bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aldose Reductase Regulates Growth Factor-Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Colon Cancer Cells
Authors: Tammali Ravinder , Ramana Kota V. , Singhal Sharad S. , Awasthi Sanjay , Srivastava Satish K. 
Published: October 2006

Abstract
Inhibition of prostaglandin E2 (PGE2) and cyclooxygenase (COX)-2 by nonsteroidal anti-inflammatory drugs reduces the progression of colon cancer. Inhibition of aldose reductase (AR; EC. 1.1.1.21.) by sorbinil or by antisense ablation prevented fibroblast growth factor–induced and platelet-derived growth factor–induced up-regulation of PGE2 synthesis in human colon cancer cells, Caco-2. AR besides reducing aldo-sugars efficiently reduces toxic lipid aldehydes and their conjugates with glutathione. Inhibition of AR prevented growth factor-induced COX-2 activity, protein, and mRNA and significantly decreased activation of nuclear factor-κB and protein kinase C (PKC) and phosphorylation of PKC-β2 as well as progression of Caco-2 cell growth but had no effect on COX-1 activity. Cell cycle analysis suggests that inhibition of AR prevents growth factor-induced proliferation of Caco-2 cells at S phase. Treatment of Caco-2 cells with the most abundant and toxic lipid aldehyde 4-hydroxy-trans-2-nonenal (HNE) or its glutathione-conjugate [glutathionyl-HNE (GS-HNE)] or AR-catalyzed product of GS-HNE, glutathionyl-1,4-dihydroxynonane (GS-DHN), resulted in increased COX-2 expression and PGE2 production. Inhibition of AR prevented HNE- or GS-HNE-induced but not GS-DHN-induced up-regulation of COX-2 and PGE2. More importantly, in vivo studies showed that administration of AR-small interfering RNA (siRNA), but not control siRNA, to nude mice bearing SW480 human colon adenocarcinoma cells completely arrested tumor progression. Collectively, these observations suggest that AR is an obligatory mediator of growth factor-induced up-regulation of COX-2, PGE2, and growth of Caco-2 cells, indicating that inhibition of AR may be a novel therapeutic approach in preventing the progression of colon cancer. (Cancer Res 2006; 66(19): 9705-13)
Enhancer of Zeste 2 as a Marker of Preneoplastic Progression in the Breast
Authors: Ding Lei , Kleer Celina G. 
Published: October 2006

Abstract
Amplification of the Polycomb group transcriptional repressor Enhancer of Zeste 2 (EZH2) occurs in various malignancies including breast cancer, where its overexpression is associated with poor outcome. We found that EZH2 is up-regulated in ductal carcinoma in situ, atypical ductal hyperplasia, and even morphologically normal breast epithelial cells from women who have an increased risk of breast cancer. This review discusses how EZH2 may promote neoplastic conversion and it surveys the evidence suggesting that EZH2 may offer a clinical tool to help identify patients at risk for developing breast cancer before precursor lesions are histologically evident. (Cancer Res 2006; 66(19): 9352-5)
Targeted Disruption of Protein Kinase Cε Reduces Cell Invasion and Motility through Inactivation of RhoA and RhoC GTPases in Head and Neck Squamous Cell Carcinoma
Authors: Pan Quintin , Bao Li Wei , Teknos Theodoros N. , Merajver Sofia D. 
Published: October 2006

