Expansion of EasyClone-MarkerFree toolkit for Saccharomyces cerevisiae genome with new integration sites.

Biotechnological production requires genetically stable recombinant strains. To ensure genomic stability, recombinant DNA is commonly integrated into the genome of the host strain. Multiple genetic tools have been developed for genomic integration into baker's yeast Saccharomyces cerevisiae. Previously, we had developed a vector toolkit EasyClone-MarkerFree for stable integration into eleven sites on chromosomes X, XI, and XII of S. cerevisiae. The markerless integration was enabled by CRISPR-Cas9 system. In this study, we have expanded the kit with eight additional intergenic integration sites located on different chromosomes. The integration efficiency into the new sites was above 80%. The expression level of green fluorescence protein (gfp) for all eight sites was similar or above XI-2 site from the original EasyClone-MarkerFree toolkit. The cellular growth was not affected by the integration into any of the new eight locations. The eight-vector expansion kit is available from AddGene.

Testing rTMS-Induced Neuroplasticity: A Single Case Study of Focal Hand Dystonia.

Focal hand dystonia in musicians is a neurological motor disorder in which aberrant plasticity is caused by excessive repetitive use. This work's purposes were to induce plasticity changes in a dystonic musician through five daily thirty-minute sessions of 1 Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left M1 by using neuronavigated stimulation and to reliably measure the effect of these changes. To this aim, the relationship between neuroplasticity changes and motor recovery was investigated using fine-grained kinematic analysis. Our results suggest a statistically significant improvement in motor coordination both in a task resembling the dystonic-inducing symptoms and in a reach-to-grasp task. This single case study supports the safe and effective use of noninvasive brain stimulation in neurologic patients and highlights the importance of evaluating outcomes in measurable ways. This issue is a key aspect to focus on to classify the clinical expression of dystonia. These preliminary results promote the adoption of kinematic analysis as a valuable diagnostic tool.

Selective reaching in macaques: evidence for action-centred attention.

When a monkey selects a piece of food lying on the ground from among other viable objects in the near vicinity, only the desired item governs the particular pattern and direction of the animal's reaching action. It would seem then that selection is an important component controlling the animal's action. But, we may ask, is the selection process in such cases impervious to the presence of other objects that could constitute potential obstacles to or constraints on movement execution? And if it is, in fact, pervious to other objects, do they have a direct influence on the organization of the response? The kinematics of macaques' reaching movements were examined by the current study that analysed some exemplars as they selectively reached to grasp a food item in the absence as well as in the presence of potential obstacles (i.e., stones) that could affect the arm trajectory. Changes in movement parameterization were noted in temporal measures, such as movement time, as well as in spatial ones, such as paths of trajectory. Generally speaking, the presence of stones in the vicinity of the acting hand stalled the reaching movement and affected the arm trajectory as the hand veered away from the stone even when it was not a physical obstacle. We concluded that nearby objects evoke a motor response in macaques, and the attentional mechanisms that allow for a successful action selection are revealed in the reaching path. The data outlined here concur with human studies indicating that potential obstacles are internally represented, a finding implying basic cognitive operations allowing for action selection in macaques.

Effects of intentional movement preparation on response times to symbolic and imitative cues.

Speeded responses to an external cue are slower when the cue interrupts preparation to perform the same or a similar action in a self-paced manner. To explore the mechanism underlying this 'cost of intention', we examined whether the size of the cost is influenced by the nature of the external cue. Specifically, we assessed whether the cost of intention is different for movements made in response to an imitative cue (an on-screen hand movement) compared to those made in response to a symbolic cue. Consistent with previous reports, externally cued responses were significantly slower on trials where participants were preparing to perform an internally driven movement later in the trial. Also as predicted, simple response times to the imitative cue were faster than those made to the symbolic cue. Critically, the cost of intention was similar for each cue type, suggesting that preparing an intentional action influenced responses cued by the symbolic and imitative cues to a similar degree. These findings suggest that the nature of the external cue does not influence the response time delay associated with concurrent intentional preparation. Together with previous findings, the results of the current study shed further light on the potential mechanisms underlying the cost of intention.

What is a number? The interplay between number and continuous magnitudes.

Leibovich et al. argue that it is impossible to control for all continuous magnitudes in a numerical task. We contend that continuous magnitudes (i.e., perimeter, area, density) can be simultaneously controlled. Furthermore, we argue that shedding light on the interplay between number and continuous magnitudes - rather than considering them independently - will provide a much more fruitful approach to understanding mathematical abilities.

