Stem cell–related gene expression in clonal populations of mesenchymal stromal cells from bone marrow

Decline in the frequency of potent mesenchymal stem cells (MSCs) has been implicated in ageing and degenerative diseases. Increasing the circulating stem cell population can lead to renewed recruitment of these potent cells at sites of damage. Therefore, identifying the ideal cells for ex vivo expansion will form a major pursuit of clinical applications. This study is a follow-up of previous work that demonstrated the occurrence of fast-growing multipotential cells from the bone marrow samples. To investigate the molecular processes involved in the existence of such varying populations, gene expression studies were performed between fast- and slow-growing clonal populations to identify potential genetic markers associated with stemness using the quantitative real-time polymerase chain reaction comprising a series of 84 genes related to stem cell pathways. A group of 10 genes were commonly overrepresented in the fast-growing stem cell clones. These included genes that encode proteins involved in the maintenance of embryonic and neural stem cell renewal (sex-determining region Y-box 2, notch homolog 1, and delta-like 3), proteins associated with chondrogenesis (aggrecan and collagen 2 A1), growth factors (bone morphogenetic protein 2 and insulin-like growth factor 1), an endodermal organogenesis protein (forkhead box a2), and proteins associated with cell-fate specification (fibroblast growth factor 2 and cell division cycle 2). Expression of diverse differentiation genes in MSC clones suggests that these commonly expressed genes may confer the maintenance of multipotentiality and self-renewal of MSCs.

Multi-events stadium Buchanan Park redevelopment

Multi-purpose Community Entertainment and Recreation Venue, catering for the Mount Isa Rodeo; including campdraft, equine sports, shows, exhibition, trade events, concerts and other community activities. The design involved redevelopment of a portion of the Buchanan Park Race Course located in Mount Isa. The project included community infrastructure planning, major landscaping and the construction of built facilities.

Informed learning: a pedagogical construct attending simultaneously to information use and learning.

The idea of informed learning, applicable in academic, workplace and community settings, has been derived largely from a program of phenomenographic research in the field of information literacy, which has illuminated the experience of using information to learn. Informed learning is about simultaneous attention to information use and learning, where both information and learning are considered to be relational; and is built upon a series of key concepts such as second–order perspective, simultaneity, awareness, and relationality. Informed learning also relies heavily on reflection as a strategy for bringing about learning. As a pedagogical construct, informed learning supports inclusive curriculum design and implementation. This paper reports aspects of the informed learning research agenda which are currently being pursued at the Queensland University of Technology (QUT). The first part elaborates the idea of informed learning, examines the key concepts underpinning this pedagogical construct, and explains its emergence from the research base of the QUT Information Studies research team. The second presents a case, which demonstrates the ongoing development of informed learning theory and practice, through the development of inclusive informed learning for a culturally diverse higher education context.

Implications of lipid biology for the pathogenesis of schizophrenia

Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. Methods: Medline databases were searched from 1966 to 2001 followed by the crosschecking of references. Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. Conclusion: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

Outcomes following operative and non-operative management of humeral midshaft fractures: a prospective, observational cohort study of 47 patients

