Impact of perfusion on neuronal development in human derived neuronal networks.

Advanced in vitro models of the brain have evolved in recent years from traditional two-dimensional (2D) ones, based on rodent derived cells, to three-dimensional (3D) ones, based on human neurons derived from induced pluripotent stem cells. To address the dynamic changes of the tissue microenvironment, bioreactors are used to control the in vitro microenvironment for viability, repeatability, and standardization. However, in neuronal tissue engineering, bioreactors have primarily been used for cell expansion purposes, while microfluidic systems have mainly been employed for culturing organoids. In this study, we explored the use of a commercial perfusion bioreactor to control the culture microenvironment of neuronal cells in both 2D and 3D cultures. Namely, neurons differentiated from human induced pluripotent stem cells (iNeurons) were cultured in 2D under different constant flow rates for 72 h. The impact of different flow rates on early-stage neuronal development and synaptogenesis was assessed by morphometric characterization and synaptic analysis. Based on these results, two involving variable flow rates were developed and applied again in 2D culture. The most effective protocol, in terms of positive impact on neuronal development, was then used for a preliminary study on the application of dynamic culturing conditions to neuronal cells in 3D. To this purpose, both iNeurons, co-cultured with astrocytes, and the human neuroblastoma cells SH-SY5Y were embedded into a hydrogel and maintained under perfusion for up to 28 days. A qualitative evaluation by immunocytochemistry and confocal microscopy was carried out to assess cell morphology and the formation of a 3D neuronal network.

Understanding empathy and De Waal's contribution within the fields of social neurosciences.

This review delves into the remarkable career and scientific contributions of Frans de Waal, a renowned figure in the field of ethology, primatology with important implications for the field of social neurosciences. Rooted in the Dutch tradition of ethology, influenced by luminaries like Niko Tinbergen and Jan Van Hooff, De Waal's career began with groundbreaking research on chimpanzees, which questioned long-held beliefs about dominance and aggression in animal behavior. His work, epitomized in his influential books, such as "Chimpanzee Politics", "The ape and the sushi master", "The age of empathy", not only revolutionized scientific thinking but also ignited discussions about empathy, morality, and complex cognitive functions in animals. De Waal's interdisciplinary approach extended to neuroscience, particularly in understanding empathy, contributing to the development of an original model: the Perception-Action Model (PAM). The fundamental concept of PAM is that even the most intricate forms of empathy stem from basic neural mechanisms of action-perception, such as mirror neurons. Some behavioral phenomena like motor mimicry and emotional contagion arise from a direct neuroanatomical network activity where sensory information about others' emotional states triggers corresponding behavioral responses. Intriguingly, even the most intricate forms of empathy such as concern, consolation and targeted helping, may have evolved from basic neural mechanisms of action-perception.Through these investigations and theoretical explorations, he advocated for a bottom-up approach to comprehending the cognitive abilities of animals. This approach challenged conventional anthropocentric perspectives and underscored the interconnected emotional and cognitive terrain shared among humans and other species. Beyond academia, De Waal's work has profound implications for how we perceive and interact with animals. By debunking notions of human exceptionalism, he highlights the rich tapestry of emotions that bind all living beings. Through his efforts, De Waal has not only advanced our scientific understanding of animal minds but also fostered a more profound appreciation for the depth of emotional connections across species.

Influence of different pressure regimes on the properties of an engineered small-diameter vascular scaffold tested in a custom-made bioreactor.

