Role of dentin matrix protein 1 in cartilage redifferentiation and osteoarthritis

Objective The aim of this study was to test the possible involvement, relevance and significance of dentin matrix protein 1 (DMP1) in chondrocyte redifferentiation and OA. Methods To examine the function of DMP1 in vitro, bone marrow stromal cells (BMSCs) and articular chondrocytes (ACs) were isolated and differentiated in micromasses in the presence or absence of DMP1 small interfering RNA and analysed for chondrogenic phenotype. The association of DMP1 expression with OA progression was analysed time dependently in the OA menisectomy rat model and in grade-specific OA human samples. Results It was found that DMP1 was strongly related to chondrogenesis, which was evidenced by the strong expression of DMP1 in the 14.5-day mouse embryonic cartilage development stage and in femoral heads of post-natal days 0 and 4. In vitro chondrogenesis in BMSCs and ACs was accompanied by a gradual increase in DMP1 expression at both the gene and protein levels. In addition, knockdown of DMP1 expression led to decreased chondrocyte marker genes, such as COL2A1, ACAN and SOX9, and an increase in the expression of COL10A and MMP13 in ACs. Moreover, treatment with IL-1β, a well-known catabolic culprit of proteoglycan matrix loss, significantly reduced the expression of DMP1. Furthermore, we also observed the suppression of DMP1 protein in a grade-specific manner in knee joint samples from patients with OA. In the menisectomy-induced OA model, an increase in the Mankin score was accompanied by the gradual loss of DMP1 expression. Conclusion Observations from this study suggest that DMP1 may play an important role in maintaining the chondrogenic phenotype and its possible involvement in altered cartilage matrix remodelling and degradation in disease conditions like OA.

The stabilising role of the costovertebral joints and spinous processes on thoracic spine stability

Introduction The importance of in vitro biomechanical testing in today’s understanding of spinal pathology and treatment modalities cannot be stressed enough. Different studies have used differing levels of dissection of their spinal segments for their testing protocols[1, 2]. The aim of this study was to assess the impact of removing the costovertebral joints and partial resection of the spinous process sequentially, on the stiffness of the immature thoracic bovine spinal segment. Materials and Methods Thoracic spines from 6-8 week old calves were used. Each spine was dissected and divided into motion segments with 5cm of attached rib on each side and full spinous processes including levels T4-T11 (n=28). They were potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37⁰C and 100% humidity, using moment control to a maximum 1.75 Nm with a loading rate of 0.3 Nm per second. They were first tested intact for ten load cycles with data collected from the tenth cycle. Progressive dissection was performed by removing first the attached ribs, followed by the spinous process at its base. Biomechanical testing was carried out after each level of dissection using the same protocol. Statistical analysis of the data was performed using repeated measures ANOVA. Results In combined flexion/extension there was a significant reduction in stiffness of 16% (p=0.002). This was mainly after resection of the ribs (14%, p=0.024) and mainly occurred in flexion where stiffness reduced by 22% (p=0.021). In extension, stiffness dropped by 13% (p=0.133). However there was no further significant change in stiffness on resection of the spinous process (<1%) (p=1.00). In lateral bending there was a significant decrease in stiffness of 13% (p<0.001). This comprised a drop of 11% on resection of the ribs (p=0.009) and a further 8% on resection of the spinous process (p=0.014). There was no difference between left and right bending. In axial rotation there was no significant change in stiffness after each stage of dissection (p=0.253). There was no difference between left and right rotation. Conclusion The costovertebral joints play a significant role in providing stability to the bovine thoracic spine in both flexion/extension and lateral bending, whereas the spinous processes play a minor role. Both elements have little effect on axial rotation stability.

