Metabolic trade-offs in childhood: Exploring the relationship between language development and body growth.

During human childhood, brain development and body growth compete for limited metabolic resources, resulting in a trade-off where energy allocated to brain development can decrease as body growth accelerates. This preregistered study explores the relationship between language skills, serving as a proxy for brain development, and body mass index at three distinct developmental stages, representing different phases of body growth. Longitudinal data from 2002 children in the EDEN mother-child cohort were analyzed using structural equation modeling. Our findings reveal a compelling pattern of associations: girls with a delayed adiposity rebound, signaling slower growth rate, demonstrated better language proficiency at ages 5-6. Importantly, this correlation appears to be specific to language skills and does not extend to nonverbal cognitive abilities. Exploratory analyses show that early environmental factors contributing to enhanced cognitive development, such as higher parental socio-economic status and increased cognitive stimulation, are positively associated with both language skills and the timing of adiposity rebound in girls. Overall, our findings lend support to the existence of an energy allocation trade-off mechanism that appears to prioritize language function over body growth investment in girls. RESEARCH HIGHLIGHTS: The high energy demand of neurocognitive development leads to a trade-off in human children between brain growth and other biological functions, including body growth. Previous studies indicate that around age 5, when the brain energy consumption peaks, children typically experience a decrease in body mass known as 'adiposity rebound'. A delayed adiposity rebound, indicating slower growth may be associated with enhanced language abilities in children. Our preregistered study confirms this correlation in girls and further associates early cognitive stimulation with improved language skills and delayed adiposity rebound time.

Early life adversity jointly regulates body-mass index and working memory development.

Previous work has proposed that balancing energy expenditure towards body and brain development in an optimal fashion results in a negative relationship between somatic and neurocognitive growth during development. An important issue, largely overlooked so far, is the extent to which this energetic trade-off is influenced by early life environmental factors. In this study, we estimated the association between neurocognitive (measured by working memory ability) and somatic (measured by body-mass index) developmental trajectories, while taking into account multiple dimensions of early life adversity. Results of our initial growth curve model were consistent with this brain-body trade-off in both girls and boys. In a subsequent model, we showed that early life adversity had positive associations with somatic and negative associations with neurocognitive growth trajectories, although the direct negative coupling between them remained consistent. Finally, a multidimensional adversity model, separating the effects of deprivation, threat and unpredictability, revealed that the dimension of deprivation-reflecting lack of access to resources and cognitive stimulation-contributed the most to both somatic and neurocognitive growth patterns. These results suggest that the way individuals balance energy between these two biological constructs during development is partly linked to environmental influences through phenotypic plasticity.

A reduced model of cell metabolism to revisit the glycolysis-OXPHOS relationship in the deregulated tumor microenvironment.

Cancer cells metabolism focuses the interest of the cancer research community. Although this process is intensely studied experimentally, there are very few theoretical models that address this issue. One of the main reasons is the extraordinary complexity of the metabolism that involves numerous interdependent regulatory networks which makes the computational recreation of this complexity illusory. In this study we propose a reduced model of the metabolism which focuses on the interrelation of the three main energy metabolites which are oxygen, glucose and lactate in order to better understand the dynamics of the core system of the glycolysis-OXPHOS relationship. So simple as it is, the model highlights the main rules allowing the cell to dynamically adapt its metabolism to its changing environment. It also makes it possible to address this impact at the tissue scale. The simulations carried out in a spheroid show non-trivial spatial heterogeneity of energy metabolism. It further suggests that the metabolic features that are commonly attributed to cancer cells are not necessarily due to an intrinsic abnormality of the cells. They can emerge spontaneously due to the deregulated over-acidic environment.

Climate is not a good candidate to account for variations in aggression and violence across space and time.

We agree with Van Lange et al. that climate is likely to affect individuals' social behavior in many ways. However, we suspect that its impact on physiology and psychology is so remote that its predictive power disintegrates almost completely through the causal chain underlying aggression and violence.

Perturbing the action observation network during perception and categorization of actions' goals and grips: state-dependency and virtual lesion TMS effects.