Vascular tissue engineering endeavors to design, fabricate, and validate biodegradable and bioabsorbable small-diameter vascular scaffolds engineered with bioactive molecules, capable of meeting the challenges imposed by commercial vascular prostheses. A comprehensive investigation of these engineered scaffolds in bioreactor is deemed essential as a prerequisite before any in vivo experimentation in order to get information regarding their behavior under physiological conditions and predict the biological activities they will possess. This study focuses on an innovative electrospun scaffold made of poly(caprolactone) and poly(glycerol sebacate), integrating quercetin, able to modulate inflammation, and gelatin, necessary to reduce permeability. A custom-made bioreactor was used to assess the performances of the scaffolds maintained under different pressure regimes, covering the human physiological pressure range. As results, the 3D microfibrous architecture was notably influenced by the release of bioactives, maintaining the adequate properties needed for the in vivo regeneration and scaffolds showed mechanical properties similar to human native artery. Release of gelatin was adequate to avoid blood leakage and useful to make the material porous during the testing period, whereas the amount of released quercetin was useful to counteract the post-surgery inflammation. This study showcases the successful validation of an engineered scaffold in a bioreactor, enabling to consider it as a promising candidate for vascular substitutes in in vivo applications. Our approach represents a significant leap forward in the field of vascular tissue engineering, offering a multifaceted solution to the complex challenges associated with small-diameter vascular prostheses. .

On the Development of Polylactic Acid/Polycaprolactone Blended Films with High Retention Capacity.

The retention capacity of polymers is related to the development of systems that combine high surface-to-volume ratio with good handling and specific functionality. Biodegradability and biocompatibility are also key features for extending the field of applications to areas such as biomedicine. With this in mind, the aim of this work is to develop biodegradable, biocompatible, and highly functionalized porous films, that ensure suitable handling and a good surface-to-volume ratio. Polylactic acid (PLA) is applied as a polymer matrix to which a polycaprolactone with a star-shaped architecture (PCL-COOH) to ensure a high concentration of carboxylic end functionalities is added. The porous films are prepared using the phase inversion technique, which, as shown by Scanning Electron Microscopy (SEM) analysis, promotes good dispersion of the PCL-COOH domains. Absorption and release measurements performed with a positively charged model molecule show that the retention capacity and release rate can be tuned by changing the PCL-COOH concentration in the systems. Moreover, the adsorption properties for the formulation with the highest PCL-COOH content are also demonstrated with a real and widely used drug, namely doxorubicin. Finally, the bio- and hemocompatibility of the films, which are enzymatically degradable, are evaluated by using human keratinocytes and red blood cells, respectively.

Social neuroscience: Primate research goes wireless.

A new study leads the way to a more ethical and ethologically meaningful way of investigating brain functions of complex behaviors in social animals.

Visual Preference for Socially Relevant Spatial Relations in Humans and Monkeys.

As a powerful social signal, a body, face, or gaze facing toward oneself holds an individual's attention. We asked whether, going beyond an egocentric stance, facingness between others has a similar effect and why. In a preferential-looking time paradigm, human adults showed spontaneous preference to look at two bodies facing toward (vs. away from) each other (Experiment 1a, N = 24). Moreover, facing dyads were rated higher on social semantic dimensions, showing that facingness adds social value to stimuli (Experiment 1b, N = 138). The same visual preference was found in juvenile macaque monkeys (Experiment 2, N = 21). Finally, on the human development timescale, this preference emerged by 5 years, although young infants by 7 months of age already discriminate visual scenes on the basis of body positioning (Experiment 3, N = 120). We discuss how the preference for facing dyads-shared by human adults, young children, and macaques-can signal a new milestone in social cognition development, supporting processing and learning from third-party social interactions.

Sensitivity to basic emotional expressions and the emotion perception space in the absence of facial mimicry: The case of individuals with congenital facial palsy.

