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Down syndrome (DS) is a genetic disorder characterized by intellectual disability whose etiology includes an additional partial or full copy of chromosome 21. Brain surface morphometry analyses can potentially assist in providing a better understanding of structural brain differences, and may help characterize DS-specific neurodevelopment. We performed a retrospective surface morphometry study of 73 magnetic resonance imaging (MRI) examinations of DS patients (aged 1 day to 22 years) and compared them to a large cohort of 993 brain MRI examinations of neurotypical participants, aged 1 day to 32 years. Surface curvature measurements, absolute surface area measurements, and surface areas as a percentage of total brain surface area (%TBSA) were extracted from each brain region in each examination. Results demonstrate broad reductions in surface area and abnormalities of surface curvature measurements across the brain in DS. After adjusting our regional surface area measurements as %TBSA, abnormally increased presentation in DS relative to neurotypical controls was observed in the left precentral, bilateral entorhinal, left parahippocampal, and bilateral perirhinal cortices, as well as Brodmann’s area 44 (left), and the right temporal pole. Findings suggest the presence of developmental abnormalities of regional %TBSA in DS that can be characterized from clinical MRI examinations.

Temporal recalibration (TR) may arise to realign asynchronous stimuli after exposure to a short, constant delay between voluntary movement and sensory stimulus. The objective of this study was to determine if awareness of the temporal lag between a motor response (i.e., a keypress) and a sensory event (i.e., a visual flash) is necessary for TR to occur. We further investigated whether manipulating the required motor and perceptual judgment tasks modified the influence of awareness on TR. Participants (n = 48) were randomly divided between two groups (Group 1: Aware and Group 2: Unaware). The Aware group was told of the temporal lag between their keypress and visual flash at the beginning of the experiment, whereas the Unaware group was not. All participants completed 8 blocks of trials, in which the motor task (single or repetitive tap), perceptual judgment task (judging the temporal order of the keypress in relation to the visual flash or judging whether the two stimuli were simultaneous or not), and fixed temporal lag between keypress and visual flash (0 ms or 100 ms) varied. TR was determined by comparing judgments between corresponding blocks of trials in which the temporal lag was 0 ms and 100 ms. Results revealed that both the Aware and Unaware groups demonstrated a similar magnitude of TR across all motor and perceptual judgment tasks, such that the magnitude of TR did not vary between Aware and Unaware participants. These results suggest that awareness of a temporal lag does not influence the magnitude of TR achieved and that motor and perceptual judgment task demands do not modulate the influence of awareness on TR.

When a two-choice “Simon task” is distributed between two people, performance in the shared go/no-go task resembles performance in the whole task alone. This finding has been described as the joint Simon effect (JSE). Unlike the individual go/no-go task, not only is the typical joint Simon task shared with another person, but also the imperative stimuli dictate whose turn it is to respond. Therefore, in the current study, we asked whether removing the agent discrimination component of the joint Simon task influences co-representation. Participants performed the typical joint Simon task, which was compared to two turn-taking versions of the task. For these turn-taking tasks, pairs predictably alternated turns on consecutive trials, with their respective imperative stimulus presented either on 100% of their turns (fully predictable group) or on 83% of their turns (response-uncertainty group, 17% no-go catch trials). The JSE was absent in the fully predictable, turn-taking task, but emerged similarly under the response-uncertainty condition and the typical joint Simon task condition where there is both turn and response-execution-related uncertainty. These results demonstrate that conflict related to agent discrimination is likely not a critical factor driving the JSE, whereas conflict surrounding the need to execute a response (and hence the degree of preparation) appears fundamental to co-representation.

