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Infant carrying provides an important context for cognitive development and social learning in the first year of life. It enables children to perceive the world from a perspective similar to that of their parents. Lateral carrying provides children with new experiences because it gives them access to a broader range of objects. It also gives them better access to socially significant stimuli and aspects of the environment that are relevant to their parents. Thus, it can significantly contribute to learning about objects and their affordances as well as agents, their actions, and mental states. The paper argues that lateral carrying not only contributes to the development of skills related to the emergence of shared intentionality but may also play an important role in the development of the understanding of the we-mode and perhaps also in the formation of associations in the mirror neuron system. The final sections of the article offer suggestions for further research. [ABSTRACT FROM AUTHOR]

Action observation (AO) is widely used as a post-stroke therapy to activate sensorimotor circuits through the mirror neuron system. However, passive observation is often considered to be less effective and less interactive than goal-directed movement observation, leading to the suggestion that observation of goal-directed actions may have stronger therapeutic potential, as goaldirected AO has been shown to activate mechanisms for monitoring action errors. Some studies have also suggested the use of AO as a form of Brain-computer interface (BCI) feedback. In this study, we investigated the potential for observation of virtual hand movements within a P300-based BCI as a feedback system to activate the mirror neuron system. We also explored the role of feedback anticipation and estimation mechanisms during movement observation. Twenty healthy subjects participated in the study. We analyzed event-related desynchronization and synchronization (ERD/S) of sensorimotor EEG rhythms and Error-related potentials (ErrPs) during observation of virtual hand finger flexion presented as feedback in the P300-BCI loop and compared the dynamics of ERD/S and ErrPs during observation of correct feedback and errors. We also analyzed these EEG markers during passive AO under two conditions: when subjects anticipated the action demonstration and when the action was unexpected. A pre-action mu-ERD was found both before passive AO and during action anticipation within the BCI loop. Furthermore, a significant increase in beta-ERS was found during AO within incorrect BCI feedback trials. We suggest that the BCI feedback may exaggerate the passive-AO effect, as it engages feedback anticipation and estimation mechanisms as well as movement error monitoring simultaneously. The results of this study provide insights into the potential of P300-BCI with AO-feedback as a tool for neurorehabilitation. [ABSTRACT FROM AUTHOR]

Injury to mature neurons induces downregulated KCC2 expression and activity, resulting in elevated intracellular [Cl−] and depolarized GABAergic signaling. This phenotype mirrors immature neurons wherein GABA-evoked depolarizations facilitate neuronal circuit maturation. Thus, injury-induced KCC2 downregulation is broadly speculated to similarly facilitate neuronal circuit repair. We test this hypothesis in spinal cord motoneurons injured by sciatic nerve crush, using transgenic (CaMKII-KCC2) mice wherein conditional CaMKIIα promoter-KCC2 expression coupling selectively prevents injury-induced KCC2 downregulation. We demonstrate, via an accelerating rotarod assay, impaired motor function recovery in CaMKII-KCC2 mice relative to wild-type mice. Across both cohorts, we observe similar motoneuron survival and re-innervation rates, but differing post-injury reorganization patterns of synaptic input to motoneuron somas—for wild-type, both VGLUT1-positive (excitatory) and GAD67-positive (inhibitory) terminal counts decrease; for CaMKII-KCC2, only VGLUT1-positive terminal counts decrease. Finally, we recapitulate the impaired motor function recovery of CaMKII-KCC2 mice in wild-type mice by administering local spinal cord injections of bicuculline (GABAA receptor blockade) or bumetanide (lowers intracellular [Cl−] by NKCC1 blockade) during the early post-injury period. Thus, our results provide direct evidence that injury-induced KCC2 downregulation enhances motor function recovery and suggest an underlying mechanism of depolarizing GABAergic signaling driving adaptive reconfiguration of presynaptic GABAergic input. [ABSTRACT FROM AUTHOR]

Self-forgiveness (SF) involves a process through which negative moral emotions directed at the self are replaced by benevolence and acceptance. Lower SF scores can be associated with less self-compassion, higher psychological distress, and lower life dissatisfaction. However, neural correlates of SF have not been investigated yet. We enrolled a total of 79 healthy individuals. The Self-Forgiveness Scale (SFS), Self-Compassion Scale (SCS), Connor-Davidson Resilience Scale (CD-RISC), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) were evaluated. Voxel-wise correlational analyses showed a significant positive correlation between the total SFS scores and gray matter volumes (GMVs) in the fusiform gyrus (FG). In addition, the GMVs in the FG were significantly positively associated with the total SCS and CD-RISC scores and negatively correlated with the total BDI-II and BAI scores. These findings suggest that the FG related to the mirror neuron system might be a neural correlate of SF. Furthermore, its increased volumes of FG in healthy individuals can be associated with the capacity to overcome stressful life events. [ABSTRACT FROM AUTHOR]

Proteorhodopsins (PRs), bacterial light-driven outward proton pumps comprise the first discovered and largest family of rhodopsins, they play a significant role in life on the Earth. A big remaining mystery was that up-to-date there was no described bacterial rhodopsins pumping protons at acidic pH despite the fact that bacteria live in different pH environment. Here we describe conceptually new bacterial rhodopsins which are operating as outward proton pumps at acidic pH. A comprehensive function-structure study of a representative of a new clade of proton pumping rhodopsins which we name "mirror proteorhodopsins", from Sphingomonas paucimobilis (SpaR) shows cavity/gate architecture of the proton translocation pathway rather resembling channelrhodopsins than the known rhodopsin proton pumps. Another unique property of mirror proteorhodopsins is that proton pumping is inhibited by a millimolar concentration of zinc. We also show that mirror proteorhodopsins are extensively represented in opportunistic multidrug resistant human pathogens, plant growth-promoting and zinc solubilizing bacteria. They may be of optogenetic interest. Summary: Proteorhodopsins act as light-driven outward proton pumps mainly at neutral and alkaline pH, however, mirror proteorhodopsins are known to operate only at acidic pH. Here, the authors report the detailed structural and functional characterization of pH mirror proteorhodopsin SpaR as well as its diverse biological roles. [ABSTRACT FROM AUTHOR]

