Biology subjects

Palmieri, M.

Publications and source records attributed to Palmieri, M..

4 recordsLinked to original sources

bioRxiv2025

Deletion of the scavenger receptor Scarb1 in osteoblast progenitors and myeloid cells does not affect bone mass

The scavenger receptor class B member 1 (SCARB1), encoded by Scarb1, is a cell surface receptor for high density lipoproteins, low density lipoproteins (LDL), oxidized LDL (OxLDL), and phosphocholine-containing oxidized phospholipids (PC-OxPLs). Scarb1 is expressed in multiple cell types, including osteoblasts and macrophages. PC-OxPLs, present on OxLDL and apoptotic cells, adversely affect bone metabolism. Overexpression of E06 IgM - a natural antibody that recognizes PC-OxPLs- increases cancellous and cortical bone at 6 months of age in both sexes and protects against age- and high fat diet- induced bone loss, by increasing bone formation. We have reported that SCARB1 is the most abundant scavenger receptor for OxPLs in osteoblastic cells, and osteoblasts derived from Scarb1 knockout mice (Scarb1 KO) are protected from the pro-apoptotic and anti-differentiating effects of OxLDL. Skeletal analysis of Scarb1 KO mice produced contradictory results, with some studies reporting elevated bone mass and others reporting low bone mass. To clarify if Scarb1 mediates the negative effects of PC-OxPLs in bone, we deleted it in osteoblast lineage cells using Osx1-Cre transgenic mice. Bone mineral density (BMD) measurements and micro-CT analysis of cancellous and cortical bone at 6 months of age did not reveal any differences between Scarb1{Delta}OSX-l mice and their wild-type (WT), Osx1-Cre, or Scarb1fl/fl littermate controls. We then investigated whether PC-OxPLs could exert their anti-osteogenic effects via activation of SCARB1 in myeloid cells by deleting Scarb1 in LysM-Cre expressing cells. BMD measurements and micro-CT analysis at 6 months of age did not show any differences between Scarb1{Delta}LysM mice and their WT, LysM-Cre, or Scarb1fl/fl controls. Based on this evidence, we conclude that Based on this evidence, we conclude that the adverse skeletal effects of PC-OxPLs in adult mice are not mediated by Scarb1 expressed in osteoblast lineage cells or myeloid cells.

cell biology↗

bioRxiv2025

Myo1e/f at the podosome base regulate podosome dynamics and promote macrophage migration

Cells of the monocyte lineage form specialized membrane-associated, actin-rich structures, called podosomes. Podosomes play important roles in cell adhesion and migration as well as the proteolytic degradation of the extracellular matrix. While podosomes are always closely associated with the plasma membrane, the structural components linking the podosome core, composed of branched actin, to the membrane are not fully understood. In this study we show that class I myosins, Myo1e and Myo1f, localize to a specific region of podosomes, underneath the podosome core and near the ventral plasma membrane, and that this localization is mainly mediated by the Myo1e/f TH2 domains. Respective knockdowns or knockouts of Myo1e/f lead to increased podosome size, altered turnover and lateral mobility, which is likely due to Myo1e/f regulating the attachment of core actin filaments to the plasma membrane. In addition, Myo1e/f double knockout macrophages were characterized by a reduction in 3D and 2D migration, even though these cells exhibited increased ability to degrade the extracellular matrix. Along with the other membrane-associated podosome components, such as the transmembrane proteins MT-MMP and CD44, and the GPI-anchored DNase X, Myo1e and Myo1f mark the membrane-proximal region of podosomes. We propose to label this region as the podosome "base", an additional substructure joining the current trifecta of the podosome cap, core, and ring.

cell biology↗

bioRxiv2024

Comprehensive Molecular Epidemiology of Influenza Viruses in Brazil: Insights from a Nationwide Analysis

