Biology subjects

Luna, E.

Publications and source records attributed to Luna, E..

15 recordsLinked to original sources

bioRxiv2026

Microglial reactivity in the hippocampal CA2 is associated with advanced neuronal α-synulceinopathy

Lewy body diseases are thought to evolve by the spread of intraneuronal -synuclein pathology. However, staging models of -synuclein pathology in the human brain seldom evaluate regions with direct synaptic connectivity to model microglial processes in disease. Here, we address this gap by testing the hypothesis that, within the well-defined synaptic connectivity of the intrahippocampal circuit, neuronal -synuclein pathology is associated with microglial reactivity. We selected a cohort of autopsy-confirmed Lewy body disease patients with hippocampal neuronal -synuclein pathology and minimal age-related co-pathologies (n=62) and as a control for other intraneuronal hippocampal pathology, we used a cohort of cognitively healthy patients with focal hippocampal tau accumulation with minimal amyloid plaques, termed primary age-related tauopathy (n=12). We immunostained consecutive hippocampal sections for -synuclein pathology and established markers of microglial reactivity, Iba1, HLA-DR, and CD68. With validated digital histology methods, we measured percent area occupied in 6 hippocampal subfields to compare the percent area occupied within subfields between patient cohorts, correlate the percent area occupied within and between subfields, and use linear-mixed effects models to compare the percent area occupied across subfields while co-varying for demographics. We also constructed two groups of either low-level hippocampal -synuclein pathology restricted to the cornu ammonis 2-3 subfields (Focal Subtype) or widespread -synuclein pathology within additional subfields (Widespread Subtype) to model hypothesized -synuclein pathological spread within the intrahippocampal circuit. Lewy body disease patients exhibited increased HLA-DR and CD68 in most hippocampal subfields compared with primary age-related tauopathy. In Lewy body disease patients, staining for all microglial markers was highest in the cornu ammonis field 2. Neuronal -synuclein pathology in the cornu ammonis field 2 consistently correlated with only HLA-DR and CD68 but not Iba1. Patients classified as the Widespread Subtype had worse cognitive impairment and increased HLA-DR and CD68 within the cornu ammonis field 2. Furthermore, HLA-DR and CD68 in the cornu ammonis field 2 correlated with distal neuronal -synuclein pathology only in subfields with retrograde connectivity. We found increased hippocampal microglial abnormalities in Lewy body disease patients compared with cognitively normal controls with primary age-related tauopathy, suggesting a relatively specific microglial/inflammatory response to neuronal -synuclein pathology. Our data is consistent with predominantly retrograde transmission of neuronal -synuclein pathology across hippocampal subfields, where the focal microglial response in the cornu ammonis field 2 may influence clinical outcomes and -synuclein pathological spread. These data suggest that microglial processes can help refine Lewy body disease histopathological staging.

neuroscience↗

bioRxiv2025

Epigenomic Landscape of Oak (Quercus robur) across Seasons and Generations

O_LISeasonal fluctuations strongly shape the physiology of long-lived trees by coordinating growth, dormancy, and stress responses. Increasing evidence points to epigenetic mechanisms, particularly DNA methylation, as regulators of these processes, yet their role in long-lived trees across seasons and generations remains poorly understood. C_LIO_LIWe generated single-base resolution maps of cytosine methylation exploring the epigenetic landscape of 180 year-old mature oak (Quercus robur) trees (genetically homogeneous) along spring, summer and autumn, and in their progeny. C_LIO_LIGenome-wide DNA-methylation revealed a progressive increase in the CHH context (H = A, T or C) from Spring to Summer and Autumn, suggesting epigenetic reprogramming is happening over season. Differentially Methylated Regions (DMRs) were concentrated in promoter regions and terminal inverted repeat (TIR). Differentially methylated transposable elements (TEs) and genes were involved in leaf development and hormonal signalling. By contrast, generational differences (parents versus offspring) were most prominent in CG and CHG contexts and were concentrated in genic regions. C_LIO_LIOaks exhibit distinct seasonal and generational DNA methylation signatures, highlighting the plasticity and developmental specificity of epigenetic regulation. These findings provide a genomic foundation for understanding how epigenetic memory contributes to phenology, developmental programming and long-term adaptation in long-lived plants. C_LI

genetics↗

bioRxiv2025

Unravelling Induced Resistance in Strawberry: Distinct Metabolomic Signatures Define Cultivar-Specific Resistance to Botrytis cinerea

