Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of limb prosthetics.

Mitotic chromosomes in different organisms adopt various dimensions. What defines these dimensions is scarcely understood. Here, we compare mitotic chromosomes in budding and fission yeasts harboring similarly sized genomes distributed among 16 or 3 chromosomes, respectively. Hi-C analyses and superresolution microscopy reveal that budding yeast chromosomes are characterized by shorter-ranging mitotic chromatin contacts and are thinner compared with the thicker fission yeast chromosomes that contain longer-ranging mitotic contacts. These distinctions persist even after budding yeast chromosomes are fused to form three fission-yeast-length entities, revealing a species-specific organizing principle. Species-specific widths correlate with the known binding site intervals of the chromosomal condensin complex. Unexpectedly, within each species, we find that longer chromosome arms are always thicker and harbor longer-ranging contacts, a trend that we also observe with human chromosomes. Arm length as a chromosome width determinant informs mitotic chromosome formation models.

We investigated how participants controlling a humanoid robotic arm's 3D endpoint position by moving their own hand are influenced by the robot's postures. We hypothesized that control would be facilitated (impeded) by biologically plausible (implausible) postures of the robot.

MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

MicroRNAs (miRNAs) modulate transcript stability and translation. Functional mature miRNAs are processed from one or both arms of the hairpin precursor. The miR-100/10 family has undergone three independent evolutionary events that have switched the arm from which the functional miRNA is processed. The dominant miR-10 sequences in the insects Drosophila melanogaster and Tribolium castaneum are processed from opposite arms. However, the duplex produced by Dicer cleavage has an identical sequence in fly and beetle. Expression of the Tribolium miR-10 sequence in Drosophila S2 cells recapitulates the native beetle pattern. Thus, arm usage is encoded in the primary miRNA sequence, but outside the mature miRNA duplex. We show that the predicted messenger RNA targets and inferred function of sequences from opposite arms differ significantly. Arm switching is likely to be general, and provides a fundamental mechanism to evolve the function of a miRNA locus and target gene network.

People with limb loss are for the first time living chronically and uninterruptedly with intimately integrated neuromusculoskeletal prostheses. This new generation of artificial limbs are fixated to the skeleton and operated by bidirectionally transferred neural information. This unprecedented level of human-machine integration is bound to have profound psychosocial effects on the individuals living with these prostheses. Here, we examined the psychosociological impact on people as they integrate neuromusculoskeletal prostheses into their bodies and lives. Three people with transhumeral amputations participated in this study, all of whom had been living with neuromusculoskeletal prostheses in their daily lives between 2 and 6 years at the time of the interview. Direct neural sensory feedback had been enabled for 6 months to 2 years. Participants were interviewed about their experiences living with the neuromusculoskeletal prostheses in their home and professional daily lives. We analyzed these interviews to elucidate themes using an interpretive phenomenological approach that regards participants' own experiences as forms of expertise and knowledge-making. Our participant-generated results indicate that people adapted and integrated the technology into functional and social arenas of daily living, with positive psychosocial effects on self-esteem, self-image, and social relations intimately linked to improved trust of the prostheses. Participants expressed enhanced prosthetic function, increased and more diverse prosthesis use in tasks of daily living, and improved relationships between their prosthesis and phantom limb. Our interviews with patients also generated critiques of the language commonly used to describe human-prosthetic relations, including terms such as "embodiment," and the need for specificity surrounding the term "natural" with regard to control versus sensory feedback. Experiences living with neuromusculoskeletal prostheses were complex and subject-dependent, and therefore future research should consider human-machine interaction as a relationship that is constantly enacted, negotiated, and deeply contextualized.

Bilateral training (BT) of the upper limb (UL) might enhance recovery of arm function after stroke. To better understand the therapeutic potential of BT, this study aimed to determine the correlation between arm motor behavior and brain structure/function as a result of bilateral arm training poststroke.

