bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Irreversible Small Molecule Inhibitors of Replication Protein A Display Single-Agent Activity and Synergize with Cisplatin
Authors: Neher Tracy M. , Bodenmiller Diane , Fitch Richard W. , Jalal Shadia I. , Turchi John J. 
Published: August 2011

AbstractReplication protein A (RPA) is a single-strand DNA-binding protein with essential roles in DNA replication, recombination, and repair. It is necessary for the formation of the preincision complex that is required for proper incision of damaged DNA nucleotides during DNA repair. We have previously identified small molecule inhibitors (SMI) with the ability to disrupt RPA-binding activity to ssDNA. Further characterization of these RPA inhibitors was done using both lung and ovarian cancer cell lines. Lung cancer cell lines showed increased apoptotic cell death following treatment with the SMI MCI13E, with IC50 values of approximately 5 μmol/L. The ovarian cancer cell line A2780 and the p53-null lung cancer cell line H1299 were particularly sensitive to MCI13E treatment, with IC50 values less than 3 μmol/L. Furthermore, a cell-cycle effect was observed in lung cancer cell lines that resulted in a lengthening of either G1 or S-phases of the cell cycle following single-agent treatment. Sequential treatment with MCI13E and cisplatin resulted in synergism. Overall, these data suggest that decreasing DNA-binding activity of RPA via a SMI may disrupt the role of RPA in cell-cycle regulation. Thus, SMIs of RPA hold the potential to be used as single-agent chemotherapeutics or in combination with current chemotherapeutic regimens to increase efficacy. Mol Cancer Ther; 10(10); 1796–806. ©2011 AACR.
Methyl Selenocysteine: Single-Dose Pharmacokinetics in Men
Authors: Marshall James R. , Ip Clement , Romano Karen , Fetterly Gerald , Fakih Marwan , Jovanovic Borko , Perloff Marjorie , Crowell James , Davis Warren , French-Christy Renee , Dew Alexander , Coomes Margerie , Bergan Raymond 
Published: August 2011

Abstract
The recently published report of the SELECT evaluation of selenium and vitamin E provided strong evidence that selenium 200 μg per day in the form of selenomethionine does not protect selenium-replete men against prostate or any other cancer. This seems to refute the result of the much smaller Nutritional Prevention of Cancer (NPC) trial of selenium. Because SELECT did not test the NPC agent, it is possible that the difference between the two trials stems partly from the use of different agents: selenomethionine in SELECT, and selenized yeast in the NPC trial. One of the organic selenium forms suspected of having strong chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine. This study characterizes the single-dose pharmacokinetics of methyl selenocysteine. Cancer Prev Res; 4(11); 1938–44. ©2011 AACR.
Red Wine Consumption is Inversely Associated with 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine–DNA Adduct Levels in Prostate
Authors: Rybicki Benjamin A. , Neslund-Dudas Christine , Bock Cathryn H. , Nock Nora L. , Rundle Andrew , Jankowski Michelle , Levin Albert M. , Beebe-Dimmer Jennifer , Savera Adnan T. , Takahashi Satoru , Shirai Tomoyuki , Tang Deliang 
Published: August 2011

