Biology subjects

Felix, L.

Publications and source records attributed to Felix, L..

4 recordsLinked to original sources

bioRxiv2026

A holocentric pangenome links karyotype evolution to meiotic recombination

Chromosomal fissions, fusions and whole-genome duplications propel genome evolution, yet their impact on meiotic recombination is obscured by the centromere constraint, since in monocentric species most large rearrangements are lethal1-4. Holocentric organisms, which distribute kinetochore activity along the entire chromosome, overcome this barrier and therefore offer a unique window onto the interplay between karyotype change and crossover control2. We assembled chromosome-scale genomes for 20 holocentric Rhynchospora species (including 56 haplotypes), representing all major clades of the genus, featuring satellite-based holocentromeres5,6, and integrated single-gamete crossover maps, high-resolution meiotic synapsis immunocytochemistry and Hi-C chromatin architecture. Breakpoint analysis shows that holocentromeric Tyba satellite arrays6,7 are recurrent hotspots for both chromosome fusions and fissions, contributing to the genuss extraordinary chromosome number variation from 2n = 4 to 36. Crossover landscapes group into two apparent modes: strongly distal-biased versus irregularly distributed, which is correlated with divergent patterns of synapsis elongation. Moreover, crossover number scales with chromosome count and meiotic axis length. In contrast, crossover density per megabase is inversely related to chromosome length and to chromatin-loop size. We propose that chromosome fissions create karyotypes with smaller chromosomes folded into shorter loops, thereby increasing the axial substrate accessible for double-strand break formation and elevating recombination frequency. Together, our results provide a structural link between large-scale structural chromosome evolution and meiotic recombination through coupled changes in chromosome number, size, loop geometry, and synapsis dynamics.

genomics↗

bioRxiv2023

Housing conditions affect adult zebrafish (Danio rerio) behavior but not their physiological status

Zebrafish is a valuable model for neuroscience research, but the housing conditions to which it is daily exposed may be impairing its welfare status. The use of environmental enrichment and the refinement of methodology for cortisol measurement could reduce stress, improving its welfare and its suitability as an animal model used in stress research. Thus, this study aimed to evaluate (I) the influence of different housing conditions on zebrafish physiology and behavior and (II) skin mucus potential for cortisol measurement in adult zebrafish. For this, AB zebrafish were raised under barren or enriched (PVC pipes and gravel image) environmental conditions. After 6 months, the behavior was assessed by different behavioral paradigms (shoaling, white-black box test, and novel tank). The physiological response was also evaluated through cortisol levels (whole-body homogenates and skin mucus) and brain oxidative stress markers. Results revealed that enriched-housed fish had an increased nearest neighbors distance and reduced activity. However, no effect on body length or stress biomarkers was observed; whole-body and skin mucus cortisol levels had the same profile between groups. In conclusion, this study highlights the skin mucus potential as a matrix for cortisol quantification and how environmental enrichment could influence the data in future studies. Simple SummaryThe delivery of proper housing conditions may translate into good fish welfare. As zebrafish housing is usually poorly enriched, the fish could be unable to express some natural behaviors, leading to distress and/ or stress mechanisms dysregulation. This work focused on the examination of zebrafish welfare raised under different housing conditions (barren or environmentally enriched) and the testing of a low-invasive technique (skin mucus collection) to measure the main stress hormone (cortisol). The data was processed to assess body length, behavior, and physiological status. Results revealed that enrichment induced minor alterations on zebrafish behavior. Thus, the influence of housing conditions should be considered in future research, depending on the purpose of the study. Also, skin mucus appears to be a promising matrix to replace whole-body to measure cortisol in zebrafish, since its collection is nonlethal and showed similar results to the traditional method.

animal behavior and cognition↗

bioRxiv2022

Novel algorithms for improved detection and analysis of fluorescent signal fluctuations