Unique strains of α-synuclein aggregates have been postulated to underlie the spectrum of clinical and pathological presentations seen across the synucleinopathies. Whereas multiple system atrophy (MSA) is associated with a predominance of oligodendroglial α-synuclein inclusions, α-synuclein aggregates in Parkinson's disease (PD) preferentially accumulate in neurons. The G51D mutation in the SNCA gene encoding α-synuclein causes an aggressive, early-onset form of PD that exhibits clinical and neuropathological traits reminiscent of both PD and MSA. To assess the strain characteristics of G51D PD α-synuclein aggregates, we performed propagation studies in M83 transgenic mice by intracerebrally inoculating patient brain extracts. The properties of the induced α-synuclein aggregates in the brains of injected mice were examined using immunohistochemistry, a conformational stability assay, and by performing α-synuclein seed amplification assays. Unlike MSA-injected mice, which developed a progressive motor phenotype, G51D PD-inoculated animals remained free of overt neurological illness for up to 18 months post-inoculation. However, a subclinical synucleinopathy was present in G51D PD-inoculated mice, characterized by the accumulation of α-synuclein aggregates in restricted regions of the brain. The induced α-synuclein aggregates in G51D PD-injected mice exhibited distinct properties in a seed amplification assay and were much more stable than those present in mice injected with MSA extract, which mirrored the differences observed between human MSA and G51D PD brain samples. These results suggest that the G51D SNCA mutation specifies the formation of a slowly propagating α-synuclein strain that more closely resembles α-synuclein aggregates associated with PD than MSA. [ABSTRACT FROM AUTHOR]

Touch is one of the primary communication tools. Interestingly, the sensation of touch can also be experienced when observed in another person. Due to the system of mirror neurons, it is, in fact, being mapped on the somatosensory cortex of the observer. This phenomenon can be triggered not only by observing touch in another individual, but also by a mirror reflection of the contralateral limb. Our study aims to evaluate and localize changes in the intracerebral source activity via sLORETA imaging during the haptic stimulation of hands, while modifying this contact by a mirror illusion. A total of 10 healthy volunteers aged 23–42 years attended the experiment. The electrical brain activity was detected via scalp EEG. First, we registered the brain activity during resting state with open and with closed eyes, each for 5 min. Afterwards, the subjects were seated at a table with a mirror reflecting their left hand and occluding their right hand. The EEG was then recorded in 2 min sequencies during four modifications of the experiment (haptic contact on both hands, stimulation of the left hand only, right hand only and without any tactile stimuli). We randomized the order of the modifications for each participant. The obtained EEG data were converted into the sLORETA program and evaluated statistically at the significance level of p ≤ 0.05. The subjective experience of all the participants was registered using a survey. A statistically significant difference in source brain activity occurred during all four modifications of our experiment in the beta-2, beta-3 and delta frequency bands, resulting in the activation of 10 different Brodmann areas varying by modification. The results suggest that the summation of stimuli secured by interpersonal haptic contact modified by mirror illusion can activate the brain areas integrating motor, sensory and cognitive functions and further areas related to communication and understanding processes, including the mirror neuron system. We believe these findings may have potential for therapy. [ABSTRACT FROM AUTHOR]

In this functional MRI (fMRI) study on 82 healthy adults using the dot perspective task, inconsistency of perspectives was associated with a significant increase of the mean reaction time and number of errors both in Self and Other conditions. Unlike the Arrow (non-mentalizing), the Avatar (mentalizing) paradigm was characterized by the recruitment of parts of the mentalizing and salience networks. These data provide experimental evidence supporting the fMRI distinction between mentalizing and non-mentalizing stimuli. A widespread activation of classical theory of mind (ToM) areas but also of salience network and decision making areas was observed in the Other compared to Self-conditions. Compared to Self-Consistent, Self-Inconsistent trials were related to increased activation in the lateral occipital cortex, right supramarginal and angular gyrus as well as inferior, superior and middle frontal gyri. Compared to the Other-Consistent, Other-Inconsistent trials yielded strong activation in the lateral occipital cortex, precuneus and superior parietal lobule, middle and superior precentral gyri and left frontal pole. These findings reveal that altercentric interference relies on areas involved in self-other distinction, self-updating and central executive functions. In contrast, egocentric interference needs the activation of the mirror neuron system and deductive reasoning, much less related to pure ToM abilities. [ABSTRACT FROM AUTHOR]

In a world that seeks precision medicine, genetic testing is gaining importance in clinical decision making. We previously reported the utility of a novel tool for longitudinally dividing core needle biopsy (CNB) tissues into two filamentous tissues that can provide paired mirror image-like tissues (mirror-tissues) that spatially match each other. In this study, we investigated its application in gene panel testing in patients who underwent prostate CNB. Four hundred and forty-three biopsy cores were obtained from 40 patients. Of them, 361 biopsy cores (81.5%) were judged by a physician to be appropriate for dividing into two pieces using the new device, of which a histopathological diagnosis was successfully reached in 358 biopsy cores (99.2%). Among them, the quality and quantity of nucleic acid in 16 appropriately divided cores were assessed and found to be sufficient for gene panel testing, and histopathological diagnosis was successfully obtained from the remaining divided cores. The novel device for longitudinally-dividing CNB tissue provided mirror image-like paired-tissues for gene panel and pathology testing. The device might be a promising tool for obtaining genetic and molecular biological information, in addition to histopathological diagnosis, helping to advance personalized medicine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Machine learning (ML) models have long overlooked innateness: how strong pressures for survival lead to the encoding of complex behaviors in the nascent wiring of a brain. Here, we derive a neurodevelopmental encoding of artificial neural networks that considers the weight matrix of a neural network to be emergent from well-studied rules of neuronal compatibility. Rather than updating the network's weights directly, we improve task fitness by updating the neurons' wiring rules, thereby mirroring evolutionary selection on brain development. We find that our model (1) provides sufficient representational power for high accuracy on ML benchmarks while also compressing parameter count, and (2) can act as a regularizer, selecting simple circuits that provide stable and adaptive performance on metalearning tasks. In summary, by introducing neurodevelopmental considerations into ML frameworks, we not only model the emergence of innate behaviors, but also define a discovery process for structures that promote complex computations. Neuroscience has long inspired AI, however the neuroevolutionary search that produces sophisticated behaviors has not been systematized. This paper defines neurodevelopmental ML as a discovery process for structures that promote complex computations. [ABSTRACT FROM AUTHOR]