Background The infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing relapsing malaria, into hypnozoites that can lie dormant for extended periods of time before activating. The liver stages of Plasmodium remain elusive because of technical challenges, including low infection rate. This has been hindering experimentations with well-established technologies, such as electron microscopy. A deeper understanding of hypnozoite biology could prove essential in the development of radical cure therapeutics against malaria. Results The liver stages of the rodent parasite Plasmodium berghei , causing non-relapsing malaria, and the simian parasite Plasmodium cynomolgi , causing relapsing malaria, were characterized in human Huh7 cells or primary non-human primate hepatocytes using Correlative Light-Electron Microscopy (CLEM). Specifically, CLEM approaches that rely on GFP-expressing parasites (GFP-CLEM) or on an immunofluorescence assay (IFA-CLEM) were used for imaging liver stages. The results from P. berghei showed that host and parasite organelles can be identified and imaged at high resolution using both CLEM approaches. While IFA-CLEM was associated with more pronounced extraction of cellular content, samples’ features were generally well preserved. Using IFA-CLEM, a collection of micrographs was acquired for P. cynomolgi liver stage schizonts and hypnozoites, demonstrating the potential of this approach for characterizing the liver stages of Plasmodium species causing relapsing malaria. Conclusions A CLEM approach that does not rely on parasites expressing genetically encoded tags was developed, therefore suitable for imaging the liver stages of Plasmodium species that lack established protocols to perform genetic engineering. This study also provides a dataset that characterizes the ultrastructural features of liver stage schizonts and hypnozoites from the simian parasite species P. cynomolgi . Graphical Abstract

Targeted protein degradation (TPD) is a novel strategy for developing therapeutics against pathogens. Prior to causing malaria, Plasmodium parasites replicate within hepatocytes as liver stages, surrounded by a parasitophorous vacuole membrane (PVM). We hypothesized that TPD can be employed to trigger host-driven degradation of essential liver stage PVM proteins and lead to parasite death. To explore this, we took advantage of the proteolysis-targeting-chimera HaloPROTAC3, a molecule that recruits the host von Hippel-Lindau (VHL) E3 ligase to the HaloTag (HT). Parasites expressing HT fused to the host cytosol-exposed domain of the PVM protein UIS4 (UIS4-HT) were generated in Plasmodium berghei and Plasmodium cynomolgi , but only P. berghei UIS4-HT enabled productive liver stage infection experiments in vitro. Although HaloPROTAC3 triggered the degradation of HT proteins in host cells, it had no impact on the survival of P. berghei UIS4-HT liver stages. Furthermore, HaloPROTAC3 bound to P. berghei UIS4-HT but did not recruit VHL or trigger ubiquitination of the PVM. Overall, although this study did not establish whether host-driven TPD can degrade Plasmodium PVM proteins, it highlights the challenges of developing TPD approaches against novel targets and offers insights for advancing this therapeutic strategy against pathogens.

A crew of two rowing together in perfect synchrony is an example of a task that requires each performer to maintain meticulous timing when coordinating their movements with the other. At the individual level, temporal coordination of the limbs has been observed in bimanual pointing movements even when made to targets of different distance. Timing of the arms is not independent; rather there is a natural temporal coupling. The aim of this experiment was to investigate whether the temporal characteristics of pointing movements can be observed under joint conditions. Sixteen pairs of participants made short and long, unimanual and bimanual pointing movements. In the unimanual and bimanual solo conditions, participants made the movements alone. In the joint condition, each participant contributed one arm to the joint “bimanual” movements. Absolute temporal coupling at movement initiation and termination was measured by the differences in reaction time and total response time. Relative temporal coupling at movement initiation and termination was measured by correlating reaction time and total response time of the left and right limbs. Pointing movements had synchronous movement termination in the bimanual solo conditions and asynchronous termination in the unimanual solo and bimanual joint conditions. The initiation and termination of the arms were not correlated in the unimanual solo condition (initiation r = 0.01, termination r = 0.03). Small-to-medium correlations (r = 0.19, r = 0.24) were observed in the bimanual joint condition, and they were larger than the unimanual solo condition (p = 0.022, p = 0.063). As expected, there were large correlations in the bimanual solo conditions (r = 0.91, r = 0.81). Our findings suggest that absolute temporal coupling does not occur between individuals, but there is evidence for relative temporal coupling in the bimanual joint condition.

