The Relative Contributions of Visual and Proprioceptive Inputs on Hand Localization in Early Childhood.

Forming an accurate representation of the body relies on the integration of information from multiple sensory inputs. Both vision and proprioception are important for body localization. Whilst adults have been shown to integrate these sources in an optimal fashion, few studies have investigated how children integrate visual and proprioceptive information when localizing the body. The current study used a mediated reality device called MIRAGE to explore how the brain weighs visual and proprioceptive information in a hand localization task across early childhood. Sixty-four children aged 4-11 years estimated the position of their index finger after viewing congruent or incongruent visuo-proprioceptive information regarding hand position. A developmental trajectory analysis was carried out to explore the effect of age on condition. An age effect was only found in the incongruent condition which resulted in greater mislocalization of the hand toward the visual representation as age increased. Estimates by younger children were closer to the true location of the hand compared to those by older children indicating less weighting of visual information. Regression analyses showed localizations errors in the incongruent seen condition could not be explained by proprioceptive accuracy or by general attention or social differences. This suggests that the way in which visual and proprioceptive information are integrated optimizes throughout development, with the bias toward visual information increasing with age.

Social context facilitates visuomotor synchrony and bonding in children and adults.

Interpersonal synchrony is a fundamental part of human social interaction, with known effects on facilitating social bonding. Moving in time with another person facilitates prosocial behaviour, however, it is unknown if the degree of synchronisation predicts the degree of social bonding. Similarly, while people readily fall in synchrony even without being instructed to do so, we do not know whether such spontaneous synchronisation elicits similar prosocial effects as instructed synchronisation. Across two studies, we investigated how context (social vs non-social stimulus) and instruction (instructed vs uninstructed) influenced synchronisation accuracy and bonding with the interaction partner in adults and children. The results revealed improved visuomotor synchrony within a social, compared to non-social, context in adults and children. Children, but not adults, synchronised more accurately when instructed to synchronise than when uninstructed. For both children and adults, synchronisation in a social context elicited stronger social bonding towards an interaction partner as compared to synchronisation in a non-social context. Finally, children's, but not adults', degree of synchrony with the partner was significantly associated with their feelings of social closeness. These findings illuminate the interaction of sensorimotor coupling and joint action in social contexts and how these mechanisms facilitate synchronisation ability and social bonding.

The Anne Boleyn Illusion is a Six-Fingered Salute to Sensory Remapping.

The Anne Boleyn Illusion exploits the somatotopic representation of touch to create the illusion of an extra digit and demonstrates the instantaneous remapping of relative touch location into body-based coordinates through visuo-tactile integration. Performed successfully on thousands, it is also a simple demonstration of the flexibility of body representations for use at public events, in schools or in the home and can be implemented anywhere by anyone with a mirror and some degree of bimanual coordination.

Give It a Tug and Feel It Grow: Extending Body Perception Through the Universal Nature of Illusory Finger Stretching.

If British teenage boy asks you to pull his finger, it is usually an indication that he simultaneously wishes to break wind. If you were to tell him that you could pull his finger and stretch it to twice its length, you might expect a similarly irreverent response yet when we pulled the fingers of nearly 600 children and adolescents, 93% reported the illusion of stretching. Grossly distorted body representations need not be the preserve of clinical disorders and can reliably be induced in healthy participants across all ages.

Are major bleeding events from falls more likely in patients on warfarin?

There is no evidence of increased risk for major bleeding as a result of falls in hospitalized patients taking warfarin (strength of recommendation [SOR]: B, based on retrospective cohort studies). In the average patient taking warfarin for atrial fibrillation, the risk of intracranial hemorrhage from a fall is much smaller than the benefit gained from reducing risk of stroke (SOR: A, based on decision analysis of systematic reviews with sensitivity analysis).

Purified human MDR 1 modulates membrane potential in reconstituted proteoliposomes.

Human multidrug resistance (hu MDR 1) cDNA was fused to a P. shermanii transcarboxylase biotin acceptor domain (TCBD), and the fusion protein was heterologously overexpressed at high yield in K(+)-uptake deficient Saccharomyces cerevisiae yeast strain 9.3, purified by avidin-biotin chromatography, and reconstituted into proteoliposomes (PLs) formed with Escherichia coli lipid. As measured by pH- dependent ATPase activity, purified, reconstituted, biotinylated MDR-TCBD protein is fully functional. Dodecyl maltoside proved to be the most effective detergent for the membrane solubilization of MDR-TCBD, and various salts were found to significantly affect reconstitution into PLs. After extensive analysis, we find that purified reconstituted MDR-TCBD protein does not catalyze measurable H(+) pumping in the presence of ATP. In the presence of physiologic [ATP], K(+)/Na(+) diffusion potentials monitored by either anionic oxonol or cationic carbocyanine are easily established upon addition of valinomycin to either control or MDR-TCBD PLs. However, in the absence of ATP, although control PLs still maintain easily measurable K(+)/Na(+) diffusion potentials upon addition of valinomycin, MDR-TCBD PLs do not. Dissipation of potential by MDR-TCBD is clearly [ATP] dependent and also appears to be Cl(-) dependent, since replacing Cl(-) with equimolar glutamate restores the ability of MDR-TCBD PLs to form a membrane potential in the absence of physiologic [ATP]. The data are difficult to reconcile with models that might propose ATP-catalyzed "pumping" of the fluorescent probes we use and are more consistent with electrically passive anion transport via MDR-TCBD protein, but only at low [ATP]. These observations may help to resolve the confusing array of data related to putative ion transport by hu MDR 1 protein.

Analysis of the antimalarial drug resistance protein Pfcrt expressed in yeast.

Mutations in the novel membrane protein Pfcrt were recently found to be essential for chloroquine resistance (CQR) in Plasmodium falciparum, the parasite responsible for most lethal human malaria (Fidock, D. A., Nomura, T., Talley, A. K., Cooper, R. A., Dzekunov, S. M., Ferdig, M. T., Ursos, L. M., Sidhu, A. B., Naude, B., Deitsch, K. W., Su, X. Z., Wootton, J. C., Roepe, P. D., and Wellems, T. E. (2000) Mol. Cell 6, 861-871). Pfcrt is localized to the digestive vacuolar membrane of the intraerythrocytic parasite and may function as a transporter. Study of this putative transport function would be greatly assisted by overexpression in yeast followed by characterization of membrane vesicles. Unfortunately, the very high AT content of malarial genes precludes efficient heterologous expression. Thus, we back-translated Pfcrt to design idealized genes with preferred yeast codons, no long poly(A) sequences, and minimal stem-loop structure. We synthesized a designed gene with a two-step PCR method, fused this to N- and C-terminal sequences to aid membrane insertion and purification, and now report efficient expression of wild type and mutant Pfcrt proteins in the plasma membrane of Saccharomyces cerevisiae and Pichia pastoris yeast. To our knowledge, this is the first successful expression of a full-length malarial parasite integral membrane protein in yeast. Purified membranes and inside-out plasma membrane vesicle preparations were used to analyze wild type versus CQR-conferring mutant Pfcrt function, which may include effects on H(+) transport (Dzekunov, S., Ursos, L. M. B., and Roepe, P. D. (2000) Mol. Biochem. Parasitol. 110, 107-124), and to perfect a rapid purification of biotinylated Pfcrt. These data expand on the role of Pfcrt in conferring CQR and define a productive route for analysis of important P. falciparum transport proteins and membrane associated vaccine candidates.