Inhibition of p38 pathway leads to OA-like changes in a rat animal model

Objectives The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway is involved in a variety of inflammatory responses, including cytokine generation, cell differentiation proliferation and apoptosis. Here, we examined the effects of systemic p38 MAPK inhibition on cartilage cells and osteoarthritis (OA) disease progression by both in vitro and in vivo approaches. Methods p38 kinase activity was evaluated in normal and OA cartilage cells by measuring the amount of phosphorylated protein. To examine the function of p38 signaling pathway in vitro, normal chondrocytes were isolated and differentiated in the presence or absence of p38 inhibitor; SB203580 and analysed for chondrogenic phenotype. Effect of systemic p38 MAPK inhibition in normal and OA (induced by menisectomy) rats were analysed by treating animals with vehicle alone (DMS0) or p38 inhibitor (SB203580). Damage to the femur and tibial plateau was evaluated by modified Mankin score, histology and immunohistochemistry. Results Our in vitro studies have revealed that a down-regulation of chondrogenic and increase of hypertrophic gene expression occurs in the normal chondrocytes, when p38 is neutralized by a pharmacological inhibitor. We further observed that the basal levels of p38 phosphorylation were decreased in OA chondrocytes compared with normal chondrocytes. These findings together indicate the importance of this pathway in the regulation of cartilage physiology and its relevance to OA pathogenesis. At in vivo level, systematic administration of a specific p38 MAPK inhibitor, SB203580, continuously for over a month led to a significant loss of proteoglycan; aggrecan and cartilage thickness. On the other hand, SB203580 treated normal rats showed a significant increase in TUNEL positive cells, cartilage hypertrophy markers such as Type 10 collagen, Runt-related transcription factor and Matrix metalloproteinase-13 and substantially induced OA like phenotypic changes in the normal rats. In addition, menisectomy induced OA rat models that were treated with p38 inhibitor showed aggravation of cartilage damage. Conclusions In summary, this study has provided evidence that the component of the p38 MAPK pathway is important to maintain the cartilage health and its inhibition can lead to severe cartilage degenerative changes. The observations in this study highlight the possibility of using activators of the p38 pathway as an alternative approach in the treatment of OA.

Occurrence of LINE, gypsy-like, and copia-like retrotransposons in the clonally propagated sweet potato (Ipomoea batatas L.)

Retrotransposons are a class of transposable elements that represent a major fraction of the repetitive DNA of most eukaryotes. Their abundance stems from their expansive replication strategies. We screened and isolated sequence fragments of long terminal repeat (LTR), gypsy-like reverse transcriptase (rt) and gypsy-like envelope (env) domains, and two partial sequences of non-LTR retrotransposons, long interspersed element (LINE), in the clonally propagated allohexaploid sweet potato (Ipomoea batatas (L.) Lam.) genome. Using dot-blot hybridization, these elements were found to be present in the ~1597 Mb haploid sweet potato genome with copy numbers ranging from ~50 to ~4100 as observed in the partial LTR (IbLtr-1) and LINE (IbLi-1) sequences, respectively. The continuous clonal propagation of sweet potato may have contributed to such a multitude of copies of some of these genomic elements. Interestingly, the isolated gypsy-like env and gypsy-like rt sequence fragments, IbGy-1 (~2100 copies) and IbGy-2 (~540 copies), respectively, were found to be homologous to the Bagy-2 cDNA sequences of barley (Hordeum vulgare L.). Although the isolated partial sequences were found to be homologous to other transcriptionally active elements, future studies are required to determine whether they represent elements that are transcriptionally active under normal and (or) stressful conditions.

Graphene-like nano-sheets for surface acoustic wave gas sensor applications

The gas sensing properties of graphene-like nano-sheets deposited on 36° YX lithium tantalate (LiTaO3) surface acoustic wave (SAW) transducers are reported. The thin graphene-like nano-sheets were produced via the reduction of graphite oxide which was deposited on SAW interdigitated transducers (IDTs). Their sensing performance was assessed towards hydrogen (H2) and carbon monoxide (CO) in a synthetic air carrier gas at room temperature (25 °C) and 40 °C. Raman and X-ray photoelectron spectroscopy (XPS) revealed that the deposited graphite oxide (GO) was not completely reduced creating small, graphitic nanocrystals ∼2.7 nm in size. © 2008 Elsevier B.V.

Preparation and characterisation of tri-calcium phosphate scaffolds with tunnel-like macro-pores for bone tissue engineering

Calcium Phosphate ceramics have been widely used in tissue engineering due to their excellent biocompatibility and biodegradability. In the physiological environment, they are able to gradually degrade, absorbed and promote bone growth. Ultimately, they are capable of replacing damaged bone with new tissue. However, their low mechanical properties limit calcium phosphate ceramics in load-bearing applications. To obtain sufficient mechanical properties as well as high biocompatibility is one of the main focuses in biomaterials research. Therefore, the current project focuses on the preparation and characterization of porous tri-calcium phosphate (TCP) ceramic scaffolds. Hydroxapatite (HA) was used as the raw material, and normal calcium phosphate bioglass was added to adjust the ratio between calcium and phosphate. It was found that when 20% bioglass was added to HA and sintered at 1400oC for 3 hours, the TCP scaffold was obtained and this was confirmed by X-ray diffraction (XRD) analysis. Test results have shown that by applying this method, TCP scaffolds have significantly higher compressive strength (9.98MPa) than those made via TCP powder (<3MPa). Moreover, in order to further increase the compressive strength of TCP scaffolds, the samples were then coated with bioglass. For normal bioglass coated TCP scaffold, compressive strength was 16.69±0.5MPa; the compressive strength for single layer mesoporous bioglass coated scaffolds was 15.03±0.63MPa. In addition, this project has also concentrated on sizes and shapes effects; it was found that the cylinder scaffolds have more mechanical property than the club ones. In addition, this project performed cell culture within scaffold to assess biocompatibility. The cells were well distributed in the scaffold, and the cytotoxicity test was performed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay. The Alkaline Phosphatase (Alp) activity of human bone marrow mesenchymal stem cell system (hBMSCs) seeded on scaffold expressed higher in vitro than that in the positive control groups in osteogenic medium, which indicated that the scaffolds were both osteoconductive and osteoinductive, showing potential value in bone tissue engineering.

What Could Socially-just Literacy Instruction Look Like?

Schools in Australia today are expected to improve student outcomes in an increasingly constrained context focused on accountability. At the same time as teachers work within these constraints, they are also working to ensure that all students are able to achieve quality outcomes from schooling while dealing with increasing diversity of the student population. So what is a teacher’s role in providing equitable possibilities for all of the students in their care? Teachers are left with the difficult task of balancing the many mandatory requirements placed on them, and on their students, such as gaining improvements on high stakes test scores, with the important work of dealing with individual students and student cohorts in equitable and socially just ways. This impacts on the work of all teachers, however for those teachers working in schools in contexts of complexity and duress these pressures are never greater.