Simultaneous magnetic resonance imaging and consolidation measurement of articular cartilage

Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer.

Progress in epithelial-mesenchymal transition research

The field of research of epithelial-mesenchymal transitions, EMT, and its reverse, mesenchymal-epithelial transitions, MET, has expanded very rapidly indeed from its beginnings, heralded by Professor Betty Hay in the 1970s and 1980s. This expansion has involved the realisation that the EMT was not just an interesting phenomenon of early developmental morphogenetic cell behaviour, but bore remarkable resemblance to clinically crucial pathological events in cancer invasion. Not surprisingly, this discipline soon became numerically dominant in the EMT publication field. Simultaneously, the EMT concept has been extended to normal physiological wound healing. Exploration revealed that these resemblances were more than skin deep: the same sets of growth factors, receptors, transcription factors, epigenetic marks and signalling pathways turned up repeatedly in EMTs and METs in a variety of contexts, both pathological and normal. This molecular genetic research in turn uncovered similarities of the EMT signature to that of fibrosis, a set of diseases which is of enormous clinical importance, rivalling that of cancer. Most recently, and more surprisingly, the EMT signature has shown considerable similarity to that found in stem cell and cancer stem cell biology.

Kiwifruit floral gene APETALA2 is alternatively spliced and accumulates in aberrant indeterminate flowers in the absence of miR172

In Arabidopsis, the identity of perianth and reproductive organs are specified by antagonistic action of two floral homeotic genes, APETALA2 (AP2) and AGAMOUS (AG). AP2 is also negatively regulated by an evolutionary conserved interaction with a microRNA, miR172, and has additional roles in general plant development. A kiwifruit gene with high levels of homology to AP2 and AP2-like genes from other plant species was identified. The transcript was abundant in the kiwifruit flower, particularly petal, suggesting a role in floral organ identity. Splice variants were identified, all containing both AP2 domains, including a variant that potentially produces a shorter transcript without the miRNA172 targeting site. Increased AP2 transcript accumulation was detected in the aberrant flowers of the mutant 'Pukekohe dwarf' with multiple perianth whorls and extended petaloid features. In contrast to normal kiwifruit flowers, the aberrant flowers failed to accumulate miR172 in the developing whorls, although accumulation was detected at the base of the flower. An additional role during dormancy in kiwifruit was proposed based on AP2 transcript accumulation in axillary buds before and after budbreak.

Synthesis of MgB2 at low temperature and autogenous pressure

High quality, micron-sized interpenetrating grains of MgB2 with high density are produced at low temperatures (~420oC < T < ~500oC) under autogenous pressure by pre-mixing Mg powder and NaBH4 and heating in an Inconel 601 alloy reactor for 5−15 hours. Optimum production of MgB2 with yields greater than 75% occurs for autogenous pressure in the range 1.0 MPa to 2.0 MPa with the reactor at ~500oC. Autogenous pressure is induced by the decomposition of NaBH4 in the presence of Mg and/or other Mg-based compounds. The morphology, transition temperature and magnetic properties of MgB2 are dependent on the heating regime. Significant improvement in physical properties accrues when the reactor temperature is held at 250oC for >20minutes prior to a hold at 500oC.

Chalcophile element geochemistry of the Boggy Plain Zoned Pluton, southeastern Australia : a S-saturated barren compositionally diverse magma

