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By using a variational Monte Carlo technique based upon Gutzwiller-projected fermionic states, we investigate the dynamical structure factor of the antiferromagnetic $S=1/2$ Heisenberg model on the honeycomb lattice, in presence of first-neighbor ($J_1$) and second-neighbor ($J_2$) couplings, for ${J_2 < 0.5 J_1}$. The ground state of the system shows long-range antiferromagnetic order for ${J_2/J_1 \lesssim 0.23}$, plaquette valence-bond order for ${0.23 \lesssim J_2/J_1 \lesssim 0.36}$, and columnar dimer order for ${J_2/J_1 \gtrsim 0.36}$. Within the antiferromagnetic state, a well-defined magnon mode is observed, whose dispersion is in relatively good agreement with linear spin-wave approximation for $J_2=0$. When a nonzero second-neighbor super-exchange is included, a roton-like mode develops around the $K$ point (i.e., the corner of the Brillouin zone). This mode softens when $J_2/J_1$ is increased and becomes gapless at the transition point, $J_2/J_1 \approx 0.23$. Here, a broad continuum of states is clearly visible in the dynamical spectrum, suggesting that nearly-deconfined spinon excitations could exist, at least at relatively high energies. For larger values of $J_2/J_1$, valence-bond order is detected and the spectrum of the system becomes clearly gapped, with a triplon mode at low energies. This is particularly evident for the spectrum of the dimer valence-bond phase, in which the triplon mode is rather well separated from the continuum of excitations that appears at higher energies.

In Drosophila melanogaster the single male chromosome X undergoes an average twofold transcriptional upregulation for balancing the transcriptional output between sexes. Previous literature hypothesised that a global change in chromosome structure may accompany this process. However, recent studies based on Hi-C failed to detect these differences. Here we show that global conformational differences are specifically present in the male chromosome X and detectable using Hi-C data on sex-sorted embryos, as well as male and female cell lines, by leveraging custom data analysis solutions. We find the male chromosome X has more mid-/long-range interactions. We also identify differences at structural domain boundaries containing BEAF-32 in conjunction with CP190 or Chromator. Weakening of these domain boundaries in male chromosome X co-localizes with the binding of the dosage compensation complex and its co-factor CLAMP, reported to enhance chromatin accessibility. Together, our data strongly indicate that chromosome X dosage compensation affects global chromosome structure., In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C data, indicating that dosage compensation affects global chromosome structure.

The desynchronization of alpha and beta oscillations (mu rhythm) in the central scalp EEG during action observation and action execution is thought to reflect neural mirroring processes. However, the extent to which mirror neurons (MNs) or other populations of neurons contribute to such EEG desynchronization is still unknown. Here, we provide the first evidence that, in the monkey, the neuronal activity recorded from the ventral premotor cortex (PMv) strongly contributes to the EEG changes occurring in the beta band over central scalp electrodes, during executed and observed actions. We simultaneously recorded scalp EEG and extracellular activity, Multi Unit Activity (MUA) and Local Field Potentials (LFP), from area F5 of two macaques executing and observing grasping actions. We found that MUA highly correlates with an increase in high gamma LFP power and, interestingly, such LFP power increase also correlates to EEG beta - and in part also to alpha - desynchronization. In terms of timing of signal changes, the increase in high gamma LFP power precedes the EEG desynchronization, during both action observation and execution, thus suggesting a causal role of PMv neuronal activity in the modulation of the alpha and beta mu-rhythm. Lastly, neuronal signals from deeper layers of PMv exert a greater contribution than superficial layers to the EEG beta rhythm modulation, especially during the motor task. Our findings have clear implications for EEG studies in that they demonstrate that the activity of different populations of neurons in PMv contribute to the generation of the mu-rhythm.

Previous developmental research suggests that motor experience supports the development of action perception across the lifespan. However, it is still unknown when the neural mechanisms underlying action-perception coupling emerge in infancy. The goal of this study was to examine the neural correlates of action perception during the emergence of grasping abilities in newborn rhesus macaques. Neural activity, recorded via electroencephalogram (EEG), while monkeys observed grasping actions, mimed actions and means-end movements during the first (W1) and second week (W2) of life was measured. Event-related desynchronization (ERD) during action observation was computed from the EEG in the alpha and beta bands, two components of the sensorimotor mu rhythm associated with activity of the mirror neuron system (MNS). Results revealed age-related changes in the beta band, but not the alpha band, over anterior electrodes, with greater desynchronization at W2 than W1 for the observation of grasping actions. Additionally, desynchronization to observed grasping actions at W2 was associated with infants’ motor skills – measured by a separate behavioral task – such that more grasping attempts were associated to greater beta ERD. These findings suggest the emergence of an early action-perception system, that relies on motor experience, shortly after birth. Keywords: Development, Mu rhythm, ERD, Mirror neuron system, Grasping actions, Electroencephalogram

We consider a robotic walking assistant used to guide senior users across a crowded space. The problem we address is how to guide the user using motorized back wheels. Our strategy aims to simulate a passive behavior in which the forward velocity is the one imposed by the user, who receives the impression of controlling the motion. The result is obtained leaving the user in control (without any actuation) when she/he follows straight lines, while the motors kick in when the user has to make a turn. We offer extensive theoretical proof of the validity of our strategy. The technique has been validated via extensive experimentation with a large group of older adults.

