Brambilla, C. | Search bioRxiv

bioRxiv2023

Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development

Hypercholesterolemia is a major risk factor for atherosclerosis and associated cardiovascular diseases. The liver plays a key role in the regulation of plasma cholesterol levels and hosts a large population of tissue-resident macrophages known as Kupffer cells (KCs). KCs are located in the hepatic sinusoids where they ensure key functions including blood immune surveillance. However, how KCs homeostasis is affected by the build-up of cholesterol-rich lipoproteins that occurs in the circulation during hypercholesterolemia remains unknown. Here, we found that embryo-derived KCs (EmKCs) accumulated large amounts of lipoprotein-derived cholesterol, in part through the scavenger receptor CD36, and massively expanded early after the induction of hypercholesterolemia. After this rapid adaptive response, EmKCs exhibited mitochondrial oxidative stress and their numbers gradually diminished while monocyte-derived KCs (MoKCs) with reduced cholesterol-loading capacities seeded the KC pool. Decreased proportion of EmKCs in the KC pool enhanced liver cholesterol content and exacerbated hypercholesterolemia, leading to accelerated atherosclerotic plaque development. Together, our data reveal that KC homeostasis is perturbed during hypercholesterolemia, which in turn alters the control of plasma cholesterol levels and increases atherosclerosis.

pathology↗

bioRxiv2022

Spatial and temporal muscle synergies provide a dual characterization of low-dimensional and intermittent control of upper-limb movements

Muscle synergy analysis is commonly used for investigating the neurophysiological mechanisms that the central nervous system employs to control muscle activations. In the last two decades, several models have been developed to decompose EMG signals into spatial, temporal or spatiotemporal synergies. However, the presence of different approaches complicates the comparison and interpretation of results. Spatial synergies represent invariant activation weights in muscle groups modulated with variant temporal coefficients, while temporal synergies are based on invariant temporal profiles that coordinate variant muscle weights. While non-negative matrix factorization (NMF) allows to extract both spatial and temporal synergies, temporal synergies and the comparison between the two approaches have been barely investigated and so far no study targeted a large set of multi-joint upper limb movements. Here we present several analyses that highlight the duality of spatial and temporal synergies as a characterization of low-dimensional and intermittent motor coordination in the upper limb, allowing high flexibility and dexterity. First, spatial and temporal synergies were extracted from two datasets representing a comprehensive mapping of proximal (REACH PLUS) and distal (NINAPRO) upper limb movements, focusing on their differences in reconstruction accuracy and inter-individual variability. For both models, we extracted synergies achieving a given level of the goodness of reconstruction (R2), and we compared the similarity of the invariant components across participants. The two models provide a compact characterization of motor coordination at spatial or temporal level, respectively. However, a lower number of temporal synergies are needed to achieve the same R2 with a higher inter-subject similarity. Spatial and temporal synergies may thus capture different levels of motor control. Second, we showed the existence of both spatial and temporal structure in the EMG data, extracting spatial and temporal synergies from a surrogate dataset in which the phases were shuffled preserving the same frequency content of the original data. Last, a detailed characterization of the structure of the temporal synergies suggested that they can be related to an intermittent control of the movement. These results may be useful to improve muscle synergy analysis in several fields such as rehabilitation, prosthesis control and motor control studies.

neuroscience↗