Biology subjects

Garcia, N.

Publications and source records attributed to Garcia, N..

10 recordsLinked to original sources

bioRxiv2026

Pan-proteome regulation of marine Synechococcus nutrient stress plasticity

Variable phytoplankton resource demands can buffer productivity to climate-driven declines in nutrient supply, but the extent of this buffering depends on limits to cellular elemental plasticity. Elemental plasticity is driven by a combination of genomic adaptation and physiological regulation, but their mechanistic links remain unresolved. Here, we combine continuous culture experiments with global proteomics and elemental analyses to determine how genomic diversity shapes nutrient stress plasticity in the globally distributed cyanobacterium Synechococcus. By maintaining fixed growth rates in chemostats under nitrogen- or phosphorus-limiting conditions, we disentangle lineage-specific resource demands from growth effects. All strains show conserved induction of nutrient acquisition pathways, yet strain identity explains most pan-proteome variance, and variation in non-core protein expression predicts deviations in elemental plasticity. Strains from oligotrophic compared to mesotrophic regions exhibit broader proteomic adjustments and wider C:P and N:P ranges. Our findings show that genomic diversity, expressed through pan-proteome regulation, amplifies physiological plasticity and increases phytoplankton nutrient stress buffering capacity under future climate conditions.

microbiology↗

bioRxiv2026

Mechanosignaling Promotes Macrophage Apoptosis Resistance in Pulmonary Fibrosis via Metabolic Reprogramming

The mechanisms underlying the progression of pulmonary fibrosis in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases remain unclear. Increased extracellular matrix stiffness is a hallmark of fibrotic lung diseases. Monocyte-derived macrophages can promote fibrosis progression. However, there is limited understanding of how the mechanical properties of the fibrotic microenvironment influence macrophage phenotypes. Profibrotic macrophages are apoptosis-resistant, and this phenotype is modulated by enhanced mitochondrial bioenergetics. The objective of the study was to determine how lung tissue stiffness impacts macrophage phenotypes and fibrotic progression. We demonstrate that mechanoactivated macrophages exhibit apoptosis-resistance, increased expression of the antiapoptotic protein Bcl-xL and increased mitochondrial oxidative phosphorylation. Critically, the metabolic reprogramming observed in mechanoactivated macrophages is dependent on increased glutaminolysis. Inhibition of glutaminolysis attenuated apoptosis resistance in mechanoactivated macrophages. Moreover, inhibition of Bcl-xL in vivo protected mice against experimental pulmonary fibrosis. Lastly, mechanoactivated primary IPF macrophages produce more profibrotic cytokines and promote extracellular matrix production in precision-cut lung slices. We describe a mechanism for acquired macrophage apoptosis resistance dependent on metabolic reprogramming regulated by extracellular matrix stiffness. Our results identify mechanoactivated apoptosis-resistant macrophages as pro-fibrotic mediators, suggesting a novel therapeutic target in IPF and related fibrotic disorders.

molecular biology↗

bioRxiv2025

Separable neural population representations are constructed from mixed single neuron selectivity in the mouse early visual system

Both sensory and non-sensory brain regions receive mixed inputs from single neurons which require decomposition and integration before proceeding through a processing hierarchy. Whether mixed input signals are used in biological neural networks to derive pure single neuron representations, or distributed as new population representations from mixed single neurons, is not clear. In this study, we measured the distribution of single neuron hue and luminance tuning in the dorsolateral geniculate nucleus (dLGN) and primary visual cortex (V1) of mice, as well as the information about and structure of hue and luminance representations in populations of hundred of simultaneously sampled neurons. We compare single neuron and population encoding to null models expected for random integration and extraction of pure categorical single neuron representation. Using both univariate and multivariate regression techniques, we consistently noted that tuning for hue and luminance, rather than clustering into categorical response structures, formed uniform distributions. While the distribution of single neuron selectivity varied across the thalamocortical circuit, we found no evidence of categorical tuning organization emerging in the hierarchy. Nevertheless, populations contained complete information, in either high-dimensional linear representations or low-dimensional non-linear representations. In summary, we find that as early as primary sensory cortex and thalamus single neurons that have mixed selectivity for hue and luminance form a high dimensional representation of those variables, which can be non-linearly embedded in multiple separable representations.

neuroscience↗

bioRxiv2024

Extending mathematical frameworks to investigate neuronal dynamics in the presence of microglial ensheathment

Recent experimental evidence has shown that glial cells, including microglia and astrocytes, can ensheathe synapses, positioning them to disrupt neurotransmitter flow between pre- and post-synaptic terminals. This study extends micro- and network-scale theoretical models to explore how varying degrees of synaptic ensheathment affect synaptic communication and network dynamics. Consistent with previous studies, our microscale model shows that ensheathment accelerates synaptic transmission while reducing its strength and reliability, with the potential to effectively switch off synaptic connections. Building on these findings, we integrate an "effective" glial cell model into a large-scale neuronal network. Specifically, we analyze a network with highly heterogeneous synaptic strengths and time constants, where glial proximity parametrizes synaptic parameters. Unlike previous models that assumed normal parameter distributions, our model uses parameters drawn from distinct distributions. This framework is applied to large networks of exponential integrate-and-fire neurons, extending linear response theory to analyze not only firing rate distributions but also noise correlations across the network. Despite the significant heterogeneity in the system, a mean-field approximation accurately captures network statistics. We demonstrate the utility of our model by reproducing experimental findings, showing that microglial ensheathment leads to post-anesthesia hyperactivity in excitatory neurons of mice. Furthermore, we explore how glial ensheathment may be used in the visual cortex to target specific neuronal subclasses, tuning higher-order network statistics.