CD8+ T cells infiltrating tumors are largely dysfunctional. Brummelman and Mazza et al. identify partially exhausted CXCR5+ TIM-3– CD8+ T cells with enhanced stem-like properties and cytotoxicity infiltrating human solid tumors. These cells express candidate immunotherapeutic targets (PD-1, TIGIT and CD27) for their reinvigoration., CD8+ T cells infiltrating tumors are largely dysfunctional, but whether a subset maintains superior functionality remains ill defined. By high-dimensional single cell analysis of millions of CD8+ T cells from 53 individuals with lung cancer, we defined those subsets that are enriched in tumors compared with cancer-free tissues and blood. Besides exhausted and activated cells, we identified CXCR5+ TIM-3– CD8+ T cells with a partial exhausted phenotype, while retaining gene networks responsible for stem-like plasticity and cytotoxicity, as revealed by single cell sequencing of the whole transcriptome. Ex vivo, CXCR5+ TIM-3– CD8+ T cells displayed enhanced self-renewal and multipotency compared with more differentiated subsets and were largely polyfunctional. Analysis of inhibitory and costimulatory receptors revealed PD-1, TIGIT, and CD27 as possible targets of immunotherapy. We thus demonstrate a hierarchy of differentiation in the context of T cell exhaustion in human cancer similar to that of chronically infected mice, which is further shown to disappear with disease progression., Graphical Abstract

Summary Genome-wide chromosome conformation capture based on high-throughput sequencing (Hi-C) has been widely adopted to study chromatin architecture by generating datasets of ever-increasing complexity and size. HiCBricks offers user-friendly and efficient solutions for handling large high-resolution Hi-C datasets. The package provides an R/Bioconductor framework with the bricks to build more complex data analysis pipelines and algorithms. HiCBricks already incorporates functions for calling domain boundaries and functions for high-quality data visualization. Availability and implementation http://bioconductor.org/packages/devel/bioc/html/HiCBricks.html. Contact francesco.ferrari@ifom.eu Supplementary information Supplementary data are available at Bioinformatics online.

In the present work, seven different extreme precipitation events, that affected Liguria region (Italy) in the past ten years, were analysed in depth by means of sub-km resolution numerical simulations with the state-of-the-art non-hydrostatic Weather Research and Forecasting (WRF) mesoscale model. The study aims at evaluating the impact on quantitative precipitation forecast of an explicit description of atmospheric boundary layer turbulence through a Large-Eddy Simulation (LES) approach versus the classical Reynolds-Averaged Navier–Stokes (RANS) modelling framework. To this purpose, three different sets of simulations were carried out. In the first set, reaching a resolution of 1.1 km through three nested domains, the best performing planetary boundary layer (PBL) parameterization scheme identified in a preliminary sensitivity analysis, was imposed on each domain. This modelling setup was chosen as the reference one. Then, a further nested domain was introduced with horizontal resolution of 367 m, on which both RANS and LES simulations were performed. Quantitative precipitation forecasts were compared with observed data coming from the regional rain gauge network, composed of about 200 professional stations. In four out of the seven considered events, results show an evident LES contribution to improve model performances, regarding both intensity and/or location of precipitation. This improvement is observed both in cases of underestimation and overestimation by the reference simulations and is mostly associated to a better description of low-level dynamics as well as convection triggering and intensity. In other cases, the effect of LES is not remarkable and simulations closely resemble the reference ones. Further investigation is necessary to strengthen these conclusions, but the results of this study can suggest the possibility to integrate LES in operational simulations.

A growing amount of evidence in literature suggests that germline sequence variants and somatic mutations in non-coding distal regulatory elements may be crucial for defining disease risk and prognostic stratification of patients, in genetic disorders as well as in cancer. Their functional interpretation is challenging because genome-wide enhancer–target gene (ETG) pairing is an open problem in genomics. The solutions proposed so far do not account for the hierarchy of structural domains which define chromatin three-dimensional (3D) architecture. Here we introduce a change of perspective based on the definition of multi-scale structural chromatin domains, integrated in a statistical framework to define ETG pairs. In this work (i) we develop a computational and statistical framework to reconstruct a comprehensive map of ETG pairs leveraging functional genomics data; (ii) we demonstrate that the incorporation of chromatin 3D architecture information improves ETG pairing accuracy and (iii) we use multiple experimental datasets to extensively benchmark our method against previous solutions for the genome-wide reconstruction of ETG pairs. This solution will facilitate the annotation and interpretation of sequence variants in distal non-coding regulatory elements. We expect this to be especially helpful in clinically oriented applications of whole genome sequencing in cancer and undiagnosed genetic diseases research.

During the last decade, great attention has been paid to drug delivery systems which are able to induce a site-specific and tunable release of biomolecules, attenuating the drawbacks of common therapy. The encapsulation of bioactive compounds, such as proteins and drugs, offers the advantage of enhancing the pharmacokinetics and bioavaliability of the entrapped molecules. The encapsulating technique and coating agents are chosen on the basis of the desired functionality of the final product, release kinetics, and fabrication costs. Calcium carbonate (CaCO3) is considered an ideal substrate to fabricate particles at the nanoscale level. In this work, CaCO3 nanoparticles were synthesized through a two-step protocol which comprised complex coacervation and mineralization, and they were loaded with bovine serum albumin (BSA) as a model protein. The synthesized nanoparticles were then functionalized with the layer-by-layer (LbL) electrostatic self-assembling technique using chitosan as a polycation and dextran sulphate as a polyanion. The multilayered architecture that covers CaCO3 nanoparticles prevented a burst release of BSA, resulting in 77.34 ± 1.22% of the released protein, after 72 h of incubation. A horseradish peroxidase-linked IgG was immobilized at the outer particle layer and its presence was detected via chemiluminescence. Multilayered and non-multilayered nanoparticles were biocompatible until 7 days using EA. hy926 endothelial cells. Here, we report a cost-effective protocol to obtain protein-loaded CaCO3 nanoparticles (diameter

Phenolic compounds (PC) of virgin olive oil exert several biochemical and pharmacological beneficial effects. Some dietary PC seem to prevent/improve obesity and metabolic-related disorders such as non-alcoholic fatty liver disease (NAFLD). We investigated the possible effects of PC extracted from olive pomace (PEOP) and of the main single molecules present in the extract (tyrosol, apigenin, oleuropein, p-coumaric and caffeic acid) in protecting hepatocytes and endothelial cells against triglyceride accumulation and oxidative stress.Rat hepatoma and human endothelial cells were exposed to a mixture of oleate/palmitate to mimic the condition of NAFLD and atherosclerosis, respectively. Then, cells were incubated for 24 h in the absence or in the presence of PC or PEOP. Different parameters were evaluated, such as lipid accumulation and oxidative stress-related markers.In hepatic cells, expression of peroxisome proliferator-activated receptors (PPARs) and of stearoyl-CoA desaturase 1 (SCD-1) were assessed as index of lipid metabolism. In endothelial cells, expression of intercellular adhesion molecule-1 (ICAM-1), activation of nuclear factor kappa-B (NF-kB), release of nitric oxide (NO), and wound-healing rate were assessed as index of inflammation.PEOP extract ameliorated hepatic lipid accumulation and lipid-dependent oxidative imbalance thus showing potential applications as therapeutic agent tuning down hepatosteatosis and atherosclerosis.

