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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 KIF1Bβ (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. This article has an associated First Person interview with the first author of the paper. [ABSTRACT FROM AUTHOR]

Breast cancer is among the most common cancers in women, second to skin cancer. Mammary gland development can influence breast cancer development in later life. Processes such as proliferation, invasion, and migration during mammary gland development can often mirror processes found in breast cancer. MicroRNAs (miRNAs), small, non-coding RNAs, can repress post-transcriptional RNA expression and can regulate up to 80% of all genes. Expression of miRNAs play a key role in mammary gland development, and aberrant expression can initiate or promote breast cancer. Here, we review the role of miRNAs in mammary development and breast cancer, and potential parallel roles. A total of 32 miRNAs were found to be expressed in both mammary gland development and breast cancer. These miRNAs are involved in proliferation, metastasis, invasion, and apoptosis in both processes. Some miRNAs were found to have contradictory roles, possibly due to their ability to target many genes at once. Investigation of miRNAs and their role in mammary gland development may inform about their role in breast cancer. In particular, by studying miRNA in development, mechanisms and potential targets for breast cancer treatment may be elucidated. [ABSTRACT FROM AUTHOR]

This paper proposes a method with an off-axis interferometer and an ensemble deep learning (I-EDL) hologram-classifier to interpret noisy digital holograms captured from the tissues of flawed biological specimens. The holograms are captured by an interferometer, which serves as a digital holographic scanner to scan the tissue with 3D information. The method achieves a high success rate of 99.60% in identifying the specimens through the tissue holograms. It is found that the ensemble deep learning hologram-classifier can effectively adapt to optical aberration coming from dust on mirrors and optical lens aberrations such as the Airy-plaque-like rings out-turn from the lenses in the interferometer. The deep learning network effectively adapts to these irregularities during the training stage and performs well in the later recognition stage without prior optical background compensations. The method does not require an intact sample with a full outline shape of the specimens or the organs to understand the objects' identities. It demonstrates a new paradigm in object identification by ensemble deep learning through a direct wavefront recognition technique. [ABSTRACT FROM AUTHOR]

Genome-wide association studies identifying hundreds of susceptibility loci for autoimmune diseases indicate that genes active in immune cells predominantly mediate risk. However, identification and functional characterization of causal variants remain challenging. Here, we focused on the immunomodulatory role of a protective variant of histone deacetylase 7 (HDAC7). This variant (rs148755202, HDAC7.p.R166H) was identified in a study of low-frequency coding variation in multiple sclerosis (MS). Through transcriptomic analyses, we demonstrate that wild-type HDAC7 regulates genes essential for the function of Foxp3+ regulatory T cells (Tregs), an immunosuppressive subset of CD4 T cells that is generally dysfunctional in patients with MS. Moreover, Treg-specific conditional hemizygous deletion of HDAC7 increased the severity of experimental autoimmune encephalitis (EAE), a mouse model of neuroinflammation. In contrast, Tregs transduced with the protective HDAC7 R166H variant exhibited higher suppressive capacity in an in vitro functional assay, mirroring phenotypes previously observed in patient samples. In vivo modeling of the human HDAC7 R166H variant by generation of a knock-in mouse model bearing an orthologous R150H substitution demonstrated decreased EAE severity linked to transcriptomic alterations of brain-infiltrating Tregs, as assessed by single-cell RNA sequencing. Our data suggest that dysregulation of epigenetic modifiers, a distinct molecular class associated with disease risk, may influence disease onset. Last, our approach provides a template for the translation of genetic susceptibility loci to detailed functional characterization, using in vitro and in vivo modeling. Regulating neuroinflammation: Regulating neuroinflammationA variant in histone deacetylase 7 (HDAC7), R166H, was previously associated with reduced risk of developing multiple sclerosis. Here, Axisa et al. aimed to understand why this was the case. Through mechanistic studies, the authors found that HDAC7 was essential for regulating proper regulatory T (Treg) cell function. Mice with Treg cells lacking HDAC7 developed more severe disease in the context of experimental autoimmune encephalitis (EAE). In contrast, when Treg cells expressed an orthologous substitution to the human R166H variant (R150H), mice developed less severe EAE. These data highlight a role for HDAC7 in Treg cells and may explain why the R116H variant reduces risk of developing multiple sclerosis. -CM [ABSTRACT FROM AUTHOR]

Neurons are connected by complex branching processes—axons and dendrites—that process information for organisms to respond to their environment. Classifying neurons according to differences in structure or function is a fundamental part of neuroscience. Here, by constructing biophysical theory and testing against empirical measures of branching structure, we develop a general model that establishes a correspondence between neuron structure and function as mediated by principles such as time or power minimization for information processing as well as spatial constraints for forming connections. We test our predictions for radius scale factors against those extracted from neuronal images, measured for species that range from insects to whales, including data from light and electron microscopy studies. Notably, our findings reveal that the branching of axons and peripheral nervous system neurons is mainly determined by time minimization, while dendritic branching is determined by power minimization. Our model also predicts a quarter-power scaling relationship between conduction time delay and body size. [ABSTRACT FROM AUTHOR]

Bi-manual therapy (BT), mirror therapy (MT), and robot-assisted rehabilitation have been conducted in hand training in a wide range of stages in stroke patients; however, the mechanisms of action during training remain unclear. In the present study, participants performed hand tasks under different intervention conditions to study bilateral sensorimotor cortical communication, and EEG was recorded. A multifactorial design of the experiment was used with the factors of manipulating objects (O), robot-assisted bimanual training (RT), and MT. The sum of spectral coherence was applied to analyze the C3 and C4 signals to measure the level of bilateral corticocortical communication. We included stroke patients with onset <6 months (n = 6), between 6 months and 1 year (n = 14), and onset >1 year (n = 20), and their Brunnstrom recovery stage ranged from 2 to 4. The results showed that stroke duration might influence the effects of hand rehabilitation in bilateral cortical corticocortical communication with significant main effects under different conditions in the alpha and beta bands. Therefore, stroke duration may influence the effects of hand rehabilitation on interhemispheric coherence. [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]

