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Finding muscle activity generating a given motion is a redundant problem, since there are many more muscles than degrees of freedom. The control strategies determining muscle recruitment from a redundant set are still poorly understood. One theory of motor control suggests that motion is produced through activating a small number of muscle synergies, i.e. muscle groups that are activated in a fixed ratio by a single input signal. Because of the reduced number of input signals, synergy-based control is low dimensional. But a major criticism on the theory of synergy-based control of muscles is that muscle synergies might reflect task constraints rather than a neural control strategy. Another theory of motor control suggests that muscles are recruited by optimizing performance. Optimization of performance has been widely used to calculate muscle recruitment underlying a given motion while assuming independent recruitment of muscles. If synergies indeed determine muscle recruitment underlying a given motion, optimization approaches that do not model synergy-based control could result in muscle activations that do not show the synergistic muscle action observed through electromyography (EMG). If, however, synergistic muscle action results from performance optimization and task constraints (joint kinematics and external forces), such optimization approaches are expected to result in low-dimensional synergistic muscle activations that are similar to EMG-based synergies. We calculated muscle recruitment underlying experimentally measured gait patterns by optimizing performance assuming independent recruitment of muscles. We found that the muscle activations calculated without any reference to synergies can be accurately explained by on average four synergies. These synergies are similar to EMG-based synergies. We therefore conclude that task constraints and performance optimization explain synergistic muscle recruitment from a redundant set of muscles.

Recently there has been a growing interest in the modular organization of leg movements, in particular those related to locomotion. One of the basic modules involves the flexion of the leg during swing and it was shown that this module is already present in neonates (Dominici, et al. 2011). In this paper, we question how these finding build upon the original work by Sherrington, who proposed that the flexor reflex is the basic building block of the flexion during swing phase. Similarly, the relation between the flexor reflex and the withdrawal reflex modules of Schouenborg et al. (1994) will be discussed. It will be argued that there is large overlap between these notions on modules and the older concepts of reflexes. In addition, it will be shown that there is a great flexibility in the expression of some of these modules during gait, thereby allowing for a phase-dependent modulation of the appropriate responses. In particular, the end of the stance phase is a period when the flexor synergy is facilitated. It is proposed that this is linked to the activation of circuitry that is responsible for the generation of locomotor patterns (CPG, central pattern generator). More specifically, it is suggested that the responses in that period relate to the activation of a flexor burst generator. The latter structure forms the core of a new asymmetric model of the CPG. This activation is controlled by afferent input (facilitation by a broad range of afferents, suppression by load afferent input). Meanwhile, many of these physiologic features have found their way in the control of very flexible walking bipedal robots.

Introduction: The main objective of this study is to examine chronic pain and limping in relation to lower extremity and pelvic fracture location in addition to fracture combinations if multiple fractures are present on the same leg that have not been previously reported. We hypothesize that fracture pattern and location of lower extremity and pelvis fractures of multiple injured patients influence their long-term pain outcome., Materials and Methods: Retrospective cohort study. Patients with treated multiple lower limb and pelvic fractures at a level 1 trauma center and followed up for at least 10 years postinjury were assessed. Lower leg pain subdivided into persistent, load-dependent and intermittent pain, as well as limping were recorded by using self-administered patient questionnaires and standardized physical examinations performed by a trauma surgeon. Descriptive statistics were used to present comparative measurements between groups., Results: Fifty-seven percent of patients (n = 301) showed chronic lower limb pain 10 years postinjury. Ten percent of all patients with chronic pain displayed persistent pain, and here the most common fracture combination was tibial shaft fractures in combination with femoral shaft or proximal tibial fractures (13%). One hundred fifty-one patients reported load-dependent pain, with the most common fracture combinations being fractures of the foot in combination with femoral shaft fractures or distal tibial fractures (11%). One hundred twenty patients reported intermittent pain, with the most common fracture combinations involving the shaft of the tibia with either the femoral shaft or distal tibia (9%). Two hundred fifteen patients showed a persistent limp, and here the most common fractures were fractures of the femoral shaft (19%), tibial shaft (17%), and pelvis (15%)., Conclusions: In multiple injured patients with lower extremity injuries, the combination of fractures and their location are critical factors in long-term outcome. Patients with chronic persistent or load-dependent pain often had underlying femoral shaft fractures in combination with joint fractures., (© 2022. The Author(s).)