The behavior of the platinum group elements (PGE) and Re in felsic magmas is poorly understood due to scarcity of data. We report the concentrations of Ni, Cu, Re, and PGE in the compositionally diverse Boggy Plain zoned pluton (BPZP), which shows a variation of rock type from gabbro through granodiorite and granite to aplite with a SiO2 range from 52 to 74 wt %. In addition, major silicate and oxide minerals were analyzed for Ni, Cu, and Re, and a systematic sulfide study was carried out to investigate the role of silicate, oxide, and sulfide minerals on chalcophile element geochemistry of the BPZP. Mass balance calculation shows that the whole rock Cu budget hosted by silicate and oxide minerals is <13 wt % and that Cu is dominantly located in sulfide phases, whereas most of the whole rock Ni budget (>70 wt %) is held in major silicate and oxide minerals. Rhenium is dominantly hosted by magnetite and ilmenite. Ovoid-shaped sulfide blebs occur at the boundary between pyroxene phenocrysts and neighboring interstitial phases or within interstitial minerals in the gabbro and the granodiorite. The blebs are composed of pyrrhotite, pyrite, chalcopyrite, and S-bearing Fe-oxide, which contain total trace metals (Co, Ni, Cu, Ag, Pb) up to ~16 wt %. The mineral assemblage, occurrence, shape, and composition of the sulfide blebs are a typical of magmatic sulfide. PGE concentrations in the BPZP vary by more than two orders of magnitude from gabbro (2.7–7.8 ppb Pd, 0.025–0.116 ppb Ir) to aplite (0.05 ppb Pd, 0.001 ppb Ir). Nickel, Cu, Re, and PGE concentrations are positively correlated with MgO in all the rock types although there is a clear discontinuity between the granodiorite and the granite in the trends for Ni, Rh, and Ir when plotted against MgO. Cu/Pd values gradually increase from 6,100 to 52,600 as the MgO content decreases. The sulfide petrology and chalcophile element geochemistry of the BPZP show that sulfide saturation occurred in the late gabbroic stage of magma differentiation. Segregation and distribution of these sulfide blebs controlled Cu and PGE variations within the BPZP rocks although the magma of each rock type may have experienced a different magma evolution history in terms of crustal assimilation and crystal fractionation. The sulfide melt locked in the cumulate rocks must have sequestered a significant portion of the chalcophile elements, which restricted the availability of these metals to magmatic-hydrothermal ore fluids. Therefore, we suggest that the roof rocks that overlay the BPZP were not prospective for magmatic-hydrothermal Cu, Au, or Cu–Au deposits.

The effect of exercise on the skeletal muscle phospholipidome of rats fed a high-fat diet

The aim of this study was to examine the effect of endurance training on skeletal muscle phospholipid molecular species from high-fat fed rats. Twelve female Sprague-Dawley rats were fed a high-fat diet (78.1% energy). The rats were randomly divided into two groups, a sedentary control group and a trained group (125 min of treadmill running at 8 m/min, 4 days/wk for 4 weeks). Forty-eight hours after their last training bout phospholipids were extracted from the red and white vastus lateralis and analyzed by electrospray-ionization mass spectrometry. Exercise training was associated with significant alterations in the relative abundance of a number of phospholipid molecular species. These changes were more prominent in red vastus lateralis than white vastus lateralis. The largest observed change was an increase of similar to 30% in the abundance of 1-palmitoyl-2-linoleoyl phosphatidylcholine ions in oxidative fibers. Reductions in the relative abundance of a number of phospholipids containing long-chain n-3 polyunsaturated fatty acids were also observed. These data suggest a possible reduction in phospholipid remodeling in the trained animals. This results in a decrease in the phospholipid n-3 to n-6 ratio that may in turn influence endurance capacity.

Oral testosterone self-administration in male hamsters

The addiction potential of anabolic steroids remains largely unexplored. Here, we demonstrate voluntary oral testosterone intake in hamsters. Using a 2-bottle choice test, males preferred an aqueous solution of 200 microg/ml testosterone over vehicle. However, the taste of testosterone is not highly preferred. Addition of testosterone at 400 microg/ml increased fluid consumption from the nonpreferred bottle in a 2-bottle choice test, but cholesterol at the same concentration reduced drinking, suggesting that testosterone reward is not common to all sterols. With food-induced drinking, testosterone maintained fluid intake when food was withdrawn. These data demonstrate that oral self-administration of testosterone is reinforcing in hamsters, suggesting the potential for dependence in human users.