Studies of the last twenty years on the motor and premotor cortices of primates demonstrated that the motor system is involved in the control and initiation of movements, and in higher cognitive processes, such as action understanding, imitation, and empathy. Mirror neurons are only one example of such theoretical shift. Their properties demonstrate that motor and sensory processing are coupled in the brain. Such knowledge has been also central for designing new neurorehabilitative therapies for patients suffering from brain injuries and consequent motor deficits. Moebius Syndrome patients, for example, are incapable of moving their facial muscles, which are fundamental for affective communication. These patients face an important challenge after having undergone a corrective surgery: reanimating the transplanted muscles to achieve a voluntarily control of smiling. We propose two new complementary rehabilitative approaches on MBS patients based on observation/imitation therapy (Facial Imitation Therapy, FIT) and on hand-mouth motor synergies (Synergistic Activity Therapy, SAT). Preliminary results show that our intervention protocol is a promising approach for neurorehabilitation of patients with facial palsy.

The structural and conformational organization of chromosomes is crucial for gene expression regulation in eukaryotes and prokaryotes as well. Up to date, gene expression data generated using either microarray or RNA-sequencing are available for many bacterial genomes. However, differential gene expression is usually investigated with methods considering each gene independently, thus not taking into account the physical localization of genes along a bacterial chromosome. Here, we present WoPPER, a web tool integrating gene expression and genomic annotations to identify differentially expressed chromosomal regions in bacteria. RNA-sequencing or microarray-based gene expression data are provided as input, along with gene annotations. The user can select genomic annotations from an internal database including 2780 bacterial strains, or provide custom genomic annotations. The analysis produces as output the lists of positionally related genes showing a coordinated trend of differential expression. Graphical representations, including a circular plot of the analyzed chromosome, allow intuitive browsing of the results. The analysis procedure is based on our previously published R-package PREDA. The release of this tool is timely and relevant for the scientific community, as WoPPER will fill an existing gap in prokaryotic gene expression data analysis and visualization tools. WoPPER is open to all users and can be reached at the following URL: https://WoPPER.ba.itb.cnr.it

Hutchinson-Gilford progeria syndrome is a genetic disease caused by an aberrant form of Lamin A resulting in chromatin structure disruption, in particular by interfering with lamina associated domains. Early molecular alterations involved in chromatin remodeling have not been identified thus far. Here, we present SAMMY-seq, a high-throughput sequencing-based method for genome-wide characterization of heterochromatin dynamics. Using SAMMY-seq, we detect early stage alterations of heterochromatin structure in progeria primary fibroblasts. These structural changes do not disrupt the distribution of H3K9me3 in early passage cells, thus suggesting that chromatin rearrangements precede H3K9me3 alterations described at later passages. On the other hand, we observe an interplay between changes in chromatin accessibility and Polycomb regulation, with site-specific H3K27me3 variations and transcriptional dysregulation of bivalent genes. We conclude that the correct assembly of lamina associated domains is functionally connected to the Polycomb repression and rapidly lost in early molecular events of progeria pathogenesis., Hutchinson-Gilford progeria syndrome is a genetic disease where an aberrant form of Lamin A disrupts chromatin by interfering with lamina associated domains. Here, the authors present the SAMMY-seq, a method for genome-wide characterization of heterochromatin dynamics and detect early stage alterations of heterochromatin structure in progeria primary fibroblasts, accompained by Polycomb dysfunctions.

Hutchinson-Gilford progeria syndrome (HGPS) is characterized by the progressive accumulation of progerin, an aberrant form of Lamin A. This leads to chromatin structure disruption, in particular by interfering with Lamina Associated Domains. Although several cellular and molecular alterations have been characterized, it is still unclear how chromatin structural changes translate into premature senescence in HGPS. Moreover, early events in chromatin remodeling have not been detected so far. We developed a new high-throughput sequencing-based method, named SAMMY-seq, for genome-wide characterization of heterochromatin accessibility changes. Using SAMMY-seq, we detected early stage alterations of chromatin structure in HGPS primary fibroblasts. Of note, these structural changes do not disrupt the distribution of H3K9me3 but are associated with site-specific H3K27me3 variations and transcriptional dysregulation of Polycomb target genes. Our results show that SAMMY-seq represents a novel and sensitive tool to characterize heterochromatin alterations. Moreover, we found that the assembly of lamin associated domains is strictly connected to the correct Polycomb repression, rapidly lost in early HGPS pathogenesis.

Numerical modeling characterizes how collective excitations change in an ensemble of quantum spins as the system transitions from an ordered magnet to a spin liquid.

Background Facial mimicry is crucial in the recognition of others’ emotional state. Thus, the observation of others’ facial expressions activates the same neural representation of that affective state in the observer, along with related autonomic and somatic responses. What happens, therefore, when someone cannot mimic others’ facial expressions? Methods We investigated whether psychophysiological emotional responses to others’ facial expressions were impaired in 13 children (9 years) with Moebius syndrome (MBS), an extremely rare neurological disorder (1/250,000 live births) characterized by congenital facial paralysis. We inspected autonomic responses and vagal regulation through facial cutaneous thermal variations and by the computation of respiratory sinus arrhythmia (RSA). These parameters provide measures of emotional arousal and show the autonomic adaptation to others’ social cues. Physiological responses in children with MBS were recorded during dynamic facial expression observation and were compared to those of a control group (16 non-affected children, 9 years). Results There were significant group effects on thermal patterns and RSA, with lower values in children with MBS. We also observed a mild deficit in emotion recognition in these patients. Conclusion Results support “embodied” theory, whereby the congenital inability to produce facial expressions induces alterations in the processing of facial expression of emotions. Such alterations may constitute a risk for emotion dysregulation.