Aims/hypothesis: Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes., Methods: Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery. Following incubation of primary human skeletal muscle cells (hSkMCs) and murine AML12 hepatocytes with WISP1 and insulin, insulin signalling was analysed by western blotting. The effect of WISP1 on insulin-stimulated glycogen synthesis and gluconeogenesis was investigated in hSkMCs and murine hepatocytes, respectively., Results: Circulating WISP1 levels were higher in obese men (independent of diabetes status) than in normal-weight men (mean [95% CI]: 70.8 [55.2, 86.4] ng/l vs 42.6 [28.5, 56.6] ng/l, respectively; p < 0.05). VAT WISP1 expression was 1.9-fold higher in obese men vs normal-weight men (p < 0.05). Circulating WISP1 levels were positively associated with blood glucose in the OGTT and circulating haem oxygenase-1 and negatively associated with adiponectin levels. In hSkMCs and AML12 hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor, Akt and its substrates glycogen synthase kinase 3β, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes., Conclusions/interpretation: Circulating WISP1 levels and WISP1 expression in VAT are increased in obesity independent of glycaemic status. Furthermore, WISP1 impaired insulin signalling in muscle and liver cells.

Objective: To assess the functioning of mesolimbic and fronto-striatal areas involved in reward-based spatial learning in teenaged girls with bulimia nervosa (BN) that might be involved in the development and maintenance of maladaptive behaviors characteristic of the disorder., Method: We compared functional magnetic resonance imaging blood oxygen level-dependent response in 27 adolescent girls with BN to that of 27 healthy, age-matched control participants during a reward-based learning task that required learning to use extra-maze cues to navigate a virtual 8-arm radial maze to find hidden rewards. We compared groups in their patterns of brain activation associated with reward-based spatial learning versus a control condition in which rewards were unexpected because they were allotted pseudo-randomly to experimentally prevent learning., Results: Both groups learned to navigate the maze to find hidden rewards, but group differences in brain activity associated with maze navigation and reward processing were detected in the fronto-striatal regions and right anterior hippocampus. Unlike healthy adolescents, those with BN did not engage the right inferior frontal gyrus during maze navigation, activated the right anterior hippocampus during the receipt of unexpected rewards (control condition), and deactivated the left superior frontal gyrus and right anterior hippocampus during expected reward receipt (learning condition). These patterns of hippocampal activation in the control condition were significantly associated with the frequency of binge-eating episodes., Conclusion: Adolescents with BN displayed abnormal functioning of the anterior hippocampus and fronto-striatal regions during reward-based spatial learning. These findings suggest that an imbalance in control and reward circuits may arise early in the course of BN. Clinical trial registration information-An fMRI Study of Self-Regulation in Adolescents With Bulimia Nervosa; https://clinicaltrials.gov/; NCT00345943., Competing Interests: Drs. Cyr, Wang, Tau, Friedl, Marsh, Mr. Zhao, Ms. Stefan, and Ms. Terranova report no biomedical financial interests or potential conflicts of interest., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Unlabelled: OBJECTIVE : The purpose of this study was to elicit feedback from simulation technicians prior to developing the first simulation technician-specific simulation laboratory in Akron, OH., Background: Simulation technicians serve a vital role in simulation centers within hospitals/health centers around the world. The first simulation technician degree program in the US has been approved in Akron, OH. To satisfy the requirements of this program and to meet the needs of this special audience of learners, a customized simulation lab is essential., Method: A web-based survey was circulated to simulation technicians prior to completion of the lab for the new program. The survey consisted of questions aimed at identifying structural and functional design elements of a novel simulation center for the training of simulation technicians. Quantitative methods were utilized to analyze data., Results: Over 90% of technicians (n=65) think that a lab designed explicitly for the training of technicians is novel and beneficial. Approximately 75% of respondents think that the space provided appropriate audiovisual (AV) infrastructure and space to evaluate the ability of technicians to be independent. The respondents think that the lab needed more storage space, visualization space for a large number of students, and more space in the technical/repair area. CONCLUSIONS : A space designed for the training of simulation technicians was considered to be beneficial. This laboratory requires distinct space for technical repair, adequate bench space for the maintenance and repair of simulators, an appropriate AV infrastructure, and space to evaluate the ability of technicians to be independent.

