Biology subjects

De Santis, D.

Publications and source records attributed to De Santis, D..

3 recordsLinked to original sources

bioRxiv2026

Different spatial profiles of aberrant N-glycans in pediatric and adult MOGHE brain tissue

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a recently recognized epilepsy-associated lesion frequently linked to brain-restricted somatic variants in SLC35A2, a gene encoding the Golgi UDP-galactose transporter. Although previous studies demonstrated altered glycosylation in SLC35A2-mutated MOGHE tissue, the spatial relationship between glycosylation defects and histopathological abnormalities remains poorly understood. We applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) using formalin-fixed paraffin-embedded brain tissue from six histologically confirmed MOGHE cases (three pediatric and three adult) and three temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). We spatially evaluated N-glycan profiles across diagnostic tissue groups, with particular attention to molecular differences between lesional and perilesional regions and to recurrent abundance trends. All MOGHE cases harboured somatic SLC35A2 variants. Histologically, oligodendroglial hyperplasia and heterotopic neurons were present in all cases, while patchy hypomyelination was restricted to pediatric cases. Unsupervised spatial segmentation, integrated with neuropathological evaluation, revealed marked molecular heterogeneity in pediatric MOGHE. In these cases, lesional and perilesional regions were clearly distinguishable in both white matter (WM) and overlying grey matter (GM) boundaries patterns, whereas adult MOGHE and TLE-HS mainly showed a clearcut separation between WM and GM. Spatial analysis confirmed enrichment of the previously reported aberrant N-glycan species m/z 2094 and, to a lesser extent, m/z 2297 within MOGHE tissue, particularly in pediatric lesional WM. Notably, the distribution of m/z 2094 closely overlapped with areas of hypomyelination. Quantitative trajectory analysis of 151 detected N-glycan ions identified recurrent abundance profiles. Three representative spatial patterns emerged: pediatric lesion-enriched, pediatric perilesion-enriched, and TLE-HS-enriched profiles. Pediatric lesions were characterized by increased abundance of multiantennary glycans lacking terminal galactose residues and reduced abundance of galactosylated biantennary and multiantennary structures, consistent with defective UDP-galactose transport. In contrast, adult lesional and perilesional tissues exhibited largely overlapping glycomic profiles. These findings provide the first spatially resolved evidence that glycosylation abnormalities in SLC35A2-mutated MOGHE are closely associated with lesional pathology, particularly hypomyelination, and are substantially more pronounced in pediatric than adult cases. Spatial glycomics may therefore offer new insights into MOGHE pathophysiology and support the development of targeted therapeutic approaches aimed at correcting galactosylation defects.

neuroscience↗

bioRxiv2023

An Exploratory Multi-Session Study of Learning High-Dimensional Body-Machine Interfacing for Assistive Robot Control

Individuals who suffer from severe paralysis often lose the capacity to perform fundamental body movements and everyday activities. Empowering these individuals with the ability to operate robotic arms, in high-dimensions, helps to maximize both functional utility and human agency. However, high-dimensional robot teleoperation currently lacks accessibility due to the challenge in capturing high-dimensional control signals from the human, especially in the face of motor impairments. Body-machine interfacing is a viable option that offers the necessary high-dimensional motion capture, and it moreover is noninvasive, affordable, and promotes movement and motor recovery. Nevertheless, to what extent body-machine interfacing is able to scale to high-dimensional robot control, and whether it is feasible for humans to learn, remains an open question. In this exploratory multi-session study, we demonstrate the feasibility of human learning to operate a body-machine interface to control a complex, assistive robotic arm in reaching and Activities of Daily Living tasks. Our results suggest the manner of control space mapping, from interface to robot, to play a critical role in the evolution of human learning.

bioengineering↗

bioRxiv2022

Diversity of Learning to Control Complex Rehabilitation Robots Using High-Dimensional Interfaces

Upper body function is lost when injuries are sustained to the cervical spinal cord. Assistive machines can support the loss in upper body motor function. To regain functionality at the level of performing activities of daily living (e.g., self-feeding), though, assistive machines need to be able to operate in high dimensions. This means there is a need for interfaces with the capability to match high-dimensional operation. The body-machine interface provides this capability and has shown to be a suitable interface even for individuals with limited mobility. This is because it can take advantage of peoples available residual body movements. Previous studies using this interface have only shown that the interface can control low-dimensional assistive machines. In this pilot study, we demonstrate the interface can scale to high-dimensional robots, can be learned to control a 7-dimensional assistive robotic arm, to perform complex reaching and functional tasks, by an uninjured population. We also share results from various analyses that hint at learning, even when performance is extremely low. Decoupling intrinsic correlations between robot control dimensions seem to be a factor in learning--that is, proficiency in activating each control dimension independently may contribute to learning and skill acquisition of high-dimensional robot control. In addition, we show that learning to control the robot and learning to perform complex movement tasks can occur simultaneously.

bioengineering↗