Biology subjects

Correia, M.

Publications and source records attributed to Correia, M..

11 recordsLinked to original sources

bioRxiv2026

Time-Evolving Immunomodulatory Activity in Green-Fixed Devitalized Cellular Materials

By decoupling biological function from cellular viability, fixed abiotic cellular materials have emerged as a promising platform for next-generation immunotherapies, preserving essential immunomodulatory activities while enabling unprecedented control over manufacturing, storage, and standardization. Nevertheless, the coupled effects of fabrication history and post-fabrication environmental cues on their biological functionality remain elusive. Here, we show that both preparation route and storage time critically affect the bioactivity of mesenchymal stromal cell (MSC)-derived microtissues. By exploring different devitalization agents, we demonstrate that an ethanol-based strategy provides a green fixation option with comparable preservation of volumetric and fixed cell architecture, as well as immunomodulatory function. Processing protocols did not merely substitute conventional fixation but tailored specific immune-related bioactivity. An unexpected processing protocol and time-dependent enhancement of immunomodulatory performance was observed, with ethanol-fixed microtissues maintaining a stable baseline bioactive profile while increasing functional potency over 8 weeks of storage. We establish a framework for the design of immunomodulatory abiotic cell-derived materials with potential for the treatment of immune-mediated diseases and regenerative therapies, and we hope that the principles uncovered here may contribute to a broader understanding of how devitalized tissues can be engineered, preserved, and functionally tuned, whether lab-made or derived from natural biological systems.

immunology↗

bioRxiv2026

Dissociable contributions of cortical thickness and surface area to cognitive ageing: evidence from multiple longitudinal cohorts.

Cortical volume, a widely-used marker of brain ageing, is the product of two genetically and developmentally dissociable morphometric features: thickness and area. However, it remains unclear whether these two features have dissociable consequences for cognitive ageing. To address this, we analyse cross-sectional and longitudinal neuroimaging and cognitive data from one discovery cohort (Cam-CAN) and two independent, pre-registered replication cohorts (OASIS-3 and HABS-HD), leveraging wide age ranges across adulthood, different follow-up intervals and diverse population backgrounds. We show that thickness declines more steeply with age than does area, and shows stronger associations with longitudinal change in fluid cognitive abilities, fairly uniformly across the cortex. Cognitive change is also dependent on baseline thickness, independent of thickness change and independent of baseline cognitive ability. In contrast, area is comparatively stable across adulthood, at least until old age, and shows weaker and more heterogeneous associations with cognitive change. Together, these findings help to reconcile inconsistencies in the literature, and indicate that thickness provides a more sensitive marker of dynamic neurobiological processes underlying cognitive ageing, whereas area seems to reflect primarily stable, trait-like variation in cognitive ability.

neuroscience↗

bioRxiv2025

Postnatal developmental temperature affects the ontogeny of heat- and cold tolerance

Thermoregulatory precision is key to maintaining fitness in thermally unstable environments. Previous research found that development in the warmth renders birds better able to handle mild heat stress, while cold postnatal development gives no apparent benefit upon mild cold exposure. It is still not known how developmental temperature affects maximal heat tolerance limits, or if there is a physiological trade-off between heat and cold tolerance. We investigated how postnatal developmental under simulated cold snap- or heatwave-like conditions from hatching until reproductive maturity impacted the ontogeny of maximal heat- and cold tolerance in Japanese quail (Coturnix japonica). To study if any such effects were reversible or permanently programmed, we transferred half of each treatment group to intermediate common garden conditions once reproductive maturity was reached and repeated the measurements several weeks later. Development in heatwave-like conditions increased evaporative water loss rate and moved heat tolerance limits upwards, whereas cold snap-like development rendered more thermogenic birds with improved cold tolerance limits. However, we found no evidence for a trade-off between thermogenic performance and evaporative cooling capacity. The common garden birds converged in nearly all thermoregulatory traits at the end of the study, suggesting that the prior emergence of temperature-dependent phenotypes reflected reversible plasticity. We suggest that improved temperature tolerance limits improve performance in matched thermal conditions, reducing the rate at which thermal injury accrues. Yet, in the short term, we found markedly lower capacity to acclimate heat tolerance compared to cold tolerance, with possible implications for life in a warming world.

ecology↗

bioRxiv2024

Development in the cold renders bird mitochondria more susceptible to heat stress

Research on birds suggests that extreme weather events during development may have long-lasting consequences on form and function. The underlying cellular mechanisms mediating such phenotypic effects are poorly studied. We raised Japanese quail in warm (30{degrees}C) or cold (10{degrees}C) temperatures from hatching until adulthood, and then measured mitochondrial metabolism in intact blood cells at representative normothermic body temperature (41{degrees}C) and a hyperthermic temperature (45{degrees}C) that quail commonly attain when heat stressed. To investigate whether any developmental effects were reversible, half of the cold- and warm-acclimated birds were assigned to a common garden (20{degrees}C) 3 weeks before the measurements. Across groups, hyperthermia was associated with increased proton leak, but decreases in both phosphorylating respiration (where ATP is produced) and working capacity of the mitochondria. Cold-acclimated birds were more strongly affected by heat stress: the increase in proton leak was 1.6-fold higher, and the decrease in phosphorylating capacity during endogenous respiration was 1.7-fold greater, compared to warm-acclimated birds. These differences did not remain in the common-garden birds. Our study suggests that developmental cold acclimation is traded off against heat tolerance at the level of cellular metabolism, with implications for our understanding of avian responses to climate change.