Background Although the non-operative management of closed humeral midshaft fractures has been advocated for years, the increasing popularity of operative intervention has left the optimal treatment choice unclear. Objective To compare the outcomes of operative and non-operative treatment of traumatic closed humeral midshaft fractures in adult patients. Methods A multicentre prospective comparative cohort study across 20 centres was conducted. Patients with AO type 12 A2, A3 and B2 fractures were treated with a functional brace or a retrograde-inserted unreamed humeral nail. Follow-up measurements were taken at 6, 12 and 52 weeks after the injury. The primary outcome was fracture healing after 1 year. Secondary outcomes included sub-items of the Constant score, general patient satisfaction, complications and cost-effectiveness parameters. Functions of the uninjured extremity were used as reference parameters. Intention-to-treat analysis was applied with the use of t-tests, Fisher’s exact tests, Mann–Whitney U-tests and adjusted analysis of variance (ANOVA). Results Forty-seven patients were included. The patient sample consisted of 23 women and 24 men, with a mean age of 52.7 years (range 17–86 years). Of the 47 cases, 14 were treated non-operatively and 33 operatively. The follow-up rate at 1 year was 81%. After 1 year, 11 fractures (100%) healed in the non-operative group and at least 24 fractures (≥89%) healed in the operative group [1 non-union patient (4%) and no data for 2 patients (7%)]. There were no significant differences in pain, range of motion (ROM) of the shoulder and elbow, and return to work after 6 weeks, 12 weeks and 1 year. Although operatively treated patients showed significantly greater shoulder abduction strength (p = 0.036), elbow flexion strength (p = 0.021), functional hand positioning (p = 0.008) and return to recreational activities (p = 0.043) after 6 weeks, no statistically significant differences existed in any outcome measure at the 1-year follow-up. Conclusions Our findings indicate that the non-operative management of humeral midshaft fractures can be expected to have similar functional outcomes and patient satisfaction at 1 year, despite an early benefit to operative treatment. If no radiological evidence of fracture healing exists in non-operatively treated patients during early follow-up, a switch to surgical treatment results in good functional outcomes and patient satisfaction. Keywords: Humeral shaft fracture, Non-operative treatment, Functional brace, Operative treatment, Unreamed humeral nail (UHN), Prospective, Cohort study

The theory and practice on pre-qualification in bidding procedure

资格预审是招标程序中重要环节.通过对投标人的资质和业绩等审查既能保证不符合 要求的投标人尽可能早地退出无谓竞争的行列,避免了大量人力"物力的损失和浪费, 又能促进建筑市场优胜劣汰,提高企业竞争力.同时鉴于目前资格预审和建筑市场存在 的问题,笔者以为通过强化资格预审可以有效推进建筑市场信用体系建设,促进行业健康发展,并且深入探讨了资格预审体系建立的具体对策和措施.

Drugs and local chemical mediators

10.1 Histamine and cytokines 10.1.1 Actions of histamine 10.1.2 Drugs that modify the actions of histamine 10.1.3 Cytokines 10.2 Eicosanoids 10.2.1 Cyclooxygenase (COX) and lipooxygenase system 10.2.2 Actions of eicosanoids 10.2.3 Drugs that modify the actions of eicosanoids 10.2.3.1 Inhibit phospholipase A2 10.2.3.2 Non-selective cyclooxygenase inhibitors 10.2.3.3 Selective COX-2 inhibitors 10.2.3.4 Agonists at prostaglandin receptors 10.2.3.5 Leukotriene receptor antagonists 10.3. 5-Hydroxtryptamine (serotonin), nitric oxide, and endothelin 10.3.1 5-HT and migraine 10.3.2 5-HT and the gastrointestinal tract 10.3.3 Nitric oxide and angina 10.3.4 Nitric oxide and erectile dysfunction 10.3.5 Endothelin and pulmonary hypertension

Evaluation of Eph receptor and ephrin expression within the human cornea and limbus

Eph receptor tyrosine kinases and their ligands, the ephrins, regulate the development and maintenance of multiple organs but little is known about their potential role within the cornea. The purpose of this study was to perform a thorough investigation of Eph/ephrin expression within the human cornea including the limbal stem cell niche. Initially, immunohistochemistry was performed on human donor eyes to determine the spatial distribution of Eph receptors and ephrins in the cornea and limbus. Patterns of Eph/ephrin gene expression in (1) immortalised human corneal endothelial (B4G12) or corneal epithelial (HCE-T) cell lines, and (2) primary cultures of epithelial or stromal cells established from the corneal limbus of cadaveric eye tissue were then assessed by reverse transcription (RT) PCR. Limbal epithelial or stromal cells from primary cultures were also assessed for evidence of Eph/ephrin-reactivity by immunofluorescence. Immunoreactivity for ephrinA1 and EphB4 was detected in the corneal endothelium of donor eyes. EphB4 was also consistently detected in the limbal and corneal epithelium and in cells located in the stroma of the peripheral cornea. Expression of multiple Eph/ephrin genes was detected in immortalised corneal epithelial and endothelial cell lines. Evidence of Eph/ephrin gene expression was also demonstrated in primary cultures of human limbal stromal (EphB4, B6; ephrinA5) and epithelial cells (EphA1, A2; ephrinA5, B2) using both RT-PCR and immunofluorescence. The expression of Eph receptors and ephrins within the human cornea and limbus is much wider than previously appreciated and suggests multiple potential roles for these molecules in the maintenance of normal corneal architecture.

