Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

The metabolic cost of in vivo constant muscle force production at zero net mechanical work

The metabolic cost per unit force is generally thought to increase with the mechanical work done by the muscle fibres. It is currently unclear how the metabolic cost of doing alternating positive and negative muscle fibre mechanical work relates to the metabolic cost of doing zero muscle fibre mechanical work at similar muscle force. The current study aimed to investigate this issue by comparing in vivo metabolic power between a dynamic and an isometric near-constant force production task. In both tasks, participants performed periodic movement about the knee joint in the gravitational field. Therefore, net external mechanical work was constrained to be zero. The tasks mainly differed from each other in average positive knee joint mechanical power, which was 4.3±0.5 W per leg during the dynamic task and 0.1±0.1 W per leg during the isometric task. Knee extension torque was near-constant around 15.2±1.7 N m during the dynamic task and around 15.7±1.7 N m during the isometric task. Owing to near-constant knee extension torque, quadriceps tendon length was presumably nearly constant during both tasks. Therefore, knee joint mechanical work was predominantly done by the muscle fibres in both tasks. Average gross metabolic power was 3.22±0.46 W kg-1 during the dynamic task and 2.13±0.36 W kg-1 during the isometric task. Because tasks differed mainly in the amount of positive muscle fibre mechanical work, these results imply that the metabolic cost of near-constant force production in vivo at zero net mechanical work can be reduced by minimizing positive muscle fibre mechanical work

Comparison of the validity of Hill and Huxley muscle–tendon complex models using experimental data obtained from rat m. soleus in situ

Cet ouvrage n’est pas un bilan historiographique et problématique de recherches en cours sur tel ou tel aspect de l’histoire du Moyen Âge européen. Il s’agit bien plutôt d’un état des lieux sur une matière, une branche de la science historique, sur ses acteurs, leurs institutions et leurs conditions de travail. Le lecteur trouvera naturellement dans cet ouvrage de nombreuses références bibliographiques et la recension de travaux récents sur les domaines en pointe de la « médiévistique » : le ..

Commentary: Validation of a ramp running protocol for determination of the true VO2max in mice

International audienceA commentary on :Validation of a Ramp Running Protocol for Determination of the True VO2max in Miceby Ayachi, M., Niel, R., Momken, I., Billat, V. L., and Mille-Hamard, L. (2016). Front. Physiol. 7:372. doi: 10.3389/fphys.2016.0037

Vertebral level specific modulation of paraspinal muscle activity based on vestibular signals during walking

Abstract: Evoking muscle responses by electrical vestibular stimulation (EVS) may help to understand the contribution of the vestibular system to postural control. Although paraspinal muscles play a role in postural stability, the vestibulo-muscular coupling of these muscles during walking has rarely been studied. This study aimed to investigate how vestibular signals affect paraspinal muscle activity at different vertebral levels during walking with preferred and narrow step width. Sixteen healthy participants were recruited. Participants walked on a treadmill for 8 min at 78 steps/min and 2.8 km/h, at two different step width, either with or without EVS. Bipolar electromyography was recorded bilaterally from the paraspinal muscles at eight vertebral levels from cervical to lumbar. Coherence, gain, and delay of EVS and EMG responses were determined. Significant EVS-EMG coupling (P &lt; 0.01) was found at ipsilateral and/or contralateral heel strikes. This coupling was mirrored between left and right relative to the midline of the trunk and between the higher and lower vertebral levels, i.e. a peak occurred at ipsilateral heel strike at lower levels, whereas it occurred at contralateral heel strike at higher levels. EVS-EMG coupling only partially coincided with peak muscle activity. EVS-EMG coherence slightly, but not significantly, increased when walking with narrow steps. No significant differences were found in gain and phase between the vertebral levels or step width conditions. In summary, vertebral level specific modulation of paraspinal muscle activity based on vestibular signals might allow a fast, synchronized, and spatially co-ordinated response along the trunk during walking. (Figure presented.). Key points: Mediolateral stabilization of gait requires an estimate of the state of the body, which is affected by vestibular afference. During gait, the heavy trunk segment is controlled by phasic paraspinal muscle activity and in rodents the medial and lateral vestibulospinal tracts activate these muscles. To gain insight in vestibulospinal connections in humans and their role in gait, we recorded paraspinal surface EMG of cervical to lumbar paraspinal muscles, and characterized coherence, gain and delay between EMG and electrical vestibular stimulation, during slow walking. Vestibular stimulation caused phasic, vertebral level specific modulation of paraspinal muscle activity at delays of around 40 ms, which was mirrored between left, lower and right, upper vertebral levels. Our results indicate that vestibular afference causes fast, synchronized, and spatially co-ordinated responses of the paraspinal muscles along the trunk, that simultaneously contribute to stabilizing the centre of mass trajectory and to keeping the head upright.</p

Metabolic cost of activation and mechanical efficiency of mouse soleus muscle fiber bundles during repetitive concentric and eccentric contractions

Currently available data on the energetics of isolated muscle preparations are based on bouts of less than 10 muscle contractions, whereas metabolic energy consumption is mostly relevant during steady state tasks such as locomotion. In this study we quantified the energetics of small fiber bundles of mouse soleus muscle during prolonged (2 min) series of contractions. Bundles (N = 9) were subjected to sinusoidal length changes, while measuring force and oxygen consumption. Stimulation (five pulses at 100 Hz) occurred either during shortening or during lengthening. Movement frequency (2-3 Hz) and amplitude (0.25-0.50 mm; corresponding to ± 4-8% muscle fiber strain) were close to that reported for mouse soleus muscle during locomotion. The experiments were performed at 32°C. The contributions of cross-bridge cycling and muscle activation to total metabolic energy expenditure were separated using blebbistatin. The mechanical work per contraction cycle decreased sharply during the first 10 cycles, emphasizing the importance of prolonged series of contractions. The mean ± SD fraction of metabolic energy required for activation was 0.37 ± 0.07 and 0.56 ± 0.17 for concentric and eccentric contractions, respectively (both 0.25 mm, 2 Hz). The mechanical efficiency during concentric contractions increased with contraction velocity from 0.12 ± 0.03 (0.25 mm 2 Hz) to 0.15 ± 0.03 (0.25 mm, 3 Hz) and 0.16 ± 0.02 (0.50 mm, 2 Hz) and was -0.22 ± 0.08 during eccentric contractions (0.25 mm, 2 Hz). The percentage of type I fibers correlated positively with mechanical efficiency during concentric contractions, but did not correlate with the fraction of metabolic energy required for activation

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions