Biology subjects

Fernandez, E.

Publications and source records attributed to Fernandez, E..

At least 19 recordsLinked to original sources

bioRxiv2026

Why phosphenes are not always dots: modeling the shapes elicited 1by intracortical stimulation of human V1

The majority of visual cortical prosthetic devices currently implanted in patients or under development rely on small depth electrodes. Reports from patients implanted with these devices suggest that stimulation with tiny electrodes does not reliably produce small punctate spots, with some patients reporting a variety of percepts, including larger spots and irregularly shaped phosphenes. Here, we compare drawings and descriptions made by a cortical implant recipient to predicted phosphene patterns, generated using a 'virtual patient' simulation based on a simple model of V1. We find that this model successfully reproduces the wide variety of percepts reported by this patient and further suggests that, for a subset of electrodes, stimulation may activate multiple locations -- possibly as a result of axonal activation.

bioengineering↗

bioRxiv2026

Mitochondrial pyruvate import in astrocytes links anaplerosis to seizure resistance

Astrocytes are glycolytic cells that convert a substantial fraction of glucose-derived pyruvate into lactate, a metabolite implicated in supporting neuronal energy demand and modulating excitability, plasticity and memory. This view has placed astrocytic lactate production and export at the centre of astrocyte-neuron metabolic coupling, but whether mitochondrial pyruvate utilization in astrocytes is dispensable in vivo or fulfils an essential function in the intact brain remains unknown. Here we show that adult astrocyte-specific deletion of Mpc2, encoding an obligatory mitochondrial pyruvate carrier subunit, causes motor deficits, neuronal hyperexcitability and seizure-associated lethality. Metabolic profiling revealed pyruvate diversion toward alanine as an unsuccessful compensatory bypass, together with impaired tricarboxylic acid-cycle metabolism and an imbalance in neurotransmitter-related pools, including glutamate, glutamine and {gamma}-aminobutyric acid. Thus, astrocytic mitochondrial pyruvate import is not primarily required for bioenergetic purposes but acts as a non-redundant anaplerotic gate that maintains neurotransmitter homeostasis, excitation-inhibition balance and seizure resistance in vivo.

neuroscience↗

bioRxiv2026

Cell-type-specific coupling of single-unit spikes and cortical ripples in macaque and human V1

Cortical ripples are brief high-frequency (80-150 Hz) oscillatory bursts in the extracellular potential, associated with memory and attention. So far, it is unclear whether they are brain-state specific and which neuron types participate in their generation. We report cortical ripples in macaque V1 at rest, present with both eyes open and closed. Using massively parallel Utah array recordings, we identify six single-unit classes and describe their relation to ripple-band oscillations. The classes differ in firing-rate modulation, phase-locking strength, and preferred ripple-band phase. One class of putative deep-layer neurons exhibits non-sinusoidal phase locking, explained by a simple thresholding mechanism in a computational model. During ripples, most units fire irregularly with transient regular bursts. The ripple-associated spiking organisation is largely preserved during natural-image viewing and confirmed in V1 of a blind human. Together, these findings suggest cortical ripples arise from a shared circuit conserved across species and conditions.

neuroscience↗

bioRxiv2026

Monoclonal anti-dsRNA antibody-based metagenomics (MADAM) reveal Pyricularia oryzae mycovirome

This study introduces MADAM (Monoclonal Anti-dsRNA Antibody-Based Metagenomics), a novel approach that integrates multiple technical modules previously used independently in other protocols. MADAM combines monoclonal antibody-mediated double-stranded RNA (dsRNA) enrichment, sequence-independent RT-PCR, and Oxford Nanopore Technologies (ONT) sequencing. Applied to Pyricularia oryzae, the causal agent of rice blast disease, MADAM enabled the comprehensive characterization of mycovirus genomes from four fungal isolates collected in Yunnan, China. The approach achieved high viral read recovery rates (46.9-72.7%) and identified 18 P. oryzae-associated RNA viruses spanning seven families: Botourmiaviridae, Deltaormycoviridae, Mymonaviridae, Partitiviridae, Polymycoviridae, Splipalmiviridae, and Ambiguiviridae. Seventeen nearly complete to complete viral genomes (1,226-6,085 nucleotides) were recovered, with sequence coverage ranging from 88% to 100%. Co-infections were detected in three of the four isolates, with notable discoveries including the first deltaormycovirus reported in P. oryzae, a putative novel member of Botourmiaviridae, and an additional genomic segment of a polymycovirus. MADAM successfully detected positive-sense, negative-sense ssRNA, and dsRNA viruses, demonstrating its broad applicability. By uncovering novel viruses and resolving complex co-infections, this method proves invaluable for fungal virology, with potential applications in diagnostics, surveillance, and biological control. Ultimately, MADAM advances our understanding of fungal viral diversity and paves the way for further exploration of mycovirus ecology and evolution.

