Biology subjects

Ramos, G.

Publications and source records attributed to Ramos, G..

5 recordsLinked to original sources

bioRxiv2025

Changes in peripheral blood leukocyte composition precede development of heart-reactive autoantibodies in patients hospitalised for acute heart failure

In a retrospective pilot study, we showed that the induction of heart-reactive autoantibodies (HRA) in the wake of acutely decompensated heart failure predicts worse outcomes. To gain deeper insights into the immunological mechanisms causing induction of HRA after heart failure decompensation we initiated the prospective Acute Heart Failure-Immunomonitoring Cohort Study (AHF-ImmunoCS). For this study, 380 patients were enrolled and will be followed up, including serial collection of biomaterials, for a period of 18 months after the index hospitalisation for AHF. Analysis of AHF-ImmunoCS samples obtained at baseline and at 6-month follow-up from 110 patients showed de novo induction of HRA - as detected by indirect immunofluorescence (IFT) - in 21% of patients (previously published percentage: 32%). The IFT results did not reflect induction of broad anti-heart autoimmunity as autoantibodies against other cardiac antigens like Troponin I3 or Myosin Light Chain 7 were not induced in parallel. To understand what drives HRA induction in these patients we longitudinally immunophenotyped peripheral blood leukocytes at baseline, 6-week and 6-month follow-up by high-resolution spectral flow cytometry. Among lymphocytes, induction of HRA in the wake of acute decompensation of heart failure was associated with a higher proportion of CD4+ T cells among lymphocytes, more CD45RA+ CCR7+ naive conventional, i.e. non-regulatory, and more CXCR3+ CCR4- Th1 cells among CD4+ T cells at baseline. Among myeloid cells, there were no differences at baseline between patients going on to develop HRA and those that did not. However, patients developing HRA had higher proportions of eosinophils (six-month follow-up) and lower proportions of Arginase+ HLA-DR- polymorphnuclear myeloid-derived suppressor cells among myeloid cells (six-week and six-month follow-up). Our data, thus, implicate that alterations in the composition of both the lymphoid and the myeloid compartments might drive HRA induction which impacts disease progression and prognosis in AHF.

immunology↗

bioRxiv2025

Common Gene Networks Orchestrate Organelle Architecture and Inter-Organelle Metabolic Flows for Mucin Production in High Endothelial and Goblet Cells

High endothelial cells (HECs) are specialized vascular gatekeepers that control lymphocyte entry into lymph nodes, a process essential for immune surveillance and adaptive responses. However, how HECs coordinate their high biosynthetic demands with the secretory apparatus to support immune function remains unclear. Using multi-omic approaches, we identify IRE1-XBP1-centered transcriptional networks that, together with CREB3L2-associated gene programs, coordinate inter-organelle metabolic and secretory pathways required for glycosylation and assembly of peripheral node addressin (PNAd), a sulfated sialomucin critical for lymphocyte homing. Genetic or pharmacological perturbation of these pathways disrupts HEC morphology and lymphocyte recruitment during homeostasis and impairs HEC induction during inflammation. Parallel transcriptional programs operate in mucin-producing intestinal goblet cells, suggesting common regulatory pathways linking metabolism and sulfated mucin specialization with the associated expansion of secretory organelles across immune and barrier tissues. Thus, our findings identify transcriptional programs that coordinately scale metabolic pathways and secretory organelles to support the biosynthetic infrastructure underlying the morphology and immune trafficking functions of HEVs. Key pointsXBP1-centered transcriptional networks coordinate metabolic and secretory programs for PNAd biosynthesis. IRE1 or S1P inhibition flattens HEVs, prevents ectopic HEV formation and, reduces lymphocyte recruitment Endothelial XBP1 deletion disrupts HEV morphology and lymphocyte trafficking. Goblet cells share secretory transcriptional programs and regulatory logic with HEV.

immunology↗

bioRxiv2024

Population genomics of Macrophomina spp. reveals cryptic host specialization and evidence for meiotic recombination

