Contribution of primary motor cortex to compensatory balance reactions

<p>Abstract</p> <p>Background</p> <p>Rapid compensatory arm reactions represent important response strategies following an unexpected loss of balance. While it has been assumed that early corrective actions arise largely from sub-cortical networks, recent findings have prompted speculation about the potential role of cortical involvement. To test the idea that cortical motor regions are involved in early compensatory arm reactions, we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants prior to evoking upper limb balance reactions in response to whole body perturbation. We hypothesized that following cTBS to the M1 hand area evoked EMG responses in the stimulated hand would be diminished. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair while holding a stable handle with both hands. The chair was held vertical by a magnet and was triggered to fall backward unpredictably. To regain balance, participants used the handle to restore upright stability as quickly as possible with both hands. Muscle activity was recorded from proximal and distal muscles of both upper limbs.</p> <p>Results</p> <p>Our results revealed an impact of cTBS on the amplitude of the EMG responses in the stimulated hand muscles often manifest as inhibition in the stimulated hand. The change in EMG amplitude was specific to the target hand muscles and occasionally their homologous pairs on the non-stimulated hand with no consistent effects on the remaining more proximal arm muscles.</p> <p>Conclusions</p> <p>Present findings offer support for cortical contributions to the control of early compensatory arm reactions following whole-body perturbation.</p

The role of ubiquitination and hepatocyte growth factor-regulated tyrosine kinase substrate in the degradation of the adrenomedullin type I receptor

Calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 2 (RAMP2) comprise a receptor for adrenomedullin (AM). Although it is known that AM induces internalization of CLR•RAMP2, little is known about the molecular mechanisms that regulate the trafficking of CLR•RAMP2. Using HEK and HMEC-1 cells, we observed that AM-induced activation of CLR•RAMP2 promoted ubiquitination of CLR. A mutant (CLRΔ9KR), lacking all intracellular lysine residues was functional and trafficked similar to the wild-type receptor, but was not ubiquitinated. Degradation of CLR•RAMP2 and CLRΔ9KR•RAMP2 was not dependent on the duration of AM stimulation or ubiquitination and occurred via a mechanism that was partially prevented by peptidase inhibitors. Degradation of CLR•RAMP2 was sensitive to overexpression of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), but not to HRS knockdown, whereas CLRΔ9KR•RAMP2 degradation was unaffected. Overexpression, but not knockdown of HRS, promoted hyperubiquitination of CLR under basal conditions. Thus, we propose a role for ubiquitin and HRS in the regulation of AM-induced degradation of CLR•RAMP2

Experimental neck muscle pain impairs standing balance in humans

Impaired postural control has been reported in patients with chronic neck pain of both traumatic and non-traumatic etiologies, but whether painful stimulation of neck muscle per se can affect balance control during quiet standing in humans remains unclear. The purpose of the present experiment was thus to investigate the effect of experimental neck muscle pain on standing balance in young healthy adults. To achieve this goal, 16 male university students were asked to stand upright as still as possible on a force platform with their eyes closed in two conditions of No pain and Pain of the neck muscles elicited by experimental painful electrical stimulation. Postural control and postural performance were assessed by the displacements of the center of foot pressure (CoP) and of the center of mass (CoM), respectively. The results showed increased CoP and CoM displacements variance, range, mean velocity, and mean and median frequencies in the Pain relative to the No pain condition. The present findings emphasize the destabilizing effect of experimental neck muscle pain per se, and more largely stress the importance of intact neck neuromuscular function on standing balance

Diversity of Tanaidacea (Crustacea: Peracarida) in the World's Oceans – How Far Have We Come?

Tanaidaceans are small peracarid crustaceans which occur in all marine habitats, over the full range of depths, and rarely into fresh waters. Yet they have no obligate dispersive phase in their life-cycle. Populations are thus inevitably isolated, and allopatric speciation and high regional diversity are inevitable; cosmopolitan distributions are considered to be unlikely or non-existent. Options for passive dispersion are discussed. Tanaidaceans appear to have first evolved in shallow waters, the region of greatest diversification of the Apseudomorpha and some tanaidomorph families, while in deeper waters the apseudomorphs have subsequently evolved two or three distinct phyletic lines. The Neotanaidomorpha has evolved separately and diversified globally in deep waters, and the Tanaidomorpha has undergone the greatest evolution, diversification and adaptation, to the point where some of the deep-water taxa are recolonizing shallow waters. Analysis of their geographic distribution shows some level of regional isolation, but suffers from inclusion of polyphyletic taxa and a general lack of data, particularly for deep waters. It is concluded that the diversity of the tanaidomorphs in deeper waters and in certain ocean regions remains to be discovered; that the smaller taxa are largely understudied; and that numerous cryptic species remain to be distinguished. Thus the number of species currently recognized is likely to be an order of magnitude too low, and globally the Tanaidacea potentially rival the Amphipoda and Isopoda in diversity