microbiology↗

bioRxiv2026

Zebra finch females flexibly communicate with each other and with AI-driven acoustic interaction models

Vocal interactions are fundamental for social functioning across animals, including humans. The diverse rules underlying these exchanges remain largely unknown, and emerging AI technologies offer promising avenues for investigation. We used computational tools to collect and analyze >1,000 hours of vocal interactions between female zebra finches and discovered that their interactions were characterized by correlated call production and structure, rapid acoustic modulation, and response selectivity. To test these interaction rules, we developed a generative audio large language model (ZF-AIM Acoustic Interaction Model) that engaged in real-time vocal exchanges with birds. When birds interacted with ZF-AIM, their vocal production and flexibility recapitulated key naturalistic features, which did not happen with non-interactive playbacks. Targeted ablations of ZF-AIM revealed that call timing and structure differentially contribute to natural vocal interactions. Using these AI-animal interactions, we demonstrate how AI can be leveraged to reveal fundamental rules underlying animal communication.

animal behavior and cognition↗

bioRxiv2026

Expression of βhpmeh gene in transgenic events of the potato variety Desiree increases resistance to bacterial wilt caused by Ralstonia solanacearum

Bacterial wilt, caused by the Ralstonia solanacearum species complex (RSSC), severely affects many important crops and significantly limits potato production worldwide. RSSC bacteria can regulate the expression of their virulence factors, including extracellular polysaccharides and endoglucanases, through quorum sensing, which enables bacteria to sense their population density through signaling molecules and collectively switch on virulence factors when a threshold density is reached. 3-hydroxy palmitic acid methyl ester is the main quorum-sensing molecule in RSSC that can be hydrolyzed by {beta}-hydroxypalmytate methyl ester hydrolase ({beta}HPMEH). In this study, we evaluated the ability of {beta}hpmeh transgenic potato (Desiree) plants to reduce bacterial wilt symptoms after artificial inoculation with two virulent RSSC strains under controlled conditions and related this to the expression of the {beta}hpmeh gene. For each transgenic event, we analyzed the phenotypic response (wilt incidence, latent infection, and area under the disease progress curve). Real-time quantitative PCR was performed to determine the relative expression levels of {beta}hpmeh in transgenic events. Several transgenic events were identified with reduced susceptibility to bacterial wilt compared to Desiree and a resistance level similar to or higher than that of potato variety Cruza 148, the most resistant variety available, which was positively correlated with {beta}hpmeh expression.

plant biology↗

bioRxiv2025

Astrocytic glycolysis attenuates mitochondrial efficiency to preserve cognition

Astrocytic glycolysis is tightly coupled to neurotransmission and thought to be essential for neurological health. However, the metabolic adaptations that enable astrocytes to maintain a durable glycolytic profile without compromising viability are elusive. Here, using in vivo approaches including cell-specific gene expression disruption, metabolic flux analyses and behavioral tests in mice, we addressed this issue. We found that Pfkfb3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3) is instrumental in maintaining the astrocytic glycolytic phenotype. Importantly, astrocytic glycolysis sustained by Pfkfb3 is required for normal cognitive performance. Mechanistically, ATP generated through glycolysis is consumed by mitochondria, via the reverse mode of ATP synthase, to conserve the proton gradient across the inner mitochondrial membrane. This enables mitochondria to attenuate pyruvate decarboxylation, tricarboxylic acid cycle and electron transport chain activity, thereby preserving pyruvate for conversion into lactate and delivery to neurons. These findings reveal that astrocytes sacrifice mitochondrial bioenergetic efficiency as a previously underappreciated strategy to support cognition.

