Biology subjects

Nadal, M.

Publications and source records attributed to Nadal, M..

9 recordsLinked to original sources

bioRxiv2025

Mechanical strain modulates Min patterning and division in E. coli filaments

Bacteria often encounter physico-chemical stresses that disrupt division, leading to filamentation, where cells elongate without dividing. While this adaptive response enhances survival, it also exposes filaments to significant mechanical strain, raising questions about the mechanochemical feedback in bacterial systems. In this study, we investigate how mechanical strain influences the Min oscillatory system, a reaction-diffusion network central to division in Escherichia coli. Through a multidisciplinary approach combining quantitative fluorescence microscopy, biophysical modeling, microfluidics, and patterned growth substrates, we demonstrate that filamentous E. coli undergoes growth-induced buckling instability. This phenomenon alters the diffusivity of membrane proteins and modulates the spatiotemporal patterning of the Min system. Moreover, we show that this mechanochemical interplay determines division site positioning after stress relief, effectively creating a mechanical "memory" for cytokinesis. Our findings underscore the critical role of mechanical forces in bacterial filamentation and provide new insights into the functional implications of mechanobiology in microbial systems.

biophysics↗

bioRxiv2025

Computational detection, characterization, and clustering of microglial cells in a mouse model of fat-induced postprandial hypothalamic inflammation

Obesity is associated with brain inflammation, glial reactivity, and immune cells infiltration. Studies in rodents have shown that glial reactivity occurs within 24 hour of high-fat diet (HFD) consumption, long before obesity development, and takes place mainly in the hypothalamus (HT), a crucial brain structure for controlling body weight. Understanding more precisely the kinetics of glial activation of two major brain cells (astrocytes and microglia) and their impact on eating behavior could prevent obesity and offer new prospects for therapeutic treatments. To understand the mechanisms pertaining to obesity-related neuroinflammation, we developed a fully automated algorithm, NutriMorph. Although some algorithms were developed in the past decade to detect and segment cells, they are highly specific, not fully automatic, and do not provide the desired morphological analysis. Our algorithm cope with these issues and performs the analysis of cells images (here, microglia of the hypothalamic arcuate nucleus), and the morphological clustering of these cells through statistical analysis and machine learning. Using the k-Means algorithm, it clusters the microglia of the control condition (healthy mice) and the different states of neuroinflammation induced by high-fat diets (obese mice) into subpopulations. This paper is an extension and re-analysis of a first published paper showing that microglial reactivity can already be seen after few hours of high-fat diet (Cansell et al., 2021). Thanks to NutriMorph algorithm, we unravel the presence of different hypothalamic microglial subpopulations (based on morphology) subject to proportion changes in response to already few hours of high-fat diet in mice.

neuroscience↗

bioRxiv2022

Disentangling leaf structural and material properties in relation to their anatomical and chemical compositional traits in oaks (Quercus L.)

The existence of sclerophyllous plants has been considered an adaptive strategy against different environmental stresses. As it literally means "hard-leaved", it is essential to quantify the leaf mechanical properties to understand sclerophylly. However, the relative importance of each leaf trait on mechanical properties is not yet well established. The genus Quercus is an excellent system to shed light on this since it minimizes phylogenetic variation while having a wide variation in sclerophylly. Thus, leaf anatomical traits and cell wall composition were measured, analyzing their relationship with LMA and leaf mechanical properties in a set of 25 oak species. Outer wall contributed strongly to leaf mechanical strength. Moreover, cellulose plays a critical role in increasing leaf strength and toughness. The PCA plot based on leaf trait values clearly separated Quercus species into two groups corresponding to evergreen and deciduous species. Sclerophyllous Quercus species are tougher and stronger due to their thicker epidermis outer wall and/or higher cellulose concentration. Furthermore, section Ilex species share common traits regardless of they occupy quite different climates. In addition, evergreen species living in Mediterranean-type climates share common leaf traits irrespective of their different phylogenetic origin.

plant biology↗

bioRxiv2022

Design of extended metal-binding β-sandwiches from de novo immunoglobulin domains

The antigen binding sites of antibodies, and derivatives such as scFvs, consist of an immunoglobulin structural framework that anchors hypervariable loops, and that is arranged as a dimer of {beta}-sandwiches (from the heavy and light chains) packing face-to-face. Yet, the naturally occurring dimer orientation of antibodies is not well suited for engineering rigid single-chain formats of increased stability and solubility, which are two key limitations of engineered antibodies. In this work, we computationally designed an extended 12-stranded {beta}-sandwich as a rigid single-chain dimer of de novo immunoglobulin domains interacting through an alternative edge-to-edge arrangement. The extended {beta}-sandwich was found to be hyperstable and structurally accurate as confirmed through X-ray crystallography. We functionalized this design by inserting a long EF-hand calcium-binding motif into the {beta}-hairpin bridge between both domains, showing high metal-binding affinity while remaining soluble and stable in solution. Finally, we propose a few designs with two EF-hand motifs in either or the same side of the scaffold with high-confidence structure predictions; altogether suggesting the robustness and versatility of our scaffold to harbor long functional loops. Our extended {beta}-sandwiches are structurally divergent to natural antibodies and open new avenues for incorporating multiple loop binding sites either for increased or bispecific activities.

