Tubulointerstitial injury and the progression of chronic kidney disease

In chronic kidney disease (CKD), once injury from any number of disease processes reaches a threshold, there follows an apparently irreversible course toward decline in kidney function. The tubulointerstitium may play a key role in this common progression pathway. Direct injury, high metabolic demands, or stimuli from various other forms of renal dysfunction activate tubular cells. These, in turn, interact with interstitial tissue elements and inflammatory cells, causing further pathologic changes in the renal parenchyma. The tissue response to these changes thus generates a feed-forward loop of kidney injury and progressive loss of function. This article reviews the mechanisms of this negative cycle mediating CKD

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

<p>Abstract</p> <p>Background</p> <p>Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between <it>nm23-H1</it>, <it>Rb, EGFR </it>and <it>p53 </it>in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).</p> <p>Methods</p> <p><it>nm23-H1</it>, <it>Rb, EGFR and p53 </it>expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.</p> <p>Results</p> <p>Overexpression of <it>EGFR </it>and <it>p53 </it>proteins was detected in 66.1% and 35.6%; respectively. Loss of <it>nm23-H1</it>and <it>Rb </it>proteins was detected in 42.4% and 57.6%; respectively. Increased <it>EGFR and </it>loss of <it>nm23-H1 </it>RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between <it>p53 </it>and <it>EGFR </it>overexpression (<it>p </it>< 0.0001), <it>nm23 </it>loss (protein and RNA), lymph node status (<it>p </it>< 0.0001); between the incidence of local recurrence and <it>EGFR </it>RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered <it>Rb </it>expression (<it>p </it>= 0.026), <it>p53 </it>overexpression (<it>p </it>< 0.0001) and mutation (<it>p </it>= 0.04). Advanced disease stage correlated significantly with increased <it>EGFR </it>(protein and RNA) (<it>p </it>= 0.003 & 0.01), reduced <it>nm23-H1 </it>RNA (<it>p </it>= 0.02), altered <it>Rb </it>(<it>p </it>= 0.023), and <it>p53 </it>overexpression (<it>p </it>= 0.004). OS rates correlated significantly, in univariate analysis, with <it>p53 </it>overexpression (<it>p </it>= 0.011), increased <it>EGFR </it>(protein and RNA, <it>p </it>= 0.034&0.031), <it>nm23-H1 RNA </it>loss (<it>p </it>= 0.021) and aberrations of ≥ 2 genes. However, multivariate analysis showed that only high <it>EGFR </it>overexpression, metastatic recurrence, high tumor grade and the combination of ≥ 2 affected markers were independent prognostic factors.</p> <p>Conclusion</p> <p><it>nm23-H1, EGFR </it>and <it>p53 </it>could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (≥ 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.</p

Expression of NRG1 and its receptors in human bladder cancer

BACKGROUND: Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role. METHODS: We measured NRG1 expression by real-time quantitative RT–PCR and ERBB receptors by western blotting and immunohistochemistry in bladder tumours and cell lines. RESULTS: NRG1a and NRG1b showed significant coordinate expression. NRG1b was upregulated in 78 % of cell lines. In tumours, there was a greater range of expression with a trend towards increased NRG1a with higher stage and grade. Increased expression o

Accurate molecular classification of cancer using simple rules

<p>Abstract</p> <p>Background</p> <p>One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often hampers the interpretability of the models. For a better understanding of the classification results, it is desirable to develop simpler rule-based models with as few marker genes as possible.</p> <p>Methods</p> <p>We screened a small number of informative single genes and gene pairs on the basis of their depended degrees proposed in rough sets. Applying the decision rules induced by the selected genes or gene pairs, we constructed cancer classifiers. We tested the efficacy of the classifiers by leave-one-out cross-validation (LOOCV) of training sets and classification of independent test sets.</p> <p>Results</p> <p>We applied our methods to five cancerous gene expression datasets: leukemia (acute lymphoblastic leukemia [ALL] vs. acute myeloid leukemia [AML]), lung cancer, prostate cancer, breast cancer, and leukemia (ALL vs. mixed-lineage leukemia [MLL] vs. AML). Accurate classification outcomes were obtained by utilizing just one or two genes. Some genes that correlated closely with the pathogenesis of relevant cancers were identified. In terms of both classification performance and algorithm simplicity, our approach outperformed or at least matched existing methods.</p> <p>Conclusion</p> <p>In cancerous gene expression datasets, a small number of genes, even one or two if selected correctly, is capable of achieving an ideal cancer classification effect. This finding also means that very simple rules may perform well for cancerous class prediction.</p

