Influence of osteocytes in the in vitro and in vivo β-tricalcium phosphate-stimulated osteogenesis

Osteocytes, known to act as the main regulators of bone homeostasis, have become a major focus in the field of bone research. Bioactive ceramics have been widely used for bone regeneration. However, there are few studies about the interaction of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in vivo osteogenesis of bioceramics are also unclear. The aim of this study was to investigate the role of osteocytes on the b-tricalcium phosphate (b-TCP) stimulated osteogenesis. It was found that osteocytes responded to the b-TCP stimulation, leading to the release of Wnt (wingless-related MMTV integration site), which enhanced osteogenic differentiation of bone marrow stromal cells via Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an osteoclast inducer, was also upregulated, indicating that osteocytes would also participated in activation of osteoclasts, which played a major role in the degradation process of b-TCP and new bone remodeling. In vivo studies further demonstrated that when the material was completely embedded by newly formed bone, the only cell contacting with the material was osteocyte. However, the material would eventually be degraded and replaced by the new bone, requiring the participation of osteoclasts and osteoblasts, which were demonstrated by using immunostaining in this study. As the only cell contacting with the material, osteocytes probably acted in a regulatory role to regulate the surrounding osteoclasts and osteoblasts. Osteocytes were also found to participate in the maturation of osteoblasts and the mineralization process of biomaterials, by upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These findings indicated that osteocytes involved in bone biomaterial-mediated osteogenesis and biomaterial degradation, providing valuable insights into the mechanism of material-stimulated osteogenesis, and a novel strategy to optimize the evaluating system for the biological properties of biomaterials.

Harnessing SD and CSR within corporate self-regulation of weak economies : a meta-regulation approach

The semantic of the terms “sustainable development” and “corporate social responsibility” have changed over time to a point where these concepts have become two interrelated processes for ensuring the far-reaching development of society. Their convergence has given dimension to the environmental and corporate regulation mechanisms in strong economies. This article deals with the question of how the ethos of this convergence could be incorporated into the self-regulation of businesses in weak economies where nonlegal drivers are either inadequate or inefficient. It proposes that the policies for this incorporation should be based on the precepts of meta-regulation that have the potential to hold force majeure, economic incentives, and assistance-related strategies to reach an objective from the perspective of weak economies.

Survey and Mapping Infrastructure Regulation 2004- Comments Relating to a 10-Year Review

Democratic governments raise taxes and charges and spend revenue on delivering peace, order and good government. The delivery process begins with a legislature as that can provide a framework of legally enforceable rules enacted according to the government’s constitution. These rules confer rights and obligations that allow particular people to carry on particular functions at particular places and times. Metadata standards as applied to public records contain information about the functioning of government as distinct from the non-government sector of society. Metadata standards apply to database construction. Data entry, storage, maintenance, interrogation and retrieval depend on a controlled vocabulary needed to enable accurate retrieval of suitably catalogued records in a global information environment. Queensland’s socioeconomic progress now depends in part on technical efficiency in database construction to address queries about who does what, where and when; under what legally enforceable authority; and how the evidence of those facts is recorded. The Survey and Mapping Infrastructure Act 2003 (Qld) addresses technical aspects of where questions – typically the officially recognised name of a place and a description of its boundaries. The current 10-year review of the Survey and Mapping Regulation 2004 provides a valuable opportunity to consider whether the Regulation makes sense in the context of a number of later laws concerned with management of Public Sector Information (PSI) as well as policies for ICT hardware and software procurement. Removing ambiguities about how official place names are to be regarded on a whole-of-government basis can achieve some short term goals. Longer-term goals depend on a more holistic approach to information management – and current aspirations for more open government and community engagement are unlikely to occur without such a longer-term vision.

Vibrational spectroscopic characterization of the phosphate mineral barbosalite Fe2+Fe3+2(PO4)2(OH)2 : implications for the molecular structure

Natural single-crystal specimens of barbosalite from Brazil, with general formula Fe2+Fe3+ 2 (PO4)2(OH)2 were investigated by Raman and infrared spectroscopy. The mineral occurs as secondary products in granitic pegmatites. The Raman spectrum of barbosalite is characterized by bands at 1020, 1033 and 1044 cm−1 cm−1, assigned to ν1 symmetric stretching mode of the HOPO3- 3 and PO3- 4 units. Raman bands at around 1067, 1083 and 1138 cm−1 are attributed to both the HOP and PO antisymmetric stretching vibrations. The set of Raman bands observed at 575, 589 and 606 cm−1 are assigned to the ν4 out of plane bending modes of the PO4 and H2PO4 units. Raman bands at 439, 461, 475 and 503 cm−1 are attributed to the ν2 PO4 and H2PO4 bending modes. Strong Raman bands observed at 312, 346 cm−1 with shoulder bands at 361, 381 and 398 cm−1 are assigned to FeO stretching vibrations. No bands which are attributable to water vibrations were found. Vibrational spectroscopy enables aspects of the molecular structure of barbosalite to be assessed.