Background: Disruptions in the children Autism spectrum’s mirror neurons has been challenged by researchers in psychological and motor behavior science for children with autism spectrum. Methods that based on the mirror neuron system, such as cooperatively observation learning, can be used to increase the imitation of autism in children, and use them in teaching. However, few studies have investigated the effect of this educational method on the learning of autistic children. Aims: The purpose of this study was to investigate the effect of observational learning by individual and dyad training on mirror neurons function and learning of movement skills in autism spectrum disorder children. Methods: The current research is a semi-experimental one that was designed and implemented in 2017. The statistical population includes 7-14-year-old boys on the autism spectrum (Asperger's and high-functioning) in Tehran, who were selected through purposive sampling. The samples were allocated to two individual and dyad training groups and trained in breaststroke skills twice a week for a period of 8 weeks. The data collection tool includes the Gars Autism Severity Scale (1994); the Chest crawl skill assessment checklist (Galaho and Ozman, 2005), and an electroencephalograph (EEG) sensor used to record brain waves. Data analysis was done by repeated measure covariance analysis, which was done in SPSS software. Results: The results of covariance analysis showed that both groups improved mirror neurons function, but significantly, the dyad training group improved mirror neurons function in post-test, the difference between two groups was significantly in benefit of the dyad training group (p<0.001). Also, the quality of swimming skill (chest) in the dyad training group was significantly improved, and the difference between the two groups in improving the swimming skill was significantly in favor of the dyad group (p <0.001). Conclusion: Training through observational learning, imitation, and observational feedback improves the activity of mirror neurons, which is effective in improving motor actions. As a result, one of the suggestions in this study is to focus on enhancing the functional capabilities of the neurons through observational learning in order to improve the motor skill of autism and neuropsychiatric rehabilitation. [ABSTRACT FROM AUTHOR]

Highlight: The AOT facilitates motor learning in patients with cognitive impairment. Intervention with AOT in patients with cognitive impairment may be effective in improving functionality of their dominant upper limb and independence in basic activities of daily living. What is the implication of the main finding? AOT could be an effective therapeutic tool in the approach to older adults with cognitive imparirment. Group therapy itself may be a determining factor in the therapeutic approach for patients with cognitive impairment. Cognitive impairment is frequent in elderly subjects. It is associated with motor impairment, a limitation in quality of life and frequently, institutionalization. The aim of this work is to test the efficacy of a therapeutic group program based on action-observation learning. Methods: a non-randomized controlled trial study was conducted. We included 40 patients with cognitive impairment from a nursing home who were categorized into mild and moderate cognitive impairment and divided separately into a control and experimental group. Experimental group performed a 4-week group work, in which each patient with mild cognitive impairment was paired with a patient with moderate cognitive impairment. Thus, patients with mild cognitive impairment observed a series of functional exercises performed by their peers and replicated them. Simultaneously, the patients with moderate cognitive impairment replicated the movement after observing it performed by a patient with mild cognitive impairment. The control group continued to receive their usual care at the center. The upper limb function, cognitive level and function in basic activities of human daily life were measured before and after the intervention and compared with the control group. Results: statistically significant differences were found in the functionality of basic activities of daily living, in the functionality of the upper limb and in the cognitive level in all patients in the experimental group regardless of the initial cognitive level. No statistically significant differences were found in the control group. Conclusions: the implementation of a group, peer-based, action-observation learning therapeutic program is effective in improving the basic activities of human daily life, cognitive level and upper limb functionality in patients with mild and moderate dementia. [ABSTRACT FROM AUTHOR]

The tyrosine kinase inhibitor (TKI) cabozantinib might impede the growth of the sunitinib-resistant cell lines by targeting MET and AXL overexpression in metastatic renal cell carcinoma (mRCC). We studied the role of MET and AXL in the response to cabozantinib, particularly following long-term administration with sunitinib. Two sunitinib-resistant cell lines, 786-O/S and Caki-2/S, and the matching 786-O/WT and Caki-2/WT cells were exposed to cabozantinib. The drug response was cell-line-specific. The 786-O/S cells were less growth-inhibited by cabozantinib than 786-O/WT cells (p-value = 0.02). In 786-O/S cells, the high level of phosphorylation of MET and AXL was not affected by cabozantinib. Despite cabozantinib hampering the high constitutive phosphorylation of MET, the Caki-2 cells showed low sensitivity to cabozantinib, and this was independent of sunitinib pretreatment. In both sunitinib-resistant cell lines, cabozantinib increased Src-FAK activation and impeded mTOR expression. The modulation of ERK and AKT was cell-line-specific, mirroring the heterogeneity among the patients. Overall, the MET- and AXL-driven status did not affect cell responsiveness to cabozantinib in the second-line treatment. The activation of Src-FAK might counteract cabozantinib activity and contribute to tumor survival and may be considered an early indicator of therapy response. [ABSTRACT FROM AUTHOR]

Across a breadth of animal taxa, early-life environmental variation has been demonstrated to have lasting effects on later-life traits, including brain morphology. Here, we use Plains Spadefoot Toads (Spea bombifrons) to evaluate how larval diet type and amount influence later-stage, juvenile brain size and the relative sizes of brain regions. We specifically investigate whether developmental plasticity in brain morphology mirrors previously documented interspecific variation with relation to nutritional restriction and carnivory. Our findings demonstrate, contrary to expectation, that exposure to dietary restriction during the larval stage causes an increase in relative juvenile brain size. However, consistent with our predictions, consuming a prey-based shrimp diet during the larval stage results in relatively larger juvenile telencephalons, an intraspecific response that parallels an interspecific pattern in frogs where more-carnivorous species possess relatively larger telencephalons. Our results demonstrate that early-life dietary restriction and early-life diet type can generate changes in juvenile brain size and morphology in ways that may influence later-life behaviors and fitness. Further, our study suggests that intraspecific and environmentally induced changes in brain morphology can mirror interspecific divergence in brain morphology, supporting a role for developmental plasticity in promoting evolutionary change. [ABSTRACT FROM AUTHOR]