Watching others grasping and using objects activates an action observation network (AON), including inferior frontal (IFC), anterior intraparietal (AIP), and somatosensory cortices (S1). Yet, causal evidence of the differential involvement of such AON sensorimotor nodes in representing high- and low-level action components (i.e., end-goals and grip type) is meager. To address this issue, we used transcranial magnetic stimulation-adaptation (TMS-A) during 2 novel action perception tasks. Participants were shown adapting movies displaying a demonstrator performing goal-directed actions with a tool, using either power or precision grips. They were then asked to match the end-goal (Goal-recognition task) or the grip (Grip-recognition task) of actions shown in test pictures to the adapting movies. TMS was administered over IFC, AIP, or S1 during presentation of test pictures. Virtual lesion-like effects were found in the Grip-recognition task where IFC stimulation induced a general performance decrease, suggesting a critical role of IFC in perceiving grips. In the Goal-recognition task, IFC and S1 stimulation differently affected the processing of "adapted" and "nonadapted" goals. These "state-dependent" effects suggest that the overall goal of seen actions is encoded into functionally distinct and spatially overlapping neural populations in IFC-S1 and such encoding is critical for recognizing and understanding end-goals.

Specifying the timescale of early life unpredictability helps explain the development of internalising and externalising behaviours.

Early life unpredictability is associated with both physical and mental health outcomes throughout the life course. Here, we classified adverse experiences based on the timescale on which they are likely to introduce variability in children's environments: variations unfolding over short time scales (e.g., hours, days, weeks) and labelled Stochasticity vs variations unfolding over longer time scales (e.g., months, years) and labelled Volatility and explored how they contribute to the development of problem behaviours. Results indicate that externalising behaviours at age 9 and 15 and internalising behaviours at age 15 were better accounted for by models that separated Stochasticity and Volatility measured at ages 3 to 5. Both externalising and internalising behaviours were specifically associated with Volatility, with larger effects for externalising behaviours. These findings are interpreted in light of evolutionary-developmental models of psychopathology and reinforcement learning models of learning under uncertainty.

Python Red Pitaya Lockbox (PyRPL): An open source software package for digital feedback control in quantum optics experiments.

We present the Python Red Pitaya Lockbox (PyRPL), an open source software package that allows the implementation of automatic digital feedback controllers for quantum optics experiments on commercially available, affordable Field-Programmable Gate Array (FPGA) boards. Our software implements the digital generation of various types of error signals, from an analog input through the application of loop filters of high complexity and real-time gain adjustment for multiple analog output signals, including different algorithms for resonance search, lock acquisition sequences, and in-loop gain optimization. Furthermore, all necessary diagnostic instruments, such as an oscilloscope, a network analyzer, and a spectrum analyzer, are integrated into our software. Apart from providing a quickly scalable, automatic feedback controller, the lock performance that can be achieved by using PyRPL with imperfect equipment, such as piezoelectric transducers and noisy amplifiers, is better than the one achievable with standard analog controllers due to the higher complexity of implementable filters and possibilities of nonlinear operations in the FPGA. This drastically reduces the cost of added complexity when introducing additional feedback loops to an experiment. The open-source character also distinguishes PyRPL from commercial solutions, as it allows users to customize functionalities at various levels, ranging from the easy integration of PyRPL-based feedback controllers into existing setups to the modification of the FPGA functionality. A community of developers provides fast and efficient implementation and testing of software modifications.

Characterization of the Intracellular Acidity Regulation of Brain Tumor Cells and Consequences for Therapeutic Optimization of Temozolomide.

A well-known feature of tumor cells is high glycolytic activity, leading to acidification of the tumor microenvironment through extensive lactate production. This acidosis promotes processes such as metastasis, aggressiveness, and invasiveness, which have been associated with a worse clinical prognosis. Moreover, the function and expression of transporters involved in regulation of intracellular pH might be altered. In this study, the capacity of tumor cells to regulate their intracellular pH when exposed to a range of pH from very acidic to basic was characterized in two glioma cell lines (F98 and U87) using a new recently published method of fluorescence imaging. Our results show that the regulation of acidity in tumors is not the same for the two investigated cell lines; U87 cells are able to reduce their intracellular acidity, whereas F98 cells do not exhibit this property. On the other hand, F98 cells show a higher level of resistance to acidity than U87 cells. Intracellular regulation of acidity appears to be highly cell-dependent, with different mechanisms activated to preserve cell integrity and function. This characterization was performed on 2D monolayer cultures and 3D spheroids. Spatial heterogeneities were exhibited in 3D, suggesting a spatially modulated regulation in this context. Based on the corpus of knowledge available in the literature, we propose plausible mechanisms to interpret our results, together with some new lines of investigation to validate our hypotheses. Our results might have implications on therapy, since the activity of temozolomide is highly pH-dependent. We show that the drug efficiency can be enhanced, depending on the cell type, by manipulating the extracellular pH. Therefore, personalized treatment involving a combination of temozolomide and pH-regulating agents can be considered.