biochemistry↗

bioRxiv2021

De Novo Design of Immunoglobulin-like Domains

Antibodies and antibody derivatives such as nanobodies contain immunoglobulin-like (Ig) {beta}-sandwich scaffolds which anchor the hypervariable antigen-binding loops and constitute the largest growing class of drugs. Current engineering strategies for this class of compounds rely on naturally existing Ig frameworks, which can be hard to modify and have limitations in manufacturability, designability and range of action. Here we develop design rules for the central feature of the Ig fold architecture - the non-local cross-{beta} structure connecting the two {beta}-sheets - and use these to de novo design highly stable seven-stranded Ig domains, confirm their structures through X-ray crystallography, and show they can correctly scaffold functional loops. Our approach opens the door to the design of a new class of antibody-like scaffolds with tailored structures and superior biophysical properties.

biochemistry↗

bioRxiv2021

Shiitake mycelium fermentation improves digestibility, nutritional value, flavor and functionality of plant proteins

Plant proteins can serve as inexpensive and environmentally friendly meat-replacements. However, poor taste characteristics and relatively low nutritional value prevent their full acceptance as meat substitutes. Fermentation of food has been historically used to improve the quality of foods. In this work we describe the improvement in digestibility, nutritional value, physical properties, and organoleptic characteristics, of a pea and rice protein concentrate blend through fermentation with shiitake mushroom mycelium. Ileal digestibility pig studies show increases in the DIAAS for the shiitake fermented pea and rice protein blend turning the blend into an "excellent source" of protein for humans. The fermentation also increases the solubility of the protein blend and reduces the content of the antinutrient compounds phytates and protease inhibitor. Mass spectrometry and sensory analyses of fermented protein blend indicates that fermentation leads to a reduction in off-note compounds substantially improving its organoleptic performance.

bioengineering↗

bioRxiv2021

Explicit expression of mesophyll conductance in the traditional leaf photosynthesis-transpiration coupled model and its physiological significances

O_LIAlmost all terrestrial biosphere models (TBMs) still assume infinite mesophyll conductance (gm) to estimate photosynthesis and transpiration. This assumption has caused low accuracy of TBMs to predict leaf gas exchange under certain conditions. C_LIO_LIIn this study, we developed a photosynthesis-transpiration coupled model that explicitly considers gm and designed an optimized parameterization solution through evaluating four different gm estimation methods in 19 C3 species at 31 experimental treatments. C_LIO_LIResults indicated that temperature responses of the maximum carboxylation rate (Fcmax) and the electron transport rate (Jmax) estimated by fusing the Bayesian retrieval algorithm and the Sharkey online calculator together with gm temperature response estimated by fusing the chlorophyll fluorescence-gas exchange method and anatomy method predicted leaf gas exchange more accurately. The gm temperature response exhibited activation energy ({Delta}Ha) of 63.13 {+/-} 36.89 kJ mol-1 and entropy ({Delta}S) of 654.49 {+/-} 11.36 J K-1 mol-1. The gm optimal temperature (Topt_gm) explained 58% of variations in photosynthesis optimal temperature (ToptA). The gm explicit expression has equally important effects on photosynthesis and transpiration estimations. C_LIO_LIResults advanced understandings of better representation of plant photosynthesis and transpiration in TBMs. C_LI

ecology↗

bioRxiv2021

Differences in Regional Grey Matter Volume Predict the Extent to which Openness influences Judgments of Beauty and Pleasantness of Interior Architectural Spaces

Hedonic evaluation of sensory objects varies from person to person. While this variability has been linked to differences in experience and personality traits, little is known about why stimuli lead to different evaluations in different people. We used linear mixed effect models to determine the extent to which the openness, contour, and ceiling height of interior architectural spaces influenced the beauty and pleasantness ratings of 18 participants. Then, by analyzing structural brain images acquired for the same group of participants we asked if any regional grey matter volume (rGMV) co-varied with these differences in the extent to which openness, contour and ceiling height influence beauty and pleasantness ratings. Voxel-based morphometry analysis revealed that the influence of openness on pleasantness ratings correlated with rGMV in the anterior prefrontal cortex (BA 10), and the influence of openness on beauty ratings correlated with rGMV in the temporal pole (BA 38) and posterior cingulate cortex (BA 31). There were no significant correlations involving contour or ceiling height. Our results suggest that regional variance in grey matter volume may play a role in the computation of hedonic valuation, and account for differences in the way people weigh certain attributes of interior architectural spaces.

neuroscience↗

bioRxiv2020

Formal model of Parkinson's disease neurons unveils possible causality links in the pathophysiology of the disease

Parkinsons Disease is the second most common neurodegenerative disease after Alzheimers disease. Despite extensive research, the initial cause of the disease is still unknown, although substantial advances were made in understanding of its genetics and the cognate neurophysiological mechanisms. Determining the causality relationships and the chronological steps pertaining to Parkinsons Disease is essential for the discovery of novel drug targets. We developed a systematic in silico model based on available data, which puts the possible sequence of events occurring in a neuron during disease onset into light. This is the first ever attempt, to our knowledge, to model comprehensively the primary modifications in the molecular pathways that manifest in compromised neurons from the commencement of the disease to the consequences of its progression. We showed that our proposed disease pathway was relevant for unveiling yet incomplete knowledge on calcium homeostasis in mitochondria, ROS production and -synuclein misfolding. Graphical abstract HighlightsO_LIVarying calcium concentration in aging dopaminergic neurons triggers disease onset. C_LIO_LIROS production in the mitochondria potentially causes iron accumulation. C_LIO_LIIron homeostasis dysregulation is linked to -synuclein aggregation. C_LI

systems biology↗