Action observation (AO) can improve motor performance in humans, probably via the human mirror neuron system. In addition, there is some evidence that transcranial direct current stimulation (tDCS) can improve motor performance. However, it is yet to be determined whether AO combined with tDCS has an enhanced effect on motor performance. We investigated the effect of AO combined with high-definition tDCS (HD-tDCS) targeting the inferior parietal lobe (IPL) and inferior frontal gyrus (IFG), the main aggregates of the human mirror neuron system, on motor performance in healthy adults and compared the immediate vs. 24-h retention test effects (anodal electrodes were placed over these regions of interest). Sixty participants were randomly divided into three groups that received one of the following single-session interventions: (1) observation of a video clip that presented reaching movement sequences toward five lighted units + active HD-tDCS stimulation (AO + active HD-tDCS group); (2) observation of a video clip that presented the same reaching movement sequences + sham HD-tDCS stimulation (AO + sham HD-tDCS group); and (3) observation of a video clip that presented neutral movie while receiving sham stimulation (NM + sham HD-tDCS group). Subjects’ reaching performance was tested before and immediately after each intervention and following 24 h. Subjects performed reaching movements toward units that were activated in the same order as the observed sequence during pretest, posttest, and retest. Occasionally, the sequence order was changed by beginning the sequence unexpectedly with a different activated unit. Outcome measures included mean Reaching Time and difference between the Reaching Time of the unexpected and expected reaching movements (Delta). In the posttest and retest, Reaching Time and Delta improved in the AO + sham HD-tDCS group compared to the NM + HD-sham tDCS group. In addition, at posttest, Delta improved in the AO + active HD-tDCS group compared to the NM + sham HD-tDCS group. It appears that combining a montage of active HD-tDCS, which targets the IPL and IFG, with AO interferes with the positive effects of AO alone on the performance of reaching movement sequences. [ABSTRACT FROM AUTHOR]

Dogs’ behavioural synchronisation with humans is of growing scientific interest. However, studies lack a comprehensive exploration of the neurocognitive foundations of this social cognitive ability. Drawing parallels from the mechanisms underlying behavioural synchronisation in humans, specifically motor resonance and the recruitment of mirror neurons, we hypothesise that dogs’ behavioural synchronisation with humans is underpinned by a similar mechanism, namely interspecific motor resonance. Based on a literature review, we argue that dogs possess the prerequisites for motor resonance, and we suggest that interspecific behavioural synchronisation relies on the activation of both human and canine mirror neurons. Furthermore, interspecific behavioural studies highlight certain characteristics of motor resonance, including motor contagion and its social modulators. While these findings strongly suggest the potential existence of interspecific motor resonance, direct proof remains to be established. Our analysis thus paves the way for future research to confirm the existence of interspecific motor resonance as the neurocognitive foundation for interspecific behavioural synchronisation. Unravelling the neurocognitive mechanisms underlying this behavioural adjustment holds profound implications for understanding the evolutionary dynamics of dogs alongside humans and improving the day-to-day management of dog–human interactions.

Whether neurovisceral integration, reflected by resting high-frequency heart rate variability (HRV), constrains or facilitates neural reactivity to other people's emotions is unclear. We assessed the relation between resting HRV and neural activation when observing and imitating emotional faces. We focused on brain regions implicated in sensorimotor resonance, salience detection and arousal. We used electrocardiogram data to compute resting HRV. Resting HRV measures were negatively correlated with activation in a portion of the inferior frontal gyrus showing mirror neuron properties, the insula and the amygdala in response to observation, but not imitation, of emotional faces. Thus, resting HRV appears to be linked to sensitivity to others' emotional cues, both in terms of the tendency to map others' emotional facial expressions onto one's own motor system and to rapidly detect and mark others' emotions as salient events. Resting HRV may reflect, in part, a threshold for increased processing of others' emotional cues.

It has been suggested that the Rorschach human movement (M) response could be associated with an embodied simulation mechanism mediated by the mirror neuron system (MNS). To date, evidence for this hypothesis comes from two electroencephalogram studies and one repetitive transcranial magnetic stimulation study. To provide additional data on this topic, the Rorschach was administered during fMRI to a sample of 26 healthy adult volunteers. Activity in MNS-related brain areas temporally associated with M responses was compared with such activity for other, non-M Rorschach responses. Data analyses focused on MNS regions of interest identified by Neurosynth, a web-based platform for large scale, automated meta-analysis of fMRI data. Consistent with the hypothesis that M responses involve embodied simulation and MNS activity, univariate region of interest analyses showed that production of M responses associated with significantly greater activity in MNS-related brain areas when compared with non-M Rorschach responses. This finding is consistent with the traditional interpretation of the M code.

Action observation (AO) is widely used as a post-stroke therapy to activate sensorimotor circuits through the mirror neuron system. However, passive observation is often considered to be less effective and less interactive than goal-directed movement observation, leading to the suggestion that observation of goal-directed actions may have stronger therapeutic potential, as goal-directed AO has been shown to activate mechanisms for monitoring action errors. Some studies have also suggested the use of AO as a form of Brain–computer interface (BCI) feedback. In this study, we investigated the potential for observation of virtual hand movements within a P300-based BCI as a feedback system to activate the mirror neuron system. We also explored the role of feedback anticipation and estimation mechanisms during movement observation. Twenty healthy subjects participated in the study. We analyzed event-related desynchronization and synchronization (ERD/S) of sensorimotor EEG rhythms and Error-related potentials (ErrPs) during observation of virtual hand finger flexion presented as feedback in the P300-BCI loop and compared the dynamics of ERD/S and ErrPs during observation of correct feedback and errors. We also analyzed these EEG markers during passive AO under two conditions: when subjects anticipated the action demonstration and when the action was unexpected. A pre-action mu-ERD was found both before passive AO and during action anticipation within the BCI loop. Furthermore, a significant increase in beta-ERS was found during AO within incorrect BCI feedback trials. We suggest that the BCI feedback may exaggerate the passive-AO effect, as it engages feedback anticipation and estimation mechanisms as well as movement error monitoring simultaneously. The results of this study provide insights into the potential of P300-BCI with AO-feedback as a tool for neurorehabilitation.