The recent steep decline in Iran's birthrate poses methodological and interpretive challenges insofar as statistical information on demographic factors cannot satisfactorily establish causalities or delineate processes of change. Our research suggests that this decline rests on the interplay of socio-cultural "idea" variables that augment factors of the developmental paradigm commonly used in population studies. Especially modernist ideas labeled "progress" in Iran have influenced reproductive behavior. Aiming to demonstrate the usefulness of idea-oriented qualitative research for understanding demographic dynamics represented quantitatively in the literature, we contribute to an explanation of a particular case as well as to demographic research methods., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

The Oct-2 transcription factor contains an inhibitory domain which is able to repress transcription following DNA binding. Here we show that within the neuronally expressed Oct-2.5 form, the inhibitory domain can strongly inhibit activation by transcription factor activation domains which are either composed predominantly of acidic residues or contain the HOB motif, whereas it has a weaker effect or no effect on proline-rich activation domains and on a glutamine-rich domain. In contrast, the isolated inhibitory domain of Oct-2 can efficiently repress all types of activation domains. This effect is observed however, only on TATA box-containing promoters and not on promoters containing an initiator motif. This widespread inhibition of different activation domains and its dependence on the nature of the basal promoter elements indicate that the inhibitory domain is likely to act by contacting a common downstream target of activation domains within the basal transcriptional complex bound at the TATA box rather than quenching specific activation domains by direct interaction. These effects are discussed in terms of the functional role of the inhibitory domain within Oct-2.5 and the mechanism by which it acts.

The B cell-specific activity of immunoglobulin (Ig) gene promoters is to a large extent mediated by the conserved octamer motif ATTTGCAT. This requires the DNA binding octamer factors Oct-1 and/or Oct-2, as well as an additional B cell-restricted non-DNA binding cofactor. We recently cloned such a coactivator specific for Oct-1 or Oct-2 from human B cells and called it OBF-1. Here we report the isolation and characterization of the murine homologue. Full-length cDNA clones as well as genomic clones were isolated and the gene structure was determined. The deduced protein sequence shows that the mouse protein has an identical length, is likewise proline rich and shows 89% overall identity to the human protein. The OBF-1 gene is expressed in a very highly B cell-specific manner and is transcribed in cells representative of all stages of B cell differentiation, including the earliest ones. We show that OBF-1 interacts in the absence of DNA with the POU domain of Oct-1 or Oct-2 and also with the general transcription factors TBP and TFIIB. Furthermore, we demonstrate that although OBF-1 efficiently activates promoter octamer sites, it does not activate enhancer octamer sites.

The lymphoid-specific transcription factor Oct-2a contains two transcriptional activation domains which are located within the N-terminal and C-terminal regions. To study their differential activation properties, we linked the isolated effector domains to the GAL4 DNA-binding domain. We have shown that both activating regions of Oct-2a, isolated from their natural context, can activate transcription as promoter factors. In contrast to the C-terminus, activation by the N-terminal domain is dependent on a yet unidentified factor(s) binding to the simian virus 40 enhancer. The results obtained by duplication of activation domains or their mixed combination suggest that the domains are functionally independent. However, activation from a remote position could only be achieved with the C-terminus of Oct-2a in B cells. In lymphoid cells, higher activation levels were observed, suggesting that distinct B-cell-specific cofactors in concert with the effector domains of Oct-2a might be involved in mediating transcription from proximal and remote positions. Furthermore, we identified a repression domain at the N-terminus of Oct-2a. When transferred to a potent activator, transcriptional stimulation was inhibited efficiently. These results underscore the modular structure of Oct-2a with separable domains for activation and repression and suggest that Oct-2a might have complex regulatory functions in vivo.

The complete nucleotide sequence of simian foamy virus type 3 (SFV-3) strain LK-3, isolated from an African green monkey, was determined. In addition to translation frames representing the gag, pol, and env genes, two open reading frames are located in the region between the env gene and the 3' long terminal repeat (LTR). Both SFV-3 and SFV-1 encode two open reading frames between env and the 3' LTR, whereas HFV encodes three open reading frames in this region. Northern blot analysis of cell cultures infected with SFV-3 revealed subgenomic RNAs for these open reading frames. The protease of SFV-3 is encoded by the pol gene in contrast to HFV which encodes the protease in the gag gene. Notably, the pol gene of SFV-3 in the +1 translational frame relative to the gag gene; this observation is in agreement with SFV-1, but differs for HFV and all other retrovirus genomes reported. Thus, gag-pol precursors of the SFVs appear to be expressed by a +1 frameshift. Nucleotide and deduced amino acid alignments of SFV-3, SFV-1, and HFV revealed an unexpected homology pattern; highest homologies are observed in the pol and env genes but low homologies are noted in the gag genes and the additional open reading frames. Analysis of phylogenetic trees confirms the classification of foamy viruses as a subfamily of retroviruses, distinct from the lentiviruses and oncoviruses.