Biology subjects

Maldonado, M.

Publications and source records attributed to Maldonado, M..

12 recordsLinked to original sources

bioRxiv2026

Hemodynamic Signals Reshape Biological Inference in Widefield Calcium Imaging

Widefield calcium imaging is widely used to study cortex-wide neural dynamics, yet fluorescence signals are strongly influenced by hemodynamic fluctuations arising from blood volume and oxygenation changes. Although hemodynamic correction is frequently applied, it remains unclear whether vascular contributions represent a modest preprocessing concern or systematically bias biological interpretations of cortical activity. Here, we used dual-wavelength imaging to determine how hemodynamic correction reshapes inference of cortical dynamics across mouse lines expressing GCaMP6s, GCaMP6f, and jGCaMP8m, across multiple analytical domains, and under healthy and glioblastoma conditions. We systematically compared uncorrected and corrected signals using analyses spanning functional parcellation, connectivity, spectral structure, brain-behavior coupling, and low-dimensional network-state dynamics. Hemodynamic correction consistently reduced global functional connectivity, increased network modularity, redistributed spectral power away from slow-frequency dominance, and reorganized multivariate representations of cortical state space. These findings demonstrate that vascular signals do not behave as unstructured measurement noise but instead introduce organized variance that propagates across analytical pipelines and influences inference of cortical dynamics. The consequences of this bias were particularly relevant in glioblastoma, where tumor-associated vascular remodeling amplifies the mismatch between fluorescence signals and underlying neuronal activity. In this disease setting, correction revealed hemispheric asymmetries, reduced network-state entropy, and constrained trajectories within cortical state space that were obscured in uncorrected recordings, demonstrating that vascular remodeling can fundamentally alter interpretation of tumor-associated brain dynamics. More broadly, vascular signals systematically biased estimates of functional organization, network architecture, brain-behavior relationships, and disease-associated phenotypes. Together, these findings establish hemodynamic correction as a critical determinant of biological interpretation in mesoscale calcium imaging rather than a simple preprocessing refinement.

neuroscience↗

bioRxiv2026

A Deterministically Synchronized Widefield Imaging and Virtual Reality Platform for Multimodal Brain Behavior Recording

ObjectiveSimultaneous recording of brain activity, behaviour, and virtual environments is essential for understanding large-scale neural dynamics during behaviour. However, existing systems often rely on software-based synchronization or post hoc alignment, introducing latency, jitter, and drift that obscure fast brain-behavior interactions. ApproachHere, we present a deterministically synchronized widefield calcium imaging platform that unifies neural imaging, high-speed behavioural monitoring, and closed-loop virtual reality (VR) under a shared hardware-defined clock. This system enables millisecond-precision temporal alignment across modalities, including dual-wavelength hemodynamic correction, pupil and orofacial tracking, locomotion sensing, and VR rendering. Main resultsThe platform achieves stable hardware-level synchronization across neural imaging, behavioural recordings, and VR rendering without reliance on software timestamps. It supports widefield imaging rates up to 100 Hz and integrates seamlessly with both ViRMEn and Blender VR engines, exhibiting a mean locomotion-to-VR update latency of [~]1.5 ms. Multimodal recordings during VR navigation demonstrate robust temporal alignment between cortical activity, facial dynamics, pupil signals, and locomotion. SignificanceThis system provides a deterministic multimodal framework for studying brain-behaviour relationships during active behaviour. By enabling millisecond-precision synchronization across neural imaging, behaviour, and virtual environments, this platform enables causal investigation of brain-behaviour interactions at millisecond precision and provides a foundation for next-generation closed-loop neuroengineering experiments.

neuroscience↗

bioRxiv2026

NeuroPupil: A generalization-first framework for scalable and biologically informative cross-species pupillometry

Quantitative pupillometry provides a noninvasive window into brain state and neurological function, but its broader use across experimental and clinical settings is limited by challenges in achieving accurate, scalable, and generalizable measurements. Here, we present NeuroPupil, a deep learning framework for high-throughput, cross-species pupillometry that emphasizes robust generalization across subjects, behavioral contexts, and imaging conditions. Through systematic benchmarking of training strategies and network architectures, we identify pooled multi-subject training combined with an optimized U-Net architecture as a key determinant of reliable and transferable pupil tracking performance. Across diverse mouse and human datasets, NeuroPupil achieves improved accuracy and substantial gains in computational efficiency compared to existing approaches, enabling practical analysis of large-scale datasets. We further demonstrate that improved pupil tracking fidelity enhances downstream biological inference: NeuroPupil-derived pupil features significantly improve prediction of distributed cortical activity in behaving mice and preserve diagnostically relevant temporal structure in human clinical recordings. These findings highlight the importance of precise and scalable measurement for linking pupil dynamics to brain activity and clinical phenotypes. By integrating benchmarking, scalability, and accessible software tools, NeuroPupil provides a reproducible framework for large-scale pupillometry and facilitates its application in systems and translational neuroscience.