Neurons in parietal cortex exhibit task-related activity during decision-making tasks. However, it remains unclear how long-term training to perform different tasks over months or even years shapes neural computations and representations. We examine lateral intraparietal area (LIP) responses during a visual motion delayed-match-to-category task. We consider two pairs of male macaque monkeys with different training histories: one trained only on the categorization task, and another first trained to perform fine motion-direction discrimination (i.e., pretrained). We introduce a novel analytical approach—generalized multilinear models—to quantify low-dimensional, task-relevant components in population activity. During the categorization task, we found stronger cosine-like motion-direction tuning in the pretrained monkeys than in the category-only monkeys, and that the pretrained monkeys' performance depended more heavily on fine discrimination between sample and test stimuli. These results suggest that sensory representations in LIP depend on the sequence of tasks that the animals have learned, underscoring the importance of considering training history in studies with complex behavioral tasks. Posterior parietal cortex supports visual categorization in macaque monkeys. Here, the authors quantify low-dimensional neural population activity using tensor regression to find that long term training history impacts encoding of categorization. [ABSTRACT FROM AUTHOR]

This preliminary study introduces a novel action observation therapy (AOT) protocol associated with electroencephalographic (EEG) monitoring to be used in the future as a rehabilitation strategy for the upper limb in patients with subacute stroke. To provide initial evidence on the usefulness of this method, we compared the outcome of 11 patients who received daily AOT for three weeks with that of patients who undertook two other approaches recently investigated by our group, namely intensive conventional therapy (ICT), and robot-assisted therapy combined with functional electrical stimulation (RAT-FES). The three rehabilitative interventions showed similar arm motor recovery as indexed by Fugl-Meyer's assessment of the upper extremity (FMA_UE) and box and block test (BBT). The improvement in the FMA_UE was yet more favourable in patients with mild/moderate motor impairments who received AOT, in contrast with patients carrying similar disabilities who received the other two treatments. This suggests that AOT might be more effective in this subgroup of patients, perhaps because the integrity of their mirror neurons system (MNS) was more preserved, as indexed by EEG recording from central electrodes during action observation. In conclusion, AOT may reveal an effective rehabilitative tool in patients with subacute stroke; the EEG evaluation of MNS integrity may help to select patients who could maximally benefit from this intervention. [ABSTRACT FROM AUTHOR]

The p38 inhibitor SB202190 is a necessary component of the medium used for normal colorectal mucosa cultures. Sato et al. suggested that the primary activity of SB202190 may be EGFR signaling stabilization, causing an increased phosphorylation of Erk1-2 sustaining organoid proliferation. However, the growth of some colorectal cancer (CRC)-derived organoid cultures is inhibited by this molecule via an unknown mechanism. We biochemically investigated SB202190 activity on a collection of 25 primary human CRC organoids, evaluating EGFR, Akt and Erk1-2 activation using Western blot. We found that Erk1-2 phosphorylation was induced by SB202190 in 20 organoid cultures and inhibited in 5 organoid cultures. A next-generation sequencing (NGS) analysis revealed that the inhibition of p-Erk1-2 signaling corresponded to the cultures with BRAF mutations (with four different hits, one being undescribed), while p-Erk1-2 induction was apparently unrelated to other mutations involving the EGFR pathway (Her2, KRAS and NRAS). We found that SB202190 mirrored the biochemical activity of the BRAF inhibitor Dabrafenib, known to induce the paradoxical activation of p-Erk1-2 signaling in BRAF wild-type cells. SB202190 was a more effective inhibitor of BRAF-mutated organoid growth in the long term than the specific BRAF inhibitors Dabrafenib and PLX8394. Overall, SB202190 can predict BRAF-activating mutations in patient-derived organoids, as well as allowing for the identification of new BRAF variants, preceding and enforcing NGS data. [ABSTRACT FROM AUTHOR]

Lipid membrane turnover and myelin repair play a central role in diseases and lesions of the central nervous system (CNS). The aim of the present study was to analyze lipid composition changes due to inflammatory conditions. We measured the fatty acid (FA) composition in erythrocytes (RBCs) and spinal cord tissue (gas chromatography) derived from mice affected by experimental allergic encephalomyelitis (EAE) in acute and remission phases; cholesterol membrane content (Filipin) and GM1 membrane assembly (CT-B) in EAE mouse RBCs, and in cultured neurons, oligodendroglial cells and macrophages exposed to inflammatory challenges. During the EAE acute phase, the RBC membrane showed a reduction in polyunsaturated FAs (PUFAs) and an increase in saturated FAs (SFAs) and the omega-6/omega-3 ratios, followed by a restoration to control levels in the remission phase in parallel with an increase in monounsaturated fatty acid residues. A decrease in PUFAs was also shown in the spinal cord. CT-B staining decreased and Filipin staining increased in RBCs during acute EAE, as well as in cultured macrophages, neurons and oligodendrocyte precursor cells exposed to inflammatory challenges. This regulation in lipid content suggests an increased cell membrane rigidity during the inflammatory phase of EAE and supports the investigation of peripheral cell membrane lipids as possible biomarkers for CNS lipid membrane concentration and assembly. [ABSTRACT FROM AUTHOR]