Electroencephalographic mu rhythm desynchronization is thought to reflect Mirror Neuron System (MNS) activity and represents an important neural correlate of the coupling between action execution and perception. It is still unclear if the MNS in human ontogeny is already available at the beginning of postnatal life and how early experience impacts its development. Premature birth provides a “natural condition” for investigating the effects of early, atypical extra-uterine experience on MNS. The main aim of the present study was to investigate whether the MNS activity is associated with prematurity. We compared the mu rhythm activity in preterm (PT) and full-term (FT) 14-month old infants during an action observation/execution (AO/AE) task. Mu rhythm desynchronization was computed over frontal, central, parietal and occipital regions. Both groups showed mu rhythm suppression in all the scalp regions during action execution. Different desynchronization patterns emerged during action observation. Specifically, FT infants showed mu suppression in the right frontal, bilateral parietal and occipital regions; whereas PT infants exhibited mu suppression only in the right parietal region. Overall, these preliminary findings indicate that an atypical extra uterine experience might have an impact on the MNS activity.

Detecting when one’s own gaze has been followed is a critical component of joint attention, but little is known about its development. To address this issue, we used electroencephalography (EEG) to record infant neural responses at 6.5 and 9.5 months during observation of an adult either turning to look at the same object as the infant (congruent actor), or turning to look at a different object (incongruent actor). We also used a preferential looking paradigm to investigate whether infants would demonstrate a preference for the congruent versus incongruent actor. Greater suppression of alpha band activity in the congruent compared to incongruent condition was revealed at both ages in central and parietal regions. However, the effect of congruency on alpha suppression was stronger at 9.5 months, and only at this age did infants demonstrate a preference towards looking at the congruent actor. Together, these results suggest that although infants are sensitive to others’ gaze following from early on, important neural and behavioural developments occur between 6.5 and 9.5 months. Keywords: Infant, Joint attention, EEG, Alpha, Preferential looking

In humans, infants respond positively to slow, gentle stroking—processed by C-tactile (CT) nerve fibers—by showing reductions in stress and increases in eye contact, smiling, and positive vocalizations. More frequent maternal touch is linked to greater activity and connectivity strength in social brain regions, and increases children’s attention to and learning of faces. It has been theorized that touch may prime children for social interactions and set them on a path towards healthy social cognitive development. However, less is known about the effects of touch on young infants’ psychological development, especially in the newborn period, a highly sensitive period of transition with rapid growth in sensory and social processing. It remains untested whether newborns can distinguish CT-targeted touch from other types of touch, or whether there are benefits of touch for newborns’ social, emotional, or cognitive development. In the present study, we experimentally investigated the acute effects of touch in newborn monkeys, a common model for human social development. Rhesus macaques (Macaca mulatta), like humans, are highly social, have complex mother-infant interactions with frequent body contact for the first weeks of life, making them an excellent model of infant sociality. Infant monkeys in the present study were reared in a neonatal nursery, enabling control over their early environment, including all caregiver interactions. One-week-old macaque infants (N = 27) participated in three 5-minute counter-balanced caregiver interactions, all with mutual gaze: stroking head and shoulders (CT-targeted touch), stroking palms of hands and soles of feet (Non-CT touch), or no stroking (No-touch). Immediately following the interaction, infants watched social and nonsocial videos and picture arrays including faces and objects, while we tracked their visual attention with remote eye tracking. We found that, during the caregiver interactions, infants behaved differently while being touched compared to the no-touch condition, irrespective of the body part touched. Most notably, in both touch conditions, infants exhibited fewer stress-related behaviors—self-scratching, locomotion, and contact time with a comfort object—compared to when they were not touched. Following CT-targeted touch, infants were faster to orient to the picture arrays compared to the other interaction conditions, suggesting CT-targeted touch may activate or prime infants’ attentional orienting system. In the No-touch condition infants attended longer to the nonsocial compared to the social video, possibly reflecting a baseline preference for nonsocial stimuli. In contrast, in both touch conditions, infants’ looked equally to the social and nonsocial videos, suggesting that touch may influence the types of visual stimuli that hold infants’ attention. Collectively, our results reveal that newborn macaques responded positively to touch, and touch appeared to influence some aspects of their subsequent attention, although we found limited evidence that these effects are mediated by CT fibers. These findings suggest that newborn touch may broadly support infants’ psychological development, and may have early evolutionary roots, shared across primates. This study illustrates the unique insight offered by nonhuman primates for exploring early infant social touch, revealing that touch may positively affect emotional and attentional development as early as the newborn period.

According to embodied simulation theories, others’ emotions are recognized by the unconscious mimicking of observed facial expressions, which requires the implicit activation of the motor programs that produce a specific expression. Motor responses performed during the expression of a given emotion are hypothesized to be directly linked to autonomic responses associated with that emotional behavior. We tested this hypothesis in 9 children (Mage=5.66) affected by Moebius syndrome (MBS) and 15 control children (Mage=6.6). MBS is a neurological congenital disorder characterized by underdevelopment of the VI and VII cranial nerves, which results in paralysis of the face. Moebius patients’ inability to produce facial expressions impairs their capacity to communicate emotions through the face. We therefore assessed Moebius children’s autonomic response to emotional stimuli (video cartoons) by means of functional infrared thermal (fIRT) imaging. Patients showed weaker temperature changes compared to controls, suggesting impaired autonomic activity. They also showed difficulties in recognizing facial emotions from static illustrations. These findings reveal that the impairment of facial movement attenuates the intensity of emotional experience, probably through the diminished activation of autonomic responses associated with emotional stimuli. The current study is the first to investigate emotional responses in MBS children, providing important insights into the role of facial expressions in emotional processing during early development.

Highlights • Touch improves infant health, but little is known about behavioral effects of touch. • We explored the influence of neonatal social touch on rhesus macaque monkeys. • Newborns who received extra handling responded more positively to novelty. • Higher rates of touch were associated with better cognitive and social development. • Neonatal touch may broadly support infants’ development., Touch is one of the first senses to develop and one of the earliest modalities for infant-caregiver communication. While studies have explored the benefits of infant touch in terms of physical health and growth, the effects of social touch on infant behavior are relatively unexplored. Here, we investigated the influence of neonatal handling on a variety of domains, including memory, novelty seeking, and social interest, in infant monkeys (Macaca mulatta; n = 48) from 2 to 12 weeks of age. Neonates were randomly assigned to receive extra holding, with or without accompanying face-to-face interactions. Extra-handled infants, compared to standard-reared infants, exhibited less stress-related behavior and more locomotion around a novel environment, faster approach of novel objects, better working memory, and less fear towards a novel social partner. In sum, infants who received more tactile stimulation in the neonatal period subsequently demonstrated more advanced motor, social, and cognitive skills—particularly in contexts involving exploration of novelty—in the first three months of life. These data suggest that social touch may support behavioral development, offering promising possibilities for designing future early interventions, particularly for infants who are at heightened risk for social disorders.