The lag effects and vulnerabilities of temperature effects on cardiovascular disease mortality in a subtropical climate zone in China

This research quantifies the lag effects and vulnerabilities of temperature effects on cardiovascular disease in Changsha—a subtropical climate zone of China. A Poisson regression model within a distributed lag nonlinear models framework was used to examine the lag effects of cold- and heat-related CVD mortality. The lag effect for heat-related CVD mortality was just 0–3 days. In contrast, we observed a statistically significant association with 10–25 lag days for cold-related CVD mortality. Low temperatures with 0–2 lag days increased the mortality risk for those ≥65 years and females. For all ages, the cumulative effects of cold-related CVD mortality was 6.6% (95% CI: 5.2%–8.2%) for 30 lag days while that of heat-related CVD mortality was 4.9% (95% CI: 2.0%–7.9%) for 3 lag days. We found that in Changsha city, the lag effect of hot temperatures is short while the lag effect of cold temperatures is long. Females and older people were more sensitive to extreme hot and cold temperatures than males and younger people.

Myogel, a novel, basement membrane-rich, extracellular matrix derived from skeletal muscle, is highly adipogenic in vivo and in vitro

Background/Aims Biological and synthetic scaffolds play important roles in tissue engineering and are being developed towards human clinical applications. Based on previous work from our laboratory, we propose that extracellular matrices from skeletal muscle could be developed for adipose tissue engineering. Methods Extracellular matrices (Myogels) extracted from skeletal muscle of various species were assessed using biochemical assays including ELISA and Western blotting. Biofunctionality was assessed using an in vitro differentiation assay and a tissue engineering construct model in the rat. Results Myogels were successfully extracted from mice, rats, pigs and humans. Myogels contained significant levels of laminin α4- and α2-subunits and collagen I compared to Matrigel™, which contains laminin 1 (α1β1γ1) and collagen IV. Levels of growth factors such as fibroblast growth factor 2 were significantly higher than Matrigel, vascular endothelial growth factor-A levels were significantly lower and all other growth factors were comparable. Myogels reproducibly stimulated adipogenic differentiation of preadipocytes in vitro and the growth of adipose tissue in the rat. Conclusions We found Myogel induces adipocyte differentiation in vitroand shows strong adipogenic potential in vivo, inducing the growth of well-vascularised adipose tissue. Myogel offers an alternative for current support scaffolds in adipose tissue engineering, allowing the scaling up of animal models towards clinical adipose tissue engineering applications.

Mesenchymal to epithelial transition in development and disease

Cellular plasticity is fundamental to embryonic development. The importance of cellular transitions in development is first apparent during gastrulation when the process of epithelial to mesenchymal transition transforms polarized epithelial cells into migratory mesenchymal cells that constitute the embryonic and extraembryonic mesoderm. It is now widely accepted that this developmental pathway is exploited in various disease states, including cancer progression. The loss of epithelial characteristics and the acquisition of a mesenchymal-like migratory phenotype are crucial to the development of invasive carcinoma and metastasis. However, given the morphological similarities between primary tumour and metastatic lesions, it is likely that tumour cells re-activate certain epithelial properties through a mesenchymal to epithelial transition (MET) at the secondary site, although this is yet to be proven. MET is also an essential developmental process and has been extensively studied in kidney organogenesis and somitogenesis. In this review we describe the process of MET, highlight important mediators, and discuss their implication in the context of cancer progression.

Defining the E-Cadherin repressor interactome in epithelial-mesenchymal transition : the PMC42 model as a case study