Botrytis cinerea is a major pathogen in strawberry, and sustainable alternatives to fungicides are needed to manage this disease. Induced resistance (IR) through chemical elicitors represents a promising strategy, but the effectiveness of such compounds remains poorly understood in commercial strawberry (Fragaria x ananassa) cultivars. In this study, we evaluated the efficacy of repeated applications of five elicitors (i.e., {beta}-aminobutyric acid (BABA), (R)-{beta}-homoserine (RBH), indole-3-carboxylic acid (I3CA), jasmonic acid (JA), and salicylic acid (SA)) in three strawberry cultivars (Rowena, Soraya, and Durban). BABA and RBH significantly reduced B. cinerea lesion sizes in Rowena and Soraya, while Durban showed no induced resistance to the elicitors. Untargeted metabolomic profiling of Rowena and Soraya revealed cultivar-specific responses to elicitor treatment and infection, with distinct patterns of metabolite accumulation under both mock- and B. cinerea-inoculated conditions. RBH in Rowena and BABA in Soraya induced the most extensive priming-associated metabolic reprogramming, including enrichment of amino acid, nucleotide, and secondary metabolite pathways such as flavonoids and phenylpropanoids. Significantly, none of the elicitors negatively affected plant growth, flowering, or fruit set. These results demonstrate that the effectiveness and mechanism of IR in strawberries depend on both the elicitor and the cultivar, providing new insights into the metabolomic basis of priming with implications for sustainable disease management in strawberry cultivation.

plant biology↗

bioRxiv2025

Multi-year study on the effects of elevated CO2 in mature oaks unravels subtle metabolic adjustments but stable biotic stress resistance

O_LIRising atmospheric CO2 levels are predicted to influence forest health directly and indirectly, yet the long-term effects of elevated CO2 (eCO2) on mature trees in natural ecosystems remain poorly understood. Understanding how eCO2 affects susceptibility to biotic stress and alters leaf metabolism is critical for predicting forest responses to climate change. C_LIO_LIWe examined the effects of eCO2 (+150 ppm) on 180-year-old Quercus robur at the Birmingham Institute of Forest Research (BIFoR) Free Air CO2 Enrichment (FACE) facility. From 2016 (pre-treatment) to 2024 (year 8 of enrichment), we monitored natural powdery mildew infection and insect herbivory, alongside targeted and untargeted metabolomic profiling of leaf material collected across the growing season. C_LIO_LIWhile seasonal patterns and an overall decline in PM and herbivory were observed, no consistent differences in biotic stress incidence emerged due to eCO2. Metabolomic data revealed subtle but widespread shifts, especially in amino acid, CoenzymeA, and redox pathways. C_LIO_LIThese results suggest that although eCO2 drives extensive metabolic changes, it does not alter biotic stress resistance in mature oaks. Instead, eCO2 appears to promote physiological plasticity that may shape future responses to combined environmental stressors. These insights offer a valuable reference point for interpreting long-term ecosystem dynamics. C_LI

plant biology↗

bioRxiv2024

Elicitor specific mechanisms of defence priming in oak seedlings against powdery mildew

Defence priming sensitises plant defences to enable a faster and/or stronger response to subsequent stress. Various chemicals can trigger priming; however, the response remains unexplored in oak. Here, we characterise salicylic acid (SA)-, jasmonic acid (JA)-, and {beta}-aminobutyric acid (BABA)-induced priming of oak seedlings against the causal agent of powdery mildew (Erysiphe alphitoides, PM). Whilst JA had no effects, BABA and SA enhanced resistance by priming callose deposition and SA-dependent gene expression, respectively. Untargeted transcriptome and metabolome analyses revealed genes and metabolites uniquely primed by BABA, SA, and JA. Enrichment analyses demonstrated a limited number of pathways differentiating the three treatments or the resistance-inducing elicitors BABA and SA. However, a similar mode of action between BABA and JA was identified. Moreover, our analyses revealed a lack of crosstalk between SA and JA. Interestingly, priming by BABA was linked to alkaloid, lignan, phenylpropanoid, and indolitic compounds biosynthesis. Moreover, integration of the omics analyses revealed the role of ubiquitination and protein degradation in priming by BABA. Our results confirm the existence of chemical-induced priming in oak and has identified specific molecular markers associated with well-characterised elicitor.

