Non-linear stimulus-response behavior of the human stance control system is predicted by optimization of a system with sensory and motor noise

We developed a theory of human stance control that predicted (1) how subjects re-weight their utilization of proprioceptive and graviceptive orientation information in experiments where eyes closed stance was perturbed by surface-tilt stimuli with different amplitudes, (2) the experimentally observed increase in body sway variability (i.e. the “remnant” body sway that could not be attributed to the stimulus) with increasing surface-tilt amplitude, (3) neural controller feedback gains that determine the amount of corrective torque generated in relation to sensory cues signaling body orientation, and (4) the magnitude and structure of spontaneous body sway. Responses to surface-tilt perturbations with different amplitudes were interpreted using a feedback control model to determine control parameters and changes in these parameters with stimulus amplitude. Different combinations of internal sensory and/or motor noise sources were added to the model to identify the properties of noise sources that were able to account for the experimental remnant sway characteristics. Various behavioral criteria were investigated to determine if optimization of these criteria could predict the identified model parameters and amplitude-dependent parameter changes. Robust findings were that remnant sway characteristics were best predicted by models that included both sensory and motor noise, the graviceptive noise magnitude was about ten times larger than the proprioceptive noise, and noise sources with signal-dependent properties provided better explanations of remnant sway. Overall results indicate that humans dynamically weight sensory system contributions to stance control and tune their corrective responses to minimize the energetic effects of sensory noise and external stimuli

Intermittent control models of human standing: similarities and differences

Two architectures of intermittent control are compared and contrasted in the context of the single inverted pendulum model often used for describing standing in humans. The architectures are similar insofar as they use periods of open-loop control punctuated by switching events when crossing a switching surface to keep the system state trajectories close to trajectories leading to equilibrium. The architectures differ in two significant ways. Firstly, in one case, the open-loop control trajectory is generated by a system-matched hold, and in the other case, the open-loop control signal is zero. Secondly, prediction is used in one case but not the other. The former difference is examined in this paper. The zero control alternative leads to periodic oscillations associated with limit cycles; whereas the system-matched control alternative gives trajectories (including homoclinic orbits) which contain the equilibrium point and do not have oscillatory behaviour. Despite this difference in behaviour, it is further shown that behaviour can appear similar when either the system is perturbed by additive noise or the system-matched trajectory generation is perturbed. The purpose of the research is to come to a common approach for understanding the theoretical properties of the two alternatives with the twin aims of choosing which provides the best explanation of current experimental data (which may not, by itself, distinguish beween the two alternatives) and suggesting future experiments to distinguish between the two alternatives

Self versus Environment Motion in Postural Control

To stabilize our position in space we use visual information as well as non-visual physical motion cues. However, visual cues can be ambiguous: visually perceived motion may be caused by self-movement, movement of the environment, or both. The nervous system must combine the ambiguous visual cues with noisy physical motion cues to resolve this ambiguity and control our body posture. Here we have developed a Bayesian model that formalizes how the nervous system could solve this problem. In this model, the nervous system combines the sensory cues to estimate the movement of the body. We analytically demonstrate that, as long as visual stimulation is fast in comparison to the uncertainty in our perception of body movement, the optimal strategy is to weight visually perceived movement velocities proportional to a power law. We find that this model accounts for the nonlinear influence of experimentally induced visual motion on human postural behavior both in our data and in previously published results

Debating the Desirability of New Biomedical Technologies: Lessons from the Introduction of Breast Cancer Screening in the Netherlands

Health technology assessment (HTA) was developed in the 1970s and 1980s to facilitate decision making on the desirability of new biomedical technologies. Since then, many of the standard tools and methods of HTA have been criticized for their implicit normativity. At the same time research into the character of technology in practice has motivated philosophers, sociologists and anthropologists to criticize the traditional view of technology as a neutral instrument designed to perform a specific function. Such research suggests that the tools and methods of more traditional forms of HTA are often inspired by an ‘instrumentalist’ conception of technology that does not fit the way technology actually works. This paper explores this hypothesis for a specific case: the assessments and deliberations leading to the introduction of breast cancer screening in the Netherlands. After reconstructing this history of HTA ‘in the making’ the stepwise model of HTA that emerged during the process is discussed. This model was rooted indeed in an instrumentalist conception of technology. However, a more detailed reconstruction of several episodes from this history reveals how the actors already experienced the inadequacy of some of the instrumentalist presuppositions. The historical case thus shows how an instrumentalist conception of technology may result in implicit normative effects. The paper concludes that an instrumentalist view of technology is not a good starting point for HTA and briefly suggests how the fit between HTA methods and the actual character of technology in practice might be improved