Congruent and Incongruent Corticospinal Activations at the Level of Multiple Effectors.

Motor resonance is defined as the subliminal activation of the motor system while observing actions performed by others. However, resonating with another person's actions is not always an appropriate response: In real life, people do not just imitate but rather respond in a suitable fashion. A growing body of neurophysiologic studies has demonstrated that motor resonance can be overridden by complementary motor responses (such as preparing a precision grip on a small object when seeing an open hand in sign of request). In this study, we investigated the relationship between congruent and incongruent corticospinal activations at the level of multiple effectors. The modulation of motor evoked potentials evoked by single-pulse TMS over the motor cortex was assessed in upper and lower limb muscles of participants observing a soccer player performing a penalty kick straight in their direction. Study results revealed a double dissociation: Seeing the soccer player kicking the ball triggered a motor resonance in the observer's lower limb, whereas the upper limb response afforded by the object was overridden. On the other hand, seeing the ball approaching the observers elicited a complementary motor activation in upper limbs while motor resonance in lower limbs disappeared. Control conditions showing lateral kicks, mimicked kicks, and a ball in penalty area were also included to test the motor coding of object affordances. Results point to a modulation of motor responses in different limbs over the course of action and in function of their relevance in different contexts. We contend that ecologically valid paradigms are now needed to shed light on the motor system functioning in complex forms of interaction.

Kick with the finger: symbolic actions shape motor cortex excitability.

A large body of research indicates that observing actions made by others is associated with corresponding motor facilitation of the observer's corticospinal system. However, it is still controversial whether this matching mechanism strictly reflects the kinematics of the observed action or its meaning. To test this issue, motor evoked potentials induced by single-pulse transcranial magnetic stimulation were recorded from hand and leg muscles while participants observed a symbolic action carried out with the index finger, but classically performed with the leg (i.e., a soccer penalty kick). A control condition in which participants observed a similar (but not symbolic) hand movement was also included. Results showed that motor facilitation occurs both in the observer's hand (first dorsal interosseous) and leg (quadriceps femoris) muscles. The present study provides evidence that both the kinematics and the symbolic value of an observed action are able to modulate motor cortex excitability. The human motor system is thus not only involved in mirroring observed actions but is also finely tuned to their symbolic value.

How posture affects macaques' reach-to-grasp movements.

Although there is a wealth of behavioral data regarding grasping movements in non-human primates, how posture influences the kinematics of prehensile behavior is not yet clearly understood. The purpose of this study was to examine and compare kinematic descriptions of grip behaviors while primates (macaque monkeys) were in a sitting posture or when stopping after quadrupedal locomotion (i.e., tripedal stance). Video footage taken while macaques grasped objects was analyzed frame-by-frame using digitalization techniques. Each of the two grip types considered (power and precision grips) was found to be characterized by specific, distinct kinematic signatures for both the reaching and the grasping components when those actions were performed in a sitting position. The grasping component did not differentiate in relation to the type of grip that was needed when, instead, the prehensile action took place in a tripedal stance. Quadrupedal locomotion affected the concomitant organization of prehensile activities determining in fact a similar kinematic patterning for the two grips regardless of the size of the object to be grasped. It is suggested that using a single kinematic grip patterning for all prehensile activities might be both the by-product of planning a grasping action while walking and a way to simplify motor programming during unstable tripedal stance.

Reaching and grasping behavior in Macaca fascicularis: a kinematic study.

The prehensile hand is one of the major traits distinguishing primates from other mammal species. All primates, in fact, are able to grasp an object and hold it in part or entirely using a single hand. Although there is a wealth of behavioral data regarding grasping movements in humans and apes, there is relatively little material on macaques, the animal model often used to investigate neuronal mechanisms responsible for grip control in humans. To date, evidence regarding free-ranging macaques is confined to observational data, while quantitative reports describe studies carried out in laboratory settings or in captivity. The purpose of the present study was to provide the first kinematic descriptions of basic grip behavior with regard to precision and power grips in free-ranging macaque monkeys. Video footage of those animals grasping objects was analyzed frame-by-frame using digitalization techniques. The results revealed that the two types of grips considered are each characterized by specific kinematic signatures. It was also found that hand kinematics was scaled depending on the type of grasp needing to be adopted and the intrinsic properties of the object to be grasped. In accordance with data concerning humans, these findings indicate that the intrinsic features of an object affect the planning and control of reach-to-grasp movements even in free-ranging macaques. The data presented here take research in the field of comparative reach-to-grasp kinematics in human and non-human primates another step forward as they are based on precise measurements of spontaneous grasping movements by animals living/acting in their natural environment.

