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The mRNA splicing machinery has been estimated to generate 100,000 known protein-coding transcripts for 20,000 human genes (Ensembl, Sept. 2024). However, this set is expanding with the massive and rapidly growing data coming from high-throughput technologies, particularly single-cell and long-read sequencing. Yet, the implications of splicing complexity at the protein level remain largely uncharted. In this review, we describe the current advances toward systematically assessing the contribution of alternative splicing to proteome function diversification. We discuss the potential and challenges of using artificial intelligence-based techniques in identifying alternative splicing proteoforms and characterising their structures, interactions, and functions., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Freehand 3D ultrasound (3D-US) is a promising technique for measuring muscle volume but it requires gel pads or water tanks to limit probe compression on the skin which makes it hard to use in clinical applications. Our objectives were to measure the effect of different compressions on muscle volume in order to assess the clinical applicability of a minimal compression method for lower limb muscles. 4 muscles of the lower limb on 15 healthy volunteers were scanned with a new commercial freehand 3D-US setup accessible to clinical experimentators. Each muscle was scanned with 3 levels of compression: standard compression, minimal compression and gel pad (method validated against MRI). Volume was calculated using software segmentation tools. Acquisitions and segmentations were done by the same examiner. There was a significant impact of standard compression on volume measurements, but no difference between minimal compression and gel pad. Standard compression underestimated volume with a mean bias of 16 mL. For minimal compression, 75 % of measured differences were below the predefined clinically acceptable limits of 10 mL. Mean bias for this method was 1.1 mL. In conclusion, standard compression in freehand 3D-US induces a systematic bias in volume calculations. But, with a trained examiner and the necessary precautions to minimize compression, this bias could be abolished and become acceptable in clinical applications. When a high accuracy is required, gel pads could still be important to consider., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Studies of the Arabidopsis cat2 mutant lacking the major leaf isoform of catalase have allowed the potential impact of intracellular H 2 O 2 on plant function to be studied. Here, we report a robust analysis of modified gene expression associated with key families involved in metabolite modification in cat2. Through a combined transcriptomic and metabolomic analysis focused on the salicylic acid (SA) and jasmonic acid (JA) pathways, we report key features of the metabolic signatures linked to oxidative stress-induced signaling via these defence hormones and discuss the enzymes that are likely to be involved in determining these features. We provide evidence that specific UDP-glycosyl transferases contribute to the glucosylation of SA that accumulates as a result of oxidative stress in cat2. Glycosides of dihydroxybenzoic acids that accumulate alongside SA in cat2 are identified and, based on the expression of candidate genes, likely routes for their production are discussed. We also report that enhanced intracellular H 2 O 2 triggers induction of genes encoding different enzymes that can metabolize JA. Integrated analysis of metabolite and transcript profiles suggests that a gene network involving specific hydrolases, hydroxylases, and sulfotransferases functions to limit accumulation of the most active jasmonates during oxidative stress., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study investigated the effects of marker placement (skin- vs shoe-mounted) on metatarsophalangeal joint (MTP) kinematics and kinetics during running. Fifteen trained men ran on a 15-m track at 10 and 13 km/h with three (low, standard and high stiffness) shoe longitudinal bending stiffnesses (LBS). Reflective markers were fixed on the shoe upper, and on the skin using holes cut in the shoe. Three-dimensional marker positions and ground reaction forces were recorded at 200 and 2000 Hz, respectively. Kinematic and kinetic parameters were analyzed using one-dimensional metrics (statistical parametric mapping). MTP joint was less dorsiflexed at midstance ([57% to 100%] of braking phase and [0% to 48%] of pushing phase), and the MTP joint plantarflexion moment was higher ([22% to 55%] of pushing phase) with the shoe markerset in comparison with the skin markerset. The effect of LBS on MTP angle was found to be significant for a larger percentage of each stride using the shoe markerset compared to the skin markerset. However, the effect of LBS on plantarflexion moment was significant with the shoe markerset only. The effect of running speed on MTP angle was significant for a larger percentage of each stride with the skin markerset. This study demonstrates that the placement of markers influences the measurement of MTP kinematics and kinetics and that these effects are mediated by other variables such as LBS or running speed. It is concluded that the shoe markerset does not fully reflect the movement of the MTP joint., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

