Biology subjects

Carrera, M.

Publications and source records attributed to Carrera, M..

4 recordsLinked to original sources

bioRxiv2026

Differential Effects of Neutral Sphingomyelinase and Serine Palmitoyltransferase Inhibitors on Alzheimer's-Like Neuropathology.

Alzheimer's disease (AD) involves progressive neurodegeneration, amyloid-{beta} (A{beta}) pathology and chronic neuroinflammation. Elevated ceramides, generated via neutral sphingomyelinase (nSMase)-mediated sphingomyelin hydrolysis or serine palmitoyltransferase (SPT)-driven de novo synthesis, amplify these processes. Here, we performed a direct comparison of pharmacological inhibition of these pathways in the PDAPP-J20 transgenic mouse model and in fibrillized A{beta}1-42-challenged BV-2 murine microglial cell line. Eight-month-old PDAPP-J20 female mice received intraperitoneal GW4869 (nSMase inhibitor, 1.25 mg/kg) or myriocin (SPT inhibitor, 0.3 mg/kg) three times weekly for 3 weeks. Neutral SMase inhibition restored spatial learning in the Barnes maze, reduced hippocampal neuronal loss and layer atrophy, decreased amyloid plaque burden, and attenuated microglial activation (Iba1 morphology and peri-plaque reactivity). In contrast, SPT inhibition worsened thigmotaxis, failed to improve cognition, and increased plaque load. In vitro, nSMase blockade (GW4869 and cambinol) suppressed A{beta}-induced NF{kappa}B p65 nuclear translocation, blunted TNF- expression, and reduced intracellular A{beta} accumulation in microglia, suggesting enhanced endolysosomal degradation. SPT inhibition lacked these anti-inflammatory and clearance-promoting effects. These results identify nSMase as a critical node linking ceramide metabolism, microglial dysfunction, and amyloid progression in AD. Targeted nSMase inhibition offers a promising molecular strategy to interrupt neuroinflammation and restore neuronal homeostasis, while broad SPT blockade appears counterproductive. Pathway-selective modulation of ceramide signaling may open new therapeutic avenues for AD.

neuroscience↗

bioRxiv2026

Foundational characterization of tomato fruit RALF peptides reveals structural and functional specialization within the SlRALF

Rapid Alkalinization Factor (RALF) peptides regulate plant growth and cell wall signaling, but their roles in fruit development remain unclear. Here, we characterized tomato (Solanum lycopersicum) fruit-associated RALF peptides and their interactions with leucine-rich repeat extensins (LRXs). Expression analyses identified SlRALF5, SlRALF7, and SlRALF10 as the main fruit-expressed RALFs. SlRALF10 was associated with early fruit development, whereas SlRALF5 and SlRALF7 remained expressed during ripening. Sequence analyses showed that SlRALF5/7 retain conserved motifs of canonical RALFs, while SlRALF10 displays divergent structural features and altered charge distribution. Synthetic SlRALF5 and SlRALF7 inhibited root growth and induced extracellular alkalinization, whereas SlRALF10 lacked both activities. Co-immunoprecipitation assays showed that all three peptides interact with the fruit-expressed proteins SlLRX2 and SlLRX5. Structural modeling predicted distinct electrostatic properties for the SlLRX5/SlRALF10 complex compared with SlRALF5. These results reveal structural and functional specialization among tomato fruit RALF peptides and suggest that distinct SlRALFs may differentially respond to cell wall remodeling during fruit development and ripening.

plant biology↗

bioRxiv2024

From North to South: Transmission Dynamics of H1N1pdm09 Swine Influenza A Viruses in Italy

The influenza A H1N1pdm09 virus continues to be a significant pathogen, posing potential risks to both animal and human health due to its zoonotic potential. Italy, which has one of the largest swine populations in Europe, plays a crucial role in monitoring the evolution of influenza viruses in livestock. This study aims to address the existing knowledge gaps regarding the genetic diversity and transmission dynamics of H1N1pdm09 circulating in Italian swine populations. Utilizing whole genome sequencing and dynamic modeling, we conducted a comprehensive analysis of virus samples collected from swine farms across Italy. Our results reveal that multiple independent viral introductions have occurred into the country, with most cases resulting in self-limited infections and limited onward transmission. However, six distinct transmission clusters were identified, suggesting instances of sustained viral spread. These clusters were found across multiple regions of Italy, highlighting the broad geographic distribution of virus lineages. Our findings indicate that while many introductions led to localized containment, certain virus lineages were able to spread within specific regions of Italy. Through a detailed examination of selective pressures, we observed that most viral genes are under strong purifying selection in both swine and human hosts, as reflected by dN/dS ratios well below 1. The hemagglutinin (HA) gene exhibited a notably higher dN/dS ratio in swine ([~]0.28) compared to humans ([~]0.22), indicating slightly relaxed selection in swine. In contrast, other genes, such as neuraminidase (NA) and non-structural protein (NS), showed similarly strong purifying selection across both hosts. These results reflect a general trend of selective pressures affecting multiple viral components, rather than emphasizing specific genes. Our study emphasizes the importance of ongoing genomic surveillance in detecting viral circulation and mitigating risks to both animal and public health. Italys efforts contribute significantly to global influenza monitoring and highlight the importance of a One Health approach that integrates human, animal, and environmental health. These findings provide essential data to inform public health policies and enhance preparedness against future zoonotic influenza outbreaks.

microbiology↗

bioRxiv2019

Reconstruction of fish allergenicity from the content and structural traits of the component β-parvalbumin isoforms

Most fish-allergic patients have anti-{beta}-parvalbumin ({beta}-PV) immunoglobulin E (IgE), which cross-reacts among fish species with variable clinical effects. Although the {beta}-PV load is considered a determinant for allergenicity, fish species express distinct {beta}-PV isoforms with unknown pathogenic contributions. To identify the role various parameters play in allergenicity, we have taken Gadus morhua and Scomber japonicus models, determined their {beta}-PV isoform composition and analyzed the interaction of the IgE from fish-allergic patient sera with these different conformations. We found that each fish species contains a major and a minor isoform, with the total PV content four times higher in Gadus morhua than in Scomber japonicus. The isoforms showing the best IgE recognition displayed protease-sensitive globular folds, and if forming amyloids, they were not immunoreactive. Of the isoforms displaying stable globular folds, one was not recognized by IgE under any of the conditions, and the other formed highly immunoreactive amyloids. The results showed that Gadus morhua muscles are equipped with an isoform combination and content that ensures the IgE recognition of all PV folds, whereas the allergenic load of Scomber japonicus is under the control of proteolysis. We conclude that the consideration of isoform properties and content may improve the explanation of fish species allergenicity differences.

biophysics↗