The mirror neuron system consists of fronto-parietal regions and responds to both goal-directed action execution and observation. The broader action observation network is specifically involved in observation of actions and is thought to play a role in understanding the goals of the motor act, the intention of others, empathy, and language. Many, but not all, studies have found mirror neuron system or action observation network dysfunction in autism spectrum disorder. The objective of this study was to use observation of a goal-directed action fMRI paradigm to examine the action observation network in autism spectrum disorder and to determine whether fronto-parietal activation is associated with language ability. Adolescents with autism spectrum disorder (n = 23) were compared to typically developing adolescents (n = 20), 11–17 years. Overall, there were no group differences in activation, however, the autism spectrum group with impaired expressive language (n = 13) had significantly reduced inferior frontal and inferior parietal activation during action viewing. In controls, right supramarginal gyrus activation was associated with higher expressive language; bilateral supramarginal and left pars opercularis activation was associated with better verbal-gesture integration. Results suggest that action-observation network dysfunction may characterize a subgroup of individuals with autism spectrum disorder with expressive language deficits. Therefore, interventions that target this dysfunctional network may improve expressive language in this autism spectrum subgroup. Future treatment studies should individualize therapeutic approaches based on brain-behavior relationships. [ABSTRACT FROM AUTHOR]

The study involved 42 individuals (including 25 women) in the age range from 18 to 41. The aim of the study was to investigate the peculiarities of oscillatory dynamics accompanying the processes of interaction with a virtual character and to localize the effects detected. During the recording of the electroencephalogram (EEG), the subjects were asked to interact with a virtual character, choosing one of three options ("offer friendship," "attack," or "avoid contact"). Faces with five types of emotional expressions (angry, happy, frightened, sad, and neutral) were used as stimuli. Analysis of equivalent dipoles revealed that the choices of active interaction ("attack" and "offer friendship"), compared to avoidance of interaction, were accompanied by a greater decrease in α- and β-rhythms, which may be related to the processes of understanding the intentions of the virtual character. The choice of friendship, as compared to interaction avoidance, was accompanied by an increase in δ-rhythm, which may indicate the presence of a motivational component. The effects detected were found in clusters of equivalent dipoles, whose localization coincides with the structures of the mentalizing network and mirror neuron network, which are involved in the processes of evaluating people's intentions. [ABSTRACT FROM AUTHOR]

Microtubules (MTs) are dynamic components of the cell cytoskeleton involved in several cellular functions, such as structural support, migration and intracellular trafficking. Despite their high similarity, MTs have functional heterogeneity that is generated by the incorporation into the MT lattice of different tubulin gene products and by their post-translational modifications (PTMs). Such regulations, besides modulating the tubulin composition of MTs, create on their surface a "biochemical code" that is translated, through the action of protein effectors, into specific MT-based functions. This code, known as "tubulin code", plays an important role in neuronal cells, whose highly specialized morphologies and activities depend on the correct functioning of the MT cytoskeleton and on its interplay with a myriad of MT-interacting proteins. In recent years, a growing number of mutations in genes encoding for tubulins, MT-interacting proteins and enzymes that post-translationally modify MTs, which are the main players of the tubulin code, have been linked to neurodegenerative processes or abnormalities in neural migration, differentiation and connectivity. Nevertheless, the exact molecular mechanisms through which the cell writes and, downstream, MT-interacting proteins decipher the tubulin code are still largely uncharted. The purpose of this review is to describe the molecular determinants and the readout mechanisms of the tubulin code, and briefly elucidate how they coordinate MT behavior during critical neuronal events, such as neuron migration, maturation and axonal transport. [ABSTRACT FROM AUTHOR]

This study reports that children exposed to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), the major toxin in Agent Orange, from the breast milk of mothers residing near the former Da Nang US air base in Vietnam may have specific alterations in higher brain functions, resulting in social and communication deficits, including autism spectrum disorder (ASD). After the age of 8 years, girls with high TCDD showed increased attention deficit hyperactivity disorder (ADHD)-like behaviors and altered mirror neuron activity, which is often observed in children with ASD. However, no significant relationship between autistic traits and toxic equivalency values of polychlorinated dibenzodioxins and polychlorinated dibenzofurans (TEQ-PCDD/Fs) was found in these children. Notably, boys with high levels of TEQ-PCDD/Fs showed poor language and motor development in the first 3 years of life, although boys with high TCDD levels did not. However, at 8 years of age, boys with high TCDD showed reading learning difficulties, a neurodevelopmental disorder. These findings suggest that perinatal TCDD exposure impacts social–emotional cognitive functions, leading to sex-specific neurodevelopmental disorders—learning difficulty in boys and ADHD in girls. Future studies with a greater number of children exposed to high levels of TCDD are necessary to estimate the threshold values for neurodevelopmental effects. [ABSTRACT FROM AUTHOR]

Sequence variants modulating gene function or expression affect various heritable traits, including the number of neurons within a population. The present study employed a forward-genetic approach to identify candidate causal genes and their sequence variants controlling the number of one type of retinal neuron, the AII amacrine cell. Data from twenty-six recombinant inbred (RI) strains of mice derived from the parental C57BL/6J (B6/J) and A/J laboratory strains were used to identify genomic loci regulating cell number. Large variation in cell number is present across the RI strains, from a low of ∼57,000 cells to a high of ∼87,000 cells. Quantitative trait locus (QTL) analysis revealed three prospective controlling genomic loci, on Chromosomes (Chrs) 9, 11, and 19, each contributing additive effects that together approach the range of variation observed. Composite interval mapping validated two of these loci, and chromosome substitution strains, in which the A/J genome for Chr 9 or 19 was introgressed on a B6/J genetic background, showed increased numbers of AII amacrine cells as predicted by those two QTL effects. Analysis of the respective genomic loci identified candidate controlling genes defined by their retinal expression, their established biological functions, and by the presence of sequence variants expected to modulate gene function or expression. Two candidate genes, Dtx4 on Chr 19, being a regulator of Notch signaling, and Dixdc1 on Chr 9, a modulator of the WNT-β-catenin signaling pathway, were explored in further detail. Postnatal overexpression of Dtx4 was found to reduce the frequency of amacrine cells, while Dixdc1 knockout retinas contained an excess of AII amacrine cells. Sequence variants in each gene were identified, being the likely sources of variation in gene expression, ultimately contributing to the final number of AII amacrine cells. [ABSTRACT FROM AUTHOR]