According to sensorimotor simulation models, recognition of another person's emotion is achieved by recreating the motor production of the perceived facial expression in oneself. Therefore, congenital difficulties in the production of facial expressions may affect emotion processing. The present study assessed a sample (N = 11) of Moebius syndrome (MBS) patients and a matched control group (N = 33), using a highly sensitive emotion recognition task. Leveraging the uniqueness of MBS, which is characterized by congenital facial paralysis, the role of facial mimicry and sensorimotor simulation in creating precise embodied concepts of emotion categories was investigated. Particularly, the research focused on how MBS patients (both as a group and individually, compared to controls) perceived the intensity of primary emotions and how well they discriminated between these and secondary (i.e., blended) emotions. The results showed that MBS patients registered significantly lower intensities for sadness, fear, anger, and disgust. Furthermore, these emotions appeared closely clustered-and therefore confused with anger and surprise-in the multidimensional scaling map, which was used to qualitatively analyze the emotion perception space. Further analysis of each MBS participant showed a stronger tendency in most patients to perceive primary emotions as less intense, relative to controls. Thus, the findings provide evidence for a residual deficit in emotion processing in adults with MBS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Engineering of poly(caprolactone) and poly(glycerol sebacate) small-diameter vascular prosthesis with quercetin.

The fabrication of biodegradable, bioabsorbable, and biocompatible vascular scaffolds with enhanced mechanical and biological properties that are able to modulate local inflammation and induce endothelialization after surgical implant is still a challenge. In this work, a fibrous scaffold, made of poly(ε-caprolactone) and poly(glycerol sebacate), was fabricated to be potentially used as a small-diameter graft in vascular surgery. The novelty of this research is represented by the direct incorporation of quercetin, a well-known antioxidant compound with several biological properties, into a polymeric scaffold obtaining a vascular construct able to modulate two key factors involved in postsurgical inflammation, matrix metalloproteinase-9 and endothelial nitric oxide synthase. For its production, an electrospinning apparatus, a solution made of the two polymers (both 20% (w/v), mixed at the ratio 1:1 (v/v)), and free quercetin (0.05% (w/v)) were used. Scanning electron and atomic force microscopies were employed to investigate the morphological properties of the fabricated electrospun scaffolds. Furthermore, physicochemical properties, including Fourier-transform infrared spectroscopy, mass loss, fluid uptake, quercetin release, mechanical properties, and biological activity of the scaffolds were studied. The expression of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and of endothelial nitric oxide synthase was evaluated when the quercetin-functionalized scaffold was exposed to  human endothelial cells treated with tumor necrosis factor-α. The results of this study confirmed the feasibility of incorporating free quercetin during the electrospinning process to impart biological properties to small-diameter vascular prostheses.

Close to me but unreachable: spotting the link between peripersonal space and empathy.

The space surrounding the body [i.e. peripersonal space (PPS)] has a crucial impact on individuals' interactions with the environment. Research showed that the interaction within the PPS increases individuals' behavioral and neural responses. Furthermore, individuals' empathy is affected by the distance between them and the observed stimuli. This study investigated empathic responses to painfully stimulated or gently touched faces presented within the PPS depending on the presence vs absence of a transparent barrier erected to prevent the interaction. To this aim, participants had to determine whether faces were painfully stimulated or gently touched, while their electroencephalographic signals were recorded. Brain activity [i.e. event-related potentials (ERPs) and source activations] was separately compared for the two types of stimuli (i.e. gently touched vs painfully stimulated faces) across two barrier conditions: (i) no-barrier between participants and the screen (i.e. no-barrier) and (ii) a plexiglass barrier erected between participants and the screen (i.e. barrier). While the barrier did not affect performance behaviorally, it reduced cortical activation at both the ERP and source activation levels in brain areas that regulate the interpersonal interaction (i.e. primary, somatosensory, premotor cortices and inferior frontal gyrus). These findings suggest that the barrier, precluding the possibility of interacting, reduced the observer's empathy.

Testing EEG functional connectivity between sensorimotor and face processing visual regions in individuals with congenital facial palsy.

Moebius syndrome (MBS) is characterized by the congenital absence or underdevelopment of cranial nerves VII and VI, leading to facial palsy and impaired lateral eye movements. As a result, MBS individuals cannot produce facial expressions and did not develop motor programs for facial expressions. In the latest model of sensorimotor simulation, an iterative communication between somatosensory, motor/premotor cortices, and visual regions has been proposed, which should allow more efficient discriminations among subtle facial expressions. Accordingly, individuals with congenital facial motor disability, specifically with MBS, should exhibit atypical communication within this network. Here, we aimed to test this facet of the sensorimotor simulation models. We estimated the functional connectivity between the visual cortices for face processing and the sensorimotor cortices in healthy and MBS individuals. To this aim, we studied the strength of beta band functional connectivity between these two systems using high-density EEG, combined with a change detection task with facial expressions (and a control condition involving non-face stimuli). The results supported our hypothesis such that when discriminating subtle facial expressions, participants affected by congenital facial palsy (compared to healthy controls) showed reduced connectivity strength between sensorimotor regions and visual regions for face processing. This effect was absent for the condition with non-face stimuli. These findings support sensorimotor simulation models and the communication between sensorimotor and visual areas during subtle facial expression processing.

Aggression: The dark side of mirror neurons sheds light on their functions.

Mirror neurons have been found mainly in neocortical structures of primates and rodents; however, their functions are still debated. A new study has discovered mirror neurons for aggressive behaviors in the ventromedial hypothalamus of mice, an evolutionarily ancient structure, highlighting a new function key for survival.

Longitudinal effects of early psychosocial deprivation on macaque executive function: Evidence from computational modelling.

Executive function (EF) describes a group of cognitive processes underlying the organization and control of goal-directed behaviour. Environmental experience appears to play a crucial role in EF development, with early psychosocial deprivation often linked to EF impairment. However, many questions remain concerning the developmental trajectories of EF after exposure to deprivation, especially concerning specific mechanisms. Accordingly, using an 'A-not-B' paradigm and a macaque model of early psychosocial deprivation, we investigated how early deprivation influences EF development longitudinally from adolescence into early adulthood. The contribution of working memory and inhibitory control mechanisms were examined specifically via the fitting of a computational model of decision making to the choice behaviour of each individual. As predicted, peer-reared animals (i.e. those exposed to early psychosocial deprivation) performed worse than mother-reared animals across time, with the fitted model parameters yielding novel insights into the functional decomposition of group-level EF differences underlying task performance. Results indicated differential trajectories of inhibitory control and working memory development in the two groups. Such findings not only extend our knowledge of how early deprivation influences EF longitudinally, but also provide support for the utility of computational modelling to elucidate specific mechanisms linking early psychosocial deprivation to long-term poor outcomes.

An extensive review on phenolic compounds and their potential estrogenic properties on skin physiology.

Polyphenolic compounds constitute a diverse group of natural components commonly occurring in various plant species, known for their potential to exert both beneficial and detrimental effects. Additionally, these polyphenols have also been implicated as endocrine-disrupting (ED) chemicals, raising concerns about their widespread use in the cosmetics industry. In this comprehensive review, we focus on the body of literature pertaining to the estrogenic properties of ED chemicals, with a particular emphasis on the interaction of isoflavones with estrogen receptors. Within this review, we aim to elucidate the multifaceted roles and effects of polyphenols on the skin, exploring their potential benefits as well as their capacity to act as ED agents. By delving into this intricate subject matter, we intend to provoke thoughtful consideration, effectively opening a Pandora's box of questions for the reader to ponder. Ultimately, we invite the reader to contemplate whether polyphenols should be regarded as friends or foes in the realm of skincare and endocrine disruption.

Degenerate pathway for processing smile and other emotional expressions in congenital facial palsy: an hdEEG investigation.