Abstract
In humans, genetic variation and dietary factors may alter the biological effects of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the major heterocyclic amines generated from cooking meats at high temperatures that has carcinogenic potential through the formation of DNA adducts. Previously, we reported grilled red meat consumption associated with PhIP–DNA adduct levels in human prostate. In this study, we expanded our investigation to estimate the associations between beverage consumption and PhIP–DNA adduct levels in prostate for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption had the strongest association with PhIP–DNA adduct levels showing an inverse correlation in both tumor (P = 0.006) and nontumor (P = 0.002) prostate cells. Red wine consumption was significantly lower in African American compared with white cases, but PhIP–DNA adduct levels in prostate did not vary by race. In African Americans compared with whites, however, associations between red wine consumption and PhIP–DNA adduct levels were not as strong as associations with specific (e.g., SULT1A1 and UGT1A10 genotypes) and nonspecific (e.g., African ancestry) genetic variation. In a multivariable model, the covariate for red wine consumption explained a comparable percentage (13%–16%) of the variation in PhIP–DNA adduct levels in prostate across the two racial groups, but the aforementioned genetic factors explained 33% of the PhIP–DNA adduct variation in African American cases, whereas only 19% of the PhIP–DNA adduct variation in whites. We conclude that red wine consumption may counteract biological effects of PhIP exposure in human prostate, but genetic factors may play an even larger role, particularly in African Americans. Cancer Prev Res; 4(10); 1636–44. ©2011 AACR.
Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies
IL6R
Polymorphism in Relation to Atrial Fibrillation
Authors: Schnabel Renate B. , Kerr Kathleen F. , Lubitz Steven A. , Alkylbekova Ermeg L. , Marcus Gregory M. , Sinner Moritz F. , Magnani Jared W. , Wolf Philip A. , Deo Rajat , Lloyd-Jones Donald M. , Lunetta Kathryn L. , Mehra Reena , Levy Daniel , Fox Ervin R. , Arking Dan E. , Mosley Thomas H. , Müller-Nurasyid Martina , Young Taylor R. , Wichmann H.-Erich , Seshadri Sudha , Farlow Deborah N. , Rotter Jerome I. , Soliman Elsayed Z. , Glazer Nicole L. , Wilson James G. , Breteler Monique M.B. , Sotoodehnia Nona , Newton-Cheh Christopher , Kääb Stefan , Ellinor Patrick T. , Alonso Alvaro , Benjamin Emelia J. , Heckbert Susan R. ,   for the Candidate Gene Association Resource (CARe) Atrial Fibrillation/Electrocardiography Working Group
Published: August 2011

Background—
The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.

Methods and Results—

We examined a panel of approximately 50 000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18 524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19 602 whites, 1544 incident strokes). SNP rs4845625 in the
IL6R
gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85–0.95;
P
=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72–1.03;
P
=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57–0.89;
P
=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16–1.69;
P
=0.0005).

Conclusions—

In a community-based cohort meta-analysis, we identified genetic association in
IL6R
with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.
Pseudepigraphy, Anonymity, and Auteur Theory
Authors: Silverman Jason M. 
Published: August 2011

AbstractOne of the striking features of Second Temple Judaism is the appearance of the phenomenon of pseudepigraphy. Intertwined with this phenomenon are the questions of authorship, fidelity to tradition, and the creative formation of new works. This paper attempts to bring to bear the debates on the “Auteur” in Film Studies to the understanding of authorial persona and voice in the Jewish writings of the Persian and Hellenistic Period. By focusing on a broader set of issues centered on creative production, this paper hopes to find new ways of viewing the old problems inherent in redaction theory.
The Biological Response following Autogenous Bone Grafting for Large-Volume Defects of the Knee
Authors: Johnson Lanny L. , DeLano Mark C. , Spector Myron , Jeng Lily , Pittsley Andrew , Gottschalk Alexander 
Published: August 2011

Objective: This report focuses on the biological events occurring at various intervals following autogenous bone grafting of large-volume defects of the knee joint’s femoral condyle secondary to osteochondritis dissecans (OCD) or osteonecrosis (ON). It was hypothesized that the autogenous bone graft would integrate and the portion exposed to the articular surface would form fibrocartilage, which would endure for years. Methods: Between September 29, 1987 and August 8, 1994, there were 51 patients treated with autogenous bone grafting for large-volume osteochondral defects. Twenty-five of the 51 patients were available for long-term follow-up up to 21 years. Patient follow-up was accomplished by clinical opportunity and intentional research. Videotapes were available on all index surgeries for review and comparison. All had preoperative and postoperative plain film radiographs. Long-term follow-up included MRI up to 21 years. Second-look arthroscopy and biopsy were obtained on 14 patients between 8 weeks and 20 years. Results: Radiological assessment showed the autogenous bone grafts integrated with the host bone. The grafts retained the physical geometry of the original placement. MRI showed soft tissue covering the grafts in all cases at long-term follow-up. Interval biopsy showed the surface covered with fibrous tissue at 8 weeks and subsequently converted to fibrocartilage with hyaline cartilage at 20 years. Conclusion: Autogenous bone grafting provides a matrix for large osteochondral defects that integrates with the host bone and results in a surface repair of fibrocartilage and hyaline cartilage that can endure for up to 20 years.
Malignancies occurring during therapy with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) and other hematologic malignancies
Authors: Verma Dushyant , Kantarjian Hagop , Strom Sara S. , Rios Mary Beth , Jabbour Elias , Quintas-Cardama Alfonso , Verstovsek Srdan , Ravandi Farhad , O'Brien Susan , Cortes Jorge 
Published: August 2011