Preferential invasion by Plasmodium merozoites and the self-regulation of parasite burden

The preferential invasion of particular red blood cell (RBC) age classes may offer a mechanism by which certain species of Plasmodia regulate their population growth. Asexual reproduction of the parasite within RBCs exponentially increases the number of circulating parasites; limiting this explosion in parasite density may be key to providing sufficient time for the parasite to reproduce, and for the host to develop a specific immune response. It is critical that the role of preferential invasion in infection is properly understood to model the within-host dynamics of different Plasmodia species. We develop a simulation model to show that limiting the range of RBC age classes available for invasion is a credible mechanism for restricting parasite density, one which is equally as important as the maximum parasite replication rate and the duration of the erythrocytic cycle. Different species of Plasmodia that regularly infect humans exhibit different preferences for RBC invasion, with all species except P. falciparum appearing to exhibit a combination of characteristics which are able to selfregulate parasite density.

Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer

We assessed whether alternative transcripts (using KLK2, KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance

The influence of cellular source on periodontal regeneration using calcium phosphate coated polycaprolactone scaffold supported cell sheets

Cell-based therapy is considered a promising approach to achieving predictable periodontal regeneration. In this study, the regenerative potential of cell sheets derived from different parts of the periodontium (gingival connective tissue, alveolar bone and periodontal ligament) were investigated in an athymic rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC) and gingival margin-derived cells (GMC) were obtained from human donors. The osteogenic potential of the primary cultures was demonstrated in vitro. Cell sheets supported by a calcium phosphate coated melt electrospun polycaprolactone (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL scaffold alone was able to promote alveolar bone formation within the defect after 4 weeks. The addition of ABC and PDLC sheets resulted in significant periodontal attachment formation. The GMC sheets did not promote periodontal regeneration on the root surface and inhibited bone formation within the CaP-PCL scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP-PCL scaffold could promote periodontal regeneration, but ABC sheets were not as effective as PDLC sheets in promoting new attachment formation.

Heat-producing crust regulation of subsurface temperatures : a stochastic model re-evaluation of the geothermal potential in western Queensland, Australia

A large subsurface, elevated temperature anomaly is well documented in Central Australia. High Heat Producing Granites (HHPGs) intersected by drilling at Innamincka are often assumed to be the dominant cause of the elevated subsurface temperatures, although their presence in other parts of the temperature anomaly has not been confirmed. Geological controls on the temperature anomaly remain poorly understood. Additionally, methods previously used to predict temperature at 5 km depth in this area are simplistic and possibly do not give an accurate representation of the true distribution and magnitude of the temperature anomaly. Here we re-evaluate the geological controls on geothermal potential in the Queensland part of the temperature anomaly using a stochastic thermal model. The results illustrate that the temperature distribution is most sensitive to the thermal conductivity structure of the top 5 km. Furthermore, the results indicate the presence of silicic crust enriched in heat producing elements between and 40 km.

Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway

Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used b-tricalcium phosphate (b-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to b-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the b-TCP stimulation, indicating that macrophage may participate in the b-TCP stimulated osteogenesis. Interestingly, when macrophageconditioned b-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials.

Regulation of the Fear Network by Mediators of Stress: Norepinephrine Alters the Balance between Cortical and Subcortical Afferent Excitation of the Lateral Amygdala

Pavlovian auditory fear conditioning involves the integration of information about an acoustic conditioned stimulus (CS) and an aversive unconditioned stimulus in the lateral nucleus of the amygdala (LA). The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE), regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased toward the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance toward the faster but more primitive subcortical input

Epigenetics underpinning the regulation of the CXC (ELR+) chemokines in non-small cell lung cancer

Background: Angiogenesis may play a role in the pathogenesis of Non-Small Cell Lung cancer (NSCLC). The CXC (ELR+) chemokine family are powerful promoters of the angiogenic response. Methods: The expression of the CXC (ELR+) family members (CXCL1-3/GROα-γ, CXCL8/IL-8, CXCR1/2) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of these chemokines was examined in normal bronchial epithelial and NSCLC cell lines. Results: Overall, expression of the chemokine ligands (CXCL1, 2, 8) and their receptors (CXCR1/2) were down regulated in tumour samples compared with normal, with the exception of CXCL3. CXCL8 and CXCR1/2 were found to be epigenetically regulated by histone post-translational modifications. Recombinant CXCL8 did not stimulate cell growth in either a normal bronchial epithelial or a squamous carcinoma cell line (SKMES-1). However, an increase was observed at 72 hours post treatment in an adenocarcinoma cell line. Conclusions: CXC (ELR+) chemokines are dysregulated in NSCLC. The balance of these chemokines may be critical in the tumour microenvironment and requires further elucidation. It remains to be seen if epigenetic targeting of these pathways is a viable therapeutic option in lung cancer treatment. © 2011 Baird et al.