Key facilitators and barriers to quality of life in residential aged care : the role of design

Australia is undergoing a critical demographic transition: the population is ageing. By 2050, one in four Australians will be older than 65 years and by 2031, the number of older Australians requiring residential aged care will increase 63%, to 1.4 million (ABS, 2005). In anticipation of this global demographic transition, the World Health Organisation has advocated ‘active ageing’, identifying health, participation and security as the three key factors that enhance quality of life for people as they age (WHO, 2002). While there is considerable discussion and acceptance of active ageing principles, little is known about the experience of ‘active ageing’ for older Australians who live in Residential Aged Care Facilities (RACF). This research addresses this knowledge gap by exploring the key facilitators and barriers to quality of life and active ageing in aged care from the perspective of aged care residents (n=12). To do this, the project documented the initial expectations and daily life experience of new residents living in a RACF over a one-year period. Combined with in-depth interviews and surveys, the project utilised Photovoice methodology - where participants used photography to record their lived experiences. The initial findings suggest satisfaction with living in aged care centers around five key themes; resident’s mental attitude to living in aged care, forming positive peer and staff relationships, self-determination and maintaining independence, opportunities to participate in interesting activities, and living in a safe and comfortable physical environment. This paper reports on the last of these five key themes, focusing on the role of design in facilitating quality of life, specifically: “living within these walls” – safety, comfort and the physical environment.

Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporters to produce efflux of dopamine and serotonin, respectively, in regions of the brain that have been implicated in reward. However, the role of serotonin/dopamine interactions in the behavioral effects of MDMA remains unclear. We previously showed that MDMA-induced locomotion, serotonin and dopamine release are 5-HT(2B) receptor-dependent. The aim of the present study was to determine the contribution of serotonin and 5-HT(2B) receptors to the reinforcing properties of MDMA. We show here that 5-HT(2B) (-/-) mice do not exhibit behavioral sensitization or conditioned place preference following MDMA (10 mg/kg) injections. In addition, MDMA-induced reinstatement of conditioned place preference after extinction and locomotor sensitization development are each abolished by a 5-HT(2B) receptor antagonist (RS127445) in wild type mice. Accordingly, MDMA-induced dopamine D1 receptor-dependent phosphorylation of extracellular regulated kinase in nucleus accumbens is abolished in mice lacking functional 5-HT(2B) receptors. Nevertheless, high doses (30 mg/kg) of MDMA induce dopamine-dependent but serotonin and 5-HT(2B) receptor-independent behavioral effects. These results underpin the importance of 5-HT(2B) receptors in the reinforcing properties of MDMA and illustrate the importance of dose-dependent effects of MDMA on serotonin/dopamine interactions.

Everyone’s watching it : the role of hype in television engagement through social media

Social media is playing an ever-increasing role in both viewers engagement with television and in the television industries evaluation of programming, in Australia – which is the focus of our study - and beyond. Twitter hashtags and viewer comments are increasingly incorporated into broadcasts, while Facebook fan pages provide a means of marketing upcoming shows and television personalities directly into the social media feed of millions of users. Additionally, bespoke applications such as FanGo and ZeeBox, which interact with the mainstream social networks, are increasingly being utilized by broadcasters for interactive elements of programming (c.f. Harrington, Highfield and Bruns, 2012). However, both the academic and industry study of these platforms has focused on the measure of content during the specific broadcast of the show, or a period surrounding it (e.g. 3 hours before until 3 am the next day, in the case of 2013 Nielsen SocialGuide reports). In this paper, we argue that this focus ignores a significant period for both television producers and advertisers; the lead-up to the program. If, as we argue elsewhere (Bruns, Woodford, Highfield & Prowd, forthcoming), users are persuaded to engage with content both by advertising of the Twitter hash-tag or Facebook page and by observing their network connections engaging with such content, the period before and between shows may have a significant impact on a viewers likelihood to watch a show. The significance of this period for broadcasters is clearly highlighted by the efforts they afford to advertising forthcoming shows through several channels, including television and social media, but also more widely. Biltereyst (2004, p.123) has argued that reality television generates controversy to receive media attention, and our previous small-scale work on reality shows during 2013 and 2014 supports the theory that promoting controversial behavior is likely to lead to increased viewing (Woodford & Prowd, 2014a). It remains unclear, however, to what extent this applies to other television genres. Similarly, while networks use of social media has been increasing, best practices remain unclear. Thus, by applying our telemetrics, that is social media metrics for television based on sabermetric approaches (Woodford, Prowd & Bruns, forthcoming; c.f. Woodford & Prowd, 2014b), to the period between shows, we are able to better understand the period when key viewing decisions may be made, to establish the significance of observing discussions within your network during the period between shows, and identify best practice examples of promoting a show using social media.

Assessing the role of spatial correlations during collective cell spreading

Spreading cell fronts are essential features of development, repair and disease processes. Many mathematical models used to describe the motion of cell fronts, such as Fisher’s equation, invoke a mean–field assumption which implies that there is no spatial structure, such as cell clustering, present. Here, we examine the presence of spatial structure using a combination of in vitro circular barrier assays, discrete random walk simulations and pair correlation functions. In particular, we analyse discrete simulation data using pair correlation functions to show that spatial structure can form in a spreading population of cells either through sufficiently strong cell–to–cell adhesion or sufficiently rapid cell proliferation. We analyse images from a circular barrier assay describing the spreading of a population of MM127 melanoma cells using the same pair correlation functions. Our results indicate that the spreading melanoma cell populations remain very close to spatially uniform, suggesting that the strength of cell–to–cell adhesion and the rate of cell proliferation are both sufficiently small so as not to induce any spatial patterning in the spreading populations.

Catalytic role of pre-adsorbed CO in platinum-based catalysts : the reduction of SO 2 by CO on Pt l Au m (CO) n

Using density functional theory, we have investigated the catalytic properties of bimetallic complex catalysts PtlAum(CO)n (l + m = 2, n = 1–3) in the reduction of SO2 by CO. Due to the strong coupling between the C-2p and metal 5d orbitals, pre-adsorption of CO molecules on the PtlAum is found to be very effective in not only reducing the activation energy, but also preventing poisoning by sulfur. As result of the coupling, the metal 5d band is broadened and down-shifted, and charge is transferred from the CO molecules to the PtlAum. As SO2 is adsorbed on the catalyst, partial charge moves to the anti-σ bonding orbitals between S and O in SO2, weakening the S–O bond strength. This effect is enhanced by pre-adsorbing up to three CO molecules, therefore the S–O bonds become vulnerable. Our results revealed the mechanism of the excellent catalytic properties of the bimetallic complex catalysts.

The role of the posterior superior temporal sulcus in audiovisual processing

In this study we investigate previous claims that a region in the left posterior superior temporal sulcus (pSTS) is more activated by audiovisual than unimodal processing. First, we compare audiovisual to visual-visual and auditory-auditory conceptual matching using auditory or visual object names that are paired with pictures of objects or their environmental sounds. Second, we compare congruent and incongruent audiovisual trials when presentation is simultaneous or sequential. Third, we compare audiovisual stimuli that are either verbal (auditory and visual words) or nonverbal (pictures of objects and their associated sounds). The results demonstrate that, when task, attention, and stimuli are controlled, pSTS activation for audiovisual conceptual matching is 1) identical to that observed for intramodal conceptual matching, 2) greater for incongruent than congruent trials when auditory and visual stimuli are simultaneously presented, and 3) identical for verbal and nonverbal stimuli. These results are not consistent with previous claims that pSTS activation reflects the active formation of an integrated audiovisual representation. After a discussion of the stimulus and task factors that modulate activation, we conclude that, when stimulus input, task, and attention are controlled, pSTS is part of a distributed set of regions involved in conceptual matching, irrespective of whether the stimuli are audiovisual, auditory-auditory or visual-visual.

Achieving superior SME performance : overarching role of marketing, innovation, and learning capabilities

While most studies examine the effect of marketing, innovation, and learning capabilities (often separately) on performance, this study develops a unified model to investigate the combined effect of these capabilities on performance. This study further examines the complementary effect of these capabilities on performance. This study draws on the resource-based view theory to examine 171 manufacturing SMEs. The findings suggest that marketing, innovation, and learning capabilities are positively related to SME performance. In addition, these capabilities interact with one another to create great synergy in achieving SME performance.

The role of intellectual resources, product innovation capability, reputational resources and marketing capability combinations in SME growth

This article examines the extent to which combinations of intellectual resources and product innovation capability, and reputational resources and marketing capability, influence the ability of small and medium-sized enterprises (SME) to meet or exceed performance goals. Empirical results drawn from 171 SMEs suggest that when the combination of intellectual resources and product innovation capability in addition to the combination of reputational resources and marketing capability are high, SME growth is enhanced. However, a high level of intellectual resources combined with a low level of product innovation capability as well as a combination of a high level of reputational resources with a low level of marketing capability (and vice versa) are not significantly related to growth. These results imply that a high level of resources cannot compensate for a low level of capabilities (and vice versa).