Microsatellite and Mitochondrial Data Provide Evidence for a Single Major Introduction for the Neartic Leafhopper Scaphoideus titanus in Europe

Scaphoideus titanus, a leafhopper native to North America and invasive in Europe, is the vector of the Flavescence dorée phytoplasma, the causal agent of the most important form of grapevine yellows in European vineyards. We studied 10 polymorphic microsatellite loci and a 623 bp fragment of the mitochondrial cytochrome oxidase II gene in native S. titanus from north-eastern America and introduced European populations, to elucidate the colonization scenario. Consistent with their recent history, invasive European populations were less genetically diverse than American populations for both types of markers, suggesting a recent bottleneck. Significant isolation by distance was detected between American populations but not between European populations. None of the European mitochondrial haplotypes was found in the American vineyards, from which they are assumed to have originated. The precise source of the invasive S. titanus populations therefore remains unclear. Nevertheless, the high heterozygosity of North-East American populations (which contained 92% of the observed alleles) suggests that this region is part of the native range of S. titanus. Clustering population genetics analyses with microsatellite and mitochondrial data suggested that European populations originated from a single introduction event. Most of the introduced populations clustered with populations from Long Island, the Atlantic Coast winegrowing region in which Vitis aestivalis occurs

Defect engineering of silicon with ion pulses from laser acceleration

Defect engineering is foundational to classical electronic device development and for emerging quantum devices. Here, we report on defect engineering of silicon with ion pulses from a laser accelerator in the laser intensity range of 1019 W cm−2 and ion flux levels of up to 1022 ions cm−2 s−1, about five orders of magnitude higher than conventional ion implanters. Low energy ions from plasma expansion of the laser-foil target are implanted near the surface and then diffuse into silicon samples locally pre-heated by high energy ions from the same laser-ion pulse. Silicon crystals exfoliate in the areas of highest energy deposition. Color centers, predominantly W and G-centers, form directly in response to ion pulses without a subsequent annealing step. We find that the linewidth of G-centers increases with high ion flux faster than the linewidth of W-centers, consistent with density functional theory calculations of their electronic structure. Intense ion pulses from a laser-accelerator drive materials far from equilibrium and enable direct local defect engineering and high flux doping of semiconductors.This work was supported by the Office of Science, Office of Fusion Energy Sciences, of the U.S. Department of Energy, under Contract No. DE-AC02-05CH11231. Experiments at the BELLA Center were enabled through facilities developed by HEP and LaserNetUS. TS and JGL gratefully acknowledge support by the coordinated research project “F11020” of the International Atomic Energy Agency (IAEA). LZT and JS were supported by the Molecular Foundry, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231Peer reviewe

Supplementary Notes - Defect engineering of silicon with ion pulses from laser acceleration

14 pages. -- Supplementary Note 1. Time lapse movie showing evaporation of the aluminum foil mask during 100 shots. -- Supplementary Note 2. Photoluminescence (PL) and Secondary Ion Mass Spectrometry (SIMS) data correlation to PL data. -- Supplementary Note 3. Details on energy deposition and heat calculations. -- Supplementary Note 4. Details on Nuclear Reaction Analysis (NRA). -- Supplementary Note 5. Details on channeling Rutherford Backscattering (ch-RBS). -- Supplementary Note 6. Supplemental material on Density Functional Theory (DFT) calculations of G and W-centers in silicon.Peer reviewe