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Cataldi, A.

Publications and source records attributed to Cataldi, A..

4 recordsLinked to original sources

Selective vulnerability of intracortical projection neurons drives long-term cortical circuit rewiring after perinatal hypoxia

Cortical circuits are built at perinatal times and gradually refined in an activity-dependent manner during a so-called postnatal period of critical plasticity. Although lesions of the central nervous system (CNS) happening during this period typically recover better than those occurring later in life, they are often associated with long-term behavioral deficits. This suggests that neuronal circuits rewiring, in particular within the cortex, may either be incomplete or inappropriate. To address this possibility, we used chronic perinatal hypoxia, a mouse model of very premature birth. We confirmed that chronic hypoxia induced a decrease in cortical thickness frequently observed in very preterm babies, which rapidly recovered 8 days later. To explore the transcriptional correlates of this recovery we next performed single-nuclei transcriptomic analysis of the cortex at short (P11) and long (P45) timepoints following hypoxia. This revealed persistent transcriptional changes within neurons, including of genes involved in mitochondrial metabolism, axonogenesis and synaptogenesis. Further, histological analysis using anterograde and retrograde tracing as well as mitochondrial labelling support persistent alterations in upper cortical neurons resulting in increased cortico-cortical connectivity within the cortex of adult hypoxic mice. Finally, behavioral testing revealed altered social behavior in mice exposed to chronic hypoxia, which amplified with age. Altogether, our results unravel how brain lesions happening early in life, alter normal cortical development and have long term consequences on cortical wiring, contributing to the observed behaviors defects appearing later in life.

neuroscience↗

IsdH binding to hemoglobin:haptoglobin is decoupled from iron acquisition in Staphylococcus aureus

Staphylococcus aureus requires iron for proliferation during infection and acquires it mainly from host hemoglobin (Hb) through the iron-regulated surface determinant (Isd) system. The hemophores IsdB and IsdH mediate the initial steps of Hb recognition. Notably, IsdH also recognizes the hemoglobin:haptoglobin (HbHp) complex, although the molecular determinants and physiological relevance of this interaction remain unclear. Here, combining cryo-electron microscopy and biochemical and cellular assays, we define the basis of HbHp recognition by IsdH. The structure reveals how IsdH engages HbHp and captures the intrinsic conformational flexibility of the HbHp assembly. Functional analyses demonstrate that, despite retaining the ability to extract heme from HbHp, IsdH does not support S. aureus growth under iron-restricted conditions when HbHp is the sole iron source. These findings suggest that HbHp recognition by IsdH may serve functions beyond nutrient iron acquisition, contributing to modulation of host-pathogen interactions.

biochemistry↗

Unraveling the Regenerative Proteomic Signature of Helix aspersa's Slime in Human Dermal Fibroblasts by Data-driven Proteomics Approach

Proteins orchestrate essential cellular processes, including metabolism, communication, survival, and regeneration, making proteomic profiling a powerful strategy to elucidate complex biological responses. Snail slime (SnS) has emerged as a bioactive material with documented pro-healing, antioxidant, and anti-inflammatory properties; however, its effects at the proteome level in normal human dermal fibroblasts (NHDFs) remain unexplored. In this study, an LC-MS-based proteomic approach (Data are available via ProteomeXchange with identifier PXD075292) combined with network and Gene Ontology enrichment analyses was employed to investigate SnS-induced molecular reprogramming in NHDFs, followed by functional assays. Results show that SnS is well tolerated for up to 72 h, confirming its cytocompatibility, followed by proteomic analysis revealing enrichment of biological processes related to apoptosis regulation, oxidative stress response, wound healing, cell migration, and anti-aging. Network analysis identified AKT, PI3K, SRC, and KRAS family members as key hub proteins, indicating convergence on central signaling pathways controlling survival, redox balance, and migratory activity. Functional assays demonstrated a time-dependent, controlled modulation of apoptosis consistent with cellular turnover, alongside a hormetic redox response characterized by transient ROS signaling followed by enhanced antioxidant capacity. Importantly, SnS significantly accelerated fibroblast migration, achieving complete wound closure within 24 h. Collectively, these findings demonstrate that SnS induces coordinated proteomic and functional reprogramming that integrates redox modulation, controlled apoptosis, and enhanced migration, providing a mechanistic basis for its pro-healing and anti-aging effects and supporting its potential as a regenerative biomaterial.

cell biology↗

Quantification of Enterohemorrhagic Escherichia coli O157:H7 proteome using TMT-Based Analysis

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a human pathogen responsible for diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS). EHEC infection is distributed worldwide and numerous outbreaks of diseases caused by enterohemorrhagic have been reported. To promote a comprehensive insight into the molecular basis of EHEC O157:H7 physiology and pathogenesis, the combined proteome of EHEC O157:H7 strains, Clade 8 and Clade 6 isolated from cattle in Argentina, and the standard EDL933 (clade 3) strain has been analyzed. TMT (Tandem Mass Tags)-based quantitative proteomic and emPAI analyses were performed to estimate the protein abundance in EHEC proteome. 2,234 non-redundant proteins of EHEC O157:H7 were identified. A comparison of this result with in silico data of EHEC O157:H7 genome showed that approximately 40% of the predicted proteome of this pathogen were covered. According to the emPAI analysis, 85 proteins were among the most abundant (e.g. GAPDH, FliC H-antigen, Enolase, and GroEL). Tellurite resistance proteins were also highly abundant. COG analysis showed that although most of the identified proteins are related to cellular metabolism, the majority of the most abundant proteins are associated with translation processes. A KEGG enrichment analysis revealed that Glycolysis / Gluconeogenesis was the most significant pathway. On the other hand, the less abundant detected proteins are those related to DNA processes, cell respiration and prophage. Among the proteins that composed the Type III Secretion System, the most abundant protein was EspA. Altogether, the results show a subset of important proteins that contribute to physiology and pathogenicity of EHEC O157:H7.\n\nIMPORTANCEThe study of the abundance of proteins present within a complex mixture of proteins in a cell, under different conditions, can provide important information about the activities of individual protein components and protein networks that are cornerstones for the comprehension of physiological adaptations in response to biological demands promoted by environmental changes. We generated a comprehensive and accurate quantitative list of EHEC O157:H7 proteome, which provides a description of the most abundant proteins produced by this pathogen that were related to physiology and pathogenesis of EHEC. This study provides information and extends the understanding on functional genomics and the biology of this pathogen.

microbiology↗