Purpose: The aim of this study was twofold: (a) to measure and compare motor proficiency in obese children with Prader-Willi syndrome (OB-PWS) to that in obese children without PWS (OB), and (b) to compare motor proficiency in OB-PWS and OB to normative data. Method: Motor proficiency was measured using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition-Complete Form, a norm-referenced assessment of motor function. Participants were 18 OB-PWS and 44 OB (8 to 11 years of age). The scores on the 8 subtests and the total motor composite were used to compare OB-PWS and OB. Furthermore, the scores on the 4 motor-area composites were used to compare OB-PWS and OB against normative data. Results: OB-PWS scored significantly lower than OB across all 8 subtests. OB-PWS also had significantly lower motor proficiency scores on all motor-area composites when compared with the normative sample. OB-PWS most frequently (67%-83%) scored well below average on the gross motor subtests. Although not as high as on the gross motor subtests, this finding also held true for the fine motor subtests with 39% to 45% of OB-PWS scoring well below average. Conclusion: Motor proficiency is very poor in OB-PWS, in particular for gross motor skills. Physical, neurological, and developmental characteristics inherent to the syndrome may explain this low performance.

The application of technologies, such as video gaming and social media for rehabilitation, is garnering interest in the medical field. However, little research has examined clinicians' perspectives regarding technology adoption by their clients. The objective of our study was to explore therapists' perceptions of how young people and adults with hemiplegia use gaming and social media technologies in daily life and in rehabilitation, and to identify barriers to using these technologies in rehabilitation. We conducted two focus groups comprised of ten occupational therapists/physiotherapists who provide neurorehabilitation to individuals with hemiplegia secondary to stroke or cerebral palsy. Data was analyzed using inductive thematic analysis. The diffusion of innovations theory provided a framework to interpret emerging themes. Therapists were using technology in a limited capacity. They identified barriers to using social media and gaming technology with their clients, including a lack of age appropriateness, privacy issues with social media, limited transfer of training, and a lack of accessibility of current systems. Therapists also questioned their role in the context of technology-based interventions. The opportunity for social interaction was perceived as a major benefit of integrated gaming and social media. This study reveals the complexities associated with adopting new technologies in clinical practice, including the need to consider both client and clinician factors. Despite reporting several challenges with applying gaming and social media technology with clinical populations, therapists identified opportunities for increased social interactions and were willing to help shape the development of an upper limb training system that could more readily meet the needs of clients with hemiplegia. By considering the needs of both therapists and clients, technology developers may increase the likelihood that clinicians will adopt innovative technologies.

Sebanz et al. (Cognition 88:B11–B21, 2003) have shown that spatial correspondence effects are observed even when the two-choice reaction time task is distributed between two people, such that each person is assigned only one of two possible stimulus–response (S–R) pairings. The effect is similar to when one person is assigned and responds to both S–R pairings. These results have been taken to suggest that two people performing a complementary task co-represent each other’s response alternatives. In our experiment, we examined performance when paired participants responded to the same S–R alternative. We reasoned that co-representation would be of little advantage as the task alternatives would be the same for both participants. Correspondence effects were absent when paired participants responded to the same S–R alternative but emerged when they responded to different alternatives.

Digital technology is becoming an increasingly popular means of delivering meaningful therapy to individuals with neurological impairments. An understanding of clients' technology use and their perspectives on incorporating technology into rehabilitation can provide researchers and designers with valuable information to inform development of technologies and technology-based rehabilitation programs. This study was designed to establish the current use and perceptions of gaming, social media, and robotics technologies for rehabilitative purposes from the perspective of adults and children with upper limb impairments to identify barriers and enablers to their adoption and use. We conducted three focus groups consisting of pediatric (n=7, mean age 11.0 years) and adult (n=8, mean age 60.8 years) participants with hemiparesis affecting their upper limb. We applied thematic analysis methods to the resulting data. We identified three key themes: (1) clients' use of technology in everyday life and rehabilitation, (2) barriers to use, and (3) enablers to therapy. Participants had limited exposure to technology for therapeutic purposes, but all acknowledged the potential benefits in providing motivation and interest for the performance of repetitive task practice. Adult participants requested efficacious, simple, and easy-to-use technology for rehabilitation with programs that could be individualized for them and expressed that they wanted these programs to provide a motivating means of repeated practice of therapeutic movements. In contrast, pediatric participants emphasized a desire for technology for rehabilitation that offered opportunities for social interaction and interactive games involving their whole body and not only their affected limb. Perceived safety and privacy were concerns for both groups. Our findings highlight that all participants were open to the integration of technology into rehabilitation. Adult participants were more pragmatically motivated by potential recovery gains, whereas pediatric participants were more intrinsically motivated by access to games.