Protein kinase C α and ε phosphorylation of troponin and myosin binding protein C reduce Ca2+ sensitivity in human myocardium

Previous studies indicated that the increase in protein kinase C (PKC)-mediated myofilament protein phosphorylation observed in failing myocardium might be detrimental for contractile function. This study was designed to reveal and compare the effects of PKCα- and PKCε-mediated phosphorylation on myofilament function in human myocardium. Isometric force was measured at different [Ca2+] in single permeabilized cardiomyocytes from failing human left ventricular tissue. Activated PKCα and PKCε equally reduced Ca2+ sensitivity in failing cardiomyocytes (ΔpCa50 = 0.08 ± 0.01). Both PKC isoforms increased phosphorylation of troponin I- (cTnI) and myosin binding protein C (cMyBP-C) in failing cardiomyocytes. Subsequent incubation of failing cardiomyocytes with the catalytic subunit of protein kinase A (PKA) resulted in a further reduction in Ca2+ sensitivity, indicating that the effects of both PKC isoforms were not caused by cross-phosphorylation of PKA sites. Both isozymes showed no effects on maximal force and only PKCα resulted in a modest significant reduction in passive force. Effects of PKCα were only minor in donor cardiomyocytes, presumably because of already saturated cTnI and cMyBP-C phosphorylation levels. Donor tissue could therefore be used as a tool to reveal the functional effects of troponin T (cTnT) phosphorylation by PKCα. Massive dephosphorylation of cTnT with alkaline phosphatase increased Ca2+ sensitivity. Subsequently, PKCα treatment of donor cardiomyocytes reduced Ca2+ sensitivity (ΔpCa50 = 0.08 ± 0.02) and solely increased phosphorylation of cTnT, but did not affect maximal and passive force. PKCα- and PKCε-mediated phosphorylation of cMyBP-C and cTnI as well as cTnT decrease myofilament Ca2+ sensitivity and may thereby reduce contractility and enhance relaxation of human myocardium

The Effectiveness of Mindfulness Training for Children with ADHD and Mindful Parenting for their Parents

This study evaluated the effectiveness of an 8-week mindfulness training for children aged 8–12 with ADHD and parallel mindful parenting training for their parents. Parents (N = 22) completed questionnaires on their child’s ADHD and ODD symptoms, their own ADHD symptoms, parenting stress, parental overreactivity, permissiveness and mindful awareness before, immediately after the 8-week training and at 8-week follow-up. Teachers reported on ADHD and ODD behavior of the child. A within-group waitlist was used to control for the effects of time and repeated measurement. Training was delivered in group format. There were no significant changes between wait-list and pre-test, except on the increase of teacher-rated ODD behavior. There was a significant reduction of parent-rated ADHD behavior of themselves and their child from pre-to posttest and from pre- to follow-up test. Further, there was a significant increase of mindful awareness from pre-to posttest and a significant reduction of parental stress and overreactivity from pre-to follow-up test. Teacher-ratings showed non-significant effects. Our study shows preliminary evidence for the effectiveness of mindfulness for children with ADHD and their parents, as rated by parents. However, in the absence of substantial effects on teacher-ratings, we cannot ascertain effects are due to specific treatment procedures

Cell-to-cell variability in troponin I phosphorylation in a porcine model of pacing-induced heart failure

We tested the hypothesis that myocardial contractile protein phosphorylation and the Ca2+ sensitivity of force production are dysregulated in a porcine model of pacing-induced heart failure (HF). The level of protein kinase A (PKA)-dependent cardiac troponin I (TnI) phosphorylation was lower in the myocardium surrounding the pacing electrode (pacing site) of the failing left ventricle (LV) than in the controls. Immunohistochemical assays of the LV pacing site pointed to isolated clusters of cardiomyocytes exhibiting a reduced level of phosphorylated TnI. Flow cytometry on isolated and permeabilized cardiomyocytes revealed a significantly larger cell-to-cell variation in the level of TnI phosphorylation of the LV pacing site than in the opposite region in HF or in either region in the controls: the interquartile range (IQR) on the distribution histogram of relative TnI phosphorylation was wider at the pacing site (IQR = 0.53) than that at the remote site of HF (IQR = 0.42; P = 0.0047) or that of the free wall of the control animals (IQR = 0.36; P = 0.0093). Additionally, the Ca2+ sensitivities of isometric force production were higher and appeared to be more variable in single permeabilized cardiomyocytes from the HF pacing site than in the healthy myocardium. In conclusion, the level of PKA-dependent TnI phosphorylation and the Ca2+ sensitivity of force production exhibited a high cell-to-cell variability at the LV pacing site, possibly explaining the abnormalities of the regional myocardial contractile function in a porcine model of pacing-induced HF

