Downregulation of intracellular nm23-H1 prevents cisplatin-induced DNA damage in oesophageal cancer cells: possible association with Na+, K+-ATPase

Previously, we showed that expression of nm23-H1 is associated inversely with sensitivity to cisplatin in human oesophageal squamous cell carcinoma (OSCC). The present study was undertaken to investigate the association of nm23-H1 expression with cisplatin-induced DNA damage in OSCC using antisense nm23-H1 transfectants. YES-2/AS-12, an antisense nm23-H1-transfected OSCC cell line, showed significantly reduced expression of intracellular nm23-H1 protein compared with that in parental YES-2 cells and YES-2/Neo transfectants. Surface expression of nm23-H1 protein was not observed in any of the three cell lines. PCR analysis for DNA damage demonstrated that YES-2/AS-12 cells were more resistant to nuclear and mitochondrial DNA damage by cisplatin than were YES-2/Neo cells. In addition, mitochondrial membrane potentials and DNA fragmentation assays confirmed that YES-2/AS-12 was more resistant than YES-2/Neo to apoptosis induced by cisplatin. In contrast, YES-2/AS-12 was more sensitive to ouabain, a selective inhibitor of Na+, K+-ATPase, than YES-2 and YES-2/Neo. Pre-treatment with ouabain resulted in no differences in cisplatin sensitivity between the three cell lines examined. Intracellular platinum level in YES-2/AS-12 was significantly lower than that in YES-2 and YES-2/Neo following incubation with cisplatin, whereas ouabain pre-treatment resulted in no differences in intracellular platinum accumulations between the three cell lines. Our data support the conclusion that reduced expression of intracellular nm23-H1 in OSCC cells is associated with cisplatin resistance via the prevention of both nuclear and mitochondrial DNA damage and suggest that it may be related to Na+, K+-ATPase activity, which is responsible for intracellular cisplatin accumulation. © 2000 Cancer Research Campaig

Peanut Chlorotic Streak Virus, a New Caulimovirus Infecting Peanuts (Arachis hypogaea) in India

Peanut (Arachis hypogaea [groundnut]) plants with reduced leaflets, chlorotic streaks, and stunting were observed during surveys for diseases caused by peanut viruses in India. These peanut plants were infected with a new caulimovirus designated peanut chlorotic streak virus (PClSV). PClSV was mechanically transmissible to several plants in Leguminosae and Solanaceae but was not transmitted by Aphis craccivora or Myzus persicae. Purified from Nicotiana clevelandii leaves, PClSV contained isometric particles 52 ± 3 nm in diameter. The virus was not related to cauliflower mosaic, figwort mosaic, or soybean chlorotic mottle viruses. Inclusion bodies similar to those produced by caulimoviruses were observed in the cytoplasm of infected Nicotiana rustica and A. hypogaea leaves. Purified PClSV contained two polypeptides with relative molecular masses of 58 and 51 kDa. The size of double-stranded DNA was estimated as approximately 8.1 kbp, which contained two single-stranded discontinuities. The physical map of the PClSV genome was distinctly different from those of other caulimoviruses

Gene and pathway identification with Lp penalized Bayesian logistic regression

<p>Abstract</p> <p>Background</p> <p>Identifying genes and pathways associated with diseases such as cancer has been a subject of considerable research in recent years in the area of bioinformatics and computational biology. It has been demonstrated that the magnitude of differential expression does not necessarily indicate biological significance. Even a very small change in the expression of particular gene may have dramatic physiological consequences if the protein encoded by this gene plays a catalytic role in a specific cell function. Moreover, highly correlated genes may function together on the same pathway biologically. Finally, in sparse logistic regression with <it>L</it>_{<it>p </it>}(<it>p </it>< 1) penalty, the degree of the sparsity obtained is determined by the value of the regularization parameter. Usually this parameter must be carefully tuned through cross-validation, which is time consuming.</p> <p>Results</p> <p>In this paper, we proposed a simple Bayesian approach to integrate the regularization parameter out analytically using a new prior. Therefore, there is no longer a need for parameter selection, as it is eliminated entirely from the model. The proposed algorithm (BLpLog) is typically two or three orders of magnitude faster than the original algorithm and free from bias in performance estimation. We also define a novel similarity measure and develop an integrated algorithm to hunt the regulatory genes with low expression changes but having high correlation with the selected genes. Pathways of those correlated genes were identified with DAVID <url>http://david.abcc.ncifcrf.gov/</url>.</p> <p>Conclusion</p> <p>Experimental results with gene expression data demonstrate that the proposed methods can be utilized to identify important genes and pathways that are related to cancer and build a parsimonious model for future patient predictions.</p

A Serious Disease of Groundnut Caused by Cowpea Mild Mottle Virus in the Sudan

A disease of groundnut characterized by stunting, downward rolling, mottling, general chlorosis and reduced leaflet size occurred in the Sudan. During 1992-94, surveys showed that the disease was restricted to irrigated groundnut crops grown between the 2 Niles. The viral causal agent had slightly flexuous filamentous particles (626 nm long) and was transmitted by whiteflies. It was identified serologically as cowpea mild mottle carlavirus (CPMMV). This appears to be the first record of natural occurrence of CPMMV on groundnut in the Sudan

Advances in post-mortem CT-angiography.

Performing a post-mortem multidetector CT (MDCT) scan has already become routine in some institutes of forensic medicine. To better visualize the vascular system, different techniques of post-mortem CT-angiography have been explored, which can essentially be divided into partial- and whole-body angiography techniques. Probably the most frequently applied technique today is the so-called multiphase post-mortem CT-angiography (MPMCTA) a standardized method for investigating the vessels of the head, thorax and abdomen. Different studies exist, describing its use for medicolegal investigations, and its advantages as well as its artefacts and pitfalls. With the aim to investigate the performance of PMCTA and to develop and validate techniques, an international working group was created in 2012 called the "Technical Working Group Post-mortem Angiography Methods" (TWGPAM). Beyond its primary perspective, the goals of this group include creating recommendations for the indication of the investigation and for the interpretation of the images and to distribute knowledge about PMCTA. This article provides an overview about the different approaches that have been developed and tested in recent years and an update about ongoing research in this field. It will explain the technique of MPMCTA in detail and give an outline of its indications, application, advantages and limitations