Influential theoretical models argue that an internal simulation mechanism (motor or sensorimotor simulation) supports the recognition of facial expressions. However, despite numerous converging sources of evidence, recent studies testing patients with congenital facial palsy (i.e. Moebius syndrome) seem to refute these theoretical models. However, these results do not consider the principles of neuroplasticity and degeneracy that could support the involvement of an alternative neural processing pathway in these patients. In the present study, we tested healthy participants and participants with Moebius syndrome in a highly sensitive facial expression discrimination task and concomitant high-density electroencephalographic recording. The results, both at the scalp and source levels, indicate the activation of two different pathways of facial expression processing in healthy participants and participants with Moebius syndrome, compatible, respectively, with a dorsal pathway that includes premotor areas and a ventral pathway. Therefore, these results support the reactivation of sensorimotor representations of facial expressions (i.e. simulation) in healthy subjects, in the place of an alternative processing pathway in subjects with congenital facial palsy. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.

Bevacizumab encapsulation into PLGA nanoparticles functionalized with immunouteroglobin-1 as an innovative delivery system for atherosclerosis.

Atherosclerosis represents one of the main causes of death in the Western world. It is a multifactorial pathology characterized by lesions that reduce the lumen of the vessels causing serious clinical events. The extra-domain B of fibronectin is overexpressed during angiogenesis and in tissues undergoing growth and extensive remodeling, i.e., atherosclerotic plaque. Bevacizumab is a recombinant humanized monoclonal antibody that can play a central role against angiogenesis reducing the risk associated with this process in atherosclerosis. In this work, an innovative nanosystem for the targeted delivery of bevacizumab to the atherosclerotic lesion is proposed. A production protocol for poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles loaded with bevacizumab and functionalized with immunouteroglobin-1 was designed. Once functionalized nanoparticles with immunouteroglobin-1 were produced, they were characterized in terms of morphology, mean diameter, ζ-potential, association and conjugation efficiencies, bevacizumab release profile, both in phosphate buffered saline and in serum, bevacizumab stability after release, cytocompatibility, and hemocompatibility. Nanoparticle mean diameter was in the range of 217-265 nm, their surface charge was between -22 and -8 mV, and the association and conjugation efficiencies of about 76 and 59 %, respectively. Fourier transform infrared spectroscopy analysis confirmed the functionalization of their surface with immunouteroglobin-1. In vitro assays showed that the studied nanoparticles were cytocompatible, once in contact with human endothelial and murine macrophage cell lines up to 72 h, and hemocompatible, once in contact with red blood cells, at different concentrations of encapsulated bevacizumab (0.1, 1, 10, and 100 µg/mL).

PCSK9 and Other Metabolic Targets to Counteract Ischemia/Reperfusion Injury in Acute Myocardial Infarction and Visceral Vascular Surgery.

Ischemia/reperfusion (I/R) injury complicates both unpredictable events (myocardial infarction and stroke) as well as surgically-induced ones when transient clampage of major vessels is needed. Although the main cause of damage is attributed to mitochondrial dysfunction and oxidative stress, the use of antioxidant compounds for protection gave poor results when challenged in clinics. More recently, there is an assumption that, in humans, profound metabolic changes may prevail in driving I/R injury. In the present work, we narrowed the field of search to I/R injury in the heart/brain/kidney axis in acute myocardial infarction, major vascular surgery, and to the current practice of protection in both settings; then, to help the definition of novel strategies to be translated clinically, the most promising metabolic targets with their modulatory compounds-when available-and new preclinical strategies against I/R injury are described. The consideration arisen from the broad range of studies we have reviewed will help to define novel therapeutic approaches to ensure mitochondrial protection, when I/R events are predictable, and to cope with I/R injury, when it occurs unexpectedly.

Bevacizumab-Controlled Delivery from Polymeric Microparticle Systems as Interesting Tools for Pathologic Angiogenesis Diseases.