Associations Between Early Life Adversity, Reproduction-Oriented Life Strategy, and Borderline Personality Disorder.

Importance: Borderline personality disorder (BPD) is often accompanied by a history of high-risk sexual behavior and somatic comorbidities. Yet, these features are most often considered in isolation and little is known about their underlying developmental pathways. Life history theory, a leading framework in evolutionary developmental biology, can help make sense of the wide range of behaviors and health issues found in BPD. Objective: To examine whether the emergence of BPD is associated with the prioritization of immediate reproductive goals over longer-term somatic maintenance goals, a life strategy that can be viewed as a developmental response to adverse early life experiences, providing rapid reproductive benefits despite costs to health and well-being. Design, Setting, and Participants: This study used cross-sectional data from the second wave of the National Epidemiologic Survey on Alcohol and Related Conditions in 2004-2005 (n = 34 653). Civilian, noninstitutionalized individuals in the US, 18 years or older, and those with and without a DSM-IV diagnosis of BPD were included. Analysis took place between August 2020 and June 2021. Main Outcomes and Measures: Structural equation models were used to examine whether early life adversity was associated with the likelihood of a BPD diagnosis, either directly or indirectly through a life strategy whereby individuals trade somatic maintenance for immediate reproduction. Results: Analyses were performed on a sample of 30 149 participants (females: 17 042 [52%]; mean [SE] age, 48.5 [0.09]; males: 12 747 [48%]; mean [SE] age, 47 [0.08]). Of these, 892 (2.7%) had a diagnosis of BPD and 29 257 (97.3%) did not have BPD. Mean early life adversity, metabolic disorder score, and body mass index were significantly higher among participants with a diagnosis of BPD. In an analysis adjusted for age, individuals with BPD reported having significantly more children than those without BPD (b =0.06; SE, 0.01; t = 4.09; P < .001). Having experienced greater levels of adversity in early life was significantly associated with a greater risk of being diagnosed with BPD later in life (direct relative risk = 0.268; SE, 0.067; P < .001). Importantly, this risk was further increased by 56.5% among respondents who prioritized short-term reproductive goals over somatic maintenance (indirect relative risk = 0.565; SE, 0.056; P < .001). Similar patterns of associations were found in male and female individuals. Conclusions and Relevance: The hypothesis of a reproduction/maintenance life history trade-off mediating the association between early life adversity and BPD helps make sense of the high dimensionality that characterizes the physiological and behavioral correlates of BPD. Additional studies are needed to confirm these results using longitudinal data.

Mentalizing under influence: abnormal dependence on prior expectations in patients with schizophrenia.

An impaired ability to appreciate other people's mental states is a well-established and stable cognitive deficit in schizophrenia, which might explain some aspects of patients' social dysfunction. Yet, despite a wealth of literature on this topic, the basic mechanisms underlying these impairments are still poorly understood, and their links with the clinical dimensions of schizophrenia remain unclear. The present study aimed to investigate the extent to which patients' impaired ability to appreciate other people's intentions (known as mentalizing) may be accounted for by abnormal interaction between the two types of information that contribute to this ability: (i) the sensory evidence conveyed by movement kinematics; and (ii) the observer's prior expectations. We hypothesized that this is not a generalized impairment, but one confined to certain types of intentions. To test this assumption, we designed four tasks in which participants were required to infer either: (i) basic intentions (i.e. the simple goal of a motor act); (ii) superordinate intentions (i.e. the general goal of a sequence of motor acts); (iii) social basic; or (iv) social superordinate intentions (i.e. simple or general goals achieved within the context of a reciprocal interaction). In each of these tasks, both prior expectations and sensory information were manipulated. We found that patients correctly inferred non-social, basic intentions, but experienced difficulties when inferring non-social superordinate intentions and both basic and superordinate social intentions. These poor performances were associated with two abnormal patterns of interaction between prior expectations and sensory evidence. In the non-social superordinate condition, patients relied heavily on their prior expectations, while disregarding sensory evidence. This pattern of interaction predicted the severity of 'positive' symptoms. Social conditions prompted exactly the opposite pattern of interaction: patients exhibited weaker dependence on prior expectations while relying strongly on sensory evidence, and this predicted the severity of 'negative' symptoms. We suggest both these patterns can be accounted for by a disturbance in the Bayesian inferential mechanism that integrates sensory evidence (conveyed by movement kinematics) into prior beliefs (about others' mental states and attitudes) to produce accurate inferences about other people's intentions.

