- Mesenchymal stem cell homing towards cancer cells is increased by enzyme activity of cathepsin D. [Journal Article]
- ECExp Cell Res 2019 Jul 12
- Mesenchymal stem cells home towards inflammatory microenvironments, such as the tumour stroma, where they have been shown to have both pro- and anti-tumorigenic effects. Here, we demonstrate that the…
Mesenchymal stem cells home towards inflammatory microenvironments, such as the tumour stroma, where they have been shown to have both pro- and anti-tumorigenic effects. Here, we demonstrate that the aspartic acid protease cathepsin D is part of the chemoattraction process. Using a Boyden chamber co-culture system, the migration of the mesenchymal stem cells and their invasion through Matrigel increased in the presence of breast cancer MDA-MB-231 cells, colon cancer HT29 cells or their conditioned media. Mesenchymal stem cell movement was reduced by protease inhibitors of matrix metalloproteinases and by pepstatin A, an inhibitor of cathepsin D. We confirmed a role for cathepsin D through addition of recombinant protein, upregulation of cathepsin D release using chloroquine and knockdown of cathepsin D expression. While all cell types expressed active cathepsin D, enzymatically inactive precursor procathepsin D was expressed only at low levels by mesenchymal stem cells. Expression in mesenchymal stem cells was increased following co-culture with cancer cells. The chemoattractive effect of cathepsin required its enzymatic activity, but not changes in mesenchymal stem cell proliferation or adhesion rates. In conclusion, cathepsin D and its precursors enhance mesenchymal stem cell homing towards tumour sites, most likely by enzymatic mechanisms.
- Changes in gain of horizontal vestibulo-ocular reflex during spaceflight. [Journal Article]
- JVJ Vestib Res 2019 Jul 06
- CONCLUSIONS: The decrease in DVOR gain early in the flight and after the flight reflects adaptive changes in central integration of vestibular and proprioceptive sensory inputs during active head movements.
- How to Observe Users' Movements in Virtual Environments: Viewpoint Control in a Power Wheelchair Simulator. [Journal Article]
- HFHum Factors 2019 Jul 15; :18720819853682
- CONCLUSIONS: Incorporating the observer into the VE, through egomotion, is an effective method for assessing users' behavior in VR with implications for the transferability of virtual experiences to the real world.
- Validation of an ambient measurement system (AMS) for physical activities in a paediatric population. [Journal Article]
- JMJ Med Eng Technol 2019 Jul 15; :1-8
- Ambient measurement systems (AMSs) can enable continuous assessment of functional performance at home, increasing the availability of data for monitoring of neuromuscular disease. An AMS passively me…
Ambient measurement systems (AMSs) can enable continuous assessment of functional performance at home, increasing the availability of data for monitoring of neuromuscular disease. An AMS passively measures movement whenever someone is in range of the sensor, without the need for any wearable sensors. The current study evaluates the performance of an AMS for three metrics associated with functional assessments in Duchenne muscular dystrophy (DMD): ambulation speed, rise-to-stand speed and arm-raise speed. Healthy paediatric subjects performed a series of functional tasks and were graded by both a human rater and an AMS. Linear mixed-effect models were fit to calculate agreement between the two measurement methods. For all activities, the AMS and human rater supplied similar measurements of average speed, with correlation coefficients of 0.76-0.92 and systematic differences ranging in magnitude from 0 to 0.48 m per second. The largest systematic difference was for the 10-m run, which was likely due to human rater reaction time. Systematic differences in arm-raise measurements were due to incomplete execution of movements by test participants. These results are consistent with previous studies comparing automated and manual measurements of movement. This study demonstrates that an AMS device is able to measure ambulation speed, rise-to-stand speed and arm-raise speed in a paediatric population in a controlled setting without the need for complicated installation, calibration or worn sensors.
