bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between CpG methylation profiles and hormone receptor status in breast cancers
Authors: Feng Weiwei , Shen Lanlan , Wen Sijin , Rosen Daniel G , Jelinek Jaroslav , Hu Xin , Huan Shaoyi , Huang Miao , Liu Jinsong , Sahin Aysegul A , Hunt Kelly K , Bast Robert C , Shen Yu , Issa Jean-Pierre J , Yu Yinhua 
Published: September 2007

Abstract
Introduction
Aberrant DNA methylation has been found frequently in human breast cancers, associated with the loss of expression of a number of regulatory genes for growth and correlated to clinical outcomes. The present study was undertaken to determine whether methylation of a set of growth-suppressor genes would correlate to the expression of estrogen receptors (ERs) and progesterone receptors (PRs).

Methods
We used a pyrosequencing methylation analysis to study the methylation of 12 known growth-suppressor genes in 90 pairs of malignant/normal breast tissues. We also examined the expression of ERs and PRs in those specimens by immunohistochemistry. Mutations of p53 in tumor cells were detected by direct sequencing.

Results
Twelve tumor-suppressor genes: ARHI, RASSF1A, HIN-1, RARβ2, hMLH1, 14-3-3 σ, RIZ1, p16, E-cadherin, RIL, CDH13, and NKD2 were selected for this methylation study. Five of them (RIL, HIN-1, RASSF1A, CDH13, and RARβ2) were frequently methylated in breast cancers (57%, 49%, 58%, 44%, and 17%, respectively) but not the normal breast (0–4%). Two panels of methylation profiles were defined. The methylation of the HIN-1/RASSFIA panel strongly correlated to the expression of ERs, PRs, and hormone receptors (HRs; which were defined as 'positive' if ERs and/or PRs were positive; p < 0.001). Conversely, the methylation of the RIL/CDH13 panel strongly correlated to negative ER, PR, and HR expression (p = 0.001, 0.025, and 0.001, respectively). The subset of triple-negative breast cancers (in other words, those with negative ER, PR, and HER-2/neu status) was positively associated with the methylation of the RIL/CDH13 panel and negatively associated with the HIN-1/RASSF1A panel. Mutations of p53 were found in nine breast tumors (11%), seven of which lacked methylation in both panels.

Conclusion
We have defined two panels (HIN-1/RASSFIA, and RIL/CDH13) of methylation profiles, which correlated, either positively or negatively, to HR status.
Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegansto infection
Authors: Wong Daniel , Bazopoulou Daphne , Pujol Nathalie , Tavernarakis Nektarios , Ewbank Jonathan J 
Published: September 2007

Abstract
Background
There are striking similarities between the innate immune systems of invertebrates and vertebrates. Caenorhabditis elegans is increasingly used as a model for the study of innate immunity. Evidence is accumulating that C. elegans mounts distinct responses to different pathogens, but the true extent of this specificity is unclear. Here, we employ direct comparative genomic analyses to explore the nature of the host immune response.

Results
Using whole-genome microarrays representing 20,334 genes, we analyzed the transcriptional response of C. elegans to four bacterial pathogens. Different bacteria provoke pathogen-specific signatures within the host, involving differential regulation of 3.5-5% of all genes. These include genes that encode potential pathogen-recognition and antimicrobial proteins. Additionally, variance analysis revealed a robust signature shared by the pathogens, involving 22 genes associated with proteolysis, cell death and stress responses. The expression of these genes, including those that mediate necrosis, is similarly altered following infection with three bacterial pathogens. We show that necrosis aggravates pathogenesis and accelerates the death of the host.

Conclusion
Our results suggest that in C. elegans, different infections trigger both specific responses and responses shared by several pathogens, involving immune defense genes. The response shared by pathogens involves necrotic cell death, which has been associated with infection in humans. Our results are the first indication that necrosis is important for disease susceptibility in C. elegans. This opens the way for detailed study of the means by which certain bacteria exploit conserved elements of host cell-death machinery to increase their effective virulence.
Phase II Study of Vandetanib or Placebo in Small-Cell Lung Cancer Patients After Complete or Partial Response to Induction Chemotherapy With or Without Radiation Therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20
Authors: Arnold Andrew M. , Seymour Lesley , Smylie Michael , Ding Keyue , Ung Yee , Findlay Brian , Lee Christopher W. , Djurfeldt Marina , Whitehead Marlo , Ellis Peter , Goss Glenwood , Chan Adrien , Meharchand Jacinta , Alam Yasmin , Gregg Richard , Butts Charles , Langmuir Peter , Shepherd Frances 
Published: September 2007