Most of our current findings on appendage formation and patterning stem from studies on chordate and ecdysozoan model organisms. However, in order to fully understand the evolution of animal appendages, it is essential to include information on appendage development from lophotrochozoan representatives. Here, we examined the basic dynamics of the Octopus vulgaris arm's formation and differentiation - as a highly evolved member of the lophotrochozoan super phylum - with a special focus on the formation of the arm's musculature.

It has been demonstrated that visual inputs can modulate pain. However, the influence of skin color on pain perception is unknown. Red skin is associated to inflamed, hot and more sensitive skin, while blue is associated to cyanotic, cold skin. We aimed to test whether the color of the skin would alter the heat pain threshold. To this end, we used an immersive virtual environment where we induced embodiment of a virtual arm that was co-located with the real one and seen from a first-person perspective. Virtual reality allowed us to dynamically modify the color of the skin of the virtual arm. In order to test pain threshold, increasing ramps of heat stimulation applied on the participants' arm were delivered concomitantly with the gradual intensification of different colors on the embodied avatar's arm. We found that a reddened arm significantly decreased the pain threshold compared with normal and bluish skin. This effect was specific when red was seen on the arm, while seeing red in a spot outside the arm did not decrease pain threshold. These results demonstrate an influence of skin color on pain perception. This top-down modulation of pain through visual input suggests a potential use of embodied virtual bodies for pain therapy.

Redundancy is a common feature of genomes, presumably to ensure robust growth under different and changing conditions. Genome compaction, removing sequences nonessential for given conditions, provides a novel way to understand the core principles of life. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system is a unique feature implanted in the synthetic yeast genome (Sc2.0), which is proposed as an effective tool for genome minimization. As the Sc2.0 project is nearing its completion, we have begun to explore the application of the SCRaMbLE system in genome compaction.

MicroRNAs act at the post-transcriptional level and guide Argonaute proteins to cleave their corresponding target transcripts. However, little attention has been paid to arm selection in miRNA precursors. In this study, small RNA high-throughput sequencing data from 29 different rice libraries were pooled to investigate tissue- and abiotic stress-specific dynamic expression of miRNAs. We found that more than half of pre-miRNAs showed changes in arm selection in different tissues and/or under different abiotic stresses. Our findings suggest that miRNA selection is remarkably prevalent in plants, providing new insights into the role of miRNAs in plant growth and development.

Treadmill experiments suggest that left-dominant arm swing is common in healthy walking adults and is modulated by cognitive dual-tasking. Little is known about arm swing asymmetry in overground walking. We report directional (dASI) and non-directional arm swing symmetry indices (ndASI) from 334 adults (mean age 68.6 ± 5.9 y) walking overground at comfortable (NW) and fast (FW) speeds and while completing a serial subtraction task (DT). dASI and ndASI were calculated from sagittal shoulder range of motion data generated by inertial measurement units affixed to the wrist. Most (91%) participants were right-handed. Group mean arm swing amplitude was significantly larger on the left in all walking conditions. During NW, ndASI was 39.5 ± 21.8, with a dASI of 21.9 ± 39.5. Distribution of dASI was bimodal with an approximately 2:1 ratio of left:right-dominant arm swing. There were no differences in ndASI between conditions but dASI was smaller during DT compared to FW (15.2 vs 24.6; p = 0.009). Handedness was unrelated to ndASI, dASI or the change in ASI metrics under DT. Left-dominant arm swing is the norm in healthy human walking irrespective of walking condition or handedness. As disease markers, ndASI and dASI may have different and complementary roles.

Many stroke survivors demonstrate arm nonuse despite good arm motor function. This retrospective secondary analysis aims to identify predictors of arm nonusers with good arm motor function after stroke rehabilitation. A total of 78 participants were categorized into 2 groups using the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) and the Motor Activity Log Amount of Use (MAL-AOU). Group 1 comprised participants with good motor function (FMA-UE ≥ 31) and low daily upper limb use (MAL-AOU ≤ 2.5), and group 2 comprised all other participants. Feature selection analysis was performed on 20 potential predictors to identify the 5 most important predictors for group membership. Predictive models were built with the five most important predictors using four algorithms. The most important predictors were preintervention scores on the FMA-UE, MAL-Quality of Movement, Wolf Motor Function Test-Quality, MAL-AOU, and Stroke Self-Efficacy Questionnaire. Predictive models classified the participants with accuracies ranging from 0.75 to 0.94 and areas under the receiver operating characteristic curve ranging from 0.77 to 0.97. The result indicates that measures of arm motor function, arm use in activities of daily living, and self-efficacy could predict postintervention arm nonuse despite good arm motor function in stroke. These assessments should be prioritized in the evaluation process to facilitate the design of individualized stroke rehabilitation programs to reduce arm nonuse.