plant biology↗

bioRxiv2023

Mechanism of 2-Fucosyllactose degradation by Human-Associated Akkermansia

Among the first microorganisms to colonize the human gut of breastfed infants are bacteria capable of fermenting human milk oligosaccharides (HMOs). One of the most abundant HMOs, 2-fucosyllactose (2-FL), may specifically drive bacterial colonization of the intestine. Recently, differential growth has been observed across multiple species of Akkermansia on various HMOs including 2FL. In culture, we found growth of two species, A. muciniphila MucT and A. biwaensis CSUN-19, in HMOS corresponded to a decrease in the levels of 2-FL and an increase in lactose, indicating that the first step in 2-FL catabolism is the cleavage of fucose. Using phylogenetic analysis and transcriptional profiling, we found that the number and expression of fucosidase genes from two glycoside hydrolase (GH) families, GH29 and GH95, varies between these two species. During mid-log phase growth, the expression of several GH29 genes was increased by 2-FL in both species, whereas the GH95 genes were induced only in A. muciniphila. We further show that one putative fucosidase and a {beta}-galactosidase from A. biwaensis are involved in the breakdown of 2-FL. Our findings indicate that that plasticity of GHs of human associated Akkermansia sp. enable access to additional growth substrates present in HMOs, including 2-FL. Our work highlights the potential for Akkermansia to influence the development of the gut microbiota early in life and expands the known metabolic capabilities of this important human symbiont. IMPORTANCEAkkermansia are mucin degrading specialists widely distributed in the human population. Akkermansia biwaensis has recently been observed to have enhanced growth relative to other human associated Akkermansia on multiple human milk oligosaccharides (HMOs). However, the mechanisms for enhanced growth are not understood. Here, we characterized the phylogenetic diversity and function of select genes involved in growth of A. biwaensis on 2-fucosyllactose (2-FL), a dominant HMO. Specifically, we demonstrate that two genes in a genomic locus, a putative {beta}-galactosidase and -fucosidase, are likely responsible for the enhanced growth on 2-FL. The functional characterization of A. biwaensis growth on 2-FL delineates the significance of a single genomic locus that may facilitate enhanced colonization and functional activity of select Akkermansia early in life.

microbiology↗

bioRxiv2023

Developmentally regulated generation of a systemic signal for long-lasting defence priming in tomato

Tomato plants can be chemically primed to express long-lasting induced resistance (IR) for the protection of fruit against pathogen infection. Here, we determined that priming results in maintenance of IR in fruit and progeny of tomato plants only when initiated at an early developmental stage. Global DNA methylation analysis revealed seedling-specific changes, which occurred in the context of lower basal methylation, suggesting a greater epigenetic imprinting capacity of young plants. Remarkably, IR was found to be transmissible from primed rootstock to grafted unprimed scions. In these scions, we identified a subset of mobile 24 nt small RNAs associated with genes with enhanced expression in response to Botrytis cinerea infection in fruit, suggesting the functional association of a systemic signal with long-lasting IR and priming. Through integrated omics approaches we have identified markers of long-lasting priming in tomato fruit which could also serve as targets for durable resistance in other crops.

plant biology↗

bioRxiv2023

Phylogenetics, Epidemiology and Temporal Patterns of Dengue Virus type 1 in Araraquara, Sao Paulo State