The meaning, mechanism, and function of imitation in early infancy have been actively discussed since Meltzoff and Moore's (1977) report of facial and manual imitation by human neonates. Oostenbroek et al. (2016) claim to challenge the existence of early imitation and to counter all interpretations so far offered. Such claims, if true, would have implications for theories of social-cognitive development. Here we identify 11 flaws in Oostenbroek et al.'s experimental design that biased the results toward null effects. We requested and obtained the authors' raw data. Contrary to the authors' conclusions, new analyses reveal significant tongue-protrusion imitation at all four ages tested (1, 3, 6, and 9 weeks old). We explain how the authors missed this pattern and offer five recommendations for designing future experiments. Infant imitation raises fundamental issues about action representation, social learning, and brain-behavior relations. The debate about the origins and development of imitation reflects its importance to theories of developmental science.

Songbirds possess mirror neurons (MNs) activating during the perception and execution of specific features of songs. These neurons are located in high vocal center (HVC), a premotor nucleus implicated in song perception, production and learning, making worth to inquire their properties and functions in vocal recognition and imitative learning. By integrating a body of brain and behavioral data, we discuss neurophysiology, anatomical, computational properties and possible functions of songbird MNs. We state that the neurophysiological properties of songbird MNs depends on sensorimotor regions that are outside the auditory neural system. Interestingly, songbirds MNs can be the result of the specific type of song representation possessed by some songbird species. At the functional level, we discuss whether songbird MNs are involved in others' song recognition, by dissecting the function of recognition in various different but possible overlapping processes: action-oriented perception, discriminative-oriented perception and identification of the signaler. We conclude that songbird MNs may be involved in recognizing other singer's vocalizations, while their role in imitative learning still require to solve how auditory feedback are used to correct own vocal performance to match the tutor song. Finally, we compare songbird and human mirror responses, hypothesizing a case of convergent evolution, and proposing new experimental directions.

Variational wave functions have enabled exceptional scientific breakthroughs related to the understanding of novel phases of matter. Examples include the Bardeen-Cooper-Schrieffer theory of superconductivity, the description of the fractional quantum Hall effect through the Laughlin state, and Feynman's variational understanding of large-scale quantum effects in liquid Helium. More recently, Gutzwiller-projected wave functions, typically constructed from fermionic degrees of freedom, have been employed to examine quantum spin models in the presence of competing interactions, where exotic phases with no spontaneous symmetry breaking and fractional excitations may exist. In this work, we investigate the aforementioned fermionic wave functions supplemented with neural networks, specifically with the so-called restricted Boltzmann machine (RBM), to boost their accuracy and obtain reliable approximations to the ground state of generic spin models. In particular, we apply our neural augmented fermionic construction to the description of both magnetically ordered and disordered phases of increasing complexity, including cases where the ground state displays a non-trivial sign structure. Even though the RBM state is by far more effective for N\'eel states endowed with a particularly simple sign structure, it provides a significant improvement over the original fermionic state in highly frustrated regimes where a complex sign structure is anticipated, thus marking the path to an understanding of strongly-correlated spin models on the lattice via neural Gutzwiller-projected variational wave functions., Comment: 13 pages, 10 figures

Robotic walkers are a promising solution for physical and cognitive support to older adults. This paper proposes a low cost path following strategy combining the advantages of a simple mechanical braking guidance, such as safety, passivity, and a low cost, and the ones of a vibrotactile haptic guidance, such as comfort and portability. The user is guided by providing indications on the directions of motion using the haptic interface so that he/she can autonomously and comfortably follow the planned path. However, whenever the user significantly departs from the path (for instance, s/he gets too close to obstacles), the braking system kicks in to safely steer the user back along the proper direction. The formal correctnesses of the hybrid strategy ruling the combination of the two guidance systems is proved theoretically. Moreover, a comprehensive experimental study with users aged 64 to 100, including also psychological evaluations, has been performed. The hybrid combination of the braking and the haptic guidance systems is shown to outperform the two individual approaches in isolation. The combination of the two retains the same level of the users' perceived comfort typical of the haptic-only guidance while ensuring the adequate path following performance typical of the braking-only guidance. In particular, the combined approach produces a mean path following error equal to 41% of the mean path following error ensured by the haptic-only approach. Conversely, thanks to the haptic feedback, the combined approach halves the activation time and the number of interventions needed in the braking-only approach.

Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect normal hematopoiesis. The analysis of human AMLs has mostly been performed using end-point materials, such as cell lines and patient derived AMLs that also carry additional contributing mutations. The molecular effects of a single oncogenic hit, such as expression of the AML associated oncoprotein AML1-ETO on hematopoietic development and transformation into a (pre-) leukemic state still needs further investigation. Here we describe the development and characterization of an induced pluripotent stem cell (iPSC) system that allows in vitro differentiation towards different mature myeloid cell types such as monocytes and granulocytes. During in vitro differentiation we expressed the AML1-ETO fusion protein and examined the effects of the oncoprotein on differentiation and the underlying alterations in the gene program at 8 different time points. Our analysis revealed that AML1-ETO as a single oncogenic hit in a non-mutated background blocks granulocytic differentiation, deregulates the gene program via altering the acetylome of the differentiating granulocytic cells, and induces t(8;21) AML associated leukemic characteristics. Together, these results reveal that inducible oncogene expression during in vitro differentiation of iPS cells provides a valuable platform for analysis of aberrant regulation in disease.