Knowledge of the factors structuring populations of pathogenic fungi is fundamental to disease management efforts and basic biology. High-quality short-read sequence data were obtained for 463 Macrophomina spp. isolates collected from 91 host plant species and soil in 23 countries. Analyses revealed high diversity, admixture, and equal mating type ratios suggesting on-going recombination. Although most tested isolates could asymptomatically colonize strawberry, only isolates from a single phylogroup caused disease. In addition to strawberry, evidence for host specialization was discovered for soybean, demonstrating this broad host range pathogen contains phylogroups with cryptic specialization. Geography x isolate genotype associations were weak, suggesting these species were frequently trafficked between regions. Re-analysis using genomic data supported current species boundaries, and new molecular markers were designed to specifically identify each species. Contrary to expectations, M. phaseolina should be considered a species with both specialist and generalist populations for which meiosis can increase genetic diversity.

genomics↗

bioRxiv2024

Should I stay or should I go? Spatio-temporal dynamics of bacterial biofilms in confined flows

Most bacteria live in sessile biofilms that colonize the confined channels, pores and crevices of natural and engineered structures. In these environments, flow delivers nutrients necessary for growth while simultaneously generating mechanical stresses that cause detachment from surfaces. Bacteria, in turn, colonize flow passages, increasing hydraulic resistance and modifying transport properties. Although the importance of advective transport and hydrodynamic forces on bacterial populations is well established, the complex feedback mechanisms governing biofilm development in confined geometries remain poorly understood. Here, we study how couplings between flow and bacterial development control the spatiotemporal dynamics of Pseudomonas aeruginosa in microchannel flows. We demonstrate that nutrient availability primarily drives the longitudinal distribution of biomass along the channel, while competition between growth and flow-induced detachment controls the transverse distribution and temporal dynamics. We find that biofilms undergo successive cycles of sloughing and regrowth, causing persistent fluctuations in the hydraulic resistance and biomass that prevent the system from ever reaching a true steady state. Our results indicate that these self-sustained fluctuations are a signature effect in confined flows, originating from a pressure build-up as growing bacteria obstruct flow paths. We further show that the sloughing dynamics can be described as a jump stochastic process with gamma-distributed interevent times, analogous to other bursting events such as earthquakes or avalanches. This stochastic framework provides a quantitative approach to characterizing the inherent randomness and apparent irreproducibility of biofilm experiments, opening new avenues for predictive modeling of biofilms in confined systems.

biophysics↗

bioRxiv2022

Sporodochia formed by Fusarium oxysporum f. sp. fragariae produce airborne conidia and are ubiquitous on diseased strawberry plants in California

Sporodochia are dense masses of fungal hyphae bearing asexual conidia. For Fusarium oxysporum, sporodochia are known to produce airborne conidia and enhance the dissemination of this otherwise soilborne pathogen. Sporodochia are small and transient, and they are documented for only a few formae speciales of Fusarium oxysporum. This study reports airborne conidia and sporodochia produced by F. oxysporum f. sp. fragariae, the cause of Fusarium wilt of strawberry, in the Monterey Bay region of California. Sporodochia were consistently present in Fusarium wilt-afflicted strawberry fields and were discovered in 21 of 24 Fusarium wilt-diseased fields. Only necrotic tissues were observed bearing sporodochia, and they were most frequently observed on petioles and peduncles. Sporodochia grew significantly longer up peduncles than petioles, extending further away from the base of the plant and toward parts of the canopy more exposed to wind. A stolon hosted the longest stretch of sporodochial growth, found covering the stolons entire 35 cm length and also the base of the daughter plant. Macroconidia were produced by all sporodochia samples, and we did not find microconidia on any samples. An initial series of experiments confirmed the potential for conidia produced by sporodochia to disperse with wind over short distances. The prevalence of sporodochia producing airborne spores of F. oxysporum f. sp. fragariae has great importance for disease management and biosecurity.

microbiology↗