Can object affordances impact on human social learning of tool use?

The author describes "higher" and "uniquely human" sociocognitive skills that he argues as being necessary for tool use. We propose that those skills could be based on simpler detection systems humans could share with other animal tool users. More specifically, we discuss the impact of object affordances on the understanding and the social learning of tool use.

Ecological assessments of activities of daily living and personal experiences with Mobus, an assistive technology for cognition: a pilot study in schizophrenia.

Mobus is a cognitive orthotic designed for people with difficulties managing Activities of Daily Living (ADL), as encountered in schizophrenia. It provides a schedule manager as well as the possibility to report occurrences of symptomatic experiences. Receiving this information by Internet, caregivers can assist the patient rehabilitation process. Our aim was to explore the use and satisfaction of Mobus by people with schizophrenia. Nine outpatients tested Mobus for 6 weeks. Indicators of cognitive functioning and autonomy were measured with the CAmbridge Neuropsychological Tests Automated Battery (CANTAB) and the Independant Living Skills Scale (ILSS). On average, 42.6% of the planned ADL were validated and more than 1 symptom per week were reported. Mainly because of technical breakdown, more than 50% of the outpatients evaluated the Mobus satisfaction below 1.7/5, nevertheless 3 participants appreciated it greatly. Some enhancements were found on subscales of CANTAB and ILSS and some participants reported that they acquired planning skills by using Mobus. To ensure ease of use, refinements are needed from rehabilitation and technical approaches, especially to personalize the device. Discussions on ethical and methodological issues lead to an improved version of Mobus that will be tested with a larger sample size.

Searching for the Metabolic Signature of Cancer: A Review from Warburg's Time to Now.

This review focuses on the evolving understanding that we have of tumor cell metabolism, particularly glycolytic and oxidative metabolism, and traces back its evolution through time. This understanding has developed since the pioneering work of Otto Warburg, but the understanding of tumor cell metabolism continues to be hampered by misinterpretation of his work. This has contributed to the use of the new concepts of metabolic switch and metabolic reprogramming， that are out of step with reality. The Warburg effect is often considered to be a hallmark of cancer, but is it really? More generally, is there a metabolic signature of cancer? We draw the conclusion that the signature of cancer cannot be reduced to a single factor, but is expressed at the tissue level in terms of the capacity of cells to dynamically explore a vast metabolic landscape in the context of significant environmental heterogeneities.

Susceptibility of agency judgments to social influence.

The experience of agency refers to the phenomenal experience of being the causal source of one's own actions, and through them, the course of events in the outside world. This experience is crucial for the production of adaptive actions, and for the adequate communication of felt action control to peers. The present study examines the possibility that, on certain occasions and under specific internal and external constraints, people rely on explicit social information provided by their peers to revise their self-reports of perceived control, i.e., their judgment of agency. To test this hypothesis, we adapted a task based on an interactive computer game. We manipulated well-known sensorimotor agency cues related to action control, as well as social information communicated to participants by two advisors. We measured the contribution of social and non-social sources of information to agency judgments. We found that at the single-trial level, participants align their JoA with advisor feedback based on their own performance during the task, the type of feedback provided by advisors, and the interaction of this social feedback with the sensorimotor agency cues. At the same time, JoA alignment in previous trial also predicted participants' tendency to revise their JoA after social feedback. Overall, these results demonstrate that agency judgment is subject to social influence. This influence is the result of the integration of social and non-social information at the scale of a single judgment, while also being driven by repeated past interactions with peers.

Cinnamomum zeylanicum Essential Oil Formulation with Poly(propylene imine) Dendrimers with Surface-Grafted Glycerol: Release Kinetics of trans-Cinnamaldehyde and Germination Inhibition Effects.