Dengue virus is a prominent arbovirus with global spread, causing approximately 390 million infections each year. In Brazil, yearly epidemics follow a well-documented pattern of serotype replacement every three to four years on average. Araraquara, located in the state of Sao Paulo, has faced significant impacts from DENV epidemics since the emergence of DENV-1 in 2010. The municipality then transitioned from low to moderate endemicity in less than 10 years. Yet, there remains an insufficient understanding of the virus circulation dynamics, particularly concerning DENV-1, in the region, as well as the genetic characteristics of the virus. To address this, we generated 37 complete or partial DENV-1 genomes sampled from 2015 to 2022 in Araraquara. Then, using also Brazilian and worldwide DENV-1 sequences we reconstructed the evolutionary history of DENV-1 in Araraquara and estimated the time to the most recent common ancestor (tMRCA) for the serotype 1, for the genotype V and its main lineages. Within the last ten years, there were at least three introductions of genotype V in Araraquara, distributed in the two main lineages (LIa and LIb, and LII). The tMRCA for the first sampled lineage (2015/2016 epidemics) was approximately 15 years ago (in 2008). Crucially, our analysis challenges existing assumptions regarding emergence time of the DENV-1 genotypes, suggesting that genotype V might have diverged more recently than previously described. The presence of the two lineages of genotype V in the municipality might have contributed to the extended persistence of DENV-1 in the region.

genomics↗

bioRxiv2023

Elevated CO2 alters photosynthesis, growth and susceptibility to powdery mildew of oak seedlings

Elevated CO2 (eCO2) is a determinant factor of climate change and is known to alter plant processes such as physiology, growth and resistance to pathogens. Quercus robur, a tree species integrated in most forest regeneration strategies, shows high vulnerability to powdery mildew (PM) disease at the seedling stage. PM is present in most oak forests and it is considered a bottleneck for oak woodland regeneration. Our study aims to decipher the effect of eCO2 on plant responses to PM. Oak seedlings were grown in controlled environment at ambient (aCO2, ~ 400 ppm) and eCO2 (~ 1000 ppm), and infected with Erysiphe alphitoides, the causal agent of oak PM. Plant growth, physiological parameters and disease progression were monitored. In addition, to evaluate the effect of eCO2 on induced resistance (IR), these parameters were assessed after treatments with IR elicitor {beta}-aminobutyric acid (BABA). Our results show that eCO2 increases photosynthetic rates and aerial growth but in contrast reduces root length. Importantly, under eCO2 seedlings were more susceptible to PM. Treatments with BABA protected seedlings against PM, however, this effect was less pronounced under eCO2. Moreover, irrespectively of the concentration of CO2, BABA did not significantly change aerial growth but resulted in longer radicular systems, thus mitigating the effect of eCO2 in root shortening. Our results demonstrate the impact of eCO2 in plant physiology, growth and defence, and warrant further biomolecular studies to unravel the mechanisms by which eCO2 increases oak seedling susceptibility to PM.

plant biology↗

bioRxiv2022

Data science approaches provide a roadmap to understanding the role of abscisic acid in defence

Abscisic acid is a plant hormone well known to regulate abiotic stress responses. ABA is also recognised for its role in biotic defence, but there is currently a lack of consensus on whether it plays a positive or negative role. Here, we used supervised machine learning to analyse experimental observations on ABA to identify the most influential factors determining disease phenotypes. ABA concentration, plant age and pathogen lifestyle were identified in our computational predictions. We explored these predictions with new experiments in tomato, demonstrating that phenotypes after ABA treatment were highly dependent on plant age and pathogen lifestyle. Integration of these new results into the statistical framework refined the quantitative model of ABA influence, suggesting a framework for proposing and exploiting further research to make more progress on this complex question. Our approach provides a unifying road map to guide future studies involving the role of ABA in defence.

plant biology↗

bioRxiv2021

Utilization efficiency of human milk oligosaccharides by human-associated Akkermansia is strain-dependent

