372 research outputs found
Biomarkers for epithelial-mesenchymal transitions
No full textSomatic cells that change from one mature phenotype to another exhibit the property of plasticity. It is increasingly clear that epithelial and endothelial cells enjoy some of this plasticity, which is easily demonstrated by studying the process of epithelial-mesenchymal transition (EMT). Published reports from the literature typically rely on ad hoc criteria for determining EMT events; consequently, there is some uncertainty as to whether the same process occurs under different experimental conditions. As we discuss in this Personal Perspective, we believe that context and various changes in plasticity biomarkers can help identify at least three types of EMT and that using a collection of criteria for EMT increases the likelihood that everyone is studying the same phenomenon - namely, the transition of epithelial and endothelial cells to a motile phenotype
Mechanisms of Tubulointerstitial Fibrosis
No full textThe pathologic paradigm for renal progression is advancing tubulointerstitial fibrosis. Whereas mechanisms underlying fibrogenesis have grown in scope and understanding in recent decades, effective human treatment to directly halt or even reverse fibrosis remains elusive. Here, we examine key features mediating the molecular and cellular basis of tubulointerstitial fibrosis and highlight new insights that may lead to novel therapies. How to prevent chronic kidney disease from progressing to renal failure awaits even deeper biochemical understanding
Differential expression of type IV collagen isoforms in rat glomerular endothelial and mesangial cells
No full textPerturbations of Short RNA Helices
No full textA variety of short oligoribonucleotide sequences were synthesized using the phosphotriester chemical synthesis developed in Neilson's laboratory. These sequences were designed to incorporate a variety of features that would aid in the study of perturbations of helix structure and stability. Variable temperature proton nuclear magnetic resonance (NMR) spectroscopy was used in this study and provides a powerful technique for the study of nucleic acid conformations and for the investigation of the effects of the mispairing and single stranded regions caused by the helix imperfections introduced. The assignment procedure for NMR spectra was improved through the study of a series of related sequences. This study determined the effects that the addition of a nucleotide to the terminus of a sequence or the insertion of a nucleotide into the middle of a sequence would have on the chemical shifts from the rest of the sequence. A series of self-complementary pentaribonucleotides, with a central non-base paired opposition (AGXCU, where X ≡ A, G, C or U), was studied to determine the effects of small loops on duplex stability. In contrast to earlier results, these pentamers formed stable duplexes when X ≡ A or C, although the duplex Tm's were significantly, reduced. These sequences also provided the opportunity to study the sequence effects of adjacent internal G.C base pairs on duplex stability when the middle base pair was A·U, G·C or G.U. Comparison with earlier results using corresponding A·U base pair neighbours, demonstrated the enhanced stabilization of G·C base pairs. The effects of terminal non-base paired (dangling) adenosines were more closely investigated and found to contribute an average of 11°c to the thermal stability of the duplex formed. This study also demonstrated that 5'-dangling adenosines contribute less to overall stability than do 3'-dangling adenosines. However, this effect did display some sequence dependence. The triribonucleotide GpCpA was the first trimer shown to form a stable RNA duplex (Tm = 33°C). The duplex consisted of two G·C base pairs and two 3'-dangling adenosines and had a stability equal to that of the tetramer duplex UpGpCpA with four Watson-Crick base pairs. The influence of base stacking on duplex formation was studied and it was discovered that the direction of base stacking had a definite influence on helix stability. Stacking in the 5'→3' direction was more favourable to duplex formation than stacking in the 3'→5' direction. Lastly, the significance of invariant adenosines at position 14 and 21, in the D-stem of tRNA, was investigated through a model study that suggested the adenosines contributed to D-stem stability. Most of the results presented in this thesis have been published or accepted for publication in: 1. Jeremy R. Everett, Donald W. Hughes, Russell A. Bell, Dirk Alkema, Thomas Neilson and Paul J. Romaniuk. "Nearest-Neighbour and Next-Nearest-Neighbour Effects in the Proton NMR Spectra of the Oligoribonucleotides ApGpX and CpApX." (1980) Biopolymers 19, 557. 2. Thomas Neilson, Paul J. Romaniuk, Dirk Alkema, Donald W. Hughes, Jeremy R. Everett and Russell A. Bell. "The Effects of Base Sequence on the Stability of Short Ribonucleic Acid Duplexes." (1980) Nucleic Acids Res. Sym. Series No. 7, 293. 3. Dirk Alkema, R.A. Bell, P.A. Hader and T. Neilson. "Triplet GpCpA Forms a Stable RNA Duplex." (1981) J. Am. Chem. Soc. 103, 2866. 4. Russell A. Bell, Jeremy R. Everett, Donald W. Hughes, Dirk Alkema, Paul Hader, Thomas Neilson and Paul J. Romaniuk. "Nearest-Neighbour and Next-Nearest-Neighbour Effects in the Proton NMR Spectra of the Oligoribonucleotides ApXpG, CpXpG, CpApXpUpG, ApGpXpC and ApGpXpCpU." (1981) Biopolymers 20, 1383. 5. Dirk Alkema, Russell A. Bell, Paul A. Hader and Thomas Neilson. "Short RNA duplex Stability: Contribution from non-base paired residues to the direction of stacking." (1981) in "Biomolecular Stereodynamics" R.H. Sarma, ed., Adenine Press, Elmsford, NY., p. 417. 6. Dirk Alkema, Russell A. Bell, Paul A. Hader and Thomas Neilson. "Invariant Adenosine Residues Stabilize tRNA D-steins." (1982) Accepted for publication in FEBS Letters. 7. Dirk Alkema, Paul A. Hader, Russell A. Bell and Thomas Neilson. "Effects of Flanking G·U· Base Pairs on Internal Watson-Crick, G·U and Non-Bonded Base Pairs Within a Short RNA Duplex." (1982) Accepted for publication in-Biochemistry. Two additional publications will appear shortly: 1. Paul A. Hader, Thomas Neilson, Dirk Alkema, Eric C. Kofoid and M.C. Ganoza. "Sequencing of Short RNA Oligomers by Proton Nuclear Magnetic Resonance." (1982) Accepted for publication in FEBS Letters. 2. Paul A. Hader, Dirk Alkema, Russell A. Bell and Thomas Neilson. "Parameters for Proton Chemical Shift Prediction in Oligoribonucleotides." (1982) J. Chem. Comm. (in press).Doctor of Philosophy (PhD
Is immunologic tolerance of self modulated through antigen presentation by parenchymal epithelium?
No full textThe p53Pro72Arg Polymorphism is Associated with Albuminuria among Aboriginal Australians
No full textAlbuminuria is a widely recognized marker of renal disease and cardiovascular risk. This is especially true in Aboriginal Australians living in remote communities who suffer high rates of end-stage renal disease and cardiovascular mortality. During a survey of risk factors for renal and cardiovascular disease in one such community, an association between a common polymorphism at codon 72 (Arg/Pro) of the p53 gene and markers of renal disease was sought. A cross-sectional community survey including 217 people was performed. Genotypes of the polymorphism were distributed in Hardy-Weinberg equilibrium, with p53Arg allele frequency of 0.45 (range, 0.41 to 0.50). Overall prevalence of albuminuria was high (31% microalbuminuria; 14% overt albuminuria). Urine albumin/creatinine ratio (ACR) was significantly associated with the number of p53Pro alleles (P = 0.01), and there was an interaction with tobacco smoking (P = 0.04). The p53 genotype was also associated with increasing HbA1c, but the relationship between p53 and ACR was independent of this. This is a previously unreported association. This study does not address the mechanism, but this finding, if confirmed, expands the described effects of p53 in cellular proliferation and apoptosis to include a role in the course of renal and possibly cardiovascular disease in this population
Scalable production of photovoltaic-grade WSe2 via tungsten selenization