Examining the role of within functional area resource–capability complementarity in achieving customer and product-based performance outcomes

Adopting both the resource-based view and dynamic capability theory this study advances the contention that firms must possess both resources and capabilities at a superior level to achieve superior customer and product performance. To examine this contention this study investigates the individual effect of the complementarity between marketing resources and capability and complementarity between innovation resources and capability on customer and product performance respectively. The results of a survey of 171 B2B manufacturing firms show a significant main effect for complementarity between marketing resources–capability and complementarity between innovation resources–capability on customer and product performance. The findings also show that complementarity marketing resources–capability has a stronger positive relationship with customer performance than with product performance, while complementarity between innovation resources–capability has a stronger positive relationship with product performance than with customer performance.

Understanding service firms brand value creation : a multilevel perspective including the overarching role of service brand marketing capability

Purpose This study seeks to extend the existing literature on value creation by specifically focusing on service brand value creation (SBVC) and the role of brand marketing. Design/methodology/approach The authors first develop a model of SBVC and simultaneously investigate SBVC from the firm perspective (service brand value offering – SBVO) and from the customer perspective (service brand perceive value-in use – SBPVI). Subsequently, they investigate the effects of SBVO on SBPVI and integrate the moderation role of service brand marketing capability (SBMC) on the relationship between SBVO-SBPVI outcomes. SBVO is viewed as the firms' interpretation of and responsiveness to customer requirements via the delivery of superior performance the value offering through the service brand and SBPVI customers' perceived value from the firms' service brand. The contributions of SBVC to customer-based performance outcomes are then investigated. Hypotheses were tested using a sample of the senior managers of service firms in Cambodia and their customers. A survey was used to gather data via a drop-and-collect approach. Findings Results indicated that SBVO is positively related to SBPVI and SBPVI is positively related to customer-based performance. Noticeably, the results revealed that SBMC enhances the positive relationship between the firm SBVO and the customers SBPVI. Originality/value The paper extends the previous literature on value creation to capture SBVC. More significantly, the premise of the theoretical framework provides a breakthrough in the current SBVC literature which has so far neglected to take into account the dyadic approach (firm-customer) in understanding value creation and more specifically SBVC. The model is expanded by looking at the contingency role of SBMC in communicating value to customers.

The nurse's role in managing chemotherapy-induced nausea and vomiting

Background Nurses play a substantial role in the prevention and management of chemotherapy-induced nausea and vomiting (CINV). Objectives This study set out to describe nurses’ roles in the prevention and management of CINV and to identify any gaps that exist across countries. Methods A self-reported survey was completed by 458 registered nurses who administered chemotherapy to cancer patients in Australia, China, Hong Kong, and 9 Latin American countries. Results More than one-third of participants regarded their own knowledge of CINV as fair to poor. Most participants (>65%) agreed that chemotherapy-induced nausea and chemotherapy-induced vomiting should be considered separately (79%), but only 35% were confident in their ability to manage chemotherapy-induced nausea (53%) or chemotherapy-induced vomiting (59%). Only one-fifth reported frequent use of a standardized CINV assessment tool and only a quarter used international clinical guidelines to manage CINV. Conclusions Participants perceived their own knowledge of CINV management to be insufficient. They recognized the need to develop and use a standardized CINV assessment tool and the importance of adopting international guidelines to inform the management of CINV. Implications for Practice: Findings indicate that international guidelines should be made available to nurses in clinically relevant and easily accessible formats, that a review of chemotherapy assessment tools should be undertaken to identify reliable and valid measures amenable to use in a clinical settings, and that a CINV risk screening tool should be developed as a prompt for nurses to enable timely identification of and intervention for patients at high risk of CINV.

Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing

Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

Role of microRNAs in improved osteogenicity of topographically modified titanium implant surfaces

This project aimed at understanding the molecular mechanisms involved in the superior integration of micro-roughened titanium implant surfaces with the surrounding bone, when compared with their smooth surfaces. It involved studying the role of microRNAs and cell signaling pathways in the molecular regulation of bone cells on topographically modified titanium dental implants. The findings suggest a highly regulated microRNA-mediated control of molecular mechanisms during the process of bone formation that may be responsible for the superior osseointegration properties on micro-roughened titanium implant surfaces and indicate the possibility of using microRNA modulators to enhance osseointegration in clinically demanding circumstances.