Abstract
Over 70% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced stage III and IV disease. In spite of aggressive therapy, locoregional disease recurs in 60% and metastatic disease develops in 15% to 25% of patients causing a major decline in quality and length of life. Therefore, there is a need to identify and understand genes that are responsible for inducing an aggressive HNSCC phenotype. Evidence has shown that protein kinase C (PKC) ε is a transforming oncogene and may play a role in HNSCC progression. In this study, we determine the downstream signaling pathway mediated by PKCε to promote an aggressive HNSCC phenotype. RNA interference knockdown of PKCε in UMSCC11A and UMSCC36, two highly invasive and motile HNSCC cell lines with elevated endogenous PKCε levels, resulted in cells that were significantly less invasive and motile than the small interfering RNA–scrambled control transfectants; 51 ± 5% (P &lt; 0.006) and 49 ± 3% (P &lt; 0.010) inhibition in invasion and 69 ± 1% (P &lt; 0.0005) and 66 ± 3% (P &lt; 0.0001) inhibition in motility, respectively. PKCε-deficient UMSCC11A clones had reduced levels of active and serine-phosphorylated RhoA and RhoC. Moreover, constitutive active RhoA completely rescued the invasion and motility defect, whereas constitutive active RhoC completely rescued the invasion and partially rescued the motility defect of PKCε-deficient UMSCC11A clones. These results indicate that RhoA and RhoC are downstream of PKCε and critical for PKCε-mediated cell invasion and motility. Our study shows, for the first time, that PKCε is involved in a coordinated regulation of RhoA and RhoC activation, possibly through direct post-translational phosphorylation. (Cancer Res 2006; 66(19): 9379-84)
The Predictability of Interdecadal Changes in ENSO Activity and ENSO Teleconnections
Authors: Power Scott , Haylock Malcolm , Colman Rob , Wang Xiangdong 
Published: October 2006

Abstract
El Niño–Southern Oscillation (ENSO) in a century-long integration of a Bureau of Meteorology Research Centre (BMRC) coupled general circulation model (CGCM) drives rainfall and temperature changes over Australia that are generally consistent with documented observational changes: dry/hot conditions occur more frequently during El Niño years and wet/mild conditions occur more frequently during La Niña years. The relationship between ENSO [as measured by Niño-4 or the Southern Oscillation index (SOI), say] and all-Australia rainfall and temperature is found to be nonlinear in the observations and in the CGCM during June–December: a large La Niña sea surface temperature (SST) anomaly is closely linked to a large Australian response (i.e., Australia usually becomes much wetter), whereas the magnitude of an El Niño SST anomaly is a poorer guide to how dry Australia will actually become. Australia tends to dry out during El Niño events, but the degree of drying is not as tightly linked to the magnitude of the El Niño SST anomaly. Nonlinear or asymmetric teleconnections are also evident in the western United States/northern Mexico. The implications of asymmetric teleconnections for prediction services are discussed.
The relationship between ENSO and Australian climate in both the model and the observations is strong in some decades, but weak in others. A series of decadal-long perturbation experiments are used to show that if these interdecadal changes are predictable, then the level of predictability is low. The model’s Interdecadal Pacific Oscillation (IPO), which represents interdecadal ENSO-like SST variability, is statistically linked to interdecadal changes in ENSO’s impact on Australia during June–December when ENSO’s impact on Australia is generally greatest. A simple stochastic model that incorporates the nonlinearity above is used to show that the IPO [or the closely related Pacific Decadal Oscillation (PDO)] can appear to modulate ENSO teleconnections even if the IPO–PDO largely reflect unpredictable random changes in, for example, the relative frequency of El Niño and La Niña events in a given interdecadal period.
Note, however, that predictability in ENSO-related variability on decadal time scales might be either underestimated by the CGCM, or be too small to be detected by the modest number of perturbation experiments conducted. If there is a small amount of predictability in ENSO indices on decadal time scales, and there may be, then the nonlinearity described above provides a mechanism via which ENSO teleconnections could be modulated on decadal time scales in a partially predictable fashion.
Estimates of Power Consumed by Mixing in the Ocean Interior
Authors: St. Laurent Louis , Simmons Harper 
Published: October 2006