Fluorescent dyes and genetically encoded fluorescence indicators (GEFI) are common tools for visualizing concentration changes of specific ions and messenger molecules during intra-as well as intercellular communication. Using advanced imaging technologies, fluorescence indicators are a prerequisite for the analysis of physiological molecular signaling. Automated detection and avnalysis of fluorescence signals requires to overcome several challenges, including correct estimation of fluorescence fluctuations at basal concentrations of messenger molecules, detection and extraction of events themselves as well as proper segmentation of neighboring events. Moreover, event detection algorithms need to be sensitive enough to accurately capture localized and low amplitude events exhibiting a limited spatial extent. Here, we present two algorithms (PBasE and CoRoDe) for accurate baseline estimation of fluorescent detection of messenger molecules and automated detection of fluorescence fluctuations. Author summaryAnalyzing molecular signalling is crucial in understanding intra- and intercellular communication. These signals are visualized using fluorescent dyes or genetically encoded fluorescence indicators. In the brain, Ca2+ signals of glial cells are essential in deciphering complex regulatory functions in health and disease. Due to signal heterogeneity, detection and analysis are highly challenging. They can be stationary, with low amplitude and localized in cell processes, occur as prominent somatic signals or propagate as waves across cellular networks. We have developed two algorithms to analyze fluorescence transients, each tackling a specific problem. PBasE performs automatic and adaptive background correction, removing basal fluorescence fluctuations. CoRoDe automatically extracts regions of interest, explicitly including temporal information to obtain a precise segmentation, which is essential for accurate transient extraction. Combined, these algorithms are able to detect regions exhibiting low amplitude transients with small spatial extent as well as large, high amplitude signals. Extracted transients are categorized based on their peak amplitude, allowing detailed analyses by comparing changes of specific properties. In order to make these algorithms accessible, an interactive application, called Msparkles, has been designed.

neuroscience↗

bioRxiv2020

On the Origin of Ultraslow Spontaneous Na+ Fluctuations in Neurons of the Neonatal Forebrain

Spontaneous neuronal and astrocytic activity in the neonate forebrain is believed to drive the maturation of individual cells and their integration into complex brain-region-specific networks. The previously reported forms include bursts of electrical activity and oscillations in intracellular Ca2+ concentration. Here, we use ratiometric Na+ imaging to demonstrate spontaneous fluctuations in the intracellular Na+ concentration of CA1 pyramidal neurons and astrocytes in tissue slices obtained from the hippocampus of mice at postnatal days 2-4 (P2-4). These occur at very low frequency ([~]2/h), can last minutes with amplitudes up to several mM, and mostly disappear after the first postnatal week. To further study the mechanisms that may generate such spontaneous fluctuations in neurons, we model a network consisting of pyramidal neurons and interneurons. Experimentally observed Na+ fluctuations are mimicked when GABAergic inhibition in the simulated network is inverted. Both our experiments and computational model show that the application of tetrodotoxin to block voltage-gated Na+ channels or of inhibitors targeting GABAergic signaling respectively, significantly diminish the neuronal Na+ fluctuations. On the other hand, blocking a variety of other ion channels, receptors, or transporters including glutamatergic pathways, does not have significant effects. In addition, our model shows that the amplitude and duration of Na+ fluctuations decrease as we increase the strength of glial K+ uptake. Furthermore, neurons with smaller somatic volumes exhibit fluctuations with higher frequency and amplitude. As opposed to this, the larger relative size of the extracellular with respect to intracellular space observed in neonatal brain exerts a dampening effect. Finally, our model also predicts that these periods of spontaneous Na+ influx leave neonatal neuronal networks more vulnerable to hyperactivity when compared to mature brain. Taken together, our model thus confirms the experimental observations, and offers additional insight into how the neonatal environment shapes early signaling in the brain. Author SummarySpontaneous neuronal and astrocytic activity during the early postnatal period is crucial to the development and physiology of the neonate forebrain. Elucidating the origin of this activity is key to our understanding of the cell maturation and formation of brain-region-specific networks. This study reports spontaneous, ultraslow, large-amplitude, long-lasting fluctuations in the intracellular Na+ concentration of neurons and astrocytes in the hippocampus of mice at postnatal days 2-4 that mostly disappear after the first postnatal week. We combine ratiometric Na+ imaging and pharmacological manipulations with a detailed computational model of neuronal networks in the neonatal and adult brain to provide key insights into the origin of these Na+ fluctuations. Furthermore, our model predicts that these periods of spontaneous Na+ influx leave neonatal neuronal networks more vulnerable to hyperactivity when compared to mature brain.

neuroscience↗