Increasing fitness with FES rowing

Functional electrical stimulation assisted rowing (FES-rowing) can be used as a rehabilitation procedure and recreational activity for persons with lower-limbs paralysis1. In FES-rowing typically quadriceps and hamstring muscles are stimulated, which improves the status of the cardiovascular system and increases muscle mass2,3; thereby, the risk from secondary complications associated with the sedentary lifestyle imposed on those who are unable to ambulate is reduced. The aims of the present study were (i) to assess the effectiveness of FES-rowing in young healthy subjects as compared with rowing alone; (ii) to evaluate the feasibility of rowing combined with the coordinated stimulation of 3 muscle groups (quadriceps, hamstrings and triceps surae)

Optimisation of industrial production of low-force sensors – adhesive bonding of force-centring ball

This work addresses the issue of attaching the force-centring part (a round ball) to the load cell of a force sensor, a piezoresistive thick-film Wheatstone bridge deposited onto a ceramic cantilever. As the current soldering process requires expensive metallisation steps for both the ball and the cantilever, and subjects the solder pads used for mounting the cantilever to an additional reflow cycle, an alternative adhesive bonding process was developed, allowing both simpler production and the use of other ball materials such as ceramic and glass. The self-centring action of solder capillary forces was ensured by structuring the adhesive so as to form a mechanical cuvette allowing centring of the ball by gravity. The selected adhesive materials exhibited good printability and bonding, as well as surviving the subsequent soldering and cleaning process steps

Alix is required for activity-dependent bulk endocytosis at brain synapses

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activitydependent bulk endocytosis (ADBE). Alix (ALG-2-interacting protein X/PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrinindependent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons, we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ADBE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix leads to abnormal synaptic recovery during physiological or pathological repeated stimulations

The Scaffolding Protein Dlg1 Is a Negative Regulator of Cell-Free Virus Infectivity but Not of Cell-to-Cell HIV-1 Transmission in T Cells

Background: Cell-to-cell virus transmission of Human immunodeficiency virus type-1 (HIV-1) is predominantly mediated by cellular structures such as the virological synapse (VS). The VS formed between an HIV-1-infected T cell and a target T cell shares features with the immunological synapse (IS). We have previously identified the human homologue of the Drosophila Discs Large (Dlg1) protein as a new cellular partner for the HIV-1 Gag protein and a negative regulator of HIV-1 infectivity. Dlg1, a scaffolding protein plays a key role in clustering protein complexes in the plasma membrane at cellular contacts. It is implicated in IS formation and T cell signaling, but its role in HIV-1 cell-to-cell transmission was not studied before. Methodology/Principal Findings: Kinetics of HIV-1 infection in Dlg1-depleted Jurkat T cells show that Dlg1 modulates the replication of HIV-1. Single-cycle infectivity tests show that this modulation does not take place during early steps of the HIV-1 life cycle. Immunofluorescence studies of Dlg1-depleted Jurkat T cells show that while Dlg1 depletion affects IS formation, it does not affect HIV-1-induced VS formation. Co-culture assays and quantitative cell-to-cell HIV-1 transfer analyses show that Dlg1 depletion does not modify transfer of HIV-1 material from infected to target T cells, or HIV-1 transmission leading to productive infection via cell contact. Dlg1 depletion results in increased virus yield and infectivity of the viral particles produced. Particles with increased infectivity present an increase in their cholesterol content and during the first hours of T cell infection these particles induce higher accumulation of total HIV-1 DNA

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Je relie système complexe, combinatoire, biologie des systèmes et apprentissage profond, qui suis-je ? Hyper-réseau, définitions et cas d’usage

National audienceHypernetworks appeared in many fields and uses including combinatorics problems, the theory of complex systems, the systems biology and deep learning with different semantics. It is important to understand the uses of the term hypernetwork in the literature to avoid confusion. The objective of this article to make a state of the art of the definitions of the hypernetwork according to the field of use. In particular, we will try to situate hypernetworks in our research context on artificial intelligence.Les hyper-réseaux apparaissaient dans de nombreux domaines et usages dont des problèmes de combinatoire, la théorie des systèmes complexes, la biologie des systèmes et l’apprentissage profond avec une sémantique différente. Il est important de comprendre les utilisations du terme hyper-réseau dans la littérature afin d’éviter toute confusion. L’objectif de cet article est de faire un état de l’art des définitions de l’hyper-réseau suivant le domaine d’utilisation. Nous nous attacherons notamment à situer les hyper-réseaux dans notre contexte de recherche sur l’intelligence artificielle

Metal-Coordination-Assisted Folding and Guest Binding in Helical Aromatic Oligoamide Molecular Capsules

The development of foldamer-based receptors is driven by the design of monomers with specific properties. Herein, we introduce a pyridazine-pyridine-pyridazine diacid monomer and its incorporation into helical aromatic oligoamide foldamer containers. This monomer codes for a wide helix diameter and can sequester metal ions on the inner wall of the helix cavity. Crystallographic studies and NMR titrations show that part of the metal coordination sphere remains available and may then promote the binding of a guest within the cavity. In addition to metal coordination, binding of the guest is assisted by cooperative interactions with the helix host, thereby resulting in significant enhancements depending on the foldamer sequence, and in slow guest capture and release on the NMR time scale. In the absence of metal ions, the pyridazine-pyridine-pyridazine monomer promotes an extended conformation of the foldamer that results in aggregation, including the formation of an intertwined duplex

Metal-Coordination-Assisted Folding and Guest Binding in Helical Aromatic Oligoamide Molecular Capsules

International audienceThe development of foldamer-based receptors is driven by the design of monomers with specific properties. Herein, we introduce a pyridazine-pyridine-pyridazine diacid monomer and its incorporation into helical aromatic oligoamide foldamer containers. This monomer codes for a wide helix diameter and can sequester metal ions on the inner wall of the helix cavity. Crystallographic studies and NMR titrations show that part of the metal coordination sphere remains available and may then promote the binding of a guest within the cavity. In addition to metal coordination, binding of the guest is assisted by cooperative interactions with the helix host, thereby resulting in significant enhancements depending on the foldamer sequence, and in slow guest capture and release on the NMR time scale. In the absence of metal ions, the pyridazine-pyridine-pyridazine monomer promotes an extended conformation of the foldamer that results in aggregation, including the formation of an intertwined duple

Gut Microbiota Remodeling and Intestinal Adaptation to Lipid Malabsorption After Enteroendocrine Cell Loss in Adult MiceSummary

Background &amp; Aims: Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete various hormones acting locally or at a distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has yet to be directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome, and microbiota. Methods: We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites, and transcriptomic responses in the proximal and distal small intestines of mice lacking EECs. We also determined the high-fat diet-induced transcriptomic changes in sorted Neurog3eYFP/+ EECs. Results: Induction of EEC deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced, and lipid absorption is impaired and delayed in the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism, and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after EECs depletion and is characterized by decreased α-diversity. Bacteroides and Lactobacillus were progressively enriched, whereas Lachnospiraceae declined without impacting fecal short-chain fatty acid concentrations. Conclusions: EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption, leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota