13,280 research outputs found
Viscoelastic Cell Mechanics and actin remodelling are dependent on the rate of applied pressure
No full textBackground: living cells are subjected to external and internal mechanical stresses. The effects of these stresses on the deformation and subsequent biological response of the cells remains unclear. This study tested the hypothesis that the rate at which pressure (or stress) is applied influence the viscoelastic properties of the cell associated with differences in the dynamics of the actin cytoskeleton.Principal finding: micropipette aspiration was used to determine the instantaneous and equilibrium moduli and the viscosity of isolated chondrocytes based on the standard linear solid (SLS) model and a variation of this incorporating Boltzmann superposition. Cells were visualised for 180 seconds following aspiration to 7 cmH2O at 0.35, 0.70 and 5.48 cmH2O/sec. Cell recovery was then examined for a further 180 seconds once the pressure had been removed. Reducing the rate of application of pressure reduced the levels of cell deformation and recovery associated with a significant increase in modulus and viscosity. Using GFP transfection and confocal microscopy, we show that chondrocyte deformation involves distortion, disassembly and subsequent reassembly of the cortical actin cytoskeleton. At faster pressure rates, cell deformation produced an increase in cell volume associated with membrane bleb formation. GFP-actin transfection inhibited the pressure rate dependent variation in cell mechanics indicating that this behaviour is regulated by GFP-sensitive actin dynamics.Conclusion: we suggest that slower rates of aspiration pressure enable greater levels of cortical actin distortion. This is partially inhibited by GFP or faster aspiration rates leading to membrane bleb formation and an increase in cell volume. Thus the rate of application of pressure regulates the viscoelastic mechanical properties of living cells through pressure rate sensitive differences in actin dynamics. Therefore cells appear softer when aspirated at a faster rate in contrast to what is expected of a normal viscoelastic materia
[Letter from Truman M. Martin regarding Public Proclamation No. 3]
No full textA draft letter from Truman M. Martin, Public Relations Officer, Western Defense Command and Fourth Army, that requests a newspaper publish Public Proclamation No. 3 and related press release. The letter also requests a copy of the issue containing the two items. The letter is generic and most likely meant to be sent to many newspapers in Military Area No. 1.The War Relocation Authority (WRA), together with the Wartime Civil Control Administration (WCCA), the Civil Affairs Division (CAD) and the Office of the Commanding General (OFG) of the Western Defense Command (WDC) operated together to segregate and house some 110,000 men women and children from 1942 to 1945. The collection contains documents and photographs relating to the establishment and administrative workings of the (WDC), the (WRA) and the (WCCA) for the year 1942
The Role of the Primary Cilium in Chondrocyte Response to Mechanical Loading
No full textArticular cartilage, like many other living tissues, experiences a complex physiological mechanical loading environment which regulates cell function and tissue homeostasis through a process of mechanotransduction. The underlying signalling pathways and mechanotransduction mechanisms are poorly understood but recent studies point to the involvement of a fascinating and previously over looked cellular organelle called the primary cilium. In other cell types, including epithelial cells and osteocytes, primary cilia have been shown to function as mechanoreceptors. This appears to involve deflection of the cilium in response to fluid shear forces which then activates calcium signalling pathways. In this chapter we examine the structure and function of the primary cilium and its potential role in mechanotransduction in articular chondrocytes. In particular we review exciting recent studies which suggest that the primary cilium mediates chondrocyte mechanotransduction through regulation of purinergic calcium signalling leading to changes in extracellular matrix synthesis. Furthermore we examine how other cilia-mediated mechanotransduction pathways, most notably hedgehog signalling, are also regulated by mechanical forces thereby controlling cell proliferation and tissue development. Finally we describe the regulation of primary cilia structure and how mechanical forces may influence the complex balance of cilia assembly and disassembly leading to alterations in cilia function. In summary this chapter explores the rapidly evolving area of primary cilia and their response to mechanical forces with a particular focus on articular cartilage for which mechanical loading is critical for homeostasis and functionality. Understanding the role of the primary cilium in mechanobiology will aid the development of novel therapeutic strategies for pathologies, such as osteoarthritis, that involve disruption of primary cilia function.</p
Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.
No full textBACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation
The archaeoacoustics of San Vitale, Ravenna
No full textThis research tests and assesses whether sixth-century social and cultural dynamics can be archaeologically identified by including the study of acoustics in the context of extant Late Antique Christian architecture, namely the centrally planned domed octagonal church of San Vitale at Ravenna. Implementing a holistic archaeological research strategy that includes human sensory perception of acoustical phenomena is the best approach to unravelling the complexities of social and cultural mechanisms operating in the sixth-century Mediterranean basin. The methods and issues of Archaeoacoustics are critiqued and developed in order to comment on the intentionality of acoustic attributes in sixth-century ecclesiastical architecture.The space syntax of San Vitale has been considered for isovists at key locations during the liturgical procession and sequence of the Mass celebration. These are compared with mapped areas of perceiving the acoustic characteristics of Clarity and Reverberation Time. Combining the visual and acoustic analysis of San Vitale, with a better understanding of its date and construction phases, the physical geometry and temporal logic of the church are discussed in relation to the reflexive exchange of influence between Ravenna, Milan and Constantinople. It is posited that liturgical and musical time and tempo is materially expressed in the evident and conceptual substance of San Vitale, a suggestion that offers a springboard for future study and debate
Martin Andersen Nexø
No full textThis is a short presentation of the main works of the Danish author Martin Andersen Nexø
An interspecific comparison of foraging range and nest density of four bumblebee (Bombus) species
No full textBumblebees are major pollinators of crops and wildflowers in northern temperate regions. Knowledge of their ecology is vital for the design of effective management and conservation strategies but key aspects remain poorly understood. Here we employed microsatellite markers to estimate and compare foraging range and nest density among four UK species: Bombus terrestris, Bombus pascuorum, Bombus lapidarius, and Bombus pratorum. Workers were sampled along a 1.5-km linear transect across arable farmland. Eight or nine polymorphic microsatellite markers were then used to identify putative sisters. In accordance with previous studies, minimum estimated maximum foraging range was greatest for B. terrestris (758 m) and least for B. pascuorum (449 m). The estimate for B. lapidarius was similar to B. pascuorum (450 m), while that of B. pratorum was intermediate (674 m). Since the area of forage available to bees increases as the square of foraging range, these differences correspond to a threefold variation in the area used by bumblebee nests of different species. Possible explanations for these differences are discussed. Estimates for nest density at the times of sampling were 29, 68, 117, and 26/km(2) for B. terrestris, B. pascuorum, B. lapidarius and B. pratorum, respectively. These data suggest that even among the most common British bumblebee species, significant differences in fundamental aspects of their ecology exist, a finding that should be reflected in management and conservation strategies
Heritability and Linkage Analysis of Appendicitis Utilizing Age at Onset
No full textAppendicitis usually afflicts the young, but there is a large tail in the distribution of onset age. The genetics of this disease are still not well understood. A heritability analysis and genome wide linkage analysis of a large twin dataset was undertaken. Treating age of onset of appendicitis as a censored survival trait revealed a heritability of 0.21, and found evidence of linkage to Chromosome 1p37.3. Author(s): Christopher Oldmeadow 1 * | Kerrie Mengersen 2 | Nicholas Martin 3 | David L. Duffy
The potential of pulsed low intensity ultrasound to stimulate chondrocytes matrix synthesis in agarose and monolayer cultures
No full textPulsed low intensity ultrasound (PLIUS) has been used successfully for bone fracture repair and has therefore been suggested for cartilage regeneration. However, previous in vitro studies with chondrocytes show conflicting results as to the effect of PLIUS on the elaboration of extracellular matrix. This study tests the hypothesis that PLIUS, applied for 20 min/day, stimulates the synthesis of sulphated glycosaminoglycan (sGAG) by adult bovine articular chondrocytes cultured in either monolayer or agarose constructs. For both culture models, PLIUS at either 30 or 100 mW/cm2 intensity had no net effect on the total sGAG content. Although PLIUS at 100 mW/cm2 did induce a 20% increase in sGAG content at day 2 of culture in agarose, this response was lost by day 5. Intensities of 200 and 300 mW/cm2 resulted in cell death probably due to heating from the ultrasound transducers. The lack of a sustained up-regulation of sGAG synthesis may reflect the suggestion that PLIUS only induces a stimulatory effect in the presence of a tissue injury response. These results suggest that PLIUS has a limited potential to provide an effective method of stimulating matrix production as part of a tissue engineering strategy for cartilage repair. <br/
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