Cardiac myosin binding protein C phosphorylation in cardiac disease

Perturbations in sarcomeric function may in part underlie systolic and diastolic dysfunction of the failing heart. Sarcomeric dysfunction has been ascribed to changes in phosphorylation status of sarcomeric proteins caused by an altered balance between intracellular kinases and phosphatases during the development of cardiac disease. In the present review we discuss changes in phosphorylation of the thick filament protein myosin binding protein C (cMyBP-C) reported in failing myocardium, with emphasis on phosphorylation changes observed in familial hypertrophic cardiomyopathy caused by mutations in MYBPC3. Moreover, we will discuss assays which allow to distinguish between functional consequences of mutant sarcomeric proteins and (mal)adaptive changes in sarcomeric protein phosphorylation

Can we predict personality in fish? searching for consistency over time and across contexts

The interest in animal personality, broadly defined as consistency of individual behavioural traits over time and across contexts, has increased dramatically over the last years. Individual differences in behaviour are no longer recognised as noise around a mean but rather as adaptive variation and thus, essentially, raw material for evolution. Animal personality has been considered evolutionary conserved and has been shown to be present in all vertebrates including fish. Despite the importance of evolutionary and comparative aspects in this field, few studies have actually documented consistency across situations in fish. In addition, most studies are done with individually housed fish which may pose additional challenges when interpreting data from social species. Here, we investigate, for the first time in fish, whether individual differences in behavioural responses to a variety of challenges are consistent over time and across contexts using both individual and grouped-based tests. Twenty-four juveniles of Gilthead seabream Sparus aurata were subjected to three individual-based tests: feed intake recovery in a novel environment, novel object and restraining and to two group-based tests: risk-taking and hypoxia. Each test was repeated twice to assess consistency of behavioural responses over time. Risk taking and escape behaviours during restraining were shown to be significantly consistent over time. In addition, consistency across contexts was also observed: individuals that took longer to recover feed intake after transfer into a novel environment exhibited higher escape attempts during a restraining test and escaped faster from hypoxia conditions. These results highlight the possibility to predict behaviour in groups from individual personality traits.European Commission [265957 COPEWELL]; European Social Fund of Andalusia; Foundation for Science and Technology, Portugal [SFRH/BPD/77210/2011]info:eu-repo/semantics/publishedVersio

Effects of bovine spermatozoa preparation on embryonic development in vitro

The aim of our research was to examine the ability of density gradient preparation BoviPure(® )and swim up method on bull sperm separation and in vitro embryo production (IVP) systems. Frozen/thawed semen from six Simmental bulls was pooled and treated using both methods. The sperm motility, concentration, membrane activity, membrane integrity and acrosomal status were evaluated and compared before and after sperm processing using BoviPure(® )and swim up methods. We also evaluated and compared cleavage rates, embryo yield and quality between the methods. There were significant differences (P < 0.05) between the sperm characteristics before and after BoviPure(®), but not after swim up method. However, there were significant differences for sperm results among those two mentioned methods. A total of 641 oocytes were matured and fertilized in vitro and cultured in SOFaaBSA. The percentage of cleavage (Day 2) and the percentage of hatched embryos (Day 9) were similar for both methods. However, embryo production rate (Day 7) was significantly higher using BoviPure(® )method (P < 0.05). Also, total cell number and embryo differential staining (inner cell mass and trophectoderm cells) of Day 7 morulas and blastocysts showed that BoviPure(® )treated sperm displayed higher quality embryos compared to swim up method (P < 0.05). Our results indicate that BoviPure(® )method has an enhanced capacity in sperm selection for in vitro embryo production when compared with swim up method. So, we concluded that BoviPure(® )could be considered as a better alternative to swim up method for separating bull spermatozoa from frozen/thawed semen for IVP of bovine embryos