AbstractMuch attention has focused on the power required for driving mixing processes in the ocean interior, the thermohaline circulation, and the related meridional overturning circulation (MOC). Recent estimates range from roughly 0.5 to 2 TW (1 TW = 1 × 1012 W), based on differing arguments for the closure of the MOC mass budget. While these values are both O(1) TW, the thermodynamic implications of the estimates are significantly different. In addition, these numbers represent an integral constraint on the global circulation, and the apparent discrepancy merits careful examination. Through basic thermodynamic considerations on water mass mixing, a mechanical power consumption of 3 ± 1 TW is found to be consistent with a basic knowledge of the distribution and magnitude of oceanic turbulence diffusivities. This estimate is somewhat independent of any specific model for mass closure of the MOC. In addition, this estimate is based on a thermocline diffusivity of only 0.1 cm2 s−1, with enhanced diffusivities acting only in the deep and bottom waters. Adding enhanced diffusivities in the upper ocean, or lowering the mixing efficiency below 20%, will increase the power estimate. Moreover, 3 TW is a reasonable estimate for the power availability to processes acting beneath the oceanic mixed layer.
Two Approaches to Quantifying Uncertainty in Global Temperature Changes
Authors: Lopez Ana , Tebaldi Claudia , New Mark , Stainforth Dave , Allen Myles , Kettleborough Jamie 
Published: October 2006

Abstract
A Bayesian statistical model developed to produce probabilistic projections of regional climate change using observations and ensembles of general circulation models (GCMs) is applied to evaluate the probability distribution of global mean temperature change under different forcing scenarios. The results are compared to probabilistic projections obtained using optimal fingerprinting techniques that constrain GCM projections by observations. It is found that, due to the different assumptions underlying these statistical approaches, the predicted distributions differ significantly in particular in their uncertainty ranges. Results presented herein demonstrate that probabilistic projections of future climate are strongly dependent on the assumptions of the underlying methodologies.
State of the Ground: Climatology and Changes during the Past 69 Years over Northern Eurasia for a Rarely Used Measure of Snow Cover and Frozen Land
Authors: Groisman Pavel Ya , Knight Richard W. , Razuvaev Vyacheslav N. , Bulygina Olga N. , Karl Thomas R. 
Published: October 2006

Abstract
Significant climatic changes over northern Eurasia during the twentieth century are revealed in numerous variables including those affecting and characterizing the state of the cryosphere. In addition to commonly used in situ observations of snow cover such as snow depth and snow courses, synoptic archives in the former Soviet Union contain regular daily and semidaily reports about the state of the ground in the area surrounding the station. Information about frozen, dry, wet, ponded, and snow-covered land, and in the case of snow-covered land, about the characteristics of snow cover, is available in these reports. A new Global Synoptic Data Network (GSDN) consisting of 2100 stations within the boundaries of the former Soviet Union created jointly by the National Climatic Data Center (NCDC) and Russian Institute for Hydrometeorological Information (RIHMI) was used to assess the climatology of snow cover, frozen and unfrozen ground reports, and their temporal variability for the period from 1936 to 2004. Comparison with satellite measurements of snow cover extent is also presented.
During the second half of the twentieth century and over many regions in northern Eurasia, an increase in unfrozen ground conditions (5 days since 1956 over the Russian Federation) was observed. The most prominent changes occurred in the spring season in Siberia and the Far East north of 55°N during April and May by 3 to 5 days, which constitute a 15%–35% change in these regions compared to long-term mean values. Since the beginning of the dataset, surface temperature changes in high latitudes have not been monotonic. As a result, linear trend analyses applied to the entire period of observations can lead to paradoxical conclusions. Specifically, changes in snow cover extent during the 1936–2004 period cannot be linked with “warming” (particularly with the Arctic warming) because in this particular period the Arctic warming was absent.
An Approximate Footprint Model for Flux Measurements in the Convective Boundary Layer
Authors: Wang Weiguo , Davis Kenneth J. , Ricciuto Daniel M. , Butler Martha P. 
Published: October 2006