The reading of action verbs has been shown to activate motor areas, whereby sentence context may serve to either globally strengthen this activation or to selectively sharpen it. To investigate this issue, we manipulated the presence of manual actions and sentence context, assessing the level of corticospinal excitability by means of transcranial magnetic stimulation. We hypothesized that context would serve to sharpen the neural representation of the described actions in the motor cortex, reflected in context-specific modulation of corticospinal excitability. Participants silently read manual action verbs and non-manual verbs, preceded by a full sentence (rich context) or not (minimal context). Transcranial magnetic stimulation pulses were delivered at rest or shortly after verb presentation. The coil was positioned over the cortical representation of the right first dorsal interosseous (pointer finger). We observed a general increase of corticospinal excitability while reading both manual action and non-manual verbs in minimal context, whereas the modulation was action-specific in rich context: corticospinal excitability increased while reading manual verbs, but did not differ from baseline for non-manual verbs. These findings suggest that sentence context sharpens motor representations, activating the motor cortex when relevant and eliminating any residual motor activation when no action is present., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objectives: Among interstitial pneumonia with autoimmune features (IPAF) patients, identifying those at risk to develop a connective tissue disease (CTD) during the disease course is a key issue. The aim of this study was to evaluate the incidence of definite CTD diagnosis in IPAF patients during follow-up., Methods: We performed a multicentric cohort study of interstitial lung disease (ILD) from 2010 to 2017 in pneumology and immunology departments of tertiary care centers. Patients with a known cause of ILD (including established CTD) at diagnosis were excluded. Among patients with idiopathic ILD and at least three years of follow-up, two groups (IPAF and non-IPAF) were retrospectively analyzed at time of diagnosis., Results: A total of 249 patients with ILD were enrolled, including 70 IPAF and 179 non-IPAF patients. After a mean follow-up time of 77 ± 44 months, 18/70 IPAF patients (26%) had a CTD diagnosis - 9 antisynthetase syndrome, 8 systemic sclerosis and 1 overlap myositis - compared with 4/179 non-IPAF patients (2%). IPAF patients were at higher risk of CTD occurrence at 3 years of follow-up compared to non-IPAF patients (HR 10.1, 95% CI 3.1-33.1, p < 0. 01). IPAF patients progressing to CTD tended to be younger, more often female and have more frequently puffy fingers, capillaroscopy abnormalities and antisynthetase antibodies at diagnosis., Conclusions: We found that a significant proportion of IPAF patients had associated CTD diagnosis during follow-up. Prospective studies are needed to confirm baseline predictive factors of CTD occurrence in IPAF patients., (Copyright © 2021 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

While a soft film itself is not able to induce cell spreading, BMP-2 presented via such soft film (so called "matrix-bound BMP-2") was previously shown to trigger cell spreading, migration and downstream BMP-2 signaling. Here, we used thin films of controlled stiffness presenting matrix-bound BMPs to study the effect of four BMP members (BMP-2, 4, 7, 9) on cell adhesion and differentiation of skeletal progenitors. We performed automated high-content screening of cellular responses, including cell number, cell spreading area, SMAD phosphorylation and alkaline phosphatase activity. We revealed that the cell response to bBMPs is BMP-type specific, and involved certain BMP receptors and beta chain integrins. In addition, this response is stiffness-dependent for several receptors. The basolateral presentation of the BMPs allowed us to discriminate the specificity of cellular response, especiallyd the role of type I and II BMP receptors and of β integrins in a BMP-type and stiffness-dependent manner. Notably, BMP-2 and BMP-4 were found to have distinct roles, while ALK5, previously known as a TGF-β receptor was revealed to be involved in the BMP-pathway., (Copyright © 2022. Published by Elsevier Ltd.)

Substance use disorder develops from complex interactions between socio-environmental and neurobiological factors. A neurocognitive model of addiction, the triadic model, proposes that Alcohol Use Disorder (AUD) is the result of an imbalance between the reflective and the impulsive subcomponents along with a disruption of the regulatory subcomponent. Physical activity is considered as an emerging treatment for severe AUD (sAUD). This short review examines the efficacy and mechanisms of action of physical intervention as an adjunctive treatment in severe AUD (sAUD) within the theoretical framework of the triadic model. Physical activity is a feasible, safe, and less stigmatizing approach than classical treatments. It improves sAUD patients' mental and physical comorbidities. The key finding of this short review is that physical activity could contribute to a rebalancing of the triadic model in sAUD patients by 1) improving neuroplasticity and cognitive functioning, 2) reducing impulsivity and urgency, and improving emotional regulation, and 3) reducing craving. This rebalancing could eventually reduce the risk of relapse. However, due to methodological issues, it remains difficult to observe an effect of physical activity on drinking outcomes. At best, a trend towards a reduction in alcohol consumption was noted. The mechanisms that could explain the benefits of physical activity in sAUD patients involve multiple physiological processes such as dopaminergic or glutamatergic transmission and signaling or neuroplasticity. Future randomized controlled trials should include neuropsychological and impulsivity assessments, in more controlled environments. Physical activity could contribute to a personalization of sAUD treatment using each subcomponent of the triadic model as a therapeutic target. Physical exercise could be an adjunctive treatment for sAUD patients, favoring the benefit of more usual treatments such as cognitive behavioral therapies. It could also be a stand-alone intervention in less severe patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Neuropsychological impairments found in recently detoxified patients with alcohol use disorder (AUD) can limit the benefit of psychosocial treatments and increase the risk of relapse. These neuropsychological deficits are reversible with abstinence. The aim of this retrospective clinical study was to investigate whether a short-term stay as inpatients in a convalescent home enables neuropsychological deficits observed in recently detoxified AUD patients to recover and even performance to return to normal., Methods: Neuropsychological data were collected in 84 AUD patients. Five neuropsychological components were assessed before and after a three-week stay in a convalescent home offering multidisciplinary support. Baseline and follow-up performance were compared in the entire group of patients and in subgroups defined by the nature and intensity of the therapy (OCCASIONAL: occasional occupational and physical therapy; INTENSIVE: intensive occupational and physical therapy and neuropsychological training)., Results: In the entire group of patients, neuropsychological performance significantly improved between baseline and follow-up for all 5 components and even returned to a normal level for 4 of them. The ratio of patients with impaired performance was significantly lower at follow-up than baseline examination for 3 components in the INTENSIVE group only., Conclusion: Recently detoxified AUD patients with cognitive deficits benefit from a short-term stay in an environment ensuring sobriety and healthy nutrition. Cognitive recovery may be enhanced by intensive care including neuropsychological training. Alcohol programs could be postponed in patients with cognitive deficits in order to offer psychosocial treatment when patients are cognitively able to benefit from it., (Copyright © 2020. Published by Elsevier Ltd.)