neuroscience↗

bioRxiv2025

Structure of Photosystem I-FCP from giant kelp uncovers drivers of antenna evolution across the red lineage

Brown algae and other red-algae-derived organisms such as diatoms are major contributors to global CO2 fixation via photosynthesis. To understand the photosynthetic function of brown algae, we obtained the structure of giant kelp Macrocystis pyrifera photosystem I (PSI) with a fucoxanthin-chlorophyll-protein (FCP) antenna and compared it to known structures from the red-algal lineage. We identified differences in M. pyriferas antenna composition, architecture and chlorophyll networks, as well as a pronounced variation in transmembrane hydrophobic thickness across the PSI-FCP supercomplex, with implications for photochemical function. Our work lays the foundation to understand kelps high photosynthetic productivity, reveals new drivers of antenna conservation and diversification, and sheds light on evolutionary relationships between organisms of the red lineage.

biochemistry↗

bioRxiv2025

DeepFace: A High-Precision and Scalable Deep Learning Pipeline for Predicting Large-Scale Brain Activity from Facial Dynamics in Mice

We present DeepFace, a next-generation facial analysis pipeline that enhances orofacial tracking and cortical activity prediction in mice. Rather than replacing existing tools, DeepFace builds upon DeepLabCut and Facemap to address scalability bottlenecks and improve behavioral quantification. It offers high precision, keypoint customization, and robust performance across GCaMP6s, GCaMP6f, and jGCaMP8m lines. With scalable batch processing and high-performance computing compatibility, DeepFace enables high-throughput brain-behavior analysis in large-scale preclinical neuroscience.

neuroscience↗

bioRxiv2023

Phylomitogenomics bolsters the high-level classification of Demospongiae (phylum Porifera)

Class Demospongiae - the largest in the phylum Porifera (Sponges) - encompasses nearly 8,000 accepted species in three subclasses: Keratosa, Verongimorpha, and Heteroscleromorpha. Subclass Heteroscleromorpha contains [~]90% of demosponge species and is subdivided into 17 orders. The higher level classification of demosponges underwent major revision as the result of nearly three decades of molecular studies. However, because most of the previous molecular work only utilized partial data from a small number of nuclear and mitochondrial (mt) genes, this classification scheme needs to be tested by larger datasets. Here we compiled a mt dataset for 136 demosponge species - including 64 complete or nearly complete and six partial mt-genome sequences determined or assembled for this study - and used it to test phylogenetic relationships among Demospongiae in general and Heteroscleromorpha in particular. We also investigated the phylogenetic position of Myceliospongia araneosa - a highly unusual demosponge without spicules and spongin fibers, currently classified as Demospongiae incertae sedis, for which molecular data were not available. Our results support the previously inferred sister-group relationship between Heteroscleromorpha and Keratosa + Verongimorpha and suggest five main clades within Heteroscleromorpha: Clade C0 composed of order Haplosclerida; Clade C1 composed of Scopalinida, Sphaerocladina, and Spongillida; Clade C2 composed of Axinellida, Biemnida, Bubarida; Clade C3 composed of Tetractinellida; and Clade C4 composed of Agelasida, Clionaida, Desmacellida, Merliida, Suberitida, Poecilosclerida, Polymastiida, and Tethyida. The inferred relationships among these clades were (C0(C1(C2(C3+C4)))). Analysis of molecular data from M. araneosa placed it in the C3 clade as a sister taxon to the highly skeletonized tetractinellids Microscleroderma sp. and Leiodermatium sp. Molecular clock analysis dated divergences among the major clades in Heteroscleromorpha from the Cambrian to the Early Silurian, the origins of most heteroscleromorph orders in the middle Paleozoic, and the most basal splits within these orders around the Paleozoic to Mesozoic transition. Overall, the results of this study are mostly congruent with the accepted classification of Heteroscleromorpha, but add temporal perspective and new resolution to phylogenetic relationships within this subclass.

evolutionary biology↗

bioRxiv2022

Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation

Pancreatic islets are 3-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combining genetic animal models, imaging tools, and gene expression profiling, we demonstrate that islet aggregation is regulated by extracellular matrix signaling and cell-cell adhesion. Islet endocrine cell-specific inactivation of extracellular matrix receptor Integrin {beta}1 disrupted blood vessel interactions but promoted cell-cell adhesion and the formation of larger islets. In contrast, ablation of cell-cell adhesion molecule -Catenin promoted blood vessel interactions yet compromised islet clustering. Simultaneous removal of Integrin {beta}1 and -Catenin disrupts islet aggregation and the endocrine cell maturation process, demonstrating that establishment of islet aggregates is essential for functional maturation. Our study provides new insights into understanding the fundamental self-organizing mechanism for islet aggregation, architecture, and functional maturation. HIGHLIGHTSO_LIIslet vascularization and aggregation are regulated via ECM-Itgb1 signaling C_LIO_LIECM-Itgb1 signaling negatively controls islet aggregation via regulation of cell-cell adhesion during development C_LIO_LICell-cell adhesion negatively regulates the interaction of endocrine cell-vasculature in islets C_LIO_LIDifferential cell adhesion regulates the establishment of islet architecture C_LIO_LIEndocrine functional maturation depends on islet aggregation regulated by the coordination of ECM-Itgb1 signaling and cell-cell adhesion C_LI

developmental biology↗

bioRxiv2021

Sponge contribution to the silicon cycle of a diatom-rich shallow bay

In coastal systems, planktonic and benthic silicifiers compete for the pool of dissolved silicon, a nutrient required to make their skeletons. The contribution of planktonic diatoms to the cycling of silicon in coastal systems is often well characterized, while that of benthic silicifiers such as sponges has rarely been quantified. Herein, silicon fluxes and stocks are quantified for the sponge fauna in the benthic communities of the Bay of Brest (France). A total of 45 siliceous sponge species living in the Bay account for a silicon standing stock of 1215 tons, while that of diatoms is only 27 tons. The silicon reservoir accumulated as sponge skeletons in the superficial sediments of the Bay rises to 1775 tons, while that of diatom skeletons is only 248 tons. These comparatively large stocks of sponge silicon were estimated to cycle two orders of magnitude slower than the diatom stocks. Sponge silicon stocks need years to decades to be renewed, while diatom turnover lasts only days. Although the sponge monitoring over the last 6 years indicates no major changes of the sponge stocks, our results do not allow to conclude if the silicon sponge budget of the Bay is at steady state, and potential scenarios are discussed. The findings buttress the idea that sponges and diatoms play contrasting roles in the marine silicon cycle. The budgets of these silicon major users need to be integrated and their connections revealed, if we aim to reach a full understanding of the silicon cycling in coastal ecosystems.

ecology↗

bioRxiv2020

Transient genomic instability drives tumorigenesis through accelerated clonal evolution

Abnormal numerical and structural chromosome content is frequently found in human cancer. To test the role of aneuploidy in tumor initiation and progression, we compared tumor development in mice with chronic chromosome instability (CIN) induced by inactivation of the spindle assembly checkpoint (produced by Mad2 deficiency) and mice with transient CIN through transiently increased expression of polo-like kinase 4 (PLK4), a master regulator of centrosome number. Tumors forming under chronic CIN gradually trended toward chromosomal gains producing a specific karyotype profile that could only be partially maintained in end-stage tumors, as determined by single-cell whole genome DNA sequencing. Short term CIN from transient PLK4 induction generated significant centrosome amplification and aneuploidy resulting in formation of aggressive T cell lymphomas in mice with heterozygous inactivation of one p53 allele or accelerated tumor development in the absence of p53. Transient CIN increased the frequency of lymphomainitiating cells (as revealed by T cell receptor sequencing) with a specific karyotype profile containing triploid chromosomes 4, 5, 14, and 15 occurring early in tumorigenesis. Overall, our evidence demonstrates that distinct CIN mechanisms drive cancers presenting specific, complex chromosomal alterations with transient CIN rapidly enhancing tumor formation by accelerating the generation of such events.

cancer biology↗

bioRxiv2020

Atomic structures of respiratory complex III2 , complex IV and supercomplex III2+IV from vascular plants

Mitochondrial complex III (CIII2) and complex IV (CIV), which can associate into a higher-order supercomplex (SC III2+IV), play key roles in respiration. However, structures of these plant complexes remain unknown. We present atomic models of CIII2, CIV and SC III2+IV from Vigna radiata determined by single-particle cryoEM. The structures reveal plant-specific differences in the MPP domain of CIII2 and define the subunit composition of CIV. Conformational heterogeneity analysis of CIII2 revealed long-range, coordinated movements across the complex, as well as the motion of CIII2s iron-sulfur head domain. The CIV structure suggests that, in plants, proton translocation does not occur via the H-channel. The supercomplex interface differs significantly from that in yeast and bacteria in its interacting subunits, angle of approach and limited interactions in the mitochondrial matrix. These structures challenge long-standing assumptions about the plant complexes, generate new mechanistic hypotheses and allow for the generation of more selective agricultural inhibitors.

plant biology↗

bioRxiv2019

Phylogenetic relationships of heteroscleromorph demosponges and the affinity of the genus Myceliospongia (Demospongiae incertae sedis)

Class Demospongiae - the largest in the phylum Porifera (Sponges) - encompasses 7,581 accepted species across the three recognized subclasses: Keratosa, Verongimorpha, and Heteroscleromorpha. The latter subclass contains the majority of demosponge species and was previously subdivided into subclasses Heteroscleromorpha sensu stricto and Haploscleromorpha. The current classification of demosponges is the result of nearly three decades of molecular studies that culminated in a formal proposal of a revised taxonomy (Morrow and Cardenas, 2015). However, because most of the molecular work utilized partial sequences of nuclear rRNA genes, this classification scheme needs to be tested by additional molecular markers. Here we used sequences and gene order data from complete or nearly complete mitochondrial genomes of 117 demosponges (including 60 new sequences determined for this study and 6 assembled from public sources) and three additional partial mt-genomes to test the phylogenetic relationships within demosponges in general and Heteroscleromorpha sensu stricto in particular. We also investigated the phylogenetic position of Myceliospongia araneosa - a highly unusual demosponge without spicules and spongin fibers, currently classified as Demospongiae incertae sedis.\n\nOur results support the sub-class relationship within demosponges and reveal four main clades in Heteroscleromorpha sensu stricto: Clade 1 composed of Spongillida, Sphaerocladina, and Scopalinida; Clade 2 composed of Axinellida, Biemnida, Bubarida; Clade 3 composed of Tetractinellida and \"Rhizomorina\" lithistids; and Clade 4 composed of Agelasida, Polymastida, Clionaida, Suberitida, Poecilosclerida, and Tethyida. The four clades appear to be natural lineages that unite previously defined taxonomic orders. Therefore, if those clades are to be systematically interpreted, they will have the rank of superorders (hence S1-S4). We inferred the following relationships among the newly defined clades: (S1(S2(S3+S4))). Analysis of molecular data from Myceliospongia araneosa - first from this species/genus - placed it in S3 as a sister group to Microscleroderma sp. and Leiodermatium sp. (\"Rhizomorina\").\n\nMolecular clock analysis indicated that the origin of the Heteroscleromorpha sensu stricto as well as the basal split in this group between S1 and the rest of the superorder go back to Cambrian, while the divergences among the three other superorders occurred in Ordovician (with the 95% standard variation from Late Cambrian to Early Silurian). Furthermore most of the proposed orders within Heteroscleromorpha appear to have middle Paleozoic origin, while crown groups within order date mostly to Paleozoic to Mesozoic transition. We propose that these molecular clock estimates can be used to readjust ranks for some of the higher taxa within Heteroscleromorpha.\n\nIn addition to phylogenetic information, we found several unusual mtgenomic features among the sampled species, broadening our understanding of mitochondrial genome evolution in this group and animals in general. In particular, we found mitochondrial introns within cox2 (first in animals) and rnl (first in sponges).

genomics↗

bioRxiv2019

PulmonDB: a curated lung disease gene expression database

Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) have contrasting clinical and pathological characteristics, and interesting whole-genome transcriptomic profiles. However, data from public repositories are difficult to reprocess and reanalyze. Here we present PulmonDB, a web-based database (http://pulmondb.liigh.unam.mx/) and R library that facilitates exploration of gene expression profiles for these diseases by integrating transcriptomic data and curated annotation from different sources. We demonstrated the value of this resource by presenting the expression of already well-known genes of COPD and IPF across multiple experiments and the results of two differential expression analyses in which we successfully identified differences and similarities. With this first version of PulmonDB, we create a new hypothesis and compare the two diseases from a transcriptomics perspective.

bioinformatics↗