Purpose: This study aims to analyze the most effective type of emoji for deriving positive marketing results by determining whether the relationship between brand attitude, brand attachment and purchase intention is moderated by the various types of prosocial expression-based brand emojis used. Design/methodology/approach: An online survey was administered to Koreans in their 20s. Starbucks brand emojis were classified into three types: static gesture, animated gesture and a combined animated gesture and displayed word. A moderated–mediation analysis was performed to verify the research hypotheses. Gender, age, region of residence, frequency of Starbucks use and Starbucks favorability were used as control variables. Findings: Animations in emojis were shown to strengthen the marketing effect. Further, combining animated prosocial gestures and displayed words had a more positive marketing effect than merely applying animated prosocial gestures. Originality/value: This study closely examined the role of verbal, in the form of colloquial words, and nonverbal aspects, in the form of emojis, in the creation of positive business outcomes. Additionally, the positive marketing effect of animated emojis is discussed from a mechanistic point of view by linking research results to those in the field of neuroscience (mirroring by mirror neurons). [ABSTRACT FROM AUTHOR]

Slit-Robo signaling regulates midline crossing of commissural axons in different systems. In zebrafish, all retinofugal axons cross at the optic chiasm to innervate the contralateral tectum. Here, the mutant for the Robo2 receptor presents severe axon guidance defects, which were not completely reproduced in a Slit2 ligand null mutant. Since slit3 is also expressed around this area at the stage of axon crossing, we decided to analyze the possibility that it collaborates with Slit2 in this process. We found that the disruption of slit3 expression by sgRNA-Cas9 injection caused similar, albeit slightly milder, defects than those of the slit2 mutant, while the same treatment in the slit2−/−mz background caused much more severe defects, comparable to those observed in robo2 mutants. Tracking analysis of in vivo time-lapse experiments indicated differential but complementary functions of these secreted factors in the correction of axon turn errors around the optic chiasm. Interestingly, RT-qPCR analysis showed a mild increase in slit2 expression in slit3-deficient embryos, but not the opposite. Our observations support the previously proposed "repulsive channel" model for Slit-Robo action at the optic chiasm, with both Slits acting in different manners, most probably relating to their different spatial expression patterns. [ABSTRACT FROM AUTHOR]

This study focuses on age and digital exposure as factors driving individuals to be (1) employees or entrepreneurs, (2) full-time or part-time, or (3) opportunity or necessity entrepreneurs. It extends occupational choice models, relying on a utility maximization framework, to entrepreneur types incorporating age and digital exposure effects. Using 132 months of Current Population Survey data and multilevel modelling with individuals' fixed effects and metropolitan area random effects, the study finds that (1) workers with low- and high- digital exposure are more likely to become entrepreneurs than peers with medium digital exposure, mirroring digitization's "push" and "pull" mechanisms on entrepreneurship; (2) age strengthens digitization's "pull" mechanism to be entrepreneurs (versus employees) and opportunity (versus necessity) entrepreneurs; (3) digital exposure has a weak marginal potential to increase workers' odds to be part-time (versus full-time) entrepreneurs. The study also notes the importance of location and concludes with discussion and implications. [ABSTRACT FROM AUTHOR]

• fMRI assessed neural correlates of understanding expected and unexpected actions. • Mirror neuron system brain regions responded to expected actions. • The mirror neuron system and mentalizing system function in concert for unexpected actions. • Functional coupling of both networks and other brain regions occurs only during unexpected actions. • Action expectancy is an important factor affecting action representation. Action understanding involves two distinct processing levels that engage separate neural mechanisms: perception of concrete kinematic information and recognition of abstract action intentions. The mirror neuron system and the mentalizing system have both been linked to concrete action and abstract information processing, but their specific roles remain debatable. Here, we conducted a functional magnetic resonance imaging study with 26 participants who passively observed expected and unexpected actions. We performed whole-brain activation, region of interest, and effective connectivity analyses to investigate the neural correlates of these actions. Whole-brain activation analyses revealed that expected actions were associated with increased activation in the left medial superior frontal gyrus, while unexpected actions were linked to heightened activity in the left supramarginal gyrus, left superior parietal lobule, right inferior temporal gyrus, and left middle frontal gyrus. Region of interest analyses demonstrated that the left ventral premotor cortex exhibited greater activation during the observation of expected actions compared to unexpected actions, while the left inferior frontal gyrus, left superior parietal lobule, and left precuneus showed stronger activation during the observation of unexpected actions. Effective connectivity was observed between the left ventral premotor cortex and the left angular gyrus, left intraparietal sulcus, left dorsal premotor cortex, and left ventromedial prefrontal cortex with the middle frontal gyrus when observing unexpected, but not expected, actions. These findings suggest that expected actions are primarily processed by the mirror neuron system, whereas unexpected actions engage both the mirror neuron system and the mentalizing system, with these systems playing complementary roles in the understanding of unexpected actions. [ABSTRACT FROM AUTHOR]

• This study investigated the neural mechanisms involved during joint actions. • We employed EEG dual-recordings during subjects performed a motor task. • We present multiple-brain connectivity and source localization results. • Mirror neuron system and mentalizing system showed a solid intra-brain connection. • Synchronization of both systems affects how interacting agents affect each other. Cooperative action involves the simulation of actions and their co-representation by two or more people. This requires the involvement of two complex brain systems: the mirror neuron system (MNS) and the mentalizing system (MENT), both of critical importance for successful social interaction. However, their internal organization and the potential synergy of both systems during joint actions (JA) are yet to be determined. The aim of this study was to examine the role and interaction of these two fundamental systems—MENT and MNS—during continuous interaction. To this hand, we conducted a multiple-brain connectivity analysis in the source domain during a motor cooperation task using high-density EEG dual-recordings providing relevant insights into the roles of MNS and MENT at the intra- and interbrain levels. In particular, the intra-brain analysis demonstrated the essential function of both systems during JA, as well as the crucial role played by single brain regions of both neural mechanisms during cooperative activities. Specifically, our intra-brain analysis revealed that both neural mechanisms are essential during Joint Action (JA), showing a solid connection between MNS and MENT and a central role of the single brain regions of both mechanisms during cooperative actions. Additionally, our inter-brain study revealed increased inter-subject connections involving the motor system, MENT and MNS. Thus, our findings show a mutual influence between two interacting agents, based on synchronization of MNS and MENT systems. Our results actually encourage more research into the still-largely unknown realm of inter-brain dynamics and contribute to expand the body of knowledge in social neuroscience. [ABSTRACT FROM AUTHOR]