The theory of embodied language states that language comprehension relies on an internal reenactment of the sensorimotor experience associated with the processed word or sentence. Most evidence in support of this hypothesis had been collected using linguistic material without any emotional connotation. For instance, it had been shown that processing of arm-related verbs, but not of those leg-related verbs, affects the planning and execution of reaching movements; however, at present it is unknown whether this effect is further modulated by verbs evoking an emotional experience. Showing such a modulation might shed light on a very debated issue, i.e. the way in which the emotional meaning of a word is processed. To this end, we assessed whether processing arm/hand-related verbs describing actions with negative connotations (e.g. to stab) affects reaching movements differently from arm/hand-related verbs describing actions with neutral connotation (e.g. to comb). We exploited a go/no-go paradigm in which healthy participants were required to perform arm-reaching movements toward a target when verbs expressing emotional hand actions, neutral hand actions or foot actions were shown, and to refrain from moving when no-effector-related verbs were presented. Reaction times and percentages of errors increased when the verb involved the same effector as used to give the response. However, we also found that the size of this interference decreased when the arm/hand-related verbs had a negative emotional connotation. Crucially, we show that such modulation only occurred when the verb semantics had to be retrieved. These results suggest that the comprehension of negatively valenced verbs might require the simultaneous reenactment of the neural circuitry associated with the processing of the emotion evoked by their meaning and of the neural circuitry associated with their motor features.

Tasks of daily life require the independent use of the arms and hands. Individuals with hemiparetic cerebral palsy (HCP) often experience difficulty with fine motor tasks demonstrating mirrored movements between the arms. In this study, bilateral muscle activations were quantified during single arm isometric maximum efforts and submaximal reaching tasks. The magnitude and direction of mirrored activation was examined in 14 individuals with HCP and 9 age-matched controls. Participants generated maximum voluntary torques (MVTs) in five different directions and completed ballistic reaches while producing up to 80% of shoulder abduction MVT. Electromyography (EMG) signals were recorded from six upper extremity muscles bilaterally. Participants with HCP demonstrated more mirrored activation when volitionally contracting the non-paretic (NP) arm than the paretic arm (F = 83.543, p < 0.001) in isometric efforts. Increased EMG activation during reach acceleration resulted in a larger increase in rest arm co-activation when reaching with the NP arm compared to the paretic arm in the HCP group (t = 8.425, p < 0.001). Mirrored activation is more pronounced when driving the NP arm and scales with effort level. This directionality of mirroring is indicative of the use of ipsilaterally terminating projections of the corticospinal tract (CST) originating in the non-lesioned hemisphere. Peripheral measures of muscle activation provide insight into the descending pathways available for control of the upper extremity after early unilateral brain injury.

Could it be possible that, in the not-so-distant future, we will be able to reshape the human body so as to have extra limbs? A third arm helping us out with the weekly shopping in the local grocery store, or an extra artificial limb assisting a paralysed person? Here we report a perceptual illusion in which a rubber right hand, placed beside the real hand in full view of the participant, is perceived as a supernumerary limb belonging to the participant's own body. This effect was supported by questionnaire data in conjunction with physiological evidence obtained from skin conductance responses when physically threatening either the rubber hand or the real one. In four well-controlled experiments, we demonstrate the minimal required conditions for the elicitation of this "supernumerary hand illusion". In the fifth, and final experiment, we show that the illusion reported here is qualitatively different from the traditional rubber hand illusion as it is characterised by less disownership of the real hand and a stronger feeling of having two right hands. These results suggest that the artificial hand 'borrows' some of the multisensory processes that represent the real hand, leading to duplication of touch and ownership of two right arms. This work represents a major advance because it challenges the traditional view of the gross morphology of the human body as a fundamental constraint on what we can come to experience as our physical self, by showing that the body representation can easily be updated to incorporate an additional limb.