physiology↗

bioRxiv2024

No evidence that shrinking and shapeshifting meaningfully affect how birds respond to warming and cooling

Across the globe, birds and mammals are becoming smaller and longer-limbed. Although the cause of these changes is unclear, many argue that each provide thermoregulatory benefits in a warmer world by easing heat dissipation. Here, we show that neither body size nor limb length in a model species (the Japanese quail) influenced metabolic costs of warming during a cold challenge. In the heat, larger body sizes increased metabolic costs of thermoregulation, however, this effect was moderate and almost always negated by cooling from the limbs (>97% of cases). Rearing in the warmth (30{degrees}C) relative to the cold (10{degrees}C) reduced body sizes and increased limb lengths at adulthood but thermoregulatory benefits of these changes in later heat exposures were absent. Our findings demonstrate that shrinking and shape-shifting are unlikely to ease thermoregulation in contemporary birds or reflect selection for such. Alternative contributors, including neutral or non-adaptive plasticity, should be further investigated. TeaserUsing experimental data, we show for the first time that shrinking and shape-shifting - which has been described as the third general response to climate change in animals - does not inherently provide thermoregulatory benefits to birds in a warming world. Further research evaluating the drivers of shape-shifts (including neutral plasticity and temporal reductions in resource abundance) is needed before we can determine why animals shrink under climate change.

physiology↗

bioRxiv2024

Metabolic and age-associated epigenetic barriers during direct reprogramming of mouse fibroblasts into induced cardiomyocytes

Heart disease is the leading cause of mortality in developed countries novel regenerative procedures are warranted for improving patients well fare. Direct cardiac conversion (DCC) can create induced cardiomyocytes (iCMs) and besides holding great promise, lacks clinical effectiveness for cardiac regeneration as metabolic and age-associated barriers remains elusive. Here, we identify by histone post-translational analysis that DCC triggers major age-dependent alterations in the epigenetic landscape. Metabolomics revealed decrease abundance of anabolic metabolites related to TCA cycle and glutaminolysis and profound mitochondrial network remodeling, with increased elongation and interconnectivity and reliance in mitochondrial respiration in iCMs. Importantly, adult-derived iCMs present increase accumulation of oxidative stress in the mitochondria and pharmacological activation of mitophagy increase DCC of adult fibroblasts in vitro. Metabolic modulation in vitro and dietary manipulations in vivo improves DCC efficiency and are accompanied by significant alterations in the histone acetylation and methylation landscape and mitochondria homeostasis. Our study provides evidence that metaboloepigenetics as a direct role in cell fate transitions driving direct cardiac conversion into iCMs, highlighting the potential use of metabolic modulation in increasing cardiac regenerative strategies.

cell biology↗

bioRxiv2021

Systematic Transmission Electron Microscopy-Based Identification of Cellular Degradation Machinery

Many interconnected degradation machineries including autophagosomes, lysosomes, and endosomes work in tandem to conduct autophagy, an intracellular degradation system that is crucial for cellular homeostasis. Altered autophagy contributes to the pathophysiology of various diseases, including cancers and metabolic diseases. Although many studies have investigated autophagy to elucidate disease pathogenesis, identification of specific components of the autophagy machinery has been challenging. The goal of this paper is to describe an approach to reproducibly identify and distinguish subcellular structures involved in macro autophagy. We provide methods that help avoid common pitfalls, including a detailed explanation for distinguishing lysosomes and lipid droplets and discuss differences between autophagosomes and inclusion bodies. These methods are based on using transmission electron microscopy (TEM), capable of generating nanometer-scale micrographs of cellular degradation components in a fixed sample. We also utilize serial block face-scanning electron microscopy (SBF-SEM) to offer a protocol for visualizing 3D morphology of degradation machinery. In addition to TEM and 3D reconstruction, we discuss other imaging techniques, such as immunofluorescence and immunogold labeling that can be utilized to reliably and accurately classify cellular organelles. Our results show how these methods may be used to accurately quantify the cellular degradation machinery under various conditions, such as treatment with the endoplasmic reticulum stressor thapsigargin or ablation of the dynamin-related protein 1.

biophysics↗

bioRxiv2021

Global and regional ecological boundaries drive abrupt changes in avian frugivory interactions