When intracellular, pathogenic Salmonella reside in a membrane compartment composed of interconnected vacuoles and tubules, the formation of which depends on the translocation of bacterial effectors into the host cell. Cytoskeletons and their molecular motors are prime targets for these effectors. In this study, we show that the microtubule molecular motor KIF1Bß (a splice variant of KIF1B), a member of the kinesin-3 family, is a key element for the establishment of the Salmonella replication niche as its absence is detrimental to the stability of bacterial vacuoles and the formation of associated tubules. Kinesin-3 interacts with the Salmonella effector SifA but also with SKIP (also known as PLEKHM2), a host protein complexed to SifA. The interaction with SifA is essential for the recruitment of kinesin-3 on Salmonella vacuoles whereas that with SKIP is incidental. In the non-infectious context, however, the interaction with SKIP is essential for the recruitment and activity of kinesin-3 only on a fraction of the lysosomes. Finally, our results show that, in infected cells, the presence of SifA establishes a kinesin-1 and kinesin-3 recruitment pathway that is analogous to and functions independently of that mediated by the Arl8a and Arl8b GTPases. [ABSTRACT FROM AUTHOR]

Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products. [ABSTRACT FROM AUTHOR]

Understanding of resource requirements of vulnerable species is key for conservation planning. Here, we used stable carbon (δ13C) and nitrogen isotopes (δ15N) of hair from giant armadillos (Priodontes maximus) to understand individual resource use. We collected hair from 19 giant armadillos analyzing 34 samples from the Brazilian Pantanal and compared the resource use between sexes and age classes. We also assessed the relationship of isotopic values with individuals' body mass and the habitat type used. We observed a wide variation in resource use by giant armadillos, showing that individuals consume prey that feeds on distinct resources and occupies different habitat types, indicating that there is individual variation in foraging behavior. Most giant armadillos presented a mixed diet (C3/C4 resources, forests/open areas), but a quarter of individuals had strictly C4 diets (open areas). Males are more prone to forage on C4 resources, presenting an isotopic niche 2.6‐times larger than that of females. Subadults presented diets more associated with habitats with high arboreal cover (C3 resources, forests), while adults foraged more in open areas (C4 resources). This result is mirrored by the positive relationship between δ13C values and body mass, suggesting that larger giant armadillos tend to feed more in open areas. We observed that δ13C values decreased as individuals increased the use of habitats with high arboreal cover. We stress the importance of conserving the natural mosaic in the Pantanal landscape for the species persistence, given that giant armadillos require all habitat types to fulfill their dietary, spatial, and developmental needs. [ABSTRACT FROM AUTHOR]

Mirror neurons are brain cells that are activated by the execution/observation of a movement. It has been proposed that its functions are altered in autism spectrum disorder (ASD), which is evidenced by the absence of desynchronization of the mu rhythm of the electroencephalogram when observing a biological movement, a theory known as broken mirror. The objective of this study was to test this theory in a Colombian sample. Desynchronizations of the mu rhythm of the electroencephalogram were evaluated in conditions of observation/imitation of a biological movement and in the observation of two non-biological movements in 35 cases and 19 control pairs, with ages between 6 and 16 years old. Participants with ASD presented lower desynchronizations than controls when observing/imitation of biological movement, but higher when observing inert elements. Participants with ASD established greater connection with objects than with other individuals. The broken mirror was not a homogeneous phenomenon in ASD nor a discriminating characteristic between cases and controls. Individual differences played an important role in the functioning of mirror neurons. We propose strategies based on these findings for people with Autism Spectrum Disorder in clinical, educational, productive and social contexts. [ABSTRACT FROM AUTHOR]

Observation of others' actions activates motor representations in sensorimotor cortex. Although action observation in the real-world often involves multiple agents displaying varying degrees of action involvement, most lab studies on action observation studied individual actions. We recorded EEG-mu suppression over sensorimotor cortex to investigate how the multi-agent nature of observed hand/arm actions is incorporated in sensorimotor action representations. Hereto we manipulated the extent of agent involvement in dyadic interactions presented in videos. In all clips two agents were present, of which agent-1 always performed the same action, while the involvement of agent-2 differed along three levels: (1) passive and uninvolved, (2) passively involved, (3) actively involved. Additionally, a no-action condition was presented. The occurrence of these four conditions was predictable thanks to cues at the start of each trial, which allowed to study possible mu anticipation effects. Dyadic interactions in which agent-2 was actively involved resulted in increased power suppression of the mu rhythm compared to dyadic interactions in which agent-2 was passively involved. The latter did not differ from actions in which agent-2 was present but not involved. No anticipation effects were found. The results suggest that the sensorimotor representation of a dyadic interaction takes into account the simultaneously performed bodily articulations of both agents, but no evidence was found for incorporation of their static articulated postures. [ABSTRACT FROM AUTHOR]

Kleptoplastidic, or chloroplast stealing, lineages transiently retain functional photosynthetic machinery from algal prey. This machinery, and its photosynthetic outputs, must be integrated into the host's metabolism, but the details of this integration are poorly understood. Here, we study this metabolic integration in the ciliate Mesodinium chamaeleon, a coastal marine species capable of retaining chloroplasts from at least six distinct genera of cryptophyte algae. To assess the effects of feeding history on ciliate physiology and gene expression, we acclimated M. chamaeleon to four different types of prey and contrasted well‐fed and starved treatments. Consistent with previous physiological work on the ciliate, we found that starved ciliates had lower chlorophyll content, photosynthetic rates, and growth rates than their well‐fed counterparts. However, ciliate gene expression mirrored prey phylogenetic relationships rather than physiological status, suggesting that, even as M. chamaeleon cells were starved of prey, their overarching regulatory systems remained tuned to the prey type to which they had been acclimated. Collectively, our results indicate a surprising degree of prey‐specific host transcriptional adjustments, implying varied integration of prey metabolic potential into many aspects of ciliate physiology. [ABSTRACT FROM AUTHOR]