Cell-Surface Marker Signatures for the Isolation of Neural Stem Cells, Glia and Neurons Derived from Human Pluripotent Stem Cells

Neural induction of human pluripotent stem cells often yields heterogeneous cell populations that can hamper quantitative and comparative analyses. There is a need for improved differentiation and enrichment procedures that generate highly pure populations of neural stem cells (NSC), glia and neurons. One way to address this problem is to identify cell-surface signatures that enable the isolation of these cell types from heterogeneous cell populations by fluorescence activated cell sorting (FACS).We performed an unbiased FACS- and image-based immunophenotyping analysis using 190 antibodies to cell surface markers on naïve human embryonic stem cells (hESC) and cell derivatives from neural differentiation cultures. From this analysis we identified prospective cell surface signatures for the isolation of NSC, glia and neurons. We isolated a population of NSC that was CD184(+)/CD271(-)/CD44(-)/CD24(+) from neural induction cultures of hESC and human induced pluripotent stem cells (hiPSC). Sorted NSC could be propagated for many passages and could differentiate to mixed cultures of neurons and glia in vitro and in vivo. A population of neurons that was CD184(-)/CD44(-)/CD15(LOW)/CD24(+) and a population of glia that was CD184(+)/CD44(+) were subsequently purified from cultures of differentiating NSC. Purified neurons were viable, expressed mature and subtype-specific neuronal markers, and could fire action potentials. Purified glia were mitotic and could mature to GFAP-expressing astrocytes in vitro and in vivo.These findings illustrate the utility of immunophenotyping screens for the identification of cell surface signatures of neural cells derived from human pluripotent stem cells. These signatures can be used for isolating highly pure populations of viable NSC, glia and neurons by FACS. The methods described here will enable downstream studies that require consistent and defined neural cell populations

Neural Stem/Progenitor Cells from the Adult Human Spinal Cord Are Multipotent and Self-Renewing and Differentiate after Transplantation

Neural stem/progenitor cell (NSPC) transplantation is a promising therapy for spinal cord injury (SCI). However, little is known about NSPC from the adult human spinal cord as a donor source. We demonstrate for the first time that multipotent and self-renewing NSPC can be cultured, passaged and transplanted from the adult human spinal cord of organ transplant donors. Adult human spinal cord NSPC require an adherent substrate for selection and expansion in EGF (epidermal growth factor) and FGF2 (fibroblast growth factor) enriched medium. NSPC as an adherent monolayer can be passaged for at least 9 months and form neurospheres when plated in suspension culture. In EGF/FGF2 culture, NSPC proliferate and primarily express nestin and Sox2, and low levels of markers for differentiating cells. Leukemia inhibitory factor (LIF) promotes NSPC proliferation and significantly enhances GFAP expression in hypoxia. In differentiating conditions in the presence of serum, these NSPC show multipotentiality, expressing markers of neurons, astrocytes, and oligodendrocytes. Dibutyryl cyclic AMP (dbcAMP) significantly enhances neuronal differentiation. We transplanted the multipotent NSPC into SCI rats and show that the xenografts survive, are post-mitotic, and retain the capacity to differentiate into neurons and glia

Hippocampal IGF-1 expression, neurogenesis and slowed aging: clues to longevity from mutant mice

Recent studies point out the important role of IGF and insulin-related signaling pathways in the control of longevity of laboratory animals. The Ames dwarf mouse is a murine model of circulating GH and IGF-1 deficiency that exhibits dwarf phenotype characteristics and significantly extends lifespan. It is interesting to know that Ames dwarf mice do not experience an age-related decline in cognitive function when compared to their young counterparts. In this study, the most recent works on local GH and IGF-1 expression in the hippocampus of Ames mice are briefly reviewed

Predicting youth participation in urban agriculture in Malaysia: insights from the theory of planned behavior and the functional approach to volunteer motivation

This study examines factors associated with the decision of Malaysian youth to participate in a voluntary urban agriculture program. Urban agriculture has generated significant interest in developing countries to address concerns over food security, growing urbanization and employment. While an abundance of data shows attracting the participation of young people in traditional agriculture has become a challenge for many countries, few empirical studies have been conducted on youth motivation to participate in urban agriculture programs, particularly in non-Western settings. Drawing on the theories of planned behavior and the functional approach to volunteer motivation, we surveyed 890 students from a public university in Malaysia about their intention to join a new urban agriculture program. Hierarchical regression findings indicated that the strongest predictor of participation was students’ attitude toward urban agriculture, followed by subjective norms, career motives and perceived barriers to participation. The findings from this study may provide useful information to the university program planners in Malaysia in identifying mechanisms for future students’ involvement in the program