Outer-arm dynein is the main engine providing the motive force in cilia. Using three-dimensional tracking microscopy, we found that contrary to previous reports Tetrahymena ciliary three-headed outer-arm dynein (αβγ) as well as proteolytically generated two-headed (βγ) and one-headed (α) subparticles showed clockwise rotation of each sliding microtubule around its longitudinal axis in microtubule corkscrewing assays. By measuring the rotational pitch as a function of ATP concentration, we also found that the microtubule corkscrewing pitch is independent of ATP concentration, except at low ATP concentrations where the pitch generated by both three-headed αβγ and one-headed α exhibited significantly longer pitch. In contrast, the pitch driven by two-headed βγ did not display this sensitivity. In the assays on lawns containing mixtures of α and βγ at various ratios, the corkscrewing pitch increased dramatically in a nonlinear fashion as the ratio of α in the mixture increased. Even small proportions of α-subparticle could significantly increase the corkscrewing pitch of the mixture. Our data show that torque generation does not require the three-headed outer-arm dynein (αβγ) but is an intrinsic property of the subparticles of axonemal dyneins and also suggest that each subparticle may have distinct mechanical properties.

microRNAs have been reported to play critical roles in cancer and to have potential as diagnostic biomarkers. During miRNA biogenesis, one strand of the miRNA hairpin precursor is preferentially selected as a functionally mature miRNA, while the other strand is typically degraded. Arm switching occurs when the strand preference is changed. This preference can be different and can change dynamically depending upon the species, tissue types, or development stages. Due to recent advances in next-generation sequencing methods, arm switching has been observed in a variety of cancers.

Traditionally, brain-machine interfaces (BMIs) extract motor commands from a single brain to control the movements of artificial devices. Here, we introduce a Brainet that utilizes very-large-scale brain activity (VLSBA) from two (B2) or three (B3) nonhuman primates to engage in a common motor behaviour. A B2 generated 2D movements of an avatar arm where each monkey contributed equally to X and Y coordinates; or one monkey fully controlled the X-coordinate and the other controlled the Y-coordinate. A B3 produced arm movements in 3D space, while each monkey generated movements in 2D subspaces (X-Y, Y-Z, or X-Z). With long-term training we observed increased coordination of behavior, increased correlations in neuronal activity between different brains, and modifications to neuronal representation of the motor plan. Overall, performance of the Brainet improved owing to collective monkey behaviour. These results suggest that primate brains can be integrated into a Brainet, which self-adapts to achieve a common motor goal.

Motor imagery (MI) is known to engage motor networks and is increasingly used as a relevant strategy in functional rehabilitation following immobilization, whereas its effects when applied during immobilization remain underexplored. Here, we hypothesized that MI practice during 11 h of arm-immobilization prevents immobilization-related changes at the sensorimotor and cortical representations of hand, as well as on sleep features. Fourteen participants were tested after a normal day (without immobilization), followed by two 11-h periods of immobilization, either with concomitant MI treatment or control tasks, one week apart. At the end of each condition, participants were tested on a hand laterality judgment task, then underwent transcranial magnetic stimulation to measure cortical excitability of the primary motor cortices (M1), followed by a night of sleep during which polysomnography data was recorded. We show that MI treatment applied during arm immobilization had beneficial effects on (1) the sensorimotor representation of hands, (2) the cortical excitability over M1 contralateral to arm-immobilization, and (3) sleep spindles over both M1s during the post-immobilization night. Furthermore, (4) the time spent in REM sleep was significantly longer, following the MI treatment. Altogether, these results support that implementing MI during immobilization may limit deleterious effects of limb disuse, at several levels of sensorimotor functioning.