Grasping with tools: corticospinal excitability reflects observed hand movements.

Although facilitation of the corticospinal system during action observation is widely accepted, it remains controversial whether this facilitation reflects a replica of the observed movements or the goal of the observed motor acts. In the present study, we asked whether, when an object is grasped by using a tool, corticospinal facilitation represents 1) the movements of the hand, 2) the movements of the tool, or 3) the distal goal of the action. To address this question, we recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation while participants observed a hand reaching and grasping a mothball by using 3 types of pliers, requiring different hand-tool movements to achieve the same goal (grasping the object). We found that MEPs recorded from the opponens pollicis and from the first dorsal interosseous reflected the observed hand movements rather than the movements of the tool or the distal goal of the action. These results suggest that during observation of tool actions, detailed motor matching recruits online the same muscles as those used in the observed action.

What is missing in the study of emotion expression?

While approaching celebrations for the 150 years of "The Expression of the Emotions in Man and Animals", scientists' conclusions on emotion expression are still debated. Emotion expression has been traditionally anchored to prototypical and mutually exclusive facial expressions (e.g., anger, disgust, fear, happiness, sadness, and surprise). However, people express emotions in nuanced patterns and - crucially - not everything is in the face. In recent decades considerable work has critiqued this classical view, calling for a more fluid and flexible approach that considers how humans dynamically perform genuine expressions with their bodies in context. A growing body of evidence suggests that each emotional display is a complex, multi-component, motoric event. The human face is never static, but continuously acts and reacts to internal and environmental stimuli, with the coordinated action of muscles throughout the body. Moreover, two anatomically and functionally different neural pathways sub-serve voluntary and involuntary expressions. An interesting implication is that we have distinct and independent pathways for genuine and posed facial expressions, and different combinations may occur across the vertical facial axis. Investigating the time course of these facial blends, which can be controlled consciously only in part, is recently providing a useful operational test for comparing the different predictions of various models on the lateralization of emotions. This concise review will identify shortcomings and new challenges regarding the study of emotion expressions at face, body, and contextual levels, eventually resulting in a theoretical and methodological shift in the study of emotions. We contend that the most feasible solution to address the complex world of emotion expression is defining a completely new and more complete approach to emotional investigation. This approach can potentially lead us to the roots of emotional display, and to the individual mechanisms underlying their expression (i.e., individual emotional signatures).

Digital Intentions in the Fingers: I Know What You Are Doing with Your Smartphone.

Every day, we make thousands of finger movements on the touchscreen of our smartphones. The same movements might be directed at various distal goals. We can type "What is the weather in Rome?" in Google to acquire information from a weather site, or we may type it on WhatsApp to decide whether to visit Rome with a friend. In this study, we show that by watching an agent's typing hands, an observer can infer whether the agent is typing on the smartphone to obtain information or to share it with others. The probability of answering correctly varies with age and typing style. According to embodied cognition, we propose that the recognition process relies on detecting subtle differences in the agent's movement, a skill that grows with sensorimotor competence. We expect that this preliminary work will serve as a starting point for further research on sensorimotor representations of digital actions.

When Corticospinal Inhibition Favors an Efficient Motor Response.

Many daily activities involve responding to the actions of other people. However, the functional relationship between the motor preparation and execution phases still needs to be clarified. With the combination of different and complementary experimental techniques (i.e., motor excitability measures, reaction times, electromyography, and dyadic 3-D kinematics), we investigated the behavioral and neurophysiological signatures characterizing different stages of a motor response in contexts calling for an interactive action. Participants were requested to perform an action (i.e., stirring coffee or lifting a coffee cup) following a co-experimenter's request gesture. Another condition, in which a non-interactive gesture was used, was also included. Greater corticospinal inhibition was found when participants prepared their motor response after observing an interactive request, compared to a non-interactive gesture. This, in turn, was associated with faster and more efficient action execution in kinematic terms (i.e., a social motor priming effect). Our results provide new insights on the inhibitory and facilitatory drives guiding social motor response generation. Altogether, the integration of behavioral and neurophysiological indexes allowed us to demonstrate that a more efficient action execution followed a greater corticospinal inhibition. These indexes provide a full picture of motor activity at both planning and execution stages.

The Spatiotemporal Dynamics of Facial Movements Reveals the Left Side of a Posed Smile.

