Biology subjects

Rios, M.

Publications and source records attributed to Rios, M..

8 recordsLinked to original sources

bioRxiv2026

Metabolite profiles distinguish exposure to Dengue and Zika flaviviruses in human induced pluripotent stem cells (hiPSCs)

Flaviviruses such as Dengue virus (DENV), Zika virus (ZIKV) and West Nile Virus (WNV) pose growing public health threats, exacerbated by asymptomatic infections and non-vector transmission. Current diagnostics, including nucleic acid tests and serology, are limited by transient viremia and antibody cross-reactivity, underscoring the need for improved detection methods. We utilized untargeted metabolomics to differentiate DENV and ZIKV infections in human induced pluripotent stem cells (hiPSCs), a model relevant to study virus-host interactions, drug screening, and therapeutic safety. LC-MSbased profiling revealed virus-specific metabolic reprogramming during both acute and long-term infections. DENV3 induced early and sustained activation of metabolic features, while ZIKV-MR766 triggered transient suppression. Long term infection with DENV2, DENV3, or ZIKV-PRV resulted in distinct metabolic signatures in hiPSCs, with ZIKV-PRV showing the greatest divergence. Shared metabolite changes across conditions included amino acids (e.g., tryptophan, glutamate), lipids, and nucleosides. Functional studies demonstrated that tryptophan metabolism regulates infection dynamics: inhibiting serotonin biosynthesis reduced viral load, whereas blocking kynurenine synthesis enhanced viral replication. These findings position metabolomics as a viable approach for flavivirus detection and highlight metabolic pathways as potential therapeutic targets. ImportanceAccurate diagnosis of flavivirus infections remains challenging due to short periods of viremia, high rates of asymptomatic infection, and extensive serologic cross-reactivity among related viruses such as DENV and ZIKV. These limitations complicate clinical diagnosis, surveillance, and screening of human donor tissues. In this study, we demonstrate that untargeted metabolomics can distinguish ZIKV and DENV infections by identifying virus-specific host metabolic signatures during both acute and long-term infection. Using human induced pluripotent stem cells as a clinically relevant model, we show that metabolic reprogramming persists even in the absence of overt cytopathic effects and can reveal functional pathways that regulate viral replication. Our findings highlight host metabolite profiling as a complementary diagnostic strategy that may improve detection of flavivirus exposure, particularly in asymptomatic individuals or settings where conventional molecular and serologic tests are insufficient.

microbiology↗

bioRxiv2024

Zika and Dengue Viruses Differentially Modulate Host mRNA Processing Factors Defining Its Virulence

Rising global temperatures coupled with increasing international travel, and trade are contributing to spread of vectors such as ticks and mosquitoes, resulting in a surge of vector-borne flavivirus infection in human population. Furthermore, this increase in flavivirus infection pose threat to the safety of biologics such as cell and gene therapy products as human-derived materials are commonly used during manufacturing of these drug products. In this study, we conducted time-course transcriptomic and protein analyses to uncover the host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in the context of host defense mechanisms, as these two viruses have caused the most recent and significant flavivirus outbreaks. Compared to DENV, ZIKV exhibited stronger virulence and cytopathic effects. RNA sequencing analysis revealed differential expression of various cellular factors, including RNA processing factors. Further investigation identified cell-type and time-dependent upregulation nonsense-mediated RNA decay (NMD), RNA degradation factors and nuclear pore complex (NPC) transcripts. Protein analysis showed that ZIKV, unlike DENV, degrades NMD factors in host cells, which along with mis-regulation of RNA degradation factors resulted in accumulation in host intronic transcripts as revealed by RNA-seq data. We also found that active nuclear transport is required for ZIKV replication, suggesting that therapeutic targeting of the NPC could potentially be effective in controlling ZIKV infection. Furthermore, from our findings we hypothesize that, ZIKV, but not DENV, drives early host cell cytopathy through targeted protein degradation. Current studies are underway to develop novel strategies to detect ZIKV, DENV and other flaviviruses in biologics based on transcriptomics and proteomics. TeaserExploring the molecular basis of flavivirus virulence in host cells.

genomics↗

bioRxiv2024

Postglacial Genetic Legacies, Demography, and Climate Change: Setting Conservation Priorities for Silver Fir

AimClimate change challenges the adaptive capacity of several tree species. This study explores the genetic diversity and past range dynamics of silver fir (Abies alba) with the objective of set hotspots of population diversity and priorities for conservation based on climate change-induced dieback. LocationMediterranean, Europe MethodsWe perform genome-wide analysis by RAD-seq to range-wide 26 A. alba populations. ResultsWe identified two lineages in the southern range, formed by populations from the Apennine chain, from the west side, and those from the Balkans and Carpathians, from the east side. Northern range populations showed two lineages, with definite genetic differences between the westernmost populations from those from the eastern. Populations from the Northern Balkans and the NE Apennine were situated in the intermediate positions. Regarding demographics, southern populations remained stable as glacial refuges, while northern populations experienced a population decline during the middle Pleistocene due to glaciations. Although the demographic events that shaped the current spatial structure of genetic diversity of silver fir go back to the Pleistocene, human pressure during the Holocene likely led to an abrupt range decline, while recent drought events have caused widespread dieback. Main ConclusionsWe provide a generic framework for setting silver fir conservation priorities based on the phylogeographical lineages and current dieback symptoms induced by climate change. Our results support that rear edge populations might be disproportionately important for the adaptive capacity of silver fir under a climate change scenario.

evolutionary biology↗

bioRxiv2024

A Receptor Like Cytoplasmic Kinase evolved in Aeschynomene legumes to mediate Nod-independent rhizobial symbiosis