PurposeThis double-blind randomized phase II trial examined whether vandetanib, an inhibitor of vascular endothelial and epidermal growth factor receptors, could prolong progression-free survival in responding patients with small-cell lung cancer.Patients and MethodsEligible patients with complete response (CR) or partial response (PR) to combination chemotherapy (± thoracic or prophylactic cranial radiation) received oral vandetanib 300 mg/d or matched placebo. With 100 patients and 77 events, the study had 80% power to detect an improvement in median progression-free survival from 4 to 6.5 months (one-sided, 10%-level test).ResultsBetween May 2003 and March 2006, 107 patients were accrued; 46 had limited disease and 61 extensive disease. There were fewer patients with a performance status of 0 (n = 11 v 20), and fewer had CR to initial therapy (n = 4 v 8) in the vandetanib arm. Vandetanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash. Asymptomatic Corrected QT interval (QTC) prolongation was observed in eight vandetanib patients. Median progression-free survival for vandetanib and placebo was 2.7 and 2.8 months, respectively (hazard ratio [HR], 1.01; 80% CI, 0.75 to 1.36; one-sided P = .51). Overall survival for vandetanib was 10.6 versus 11.9 months for placebo (HR, 1.43; 80% CI, 1.00 to 2.05; one-sided P = 0.9). In planned subgroup analyses, a significant interaction was noted (P = .01): limited-stage vandetanib patients had longer overall survival (HR, 0.45; one-sided P = .07) and extensive-stage vandetanib patients shorter survival compared with placebo (HR, 2.27; one-sided P = .996).ConclusionVandetanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer.
Variable Rainfall Intensity and Tillage Effects on Runoff, Sediment, and Carbon Losses from a Loamy Sand under Simulated Rainfall
Authors: Truman C.C. , Strickland T.C. , Potter T.L. , Franklin D.H. , Bosch D.D. , Bednarz C.W. 
Published: September 2007

AbstractThe low‐carbon, intensively cropped Coastal Plain soils of Georgia are susceptible to runoff, soil loss, and drought. Reduced tillage systems offer the best management tool for sustained row crop production. Understanding runoff, sediment, and chemical losses from conventional and reduced tillage systems is expected to improve if the effect of a variable rainfall intensity storm was quantified. Our objective was to quantify and compare effects of a constant (Ic) intensity pattern and a more realistic, observed, variable (Iv) rainfall intensity pattern on runoff (R), sediment (E), and carbon losses (C) from a Tifton loamy sand cropped to conventional‐till (CT) and strip‐till (ST) cotton (Gossypium hirsutumL.). Four treatments were evaluated: CT‐Ic, CT‐Iv, ST‐Ic, and ST‐Iv, each replicated three times. Field plots (n = 12), each 2 by 3 m, were established on each treatment. Each 6‐m2field plot received simulated rainfall at a constant (57 mm h−1) or variable rainfall intensity pattern for 70 min (12‐run ave. = 1402 mL; CV = 3%). The Ivpattern represented the most frequent occurring intensity pattern for spring storms in the region. Compared with CT, ST decreased R by 2.5‐fold, E by 3.5‐fold, and C by 7‐fold. Maximum runoff values for Ivevents were 1.6‐fold higher than those for Icevents and occurred 38 min earlier. Values for Etotand Ctotfor Ivevents were 19–36% and 1.5‐fold higher than corresponding values for Icevents. Values for Emaxand Cmaxfor Ivevents were 3‐fold and 4‐fold higher than corresponding values for Icevents. Carbon enrichment ratios (CER) were ≤1.0 for ST plots and ≥1.0 for CT plots (except for first 20 min). Maximum CER for CT‐Ic, CT‐Iv, ST‐Ic, and ST‐Ivwere 2.0, 2.2, 1.0, and 1.2, respectively. Transport of sediment, carbon, and agrichemicals would be better understood if variable rainfall intensity patterns derived from natural rainfall were used in rainfall simulations to evaluate their fate and transport from CT and ST systems.
Increase in Phosphorus Losses from Grassland in Response to Olsen‐P Accumulation
Authors: Watson C. J. , Smith R. V. , Matthews D. I. 
Published: September 2007