Abstract
An explicit footprint model for flux measurements of passive scalars in the lower part of the convective boundary layer (CBL) is introduced. A simple footprint model is derived analytically in an idealized CBL. The simple model can simulate the overall characteristics of the flux footprint. Then a method is proposed to adjust the analytical solutions to those from a Lagrangian stochastic model that considers more realistic atmospheric conditions in the vertical direction. The adjusted footprint model is a function of Monin–Obukhov length (L), roughness length, receptor height, and CBL depth (h). Comparison between the results from the adjusted footprint model and stochastic model suggests that the adjusted footprint model can well simulate the streamwise extent of the footprint within the dimensionless upwind distance X &lt; 1, which accounts for a majority of the footprint. The model applies to stabilities of –L/h between 0.01 and 0.1 and roughness lengths between 10−5 and 2 × 10−3h in the lower part of the mixed layer (from 0.1h to 0.6h).
Loss of imprinting at the Dlk1-Gtl2 locus caused by insertional mutagenesis in the Gtl2 5' region
Authors: Steshina Ekaterina Y , Carr Michael S , Glick Elena A , Yevtodiyenko Aleksey , Appelbe Oliver K , Schmidt Jennifer V 
Published: October 2006

AbstractBackgroundTheDlk1andGtl2genes define a region of mouse chromosome 12 that is subject to genomic imprinting, the parental allele-specific expression of a gene. Although imprinted genes play important roles in growth and development, the mechanisms by which imprinting is established and maintained are poorly understood. Differentially methylated regions (DMRs), which carry methylation on only one parental allele, are involved in imprinting control at many loci. TheDlk1-Gtl2region contains three known DMRs, theDlk1DMR in the 3' region ofDlk1, the intergenic DMR 15 kb upstream ofGtl2, and theGtl2DMR at theGtl2promoter. Three mouse models are analyzed here that provide new information about the regulation ofDlk1-Gtl2imprinting.ResultsA previously existing insertional mutation (Gtl2lacZ), and a targeted deletion in which theGtl2upstream region was replaced by aNeocassette (Gtl2Δ5'Neo), display partial lethality and dwarfism upon paternal inheritance. Molecular characterization shows that both mutations cause loss of imprinting and changes in expression of theDlk1,Gtl2andMeg8/Riangenes.Dlk1levels are decreased upon paternal inheritance of either mutation, suggestingDlk1may be causative for the lethality and dwarfism. Loss of imprinting on the paternal chromosome in bothGtl2lacZandGtl2Δ5'Neomice is accompanied by the loss of paternal-specificGtl2DMR methylation, while maternal loss of imprinting suggests a previously unknown regulatory role for the maternalGtl2DMR. Unexpectedly, when theNeogene is excised,Gtl2Δ5'animals are of normal size, imprinting is unchanged and theGtl2DMR is properly methylated. The exogenous DNA sequences integrated upstream ofGtl2are therefore responsible for the growth and imprinting effects.ConclusionThese data provide further evidence for the coregulation of the imprintedDlk1andGtl2genes, and support a role forDlk1as an important neonatal growth factor. The ability of theGtl2lacZandGtl2Δ5'Neomutations to cause long-range changes in imprinting and gene expression suggest that regional imprinting regulatory elements may lie in proximity to the integration site.
The four serotypes of dengue recognize the same putative receptors in Aedes aegypti midgut and Ae. albopictus cells
Authors: Mercado-Curiel Ricardo F , Esquinca-Avilés Héctor Armando , Tovar Rosalinda , Díaz-Badillo Álvaro , Camacho-Nuez Minerva , Muñoz María de Lourdes 
Published: October 2006

AbstractBackgroundDengue viruses (DENV) attach to the host cell surface and subsequently enter the cell by receptor-mediated endocytosis. Several primary and low affinity co-receptors for this flavivirus have been identified. However, the presence of these binding molecules on the cell surface does not necessarily render the cell susceptible to infection. Determination of which of them serve asbona fidereceptors for this virus in the vector may be relevant to treating DENV infection and in designing control strategies.Results(1) Overlay protein binding assay showed two proteins with molecular masses of 80 and 67 kDa (R80 and R67). (2) Specific antibodies against these two proteins inhibited cell binding and infection. (3) Both proteins were bound by all four serotypes of dengue virus. (4) R80 and R67 were purified by affinity chromatography fromAe. aegyptimosquito midguts and fromAe albopictusC6/36 cells. (5) In addition, a protein with molecular mass of 57 kDa was purified by affinity chromatography from the midgut extracts. (6) R80 and R67 from radiolabeled surface membrane proteins of C6/36 cells were immunoprecipitated by antibodies againstAe. aegyptimidgut.ConclusionOur results strongly suggest that R67 and R80 are receptors for the four serotypes of dengue virus in the midgut cells ofAe. aegyptiand in C6/36Ae.albopictuscells.
Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease
Authors: Skogen Michael , Roth Jennifer , Yerkes Sarah , Parekh-Olmedo Hetal , Kmiec Eric 
Published: October 2006