Epithelial-mesenchymal transition (EMT) is a feature of migratory cellular processes in all stages of life, including embryonic development and wound healing. Importantly, EMT features cluster with disease states such as chronic fibrosis and cancer. The dissolution of the E-cadherin-mediated adherens junction (AJ) is a key preliminary step in EMT and may occur early or late in the growing epithelial tumour. This is a first step for tumour cells towards stromal invasion, intravasation, extravasation and distant metastasis. The AJ may be inactivated in EMT by directed E-cadherin cleavage; however, it is increasingly evident that the majority of AJ changes are transcriptional and mediated by an expanding group of transcription factors acting directly or indirectly to repress E-cadherin expression. A review of the current literature has revealed that these factors may regulate each other in a hierarchical pattern where Snail1 (formerly Snail) and Snail2 (formerly Slug) are initially induced, leading to the activation of Zeb family members, TCF3, TCF4, Twist, Goosecoid and FOXC2. Within this general pathway, many inter-regulatory relationships have been defined which may be important in maintaining the EMT phenotype. This may be important given the short half-life of Snail1 protein. We have investigated these inter-regulatory relationships in the mesenchymal breast carcinoma cell line PMC42 (also known as PMC42ET) and its epithelial derivative, PMC42LA. This review also discusses several newly described regulators of E-cadherin repressors including oestrogen receptor-α and new discoveries in hypoxia- and growth factor-induced EMT. Finally, we evaluated how these findings may influence approaches to current cancer treatment.

Vimentin and epithelial-mesenchymal transition in human breast cancer : observations in vitro and in vivo

Breast cancer is a highly prevalent disease among women worldwide. While the expression of certain proteins within these tumours is used for prognosis and selection of therapies, there is a continuing need for additional markers to be identified. A considerable amount of current literature, based predominantly on cell culture systems, suggests that a major mechanism responsible for the progression of breast cancer is due to tumour cells losing their epithelial features and gaining mesenchymal properties. These events are proposed to be very similar to the epithelial-mesenchymal transition (EMT) process that has been well characterised in embryonic development. For the developmental and putative cancer EMT, the cell intermediate filament status changes from a keratin-rich network which connects to adherens junctions and hemidesmosomes, to a vimentin-rich network connecting to focal adhesions. This review summarises observations of vimentin expression in breast cancer model systems, and discusses the potential role of EMT in human breast cancer progression, and the prognostic usefulness of vimentin expression.

Cells Tissues Organs : preface

This volume stems from the 1st International Conference on Epithelial-Mesenchymal Transitions (EMT), which was convened by the editors on October 5–8, 2003 in the beautiful setting of Port Douglas, Queensland, Australia. EMT, the name given to the transformation of cells arranged in a coherent layer – epithelial cells – to more individualistic and potential motile cells – mesenchymal cells – was recognized decades ago by Prof. Elisabeth (Betty) Hay (Harvard Medical School, Boston, Mass., USA) as a primary mechanism in embryogenesis for remodelling tissues. More recently EMT has been seen as crucial to the spread and invasion of carcinoma, and more recently still, EMT-like changes have been detected in various pathologies marked by fi brosis. Despite the basic and clinical importance of EMT, this extremely rapidly growing fi eld had never previously had a conference devoted to it, and indeed the disciplines of developmental biology, cancer and pathology rarely interact although they have much to share. The chapters assembled for this volume encompass these three major themes of the meeting, development, pathology and cancer, and further highlight the commonality in terms of mechanisms and outcomes among them...

Epithelial-mesenchymal transitions - new insights into signaling, development and pathogenesis

This 2nd special edition of Cells Tissues Organs on epithelial-mesenchymal transitions (EMT) stems from the 2nd International Conference on EMT, which was convened by Shoukat Dedhar and Raghu Kalluri on October 1–3, 2005, in Vancouver, B.C., Canada. EMT – the transformation of epithelial cells which are usually arranged in a coherent layer and sessile, into more individualistic and motile cells, mesenchymal cells – is well recognized as an important primary mechanism in embryogenesis for remodeling tissues, as is the reverse transition. This has obvious implications in numerous pathophysiologies, and in particular EMT has emerged as an important feature of fibrosis in a growing number of organ types. It is now clear that about a third of the fibroblasts in the setting of organ fibrosis are likely derived from the epithelium. Cancer EMT remains topical, and although EMT has been reported in many cancer studies, this meeting was held against a backdrop of controversy in the cancer community as to the prevalence of EMT in clinical scenarios [Tarin et al.: Cancer Res 2005;65:5996–6000; Thompson et al.: Cancer Res 2005;65:5991–5995]...