1,721,019 research outputs found
Three-dimensional spheroidal culture of cytotrophoblast cells mimics the phenotype and differentiation of cytotrophoblasts from normal and preeclamptic pregnancies
No full textNormal placental development is dependent on the orchestrated differentiation of cytotrophoblast (CTB) cells. This study was aimed at studying cytotrophoblast cells from normal and preeclamptic pregnancies in a three-dimensional spheroid-based cell culture model. First trimester cytotrophoblast cells cultured as spheroids maintain their high proliferative and invasive phenotype and respond to different cytokines upon stimulation in a three-dimensional invasion assay. In contrast, third trimester cytotrophoblast spheroids maintain their quiescent nonproliferating phenotype and invasion can only be induced by EGF. Contrasting the regular spheroidal arrangement of cytotrophoblast cells from normal third trimester pregnancies, spheroidal organization of preeclamptic cytotrophoblast cells is disturbed and the cells downregulate CD105 in vivo and in vitro. Furthermore, the invasion of both normal and preeclamptic third trimester, but not first trimester cytotrophobtast cells, is inhibited by pro-inflammatory cytokines. Plasma samples from pregnant women with preeclampsia significantly stimulate the invasion of first trimester cytotrophoblast cells and the sprouting of human umbilical vein endothelial cells (HUVECs) compared to plasma samples from healthy pregnant women. Taken together, the data establish the spheroidal cytotrophoblast model as a powerful system to mimic the in vivo phenotype of first and third trimester and preeclamptic cytotrophoblast cells and demonstrate that plasma-derived factors modulate the differentiation of cytotrophoblast cells. (C) 2004 Elsevier Inc. All rights reserved
Age-related differences in adaptation during childhood: The influences of muscular power production and segmental energy flow caused by muscles
No full textAcquisition of skillfulness is not only characterized by a task-appropriate application of muscular forces but also by the ability to adapt performance to changing task demands. Previous research suggests that there is a different developmental schedule for adaptation at the kinematic compared to the neuro-muscular level. The purpose of this study was to determine how age-related differences in neuro-muscular organization affect the mechanical construction of pedaling at different levels of the task. By quantifying the flow of segmental energy caused by muscles, we determined the muscular synergies that construct the movement outcome across movement speeds. Younger children (5-7 years; n = 11), older children (8-10 years; n = 8), and adults (22-31 years; n = 8) rode a stationary ergometer at five discrete cadences (60, 75, 90, 105, and 120 rpm) at 10% of their individually predicted peak power output. Using a forward dynamics simulation, we determined the muscular contributions to crank power, as well as muscular power delivered to the crank directly and indirectly (through energy absorption and transfer) during the downstroke and the upstroke of the crank cycle. We found significant age × cadence interactions for (1) peak muscular power at the hip joint [Wilks' Lambda = 0.441, F(8,42) = 2.65, p = 0.019] indicating that at high movement speeds children produced less peak power at the hip than adults, (2) muscular power delivered to the crank during the downstroke and the upstroke of the crank cycle [Wilks' Lambda = 0.399, F(8,42) = 3.07, p = 0.009] indicating that children delivered a greater proportion of the power to the crank during the upstroke when compared to adults, (3) hip power contribution to limb power [Wilks' Lambda = 0.454, F(8,42) = 2.54, p = 0.023] indicating a cadence-dependence of age-related differences in the muscular synergy between hip extensors and plantarflexors. The results demonstrate that in spite of a successful performance, children construct the task of pedaling differently when compared to adults, especially when they are pushed to their performance limits. The weaker synergy between hip extensors and plantarflexors suggests that a lack of inter-muscular coordination, rather than muscular power production per se, is a factor that limits children's performance ranges
Mechanical muscle properties and intermuscular coordination in maximal and submaximal cycling: theoretical and practical implications
Get PDFThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel UniversityThe ability of an individual to perform a functional movement is determined by a range of mechanical properties including the force and power producing capabilities of muscle, and the interplay of force and power outputs between different muscle groups (intermuscular coordination). Cycling presents an ideal experimental model to investigate these factors as it is an ecologically valid multi-joint movement in which kinematics and resistances can be tightly controlled. The overall goal of this thesis was thereby to investigate mechanical muscle properties and intermuscular coordination during maximal and submaximal cycling. The specific research objectives were (a) to determine the contribution of these factors to maximal and submaximal cycling, and (b) to determine the extent to which these factors set the limit of performance in maximal cycling. The contribution of mechanical muscle properties and intermuscular coordination were investigated by observing joint kinetics and joint kinematics across variations in crank lengths and pedalling rates during maximal and submaximal cycling. The extent to which these factors set the limit of performance in maximal cycling was assessed by observing joint-level kinetics of world-class track sprint cyclists. The findings of this investigation formed the rationale for the fourth study which used an ankle brace intervention to investigate the effects of a fixed ankle on joint biomechanics and performance during maximal cycling. Sophisticated intermuscular coordination strategies were observed in both submaximal and maximal cycling, supporting the generalised notion that high levels of intermuscular coordination are required to perform functional multi-joint