Abstract

Background
Huntington's Disease (HD) is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt) is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions.

Results
As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG) as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP). Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene.

Conclusion
Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.
General practitioner practices in requesting laboratory tests for patients with gastroenteritis in the Netherlands, 2001–2002
Authors: van den Brandhof Winette E , Bartelds Aad IM , Koopmans Marion PG , van Duynhoven Yvonne THP 
Published: October 2006

Abstract

Background
The objective of this study was to estimate the (selective) proportion of patients consulting their GP for an episode of gastroenteritis for whom laboratory tests were requested. In addition adherence of GPs to the guidelines for diagnostic test regime was ascertained.

Methods
Data were collected from a GP network in the Netherlands. Information was also collected on the reason for requesting the test, test specifications, and test results.

Results
For 12% of the GP patients with gastroenteritis, a stool sample was requested and tested for enteric pathogens. In most patients, the duration, followed by severity of complaints or a visit to a specific, high-risk country were reported as reasons to request laboratory diagnostics. Tests were requested most often in summer months and in February. Campylobacter (requested for 87% of the tests), Salmonella (84%), Shigella (78%) and Yersinia (56%) were most frequently included in the stool tests. Campylobacter was detected most often in patients.

Conclusion
Test requests did not always comply with existing knowledge of the etiology of gastroenteritis in GP patients and were not always consistent with the Dutch GP guidelines. Therefore, the data of this study can be used to develop educational approaches for GP's as well as for revision of the guidelines.
Targeting of mutant hogg1in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress
Authors: Chatterjee Aditi , Mambo Elizabeth , Zhang Yonggang , DeWeese Theodore , Sidransky David 
Published: October 2006

Abstract

Background
Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, aging and cancer. The modified guanine, 7,8-dihydro-8-oxoguanine (also known as 8-hydroxyguanine) is one of the major oxidized bases generated in DNA by reactive oxygen species and has gained most of the attention in recent years as a marker of oxidative DNA injury and its suspected role in the initiation of carcinogenesis. 8-hydroxyguanine is removed by hOgg1, a DNA glycosylase/AP lyase involved in the base excision repair pathway.

Methods
We over-expressed wild type and R229Q mutant hOGG1 in the nucleus and mitochondria of cells lacking mitochondrial hOGG1 expression through an expression vector containing nuclear and mitochondrial targeting sequence respectively. We used quantitative real time PCR to analyze mtDNA integrity after exposure to oxidative damaging agents, in cells transfected with or without mitochondrially-targeted mutant hogg1.

Result
Over-expression of wild type hOgg1 in both nucleus and mitochondria resulted in increased cellular survival when compared to vector or mutant over-expression of hOGG1. Interestingly, mitochondrially-targeted mutant hogg1 resulted in more cell death than nuclear targeted mutant hogg1 upon exposure of cells to oxidative damage. Additional we examined mitochondrial DNA integrity after oxidative damage exposure using real-time quantitative PCR. The presence of mutant hogg1 in the mitochondria resulted in reduced mitochondrial DNA integrity when compared to the wild type. Our work indicates that the R229Q hOGG1 mutation failed to protect cells from oxidative damage and that such mutations in cancer may be more detrimental to cellular survival when present in the mitochondria than in the nucleus.

Conclusion
These findings suggest that deficiencies in hOGG1, especially in the mitochondria may lead to reduced mitochondrial DNA integrity, consequently resulting in decreased cell viability.