cell biology↗

bioRxiv2025

Exhaled breath condensate proteomics using amphipols improves protein detection but reveals statistical challenges in respiratory disease biomarker discovery

BackgroundInvasive diagnostic techniques for pleural mesothelioma (PM) delay early detection, underscoring the need for non-invasive biomarkers. Exhaled breath condensate (EBC) is a promising matrix but has extremely low protein concentration. This study applies an amphipol (APol)-based concentration method to enhance detection of potential PM biomarkers in the EBC proteome. MethodsFour replicate EBC samples from a healthy individual were processed using APols or lyophilization. Subsequently, 145 EBC samples from PM patients (n=25), lung cancer patients (n=28), asymptomatic asbestos-exposed individuals (n=60) or healthy controls (n=32) were concentrated with APols and analysed by liquid chromatography coupled with tandem mass spectrometry. Technical variability from batch effects and collection devices was addressed using omicsGMF, for simultaneous imputation and covariates correction. Statistical analysis employed linear models with technical and clinical covariates. ResultsAPols outperformed lyophilization, yielding 1.7-fold higher proteome coverage and improved reproducibility. Although high data missingness was observed, proteome analysis across 145 samples identified 248 unique proteins. OmicsGMF corrected the substantial variability, while maintaining biological signal. Whereas unsupervised clustering did not reveal distinct disease-specific patterns, supervised statistical analysis detected overall subtle differences between clinical groups (PERMANOVA p-value = 0.008), though no individual proteins reached statistical significance after adjustment for technical and clinical covariates and correction for multiple testing. ConclusionAPols outperforms lyophilization for concentrating proteins in low-abundant EBC samples, enabling enhanced proteome coverage for biomarker discovery studies. However, the inherent high variability of EBC proteomes has a strong effect on detecting possible biomarkers across clinical groups. Key messageO_ST_ABSWhat is already known on this topicC_ST_ABSExhaled breath condensate (EBC) is an attractive non-invasive biofluid for respiratory disease biomarker discovery, but no protein biomarkers have reached clinical application despite extensive investigation. What this study addsUsing superior APols-based protein concentration and rigorous analytical and statistical methods in 145 EBC samples, we demonstrate that fundamental limitations - 96% peptide missingness, 80% skin-protein contamination, high variability, low protein identifications and low fold-changes- make EBC unsuitable for reliable protein biomarker discovery, when proper covariate adjustment is applied. How this study might affect research, practice or policyResearchers pursuing EBC proteomics should be cautious, as inadequate handling of missingness and variability, particularly without proper covariate adjustment, may yield findings that do not reflect true biological differences.

pathology↗

bioRxiv2025

Deep Learning-Based Control of Electrically Evoked Activity in Human Visual Cortex

Visual cortical prostheses offer a promising path to sight restoration, but current systems elicit crude, variable percepts and rely on manual electrode-by-electrode calibration that does not scale. This work introduces an automated data-driven neural control method for a visual neuroprosthesis using a deep learning framework to generate optimal multi-electrode stimulation patterns that evoke targeted neural responses. Using a 96-channel Utah electrode array implanted in the occipital cortex of a blind participant, we trained a deep neural network to predict single-trial evoked responses. The network was used in two complementary control strategies: a learned inverse network for real-time stimulation synthesis and a gradient-based optimizer for precise targeting of desired neural responses. Both approaches significantly outperformed conventional methods in controlling neural activity, required lower stimulation currents, and adapted stimulation parameters to resting state data, reliably evoking more stable percepts. Crucially, recorded neural responses better predicted perceptual outcomes than stimulation parameters alone, underscoring the value of our neural population control framework. This work demonstrates the feasibility of data-driven neural control in a human implant and offers a foundation for next-generation, model-driven neuroprosthetic systems, capable of enhancing sensory restoration across a range of clinical applications.

neuroscience↗

bioRxiv2025

Graphene Micro-transistor Arrays Reveal Perfusion-Dependent Electrophysiological and Haemodynamic Signatures of Cortical Spreading Depolarizations in Ischaemic Stroke