Diffuse midline gliomas (DMG) are aggressive paediatric brain tumors for which there is no effective treatment. Recent pre-clinical studies suggest that adoptive transfer of chimeric antigen receptor (CAR) T-cells targeting the disialoganglioside antigen GD2 (GD2-CAR) has a significant therapeutic potential for H3K27M-mutant DMG. Still, some tumor cells resist to treatment suggesting that a multimodal approach may be necessary to treat more efficiently the disease. Our aim was to identify chemical compounds that, in combination with CAR T-cells, would enhance anti-tumor efficacy. After having confirmed the GD2 expression in tissue samples and patient-derived H3K27M-mutant DMG cells, we developed a high throughput cell-based assay to screen 40 kinase inhibitors in combination with T-cells expressing the GD2-CAR.CD28.4-1BB.z construct. The screening led to the identification of the dual IGF1R/IR antagonists, BMS-754807 and linsitinib, which, in combination with GD2-CAR T-cells, improved antitumor activity by 25% (p

Considering the properties of mirror neurons (MNs) in terms of development and phylogeny, we offer a novel, unifying, and testable account of their evolution according to the available data and try to unify apparently discordant research, including the plasticity of MNs during development, their adaptive value and their phylogenetic relationships and continuity. We hypothesize that the MN system reflects a set of interrelated traits, each with an independent natural history due to unique selective pressures, and propose that there are at least three evolutionarily significant trends that gave raise to three subtypes: hand visuomotor, mouth visuomotor, and audio–vocal. Specifically, we put forward a mosaic evolution hypothesis, which posits that different types of MNs may have evolved at different rates within and among species. This evolutionary hypothesis represents an alternative to both adaptationist and associative models. Finally, the review offers a strong heuristic potential in predicting the circumstances under which specific variations and properties of MNs are expected. Such predictive value is critical to test new hypotheses about MN activity and its plastic changes, depending on the species, the neuroanatomical substrates, and the ecological niche.

PURPOSE: To assess vitreous concentrations of nonsteroidal anti-inflammatory drugs (NSAIDs) and prostaglandin E2 (PGE2) in patients treated with NSAIDs before vitrectomy for macular pucker. METHODS: A prospective, investigator-masked, randomized study was performed in 64 patients scheduled to undergo vitrectomy. The patients were randomized 1:1:1:1 to receive indomethacin 0.5%, bromfenac 0.09%, nepafenac 0.1%, or placebo three times a day. NSAIDs and PGE2 levels were evaluated in vitreous samples collected at the beginning of surgery. RESULTS: Mean (SD) vitreous concentrations of the study drugs were 503.13 (241.1) pg/mL for indomethacin, 302.5 (91.03) pg/mL for bromfenac, and 284.38 (128.2) pg/mL for nepafenac. Mean (SD) vitreous PGE2 levels were 247.9 (140.9) pg/mL for indomethacin, 322.12 (228.1) pg/mL for bromfenac, 448.8 (261.1) pg/mL for nepafenac, and 1,133 (323.9) pg/mL for placebo. All three NSAIDs reduced vitreous PGE2 levels to a statistically significant extent, without a significant difference among them. CONCLUSION: All assessed NSAIDs penetrated the vitreous and lowered basal PGE2 levels. A greater penetration was associated with pseudophakic eyes. The important inhibition of prostaglandins in the retina may have a clinical effect on the management of inflammatory retina diseases.

The current study harnessed the variability in infants’ neural and behavioral responses as a novel method for evaluating the potential relations between motor system activation and social behavior. We used electroencephalography (EEG) to record neural activity as 7-month-old infants observed and responded to the actions of an experimenter. To determine whether motor system activation predicted subsequent imitation behavior, we assessed event-related desynchronization (ERD) at central sites during action observation as a function of subsequent behavior. Greater mu desynchronization over central sites was observed when infants subsequently reproduced the experimenter’s goal than when they did not reproduce the goal and instead selected the nongoal object. We also found that mu desynchronization during action execution predicted the infants’ later propensity to reproduce the experimenter’s goal-directed behavior. These results provide the first evidence that motor system activation predicts the imitation of other individuals’ goals during infancy.

Mirror neurons (MNs) in the inferior parietal lobule and ventral premotor cortex (PMv) can code the intentions of other individuals using contextual cues. Gaze direction is an important social cue that can be used for understanding the meaning of actions made by other individuals. Here we addressed the issue of whether PMv MNs are influenced by the gaze direction of another individual. We recorded single-unit activity in macaque PMv while the monkey was observing an experimenter performing a grasping action and orienting his gaze either toward (congruent gaze condition) or away (incongruent gaze condition) from a target object. The results showed that one-half of the recorded MNs were modulated by the gaze direction of the human agent. These gaze-modulated neurons were evenly distributed between those preferring a gaze direction congruent with the direction where the grasping action was performed and the others that preferred an incongruent gaze. Whereas the presence of congruent responses is in line with the usual coupling of hand and gaze in both executed and observed actions, the incongruent responses can be explained by the long exposure of the monkeys to this condition. Our results reveal that the representation of observed actions in PMv is influenced by contextual information not only extracted from physical cues, but also from cues endowed with biological or social value.SIGNIFICANCE STATEMENTIn this study, we present the first evidence showing that social cues modulate MNs in the monkey ventral premotor cortex. These data suggest that there is an integrated representation of other's hand actions and gaze direction at the single neuron level in the ventral premotor cortex, and support the hypothesis of a functional role of MNs in decoding actions and understanding motor intentions.

The aim of the project was to investigate the effects of two strategies of teaching new sport actions on performance of eight-year-old children: observational-imitative method (OIM) and descriptive-directive method (DDM). The OIM group was provided with a pre-practice instruction in the form of expert modeling observation by an expert athlete. The DDM group received only verbal explanations of few selected static images. Thirty-six children (18 males and 18 females, mean age = 8,8) participated in the experiment. Subjects were randomly assigned to the OIM or DDM groups. Participants were instructed to perform four sport motor sequences never performed before (shoulder stand, soccer action, vortex howler throw, step action). Actions were videotaped and 2D kinematic analysis performed. A 10-point Likert questionnaire was administered to blind sport experts to assess the correctness and accuracy of each action. Results suggest that the OIM is the most effective instruction method when participants have no experience with the sport action to be performed. On the contrary, if the athlete needs to learn specific aspects of an exercise (such as grasping a tool) the best method is the DDM. In fact, detailed information on how to grab the vortex helped children in throwing it. We also found gender differences which might reflect cultural influences in specific sports (e.g. soccer). Finally, repetition of the exercise also improved the DDM group's performance. This has potential applications in sport teaching, suggesting that in the absence of a model performing the action to be imitated, the DDM can be as effective as the OIM if the observer repeats the sport action many times.

