Biology subjects

Carotenuto, A.

Publications and source records attributed to Carotenuto, A..

3 recordsLinked to original sources

bioRxiv2021

The kinectome: a comprehensive kinematic map of human motion in health and disease

Effective human movement requires the coordinated participation of the whole musculoskeletal system. Here we propose to represent the human body movements as a network (that we named "kinectome"), where nodes are body parts, and edges are defined as the correlations of the accelerations between each pair of body parts during gait. We apply this framework in healthy individuals and patients with Parkinsons disease (PD). The network dynamics in Parkinsons display high variability, as conveyed by the high variance and the modular structure in the patients kinectomes. Furthermore, our analysis identified a set of anatomical elements that are specifically related to the balance impairment in PD. Furthermore, each participant could be identified based on its kinectome patterns, akin to a "fingerprint" of movement, confirming that our approach captures relevant features of gait. We hope that applying network approaches to human kinematics yields new insights to characterize human movement.

bioengineering↗

bioRxiv2020

Membrane-tethered peptides derived from intracellular loops 2 and 3 of the urotensin II receptor act as allosteric biased ligands

Over the last decade, the urotensinergic system has garnered significant attention as a promising new target for the treatment of various cardiovascular diseases and also cancer. Significant investment toward the development of clinically relevant UT ligands for therapeutic intervention has been made but have met little to no success to date. The UT system, which has yet to be effectively targeted, therefore remains to be therapeutically exploited. The discovery of allosteric sites that allow modulation of receptor activity will increase the searchable chemical space against a disease-relevant target. Pepducins and other lipidated peptides have been used as both mechanistic probes and potential therapeutics. Therefore, pepducins derived from the human urotensin II receptor might represent unique tools to generate signaling bias and study UT signaling networks. Two hUT-derived pepducins, derived from the second and the third intracellular loop of UT, respectively, have been synthesized and pharmacologically characterized. Our results demonstrated that hUT-Pep2 and [Trp1, Leu2]hUT-Pep3 acted as biased ago-allosteric modulators, triggered ERK1/2 phosphorylation and to a lesser extent, IP1 production, stimulated cell proliferation yet were devoid of contractile activity. Interestingly, both hUT-derived pepducins were able to modulate hUII- and URP-mediated contraction albeit to different extents. These new derivatives represent unique tools to reveal the intricacies of hUT signaling and also a novel avenue to design allosteric ligands selectively targeting UT signaling that could prove to be useful for the treatment of hUT-associated diseases.

pharmacology and toxicology↗

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↗