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Cell function depends on tissue rigidity, which cells probe by applying and transmitting forces to their extracellular matrix, and then transducing them into biochemical signals. Here we show that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin–talin–integrin–fibronectin clutch. We demonstrate that force transmission is regulated by a dynamic clutch mechanism, which unveils its fundamental biphasic force/rigidity relationship on talin depletion. Force transduction is triggered by talin unfolding above a stiffness threshold. Below this threshold, integrins unbind and release force before talin can unfold. Above the threshold, talin unfolds and binds to vinculin, leading to adhesion growth and YAP nuclear translocation. Matrix density, myosin contractility, integrin ligation and talin mechanical stability differently and nonlinearly regulate both force transmission and the transduction threshold. In all cases, coupling of talin unfolding dynamics to a theoretical clutch model quantitatively predicts cell response. Integrins and talin are parts of a ‘molecular clutch’ that mechanically links the actin cytoskeleton to the extracellular matrix. Elosegui-Artola et al.  now reveal a tunable rigidity threshold, above which talin unfolds to mediate force transduction.

Attention Deficit Hyperactivity Disorder (ADHD) is a developmental disorder, with an onset in childhood, that accompanies the person throughout their life, with prevalence between 3 and 5% in adults. Recent studies point towards a fourth core symptom of the disorder related to the emotional information processing that would explain the repercussions that ADHD has on the social, academic, and professional life of the people affected. This review aims to describe emotion dysregulation features as well as the brain activity associated in adults with ADHD. A search of the scientific literature was launched in specialized databases: PsycInfo, Medline, Eric, PsycArticle, Psicodoc and Scopus, following PRISMA guidelines. Twenty-two articles met the inclusion criteria: (a) an ADHD clinical diagnosis, (b) participants over 18 years old, (c) emotion regulation measurement, (d) empirical studies, and (c) in English. Due to the heterogeneity of the studies included, they were classified into three sections: measures and features of emotion regulation (ER) in people with ADHD, neurological and psychophysiological activity related to ER, and treatments. The studies found that meet the selection criteria are scarce and very heterogeneous both in aims and in sample features. Adults with ADHD show a more frequent use of non-adaptive emotion regulation strategies compared to people without ADHD symptoms. Moreover, emotion dysregulation was associated with symptom severity, executive functioning, psychiatric comorbidities, and even with criminal conviction. Different patterns of brain activity were observed when people with and without ADHD were compared. These results may suggest that psychopharmacological treatments as well as behavioral therapies could be useful tools for improving emotional difficulties in adult ADHD.

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology. Cancer-associated fibroblasts (CAFs) can produce ECM and form a physical barrier around the tumour. Here, the authors show in transgenic mouse models and in vitro systems that CAFs are able to actively compress cancer cells using actomyosin contractility and this leads to a modulation of cancer cell mechanosensing and tumour reorganisation.

Intestinal organoids capture essential features of the intestinal epithelium such as crypt folding, cellular compartmentalization and collective movements. Each of these processes and their coordination require patterned forces that are at present unknown. Here we map three-dimensional cellular forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the extracellular matrix and folds through apical constriction, whereas the transit amplifying zone pulls the extracellular matrix and elongates through basal constriction. The size of the stem cell compartment depends on the extracellular-matrix stiffness and endogenous cellular forces. Computational modelling reveals that crypt shape and force distribution rely on cell surface tensions following cortical actomyosin density. Finally, cells are pulled out of the crypt along a gradient of increasing tension. Our study unveils how patterned forces enable compartmentalization, folding and collective migration in the intestinal epithelium. Pérez-González et al. explore the mechanical properties of intestinal organoids, and report the existence of distinct mechanical domains and that cells are pulled out of the central crypt along a gradient of increasing tension.

Echolocating animals that forage in social groups can potentially benefit from eavesdropping on other group members, cooperative foraging or social defence, but may also face problems of acoustic interference and intra-group competition for prey. Here, we investigate these potential trade-offs of sociality for extreme deep-diving Blainville′s and Cuvier's beaked whales. These species perform highly synchronous group dives as a presumed predator-avoidance behaviour, but the benefits and costs of this on foraging have not been investigated. We show that group members could hear their companions for a median of at least 91% of the vocal foraging phase of their dives. This enables whales to coordinate their mean travel direction despite differing individual headings as they pursue prey on a minute-by-minute basis. While beaked whales coordinate their echolocation-based foraging periods tightly, individual click and buzz rates are both independent of the number of whales in the group. Thus, their foraging performance is not affected by intra-group competition or interference from group members, and they do not seem to capitalize directly on eavesdropping on the echoes produced by the echolocation clicks of their companions. We conclude that the close diving and vocal synchronization of beaked whale groups that quantitatively reduces predation risk has little impact on foraging performance.