Akkermansia muciniphila are mucin degrading bacteria found in the human gut and are often associated with positive human health. However, despite being detected as early as one month of age, little is known about the role of Akkermansia in the infant gut. Human milk oligosaccharides (HMOs) are abundant components of human milk and are structurally similar to the oligosaccharides that comprise mucin, the preferred growth substrate of human-associated Akkermansia. A limited subset of intestinal bacteria has been shown to grow well on HMOs and mucin. We therefore examined the ability of genomically diverse strains of Akkermansia to grow on HMOs. First, we screened 85 genomes representing the four known Akkermansia phylogroups to examine their metabolic potential to degrade HMOs. Furthermore, we examined the ability of representative isolates to grow on individual HMOs in a mucin background and analyzed the resulting metabolites. All Akkermansia genomes were equipped with an array of glycoside hydrolases associated with HMO-deconstruction. Representative strains were all able to grow on HMOs with varying efficiency and growth yield. Strain CSUN-19 belonging to the AmIV phylogroup, grew to the highest level in the presence of fucosylated and sialylated HMOs. This activity may be partially related to the increased copy numbers and/or the enzyme activities of the -fucosidases, -sialidases, and {beta}-galactosidases. Utilization of HMOs by strains of Akkermansia suggests that ingestion of HMOs by an infant may enrich for these potentially beneficial bacteria. Further studies are required to realize this opportunity and deliver long-lasting metabolic benefits to the human host. ImportanceHuman milk oligosaccharides (HMOs) are utilized by a limited subset of bacteria in the infant gut. Akkermansia are detected in infants as young as one month of age and are thought to contribute to the HMO deconstruction capacity of the infant. Here, using phylogenomics, we examined the genomic capacity of different Akkermansia phylogroups to potentially deconstruct HMOs. Furthermore, we experimentally showed that strains from all the currently known phylogroups of Akkermansia can deconstruct all the major types of HMOs, albeit with different utilization efficiencies. This study thus examines Akkermansia-HMO interactions that can potentially influence the gut microbial ecology during the first 1,000 days of life - a critical phase for the development of the gut microbiome and infant health. This study will be of interest to a wide range of scientists from microbiologists, glycochemists/glycobiologists, to functional food developers investigating Akkermansia as probiotics or functional foods containing milk oligosaccharides as prebiotics.

microbiology↗

bioRxiv2020

Chitosan primes plant defence mechanisms against Botrytis cinerea, including expression of Avr9/Cf-9 rapidly-elicited genes

Current crop protection strategies against the fungal pathogen Botrytis cinerea rely on a combination of conventional fungicides and host genetic resistance. However, due to pathogen evolution and legislation in the use of fungicides, these strategies are not sufficient to protect plants against this pathogen. Defence elicitors can stimulate plant defence mechanisms through a phenomenon known as priming. Priming results in a faster and/or stronger expression of resistance upon pathogen recognition by the host. This work aims to study priming of a commercial formulation of the elicitor chitosan. Treatments with chitosan result in induced resistance in solanaceous and brassicaceous plants. In tomato plants, enhanced resistance has been linked with priming of callose deposition and accumulation of the plant hormone jasmonic acid (JA). Large-scale transcriptomic analysis revealed that chitosan primes gene expression at early time-points after infection. In addition, two novel tomato genes with a characteristic priming profile were identified, Avr9/Cf-9 rapidly-elicited protein 75 (ACRE75) and 180 (ACRE180). Transient and stable overexpression of ACRE75, ACRE180 and their Nicotiana benthamiana homologs, revealed that they are positive regulators of plant resistance against B. cinerea. This provides valuable information in the search for strategies to protect Solanaceae plants against B. cinerea.

plant biology↗

bioRxiv2019

Alpha-synuclein antisense oligonucleotides as a disease-modifying therapy for Parkinson’s disease

Parkinsons disease (PD) is a prevalent neurodegenerative disease with no approved disease-modifying therapies. Multiplications, mutations, and single nucleotide polymorphisms in the SNCA gene, encoding alpha-synuclein protein (aSyn), either cause or increase risk for PD. Intracellular accumulations of aSyn are pathological hallmarks of PD. Taken together, reduction of aSyn production may provide a disease-modifying therapy for PD. We show that antisense oligonucleotides (ASOs) reduce production of aSyn in rodent pre-formed fibril (PFF) models of PD. Reduced aSyn production leads to prevention and removal of established aSyn pathology and prevents dopaminergic cell dysfunction. In addition, we address the translational potential of the approach through characterization of human SNCA targeting ASOs that efficiently suppress the human SNCA transcript in vivo. We demonstrate broad activity and distribution of the human SNCA ASOs throughout the non-human primate brain and a corresponding decrease in aSyn cerebral spinal fluid (CSF) levels. Taken together, these data suggest that by inhibiting production of aSyn it may be possible to reverse established pathology and thus supports the development of SNCA ASOs as a potentially disease modifying therapy for PD and related synucleinopathies.\n\nSummaryAntisense oligonucleotides designed against SNCA, which are progressing to the clinic, have the potential to be a disease modifying therapeutic for Parkinsons disease patients.