Mirror neurons show activity during both the execution (AE) and observation of actions (AO). The Mirror Neuron System (MNS) could be involved during motor imagery (MI) as well. Extensive research suggests that the cerebellum is interconnected with the MNS and may be critically involved in its activities. We gathered evidence on the cerebellum's role in MNS functions, both theoretically and experimentally. Evidence shows that the cerebellum plays a major role during AO and MI and that its lesions impair MNS functions likely because, by modulating the activity of cortical inhibitory interneurons with mirror properties, the cerebellum may contribute to visuomotor matching, which is fundamental for shaping mirror properties. Indeed, the cerebellum may strengthen sensory-motor patterns that minimise the discrepancy between predicted and actual outcome, both during AE and AO. Furthermore, through its connections with the hippocampus, the cerebellum might be involved in internal simulations of motor programs during MI. Finally, as cerebellar neuromodulation might improve its impact on MNS activity, we explored its potential neurophysiological and neurorehabilitation implications. • The cerebellum is connected with brain areas of the Mirror Neuron System (MNS). • The cerebellum is critically involved in Action Observation and Motor Imagery. • Cerebellar role in visuomotor matching seems crucial for shaping mirror properties. • Cerebellar modulation of cortical interneurons might affect MNS activities. • Cerebellar neuromodulation might enhance rehabilitation outcomes through the MNS. [ABSTRACT FROM AUTHOR]

Individuals with autism and intellectual impairments tend to be excluded from research due to their difficulties with methodological compliance. This study focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare children with autism and a IQ ≤ 80 to participate in a study on neurofeedback training (NFT). Seven children (ages 6-8) learned the prerequisite skills identified in a task analysis in an average of 5 h of TAGteach training, indicating that this is a feasible method of preparing intellectually-impaired children with autism to participate in NFT and task-dependent electroencephalography measures. TAGteach may thus have the potential to augment this population's ability to participate in less accessible treatments and behavioral neuroscientific studies.

Autism has been characterized by atypical task-related brain activation and functional connections, coinciding with deficits in sociocommunicative abilities. However, evidence of the brain's experience-dependent plasticity suggests that abnormal activity patterns may be reversed with treatment. In particular, neurofeedback training (NFT), an intervention based on operant conditioning resulting in self-regulation of brain electrical oscillations, has shown increasing promise in addressing abnormalities in brain function and behavior. We examined the effects of ≥ 20 h of sensorimotor mu-rhythm-based NFT in children with high-functioning autism spectrum disorders (ASD) and a matched control group of typically developing children (ages 8-17). During a functional magnetic resonance imaging imitation and observation task, the ASD group showed increased activation in regions of the human mirror neuron system following the NFT, as part of a significant interaction between group (ASD vs. controls) and training (pre- vs. post-training). These changes were positively correlated with behavioral improvements in the ASD participants, indicating that mu-rhythm NFT may be beneficial to individuals with ASD.

Embodied theories of cognition emphasize the central role of sensorimotor transformations in the representation of others' actions. Support for these theories is derived from the discovery of the mirror neuron system (MNS) in primates, from noninvasive techniques in humans, and from a limited number of intracranial studies. To understand the neural dynamics of the human MNS, more studies with precise spatial and temporal resolutions are essential. We used electrocorticography to define activation patterns in sensorimotor, parietal and/or frontal neuronal populations, during a viewing and grasping task. Our results show robust high gamma activation for both conditions in classic MNS sites. Furthermore, we provide novel evidence for 2 different populations of neurons: sites that were only active for viewing and grasping ("pure mirroring") and sites that were also active between viewing and grasping, and perhaps serve a more general attentional role. Lastly, a subgroup of parietal electrodes showed earlier peaks than all other regions. These results highlight the complexity of spatial-temporal patterns within the MNS and provide a critical link between single-unit research in monkeys and noninvasive techniques in human.

The article focuses on the author's experiences as an OD consultant in an NGO, highlighting three phases: early success, organizational turmoil and conflicting expectations and reassessing expectations and setting a new course. The author also reflects on the lessons learned, including the importance of managing expectations, recognizing organizational complexities and cultivating a sense of agency by focusing on what can be changed.

Brain activity was recorded using a whole-head magnetoencephalography system followed by coherence analysis to assess neural connectivity in 10 healthy right-handed adults to clarify differences in neural connectivity in brain regions during action observation from several perspectives. The subjects were instructed to observe and memorize or imitate the hand action from a first-person or second-person visual perspective. The brain activity in coherence was modified among frontal and central, sensorimotor, and mirror neuron system-related regions based on the visual perspectives of finger movements. The regional activity in coherence changed similarly under the imitation and observation tasks compared with the condition of observing static hand figures. The information from different visual perspectives of body movements was processed in the frontal-central regions related to sensorimotor processes and partially in mirror neuron system. [ABSTRACT FROM AUTHOR]

In this paper, we investigate brain activity associated with complex visual tasks, showing that electroencephalography (EEG) data can help computer vision in reliably recognizing actions from video footage that is used to stimulate human observers. Notably, we consider not only typical "explicit" video action benchmarks, but also more complex data sequences in which action concepts are only referred to, implicitly. To this end, we consider a challenging action recognition benchmark dataset—Moments in Time—whose video sequences do not explicitly visualize actions, but only implicitly refer to them (e.g., fireworks in the sky as an extreme example of "flying"). We employ such videos as stimuli and involve a large sample of subjects to collect a high-definition, multi-modal EEG and video data, designed for understanding action concepts. We discover an agreement among brain activities of different subjects stimulated by the same video footage. We name it as subjects consensus, and we design a computational pipeline to transfer knowledge from EEG to video, sharply boosting the recognition performance. [ABSTRACT FROM AUTHOR]