This randomized controlled trial aims to evaluate the efficacy of a cognitive training program using video games in improving neuropsychological, neurological, immunological, and inflammatory parameters in childhood cancer survivors. This study will recruit 56 patients aged 8–17 years who have completed cancer treatment 1–8 years prior to enrollment. Participants will be randomized to either the video game intervention or waiting group. The primary objectives are analyzing potential changes in neuropsychological tests covering all neurocognitive domains, neuroimaging tests (structural, diffusion, and functional imaging), and immune and inflammatory biomarker levels after video game intervention. The secondary objectives are to define the prevalence of neurocognitive deficits in the study population, analyze psychological and emotional self-perception and parental perception after the intervention, and assess the feasibility of implementing this new intervention methodology. The inclusion criteria comprise specific diagnoses (central nervous system [CNS] cancer, hematologic malignancies, extracranial solid tumors, and nonmalignant hematological diseases requiring allogeneic hematopoietic progenitor transplantation) and treatments (CNS surgery, radiotherapy, intrathecal/intraventricular chemotherapy, neurotoxic systemic chemotherapy, and hematopoietic stem cell transplantation). Patients with active disease, relapse, or prior neurological or psychiatric pathology will be excluded. This study will improve the understanding and management of neurocognitive sequelae in childhood cancer survivors and ultimately enhance their quality of life. Trial identifier: NCT06312969

Educational research published over the past five years reveals a sustained shift from content-delivery models toward learning ecologies that explicitly interweave place, subjectivity, and institutional responsibility [...]

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behaviour of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between two-dimensional epithelial monolayers and three-dimensional spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell–cell and cell–substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic length scale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting—a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumour progression.

Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers in human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of primary human epithelial ovarian cancers (EOCs) from 100 patients. We found that rigorous quantitation of centrosome number in tumor samples was extremely challenging due to tumor heterogeneity and extensive tissue disorganization. Interestingly, even if centrosome clusters could be identified, the incidence of centrosome amplification was not comparable to what has been described in cultured cancer cells. Surprisingly, centrosome loss events where a few or many nuclei were not associated with centrosomes were clearly noticed and overall more frequent than centrosome amplification. Our findings highlight the difficulty of characterizing centrosome numbers in human tumors, while revealing a novel paradigm of centrosome number defects in EOCs. Synopsis Characterization of the centrosome number in epithelial ovarian cancers (EOCs) is challenging because these tumors are extremely disorganized and heterogeneous in respect to centrosome number. Centrosomes are the major microtubule‐organizing center of animal cells. Centrosome number normally varies between 1 and 2 according to cell cycle stage. We characterized centrosome numbers in 100 EOCs. Intra and inter‐tumor heterogeneity for centrosome number was noticed. In EOCs, cells with amplified centrosomes, which have been described in cancer cell lines, are not common. Cells without centrosomes are frequently found in EOCs. Graphical Abstract Characterization of the centrosome number in epithelial ovarian cancers (EOCs) is challenging because these tumors are extremely disorganized and heterogeneous in respect to centrosome number.

The purpose of this research is, on the one hand, to analyze the self-perception of future teachers of childhood education and primary education, and those studying for a master’s degree in secondary education teacher training on their Teacher Digital Competence (TDC), as well as the potential influence of gender, country and university institution of origin in their representations. On the other hand, it seeks to analyze the perception of future teachers on the TDC of their university trainers (formative perception). In accordance with these aims, a quantitative methodology of a non-experimental nature and of a prospective cross-sectional ex post facto approach has been used. A total of 428 students from two Spanish universities and from a French university agreed to participate in the research. The results report a positive and differential self-perception by gender of the TDC acquired and unfavorable perceptions of the digital competences of their teachers. These results confirm the need to improve the technological-manipulative and didactic training of university teachers, and to adapt the teaching competences to the demands of the Information and Communication Society (ICS) and to the guidelines of the Common Digital Competence Framework.