Humans can recombine thousands of different facial expressions. This variability is due to the ability to voluntarily or involuntarily modulate emotional expressions, which, in turn, depends on the existence of two anatomically separate pathways. The Voluntary (VP) and Involuntary (IP) pathways mediate the production of posed and spontaneous facial expressions, respectively, and might also affect the left and right sides of the face differently. This is a neglected aspect in the literature on emotion, where posed expressions instead of genuine expressions are often used as stimuli. Two experiments with different induction methods were specifically designed to investigate the unfolding of spontaneous and posed facial expressions of happiness along the facial vertical axis (left, right) with a high-definition 3-D optoelectronic system. The results showed that spontaneous expressions were distinguished from posed facial movements as revealed by reliable spatial and speed key kinematic patterns in both experiments. Moreover, VP activation produced a lateralization effect: compared with the felt smile, the posed smile involved an initial acceleration of the left corner of the mouth, while an early deceleration of the right corner occurred in the second phase of the movement, after the velocity peak.

Mirabegron and Anticholinergics in the Treatment of Overactive Bladder Syndrome: A Meta-analysis.

OBJECTIVE: To compare the use of mirabegron with anticholinergics drugs for the treatment of overactive bladder (OB). DATA SOURCE: Systematic searches were conducted in EMBASE, PUBMED, Cochrane, and LILACS databases from inception to September 2021. We included RCTs, women with clinically proven OB symptoms, studies that compared mirabegron to antimuscarinic drugs, and that evaluated the efficacy, safety or adherence. DATA COLLECTION: RevMan 5.4 was used to combine results across studies. We derived risk ratios (RRs) and mean differences with 95% CIs using a random-effects meta-analytic model. Cochrane Collaboration Tool and GRADE was applied for risk of bias and quality of the evidence. DATA SYNTHESIS: We included 14 studies with a total of 10,774 patients. Fewer total adverse events was reported in mirabegron group than in antimuscarinics group [RR 0.93 (0.89-0.98)]. The risk of gastrointestinal tract disorders and dry mouth were lower with mirabegron [RR 0,58 (0.48-0.68); 9375 patients; RR 0.44 (0.35-0.56), 9375 patients, respectively]. No difference was reported between mirabegron and antimuscarinics drugs for efficacy. The adherence to treatment was 87.7% in both groups [RR 0.99 (0.98-1.00)]. CONCLUSION: Mirabegron and antimuscarinics have comparable efficacy and adherence rates; however, mirabegron showed fewer total and isolated adverse events.

OBJETIVO: Comparar o uso de mirabegrom com anticolinérgicos para o tratamento da bexiga hiperativa (BH). FONTE DE DADOS: Buscas sistemáticas foram realizadas nas bases de dados EMBASE, PUBMED, Cochrane e LILACS desde o início até setembro de 2021. Incluímos ECR, mulheres com sintomas de BH clinicamente comprovados, estudos que compararam mirabegrom a medicamentos antimuscarínicos e avaliaram a eficácia, segurança ou adesão. COLETA DE DADOS: RevMan 5.4 foi usado para combinar os resultados entre os estudos. Derivamos razões de risco (RRs) e diferenças médias com intervalo de confiança (IC) de 95% usando um modelo meta-analítico de efeitos aleatórios. Cochrane Collaboration Tool e GRADE foi aplicado para risco de viés e qualidade da evidência. SíNTESE DOS DADOS: Foram incluídos 14 estudos com um total de 10.774 pacientes. Menos eventos adversos totais foram relatados no grupo mirabegrom do que no grupo antimuscarínicos [RR: 0,93 (0,89­0,98)]. O risco de distúrbios do trato gastrointestinal e boca seca foram menores com mirabegrom [RR: 0,58 (0,48­0,68); 9.375 pacientes; RR: 0,44 (0,35­0,56), 9.375 pacientes, respectivamente]. Nenhuma diferença foi relatada entre mirabegrom e drogas antimuscarínicos para eficácia. A adesão ao tratamento foi de 87,7% em ambos os grupos [RR: 0,99 (0,98­1,00)]. CONCLUSãO: Mirabegrom e antimuscarínicos têm eficácia e taxas de adesão comparáveis, porém o mirabegrom apresentou menos eventos adversos totais e isolados.

Social grasping: from mirroring to mentalizing.