neuroscience↗

bioRxiv2024

Unveiling the control of N and P on DOM fate in a Mediterranean coastal environment

Dissolved organic matter (DOM) and heterotrophic prokaryotes (HP) are key players in the oceanic carbon cycle. Although several biotic and abiotic factors controlling DOM fates are known, the hierarchy of their respective influences is still debated. Two contrasting Mediterranean coastal sites were sampled: a harbour under strong continental and anthropogenic influence (T) and an open coastal area (G). Interestingly, similar dissolved organic carbon (DOC) concentrations were observed in both samples. However, they showed marked differences in dissolved inorganic nitrogen and organic phosphorus concentrations (60-fold and 80% higher value in T), as well as in DOM optical properties and molecular composition. Incubation experiments were performed to expose the HP communities of each site to dissolved substances from T and G for three weeks. DOC removal was similar (-10 %) regardless HP origin and dissolved substances characteristics. HP growth and their maximal abundance were higher (+ 300 %) with dissolved substances from T, regardless HP origins. This indicates different fates of DOC processed by microbial communities as a function of abiotic determinants. Higher HP growth was associated to elevated initial content and higher consumption of inorganic nitrogen, organic phosphorus, three fluorescent DOM components, nitrogen-containing molecules and carbohydrates. These results provide insights into the main drivers of marine DOM fate: at similar DOC concentrations and low inorganic P concentrations. We evience the preferential consumption of lignin-like compounds where theoretically more labile molecules were available, thus reinforcing the need of in depth molecular studies for a better understanding of DOM-microbes interactions in the ocean.

ecology↗

bioRxiv2024

Hypervariable DOM properties in coastal NW Mediterranean Sea -Evidences of strong human influences and potential consequences for the heterotrophic base of planktonic food webs

Marine DOM plays a key role in the carbon cycle. Though there is growing interest for its chemical and ecological properties, its variability in the very heterogeneous coastal environment is poorly documented. In this study, we assessed the spatial and temporal variations in marine coastal DOM chemical properties and its potential to support the growth of the heterotrophic basis of the planktonic food-web. For that, we considered two NW Mediterranean coastal sampling stations under contrasted continental and human influences. From January to July 2022, DOC concentration demonstrated a progressive increasing trend in addition to marked spatial differences. DOM composition presented more variations in time than in space. These variations appeared related to a combination of direct freshwater inputs tracked by salinity variations, direct human contaminations tracked by concentrations in Cu and Pb, and phytoplanktonic production. An experimental approach was also used at each sampling date to evaluate DOM ability to support the growth of heterotrophic prokaryotes. Significantly higher growth was observed with DOM from a site under higher continental and human influences. Water temperature exerted a higher control on growth than DOM properties. Correlation analysis with DOM sources suggested the uncoupling of phytoplanktonic production and growth of heterotrophic prokaryotes, which appeared better supported by human contaminations and, to a lesser extent, freshwater inputs. Sediment resuspension in harbors and antifouling paints could represent two important sources of bioavailable resources, favoring fast heterotrophic growth and higher net production, respectively.

ecology↗

bioRxiv2023

Intraspecific trait variation modulates the temperature effect on elemental quotas and stoichiometry in marine Synechococcus

Diverse phytoplankton modulate the coupling between the ocean carbon and nutrient cycles through life-history traits such as cell size, elemental quotas, and ratios. Biodiversity is mostly considered at broad functional levels, but major phytoplankton lineages are themselves highly diverse. As an example, Synechococcus is found in nearly all ocean regions and contain extensive intraspecific variation. Here, we grew four closely related Synechococcus isolates in semi-continuous cultures across a range of temperatures (16-25{degrees}C) to quantify for the relative role of intraspecific trait variation vs. environmental change. We report differences in cell size (p<0.01) as a function of strain and clade (p<0.01). The carbon (QC), nitrogen (QN), and phosphorus (QP) cell quotas all increased with cell size. Furthermore, cell size has an inverse relationship to growth rate. Within our experimental design, temperature alone had a weak physiological effect on cell quota and elemental ratios. Instead, we find systemic intraspecific variance of C:N:P, with cell size and N:P having an inverse relationship. Our results suggest a key role for intraspecific life history traits in determining elemental quotas and stoichiometry. Thus, the extensive biodiversity harbored within many lineages may modulate the impact of environmental change on ocean biogeochemical cycles.

ecology↗

bioRxiv2021

Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike

Memory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.

immunology↗

bioRxiv2020

High spatial resolution global ocean metagenomes from Bio-GO-SHIP repeat hydrography transects

Detailed descriptions of microbial communities have lagged far behind physical and chemical measurements in the marine environment. Here, we present 720 globally distributed surface ocean metagenomes collected at high spatio-temporal resolution. Our low-cost metagenomic sequencing protocol produced 2.75 terabases of data, where the median number of base pairs per sample was 3.48 billion. The median distance between sampling stations was 26 km. The metagenomic libraries described here were collected as a part of a biological initiative for the Global Ocean Ship-based Hydrographic Investigations Program, or "Bio-GO-SHIP." One of the primary aims of GO-SHIP is to produce high spatial and vertical resolution measurements of key state variables to directly quantify climate change impacts on ocean environments. By similarly collecting marine metagenomes at high spatiotemporal resolution, we expect that this dataset will help answer questions about the link between microbial communities and biogeochemical fluxes in a changing ocean.

genomics↗

bioRxiv2020

3D-printed drug testing platform based on a 3D model of aged human skeletal muscle

Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modelling, the bioengineered muscle is treated with tumor necrosis factor to mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline(R) Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.

bioengineering↗