The Third-generation glycerodendrimer polypropylenimine (GD-PPI-3) can be used in an aqueous formulation of Cinnamomum zeylanicum essential oil (CEO). The purpose was to give an overview of this innovative method of retaining and releasing essential oils. The formulation consisted of 366 min stirring at 1735 rpm of the aqueous solution of 2 mM GD-PPI-3 with CEO. Some physicochemical properties of these formulations, as well as the release of trans-cinnamaldehyde, have been studied. A bimodal distribution and no concentration or aging effect were observed by optical microscopy. Moreover, the release kinetics showed the retention of volatile molecules in solution under various environmental conditions. The release profile was characterized by an initial burst followed by a steady release. The dendrimers allowed us to reduce this initial burst and extended the release by at least 15 h. In addition, the herbicidal effect was evaluated: inhibition of Arabidopsis thaliana seed germination was obtained for 7 days with a formulation of 12.5 mg/L CEO in a closed space and 360 mg/L CEO in an open space.

Metabolic Reprogramming, Questioning, and Implications for Cancer.

The expression "metabolic reprogramming" has been encountered more and more in the literature since the mid-1990s. It seems to encompass several notions depending on the author, but the lack of a clear definition allows it to be used as a "catch-all" expression. Our first intention is to point out the inconsistencies in the use of the reprogramming terminology for cancer metabolism. The second is to address the over-focus of the role of mutations in metabolic adaptation. With the increased interest in metabolism and, more specifically, in the Warburg effect in cancer research, it seems appropriate to discuss this terminology and related concepts in detail.

Social information use and social information waste.

Social information is immensely valuable. Yet we waste it. The information we get from observing other humans and from communicating with them is a cheap and reliable informational resource. It is considered the backbone of human cultural evolution. Theories and models focused on the evolution of social learning show the great adaptive benefits of evolving cognitive tools to process it. In spite of this, human adults in the experimental literature use social information quite inefficiently: they do not take it sufficiently into account. A comprehensive review of the literature on five experimental tasks documented 45 studies showing social information waste, and four studies showing social information being over-used. These studies cover 'egocentric discounting' phenomena as studied by social psychology, but also include experimental social learning studies. Social information waste means that human adults fail to give social information its optimal weight. Both proximal explanations and accounts derived from evolutionary theory leave crucial aspects of the phenomenon unaccounted for: egocentric discounting is a pervasive effect that no single unifying explanation fully captures. Cultural evolutionary theory's insistence on the power and benefits of social influence is to be balanced against this phenomenon. This article is part of the theme issue 'Foundations of cultural evolution'.

The Cognitive, Ecological, and Developmental Origins of Self-Disturbance in Borderline Personality Disorder.

Self-disturbance is recognized as a key symptom of Borderline Personality Disorder (BPD). Although it is the source of significant distress and significant costs to society, it is still poorly specified. In addition, current research and models on the etiology of BPD do not provide sufficient evidence or predictions about who is at risk of developing BPD and self-disturbance, and why. The aim of this review is to lay the foundations of a new model inspired by recent developments at the intersection of social cognition, behavioral ecology, and developmental biology. We argue that the sense of agency is an important dimension to consider when characterizing self-disturbances in BPD. Second, we address the poorly characterized relation between self-disturbances and adverse life conditions encountered early in life. We highlight the potential relevance of Life-History Theory-a major framework in evolutionary developmental biology-to make sense of this association. We put forward the idea that the effect of early life adversity on BPD symptomatology depends on the way individuals trade their limited resources between competing biological functions during development.

The ecological roots of human susceptibility to social influence: a pre-registered study investigating the impact of early-life adversity.

There is considerable variability in the degree to which individuals rely on their peers to make decisions. Although theoretical models predict that environmental risks shift the cost-benefit trade-off associated with social information use, this idea has received little empirical support. Here we aim to test the effect of childhood environmental adversity on humans' susceptibility to follow others' opinion in the context of a standard face evaluation task. Results collected in a pilot study involving 121 adult participants tested online showed that susceptibility to social influence and childhood environmental adversity are positively associated. Computational analyses further confirmed that this effect is not explained by the fact that participants exposed to early adversity produce noisier decisions overall but that they are indeed more likely to follow the group's opinion. To test the robustness of these findings, a pre-registered direct replication using an optimal sample size was run. The results obtained from 262 participants in the pre-registered study did not reveal a significant association between childhood adversity and task performance but the meta-analysis ran on both the pilot and the pre-registered study replicated the initial finding. This work provides experimental evidence for an association between individuals' past ecology and their susceptibility to social influence.