neuroscience↗

bioRxiv2019

Chagas disease awareness and socioeconomic characteristics of Bolivian immigrants living in Sao Paulo, Brazil.

In this study, part of a research project on Chagas disease among residents of Bolivia in Sao Paulo, we describe socioeconomic characteristics, knowledge about the disease and access to health services. A structured questionnaire was applied to a sample of 472 Bolivian adults (> 18 years) living in Sao Paulo enrolled in the Barra Funda School Health Center. The median age of participants was 28.5 years, 75.0% from the Bolivian department of La Paz, who were living in Sao Paulo for an average of 5.8 years. Regarding knowledge about the disease and exposure to certain risk factors, 47.7% indicated familiarity with the vector, 23.9% had seen vinchuca in their homes in Bolivia and 6.4% reported having been bitten by a triatomine. The conditions of living in rural areas in Bolivia or in other department than La Paz, have a relative with illness, high school graduation and have seen or been bitten by a vinchuca were significantly associated with the knowledge of the vector. This study provides a view on migration that has important implications for the distribution of Chagas disease and access to health care by providing subsidies for proposing public health policies.\n\nAuthor summaryThis article expresses part of the results of a research project called \"Chagas disease in a population of Bolivian immigrants in Sao Paulo: an analysis of the prevalence of Trypanosoma cruzi infection and morbidity of Chagas disease, knowledge of the population about the disease and access to different levels of health care\". The problem of chronic Chagas disease occurs in many countries, including those not considered endemic, as a result of population movements, mainly by immigration due to urbanization which has led to its globalization. It is now considered an emerging disease with significant potential for transmission via blood transfusions, organ transplants and congenital via, in the absence of appropriate strategies in terms of public health, as well as reactivation of chronic disease in urban centers. Its no different this phenomenon to the city of Sao Paulo. This study analyzed the sociodemographic inserts, labor, migration and knowledge about Chagas disease and its impact on personal, family and professional life of Bolivian immigrants living in Sao Paulo.

scientific communication and education↗

bioRxiv2019

Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associated Akkermansia

BackgroundAkkermansia muciniphila is a mucin-degrading bacterium found in the gut of most healthy humans and is considered a next-generation probiotic. However, knowledge of the genomic and physiological diversity of human associated Akkermansia is limited, as only one species has been formally described. ResultsTo begin to fill this knowledge gap, we reconstructed 35 high-quality metagenome assembled genomes from children and combined them with 40 other publicly available genomes from adults and mice for comparative genomic analysis. We identified at least four species-level phylogroups (AmI-AmIV) with distinct functional potentials. Most notably, we identified the presence of putative cobalamin (vitamin B12) biosynthesis genes within the AmII (n=26/28) and AmIII (n=2/2) phylogroups. To test these predictions, 10 novel strains of Akkermansia were isolated from adults and screened for essential vitamin B12 biosynthesis genes via PCR. Two strains of the AmII phylogroup were positive for the presence of vitamin B12 biosynthesis genes, while all AmI strains, including the type strain A. muciniphila MucT, were negative. To demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups since cobalamin is a cofactor in propionate metabolism. Results show that the Akkermansia AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of de novo vitamin B12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B12 was not supplied in the culture medium. ConclusionsWe identified Akkermansia strains as potentially important vitamin B12 biosynthetic bacteria in the human gut. This novel physiological trait of human associated Akkermansia may impact how these bacteria interact with the human host and other members of the human gut microbiome.

genomics↗