movement tasks. Furthermore, it was found that the maximal cycling task is governed by the interaction of the force-velocity relationship and excitation-relaxation kinetics, suggesting that task-specific mechanical muscle properties are the dominant contributing factor in maximal movements. In terms of the extent to which these factors limit performance in maximal cycling, it was demonstrated that world-class track sprint cycling performance is governed by the ability to generate higher joint moments at the ankle and knee, and that these joint moments are facilitated by enhanced muscular strength about these joints. These findings allow us to speculate that the limits of performance in maximal human movements lie in extraordinary muscular strength in task-specific joint actions. These findings give an insight into the mechanisms that underpin maximal and submaximal cycling, and provide a theoretical framework with which to understand sprint cycling performance. This knowledge has significant applied relevance for athletes and coaches seeking to improve sprint cycling performance.Physical Sciences Research Council and The English Institute of Spor
An examination of muscle and tendon properties in children with spastic cerebral palsy and their response to stretch: a theoretical basis for evidence-based clinical practice
Get PDFThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Cerebral palsy (CP) is a heterogeneous disorder in which movement and posture are affected. Increased excitation of the central nervous system leads to neural symptoms, which can cause spasticity and muscle weakness. These neural abnormalities result in secondary CP-related mechanical adaptations of muscles and tendons, which can lead to muscle contracture, joint deformities and pain. Therapeutic interventions are therefore essential to treat CP-induced abnormalities. Passive stretching in particular is a popular treatment method in clinical practice. However, due to a lack of scientific evidence, clinicians often have to make assumptions about the mechanical adaptability of muscles and tendons. Currently, the mechanical properties of muscles and tendons in children with CP and their adaptability are not well understood, which makes it difficult to implement evidence-based practice in clinical settings. Therefore, the overall purpose of this research was to examine the mechanical properties of the medial gastrocnemius muscle and Achilles tendon in children with spastic CP, and the adaptations of the muscle and tendon to acute and long-term passive stretching. The first experimental Chapter (3) was carried out in healthy adults, to assess the agreement between two methods of deriving Achilles tendon stiffness (i) active contraction of the triceps surae muscles to elongate the Achilles tendon, or (ii) passive rotation of the ankle joint. Taking into consideration the tendon’s viscoelastic response, the effects of strain-rate on Achilles tendon stiffness were also described. Results revealed that tendon stiffness measured using the “active method” was 6% greater than the “passive method”. There was also a significant increase in Achilles tendon stiffness in response to increased strain-rate. As the more commonly used active method is problematic to be used in children with CP, due to muscle weakness and excessive co-contraction, the passive method of deriving tendon stiffness was used in subsequent experimental studies. In experimental Chapter 4, differences in the mechanical properties of the Achilles tendon and triceps surae muscles between children with CP and their typically developing (TD) peers, were investigated. The results revealed that estimates of triceps surae muscle stiffness were significantly greater in children with CP compared to TD children. The results also showed that despite a smaller tendon cross-sectional area in children with CP, Achilles tendon stiffness was not different between groups. In addition, children with CP had a steeper tendon stiffness-strain-rate relationship compared to TD children. These results have significant clinical implications regarding the diagnosis of spasticity using the current clinical methods. Experimental Chapters 5 and 6 examined the muscle’s and tendon’s response to stretch. Passive stretching, implemented by a clinician or by the children themselves, is a commonly used intervention for children with CP with the aim of inducing structural alterations in muscles and tendons to improve function. In order for these alterations to take place, elongation of the muscle and fascicles would presumably need to occur with acute stretching. To date, this assumption has not been tested. Thus, the purpose of Chapter 5 was to investigate the medial gastrocnemius and muscle fascicle response to acute stretching, using two commonly used stretch techniques. Results of this study revealed that 100 s of stretching caused a transient increase in tendon (1.0 cm), muscle (0.8 cm) and fascicle lengths (0.6 cm). This effect was independent of stretch technique. These results provide evidence that the muscle and fascicles are capable of elongating in response to stretch in children with spastic CP. They provide a basis for the hypothesis that the spastic muscle may be able to adapt in response to long-term stretching. Thus, the purpose of the final experimental Chapter (6) was to assess the effects of a six week passive stretching intervention (four days per week, 15 minutes per day) on muscle and tendon properties, and gait parameters in children with CP. Results revealed there was a significant reduction in joint stiffness in the experimental group following six weeks of stretching. This was accompanied by a reduction in muscle stiffness, but with no alterations in Achilles tendon stiffness. Additionally, there were no positive effects of passive stretching on gait parameters. Together, the results of the present series of investigations demonstrates how fundamental knowledge of muscle and tendon mechanics in children with spastic CP, can be implemented to support evidence-based clinical practice
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The effects of age- and training-related changes in tendon stiffness on muscular force production and neuro-motor control during childhood
