Altered cell interactions of subchondral bone osteoblasts and articular chondrocytes in osteoarthritis is through the mediation of ERK1/2 phosphorylation

Introduction: Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo a typical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. However, the mechanism(s) by which these changes occur during the OA development are not completely understood. Materials and Methods: ACCs and subchondral bone osteoblasts (SBOs) were harvested from OA and healthy patients for the cross-talk studies between normal and OA ACCs and SBOs. The involvement of mitogen activated protein kinase (MAPK) signalling pathway during the cell-cell interactions was analysed by zymography, ELISA and western blotting methods. Results: The direct and in-direct co-culture studies showed that OA (ACCs and SBOs) cells induced osteoarthritic changes of normal (ACC and SBOs) cells. This altered cell interaction induced by OA cells significantly aggravated the proteolytic activity, which resulted cartilage degeneration. The altered cell interaction appeared to significantly activate ERK 1/2 phosphorylation and inhibition of MAPK-ERK 1/2 pathway reversed the osteoarthrtitic phenotypic changes. Discussion and Conclusion: Our study has demonstrated that the altered bi-directional communication of SBOs and ACCs are critical for initiation and progression of OA related changes and that this process is mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA related disorders.

Communicating friendships : a case study of women in an Australian 'seachange' town

This thesis proposes =friendworks‘ as an important sub-group of social networks, comprised of networks of friends. It investigates friendworks of a particular group of adult Australian women as a way of understanding neglected aspects of social networking practices. Friendworks are contextualised to highlight two main themes of interest: population mobility and communication practices. The impact of relocation on individuals, local communities and the wider society is explored through a case study of female friendworks in a seachange community. Research findings point to the importance of friendworks in building and cohering social and emotional support, well-being, belonging and senses of place and community. Different types of communication methods were used by research participants for mediating different kinds of social ties within the friendworks considered here. Communication patterns were influenced by geographical proximity to friends, and the type of social support required of them (emotional, instrumental or companionship). Most findings were consistent with broader social patterns of communication. For example, face-to-face interactions were the dominant and most favoured communication method between local friends, regardless of whether they were weak or strong ties. The fixed-telephone and the internet were commonly in use to maintain old and geographically distant social ties, while mobile phones were used the least among friends in comparison with other communication methods. The key finding of this thesis is that friendworks are an extremely important solid network in contemporary society, providing mooring relations in a mobile world. Paradoxically, however, for women in this study, the mobile phone, which is popularly perceived as a flexible, multi-purpose communication technology for people on the move, was the least versatile of all technologies for maintaining friendworks. The cost of services was the main inhibitor here. The internet was found to be the most versatile communication technology and was used to support various types of social ties: strong, weak, local and distant. This thesis also highlights the value of the concept of friendworks as well as networks for communication research and policy investigating individuals‘ motivations and practices.

A solid state Marx generator with a novel configuration

The new configuration proposed in this paper for Marx Generator (MG) aims to generate high voltage for pulsed power applications through reduced number of semiconductor components with a more efficient load supplying process. The main idea is to charge two groups of capacitors in parallel through an inductor and take advantage of resonant phenomenon in charging each capacitor up to a double input voltage level. In each resonant half a cycle, one of those capacitor groups are charged, and eventually the charged capacitors will be connected in series and the summation of the capacitor voltages can be appeared at the output of the topology. This topology can be considered as a modified Marx generator which works based on the resonant concept. Simulated models of this converter have been investigated in Matlab/SIMULINK platform and a prototype set up has been implemented in laboratory. The acquired results of either fully satisfy the anticipations in proper operation of the converter.

A solid state Marx generator with a novel configuration

The new configuration proposed in this paper for Marx Generator (MG.) aims to generate high voltage for pulsed power applications through reduced number of semiconductor components with a more efficient load supplying process. The main idea is to charge two groups of capacitors in parallel through an inductor and take the advantage of resonant phenomenon in charging each capacitor up to a double input voltage level. In each resonant half a cycle, one of those capacitor groups are charged, and eventually the charged capacitors will be connected in series and the summation of the capacitor voltages can be appeared at the output of the topology. This topology can be considered as a modified Marx generator which works based on the resonant concept. Simulated models of this converter have been investigated in Matlab/SIMULINK platform and the acquired results fully satisfy the anticipations in proper operation of the converter.

‘It’s not like we’re going to jump them’: how transgressing heteronormativity shapes police interactions with LGBT young people

This paper explores how visibly transgressing heteronormativity shapes police interactions with LGBT young people. While research evidences how sexually and gender diverse bodies can be abused in schools, policing is overlooked. Interviews with 35 LGBT young people demonstrate how bodies transgressing heteronormativity (that is, non-heteronormative bodies) mediate their policing experiences in Queensland, Australia. Drawing on Foucault, Butler, and others, the paper suggests police interactions and use of discretion with LGBT young people was informed by non-heteronormative bodies discursively performing queerness in ways read by police. The paper concludes noting tensions produced for youthful LGBT bodies in public spaces.