Although it is established that F5 neurons can distinguish between nonsocial goals such as bringing food to the mouth for eating or placing it in a container, it is not clear whether they discriminate between social and nonsocial goals. Here, we recorded single-unit activity in the ventral premotor cortex of two female macaques and used a simple reach-to-grasp motor task in which a monkey grasped an object with a precision grip in three conditions, which only differed in terms of their final goal, that is, a subsequent motor act that was either social (placing in the experimenter's hand [“Hand” condition]) or nonsocial (placing in a container [“Container” condition] or bringing to the mouth for eating [“Mouth” condition]). We found that, during the execution of the grasping motor act, the response of a sizable proportion of F5 motor neurons was modulated by the final goal of the action, with some having a preference for the social goal condition. Our results reveal that the representation of goal-directed actions in ventral premotor cortex is influenced by contextual information not only extracted from physical cues but also from cues endowed with biological or social value. Our study suggests that the activity of grasping neurons in the premotor cortex is modulated by social context.

In the epigenetics field, large-scale functional genomics datasets of ever-increasing size and complexity have been produced using experimental techniques based on high-throughput sequencing. In particular, the study of the 3D organization of chromatin has raised increasing interest, thanks to the development of advanced experimental techniques. In this context, Hi-C has been widely adopted as a high-throughput method to measure pairwise contacts between virtually any pair of genomic loci, thus yielding unprecedented challenges for analyzing and handling the resulting complex datasets. In this review, we focus on the increasing complexity of available Hi-C datasets, which parallels the adoption of novel protocol variants. We also review the complexity of the multiple data analysis steps required to preprocess Hi-C sequencing reads and extract biologically meaningful information. Finally, we discuss solutions for handling and visualizing such large genomics datasets.

According to the Darwinian perspective, facial expressions of emotions evolved to quickly communicate emotional states and would serve adaptive functions that promote social interactions. Embodied cognition theories suggest that we understand others' emotions by reproducing the perceived expression in our own facial musculature (facial mimicry) and the mere observation of a facial expression can evoke the corresponding emotion in the perceivers. Consequently, the inability to form facial expressions would affect the experience of emotional understanding. In this review, we aimed at providing account on the link between the lack of emotion production and the mechanisms of emotion processing. We address this issue by taking into account Moebius syndrome, a rare neurological disorder that primarily affects the muscles controlling facial expressions. Individuals with Moebius syndrome are born with facial paralysis and inability to form facial expressions. This makes them the ideal population to study whether facial mimicry is necessary for emotion understanding. Here, we discuss behavioral ambiguous/mixed results on emotion recognition deficits in Moebius syndrome suggesting the need to investigate further aspects of emotional processing such as the physiological responses associated with the emotional experience during developmental age.

We employ a variational Monte Carlo approach to efficiently obtain the dynamical structure factor for the spin-1/2 $J_1-J_2$ Heisenberg model on the square lattice. Upon increasing the frustrating ratio $J_2/J_1$, the ground state undergoes a continuous transition from a N\'eel antiferromagnet to a $\mathbb{Z}_{2}$ gapless spin liquid. We identify the characteristic spectral features in both phases and highlight the existence of a broad continuum of excitations in the proximity of the spin-liquid phase. The magnon branch, which dominates the spectrum of the unfrustrated Heisenberg model, gradually loses its spectral weight, thus releasing nearly-deconfined spinons, whose signatures are visible even in the magnetically ordered state. Our results show how free spinons emerge across a quantum critical point, providing evidence for the fractionalization of magnons into deconfined spinons., Comment: 5 pages, 3 figures + supplemental materials

Intranasal administration of oxytocin (OT) has been found to facilitate prosocial behaviors, emotion recognition and cooperation between individuals. Recent electroencephalography (EEG) investigations have reported enhanced mu rhythm (alpha: 8–13 Hz; beta: 15–25 Hz) desynchronization during the observation of biological motion and stimuli probing social synchrony after the administration of intranasal OT. This hormone may therefore target a network of cortical circuits involved in higher cognitive functions, including the mirror neuron system (MNS). Here, in a double-blind, placebo-controlled, between-subjects exploratory study, we investigated whether intranasal OT modulates the cortical activity from sensorimotor areas during the observation and the execution of social and non-social grasping actions. Participants underwent EEG testing after receiving a single dose (24 IU) of either intranasal OT or placebo. Results revealed an enhancement of alpha - but not beta - desynchronization during observation and execution of social grasps, especially over central and parietal electrodes, in participants who received OT (OT group). No differences between the social and non-social condition were found in the control group (CTRL group). Moreover, we found a significant difference over the cortical central-parietal region between the OT and CTRL group only within the social condition. These results suggest a possible action of intranasal OT on sensorimotor circuits involved in social perception and action understanding, which might contribute to facilitate the prosocial effects typically reported by behavioral studies.

From birth, human and nonhuman primates attend more to faces with direct gaze compared with averted gaze, and previous studies report that attention to the eyes is linked to the emergence of later social skills. Here, we explored whether early experiences influence attraction to eye contact in infant macaques by examining their attention to face pairs varying in their gaze direction across the first 13 weeks of life. Infants raised by human caretakers had limited conspecific interactions (nursery‐reared; N = 16) and were compared to infants raised in rich social environments (mother‐reared; N = 20). Both groups looked longer to faces and the eyes of direct compared to averted‐gaze faces. Looking to all faces and eyes also increased with age. Nursery‐reared infants did not display age‐associated increases in attention to direct‐gaze faces specifically, suggesting that, while there may be an initial preference for direct‐gaze faces from birth, social experiences may support its early development.

The dynamical spin structure factor is computed within a variational framework to study the one-dimensional $J_1-J_2$ Heisenberg model. Starting from Gutzwiller-projected fermionic wave functions, the low-energy spectrum is constructed from two-spinon excitations. The direct comparison with Lanczos calculations on small clusters demonstrates the excellent description of both gapless and gapped (dimerized) phases, also including incommensurate structures for $J_2/J_1>0.5$. Calculations on large clusters show how the intensity evolves when increasing the frustrating ratio and give an unprecedented accurate characterization of the dynamical properties of (non-integrable) frustrated spin models.

