Biology subjects

Pellegrini, C.

Publications and source records attributed to Pellegrini, C..

3 recordsLinked to original sources

bioRxiv2026

Alterations of gut microbiota in Down syndrome and their association with Alzheimer's disease

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSAdults with Down syndrome (DS) have a higher risk of developing Alzheimers disease (AD). As gut microbiota (GM) alterations have been reported in AD, we investigated their association with cognitive decline and plasma AD biomarkers in DS. METHODSFecal and plasma samples were collected from 58 adults with DS (21-75 years) and 30 euploid controls (CTRL; 25-83 years). GM was profiled using 16S rRNA sequencing. Major Neurocognitive Disorder (NcD) was diagnosed according to DSM-5 criteria. Plasma levels of p-Tau181, NfL, and GFAP were measured using the Simoa platform. RESULTSCompared with CTRL, DS showed significant changes in UBA1819 and Intestinibacter genera, previously reported to be associated with mild cognitive impairment. Furthermore, DS with NcD were characterized by a reduced abundance of Roseburia genus, which was also negatively associated with plasma levels of AD biomarkers. CONCLUSIONAdults with DS display AD-associated changes in GM partially resembling those previously reported in euploid AD patients

microbiology↗

bioRxiv2025

Multimodal Connectivity-based Cortical Segmentation with Graph Neural Networks

Due to the significant amount of time and expertise needed for manual segmentation of the brain cortex from magnetic resonance imaging (MRI) data, there is a substantial need for efficient and accurate algorithms to replace the need for human involvement. In this work, we explore the capabilities of Graph Neural Networks (GNNs) to segment the brain surface based on structural brain connectivity. We train three different GNN architectures, the Graph Convolutional Network (GCN), the Graph Attention Network (GAT), and the Graph U-Net, and evaluate their performances when trained on silver-standard cortical region labels created by FreeSurfer. We take a multimodal approach to brain segmentation by examining the influence of the structural connectivity values inferred from diffusion MRI (dMRI) in addition to using values from structural MRI (sMRI). Our results demonstrate the utility of GNN models, particularly the GAT architecture, which achieved Dice scores competitive to those reported in the literature with non-graph methods. Additionally, structural connectivity derived from dMRI revealed significant value in improving automatic segmentation, as models trained on combined attributes from dMRI and sMRI outperformed those trained only on sMRI. Finally, we compared the GNN-based and the FreeSurfer segmentations in their ability to predict demographic/clinical data, where neither of the two approaches was statistically significantly superior to the other.

neuroscience↗

bioRxiv2021

One gene - two proteins: The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of seven transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is upregulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here it controls oxygen consumption, cell proliferation and the formation of reactive oxygen species by reducing oxidative phosphorylation. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human induced pluripotent stem cells, reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signalling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism thar cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration.

cell biology↗