Because the way we grasp an object varies depending on the intention with which the object is grasped, monitoring the properties of prehensile movements may provide access to a person's intention. Here we investigate the role of visual kinematics in the implicit coding of intention, by using functional brain imaging while participants observed grasping movements performed with social versus individual intents. The results show that activation within the mirror system is stronger during the observation of socially intended movements relative to individual movements. Moreover, areas that form the mentalizing system are more active during social grasping movements. These findings demonstrate that, in the absence of context information, social information conveyed by action kinematics modulates intention processing, leading to a transition from mirroring to mentalizing.

The transfer of motor functional strategies via action observation.

When someone is choosing one piece from a bowl full of fruit, many pieces are within reach and visible. Although the desired piece seems to govern the particular pattern and direction of that person's reaching movement, the selection process is not impervious to the presence of task-irrelevant information (i.e. the other fruits). Evidence suggests that the kinematics of reach-to-grasp actions for a desired object integrates the motor features of all the objects which might become potential targets. Transcranial magnetic stimulation (TMS) and motor-evoked potentials (MEPs) were used by us to establish if that motor integration process can be transferred to an onlooker. Our results indicate that observation of hybrid reach-to-grasp movement kinematics is reflected in the observer's pattern of MEP amplitudes. This effect can be defined as a form of motor resonance which operates by 'reading' the kinematics of an observed action. The brain's ability to mirror motor integration processes while observing someone else's action helps an onlooker to understand what the other person is doing and to predict his/her motor alternatives.

Corticospinal excitability and conductivity are related to the anatomy of the corticospinal tract.

Probing the brain structure-function relationship is at the heart of modern neuroscientific explorations, enabled by recent advances in brain mapping techniques. This study aimed to explore the anatomical blueprint of corticospinal excitability and shed light on the structure-function relationship within the human motor system. Using diffusion magnetic resonance imaging tractography, based on the spherical deconvolution approach, and transcranial magnetic stimulation (TMS), we show that anatomical inter-individual variability of the corticospinal tract (CST) modulates the corticospinal excitability and conductivity. Our findings show for the first time the relationship between increased corticospinal excitability and conductivity in individuals with a bigger CST (i.e., number of streamlines), as well as increased corticospinal microstructural organization (i.e., fractional anisotropy). These findings can have important implications for the understanding of the neuroanatomical basis of TMS as well as the study of the human motor system in both health and disease.

Corticospinal excitability is specifically modulated by the social dimension of observed actions.

A large body of research reports that perceiving body movements of other people activates motor representations in the observer's brain. This automatic resonance mechanism appears to be imitative in nature. However, action observation does not inevitably lead to symmetrical motor facilitation: mirroring the observed movement might be disadvantageous for successfully performing joint actions. In two experiments, we used transcranial magnetic stimulation (TMS) to investigate whether the excitability of the corticospinal system was selectively modulated by the social dimension of an observed action. We recorded motor-evoked potentials (MEPs) from right-hand muscles during the observation of an action sequence which, depending on context, might or might not elicit a complementary response. The results demonstrate a differential motor facilitation depending on action context. Specifically, when the context called for a complementary action, the excitability pattern reflected the under-threshold activation of a complementary action, whereas when the context did not imply acting in a complementary manner, the observer's corticospinal activity reflected symmetrical motor resonance. We contend that the mechanisms underlying action observation are flexible and respond to contextual factors that guide the social interaction between individuals beyond emulation.

Cooperation or competition? Discriminating between social intentions by observing prehensile movements.

Body movement provides a rich source of information about other people's goals and intentions. In the present study, we examined a particular aspect concerned with the interpretation of bodily movement--how well people can distinguish between different social intentions by observing a reach-to-grasp movement. To ascertain to what extent intention-from-motion judgements rely on visual kinematics, we compared prediction performance on a typical temporal-occlusion video task with prediction performance on a temporal-occlusion point-light task. In the video task, participants observed videos showing a model reaching towards and grasping a wooden block with different intents: to cooperate with a partner in building a tower, compete with an opponent to be the first to put the object in the middle of the working surface, or perform an individual action. In the point-light task, participants observed point-light displays of the same movements. Although predictions were more accurate for the video task, prediction performance was not disrupted for the point-light task, suggesting that essential kinematic information available in point-light displays was indeed sufficient for intention-from-motion judgement. Importantly, the same kinematic landmarks were used to discriminate between social intentions for the video and the point-light task. This suggests that observers not only have the ability to use kinematic information when no other information is available, but they use kinematic information to discriminate between intentions when watching the motion of others under full light conditions.