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The research described in this thesis examined age- and strength training-related changes in Achilles tendon stiffness and plantarflexor force production in prepubertal children. The measurement of both Achilles tendon stiffness and muscular force production requires in vivo moment arm lengths to be known. Currently, this is possible only by using expensive and time-consuming medical imaging methodologies. Therefore, the predictability of the Achilles tendon moment arm from surface anthropometric measurements was assessed in the first experimental study (Chapter 3). The results demonstrated that a combination of foot length and the distance between the calcaneal tuberosity and 1st metatarsal head could explain 49% of the variability in Achilles tendon moment arm length in 5 – 12 year-old children. This was considered to be unacceptable for further use, thus an ultrasound-based method was decided upon for obtaining moment arm length in subsequent experimental studies. In the second and third experimental studies (Chapters 4 and 5), age-related changes in tendon mechanical and structural properties were documented and their relationship with changes in force production ability were examined in prepubertal children (5 – 12 years) and adult men and women. In Chapter 4, Achilles tendon stiffness was shown to increase with age through to adulthood, and that changes in tendon stiffness were strongly and independently associated with body mass (R2 = 0.58) and peak force production capacity (R2 = 0.51),which may provide the tendon with an increasing mechanical stimulus for growth and microadaptation. These increases in tendon stiffness were associated with a greater increase in tendon CSA (~105%) than that found for tendon length (~60%), in addition to an increase in Young’s modulus (~139%), suggesting that gross increases in tendon size as well as changes in its microstructure underpinned the increase in stiffness. In Chapter 5, the relationships between Achilles tendon stiffness and both electro-mechanical delay (EMD) and rate of force development (RFD) were determined during maximal isometric plantarflexion contractions. Moderate correlations were found between tendon stiffness and both EMD (r = -0.66) and RFD (r = 0.58). RFD was significantly better predicted when muscle activation (estimated as the rate of EMG rise) was included in a regression model. These data clearly show that increases in tendon stiffness with age through to adulthood are associated with decreases in EMD and increases in RFD, and that the rate of muscle activation has an additional influence on RFD during growth. Given that 1) Achilles tendon stiffness was lower in children than adults, 2) this lower stiffness was associated with a longer EMD and slower RFD, and 3) that strength training in adults had previously been shown to increase tendon stiffness and RFD, the adaptability of the developing Achilles tendon to a resistance training programme, and consequence of the potential changes on force production capacity were examined in the final experimental study (Chapter 6). Significant increases in Achilles tendon stiffness and Young’s modulus were found after 10 weeks of twice-weekly plantarflexor strength training in 8-9 year-old boys and girls, which demonstrates that the larger muscle force production provided a sufficient stimulus for tendon microadaptation. The training also resulted in a decrease in EMD, which was moderately correlated with the change in tendon stiffness (r = 55), but no change in RFD. Thus, the increasing tendon stiffness with training was associated with a decreasing EMD, but had no detectable effect on RFD. This would likely have a significant effect on the performance of tasks requiring rapid muscle force production. Together, the results of the present series of investigations demonstrate that the tendon loading experienced from both normal ageing and overloading (strength training) can increase tendon stiffness in children, and that these changes have a detectable effect on rapid force production.EPSR
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Blood vessel maturation in a 3‐dimensional spheroidal coculture model: direct contact with smooth muscle cells regulates endothelial cell quiescence and abrogates VEGF responsiveness
No full textParacrine interactions between endothelial cells (EC) and mural cells act as critical regulators of vessel wall assembly, vessel maturation and define a plasticity window for vascular remodeling. The present study was aimed at studying blood vessel maturation processes in a novel 3-dimensional spheroidal coculture system of EC and smooth muscle cells (SMC). Coculture spheroids differentiate spontaneously in a calcium-dependent manner to organize into a core of SMC and a surface layer of EC, thus mimicking the physiological assembly of blood vessels with surface lining EC and underlying mural cells. Coculture of EC with SMC induces a mature, quiescent EC phenotype as evidenced by 1) a significant increase in the number of junctional complexes of the EC surface layer, 2) a down-regulation of PDGF-B expression by cocultured EC, and 3) an increased resistance of EC to undergo apoptosis. Furthermore, EC cocultured with SMC become refractory to stimulation with VEGF (lack of CD34 expression on VEGF stimulation; inability to form capillary-like sprouts in a VEGF-dependent manner in a S-dimensional in gel angiogenesis assay). In contrast, costimulation with VEGF and Ang-2 induced sprouting angiogenesis originating from coculture spheroids consistent with a model of Ang-2-mediated vessel destabilization resulting in VEGF responsiveness. Ang-2 on its own was able to stimulate endothelial cells in the absence of Ang-l producing SMC, inducing lateral sheet migration as well as in gel sprouting angiogenesis. Taken together, the data establish the spheroidal EC/SMC system as a powerful cell. culture model to study paracrine interactions in the vessel wall and provide functional evidence for smooth muscle cell-mediated quiescence effects on endothelial cells
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