- Dysfunctional striatal dopamine signaling in Huntington's disease. [Review]
- JNJ Neurosci Res 2019 Jul 15
- Dopamine signaling in the striatum is critical for a variety of behaviors including movement, behavioral flexibility, response to reward and many forms of learning. Alterations to dopamine transmissi…
Dopamine signaling in the striatum is critical for a variety of behaviors including movement, behavioral flexibility, response to reward and many forms of learning. Alterations to dopamine transmission contribute to pathological features of many neurological diseases, including Huntington's disease (HD). HD is an autosomal dominant genetic disorder caused by a CAG repeat expansion in the Huntingtin gene. The striatum is preferentially degenerated in HD, and this region receives dopaminergic input from the substantia nigra. Studies of HD patients and genetic rodent models have shown changes to levels of dopamine and its receptors in the striatum, and alterations in dopamine receptor signaling and modulation of other neurotransmitters, notably glutamate. Throughout his career, Dr. Michael Levine's research has furthered our understanding of dopamine signaling in the striatum of healthy rodents and HD mouse models. This review will focus on the work of his group and others in elucidating alterations to striatal dopamine signaling that contribute to pathophysiology in HD mouse models, and how these findings relate to human HD studies. We will also discuss current and potential therapeutic interventions for HD that target the dopamine system, and future research directions for this field.
- Conceptualizing the 'whole university' approach: an international qualitative study. [Journal Article]
- HPHealth Promot Int 2019 Jul 15
- Focusing on the conceptualization of a whole university approach, this paper reports on an international qualitative study that explored vice-chancellors' and network members' understanding of and co…
Focusing on the conceptualization of a whole university approach, this paper reports on an international qualitative study that explored vice-chancellors' and network members' understanding of and commitment to Health Promoting Universities, examined perspectives on leadership and investigated the Okanagan Charter's potential to catalyse whole university leadership and change. A multi-method qualitative approach was used: semi-structured interviews and focus groups were conducted face-to-face with vice-chancellors (n = 12) and Health Promoting University co-ordinators who were members of the UK Healthy Universities Network (n = 8); telephone interviews were conducted with a mix of UK and non-UK Health Promoting University co-ordinators (n = 5) and two online questionnaires were distributed to non-UK network co-ordinators (n = 6) and non-UK Health Promoting University co-ordinators (n = 10). Through thematic analysis, a number of key themes emerged that build a new conceptualization of the whole university approach (see Figure 1): building a broad understanding and framing of health; developing a supportive ethos and culture; embedding health into the university and joining up areas of work; focusing on the whole population and facing challenges and seizing opportunities. The study elicited rich and wide-ranging views from multiple stakeholders from universities and networks across four continents, confirming Health Promoting Universities as a truly global movement. Looking ahead, there are clear opportunities and challenges. First, the media narrative of a student mental health 'crisis' has focused universities' attention on 'health', but from a single issue 'illness' perspective. This risks detracting from the whole system Health Promoting Universities approach. Second, even with the Okanagan Charter inspiring individuals and universities, there are still major challenges in translating the rhetoric of whole system approaches into meaningful action within large, complex and culturally diverse organizations.
- A quasi three-dimensional visualization of unsteady wake flow in human undulatory swimming. [Journal Article]
- JBJ Biomech 2019 Jul 04
- Human undulatory underwater swimming (UUS) is an underwater propelling technique in competitive swimming and its propulsive mechanism is poorly understood. The purpose of this study was to visualize …
Human undulatory underwater swimming (UUS) is an underwater propelling technique in competitive swimming and its propulsive mechanism is poorly understood. The purpose of this study was to visualize the three-dimensional (3D) flow field in the wake region during human UUS in a water flume. A national level male swimmer performed 41 UUS trials in a water flume. A motion capture system and stereo particle image velocimetry (PIV) equipment were used to investigate the 3D coordinates of the swimmer and 3D flow fields in the wake region. After one kick cycle was divided into eight phases, we conducted coordinate transformations and phase averaging method to construct quasi 3D flow fields. At the end of the downward kick, the lower limbs external rotations of the lower limbs were observed, and the feet approached towards each other. A strong downstream flow, i.e. a jet was observed in the wake region during the downward kick, and the paired vortex structure was accompanied by a jet. In the vortex structure, a cluster of vortices and a jet were generated in the wake during the downward kick, and the vortices were subsequently shed from the feet by the rotated leg motion. This suggested that the swimmer gained a thrust by creating vortices around the foot during the downward kick, which collided to form a jet. This paper describes, illustrates, and explains the propulsive mechanism of human UUS.