AbstractThe Olsen‐P status of grazed grassland (Lolium perenne L.) swards in Northern Ireland was increased over a 5‐yr period (March 2000 to February 2005) by applying different rates of P fertilizer (0, 10, 20, 40, or 80 kg P ha−1 yr−1) to assess the relationship between soil P status and P losses in land drainage water and overland flow. Plots (0.2 ha) were hydrologically isolated and artificially drained to v‐notch weirs, with flow proportional monitoring of drainage water and overland flow. Annually, the collectors for overland flow intercepted between 11 and 35% of the surplus rainfall. Single flow events accounted for up to 52% of the annual dissolved reactive phosphorus (DRP) load. The Olsen‐P status of the soil influenced DRP and total phosphorus (TP) concentrations in land drainage water and overland flow. Annual TP loss was highly variable and ranged from 0.19 to 1.55 kg P ha−1 yr−1 for the plot receiving no P fertilizer and from 0.35 to 2.94 kg P ha−1 yr−1 for the plot receiving 80 kg P ha−1 yr−1 Despite the Olsen‐P status in the soils ranging from 22 to 99 mg P kg−1, after 5 yr of fertilizer P applications it was difficult to identify a clear Olsen‐P concentration at which P losses increased. Any relationship was confounded by annual variability of hydrologic events and flows and by hydrologic differences between plots. Withholding P fertilizer for over 5 yr was not long enough to lower P losses or to have an adverse effect on herbage P concentrations.
Factors Affecting the Spatial Pattern of Nitrate Contamination in Shallow Groundwater
Authors: Kaown Dugin , Hyun Yunjung , Bae Gwang‐Ok , Lee Kang‐Kun 
Published: September 2007

AbstractThe elevated level of nitrate in groundwater is a serious problem in Korean agricultural areas. To control and manage groundwater quality, the characterization of groundwater contamination and identification of the factors affecting the nitrate concentration of groundwater are significant. The characterization of groundwater contamination at a hydrologically complex agricultural site in Yupori, Chuncheon (Korea) was undertaken by analyzing the hydrochemical data of groundwater within a statistical framework. Multivariate statistical tools such as cluster analyses and Tobit regression were applied to investigate the spatial variation of nitrate contamination and to analyze the factors affecting the NO3–N concentration in a shallow groundwater system. The groundwater groups from the cluster analysis were consistent with the land use pattern of the study area. The clustered group of a gentle‐slope area with lower elevations showed higher NO3–N contamination of groundwater than groups on a hillside with higher elevations. Tobit regression results indicated that the agricultural activity in the vegetable fields and barns were the major factors affecting the elevated NO3–N concentration while the land slopes and elevations were negatively correlated with the NO3–N concentration. This shows that topographic characteristics such as land slopes and elevations should be considered to evaluate the land use impact on shallow groundwater quality.
Direct Link between Fluoranthene Biodegradation and the Mobility and Sequestration of its Residues during Aging
Authors: Vessigaud S. , Perrin‐Ganier C. , Belkessam L. , Denys S. , Schiavon M. 
Published: September 2007

AbstractThe aim of this study was to assess the influence of the polycyclic aromatic hydrocarbons (PAH)‐degrading activity in the fate of fluoranthene in soils. Three soil samples with different degrading activities (an industrial soil, the same industrial soil after biostimulation, and an agricultural soil) were spiked with 14C‐fluoranthene and incubated for 6 mo with monitoring of biodegradation and mineralization. To follow the distribution of the 14C‐fluoranthene residues (i.e., 14C‐fluoranthene and its degradation products) among the soil compartments, we performed successively leaching, centrifugation (to collect intra‐aggregate pore water), solvent extraction, and combustion of the soil columns. In the industrial soil, no mineralization of 14C‐fluoranthene was observed, and only 3% of the initial 14C‐activity was non‐extractable (with acetone:dichloromethane) after 165 d of incubation. The biostimulation (addition of unlabeled polycyclic aromatic hydrocarbons) increased the degrading activity in this soil (59% of 14C‐fluoranthene was mineralized) and increased the residues sequestration (13% of 14C‐activity was non‐extractable). The microflora of the agricultural soil mineralized 14C‐fluoranthene more slowly and to a lesser extent (25%) than the biostimulated soil, but a higher amount of 14C‐activity was sequestered (41%). Thus, the rate and extent of 14C‐fluoranthene mineralization seemed to be related to the 14C‐activity sequestration by controlling the accumulation of degradation products in the soil. 14C‐Fluoranthene biodegradation enhanced the concentration of 14C‐polar compounds in the intra‐aggregate pore water. Our results point out the close link between fluoranthene biodegradation and two key aging processes, diffusion and sequestration, in soils. Biodegradation controls the mobility and sequestration of residues by transforming fluoranthene into more polar molecules that can diffuse into the intra‐aggregate pore water and then might become bound to the matrix or entrapped in the microporosity.
Measuring Bioavailability: From a Scientific Approach to Standard Methods
Authors: Harmsen Joop 
Published: September 2007

