life cycle progresses, being particularly prevalent in the non-proliferative stumpy form, as more methylated transcripts are found at this insect-infective stage than in slender and procyclic forms. We further show that the not all parasite surface proteins are regulated by m6A and that the previously identified link between m6A methylation and the expression level of the major surface protein of bloodstream forms applies to the active variant surface glycoprotein, but not always to silent genes, suggesting two distinct regulatory mechanisms of (de)methylation.

molecular biology↗

bioRxiv2023

SOX2 and NR2F1 coordinate the gene expression program of the early postnatal visual thalamus

The thalamic dorsolateral geniculate nucleus, (dLGN) receives visual input from the retina via the optic nerve, and projects to the cortical visual area, where eye-derived signals are elaborated. The transcription factors SOX2 and NR2F1 are directly involved in the differentiation of dLGN neurons, based on mouse work and patient mutations leading to vision defects. However, whether they regulate each other, or control common targets is still unclear. By RNA-seq analysis of neonatal dLGN from thalamo-specific Sox2 and Nr2f1 mouse mutants, we found a striking overlap of deregulated genes. Among them, VGF, a cytokine transported along thalamic-cortical axons is strongly downregulated in both mutants. CUT&RUN analysis of SOX2 binding in dLGN chromatin identified a binding pattern characteristic of the dLGN. Collectively, the SOX2 and NR2F1- coregulated genes, and cognate SOX2 binding sites, contribute as a basis to understand the gene regulatory network driving the differentiation and connectivity of thalamic neurons.

developmental biology↗

bioRxiv2023

A neuronal substrate for translating nutrient state and resource density estimations into foraging decisions

Foraging animals must balance the costs of exploring their surroundings with the potential benefits of finding nutritional resources. Each time an animal encounters a food source it must decide whether to initiate feeding or continue searching for potentially better options. Experimental evidence and patch foraging models predict that this decision depends on both nutritional state and the density of available resources in the environment. How the brain integrates such internal and external states to adapt the so-called exploration-exploitation trade-off remains poorly understood. We use video-based tracking to show that Drosophila regulates the decision to engage with food patches based on nutritional state and travel time between food patches, the latter being a measure of food patch density in the environment. To uncover the neuronal basis of this decision process, we performed a neurogenetic silencing screen of more than 400 genetic driver lines with sparse expression patterns in the fly brain. We identified a population of neurons in the central complex that acts as a key regulator of the decision to engage with a food patch. We show that manipulating the activity of these neurons alters the probability to engage, that their activity is modulated by the protein state of the animal, and that silencing these neurons perturbs the ability of the animal to adjust foraging decisions to the flys travel time between food patches. Taken together, our results reveal a neuronal substrate that integrates nutritional state and patch density information to control a specific foraging decision, and therefore provide an important step towards a mechanistic explanation of the cognitive computations that resolve complex cost-benefit trade-offs.

neuroscience↗

bioRxiv2023

Highly pathogenic avian influenza causes mass mortality in Sandwich tern (Thalasseus sandvicensis) breeding colonies across northwestern Europe

AO_SCPLOWBSTRACTC_SCPLOWIn 2022, highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b became enzootic and caused mass mortality in Sandwich terns and other seabird species across northwestern Europe. We present data on characteristics of the spread of the virus between breeding colonies and the number of dead adult Sandwich terns recorded at breeding sites throughout northwestern Europe. Within two months after the first mortalities were reported, in total 20,531 adult Sandwich terns were found dead, which is >17% of the total northwestern European breeding population. Losses are likely higher, as we expect that many victims were not found (mortality rate might be up to 74% of the breeding population). Inside the colonies almost all chicks died. After the peak of the outbreak, in a colony established by late breeders, 25.7% of adults showed immunity against HPAI subtype H5. Removal of carcasses helped in reducing the spread of the disease and consequently total mortality. More research on the sources and modes of transmission, incubation times, effective containment and immunity is urgently needed to combat this major threat for colonial seabirds.