Cortical spreading depolarizations (CSDs) are large-scale disruptions of neuronal homeostasis that contribute to secondary injury in ischaemic stroke. In healthy cortex, CSDs induce vasodilation to meet metabolic demand, whereas in ischaemic tissue, they can provoke vasoconstriction and sustained hypoperfusion, exacerbating damage. We present a multimodal neurotechnology platform integrating flexible, transparent graphene solution-gated field-effect transistor (gSGFET) arrays with laser speckle contrast imaging (LSCI), enabling simultaneous DC-coupled electrophysiological recordings and cerebral blood flow imaging with high spatiotemporal fidelity. gSGFETs enable stable, distortion-free recording of infraslow potentials essential for resolving CSD waveforms in vivo. In two murine stroke models, we show that CSD waveform duration and morphology scale with local perfusion, delineating electrophysiological subtypes predictive of tissue viability and haemodynamic response. In metabolically compromised cortex, CSDs exhibit double peaks or negative ultraslow components that result in vasoconstriction, contrasting with narrow, monophasic waveforms eliciting vasodilation in healthy regions. Systemic ketamine shortens CSD duration and converts vasoconstriction to vasodilation in perfusion-deficit tissue, revealing a mechanism for its neuroprotective action. This platform enables high-fidelity investigation of brain-blood flow interactions in vivo.

neuroscience↗

bioRxiv2025

Lack of AtMC1 catalytic activity triggers autoimmunity dependent on NLR stability

Plants utilize cell surface-localized pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLR) receptors to detect non-self and elicit robust immune responses. Fine-tuning the homeostasis of these receptors is critical to prevent their hyperactivation. Here, we show that Arabidopsis plants lacking metacaspase 1 (AtMC1) display autoimmunity dependent on immune signalling components downstream of NLR and PRR activation. Overexpression of a catalytically inactive AtMC1 in an atmc1 background triggers severe autoimmunity partially dependent on the same immune signalling components. Overexpression of the E3 ligase SNIPER1, a master regulator of NLR homeostasis, fully reverts the AtMC1-dependent autoimmunity phenotype, inferring that a broad defect in NLR turnover may underlie the severe phenotype observed. Catalytically inactive AtMC1 localizes to punctate structures that are degraded through autophagy. Altogether and considering previous evidence on the proteostatic functions of AtMC1, we speculate that Wt AtMC1 may either directly or indirectly control NLR protein levels, thereby preventing autoimmunity.

plant biology↗

bioRxiv2025

Bayesian optimization of cortical neuroprosthetic vision using perceptual feedback

The challenge in cortical neuroprosthetic vision is determining the optimal, safe stimulation patterns for the visual cortex in order to evoke the desired perception in blind individuals--specifically, light perceptions known as phosphenes. Currently, clinical studies gain insights into the perceptual characteristics of the perceived phosphenes by asking for descriptions of provided stimulation protocols. However, the huge parameter space for multi-electrode stimulation settings makes it difficult to draw conclusions about the optimality of the stimulation patterns that lead to well-perceived phosphenes. A systematic search in the parameter space of the electrical stimulation is needed to achieve good perception. Bayesian optimization (BO) is a framework for finding optimal parameters efficiently. Using the patients scoring of the perception as feedback, a model of the patients response based on iteratively generated stimulation protocols can be built to maximize perception quality. A patient implanted with an intracortical 96-channel microelectrode array in their visual cortex was tested by iteratively presenting stimulation protocols, generated via BO for the first and random generation (RG) for the second experiment. Whereas standard BO methods do not scale well to problems with over a dozen inputs, we propose to optimize a set of 40 electrode currents using trust region-based BO. The generated protocols determine which electrodes are concurrently stimulated from the set and with how much current from a range of 0-50 {micro}A, on a maximum total current constraint of 500 {micro}A. The patient provided feedback for each stimulation based on their liking of the perception quality on a Likert scale, where a score of 7 indicated the highest quality and 0 no perception. In the BO experiment, the patient perception quality ratings gradually converged on higher values compared to the RG experiment. Similarly, gradually higher total current values were chosen by BO, in line with the observed preference of patients for higher currents due to brighter phosphenes. Finally, the electrodes that were observed to be more effective in producing phosphene perception in previous studies were gradually chosen more by BO also with the allocation of higher current values. This study demonstrates the power of BO in converging to optimal stimulation protocols based on patient feedback, providing a more efficient search for stimulation parameters for clinical studies.