Species interactions can propagate disturbances across space, though ecological and biogeographic boundaries may limit this spread. We tested whether large-scale ecological boundaries (ecoregions and biomes) and human disturbance gradients increase dissimilarity among ecological networks, while accounting for background spatial and elevational effects and differences in network sampling. We assessed network dissimilarity patterns over a broad spatial scale, using 196 quantitative avian frugivory networks (encompassing 1,496 plant and 1,003 bird species) distributed across 67 ecoregions and 11 biomes. Dissimilarity in species and interactions, but not in network structure, increased significantly across ecoregion and biome boundaries and along human disturbance gradients. Our findings suggest that ecological boundaries contribute to maintaining the worlds biodiversity of interactions and mitigating the propagation of disturbances at large spatial scales. One-Sentence SummaryEcoregions and biomes delineate the large-scale distribution of plant-frugivore interactions.

ecology↗

bioRxiv2021

Androglobin, a chimeric mammalian globin, is required for male fertility

Spermatogenesis is a highly specialised process, involving multiple dedicated pathways and regulatory check-points. Defects ultimately lead to male sub-fertility or sterility, and numerous aspects of mammalian sperm formation remain unknown. The predominant expression of the latest globin family member, androglobin (Adgb) in mammalian testis tissue prompted us to assess its physiological function in spermatogenesis. Adgb knockout mice display male infertility, reduced testis weight, impaired maturation of elongating spermatids, abnormal sperm shape and ultrastructural defects in microtubule and mitochondrial organisation. Epididymal sperm from Adgb knockout animals display multiple flagellar malformations including coiled, bifide or shortened flagella, and erratic acrosomal development. Following immunoprecipitation and mass spectrometry, we could identify septin 10 (Sept10) as interactor of Adgb. The Sept10-Adgb interaction was confirmed both in vivo using testis lysates, and in vitro by reciprocal co-immunoprecipitation experiments. Furthermore, absence of Adgb leads to mislocalisation of Sept10 in sperm, indicating defective manchette and sperm annulus formation. Finally, in vitro data suggest that Adgb contributes to Sept10 proteolysis in a calmodulin (CaM)-dependent manner. Collectively, our results provide evidence that Adgb is essential for murine spermatogenesis and further suggest that interdependence between Adgb and Sept10 is required for sperm head shaping via the manchette and proper flagellum formation.

developmental biology↗

bioRxiv2021

Tripartite networks show that keystone species can multitask

Keystone species are disproportionately important for ecosystem functioning (1,2). However, while all species engage in multiple interaction types with other species, the importance of keystone species is often defined based on a single dimension of their Eltonian niche (3), that is, one type of interaction (e.g., keystone predator). Therefore, it remains unclear whether the importance of keystone species is unidimensional or if it extends across interaction types. We conducted a meta-analysis of tripartite interaction networks to examine whether species importance in one dimension of their niche is mirrored in other niche dimensions, and whether this is associated with interaction outcome, intimacy, or species richness. We show that keystone species importance is positively associated across multiple ecological niche dimensions, independently of species abundance, and find no evidence that multidimensionality of keystone species is influenced by the explanatory variables. We propose that the role of keystone species extends across multiple ecological niche dimensions, with important implications for ecosystem resilience and conservation. Significance StatementKeystone species are often identified by focusing on a single type of interaction (e.g., predation, pollination, herbivory) which contrasts with the multiple roles that species play in biological communities. We conducted a meta-analysis of 18 tripartite interaction networks to explore if keystonness is correlated across the multiple dimensions of species Eltonian niches. Our results suggest that species importance tends to span across multiple interaction types, independently from abundance, which can be key to understand community resilience and collapse in face of multiple threats.

ecology↗

bioRxiv2017

Optimization of a free water elimination two-compartment model for diffusion tensor imaging.

Typical diffusion-weighted imaging (DWI) is susceptible to partial volume effects: different types of tissue that reside in the same voxel are inextricably mixed. For instance, in regions near the cerebral ventricles or parenchyma, fractional anisotropy (FA) from diffusion tensor imaging (DTI) may be underestimated, due to partial volumes of cerebral spinal fluid (CSF). Free-water can be suppressed by adding parameters to diffusion MRI models. For example, the DTI model can be extended to separately take into account the contributions of tissue and CSF, by representing the tissue compartment with an anisotropic diffusion tensor and the CSF compartment as an isotropic free water diffusion coefficient. Recently, two procedures were proposed to fit this two-compartment model to diffusion-weighted data acquired for at least two different non-zero diffusion MRI b-values. In this work, the first open-source reference implementation of these procedures is provided. In addition to presenting some methodological improvements that increase model fitting robustness, the free water DTI procedures are re-evaluated using Monte-Carlo multicompartmental simulations. Analogous to previous studies, our results show that the free water elimination DTI model is able to remove confounding effects of fast diffusion for typical FA values of brain white matter. In addition, this study confirms that for a fixed scanning time the fwDTI fitting procedures have better performance when data is acquired for diffusion gradient direction evenly distributed along two b-values of 500 and 1500 s/mm2.

neuroscience↗