ecology↗

bioRxiv2022

A CRISPRi-based genetic resource to study essential Staphylococcus aureus genes

We have optimized a CRISPR interference system to facilitate gene knockdown in the gram-positive bacterial pathogen Staphylococcus aureus. Our approach used a CRISPRi system derived from Streptococcus pyogenes, which involves the co-expression of the dcas9 gene encoding a catalytically inactive Cas9 protein and a customizable single guide RNA (sgRNA). In our system, dcas9 is expressed from a single copy in the chromosome of methicillin resistant S. aureus (MRSA) strains COL or JE2, under the control of a tightly regulated promoter, inducible by anhydrotetracycline. The sgRNAs are expressed from a replicative plasmid under the control of a constitutively active promoter. This system enables efficient, inducible, knockdown of both essential and non-essential genes. Using this approach, we constructed the Lisbon CRISPRi Mutant Library (LCML) comprising 261 strains, in the JE2 background, containing sgRNAs targeting 200 essential genes/operons. This library facilitates the study of the function of essential S. aureus genes and is complementary to the Nebraska Transposon Mutant Library which consists of nearly 2000 strains, each carrying a transposon insertion within a non-essential gene. The availability of these two libraries will facilitate the study of S. aureus pathogenesis and biology. Abstract ImportanceStaphylococcus aureus is an important clinical pathogen that causes a high number of antibiotic resistant infections. The study of S. aureus biology, and particularly of the function of essential proteins, is of particular importance to develop new approaches to combat this pathogen. We have optimized a CRISPRi system that allows efficient targeting of essential S. aureus genes. Furthermore, we have used that system to construct a library of 261 strains which allow the depletion of essential proteins encoded in 200 genes/operons. This library, which we have named Lisbon CRISPRi Mutant Library (LCML), should facilitate the study of S. aureus pathogenesis and biology.

microbiology↗

bioRxiv2020

An early Sox2-dependent gene expression program required for hippocampal dentate gyrus development

The hippocampus is a brain area central for cognition. Mutations in the human SOX2 transcription factor cause neurodevelopmental defects, leading to intellectual disability and seizures, together with hippocampal dysplasia. We generated an allelic series of Sox2 conditional mutations in mouse, deleting Sox2 at different developmental stages. Late Sox2 deletion (from E11.5, via Nestin-Cre) affects only postnatal hippocampal development; earlier deletion (from E10.5, Emx1-Cre) significantly reduces the dentate gyrus, and the earliest deletion (from E9.5, FoxG1-Cre) causes drastic abnormalities, with almost complete absence of the dentate gyrus. We identify a set of functionally interconnected genes (Gli3, Wnt3a, Cxcr4, p73 and Tbr2), known to play essential roles in hippocampal embryogenesis, which are downregulated in early Sox2 mutants, and (Gli3 and Cxcr4) directly controlled by SOX2; their downregulation provides plausible molecular mechanisms contributing to the defect. Electrophysiological studies of the Emx1Cre mouse model reveal altered excitatory transmission in CA1 and CA3 regions.

developmental biology↗

bioRxiv2019

Metabolic cross-feeding allows a gut microbial community to overcome detrimental diets and alter host behaviour

The impact of commensal bacteria on the host arises from complex microbial-diet-host interactions. Mapping metabolic interactions in gut microbial communities is therefore key to understand how the microbiome influences the host. Here we use an interdisciplinary approach including isotope-resolved metabolomics to show that in Drosophila melanogaster, Aceto-bacter pomorum (Ap) and Lactobacillus plantarum (Lp) establish a syntrophic relationship to overcome detrimental host diets and identify Ap as the bacterium altering the hosts feeding decisions. Specifically, we show that Lp generates lactate which is used by Ap to produce and provide amino acids that are essential to Lp allowing it to grow in imbalanced diets. Lactate is also necessary and sufficient for Ap to alter the flys protein appetite. Our data show that gut bacterial communities use metabolic interactions to become resilient to detrimental host diets and to ensure the constant flow of metabolites used by effector bacteria to alter host behaviour.