Traditional and new disciplines converge in suggesting that the parietal lobe underwent a considerable expansion during human evolution. Through the study of endocasts and shape analysis, paleoneurology has shown an increased globularity of the braincase and bulging of the parietal region in modern humans, as compared to other human species, including Neandertals. Cortical complexity increased in both the superior and inferior parietal lobules. Emerging fields bridging archaeology and neuroscience supply further evidence of the involvement of the parietal cortex in human-specific behaviors related to visuospatial capacity, technological integration, self-awareness, numerosity, mathematical reasoning and language. Here, we complement these inferences on the parietal lobe evolution, with results from more classical neuroscience disciplines, such as behavioral neurophysiology, functional neuroimaging, and brain lesions; and apply these to define the neural substrates and the role of the parietal lobes in the emergence of functions at the core of material culture, such as tool-making, tool use and constructional abilities. [ABSTRACT FROM AUTHOR]

The ability to identify others' actions and intentions, "action understanding," is crucial for successful social interaction. Under direct accounts, action understanding takes place without the involvement of inferential processes, a claim that has yet to be tested using behavioural measures. Using a dual-task paradigm, the present study aimed to establish whether the identification of others' actions and intentions depends on automatic or inferential processing, by manipulating working memory load during performance of a task designed to target the identification of actions and intentions. Experiment 1 tested a novel action understanding task targeting action identification and intention identification. This task was then combined with two working memory manipulations (cognitive: Experiment 2; perceptual: Experiment 3) to determine whether action identification and intention identification are disrupted by concurrent cognitive or perceptual load. Both action identification and intention identification were impaired by concurrent cognitive and perceptual processing, indicating that action understanding requires additional perceptual and cognitive resources. These findings contradict a direct account of action understanding. [ABSTRACT FROM AUTHOR]

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Rehabilitation is essential for post-stroke body function recovery. Supported by the mirror neuron theory, motor imagery (MI) has been proposed as a potential stroke therapy capable of facilitating the rehabilitation. However, it is often quite difficult to estimate the degree of the participation of patients during traditional MI training as well as difficult to evaluate the efficacy of MI based rehabilitation methods. The goal of this paper is to develop a virtual reality (VR) based MI training system combining electromyography (EMG) based real-time feedback for poststroke rehabilitation, with the immersive scenario of the VR system providing a shooting basketball training for bilateral upper limbs. Through acquiring electroencephalography (EEG) signal, the brain activity in alpha and beta frequency bands was mapped and the correlation analysis could be achieved. Furthermore, EMG data of each patient was collected and calculated as threshold with root-mean-square algorithm for feedback of the performance score of the shooting basketball training in virtual environment. To investigate the feasibility of this newly-built rehabilitation training system, four experiments namely initial assessment experiment, motor imagery (MI), action observation (AO), and combined motor imagery and action observation (MI+AO) were carried out on stroke patients at different recovery stages. The result shows that MI+AO can generate more pronounced event-related desynchronization (ERD) in alpha band compared to other cases and induce relatively obvious ERD in beta band compared to AO, which demonstrates that VR-based observation has ability to facilitate MI training. Furthermore, it has been found that the muscle strength from MI+AO is the highest through the EMG analysis. This proves that the feedback of EMG can be used to quantify patient’s training engagement and promote MI training at a certain extent. Hence, by incorporating such an EMG feedback, a VR-based MI training system has the potential to achieve higher efficacy for post-stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Neurons that fire both during execution and observation of a motor act, called mirror neurons, provide strong evidence of its existence in humans. Real, observed and imagined movements seem to share most of the same neural pathways. However, little is known about the neural mechanisms and functional processes of the different areas and the integration of information between the observation and imagined systems. Objective: Compare alpha absolute power levels in sensorimotor areas between real, imagined and observed movement conditions. Methods: The sample consisted of a group of 12 healthy young individuals (4 men and 8 women), right-handed and with mean age of 30 ± 10. The task consisted of 4 blocks of 20 trials of rhythmic flexion- extension movements of the index finger by pressing the left button of a mouse properly fixed on a table. The activation level was analyzed by measuring the absolute power of the alpha band (8-13hz). Results: ANOVA with repeated measures showed that in the real condition, alpha absolute power was higher in the electrodes Cz, P3 and Pz compared to the electrode C3. In the imagined condition, the electrodes P3 and Pz presented higher alpha absolute power compared to the electrode C3. For the observed condition, electrodes P3, Pz and P4 presented higher alpha power compared to the electrode C3. In addition, higher alpha absolute power was observed in the electrode Pz compared to the electrodes Cz and C4. Conclusion: Higher alpha activation was observed on the electrode C3 in all conditions. These findings indicate that the observed movement also shares neural circuits when compared to the real and imagined movements. It was observed that in all conditions there was a significant decrease in alpha power on the C3 electrode, which indicates activation of the motor cortex in a similar way in the conditions. [ABSTRACT FROM AUTHOR]

In healthy people, motor resonance mechanisms are flexible to negative emotional contextual clues with greater motor resonance during the observation of a reach to grasp movement performed in an environment eliciting disgust. The link between emotion and motor control has become an interesting topic in Parkinson's disease (PD). Here, we aimed to study the response of the mirror neuron system, specifically motor resonance, to an emotion-enriched context in people with PD. Corticospinal excitability was recorded in a total of 44 participants, divided into two groups (23 PD patients and 21 healthy subjects). We recorded motor-evoked potentials from a muscle involved in the grasping movement while participants were watching the same reach-to-grasp movement embedded in surrounds with negative emotional valence, but different levels of arousal: sadness (low arousal) and disgust (high arousal). Basic motor resonance mechanisms were less efficient in PD than controls. Responsiveness to emotional contextual clues eliciting sadness was similar between PD and controls, whereas responsiveness to emotional contextual clues eliciting disgust was impaired in PD patients. Our findings show reduced motor resonance flexibility to the disgusting context, supporting the hypothesis that PD patients may have a deficit in "translating" an aversive motivational state into a physiologic response. The amygdala, which is implicated in the appraisal of fearful stimuli and response to threatening situations, might be implicated in this process. [ABSTRACT FROM AUTHOR]

Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products. [ABSTRACT FROM AUTHOR]