Metastable carbon in two chondritic porous interplanetary dust particles

An understanding of carbonaceous matter in primitive extraterrestrial materials is an essential component of studies on dust evolution in the interstellar medium and the early history of the Solar System. We have suggested previously that a record of graphitization is preserved in chondritic porous (CP) aggregates and carbonaceous chondrites1,2 and that the detailed mineralogy of CP aggregates can place boundary conditions on the nature of both physical and chemical processes which occurred at the time of their formation2,3. Here, we report further analytical electron microscope (AEM) studies on carbonaceous material in two CP aggregates which suggest that a record of hydrocarbon carbonization may also be preserved in these materials. This suggestion is, based upon the presence of well-ordered carbon-2H (lonsdaleite) in CP aggregates W7029*A and W7010*A2. This carbon is a metastable phase resulting from hydrous pyrolysis below 300-350°C and may be a precursor to poorly graphitized carbons (PGCs) in primitive extraterrestrial materials2. © 1987 Nature Publishing Group.

Analysis and control of cracking due to shrinkage in cast-in-place reinforced concrete slabs

The numerical analysis method of cracking in cast-in-place reinforced concrete slabs is presented. T he results agree w ell with the actual conditions. T he current state of knowledge and some new research findings on crack-control are introduced such as increasing the quantities of the distribution steel, adopting fibre reinforced concrete etc. Some recommended crack-control procedures used in design construction is presented based on the investigation and study of cracking in a frame structure.

COX-derived prostanoid pathways in gastrointestinal cancer development and progression : novel targets for prevention and intervention

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE 2, which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2. Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. © 2011 Elsevier B.V.

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer

Prostacyclin synthase and thromboxane synthase signaling via arachidonic acid metabolism affects a number of tumor cell survival pathways such as cell proliferation, apoptosis, tumor cell invasion and metastasis, and angiogenesis. However, the effects of these respective synthases differ considerably with respect to the pathways described. While prostacyclin synthase is generally believed to be anti-tumor, a pro-carcinogenic role for thromboxane synthase has been demonstrated in a variety of cancers. The balance of oppositely-acting COX-derived prostanoids influences many processes throughout the body, such as blood pressure regulation, clotting, and inflammation. The PGI2/TXA2 ratio is of particular interest in-vivo, with the corresponding synthases shown to be differentially regulated in a variety of disease states. Pharmacological inhibition of thromboxane synthase has been shown to significantly inhibit tumor cell growth, invasion, metastasis and angiogenesis in a range of experimental models. In direct contrast, prostacyclin synthase overexpression has been shown to be chemopreventive in a murine model of the disease, suggesting that the expression and activity of this enzyme may protect against tumor development. In this review, we discuss the aberrant expression and known functions of both prostacyclin synthase and thromboxane synthase in cancer. We discuss the effects of these enzymes on a range of tumor cell survival pathways, such as tumor cell proliferation, induction of apoptosis, invasion and metastasis, and tumor cell angiogenesis. As downstream signaling pathways of these enzymes have also been implicated in cancer states, we examine the role of downstream effectors of PGIS and TXS activity in tumor growth and progression. Finally, we discuss current therapeutic strategies aimed at targeting these enzymes for the prevention/treatment of cancer. © 2010 Elsevier B.V. All rights reserved.