• Foliar application of moringa leaf extract (MLE) effectively promoted growth and biomass of safflower plants. • MLE application conspicuously enhanced maximum quantum efficiency of PSII, antioxidant system and attenuated the oxidative stress mirrored as lower H 2 O 2 and MDA content. • MLE application substantially improved leaf Ca2+ and K + content. • The application of MLE 20% performed significantly better than MLE 3%. The use of synthetic fertilizers is a potential source of environmental hazards. Natural plant-based growth regulators are eco-friendly, inexpensive and their use is highly recommended. Moringa (Moringa oleifera L.) is also known as a miracle plant with high nutritional content, medicinal and plant growth-promoting properties due to the presence of appreciable levels of hormones, vitamins, micro, and macronutrients. However, no literature has been found regarding the effect of moringa leaf extract (MLE) application on safflower plants (Carthamus tinctorius L.). Therefore, the present experiment investigated the effect of two different concentrations of MLE (3 and 20%) on various biochemical, mineral content, growth, and biomass-related attributes of safflower plants. Results revealed that application of MLE significantly improved chlorophyll content, maximum quantum yield of photosystem II (Fv/Fm), shoot and root length, fresh and dry biomass. Moreover, MLE application also significantly enhanced activities of leaf superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) while decreasing H 2 O 2 and MDA content. Foliar application of MLE also resulted in a notable increase in proline, glycine betaine, and mineral content. The application of MLE (20%) manifested maximum improvement in all attributes when compared to MLE (3%). Pearson's correlation analysis revealed positive correlation among growth, biomass, biochemical and mineral content, whereas a strong negative correlation was found between these traits and oxidative stress markers (H 2 O 2 and MDA) under MLE application. The present experimental findings indicate that MLE application can be employed as a natural plant growth regulator. Furthermore, the MLE enhanced the antioxidant system and reduced oxidative stress, therefore, it can be used to ameliorate the detrimental effects of environmental adversities on plants. [ABSTRACT FROM AUTHOR]

Previous studies have struggled to determine the relationship between mirror neuron brain regions and two distinct "action understanding" processes: identifying actions and identifying the intentions underlying those actions. This may be because the identification of intentions from others' actions requires an initial action identification process. Disruptive transcranial magnetic stimulation was administered to left inferior frontal gyrus (lIFG) during a novel cognitive task to determine which of these "action understanding" processes is subserved by mirror neuron brain regions. Participants identified either the actions performed by observed hand actions or the intentions underlying those actions. The extent to which intention identification was disrupted by lIFG (vs. control site) stimulation was dependent on the level of disruption to action identification. We subsequently performed functional magnetic resonance imaging during the same task. During action identification, responses were widespread within mirror neuron areas including lIFG and inferior parietal lobule. However, no independent responses were found in mirror neuron brain regions during intention identification. Instead, responses occurred in brain regions associated with two distinct mentalizing localizer tasks. This supports an account in which mirror neuron brain regions are involved in an initial action identification process, but the subsequent identification of intentions requires additional processing in mentalizing brain regions. [ABSTRACT FROM AUTHOR]

AGXT1 encodes alanine:glyoxylate aminotransferase 1 (AGT1), a liver peroxisomal pyridoxal 5′-phosphate dependent-enzyme whose deficit causes Primary Hyperoxaluria Type 1 (PH1). PH1 is a rare disease characterized by overproduction of oxalate, first leading to kidney stones formation, and possibly evolving to life-threatening systemic oxalosis. A minority of PH1 patients is responsive to pyridoxine, while the option for non-responders is liver-kidney transplantation. Therefore, huge efforts are currently focused on the identification of new therapies, including the promising approaches based on RNA silencing recently approved. Many PH1-associated mutations are missense and lead to a variety of kinetic and/or folding defects on AGT1. In this context, the availability of a reliable in vitro disease model would be essential to better understand the phenotype of known or newly-identified pathogenic variants as well as to test novel drug candidates. Here, we took advantage of the CRISPR/Cas9 technology to specifically knock-out AGXT1 in HepG2 cells, a hepatoma-derived cell model exhibiting a conserved glyoxylate metabolism. AGXT1 -KO HepG2 displayed null AGT1 expression and significantly reduced transaminase activity leading to an enhanced secretion of oxalate upon glycolate challenge. Known pathogenic AGT1 variants expressed in AGXT1 -KO HepG2 cells showed alteration in both protein levels and specific transaminase activity, as well as a partial mitochondrial mistargeting when associated with a common polymorphism. Notably, pyridoxine treatment was able to partially rescue activity and localization of clinically-responsive variants. Overall, our data validate AGXT1 -KO HepG2 cells as a novel cellular model to investigate PH1 pathophysiology, and as a platform for drug discovery and development. [Display omitted] • CRISPR/Cas9 technology leads to effective editing of AGXT1 gene in HepG2 cells. • AGXT1 -KO cells recapitulate the main biochemical features of AGXT1 deficiency. • Response to pyridoxine of common PH1-variants mirrors clinical evidence. • AGXT1 -KO cells are a new model for pathogenesis studies and drug discovery. [ABSTRACT FROM AUTHOR]

Physiological constraints related to atmospheric temperature pose a limit to body and appendage size in endothermic animals. This relationship has been summarised by two classical principles of biogeography: Bergmann's and Allen's rules. Body size may also constrain other phenotypic traits important in ecology, evolution and behaviour, and such effects have seldom been investigated at a continental scale. Through a multilevel‐modelling approach, we demonstrate that continent‐wide morphology of related African barbets follows predictions of Bergmann's rule, and that body size mirrors variation in song pitch, an acoustic trait important in species recognition and sexual selection. Specifically, effects on song frequency in accordance with Bergmann's rule dwarf those of acoustic adaptation at a continental scale. Our findings suggest that macroecological patterns of body size can influence phenotypic traits important in ecology and evolution, and provide a baseline for further studies on the effects of environmental change on bird song. [ABSTRACT FROM AUTHOR]

