Biology subjects

Diez, A.

Publications and source records attributed to Diez, A..

5 recordsLinked to original sources

bioRxiv2026

Hypoxia increases neural proliferation, alters vascular structure, and reprograms the transcriptome and proteome of the speckled sanddab brain

Hypoxia (low oxygen availability) is a common environmental stressor in estuarine ecosystems that negatively affects fish survival as well as physiological and behavioral responses. However, the effects of hypoxia on the brain remains poorly understood, particularly in non-model species. Here, we investigated how prolonged hypoxia influences neural, vascular, and molecular responses in the brain of the speckled sanddab (Citharichthys stigmaeus), an ecologically relevant estuarine flatfish. Fish were exposed to normoxic or hypoxic conditions for seven days, and responses were assessed using histological analyses of neural proliferation and vascular structure, alongside transcriptomic and proteomic profiling. Hypoxia increased neural cell proliferation and progenitor activation in the hypothalamic nucleus recessus lateralis (NRL) and optic tectum, while reducing survival of newly generated cells. At the tissue level, hypoxia induced region-specific vascular remodeling, characterized by increased vessel area and vessel number without evidence of widespread endothelial proliferation. At the molecular level, transcriptomic and proteomic analyses revealed consistent enrichment of biological processes related to stress responses, development, metabolism, and cellular homeostasis, despite limited overlap between individual genes and proteins. Gene- and protein-level analyses further indicated activation of hypoxia-responsive pathways, including HIF signaling and oxidative stress protection, alongside selective metabolic reprogramming. Together, these findings demonstrate that hypoxia induces multi-level changes in the brain, linking neural plasticity, vascular remodeling, and molecular responses. This integrated response likely supports brain function under reduced oxygen availability in dynamic estuarine environments and highlights the role of the brain in regulating responses to environmental stress.

physiology↗

bioRxiv2025

Single-cell multiomics reveals epigenetic rewiring of splenic memory B cells during murine malaria reinfection

Malaria induces slow, gradually acquired, non-sterilizing immunity whose cellular and regulatory underpinnings remain incompletely understood. Here, we combine a sequential Plasmodium yoelii 17XNL infection model in BALB/c mice, in which primary parasitemia resolves spontaneously and confers robust protection upon homologous reinfection, with single-cell RNA and chromatin accessibility profiling to dissect how primary infection and recall reshape splenic immunity, with a focus on B cells. We generate a multiomic atlas of >50,000 splenic mononuclear cells, resolving thirteen major immune lineages and 48 subpopulations, and show that B cells dominate the response and diversify into naive/mature, germinal center, memory, and plasmablast compartments. Trajectory analysis reveals distinct differentiation paths towards germinal center, memory, and mature B cells, and uncovers infection-dependent shifts in transcription factor activity, cis-regulatory element usage, and gene regulatory networks. Reinfection is associated with a shift in memory B-cell composition and transcriptional programs towards extrafollicular-like, IgM- conventional memory B cells together with epigenetic modules linked to rapid antibody production. Together, these data provide a systems-level view of B cell plasticity in experimental malaria and provides a mechanistic framework from a highly protective P. yoelii reinfection model with implications for understanding non-sterilizing immunity in endemic settings.

genomics↗

bioRxiv2023

Turing pattern formation in reaction-cross-diffusion systems with a bilayer geometry

Conditions for self-organisation via Turings mechanism in biological systems represented by reaction-diffusion or reaction-cross-diffusion models have been extensively studied. Nonetheless, the impact of tissue stratification in such systems is under-explored, despite its ubiquity in the context of a thin epithelium overlying connective tissue, for instance the epidermis and underlying dermal mesenchyme of embryonic skin. In particular, each layer can be subject to extensively different biochemical reactions and transport processes, with chemotaxis - a special case of cross- diffusion - often present in the mesenchyme, contrasting the solely molecular transport typically found in the epidermal layer. We study Turing patterning conditions for a class of reaction-cross- diffusion systems in bilayered regions, with a thin upper layer and coupled by a linear transport law. In particular, the role of differential transport through the interface is explored together with the presence of asymmetry between the homogeneous equilibria of the two layers. A linear stability analysis is carried out around a spatially homogeneous equilibrium state in the asymptotic limit of weak and strong coupling strengths, where quantitative approximations of the bifurcation curve can be computed. Our theoretical findings, for an arbitrary number of reacting species, reveal quantitative Turing conditions, highlighting when the coupling mechanism between the layered regions can either trigger patterning or stabilize a homogeneous equilibrium regardless of the inde- pendent patterning state of each layer. We support our theoretical results through direct numerical simulations, and provide an open source code to explore such systems further.

developmental biology↗

bioRxiv2023

Vertical transmission of maternal mitochondrial DNA through extracellular vesicles modulates embryo bioenergetics

The transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. We aimed to investigate the potential for vertical DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics. We discovered that the human endometrium secretes all three general subtypes of EV - apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) - into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of mitochondrial (mt)DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived nuclear-encoded (n)DNA/mtDNA by trophoblast cells of murine embryos, which associates with a reduction in mitochondrial respiration and ATP production. These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that nDNA/mtDNA become packaged into secreted EVs that the embryo uptakes, and that the transfer of DNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation.

developmental biology↗

bioRxiv2019

Plasmodium falciparum immunodominant IgG epitopes in subclinical malaria

Incomplete non-sterile immunity to malaria is attained in endemic regions after recurrent infections by a large percentage of the adult population, who carry the malaria parasite asymptomatically. Although blood-stage Plasmodium falciparum rapidly elicits IgG responses, the target antigens of partially protective and non-protective IgG antibodies as well as the basis for the acquisition of these antibodies remain largely unknown. We performed IgG-immunomics to screen for P. falciparum antigens and to identify epitopes associated with exposure and clinical disease. Sera from malaria cases identified five prevalent antigens recognized by all analyzed patients IgGs. For further epitope mapping, peptide microarrays designed to cover their sequences were probed with a set of 38 sera samples from adult individuals of an endemic malaria region in Ghana. Eight 20-mer peptides with the highest affinity and frequency of recognition among the population were subsequently validated with 16 sera from the same region, segregated into patients with positive or negative subclinical detection of P. falciparum. Significant binding specificity for two immunodominant antigenic regions was uncovered within the START-related lipid transfer protein and the protein disulfide isomerase PDI8. These 20-mer peptides challenged with sera samples from children under 5 years old displayed specific IgG binding in those with detectable parasitemia, even at subclinical level. These results suggest that the humoral response against START and PDI8 antigens may be triggered even at submicroscopic parasitemia levels in children and may eventually be used to differentially diagnose subclinical malaria in children.\n\nSignificanceMalaria in Africa is a leading cause of morbidity and mortality. The reservoirs of the malaria parasite are asymptomatic patients who carry it subclinically. Identifying the parasite antigens and its fragments that trigger the most common immunity response by immunoglobulin G that partially protect people can have profound implications for both, development of a malaria vaccine and diagnosis of the subclinical parasite carriers. Antigen discovery and mapping, validated with sera from subclinical carriers, showed that immunoglobulin G responses in children against parasites START and PDI8 may eventually be used to differentially diagnose non-infected from subclinical cases. Furthermore, anti-START and anti-PDI8 endemic immunodominance provides association of these antigens with long-term acquired immunity and immune evasion to malaria.

microbiology↗