bioengineering↗

bioRxiv2025

Cortical Response to Acute Implantation of the Utah Optrode Array in Macaque Cortex

Optogenetics has transformed the study of neural circuit function, but limitations in its application to species with large brains, such as non-human primates (NHPs), remain. A major challenge in NHP optogenetics is delivering light to sufficiently large volumes of deep neural tissue with high spatiotemporal precision, without simultaneously affecting superficial tissue. To overcome these limitations, we recently developed and tested in vivo in NHP cortex, the Utah Optrode Array (UOA). This is a 10x10 array of penetrating glass shanks, tiling a 4x4mm2 area, bonded to interleaved needle-aligned and interstitial {micro}LED arrays, which allows for independent photostimulation of deep and superficial brain tissue. Here, we investigate the acute biological response to UOA implantation in NHP cortex, with the goal of optimizing device design for reduced insertion trauma and subsequent chronic response. To this goal, we systematically vary UOA shank diameter, surface texture, tip geometry, and insertion pressure, and assess their effects on astrocytes, microglia, and neuronal viability, following acute implantation. We find that UOAs with shanks of smaller diameter, smooth surface texture and round tips cause the least damage. Higher insertion pressures have limited effects on the inflammatory response, but lead to greater tissue compression. Our results highlight the importance of balancing shank diameter, tip geometry, and insertion pressure in UOA design for preserving tissue integrity and improving long-term UOA performance and biocompatibility.

bioengineering↗

bioRxiv2023

Old foe, new host: epidemiology, genetic diversity and pathogenic characterization of maize streak virus in rice fields from Burkina Faso.

Rice is of critical significance regarding food security worldwide including in Africa. Only two viruses impacting rice production in Africa have been deeply investigated for decades: the rice yellow mottle virus (Solemoviridae) and the rice stripe necrosis virus (Benyviridae). Using viral metagenomics, we aimed at exploring the diversity of viruses circulating in Burkina Faso rice fields. We performed an epidemiological survey in this country between 2016 and 2019 involving 57 small farmers rice fields under two production systems (rainfed lowlands and irrigated areas). More than 2700 rice samples were collected without a priori (not based on symptom observation) following a regular scheme. In addition, wild and cultivated (maize and sugarcane) Poaceae growing nearby rice fields were also collected. Unexpectedly, metagenomics detected maize streak virus (MSV, Geminiviridae) in analyzed rice samples. Further molecular analyses using RCA-PCR showed that MSV is widely distributed and highly prevalent in both rainfed lowlands and irrigated rice areas. MSV-A and MSV-G strains were identified. MSV-G, exclusively identified so far in wild grasses, was the most prevalent strain while MSV-A, known to cause severe symptoms in maize, was sporadically identified. No genetic differentiation was detected between MSV isolates either infecting wild or cultivated plant species. Using infectious clones in experimental conditions, we confirmed the pathogenicity of both MSV strains on rice. Thus, in addition to contribute to the epidemiological surveillance of rice production in Africa, our results illuminate new epidemiological and pathogenic aspects of one of the most studied plant viruses with significant economic consequences in Africa. FundingFrench National Research Agency < > program (ANR-10-LABX-001-01), Agropolis Fondation (ANR-16-IDEX-006), French National Research Agency "young researchers" program (ANR-20-CE35-0008-01), CGIAR Research Program on Rice Agri-food Systems (RICE), Cooperation and cultural action department of the French Embassy (SCAC) in Burkina Faso.