The author describes how his experiencing of the husband in a neurodiverse‐neurotypical couples therapy as narcissistic, led to a countertransference impasse. Using clinical material, he describes how his understanding of neuroscience helped him to view his patient as suffering from high functioning Asperger syndrome, and how this understanding helped in the resolution of the impasse. It is hoped that this clinical situation will emphasize the value of having a greater integration between our psychoanalytic and neurological understandings. [ABSTRACT FROM AUTHOR]

Vitamin D metabolism centers on kidney regulation of Cyp27b1 by mineralotropic hormones, including induction by parathyroid hormone (PTH), suppression by fibroblast growth factor 23 (FGF23) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and reciprocal regulations for Cyp24a1. This coordinated genomic regulation results in production of endocrine 1,25(OH)2D3, which, together with PTH and FGF23, controls mineral homeostasis. However, how these events are coordinated is unclear. Here, using in vivo chromatin immunoprecipitation sequencing in mouse kidney, we demonstrate that PTH activation rapidly induces increased recruitment of phosphorylated (p-133) CREB (pCREB) and its coactivators, CBP (CREBbinding protein) and CRTC2 (CREB-regulated transcription coactivator 2), to previously defined kidney-specificM1 and M21 enhancers near the Cyp27b1 gene. At distal enhancers of the Cyp24a1 gene, PTH suppression dismisses CBP with only minor changes in pCREB and CRTC2 occupancy, all of which correlate with decreased genomic activity and reduced transcripts. Treatment of mice with salt-inducible kinase inhibitors (YKL-05-099 and SK-124) yields rapid genomic recruitment of CRTC2 to Cyp27b1, limited interaction of CBP, and a transcriptional response for both Cyp27b1 and Cyp24a1 that mirrors the actions of PTH. Surprisingly, we find that 1,25(OH)2D3 suppression increases the occupancy of CRTC2 in the M1 enhancer, a novel observation for CRTC2 and 1,25(OH)2D3 action. Suppressive actions of 1,25(OH)2D3 and FGF23 at the Cyp27b1 gene are associated with reduced CBP recruitment at these CREB-module enhancers that disrupts full PTH induction. Our findings show that CRTC2 contributes to transcription of both Cyp27b1 and Cyp24a1, demonstrate salt-inducible kinase inhibition as a key modulator of vitamin D metabolism, and provide molecular insight into the coordinatedmechanistic actions of PTH, FGF23, and 1,25(OH)2D3 in the kidney that regulate mineral homeostasis. [ABSTRACT FROM AUTHOR]

We present a novel Neural Embedding Spatio-Temporal (NEST) point process model for spatio-temporal discrete event data and develop an efficient imitation learning (a type of reinforcement learning) based approach for model fitting. Despite the rapid development of one-dimensional temporal point processes for discrete event data, the study of spatial-temporal aspects of such data is relatively scarce. Our model captures complex spatio-temporal dependence between discrete events by carefully design a mixture of heterogeneous Gaussian diffusion kernels, whose parameters are parameterized by neural networks. This new kernel is the key that our model can capture intricate spatial dependence patterns and yet still lead to interpretable results as we examine maps of Gaussian diffusion kernel parameters. The imitation learning model fitting for the NEST is more robust than the maximum likelihood estimate. It directly measures the divergence between the empirical distributions between the training data and the model-generated data. Moreover, our imitation learning-based approach enjoys computational efficiency due to the explicit characterization of the reward function related to the likelihood function; furthermore, the likelihood function under our model enjoys tractable expression due to Gaussian kernel parameterization. Experiments based on real data show our method’s good performance relative to the state-of-the-art and the good interpretability of NEST’s result. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) continues to have a negative impact on healthcare systems around the world, though the vaccines have been developed and national vaccination coverage rate is steadily increasing. At the current stage, automatically segmenting the lung infection area from CT images is essential for the diagnosis and treatment of COVID-19. Thanks to the development of deep learning technology, some deep learning solutions for lung infection segmentation have been proposed. However, due to the scattered distribution, complex background interference and blurred boundaries, the accuracy and completeness of the existing models are still unsatisfactory. To this end, we propose a boundary guided semantic learning network (BSNet) in this paper. On the one hand, the dual-branch semantic enhancement module that combines the top-level semantic preservation and progressive semantic integration is designed to model the complementary relationship between different high-level features, thereby promoting the generation of more complete segmentation results. On the other hand, the mirror-symmetric boundary guidance module is proposed to accurately detect the boundaries of the lesion regions in a mirror-symmetric way. Experiments on the publicly available dataset demonstrate that our BSNet outperforms the existing state-of-the-art competitors and achieves a real-time inference speed of 44 FPS. The code and results of our BSNet can be found from the link of https://github.com/rmcong/BSNet. [ABSTRACT FROM AUTHOR]

Early social experience has lasting effects on adult social interactions, but less is known about how and why experience impacts social behavior. One way experience may alter adult behavior is by affecting the development of communication. Here, we test how early experience impacts individual face learning, a key aspect of communication in Polistes fuscatus wasps. We reared P. fuscatus workers in five social environments: with conspecifics, alone with a mirror, alone with a wasp visible through glass, alone with pictures of P. fuscatus, and completely alone. Then, we tested the wasps' ability to learn and remember individual conspecifics. We found that experience with conspecifics improved wasps' capacity for individual face learning. Wasps reared in normal social environments were adept at learning and remembering faces, while isolated wasps and wasps exposed to only pictures were unable to learn faces. Notably, even limited social experience improved face learning, as wasps exposed to a mirror or a conspecific through glass had intermediate capacity for learning faces. Thus, the development of individual face learning is strongly influenced by the type and amount of early social experience. Although the development of many aspects of behavior requires little experience, behaviors like individual recognition may depend on consistent social interactions. Significance statement: Individual face learning is a challenging task that requires organisms to learn and remember the unique faces of others. Developing the capacity for individual face learning may require extensive social experience, but little work has evaluated the amounts and types of experience needed. Here, we show that the type and amount of social experience influences individual face learning. Wasps with more social experience are better able to learn faces than wasps with less social experience. Surprisingly little social experience is sufficient, as wasps that viewed a single individual without any direct social contact were able to discriminate individual conspecific face more accurately than wasps reared alone. In the wild, animals may experience a range of different social environments, so there is much room for future work exploring how experience influences animal communication and recognition. [ABSTRACT FROM AUTHOR]