neuroscience↗

bioRxiv2019

Hybrid assembly of the genome of the entomopathogenic nematode Steinernema carpocapsae identifies the X-chromosome

Entomopathogenic nematodes from the genus Steinernema are lethal insect parasites that quickly kill their insect hosts with the help of their symbiotic bacteria. Steinernema carpocapsae is one of the most studied entomopathogens due to its broad lethality to diverse insect species and its effective commercial use as a biological control agent for insect pests, as well as a genetic model for studying parasitism, pathogenesis, and symbiosis. In this study, we used long-reads from the Pacific Biosciences platform and BioNano Genomics Irys system to assemble the best genome of S. carpocapsae ALL strain to date, comprising 84.5 Mb in 16 scaffolds, with an N50 of 7.36Mb. The largest scaffold, with 20.9Mb, was identified as chromosome X based on sex-specific genome sequencing. The high level of contiguity allowed us to characterize gene density, repeat content, and GC content. RNA-seq data from 17 developmental stages, spanning from embryo to adult, were used to predict 30,957 gene models. Using this new genome, we performed a macrosyntenic analysis to Caenorhabditis elegans and Pristionchus pacificus and found S. carpocapsaes chromosome X to be primarily orthologous to C. elegans and P. pacificus chromosome II and IV. We also investigated the expansion of protein families and gene expression differences between male and female stage nematodes. This new genome and more accurate set of annotations provide a foundation for new comparative genomic and gene expression studies within the Steinernema clade and across the Nematoda phylum.\n\nArticle SummaryThe insect killing worms Steinernema carpocapsae is a model organism for parasitism and symbiosis. The authors have used long reads and optical mapping to generate substantially contiguous assembly and a new set of gene annotations. They have identified the X chromosome as well as expansions in specific family proteases found in the venom of this worm. A macrosyntenic analysis with C. elegans shows a broad conservation of ancestral chromosomes with the exception of chromosome X. This new assembly will be useful to the Steinernema community and the broader nematode genomics community.

genomics↗

bioRxiv2019

A data-driven method to locate nest sites and estimate reproductive outcome from avian telemetry data

Recursive movement patterns have been used to detect behavioral structure within individual movement trajectories in the context of foraging ecology, home-ranging behavior, and predator avoidance. Some animals exhibit movement recursions to locations that are tied to reproductive functions, including nests and dens; while existing literature recognizes that, no method is currently available to explicitly target different types of revisited locations. Moreover, the temporal persistence of recursive movements to a breeding location can carry information regarding the fate of breeding attempts, but it has never been used as a metric to quantify recursive movement patterns. Here, we introduce a method to locate breeding attempts and estimate their fate from GPS-tracking data of central place foragers. We tested the performance of our method in three bird species differing in breeding ecology (wood stork (Mycteria americana), lesser kestrel (Falco naumanni), Mediterranean gull (Ichthyaetus melanocephalus)) and implemented it in the R package nestR. We identified breeding sites based on the analysis of recursive movements within individual tracks. Using trajectories with known breeding attempts, we estimated a set of species-specific criteria for the identification of nest sites, which we further validated using non-reproductive individuals as controls. We then estimated individual nest survival as a binary measure of reproductive fate (success, corresponding to fledging of at least one chick, or failure) from nest-site revisitation histories during breeding attempts, using a Bayesian hierarchical modeling approach that accounted for temporally variable revisitation patterns, probability of visit detection, and missing data. Across the three species, positive predictive value of the nest-site detection algorithm varied between 87-100% and sensitivity between 88-92%, and we correctly estimated the fate of 86-100% breeding attempts. By providing a method to formally distinguish among revisited locations that serve different ecological functions and introducing a probabilistic framework to quantify temporal persistence of movement recursions, we demonstrated how the analysis of recursive movement patterns can be applied to estimate reproduction in central place foragers. Beyond avian species, the principles of our method can be applied to other central place foraging breeders such as denning mammals. Our method estimates a component of individual fitness from movement data and will help bridge the gap between movement behavior, environmental factors, and their fitness consequences.

ecology↗