The international regulation of persons displaced by climate change

It is certain that there will be changes in environmental conditions across the globe as a result of climate change. Such changes will require the building of biological, human and infrastructure resilience. In some instances, the building of such resilience will be insufficient to deal with extreme changes in environmental conditions and legal frameworks will be required to provide recognition and support for people relocating as a result of environmental change. International legal frameworks do not currently recognise or assist people displaced as a result of environmental factors. The objective of this chapter is to examine the areas of international law relevant to displacement arising from environmental factors, consider some of the proposed climate displacement instruments and suggest the most suitable international institution to host a program addressing climate displacement. In order to determine the most appropriate institution to address and regulate climate displacement, it is imperative to consider issues of governance. This paper seeks to examine this issue and determine whether it is preferable to place climate displacement programs into existing international legal frameworks, or whether it is necessary to regulate this area in an entirely new institution specifically designed to deal with the complex and cross-cutting issues surrounding the topic...

Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer

BACKGROUND: Prostacyclin synthase (PGIS) metabolizes prostaglandin H(2), into prostacyclin. This study aimed to determine the expression profile of PGIS in nonsmall cell lung cancer (NSCLC) and examine potential mechanisms involved in PGIS regulation. METHODS: PGIS expression was examined in human NSCLC and matched controls by reverse transcriptase polymerase chain reaction (RT-PCR), Western analysis, and immunohistochemistry. A 204-patient NSCLC tissue microarray was stained for PGIS and cyclooxygenase 2 (COX2) expression. Staining intensity was correlated with clinical parameters. Epigenetic mechanisms underpinning PGIS promoter expression were examined using RT-PCR, methylation-specific PCR, and chromatin immunoprecipitation analysis. RESULTS: PGIS expression was reduced/absent in human NSCLC protein samples (P <.0001), but not mRNA relative to matched controls. PGIS tissue expression was higher in squamous cell carcinoma (P =.004) and in male patients (P <.05). No significant correlation of PGIS or COX2 expression with overall patient survival was observed, although COX2 was prognostic for short-term (2-year) survival (P <.001). PGIS mRNA expression was regulated by DNA CpG methylation and histone acetylation in NSCLC cell lines, with chromatin remodeling taking place directly at the PGIS gene. PGIS mRNA expression was increased by both demethylation agents and histone deacetylase inhibitors. Protein levels were unaffected by demethylation agents, whereas PGIS protein stability was negatively affected by histone deacetylase inhibitors. CONCLUSIONS: PGIS protein expression is reduced in NSCLC, and does not correlate with overall patient survival. PGIS expression is regulated through epigenetic mechanisms. Differences in expression patterns between mRNA and protein levels suggest that PGIS expression and protein stability are regulated post-translationally. PGIS protein stability may have an important therapeutic role in NSCLC. © 2011 American Cancer Society.

Relational regulation theory and the role of social support and organisational fairness for nurses in a general acute context

Aims and objectives. To present a novel approach to nurse stress by exploring the demand–control–support model with organisational justice through the lens of relational regulation theory. Background. Nursing is often stressful due to high demands and dissatisfaction with pay, which impacts the mental well-being and productivity of nurses. Design. A cross-sectional design. Methods. A validated questionnaire was sent to the work addresses of all nursing and midwifery staff in a medium-sized general acute hospital in Australia. A total of 190 nurses and midwives returned completed questionnaires for the analyses. Results. The multiple regression analyses demonstrated that the model applies to the prototypical context of a general acute hospital and that job control, supervisor support and outside work support improve the job satisfaction and mental health of nurses. Conclusions. Most importantly, supervisor support was found to buffer the impact of excessive work demands. Fairness of procedures, distribution of resources and the quality and consistency of information are also beneficial. Relational regulation theory is applied to these findings as a novel way to conceptualise the mechanisms of support and fairness in nursing. Relevance to clinical practice. The importance of nurses’ well-being and job satisfaction is a priority for improving clinical outcomes. Practically, this means nurse managers should be encouraging nurses in the pursuit of diverse relational activities both at work and outside work.