While the debate regarding the embodied nature of human cognition is still a research interest in cognitive science and epistemology, recent findings in neuroscience suggest that cognitive processes involved in social interaction are based on the simulation of others’ cognitive states and ours as well. However, until recently most research in social cognition continues to study mental processes in social interaction deliberately isolated from each other following 19th century’s scientific reductionism. Lately, it has been proposed that social cognition, being emerged in interactive situations, cannot be fully understood with experimental paradigms and stimuli which put the subjects in a passive stance towards social stimuli. Moreover, social neuroscience seems to concur with the idea that a simulation process of possible outcomes of social interaction occurs before the action can take place. In this “perspective” article, we propose that in the light of past and current research in social neuroscience regarding the implications of mirror neuron system and empathy altogether, these findings can be interpreted as a framework for embodied social cognition. We also propose that if the simulation process for the mentalization network works in ubiquity with the mirror neuron system, human experimentations for facial recognition and empathy need a new kind of stimuli. After a presentation of embodied social cognition, we will discuss the future of methodological prerequisites of social cognition studies in this area. On the matter, we will argue that the affective and reactive virtual agents are at the center in conducting such research. [ABSTRACT FROM AUTHOR]

Pathophysiology of Adolescent Idiopathic Scoliosis (AIS) is not yet completely understood. This exploratory study aims to investigate two aspects neglected in clinical practice: a defective postural central nervous system control in AIS, and alterations of body schema due to scoliosis spinal deformities. We recorded EEG data and balance data in four different standing positions in 14 adolescents with AIS and in 14 controls. A re-adaptation of the Image Marking Procedure (IMP) assessed body schema alterations on the horizontal (Body Perception Indices (BPIs)) and vertical direction (interacromial and bisiliac axes inclinations). Our results revealed no differences in balance control between groups; higher EEG alpha relative power over sensorimotor areas ipsilateral to the side of the curve and a significant increase of theta relative power localized over the central areas in adolescents with AIS. The difference in BPI shoulder and BPI waist significantly differed between the two groups. The inclinations of the perceived interacromial axes in adolescents with AIS was opposite to the real inclination. Increased theta activity and alpha lateralization observed may be a compensatory strategy to overcome sensorimotor dysfunction mirrored by altered body schema. Scoliosis onset might be preceded by sensorimotor control impairments that last during curve progression. [ABSTRACT FROM AUTHOR]

Background: Virtual reality (VR) has been used as a technological medium to deliver mirror therapy interventions with people after stroke in numerous applications with promising results. The recent emergence of affordable, off-the-shelf head-mounted displays (like the Oculus Rift or HTC Vive) has opened the possibility for novel and cost-effective approaches for immersive mirror therapy interventions. We have developed one such system, ART-VR, which allows people after stroke to carry out a clinically-validated mirror therapy protocol in an immersive virtual environment and within a clinical setting.Methods: A case cohort of 11 people with upper limb paresis following first time stroke at an in-patient rehabilitation facility received three interventions over a one week period. Participants carried out the BeST mirror therapy protocol using our immersive VR system as an adjunct therapy to their standard rehabilitation program. Our clinical feasibility study investigated intervention outcomes, virtual reality acceptance and user experience.Results: The results show that the combination of an immersive VR system and mirror therapy protocol is feasible for clinical use. 9 out of 11 participants showed some improvement of their affected hand after the intervention. The vast majority of the participants (9/11) reported experiencing some psycho-physical effects, such as tingling or paraesthesia, in the affected limb during the intervention.Conclusions: Our findings show that immersive VR-based mirror therapy is feasible and shows effects comparable to those of conventional mirror therapy. Trial Registration Trial was registered with the ISRCTN Registry (ISRCTN34011164) on December 3, 2021, retrospectively. [ABSTRACT FROM AUTHOR]

Cognitive skills and the underlying neural architecture are under the influence of genetics. Cognitive genomics research explores the triadic relationship between genes, brain, and cognition, with its major strategy being genotype-driven. Here we show that an inverse strategy is feasible to identify novel candidate genes for particular neuro-cognitive phenotypes in macaques. Two monkeys, originally involved in separate psychological studies, exhibited learning delay and low levels of social performance monitoring. In one monkey, mirror neurons were fewer compared to controls and mu suppression was absent in the frontal cortex. The other monkey showed heightened visual responsiveness in both frontal cortex and dopamine-rich midbrain, with a lack of inter-areal synchronization. Exome analyses revealed that the two monkeys were most likely cousins and shared variants in MAP2, APOC1, and potentially HTR2C. This phenotype-driven strategy in cognitive genomics provides a useful means to clarify the genetic basis of phenotypic variation and develop macaque models of neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

From the action potentials of neurons and cardiac cells to the amplification of calcium signals in oocytes, excitability is a hallmark of many biological signalling processes. In recent years, excitability in single cells has been related to multiple-timescale dynamics through canards, special solutions which determine the effective thresholds of the all-or-none responses. However, the emergence of excitability in large populations remains an open problem. Here, we show that the mechanism of excitability in large networks and mean-field descriptions of coupled quadratic integrate-and-fire (QIF) cells mirrors that of the individual components. We initially exploit the Ott-Antonsen ansatz to derive low-dimensional dynamics for the coupled network and use it to describe the structure of canards via slow periodic forcing. We demonstrate that the thresholds for onset and offset of population firing can be found in the same way as those of the single cell. We combine theoretical analysis and numerical computations to develop a novel and comprehensive framework for excitability in large populations, applicable not only to models amenable to Ott-Antonsen reduction, but also to networks without a closed-form mean-field limit, in particular sparse networks. Author summary: Excitability, the ability of a system to transiently amplify perturbations, is the hallmark of many biological and chemical processes and underlies their ability to send signals. Recent mathematical advances in slow-fast systems provide a rigorous framework for defining excitability in single cells. Here we combine these advances with a recent approach from statistical physics that allows us to extend the notion of excitability to networks of heterogeneous coupled cells. We show through a combination of numerics and analysis that the mechanisms of excitability in single cells pass through to these large networks even when individuals are not themselves excitable. [ABSTRACT FROM AUTHOR]