This work is a comparative study among three different biocompatible and biodegradable polymers, poly(lactic-co-glycolic acid), poly(ε-caprolactone), and poly(lactic acid), used to produce microparticles for the encapsulation of bevacizumab for drug delivery purposes. All the formulations were produced using the double emulsion water-oil-water evaporation method and characterized in terms of particle mean diameter, particle size distribution, and bevacizumab entrapment efficiency. Bevacizumab cumulative release was taken into consideration to study the dissolution kinetics from the three different polymeric delivery platforms for a period of 50 days at 37 °C in phosphate buffered saline and mathematical models of the drug release kinetic were attempted in order to describe the release phenomena from the different types of the studied microparticles. Finally, cell viability on human endothelial cell line EA.hy926 was studied to define the maximum cytocompatible concentration for each microsystem, registering the mitochondrial functionality through MTS assay.

Post-surgery Rehabilitative Intervention Based on Imitation Therapy and Mouth-Hand Motor Synergies Provides Better Outcomes in Smile Production in Children and Adults With Long Term Facial Paralysis.

Rehabilitation after free gracilis muscle transfer (smile surgery, SS) is crucial for a functional recovery of the smiling skill, mitigating social and psychological problems resulting from facial paralysis. We compared two post-SS rehabilitation treatments: the traditional based on teeth clenching exercises and the FIT-SAT (facial imitation and synergistic activity treatment). FIT-SAT, based on observation/imitation therapy and on hand-mouth motor synergies would facilitate neuronal activity in the facial motor cortex avoiding unwanted contractions of the jaw, implementing muscle control. We measured the smile symmetry on 30 patients, half of whom after SS underwent traditional treatment (control group, CG meanage = 20 ± 9) while the other half FIT-SAT (experimental group, EG meanage= 21 ± 14). We compared pictures of participants while holding two postures: maximum and gentle smile. The former corresponds to the maximal muscle contraction, whereas the latter is strongly linked to the control of muscle strength during voluntary movements. No differences were observed between the two groups in the maximum smile, whereas in the gentle smile the EG obtained a better symmetry than the CG. These results support the efficacy of FIT-SAT in modulating the smile allowing patients to adapt their smile to the various social contexts, aspect which is crucial during reciprocal interactions.

Facial Expression Time Processing in Typical Development and in Patients with Congenital Facial Palsy.

Temporal dynamics of behavior, particularly facial expressions, are fundamental for communication between individuals from very early in development. Facial expression processing has been widely demonstrated to involve embodied simulative processes mediated by the motor system. Such processes may be impaired in patients with congenital facial palsy, including those affected by Moebius syndrome (MBS). The aims of this study were to investigate (a) the role of motor mechanisms in the processing of dynamic facial expression timing by testing patients affected by congenital facial palsy and (b) age-dependent effects on such processing. Accordingly, we recruited 38 typically developing individuals and 15 individuals with MBS, ranging in age from childhood to adulthood. We used a time comparison task where participants were asked to identify which one of two dynamic facial expressions was faster. Results showed that MBS individuals performed worse than controls in correctly estimating the duration of facial expressions. Interestingly, we did not find any performance differences in relation to age. These findings provide further evidence for the involvement of the motor system in processing facial expression duration and suggest that a sensorimotor matching mechanism may contribute to such timing perception from childhood.

Dialogic Book-Sharing as a Privileged Intersubjective Space.

Parental reading to young children is well-established as being positively associated with child cognitive development, particularly their language development. Research indicates that a particular, "intersubjective," form of using books with children, "Dialogic Book-sharing" (DBS), is especially beneficial to infants and pre-school aged children, particularly when using picture books. The work on DBS to date has paid little attention to the theoretical and empirical underpinnings of the approach. Here, we address the question of what processes taking place during DBS confer benefits to child development, and why these processes are beneficial. In a novel integration of evidence, ranging from non-human primate communication through iconic gestures and pointing, archaeological data on Pre-hominid and early human art, to experimental and naturalistic studies of infant attention, cognitive processing, and language, we argue that DBS entails core characteristics that make it a privileged intersubjective space for the promotion of child cognitive and language development. This analysis, together with the findings of DBS intervention studies, provides a powerful intellectual basis for the wide-scale promotion of DBS, especially in disadvantaged populations.