Biology subjects

Segura, A.

Publications and source records attributed to Segura, A..

7 recordsLinked to original sources

bioRxiv2026

An orphan LuxR regulator controls plant developmental reprogramming during interaction with Novosphingobium resinovorum HR1a

Rhizoremediation depends on productive plant/pollutant-degrading microorganism interactions, yet the bacterial regulatory mechanisms that shape host responses remain poorly understood. We investigated the role of the previously uncharacterized orphan LuxR874 from the polycyclic aromatic hydrocarbon (PAH) degrading bacterium Novosphingobium resinovorum HR1a, in the modulation of plant physiology. Bacterial transcriptomics revealed that LuxR874 controls the expression of genes associated with aromatic and sugar metabolism, and acylCoA related functions. Inactivation of luxR874 altered bacterial responses without affecting root colonization, suggesting that this regulator contributes to the physiological state required to elicit host responses. In gnotobiotic systems, HR1a induced a root phenotype characterized by reduced primary root elongation, increased root thickness, and enhanced root hair formation. These alterations were attenuated in the luxR874 mutant and restored by complementation despite similar colonization levels among strains. Plant RNA-seq analyses revealed extensive host transcriptional reprogramming, including activation of developmental regulators, hormone associated pathways, cell wall remodeling genes, and oxidative stress responses. In contrast, plants inoculated with the luxR874 mutant displayed a weaker transcriptional response resembling the non-inoculated state. Functional analyses supported LuxR874-dependent activation of reactive oxygen species and ethylene related pathways. Our results reveal an unexpected role for an orphan LuxR regulator in coordinating multi-level responses during a rhizoremediation-relevant plant microbe interaction.

molecular biology↗

bioRxiv2025

Aberrant formation of long-range projections across different neurodevelopmental disorders converges on molecular and cellular nexuses

Establishing long-range connections during human brain development is an intricate multi-step process disturbed in many neurodevelopmental disorders (NDDs). The aberrant formation of these connections is caused by mutations in a plethora of different genes with distinct molecular functions, triggering the question of whether there are common key downstream mediators at which different pathologies are converging. We employed brain organoids to model early human brain developmental aspects of Coffin-Siris-like 9, Opitz BBB/G, and Pitt-Hopkins syndromes. These NDDs are caused by mutations in SOX11, MID1, and TCF4 respectively, and are characterized by a multitude of distinct symptoms yet share alterations in long-range projections as a common feature. Here, we uncover that mutations in all three genes phenotypically converge, showing impaired neurite extension with increased tortuosity and decreased growth speed resulting in shorter beelines. Moreover, the mutant neurites exhibit a decrease in growth persistence providing a conceptual framework explaining why long- but not short-range connections are affected. Correlating with the converging cellular phenotype, molecular characterization revealed a striking convergence on signaling pathways implicated in the interaction of neurites with their extracellular environment. In-silico modeling and perturbation of neurite outgrowth suggest that altered neurite-extracellular environment interactions are sufficient to recapitulate the mutant phenotypes but also facilitate the prediction of specific parameters causing disturbed neurite growth in mutant neurons.

developmental biology↗

bioRxiv2025

Effect of diesel contamination on bacterial populations in a pristine soil during rhizoremediation

Background and aimsContamination of soils with hydrocarbons such as diesel is of major concern as use and transport increases. In order to obtain a better understanding of how soil microorganisms face diesel during rhizoremediation of a natural soil will help us improve remediation processes. MethodsWe conducted microcosm experiments with a pristine soil contaminated or not with diesel and planted with clover, clover/ryegrass or non-planted controls. We measured the aromatic fraction of diesel by HPLC-DAD along time under the different experimental conditions and determined the bacterial communities in soil and the rhizosphere by amplicon sequencing of the 16S rRNA gene. ResultsThe presence of clover accelerates the disappearance of the aromatic components of diesel but not significantly so. The bacterial diversity is lowered by diesel contamination although this decline is mitigated by the presence of plants. Bacterial community structure is mostly affected by soil type and then by diesel contamination. Actinobacteriota and Gemmatimonadota decline while Firmicutes, Bacteroidota and Proteobacteria increase with diesel contamination and in the rhizosphere. Amplified sequence variants (ASVs) belonging to Novosphingobium and Sphingomonas are especially abundant in diesel contaminated bulk soil and ASVs belonging to Azospirillum, Rhizobium, Ohtaekwangia Faecalibacterium, and Subdoligranulum are especially abundant in diesel contaminated rhizosphere. ConclusionClover helps dissipate diesel aromatic compounds faster from a pristine soil. Clover and ryegrass mitigate the decline of bacterial diversity in soil due to diesel contamination and certain bacterial taxa which are enriched with the contaminant are identified which may play a role to remediate diesel contamination.

microbiology↗

bioRxiv2024

A murine experimental model of the unique pulmonary thrombotic effect induced by the venom of the snake Bothrops lanceolatus