pathology↗

bioRxiv2023

Weak neuronal glycolysis sustains cognition and organismal fitness

The energy cost of neuronal activity is mainly sustained by glucose1,2. However, in an apparent paradox, neurons only weakly metabolize glucose through glycolysis3,4,5,6, a circumstance that can be accounted for by the constant degradation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (Pfkfb3)3,7,8, a key glycolysis-promoting enzyme. To evaluate the in vivo physiological significance of this hypo-glycolytic metabolism, here we genetically engineered mice with their neurons transformed into active glycolytic cells through Pfkfb3 expression. In vivo molecular, biochemical, and metabolic flux analyses of these neurons revealed an accumulation of anomalous mitochondria, complex I disassembly, bioenergetic deficiency and mitochondrial redox stress. Notably, glycolysis-mediated NAD+ reduction impaired sirtuin-dependent autophagy. Furthermore, these mice displayed cognitive decline and a metabolic syndrome that was mimicked by confining Pfkfb3 expression to hypothalamic neurons. Neuron-specific genetic ablation of mitochondrial redox stress corrected these alterations. Thus, the weak glycolytic nature of neurons is required to sustain higher-order organismal functions.

cell biology↗

bioRxiv2023

Draft genome sequence of Microbacterium fakhimi sp. nov., a novel bacterium associated with the alga Chlamydomonas reinhardtii

Microbacterium fakhimi sp. nov. has been isolated from a contaminated algal culture (Chlamydomonas reinhardtii). Its genome has been fully sequenced (3,753,259 base pairs) and a tentative annotation is provided (3,704 genes). Both, genome information and growth tests suggest that M. fakhimi sp. nov. is auxotroph for biotin and thiamine and unable to use sulfate as sulfur (S) source. S-reduced forms, such as methionine and cysteine can support M. fakhimi sp. nov. growth. The potential biotechnological interest of this bacteria is discussed here and in a related research paper (Fakhimi et al., 2023b).

microbiology↗

bioRxiv2023

Chlamydomonas reinhardtii and Microbacterium fakhimi sp. nov., a mutualistic association that favor sustainable hydrogen production.

A multispecies bacterial community including Microbacterium forte sp. nov., Stenotrophomonas goyi sp. nov., and Bacillus cereus greatly promoted sustained hydrogen production by the microalga Chlamydomonas reinhardtii when cocultivated in mannitol- and yeast extract-containing medium (up to 313 mL{middle dot}L-1). Alga viability was also largely prolonged in the cocultures (>45 days) without any nutrient supplementation. Among the bacterial community, Microbacterium forte sp. nov. was the main responsible for the hydrogen production improvement. Nonetheless, the use of the entire bacterial community allowed a better growth of the alga during hydrogen production. Chlamydomonas reinhardtii and Microbacterium forte sp. nov. established a mutualistic association, based on the release of ammonium and acetic acid from the bacterium, while the alga provided sulfur-containing metabolites and complemented the bacterial auxotrophy for biotin and thiamine. This study uncovers the potential of the Chlamydomonas-bacteria consortia for durable and stable H2 production while allowing the simultaneous production of biomass.

microbiology↗

bioRxiv2023

Spatial Transcriptomics Arena (STAr): an Integrated Platform for Spatial Transcriptomics Methodology Research

The emerging field of spatially resolved transcriptomics (SRT) has revolutionized biomedical research. SRT quantifies expression levels at different spatial locations, providing a new and powerful tool to interrogate novel biological insights. An essential question in the analysis of SRT data is to identify spatially variable (SV) genes; the expression levels of such genes have spatial variation across different tissues. SV genes usually play an important role in underlying biological mechanisms and tissue heterogeneity. Currently, several computational methods have been developed to detect such genes; however, there is a lack of unbiased assessment of these approaches to guide researchers in selecting the appropriate methods for their specific biomedical applications. In addition, it is difficult for researchers to implement different existing methods for either biological study or methodology development. Furthermore, currently available public SRT datasets are scattered across different websites and preprocessed in different ways, posing additional obstacles for quantitative researchers developing computational methods for SRT data analysis. To address these challenges, we designed Spatial Transcriptomics Arena (STAr), an open platform comprising 193 curated datasets from seven technologies, seven statistical methods, and analysis results. This resource allows users to retrieve high-quality datasets, apply or develop spatial gene detection methods, as well as browse and compare spatial gene analysis results. It also enables researchers to comprehensively evaluate SRT methodology research in both simulated and real datasets. Altogether, STAr is an integrated research resource intended to promote reproducible research and accelerate rigorous methodology development, which can eventually lead to an improved understanding of biological processes and diseases. STAr can be accessed at https://lce.biohpc.swmed.edu/star/.

genomics↗