AbstractBiological effects are not related to the total concentration of a contaminant in the soil and soil‐like materials. Organisms respond only to the fraction that is biologically available. The bioavailable fractions of contaminants are dependent on soil properties and various processes varying with time and on the behavior or the target organism. Bioavailability may be assessed in two complementary ways: (i) by chemical methods (e.g., extraction methods), which determine a defined available fraction of a well defined class of contaminants; and (ii) by biological methods, which expose organisms to soil or soil eluates to monitor effects. Although there is scientific discussion on the concept of bioavailability, the literature gives enough evidence to recognize bioavailability as a promising tool in risk assessment. A large number of methods are available. Under regulatory aspects of soil protection, a risk assessment should be based on the same common concept of determination and assessment of exposure and measuring and assessment of effects. A harmonized framework on bioavailability is necessary to promote the development and introduction of workable (international) standard methods to be used in soil and site assessment. The working group ‘Bioavailability’ of ISO/TC190‐Soil Quality has developed a guidance document for development and selection of methods to assess bioavailability for different target species with regard to several classes of contaminants. The way to this standard, on the boarder of science and regulation, is described in this article.
Improved Understanding of Hyperaccumulation Yields Commercial Phytoextraction and Phytomining Technologies
Authors: Chaney Rufus L. , Angle J. Scott , Broadhurst C. Leigh , Peters Carinne A. , Tappero Ryan V. , Sparks Donald L. 
Published: September 2007

AbstractThis paper reviews progress in phytoextraction of soil elements and illustrates the key role of hyperaccumulator plant species in useful phytoextraction technologies. Much research has focused on elements which are not practically phytoextracted (Pb); on addition of chelating agents which cause unacceptable contaminant leaching and are cost prohibitive; and on plant species which offer no useful phytoextraction capability (e.g., Brassica juncea Czern). Nickel phytoextraction by Alyssum hyperaccumulator species, which have been developed into a commercial phytomining technology, is discussed in more detail. Nickel is ultimately accumulated in vacuoles of leaf epidermal cells which prevents metal toxicity and provides defense against some insect predators and plant diseases. Constitutive up‐regulation of trans‐membrane element transporters appears to be the key process that allows these plants to achieve hyperaccumulation. Cadmium phytoextraction is needed for rice soils contaminated by mine wastes and smelter emissions with 100‐fold more soil Zn than Cd. Although many plant species can accumulate high levels of Cd in the absence of Zn, when Cd/Zn > 100, only Thlaspi caerulescens from southern France has demonstrated the ability to phytoextract useful amounts of Cd. Production of element‐enriched biomass with value as ore or fertilizer or improved food (Se) or feed supplement may offset costs of phytoextraction crop production. Transgenic phytoextraction plants have been achieved for Hg, but not for other elements. Although several researchers have been attempting to clone all genes required for effective hyperaccumulation of several elements, success appears years away; such demonstrations will be needed to prove we have identified all necessary processes in hyperaccumulation.
Integrating Biodegradation and Electroosmosis for the Enhanced Removal of Polycyclic Aromatic Hydrocarbons from Creosote‐Polluted Soils
Authors: Niqui‐Arroyo José‐Luis , Ortega‐Calvo José‐Julio 
Published: September 2007