Prospect theory, arguably the most prominent theory of choice, is an obvious candidate for neural valuation models. How the activity of individual neurons, a possible computational unit, obeys prospect theory remains unknown. Here, we show, with theoretical accuracy equivalent to that of human neuroimaging studies, that single-neuron activity in four core reward-related cortical and subcortical regions represents the subjective valuation of risky gambles in monkeys. The activity of individual neurons in monkeys passively viewing a lottery reflects the desirability of probabilistic rewards parameterized as a multiplicative combination of utility and probability weighting functions, as in the prospect theory framework. The diverse patterns of valuation signals were not localized but distributed throughout most parts of the reward circuitry. A network model aggregating these signals reconstructed the risk preferences and subjective probability weighting revealed by the animals' choices. Thus, distributed neural coding explains the computation of subjective valuations under risk. It is unclear how the activity of individual neurons conform to prospect theory. Here, the authors demonstrate that the activity of single neurons in various reward-related regions in the monkey brain can be described as encoding a multiplicative combination of utility and probability weighting, and that this subjective valuation process is achieved via a distributed coding scheme. [ABSTRACT FROM AUTHOR]

Rehabilitation of severe impairment in motor function following stroke is very challenging. This is because one of the driving forces for recovery of motor function is tasks practice, something this category of patients cannot voluntarily perform. However, it has now been shown that tasks practice can equally be carried out cognitively and through observation of another person's practice, using techniques known as mental practice and tasks observation, respectively. Mental practice and tasks observation are believed to activate networks of neurons in the brain known as mirror neurons and mentalizing systems to induce recovery. The effectiveness of these techniques has, however, limited evidence at the moment. One possible explanation for this could be the nature of the protocols of these techniques, especially as regards to the intensity of practice. This article proposes ways the potentials of the mirror neurons and mentalizing systems can be harnessed to optimize recovery of severe impairment in motor function using mental practice and tasks observation. The article suggests, among other ways, protocols where tasks observation or mirror therapy are carried out first, and are then followed by mental practice, increasing the number of times the tasks are observed or mentalized, observation of significant others performing the tasks and mental practice of very familiar tasks. [ABSTRACT FROM AUTHOR]

The biological and therapeutic limits of traditional 2D culture models, which only partially mimic the complexity of cancer, have recently emerged. In this study, we used a 3D bioprinting platform to process a collagen-based hydrogel with embedded osteosarcoma (OS) cells. The human OS U-2 OS cell line and its resistant variant (U-2OS/CDDP 1 μg) were considered. The fabrication parameters were optimized to obtain 3D printed constructs with overall morphology and internal microarchitecture that accurately match the theoretical design, in a reproducible and stable process. The biocompatibility of the 3D bioprinting process and the chosen collagen bioink in supporting OS cell viability and metabolism was confirmed through multiple assays at short- (day 3) and long- (day 10) term follow-ups. In addition, we tested how the 3D collagen-based bioink affects the tumor cell invasive capabilities and chemosensitivity to cisplatin (CDDP). Overall, we developed a new 3D culture model of OS cells that is easy to set up, allows reproducible results, and better mirrors malignant features of OS than flat conditions, thus representing a promising tool for drug screening and OS cell biology research. [ABSTRACT FROM AUTHOR]

Mirror neurons have been associated with empathy. People with psychopathic traits present low levels of empathy. To analyze this, a systematic review of fMRI studies of people with psychopathic traits during an emotional facial expression processing task was performed. The regions of interest were structures associated with the mirror neuron system: ventromedial prefrontal cortex (vmPFC), inferior parietal lobe (IPL), inferior frontal gyrus and superior temporal sulcus. The analysis was also extended to structures related to affective empathy (insula, amygdala and anterior cingulate cortex) and to two more emotional processing areas (orbitofrontal cortex and fusiform gyrus). Hypoactivation was more frequently observed in regions of the mirror neuron system from people with high psychopathic traits, as well as in the emotional processing structures, and those associated with affective empathy, except for the insula, where it presented higher activity. Differences were observed for all types of emotions. The results suggest that the mirror neuron system is altered in psychopathy and their relationship with affective empathy deficits is discussed. [ABSTRACT FROM AUTHOR]

Physiotherapy improves the movement range after the onset of post-traumatic elbow stiffness and reduces the pain, which is a factor limiting elbow range of motion. However, no results have been reported for motor-cognitive intervention programs in post-traumatic elbow stiffness management. The objective was to investigate the efficacy of graded motor imagery (GMI) in post-traumatic elbow stiffness. Fifty patients with post-traumatic elbow stiffness (18 female; mean age, 41.9 ± 10.9 years) were divided into 2 groups. The GMI group (n = 25) received a program consisting of left-right discrimination, motor imagery, and mirror therapy (twice a week for 6 weeks); the structured exercise (SE) group (n = 25) received a program consisting of range-of-motion, stretching, and strengthening exercises (twice a week for 6 weeks). Both groups received a 6-week home exercise program. The primary outcome was the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. The secondary outcomes were the active range of motion (AROM), visual analog scale (VAS), Tampa Scale for Kinesiophobia (TSK), muscle strength of elbow flexors and extensors, grip strength, left-right discrimination, and Global Rating of Change. Patients were assessed at baseline, at the end of treatment (12 sessions), and a 6-week follow-up. The results indicated that both GMI and SE interventions significantly improved outcomes (P <.05). After a 6-week intervention, the DASH score was significantly improved with a medium effect size in the GMI group compared with the SE group, and improvement continued at the 6-week follow-up (F 1,45 = 3.10, P =.01). The results with a medium to large effect size were also significant for elbow flexion AROM (P =.02), elbow extension AROM (P =.03), VAS-activity (P =.001), TSK (P =.01), and muscle strength of elbow flexors and elbow extensors (P =.03) in favor of the GMI group. The GMI is an effective motor-cognitive intervention program that might be applied to the rehabilitation of post-traumatic elbow stiffness to improve function, elbow AROM, pain, fear of movement-related pain, and muscle strength. [ABSTRACT FROM AUTHOR]