BackgroundThe venom of Bothrops lanceolatus, a viperid species endemic to the Lesser Antillean Island of Martinique, induces a unique clinical manifestation, i.e., thrombosis. Previous clinical observations indicate that thromboses are more common in patients bitten by juvenile specimens. There is a need to develop an experimental model of this effect in order to study the mechanisms involved. Methodology/principal findingsThe venoms of juvenile and adult specimens of B. lanceolatus were compared by (a) describing their proteome, (b) assessing their ability to induced thrombosis in a mouse model, and (c) evaluating their in vitro procoagulant activity and in vivo hemostasis alterations. Venom proteomes of juvenile and adult specimens were highly similar. When injected by the intraperitoneal (i.p.) route, the venom of juvenile specimens induced the formation of abundant thrombi in the pulmonary vasculature, whereas this effect was less frequent in the case of adult venom. Thrombosis was not abrogated by the metalloproteinase inhibitor Batimastat. Both venoms showed a weak in vitro procoagulant effect on citrated mouse plasma and bovine fibrinogen. When administered intravenously (i.v.) venoms did not affect classical clotting tests (prothrombin time and activated partial thromboplastin time) but caused a partial drop in fibrinogen concentration. The venom of juvenile specimens induced partial alterations in some rotational thromboelastometry parameters after i.v. injection. No alterations in coagulation tests were observed when venoms were administered i.p., but juvenile and adult venoms induced a marked thrombocytopenia. Conclusions/significanceAn experimental model of the thrombotic effect induced by B. lanceolatus venom was developed. This effect is more pronounced in the case of venom of juvenile specimens, despite the observation that juvenile and adult venom proteomes are similar. Adult and juvenile venoms do not induce a consumption coagulopathy characteristic of other Bothrops sp venoms. Both venoms induce a conspicuous thrombocytopenia. This experimental model reproduces the main clinical findings described in these envenomings and should be useful to understand the mechanisms of this thrombotic effect. Author summaryEnvenomings by the viperid species Bothrops lanceolatus, endemic of the Caribbean Island of Martinique, are characterized by a unique thrombotic effect responsible for infarcts in various organs. Until now, no experimental in vivo models of this effect have been described. In this study, we developed a mouse model of thrombosis by using the intraperitoneal route of venom injection. The venom of juvenile specimens of B. lanceolatus induced the formation of abundant thrombi in the lungs, whereas the effect was much less pronounced with the venom of adult specimens. This difference in the ability of juvenile and adult venoms occurs despite both venoms having highly similar proteomic profiles. Both adult and juvenile venoms showed a weak in vitro procoagulant effect on plasma and fibrinogen, underscoring a thrombin-like (pseudo-procoagulant) activity. In vivo, the venoms did not affect the classical clotting tests (prothrombin time and activated partial thromboplastin time) but induced a partial drop in fibrinogen concentration and limited alterations in rotational thromboelastometry parameters when injected by the i.v. route. In contrast, few alterations of these parameters were observed after i.p. injection of venoms, in conditions in which thrombosis occurred, hence evidencing the lack of a consumption coagulopathy. After i.p. injection both venoms induced a pronounced thrombocytopenia. This experimental model reproduces some of the main clinical manifestations of envenoming by this species. This model can be used to identify the toxins responsible for the thrombotic effect, to study the mechanism(s) of thrombosis and to assess the preclinical efficacy of antivenoms.

pharmacology and toxicology↗

bioRxiv2021

Single cell quantification of ribosome occupancy in early mouse development

Technological limitations precluded transcriptome-wide analyses of translation at single cell resolution. To solve this challenge, we developed a novel microfluidic isotachophoresis approach, named RIBOsome profiling via IsoTachoPhoresis (Ribo-ITP), and characterized translation in single oocytes and embryos during early mouse development. We identified differential translation efficiency as a key regulatory mechanism of genes involved in centrosome organization and N6-methyladenosine modification of RNAs. Our high coverage measurements enabled the first analysis of allele-specific ribosome engagement in early development and led to the discovery of stage-specific differential engagement of zygotic RNAs with ribosomes. Finally, by integrating our measurements with proteomics data, we discovered that ribosome occupancy in germinal vesicle stage oocytes is the predominant determinant of protein abundance in the zygote. Taken together, these findings resolve the long-standing paradox of low correlation between RNA expression and protein abundance in early embryonic development. The novel Ribo-ITP approach will enable numerous applications by providing high coverage and high resolution ribosome occupancy measurements from ultra-low input samples including single cells.

developmental biology↗

bioRxiv2021

High efficacy of therapeutic equine hyperimmune antibodies against SARS CoV-2 variants of concern

SARS-CoV-2 variants of concern (VoC) show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies. We tested therapeutic equine polyclonal antibodies (pAbs) against four VoC (alpha, beta, epsilon and gamma). We show that equine pAbs efficiently neutralize VoC, suggesting they are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

microbiology↗

bioRxiv2020

Development and pre-clinical characterization of two therapeutic equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.

microbiology↗