AbstractThis paper presents a hybrid technology of soil remediation based on the integration of biodegradation and electroosmosis. We employed soils with different texture (clay soil and loamy sand) containing a mixture of polycyclic aromatic hydrocarbons (PAH) present in creosote, and inoculation with a representative soil bacterium able to degrade fluorene, phenanthrene, fluoranthene, pyrene, anthracene, and benzo[a]pyrene. Two different modes of treatment were prospected: (i) inducing in soil the simultaneous occurrence of biodegradation and electroosmosis in the presence of a biodegradable surfactant, and (ii) treating the soils sequentially with electrokinetics and bioremediation. Losses of PAH due to simultaneous biodegradation and electroosmosis (induced by a continuous electric field) were significantly higher than in control cells that contained the surfactant but no biological activity or no current. The method was especially successful with loamy sand. For example, benzo[a]pyrene decreased its concentration by 50% after 7 d, whereas 22 and 17% of the compound had disappeared as a result of electrokinetic flushing and bioremediation alone, respectively. The use of periodical changes in polarity and current pulses increased by 16% in the removal of total PAH and in up to 30% of specific compounds, including benzo[a]pyrene. With the aim of reaching lower residual levels through bioremediation, an electrokinetic pretreatment was also evaluated as a way to mobilize the less bioaccessible fraction of PAH. Residual concentrations of total biodegradable PAH, remaining after bioremediation in soil slurries, were twofold lower in electrokinetically pretreated soils than in untreated soils. The results indicate that biodegradation and electroosmosis can be successfully integrated to promote the removal of PAH from soil.
In vitro effects of the active metabolite of leflunomide, A77 1726, on feline herpesvirus–1
Authors: Williams Courtney R. , Sykes Jane E. , Mehl Margo , MacLeod Jennifer S. , Lindsay LeAnn L. , Poland Amy M. , Chen Yi-Je , Kyles Andrew E. , Waldman W. James , Gregory Clare R. 
Published: September 2007

Abstract
Objective—To determine whether the active metabolite of leflunomide, A77 1726 (A77), inhibits replication of feline herpesvirus-1 (FHV-1) in cell culture.
Study Population—Crandell Rees feline kidney (CRFK) cell cultures.
Procedures—Cell cultures were inoculated with FHV-1 and treated simultaneously with concentrations of A77 ranging from 0 to 200μM. The antiviral effect of A77 was determined by use of conventional plaque reduction assays. The effect of A77 on viral load was determined via real-time PCR analysis, and transmission electron microscopy was used to evaluate the effect of A77 on viral morphology. To determine whether the antiviral effect was attributable to alterations in CRFK cell viability and number, CRFK cells were treated with various concentrations of A77 and stained with Annexin V and propidium iodide to assess apoptosis and a mitochondrial function assay was used to determine cell viability.
Results—Concentrations of A77 ≥ 20μM were associated with substantial reduction in plaque number and viral load. Concentrations ≥ 100μM were associated with complete suppression of plaque formation. At low concentrations of A77, clusters of intracytoplasmic virus particles that appeared to lack tegument and an external membrane were detected. Treatment of uninfected CRFK cell monolayers with A77 was associated with reduction in mitochondrial function with minimal evidence of apoptosis.
Conclusions and Clinical Relevance—Leflunomide may be an alternative to current calcineurin-based immunosuppressive protocols used in feline organ transplantation because of its antiherpesviral activity.
Effect of fibroblast growth factor-2 on equine mesenchymal stem cell monolayer expansion and chondrogenesis
Authors: Stewart Allison A. , Byron Christopher R. , Pondenis Holly , Stewart Matthew C. 
Published: September 2007

Abstract
Objective—To determine whether fibroblast growth factor-2 (FGF-2) treatment of equine mesenchymal stem cells (MSCs) during monolayer expansion enhances subsequent chondrogenesis in a 3-dimensional culture system.
Animals—6 healthy horses, 6 months to 5 years of age.
Procedures—Bone marrow–derived MSCs were obtained from 6 horses. First-passage MSCs were seeded as monolayers at 10,000 cells/cm2 and in medium containing 0, 1, 10, or 100 ng of FGF-2/mL. After 6 days, MSCs were transferred to pellet cultures (200,000 cells/pellet) and maintained in chondrogenic medium. Pellets were collected after 15 days. Pellets were analyzed for collagen type II content by use of an ELISA, total glycosaminoglycan content by use of the dimethylmethylene blue dye–binding assay, and DNA content by use of fluorometric quantification. Semiquantitative PCR assay was performed to assess relative concentrations of collagen type II and aggrecan mRNAs.
Results—Use of 100 ng of FGF-2/mL significantly increased pellet DNA and glycosaminoglycan content. Collagen type II content of the pellet was also increased by use of 10 and 100 ng of FGF-2/mL. Collagen type II and aggrecan mRNA transcripts were increased by treatment with FGF-2. Some control samples had minimal evidence of collagen type II and aggrecan transcripts after 35 cycles of amplification.
Conclusions and Clinical Relevance—FGF-2 treatment of bone marrow–derived MSC monolayers enhanced subsequent chondrogenic differentiation in a 3-dimensional culture. This result is important for tissue engineering strategies dependent on MSC expansion for cartilage repair.