Many plants interact symbiotically with arbuscular mycorrhizal (AM) fungi to enhance inorganic phosphorus uptake, and legumes also develop a nodule symbiosis with rhizobia for nitrogen acquisition. Establishment and functioning of both symbioses rely on a common plant signaling pathway activated by structurally related Myc- and Nod-factors. Recently, a SPARK Receptor-like-Kinase (RLK)/Receptor-like Cytoplasmic Kinase (RLCK) complex was shown to be essential for AM in both monocot and dicot plants. Here, we show that in Aeschynomene legumes the RLCK component of this receptor complex has evolved following a gene duplication event and mediates a unique nodule symbiosis that is independent of rhizobial Nod factors. In Aeschynomene evenia, AeRLCK2 is crucial for nodule initiation but not for AM. Additionally, AeRLCK2 physically interacts with and is phosphorylated by the Cysteine-rich RLK, AeCRK, also required for nodulation. This work reveals a novel evolutionary origin of this Nod-independent symbiosis from AM.

plant biology↗

bioRxiv2023

ORM-mediated regulation of sphingolipid biosynthesis is essential for nodule formation in Aeschynomene evenia

Legumes are able to establish symbiotic interactions with nitrogen-fixing rhizobia that are accomodated in root-derived organs, the nodules. Rhizobia recognition triggers a plant symbiotic signalling pathway activating two coordinated processes: infection and nodule organogenesis. How these are orchestrated in legumes species utilizing intercellular infection and lateral root-base nodulation remain elusive. Here, we show that Aeschynomene evenia OROSOMUCOID PROTEIN 1 (AeORM1), a key regulator of sphingolipid biosynthesis, is required for nodule formation in this legume species. Using A. evenia orm1 mutants, we demonstrate that alterations in AeORM1 function result in numerous early aborted nodules, exhibiting defense-like reactions, and shortened lateral roots. Consistantly, AeORM1 was expressed during lateral root initiation and elongation, including at lateral root bases where nodule primordia form in the presence of symbiotic bradyrhizobia. Sphingolipidomics revealed that mutations in AeORM1 leaded to sphingolipid overaccumulation in roots, in particular the very-long-chain-fatty-acid (VLCFA)-containing ceramids relative to the wild-type plants. Taken together, our findings reveal that AeORM1-regulated sphingolipid homeostasis is essential for rhizobial infection and nodule organogenesis, and indicate a shared requirement for nodule formation and lateral root development in A. evenia.

plant biology↗

bioRxiv2022

Genetic analysis of the rice jasmonate receptors reveals specialized function for OsCOI2

O_LICOI1-mediated perception of jasmonate is critical for plant development and responses to environmental stresses. Monocots such as rice have two groups of COI genes due to gene duplication: OsCOI1a and OsCOI1b that are functionally equivalent to the dicotyledons COI1 on one hand and OsCOI2 whose function remains unclear. C_LIO_LIIn order to assess the function of OsCOI2 and its functional redundancy with COI1 genes, we developed a series of rice mutants in the 3 genes OsCOI1a, OsCOI1b and OsCOI2 by CRISPR Cas9 and characterized their phenotype and responses to jasmonate. C_LIO_LICharacterization of OsCOI2 uncovered important roles in root, leaf and flower development. In particular, we show that crown root growth inhibition by jasmonate relies on OsCOI2 and not OsCOI1a or OsCOI1b in rice, revealing a major function for the non-canonical OsCOI2 in jasmonate-dependent control of rice root growth. C_LIO_LICollectively, these results point to a specialized function of OsCOI2 in the regulation of plant development in rice and indicate that sub-functionalisation of jasmonate receptors has occurred in the monocot phylum. C_LI

plant biology↗

bioRxiv2018

Glia mediated ionic balance in the stem cell niche is required for the proper proliferation of neurogenic tissues and wiring of neural circuits.

The cellular niche that surrounds stem cells modulates their self-renewal and proliferative properties. In the nervous system glial cells form part of the neural stem cell niche and express a wide variety of ion channels. While the physiological roles of ion channels in glia have been mainly studied in the mature nervous system, the contribution of glial ion channel function in the niche to nervous system development is poorly understood. To gain insight we explored the function of the Drosophila ClC-a chloride channel since its human ortholog CLCN2 is expressed in glial cells and impairment of its function results in neurodevelopmental disorders. We found ClC-a expressed in the niche in cortex glia. These glial cells are in close association with neurogenic tissues and also wrap neuronal cell bodies as they mature away from the niche. Characterization of loss of function ClC-a mutants showed these animals had smaller brains and widespread axon guidance defects. Here we show that ClC-a is required in cortex glia for the proliferation of neuroepithelial cells and neuroblasts, as well as for neuronal survival. We could also relate the axon guidance defects observed in photoreceptors to impaired proliferation in a neuroblast lineage that generates guidepost glial cells essential for this process. Taken together, our results show that ion channels expressed in glia forming part of the neural stem cell niche can have a significant impact on nervous system development. We propose that ion channels can non-autonomously modulate the number of neural progenitors and the progeny of neuroblast lineages, consequently affecting the correct assembly of neural circuits.

developmental biology↗

bioRxiv2016

TrkB signaling underlies the rapid antidepressant effects of isoflurane

A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3{beta} (GSK3{beta}). Moreover, isoflurane affected neuronal plasticity by facilitating long-term potentiation in the hippocampus. We also found that isoflurane increased activity of the parvalbumin interneurons, and facilitated GABAergic transmission in wild type mice but not in transgenic mice with reduced TrkB expression in parvalbumin interneurons. Our findings strengthen the role of TrkB signaling in the antidepressant responses and encourage further evaluation of isoflurane as a rapid-acting antidepressant devoid of the psychotomimetic effects and abuse potential of ketamine.

neuroscience↗