Influenza A and B viruses pose significant global health threats, with substantial impacts on morbidity and mortality. Understanding their molecular epidemiology in Brazil, a key hub for the circulation and dissemination of these viruses in South America, remains limited. This study, part of the Center for Viral Surveillance and Serological Assessment (CeVIVAS) project, addresses this by analyzing data and samples from all Brazilian macroregions, along with publicly available sequences from 2021-2023. Phylogenetic analysis of the Hemagglutinin (HA) segment of Influenza A/H1N1pdm09, A/H3N2, and Influenza B/Victoria-lineage revealed the predominance of A/H3N2 2a.3 strain in 2021 and early 2022. This was succeeded by A/H3N2 2b until October 2022, after which A/H1N1pdm09 5a.2a and 5a.2a.1 lineages became prevalent, maintaining this status throughout 2023. B/Victoria circulated at low levels between December 2021 and September 2022, becoming co-prevalent with A/H1N1pdm09 5a.2a and 5a.2a.1 lineages. Comparing the vaccine strain A/Darwin/9/2021 with circulating A/H3N2 viruses from 2021-2023 revealed shared mutations to aspartic acid at residues 186 and 225, altering the RBD domains charge. For A/H1N1pdm09, the 2022 consensus of 5a.2a.1 and the vaccine strain A/Victoria/2570/2019 had 14 amino acid substitutions. Key residues such as H180, D187, K219, R223, E224, and T133 are involved in hydrogen interactions with sialic acids, while N130, K142, and D222 may influence distance interactions based on docking analyses. Distinct Influenza A lineage frequency patterns across Brazils macroregions underscore regional variations in virus circulation. This study characterizes the dynamics of Influenza A and B viruses in Brazil, offering valuable insights into their circulation patterns. These findings have significant public health implications, informing strategies to mitigate transmission risks, optimize vaccination efforts, and enhance outbreak control measures. Author summaryThis study investigates the molecular epidemiology of Influenza A and B viruses in Brazil from 2021 to 2023. Utilizing data from the Center for Viral Surveillance and Serological Assessment (CeVIVAS) and public databases, we performed a comprehensive phylogenetic analysis of the Hemagglutinin segments of Influenza A/H1N1pdm09, A/H3N2, and B/Victoria-lineage viruses across all Brazilian macroregions. Key findings reveal that the A/H3N2 2a.3 strain was predominant in 2021 and early 2022, followed by A/H3N2 2b, and later by A/H1N1pdm09 5a.2a and 5a.2a.1 lineages in late 2022 and throughout 2023. The B/Victoria strain circulated at low levels initially and later co-prevailed with A/H1N1pdm09 lineages. Comparing the vaccine strain A/Darwin/9/2021 with circulating A/H3N2 viruses from 2021-2023 and A/Victoria/2570/2019 with 5a.2a.1 of A/H1N1pdm09 circulating in 2022 revealed significant mutations which could affect the interaction of the viruses with sialic acids and potentially impact vaccine efficacy. Notably, we identified a substitution pattern among the predominant Influenza subtypes and observed distinct regional variations in Influenza A lineage frequencies across Brazil. These findings are critical for optimizing vaccination strategies and provide valuable data to inform public health policy and improve health outcomes.

evolutionary biology↗

bioRxiv2021

Dual MAPK and HDAC inhibition rewires the apoptotic rheostat to trigger colorectal cancer cell death

The EGFR/RAS/MEK/ERK signalling pathway (ERK/MAPK) is hyper-activated in most colorectal cancers (CRCs). A current limitation of inhibitors of this pathway is that they primarily induce cytostatic effects in CRC cells. Nevertheless, these drugs do induce expression of pro-apoptotic factors, suggesting they may prime CRC cells to undergo apoptosis. As histone deacetylase inhibitors (HDACi) induce expression of multiple pro-apoptotic proteins, we examined whether they could synergize with ERK/MAPK inhibitors to trigger CRC cell apoptosis. Combined MEK/ERK and HDAC inhibition synergistically induced apoptosis in CRC cell lines and patient-derived tumour organoids in vitro, and attenuated Apc-initiated adenoma formation in vivo. Mechanistically this effect was mediated through induction of the BH3-only pro-apoptotic proteins BIM and BMF. Importantly, we demonstrate that this treatment paradigm can be tailored to specific MAPK genotypes in CRCs, by combining HDACi with EGFR, KRASG12C or BRAFV600 inhibitors in KRAS/BRAFWT; KRASG12C, BRAFV600E CRC cell lines respectively. These findings identify a novel ERK/MAPK genotype-targeted treatment paradigm for colorectal cancer.

cancer biology↗