Reproducing successful rituals in bad times : exploring interactions of a new science teacher

Teaching is emotional work. This is especially the case in the first years of teaching when new teachers are particularly vulnerable. By understanding changes in teacher emotions in the early years of teaching we hope to identify strategies that might ultimately reduce teacher attrition. As part of a larger study of the transition of new teachers to the profession, this ethnographic case study explores how a new science teacher produced and reproduced positive emotional interaction rituals with her students in her first year of teaching. We show how dialogical interactions were positive and satisfying experiences for the teacher, and how they were reproduced successfully in different contexts. We also illustrate how both teacher and students used humor to create a structure for dialogical interactions. During these successful interactions the students used shared resources to satisfy their teacher that they were engaging in the relevant science content. The implications of what we have learned for the professional development of new teachers are discussed in relation to an expanded understanding of teacher emotions.

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

Like a set of bookends, cellular, molecular, and genetic changes of the beginnings of life mirror those of one of the most common cause of death—metastatic cancer. Epithelial to mesenchymal transition (EMT) is an important change in cell phenotype which allows the escape of epithelial cells from the structural constraints imposed by tissue architecture, and was first recognized by Elizabeth Hay in the early to mid 1980's to be a central process in early embryonic morphogenesis. Reversals of these changes, termed mesenchymal to epithelial transitions (METs), also occur and are important in tissue construction in normal development. Over the last decade, evidence has mounted for EMT as the means through which solid tissue epithelial cancers invade and metastasize. However, demonstrating this potentially rapid and transient process in vivo has proven difficult and data connecting the relevance of this process to tumor progression is still somewhat limited and controversial. Evidence for an important role of MET in the development of clinically overt metastases is starting to accumulate, and model systems have been developed. This review details recent advances in the knowledge of EMT as it occurs in breast development and carcinoma and prostate cancer progression, and highlights the role that MET plays in cancer metastasis. Finally, perspectives from a clinical and translational viewpoint are discussed

A Raman spectroscopic study of the different vanadate-groups in solid-state compounds, model case : mineral phases vésigniéite, BaCu3(VO4)2(OH)2, and volborthite, Cu3V2O7(OH)2•2H2O

Raman spectroscopy has been used to study vanadates in the solid state. The molecular structure of the vanadate minerals vésigniéite [BaCu3(VO4)2(OH)2] and volborthite [Cu3V2O7(OH)2·2H2O] have been studied by Raman spectroscopy and infrared spectroscopy. The spectra are related to the structure of the two minerals. The Raman spectrum of vésigniéite is characterized by two intense bands at 821 and 856 cm−1 assigned to ν1 (VO4)3− symmetric stretching modes. A series of infrared bands at 755, 787 and 899 cm−1 are assigned to the ν3 (VO4)3− antisymmetric stretching vibrational mode. Raman bands at 307 and 332 cm−1 and at 466 and 511 cm−1 are assigned to the ν2 and ν4 (VO4)3− bending modes. The Raman spectrum of volborthite is characterized by the strong band at 888 cm−1, assigned to the ν1 (VO3) symmetric stretching vibrations. Raman bands at 858 and 749 cm−1 are assigned to the ν3 (VO3) antisymmetric stretching vibrations; those at 814 cm−1 to the ν3 (VOV) antisymmetric vibrations; that at 508 cm−1 to the ν1 (VOV) symmetric stretching vibration and those at 442 and 476 cm−1 and 347 and 308 cm−1 to the ν4 (VO3) and ν2 (VO3) bending vibrations, respectively. The spectra of vésigniéite and volborthite are similar, especially in the region of skeletal vibrations, even though their crystal structures differ.

Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane

The dynamic lateral segregation of signaling proteins into microdomains is proposed to facilitate signal transduction, but the constraints on microdomain size, mobility, and diffusion that might realize this function are undefined. Here we interrogate a stochastic spatial model of the plasma membrane to determine how microdomains affect protein dynamics. Taking lipid rafts as representative microdomains, we show that reduced protein mobility in rafts segregates dynamically partitioning proteins, but the equilibrium concentration is largely independent of raft size and mobility. Rafts weakly impede small-scale protein diffusion but more strongly impede long-range protein mobility. The long-range mobility of raft-partitioning and raft-excluded proteins, however, is reduced to a similar extent. Dynamic partitioning into rafts increases specific interprotein collision rates, but to maximize this critical, biologically relevant function, rafts must be small (diameter, 6 to 14 nm) and mobile. Intermolecular collisions can also be favored by the selective capture and exclusion of proteins by rafts, although this mechanism is generally less efficient than simple dynamic partitioning. Generalizing these results, we conclude that microdomains can readily operate as protein concentrators or isolators but there appear to be significant constraints on size and mobility if microdomains are also required to function as reaction chambers that facilitate nanoscale protein-protein interactions. These results may have significant implications for the many signaling cascades that are scaffolded or assembled in plasma membrane microdomains.