No full textTransition metal dichalcogenides (TMDs) hold significant promise for photovoltaic applications with high specific power thanks to their high absorption coefficients enabling ultrathin form factor, desirable band gaps for solar energy harvesting, and dangling-bond-free surfaces. Nevertheless, their small-scale synthesis methods have limited their practicality for commercial use. Here, we address this shortcoming and report an industrial, wafer-scale, and rapid selenization method to synthesize thickness-tunable TMD films (i.e., WSe2) from (pre-patterned) sputtered tungsten layers, using solid source selenium or H2Se precursors. These absorbers are shown to have a smooth surface, with a layered van der Waals structure, and charge carrier lifetimes up to 144 ns, over 14× higher than large-area TMD films previously demonstrated. Such high carrier lifetimes correspond to a power conversion efficiency of nearly 22% and a specific power of nearly 64 W/g in a packaged solar cell or almost 3 W/g in a fully packaged module
Immunolocalization of fibroblast growth factor-1 (FGF-1), its receptor (FGFR-1), and fibroblast-specific protein-1 (FSP-1) in inflammatory renal disease
No full textImmunolocalization of fibroblast growth factor-1 (FGF-1), its receptor (FGFR-1), and fibroblast-specific protein-1 (FSP-1) in inflammatory renal disease.BackgroundThe fibroblast growth factor (FGF) family has functions in development, cell proliferation, migration, and differentiation. While FGF-2 induces fibrosis, the role of FGF-1 in inflammation and fibrosis is less defined. We examined the expression of FGF-1 and FGF receptor (FGFR-1) to determine if renal diseases with varying etiologies of inflammation, including lupus nephritis (LN), acute interstitial nephritis (AIN) and acute rejection superimposed on chronic allograft nephropathy (CAN), showed varying patterns of expression. We also examined the expression of fibroblast-specific protein-1 (FSP-1), which has been linked to epithelial-mesenchymal transition (EMT) and fibrosis, to determine whether it was linked to potential profibrotic and inflammatory FGF-1 mechanisms.MethodsProliferative LN (PLN) (N = 12), nonproliferative lupus nephritis (NPLN) (N = 5), AIN (N = 6), CAN (N = 4), and normal kidneys (N = 3) were studied. FGF, FGFR-1, and FSP-1 were localized by immunohistochemistry, and intensity scored on a 0 to 3+ scale. Double staining with CD68 and separate immunohistochemical staining for CD4 and CD8 with serial sections analysis were done to identify if T lymphocytes or macrophages showed staining for FGF-1 and FGFR-1 or FSP-1.ResultsIn normal kidneys, FGF-1 was expressed in mesangial cells (0.67 ± 0.58), glomerular endothelial (0.67 ± 0.58), visceral, and parietal epithelial cells (1.67 ± 0.58). FGFR-1 showed a similar pattern of staining but also was expressed in tubular epithelium, and arterial endothelium and smooth muscle. Expression of FGF-1 was increased over normal in glomerular parenchymal cells only in CAN in podocytes (2.30 ± 0.58 vs. 3.00 ± 0.00) (P < 0.05) and parietal epithelial cells (1.67 ± 0.58 vs. 2.25 ± 0.50) (P < 0.05). Infiltrating glomerular and interstitial inflammatory cells in diseased glomeruli also expressed FGF-1 and FGFR-1. Tubular cells expressed slightly increased FGFR-1 in renal diseases vs. normal, whereas tubules remained negative for FGF-1 in diseased kidneys. FSP-1 expression was prominent in the interstitium in all kidneys with interstitial inflammation, and most prominent in CAN. Interstitial FSP-1+ cells were consistent with a myofibroblast-type morphology, and did not stain with CD-68. FSP-1 expression was closely associated with inflammatory cells expressing FGF-1 and FGFR-1. FSP-1 also showed positivity within crescents and occasional podocytes in PLN.ConclusionThe expression of FGF-1 and FGFR-1 in infiltrating lymphocytes and macrophages, and of FGFR-1 in tubules, is supportive, but does not prove causality, of the possibility that FGF-1 might have both autocrine and paracrine functions in renal inflammation. However, the initial stimulus for renal inflammation, whether immune complex, hypersensitivity or rejection, did not alter expression patterns of FGF-1 or its receptor. The colocalization of inflammatory infiltrates with interstitial fibrosis supports the possibility of a contribution of FGF-1 for chemotaxis and associated fibrosis, further supported by interstitial FSP-1 expression closely associated with these inflammatory cells expressing FGF-1 and FGFR-1
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