Aim of the present work is to investigate the potential effects of dust aerosols on the structure of some severe rainfall events in Liguria. These events are typically associated with intense southerly or southwesterly flows from Southern Mediterranean and Northern Africa and are often associated with mineral dust plumes originating from Northern Sahara. In particular the flooding event occurred in Vernazza (Cinque Terre) on October 25, 2011, is analyzed here. The specific research objective can be summarized in the so called "aerosol invigoration effect", that is how the increased aerosol concentration, caused by mineral dust plumes, may enhance convection and, consequently, ex- treme rainfall events. This is equivalent to investigating the influence that aerosols-clouds-radiation interactions may have on the physics and dynamics of the rainfall events, primarily by means of the so-called aerosols direct (including semi-direct) and indirect effects. The proposed research is primarily conducted on a numerical modeling basis. In this context, the Weather Research and Forecasting model with online coupled chemistry (WRF-Chem v. 3.8.1) is applied to simulate the formation of the convective storm and its feedback with dust aerosol. The employed simulation strategy concerns various model setups, obtained varying the sectional aerosol modules, starting from the "simple" GOCART mechanism to the more sophisticated MOSAIC. For this purpose, 3 sets of simulations are performed: (a) the control simulation (RAD0), in which the mineral dust does not interact with clouds and/or radiation, (b) the " radiation" (RAD) simulation, in which the dust transport is considered and aerosols direct effects are accounted for, and (c) the "total" simulation (TOT), in which aerosols direct and indirect effects are accounted for.

The meaning, mechanism, and function of imitation in early infancy have been actively discussed since Meltzoff and Moore's (1977) report of facial and manual imitation by human neonates. Oostenbroek etal. (2016) claim to challenge the existence of early imitation and to counter all interpretations so far offered. Such claims, if true, would have implications for theories of social-cognitive development. Here we identify 11 flaws in Oostenbroek etal.'s experimental design that biased the results toward null effects. We requested and obtained the authors’ raw data. Contrary to the authors’ conclusions, new analyses reveal significant tongue-protrusion imitation at all four ages tested (1, 3, 6, and 9 weeks old). We explain how the authors missed this pattern and offer five recommendations for designing future experiments. Infant imitation raises fundamental issues about action representation, social learning, and brain–behavior relations. The debate about the origins and development of imitation reflects its importance to theories of developmental science.

The capacity to infer the mental state or the emotional status of other individuals is a necessity for thriving in a social environment. Social animals, and in particular primates, have evolved the capacities of displaying and reading signals about emotional status and about others’ intentions. Many scholars believe that the mirror neurons, or at least a mirroring mechanism, can account for some basic forms of empathy. Mouth mirror neurons and the mirroring of facial mimicry are probably at the basis of the capacity to be emotionally attuned with another individual. Although the embodiment of emotion cannot account for all types of empathic experience, it presents a parsimonious account of how a basic sharing of emotional experience with others might occur and how it might have phylogenetically developed.

Hutchinson-Gilford Progeria Syndrome (HGPS) is characterized by the progressive accumulation of progerin, an aberrant form of Lamin A, leading to chromatin structure disruption, in particular by interfering with Lamina Associated Domains. Although several cellular and molecular alterations have been characterized, it is still yet unclear how chromatin structure changes translate into premature senescence. Moreover, early events in chromatin remodeling could not be detected so far. We developed a new high-throughput sequencing-based method, for genome-wide characterization of heterochromatin accessibility changes. We named our technology SAMMY-seq (Sequential Analysis of MacroMolecules accessibilitY), as a tribute to Sammy Basso, the founder of the Italian Progeria Association. Using SAMMY-seq on early passage HGPS primary fibroblasts we were able to detect chromatin structure alterations, in terms of accessibility changes. Of note, these structural changes are not accompanied by H3K9me3 alterations but affect the regulation Polycomb regulated bivalent genes. Our findings reinforce previous studies showing that a correct chromatin architecture is necessary to cell fate determination and that alterations of PcG occur early in HGPS-derived cells.

Birth attendance has been proposed as a distinguishing feature of humans ( Homo sapiens ) and it has been linked to the difficulty of the delivery process in our species. Here, we provide the first quantitative study based on video-recordings of the social dynamics around three births in captive bonobos ( Pan paniscus ), human closest living relative along with the chimpanzee. We show that the general features defining traditional birth attendance in humans can also be identified in bonobos. As in humans, birth in bonobos was a social event, where female attendants provided protection and support to the parturient until the infant was born. Moreover, bystander females helped the parturient during the expulsive phase by performing manual gestures aimed at holding the infant. Our results on bonobos question the traditional view that the " obligatory " need for assistance was the main driving force leading to sociality around birth in our species. Indeed, birth in bonobos is not hindered by physical constraints and the mother is self-sufficient in accomplishing the delivery. Although further studies are needed both in captivity and in the wild, we suggest that the similarities observed between birth attendance in bonobos and humans might be related to the high level of female gregariousness in these species. In our view, the capacity of unrelated females to form strong social bonds and cooperate could have represented the evolutionary pre-requisite for the emergence of human midwifery.

Phenolics and lipids of Arthrospira (Spirulina) platensis are important compounds with attractive properties. The influence of two oxidative stress conditions (UV irradiation and TiO2 concentration) on the production of these added-value compounds was investigated. UV and TiO2 stresses were shown not to influence the final concentration of biomass that resulted to be 4.83 and 5.08 g L− 1, respectively. Compared to the control run, total polyphenol yield decreased by 7.5, 24.1 and 23.1% after UV exposure for 3, 6 and 9 h, respectively, whereas in the presence of 0.10, 0.25 and 0.50 g L− 1 of TiO2 such a yield increased by 8.4, 7.0 and 7.3%, respectively. However, the treatment with 9 h of UV stress led to a lipid content increase of 29.5%, but with a reduction of the FAME fraction (67.3%). While the TiO2 stress lead to a substantial decrease of total lipid fraction. These results on the whole suggest that UV irradiation could be usefully exploited to increase the lipid content of microalgae or cyanobacteria for different applications in bioenergy production (e.g. combustion, gasification and pyrolysis), while the increased phenolic content induced by the oxidative stress with TiO2 may be of some interest in both the pharmaceutical and cosmetic sectors.