Biology subjects

Tafuri, D.

Publications and source records attributed to Tafuri, D..

5 recordsLinked to original sources

bioRxiv2026

Departure from OFF-State Microstate Dynamics Tracks Levodopa Response in Parkinson's Disease

Although dopaminergic therapies in Parkinsons disease primarily restore dopamine within nigrostriatal circuits, symptoms are better indexed by whole-brain dynamics than by local activity. In this manuscript, we hypothesize that L-Dopa therapy affects whole-brain dynamics alike, which in turn relate to clinical improvement. To test this hypothesis, we conducted a repeated-measures, source-reconstructed MEG study in 13 bradykinetic-dominant PD patients, recording resting-state cortical activity OFF medication and [~]1 hour after levodopa administration (ON). We characterize brain dynamics using a microstate framework, in which transition probabilities between microstates are used to contrast pathological OFF-state dynamics with those in the ON-state. Microstate dynamics were stable within medication states but reconfigured by L-Dopa, with greater departures from the OFF-state pattern associated, at the individual level, with larger clinical improvements. Our results suggest that individualized changes in microstate dynamics may serve as a neurophysiological marker of dopaminergic responsiveness.

neuroscience↗

bioRxiv2026

Data-driven gait cycle decomposition based on whole-body coordination dynamics

The study of human locomotion has long relied on descriptive frameworks of the gait cycle, which have provided essential insights into the functional phases of walking and their underlying biomechanical demands. While these models remain highly informative, they are largely based on observational analyses and may not fully capture the continuous, global coordination that characterizes human movement. The present study proposes an integrated framework to study whole-body coordination. This framework combines network theory with non-negative matrix factorization (NNMF) to treat gait as a dynamic system of coordinated joint interactions. Using three-dimensional kinematic data from 60 healthy subjects, we constructed a representation of whole-body coordination across time, named "dynamic kinectome". It was then decomposed using NNMF to extract spatial patterns of joint coordination and their corresponding temporal activations, allowing for an interpretable characterization of locomotor organization while preserving physiological meaning. Our analysis extracted six robust, highly consistent, and symmetrical coordination patterns across participants, effectively capturing the primary functional subtasks of locomotion. Rather than challenging classical phase descriptions, these findings enrich them by showing how coordination emerges as a continuous, often proactive process that can extend across conventional phase boundaries and systematically integrates the upper limbs for dynamic stability. Overall, this study provides a holistic, data-driven perspective on human locomotion, offering a promising basis for future investigations in motor control and may contribute to the development of sensitive biomarkers for clinical and rehabilitative applications.

bioengineering↗

bioRxiv2025

An integrated enzymatic and computational pipeline for quantifying off-target base-editing

DNA base editing is increasingly used for human genetic modification, but methods for monitoring off-target editing are nascent. Here we present a simple model-independent workflow for identifying sites of off-target base-editing in relevant cell types on a genome-wide level. We report that sites of off-target editing by the ABE8e editor could be identified using an ABE8e derivative with restored DSB cleavage activity. This allows marking of enzyme-generated double-stranded (ds) DNA breaks by incorporation of dsDNA oligonucleotides that are transfected into primary target cells. DNA sequencing at sites of oligonucleotide incorporation reported both the genomic location of off-target cleavage and the extent of base-editing nearby. We present a platform combining this cellular (BEiGUIDE-Seq) and computational workflow (CRISPRito) to generate optimized amplicon panels for convenient monitoring of off-target base editing. This work introduces a generalizable strategy to evaluate off-target edits in patient-derived cells, addressing a critical safety gap for clinical base editing.

molecular biology↗

bioRxiv2020

The effects of different frequencies of rhythmic acoustic stimulation on gait kinematics and trunk sway in healthy elderly population

The use of rhythmic acoustic stimulation (RAS) in improving gait and balance in healthy elderly subjects has been widely investigated. However, methodologies and results are often controversial. In this study, we hypothesize that both the kinematic features of gait and stability, depend on the frequency at which RAS is administered. Our aim was to observe, through 3D Gait Analysis, the effect of different types of RAS (at a fixed frequency or based on the average cadence of each subject) on both gait spatio-temporal parameters and stability. The latter was estimated through an innovative measure, the trunk displacement index (TDI) that we have recently implemented. We observed that the low frequencies RAS led to a general slowdown of gait, which did not provide any clear benefit and produced harmful effects on stability when the frequency became too low compared to the individual natural frequency. On the contrary, the high frequencies of RAS showed a slight acceleration of gait, accompanied by better stability (as documented by a lower TDI value), regardless of the type of RAS. Finally, the RAS equal to the individual natural cadence also produced an increase in stability.

neuroscience↗

bioRxiv2020

A synthetic kinematic index of trunk displacement conveying the overall motor condition in Parkinson's disease

BACKGROUNDParkinsons disease (PD) is characterized by motor impairment, affecting quality of life and increasing fall risk, due to ineffective postural control. To this day, the diagnosis remains based on clinical approach. Similarly, motor evaluation is based on heterogeneous, operator-dependent observational criteria. A synthetic, replicable index to quantify motor impairment is still lacking. In this paper, we build upon the idea that the trunk is crucial in balance control. Hence, we have designed a new measure of postural stability which assesses the trunk displacement in relation to the center of mass, that we named trunk displacement index (TDI). METHODSTwenty-three PD patients and twenty-three healthy controls underwent clinical (UPDRS-III) and motor examination (3D gait analysis). The TDI was extracted from kinematic measurements using a stereophotogrammetric system. A correlation analysis was performed to assess the relationship of TDI with typical gait parameters, to verify its biomechanical value, and UPDRS-III, to observe its clinical relevance. Finally, its sensitivity was measured, comparing pre- and post-L-DOPA subclinical intake. RESULTSThe TDI showed significant correlations with many gait parameters, including both velocity and stability characteristics of gait, and with the UPDRS-III. Finally, the TDI resulted capable in discriminating between off and on state in PD, whereas typical gait parameters failed two show any difference between those two conditions. CONCLUSIONSOur results suggest that the TDI may be considered a highly sensitive biomechanical index, reflecting the overall motor condition in PD, and provided of clinical relevance due to the correlation with the clinical evaluation.

neuroscience↗