Biological brains perform real‐time processing of unstructured data with ultralow energy consumption and represent the most efficient computing systems. Emulating the working principles of biological brains brings a revolutionary breakthrough in artificial intelligence (AI), generating two kinds of imitation approaches including machine learning (ML) and neuromorphic computing (NC) with artificial neurons/synapses. Herein this review, a general description of ML methods, the concept, and principle of artificial synapses (ASs) in NC derived from biological synapses, and their relationships, is provided. Graphene, one of the most representative 2D materials, arouses considerable attention due to its unique structure and properties. The application of ML in properties prediction (electronic properties, mechanical properties, thermal properties, cytotoxicity), structure recognition (atomic structure, microscopic dimensions/shapes), inverse design (composition, structure), and task recognition (chemical recognition, motion recognition, 3D imaging) of graphene and its derivatives and composites are summarized, and corresponding methods are discussed in the case studies. Recent progress in the development and application of graphene‐based ASs (synaptic transistors and memristors) is briefly introduced, where graphene‐based materials serve as the channel materials of synaptic transistors, the memristive materials, or back electrodes of synaptic memristors. Finally, the main challenges and prospects of graphene‐incorporated ML and ASs are presented. [ABSTRACT FROM AUTHOR]

This study sheds light on the challenges of communicating knowledge in remote accounting education that has traditionally been demonstrated on a blackboard or whiteboard. In a synchronous online education setting, the study investigated whether students' learning experience is facilitated by observing the instructor's hand while examples are demonstrated. Students of two courses in fundamental accounting observed four demonstrations where the conditions instructor's hand visible/not visible were alternated using a document camera (hand visible) and a writing pad (hand not visible). The study also explored the reasons for students' preferences for demonstrations with or without visible hands. In terms of theory, the study contributes to previous research on cognitive load theory and social agency theory. Providing helpful directions for instructional design, the findings indicate that observing the instructor's hand facilitates students' learning experience to a considerably higher degree than not observing the instructor's hand. Preferences for demonstrations with visible hands primarily relate to embodied cognition effects that are generated when observing and imitating human movement due to the mirror neuron system. Other explanations relate to social cue advantages – observing the instructor's hand induces a feeling of connectedness, which in turn enhances cognitive engagement. [ABSTRACT FROM AUTHOR]

Pathogens including viruses evolve in tandem with diversity in their animal and human hosts. For SARS-coV2, the focus is generally for understanding such coevolution on the virus spike protein, since it demonstrates high mutation rates compared to other genome regions, particularly in the receptor-binding domain (RBD). Viral sequences of the SARS-coV2 19B (S) clade and variants of concern from different continents were investigated, with a focus on the A.29 lineage, which presented with different mutational patterns within the 19B (S) lineages in order to learn more about how SARS-coV2 may have evolved and adapted to widely diverse populations globally. Results indicated that SARS-coV2 went through evolutionary constrains and intense selective pressure, particularly in Africa. This was manifested in a departure from neutrality with excess nonsynonymous mutations and a negative Tajima D consistent with rapid expansion and directional selection as well as deletion and deletion–frameshifts in the N-terminal domain (NTD region) of the spike protein. In conclusion, we hypothesize that viral transmission during epidemics through populations of diverse genomic structures and marked complexity may be a significant factor for the virus to acquire distinct patterns of mutations within these populations in order to ensure its survival and fitness, explaining the emergence of novel variants and strains. [ABSTRACT FROM AUTHOR]

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In the bispotted field cricket auditory pulse pattern recognition of the speciesspecific calling song is based on a delay-line and coincidence detection network, established by the activity and synaptic connections of only 5 auditory neurons in the brain. To obtain a more detailed understanding of the network and the dynamic of the neural activity over time we analyzed the response properties of these neurons to test patterns, in which the pulse duration was kept constant while the duration of specific pulse intervals was systematically altered. We confirm that the ascending interneuron AN1 and the local interneuron LN2 copy the structure of the pulse pattern, however with limited resolution at short pulse intervals, further evident in downstream neural responses. In the non-spiking delay-line interneuron LN5 during long pulse intervals full-blown rebound potentials develop over a time course of 35-70 ms. LN5 also reveals an overall increase in its membrane potential tuned to chirps of the calling song pulse pattern. This may contribute to the pattern recognition process by driving the activity of the coincidencedetector LN3 and may indicate a further function of the delay-line neuron LN5. The activity of LN3 and of the feature detector LN4 match the tuning of the phonotactic behavior and demonstrate an increasingly sparse coding of the calling song pulse patterns as evident in the response of the feature detector LN4. The circuitry reveals a fundamental mechanism of auditory pattern recognition and demonstrates a principle of neuronal coding. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) modulate physiological responses by repressing the expression of gene networks. We found that global deletion of microRNA-7 (miR-7), the most enriched miRNA in the hypothalamus, causes obesity in mice. Targeted deletion of miR-7 in Single-minded homolog 1 (Sim1) neurons, a critical component of the hypothalamic melanocortin pathway, causes hyperphagia, obesity and increased linear growth, mirroring Sim1 and Melanocortin-4 receptor (MC4R) haplo-insufficiency in mice and humans. We identified Snca (α-Synuclein) and Igsf8 (Immunoglobulin Superfamily Member 8) as miR-7 target genes that act in Sim1 neurons to regulate body weight and endocrine axes. In humans, MIR-7-1 is located in the last intron of HNRNPK, whose promoter drives the expression of both genes. Genetic variants at the HNRNPK locus that reduce its expression are associated with increased height and truncal fat mass. These findings demonstrate that miR-7 suppresses gene networks involved in the hypothalamic melanocortin pathway to regulate mammalian energy homeostasis. The hypothalamus controls systemic energy homeostasis. Here, the authors show that loss of microRNA-7 in hypothalamic neurons causes obesity, increased growth and endocrine dysfunction in mice, and report genetic evidence that links microRNA-7 to height and adiposity in humans. [ABSTRACT FROM AUTHOR]