75 research outputs found
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
Expedition 382 Preliminary Report: Iceberg Alley and Subantarctic Ice and Ocean Dynamics
This is the final version. Available from International Ocean Discovery Program via the DOI in this record.âŻInternational Ocean Discovery Program (IODP) Expedition 382, Iceberg Alley and Subantarctic Ice and Ocean Dynamics, investigated the long-term climate history of Antarctica, seeking to understand how polar ice sheets responded to changes in insolation and atmospheric CO2 in the past and how ice sheet evolution influenced global sea level and vice versa. Five sites (U1534âU1538) were drilled east of the Drake Passage: two sites at 53.2°S at the northern edge of the Scotia Sea and three sites at 57.4°â59.4°S in the southern Scotia Sea. We recovered continuously deposited late Neogene sediment to reconstruct the past history and variability in Antarctic Ice Sheet (AIS) mass loss and associated changes in oceanic and atmospheric circulation. The sites from the southern Scotia Sea (Sites U1536âU1538) will be used to study the Neogene flux of icebergs through âIceberg Alley,â the main pathway along which icebergs calved from the mar- gin of the AIS travel as they move equatorward into the warmer wa- ters of the Antarctic Circumpolar Current (ACC). In particular, sediments from this area will allow us to assess the magnitude of iceberg flux during key times of AIS evolution, including the following: âą The middle Miocene glacial intensification of the East Antarctic Ice Sheet, âą The mid-Pliocene warm period, âą The late Pliocene glacial expansion of the West Antarctic Ice Sheet, âą The mid-Pleistocene transition (MPT), and âą The âwarm interglacialsâ and glacial terminations of the last 800 ky. We will use the geochemical provenance of iceberg-rafted detritus and other glacially eroded material to determine regional sources of AIS mass loss. We will also address interhemispheric phasing of ice sheet growth and decay, study the distribution and history of land-based versus marine-based ice sheets around the continent over time, and explore the links between AIS variability and global sea level. By comparing northâsouth variations across the Scotia Sea be- tween the Pirie Basin (Site U1538) and the Dove Basin (Sites U1536 and U1537), Expedition 382 will also deliver critical information on how climate changes in the Southern Ocean affect ocean circulation through the Drake Passage, meridional overturning in the region, water mass production, oceanâatmosphere CO2 transfer by wind- induced upwelling, sea ice variability, bottom water outflow from the Weddell Sea, Antarctic weathering inputs, and changes in oceanic and atmospheric fronts in the vicinity of the ACC. Comparing changes in dust proxy records between the Scotia Sea and Antarctic ice cores will also provide a detailed reconstruction of changes in the Southern Hemisphere westerlies on millennial and orbital timescales for the last 800 ky. Extending the ocean dust record beyond the last 800 ky will help to evaluate dust-climate couplings since the Pliocene, the potential role of dust in iron fertilization and atmospheric CO2 drawdown during glacials, and whether dust input to Antarctica played a role in the MPT. The principal scientific objective of Subantarctic Front Sites U1534 and U1535 at the northern limit of the Scotia Sea is to recon- struct and understand how ocean circulation and intermediate water formation responds to changes in climate with a special focus on the connectivity between the Atlantic and Pacific basins, the âcold water route.â The Subantarctic Front contourite drift, deposited between 400 and 2000 m water depth on the northern flank of an eastâwest trending trough off the Chilean continental shelf, is ideally situated to monitor millennial- to orbital-scale variability in the export of Antarctic Intermediate Water beneath the Subantarctic Front. During Expedition 382, we recovered continuously deposited sediments from this drift spanning the late Pleistocene (from ~0.78 Ma to recent) and from the late Pliocene (~3.1â2.6 Ma). These sites are expected to yield a wide array of paleoceanographic records that can be used to interpret past changes in the density structure of the Atlantic sector of the Southern Ocean, track migrations of the Sub- antarctic Front, and give insights into the role and evolution of the cold water route over significant climate episodes, including the following: âą The most recent warm interglacials of the late Pleistocene and âą The intensification of Northern Hemisphere glaciation.National Science Foundatio
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><sub><it>p </it></sub>(<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
Inflammatory and Immunological parameters in adults with Down syndrome
<p>Abstract</p> <p>Background</p> <p>The increase in life expectancy within the general population has resulted in an increasing number of elderly adults, including patients with Down syndrome (DS), with a current life expectancy of about 50 years. We evaluate the parameters of humoral and cellular immune response, the quantitative expression of the regulator of calcineurin1 gene (RCAN1) and the production of cytokines. The study group consisted of adults DS (n = 24) and a control group with intellectual disability without Down syndrome (ID) (n = 21) and living in a similar environmental background. It was evaluated serology, immunophenotyping, the quantitative gene expression of RCAN1 and the production of cytokines.</p> <p>Results</p> <p>In the DS group, the results showed an increase in NK cells, CD8, decreased CD19 (p < 0.05) and an increase spontaneous production of IFNgamma, TNFalpha and IL-10 (p < 0.05). There was not any difference in RCAN1 gene expression between the groups.</p> <p>Conclusions</p> <p>These data suggest a similar humoral response in the two groups. The immunophenotyping suggests sign of premature aging of the immune system and the cytokine production show a proinflammatory profile.</p
Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism
<p>Abstract</p> <p>Background</p> <p>There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism.</p> <p>Methods</p> <p>The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA), glutamate:glutamine (Glu:Gln) ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA) were determined in plasma samples from both groups.</p> <p>Results</p> <p>We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio.</p> <p>Conclusion</p> <p>A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.</p
Effects of Rewarding and Unrewarding Experiences on the Response to Host-induced Plant Odors of the Generalist Parasitoid Cotesia marginiventris (Hymenoptera: Braconidae)
The enhancing effect of excess retinol palmitate on induction of odontogenic tumors and inhibitory effect on squamous cell carcinoma of the gingiva in hamsters treated with N-methylnitrosourea
The influence of excess retinol palmitate on
induction of tumors in the oral region was examined
histopathologically. Sixty-three weanling Syrian golden
hamsters were divided into five groups and received
either 0.2% N-methylnitrosourea (MNU) (lmg1100g
body weight) or retinol palmitate (RP) (25,000 IU/100g
body weight) twice a week for 16 weeks, singly or in
combination. Animals received RP intraperitoneally or
intragastrically and then, 6 hours later, the animals
received intragastric administration of MNU. To
accelerate the cell activity of the incisal tooth buds,
intentional disocclusion of the left upper and lower
incisor of all hamsters was carried out by repeated
cutting with cooled diamond disks to a level just above
the inter-dental papilla twice a week for 12 weeks. The
right incisors were left in occlusion. In all animals
exposed to RP+MNU, while the induction of squamous
cell carcinomas of the gingiva and forestomach were
prevented, the notable findings were a significantly
increased incidence of odontogenic tumors in cut incisal
regions of the animals with intragastric administration of
RP+MNU and an induction of maxillary neurogenic
tumors. The incidence of MNU-induced disturbances in
odontogenesis in the incisors was reduced but marked
disturbances were increased. RP seemed to have
opposite effects of prevention and enhancement for
development of neoplastic changes in the oral region
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