- The role of zinc supplementation on the metallothionein system in children with autism spectrum disorder. [Journal Article]
- ANActa Neurol Belg 2019 Jul 13
- The present research was carried out to elucidate the role of zinc (Zn) supplementation on the plasma concentration and gene expression, as well as the effects on cognitive-motor performance, in a co…
The present research was carried out to elucidate the role of zinc (Zn) supplementation on the plasma concentration and gene expression, as well as the effects on cognitive-motor performance, in a cohort of children with autism spectrum disorder (ASD). The study was performed on a cohort of 30 pediatric subjects with ASD, encompassing an age range of 3-8 years. The impact of Zn supplementation was investigated in 3 months (or 12 weeks) on the ASD children. Each daily dosage of Zn was calculated as being equal to the body weight in kg plus 15-20 mg. The effect of Zn was also evaluated on the serum level of metallothionein 1 (MT-1A), and the severity of autism via scores on the Childhood Autism Rating Scale. The effect of Zn was investigated on the gene expression of MT1-A before and after Zn supplementation. The data of the present study showed an increase in cognitive-motor performance and an increased serum metallothionein concentration, as well as a significant lowering in the circulating serum levels of copper (Cu) following Zn supplementation. In the cohort of ASD patients, the genetic expression of MT-1 was higher after Zn therapy than before the treatment. In conclusion, Zn supplementation might be an important factor in the treatment of children with ASD.
- Distance perception during self-movement. [Journal Article]
- HMHum Mov Sci 2019 Jul 10; 67:102496
- The perception of distance in open fields was widely studied with static observers. However, it is a fact that we and the world around us are in continuous relative movement, and that our perceptual …
The perception of distance in open fields was widely studied with static observers. However, it is a fact that we and the world around us are in continuous relative movement, and that our perceptual experience is shaped by the complex interactions between our senses and the perception of our self-motion. This poses interesting questions about how our nervous system integrates this multisensory information to resolve specific tasks of our daily life, for example, distance estimation. This study provides new evidence about how visual and motor self-motion information affects our perception of distance and a hypothesis about how these two sources of information can be integrated to calibrate the estimation of distance. This model accounts for the biases found when visual and proprioceptive information is inconsistent.
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- Structural and functional defects of the respiratory neural system in the medulla and spinal cord of Pax6 mutant rats. [Journal Article]
- BRBrain Res Bull 2019 Jul 10
- Pax6 is an important transcription factor expressed in several discrete domains of the developing central nervous system. It has been reported that Pax6 is involved in the specification of subtypes o…
Pax6 is an important transcription factor expressed in several discrete domains of the developing central nervous system. It has been reported that Pax6 is involved in the specification of subtypes of hindbrain motor neurons. Pax6 homozygous mutant (rSey2/rSey2) rats die soon after birth, probably due to impaired respiratory movement. To determine whether the respiratory center in the medulla functions normally, we analyzed the histological and neurophysiological properties of the medulla and spinal cord in fetal rats with this mutation. First, the medulla of rSey2/rSey2 at embryonic (E) 21.5-E22.5 tended to be smaller than those from heterozygous mutant (rSey2/+) and wild-type (+/+) littermates. Through immunohistochemical analysis, we confirmed normal distribution of Phox2b-expressing cells in the parafacial respiratory group (pFRG) of rSey2/rSey2 rats. Expression of neurokinin-1 receptor (NK-1R) was weak and dispersed in rSey2/rSey2 rats. In addition, rSey2/rSey2 rats have a defect of the hypoglossal nerve root. Electrophysiological analysis using brainstem-spinal cord preparations (E21.5-E22.5) revealed that rSey2/rSey2 rats showed larger fluctuation of the amplitude of inspiratory activity monitored from the fourth cervical root although there was no significant difference in the respiratory rate among rSey2/rSey2, rSey2/+, and +/+ littermates. The response of respiratory rhythm to high CO2 was similar among all genotypes. Optical recordings of neuronal activity revealed that the activity of the pFRG tended to be weaker and inspiratory activity appeared in more scattered areas in the caudal ventral medulla in the rSey2/rSey2 rats. These results suggest that the basal activity of the respiratory system was preserved with mild impairment of the inspiratory activity in the rSey2/rSey2 rats and that the Pax6 gene is involved in the functional development of the neuronal system producing effective inspiratory motor outputs for survival.