Myofibroblastic conversion of mesothelial cells

Myofibroblastic conversion of mesothelial cells.BackgroundThe continuous chemical, physical, and inflammatory insults of prolonged continuous ambulatory peritoneal dialysis (CAPD) incite mesothelial cell responses, which may result in peritoneal fibrosis. The transforming growth factor-β (TGF-β), especially the isoform TGF-β1, has long been known to play crucial role in the fibrogenic process. Although several studies have implicated TGF-β in peritoneal fibrosis, the underlying mechanism has not been completely elucidated.MethodsTo test the effects of exogenous TGF-β1 on mesothelial cells, we assessed cytoarchitectural changes of human peritoneal mesothelial cells (HPMC) in in vitro culture by light, immunofluorescent, electron and immunoelectron microscopy, and differential gene expression analysis using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and cDNA expression array assays.ResultsThe TGF-β1–induced myofibroblastic conversion was a transdifferentiation process resulting in characteristic myofibroblastic phenotype that included prominent rough endoplasmic reticuli (rER) with dilated cisternas, conspicuous smooth muscle actin (SMA) myofilaments, frequent intercellular intermediate and gap junctions, and active deposition of extracellular matrix (ECM) and formation of fibronexus. The gene expression array analysis revealed complex modulation of gene expression involving cytoskeletal organization, cell adhesion, ECM production, cell proliferation, innate immunity, cytokine/growth factor signaling, cytoprotection, stress response, and many other essential metabolic processes in mesothelial cells.ConclusionThis report describes myofibroblastic conversion of mesothelial cells, a previously undefined, yet frequently speculated, cell adaptive or pathogenic process. Our study helps to elucidate the complex molecular and cellular events involved in myofibroblastic conversion of mesothelial cells. We propose that differentiated epithelial cells of mesothelium convert or transdifferentiate into myofibroblasts, which implies the recruitment of fibrogenic cells from mesothelium during serosal inflammation and wound healing

CAPIH: A Web interface for comparative analyses and visualization of host-HIV protein-protein interactions

<p>Abstract</p> <p>Background</p> <p>The Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS). A large number of HIV-1-related studies are based on three non-human model animals: chimpanzee, rhesus macaque, and mouse. However, the differences in host-HIV-1 interactions between human and these model organisms have remained unexplored.</p> <p>Description</p> <p>Here we present CAPIH (Comparative Analysis of Protein Interactions for HIV-1), the first web-based interface to provide comparative information between human and the three model organisms in the context of host-HIV-1 protein interactions. CAPIH identifies genetic changes that occur in HIV-1-interacting host proteins. In a total of 1,370 orthologous protein sets, CAPIH identifies ~86,000 amino acid substitutions, ~21,000 insertions/deletions, and ~33,000 potential post-translational modifications that occur only in one of the four compared species. CAPIH also provides an interactive interface to display the host-HIV-1 protein interaction networks, the presence/absence of orthologous proteins in the model organisms in the networks, the genetic changes that occur in the protein nodes, and the functional domains and potential protein interaction hot sites that may be affected by the genetic changes. The CAPIH interface is freely accessible at <url>http://bioinfo-dbb.nhri.org.tw/capih</url>.</p> <p>Conclusion</p> <p>CAPIH exemplifies that large divergences exist in disease-associated proteins between human and the model animals. Since all of the newly developed medications must be tested in model animals before entering clinical trials, it is advisable that comparative analyses be performed to ensure proper translations of animal-based studies. In the case of AIDS, the host-HIV-1 protein interactions apparently have differed to a great extent among the compared species. An integrated protein network comparison among the four species will probably shed new lights on AIDS studies.</p

What influences geography teachers' usage of geographic information systems? A structural equation analysis

Understanding the usage of the geographic information system (GIS) among geography teachers is a crucial step in evaluating the current dissemination of GIS knowledge and skills in Taiwan's educational system. The primary contribution of this research is to further our understanding of the factors that affect teachers' GIS usage. The structural equation model was employed to analyze the data collected from 725 senior high school geography teachers. This was done using a survey questionnaire inspired by the Technology Acceptance Model (TAM), which postulates the importance of how teachers perceived the usefulness and ease of use of GIS. Further, this study investigates the direct effect of GIS workshop attendance on actual GIS usage and assesses whether GIS workshop attendance mediates the relationship between perceived ease of use, perceived usefulness, and actual usage. Structural equation modeling results suggest that the perceived usefulness of adopting GIS is vital as it directly affects teachers' attendance at GIS training, and can further prompt their application of GIS in lectures. The perceived ease of GIS use does not influence actual usage directly, but does affect teachers' GIS usage in teaching through perceived usefulness and workshop attendance. Finally, workshop attendance can increase teachers' usage of GIS and mediate the association between perceived usefulness and actual usage

iGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis

<p>Abstract</p> <p>Background</p> <p>Pharmacological interactions are useful for understanding ligand binding mechanisms of a therapeutic target. These interactions are often inferred from a set of active compounds that were acquired experimentally. Moreover, most docking programs loosely coupled the stages (binding-site and ligand preparations, virtual screening, and post-screening analysis) of structure-based virtual screening (VS). An integrated VS environment, which provides the friendly interface to seamlessly combine these VS stages and to identify the pharmacological interactions directly from screening compounds, is valuable for drug discovery.</p> <p>Results</p> <p>We developed an easy-to-use graphic environment, <it>i</it>GEMDOCK, integrating VS stages (from preparations to post-screening analysis). For post-screening analysis, <it>i</it>GEMDOCK provides biological insights by deriving the pharmacological interactions from screening compounds without relying on the experimental data of active compounds. The pharmacological interactions represent conserved interacting residues, which often form binding pockets with specific physico-chemical properties, to play the essential functions of a target protein. Our experimental results show that the pharmacological interactions derived by <it>i</it>GEMDOCK are often hot spots involving in the biological functions. In addition, <it>i</it>GEMDOCK provides the visualizations of the protein-compound interaction profiles and the hierarchical clustering dendrogram of the compounds for post-screening analysis.</p> <p>Conclusions</p> <p>We have developed <it>i</it>GEMDOCK to facilitate steps from preparations of target proteins and ligand libraries toward post-screening analysis. <it>i</it>GEMDOCK is especially useful for post-screening analysis and inferring pharmacological interactions from screening compounds. We believe that <it>i</it>GEMDOCK is useful for understanding the ligand binding mechanisms and discovering lead compounds. <it>i</it>GEMDOCK is available at <url>http://gemdock.life.nctu.edu.tw/dock/igemdock.php</url>.</p

Flood Damage Reduction in Land Subsidence Areas by Groundwater Management

Continuing land subsidence can diminish the effectiveness of an existing flood mitigation system and aggravate the flood hazard. This chapter demonstrates that, through groundwater management with an effective pumping scheme, flood hazard and related flood damage in land subsidence area can be reduced. The chosen study area is in the southwest coast of Taiwan, which has long been suffering from frequent and wide-spread flooding primarily due to land subsidence induced by groundwater overpumping. Numerical investigation in the study area clearly shows that effective management of groundwater pumping can play an important role in long-term sustainable solution for controlling the spatial-temporal variability of future land subsidence, preventing the flood hazard from worsening, reducing the flood damage, and satisfying the groundwater demand

Attenuation of Brain Nitrostative and Oxidative Damage by Brain Cooling during Experimental Traumatic Brain Injury

The aim of the present study was to ascertain whether brain cooling causes attenuation of traumatic brain injury by reducing brain nitrostative and oxidative damage. Brain cooling was accomplished by infusion of 5 mL of 4°C saline over 5 minutes via the external jugular vein. Immediately after the onset of traumatic brain injury, rats were randomized into two groups and given 37°C or 4°C normal saline. Another group of rats were used as sham operated controls. Behavioral and biochemical assessments were conducted on 72 hours after brain injury or sham operation. As compared to those of the sham-operated controls, the 37°C saline-treated brain injured animals displayed motor deficits, higher cerebral contusion volume and incidence, higher oxidative damage (e.g., lower values of cerebral superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, but higher values of cerebral malondialdehyde), and higher nitrostative damage (e.g., higher values of neuronal nitric oxide synthase and 3-nitrotyrosine). All the motor deficits and brain nitrostative and oxidative damage were significantly reduced by retrograde perfusion of 4°C saline via the jugular vein. Our data suggest that brain cooling may improve the outcomes of traumatic brain injury in rats by reducing brain nitrostative and oxidative damage

Recovery of heat shock-triggered released apoplastic Ca2+ accompanied by pectin methylesterase activity is required for thermotolerance in soybean seedlings

Synthesis of heat shock proteins (HSPs) in response to heat shock (HS) is essential for thermotolerance. The effect of a Ca2+ chelator, EGTA, was investigated before a lethal HS treatment in soybean (Glycine max) seedlings with acquired thermotolerance induced by preheating. Such seedlings became non-thermotolerant with EGTA treatment. The addition of Ca2+, Sr2+ or Ba2+ to the EGTA-treated samples rescued the seedlings from death by preventing the increased cellular leakage of electrolytes, amino acids, and sugars caused by EGTA. It was confirmed that EGTA did not affect HSP accumulation and physiological functions but interfered with the recovery of HS-released Ca2+ concentration which was required for thermotolerance. Pectin methylesterase (PME, EC 3.1.1.11), a cell wall remodelling enzyme, was activated in response to HS, and its elevated activity caused an increased level of demethylesterified pectin which was related to the recovery of the HS-released Ca2+ concentration. Thus, the recovery of HS-released Ca2+ in Ca2+-pectate reconstitution through PME activity is required for cell wall remodelling during HS in soybean which, in turn, retains plasma membrane integrity and co-ordinates with HSPs to confer thermotolerance