Abstract
Success of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has given patients hope for a long disease-free-survival. A longer survival raises the question of late effects, including development of another malignancy. Records of 1445 patients with CML/myeloproliferative neoplasm or other hematologic malignancies treated with TKIs were reviewed to investigate frequency and characteristics of second malignancies (other than acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndrome). The number of second cancers was compared with the number expected from the Surveillance, Epidemiology, and End Results database. After a median follow-up of 107 months (range, 13-362 months) after CML/myeloproliferative neoplasm diagnosis, 66 patients (4.6%) developed 80 second cancers, including skin (31%), prostate (15%), melanoma (13%), digestive system (10%), kidney (4%), thyroid (4%), breast (3%), chronic lymphocytic leukemia (3%), hepatobiliary (3%), and other cancers (14%). Excluding nonmelanoma skin cancers, 55 second cancers were seen in 51 (3.5%) of all patients treated. The risk of second cancer was lower than expected (observed-to-expected ratio, 0.6; 95% confidence interval, 0.44-0.81). Second cancers occur in a small percentage of patients receiving therapy with TKIs for hematologic malignancies, mostly CML. No evidence at the moment suggests that exposure to TKIs increases the risk of developing second cancers.
A comparison of the functional modules identified from time course and static PPI network data
Authors: Tang Xiwei , Wang Jianxin , Liu Binbin , Li Min , Chen Gang , Pan Yi 
Published: August 2011

Abstract

Background
Cellular systems are highly dynamic and responsive to cues from the environment. Cellular function and response patterns to external stimuli are regulated by biological networks. A protein-protein interaction (PPI) network with static connectivity is dynamic in the sense that the nodes implement so-called functional activities that evolve in time. The shift from static to dynamic network analysis is essential for further understanding of molecular systems.

Results
In this paper, Time Course Protein Interaction Networks (TC-PINs) are reconstructed by incorporating time series gene expression into PPI networks. Then, a clustering algorithm is used to create functional modules from three kinds of networks: the TC-PINs, a static PPI network and a pseudorandom network. For the functional modules from the TC-PINs, repetitive modules and modules contained within bigger modules are removed. Finally, matching and GO enrichment analyses are performed to compare the functional modules detected from those networks.

Conclusions
The comparative analyses show that the functional modules from the TC-PINs have much more significant biological meaning than those from static PPI networks. Moreover, it implies that many studies on static PPI networks can be done on the TC-PINs and accordingly, the experimental results are much more satisfactory. The 36 PPI networks corresponding to 36 time points, identified as part of this study, and other materials are available at http://bioinfo.csu.edu.cn/txw/TC-PINs
Improving the efficiency of feed utilization in poultry by selection. 2. Genetic parameters of excretion traits and correlations with anatomy of the gastro-intestinal tract and digestive efficiency
Authors: de Verdal Hugues , Narcy Agnès , Bastianelli Denis , Chapuis Hervé , Même Nathalie , Urvoix Séverine , Le Bihan-Duval Elisabeth , Mignon-Grasteau Sandrine 
Published: August 2011

Abstract

Background
Poultry production has been widely criticized for its negative environmental impact related to the quantity of manure produced and to its nitrogen and phosphorus content. In this study, we investigated which traits related to excretion could be used to select chickens for lower environmental pollution.
The genetic parameters of several excretion traits were estimated on 630 chickens originating from 2 chicken lines divergently selected on apparent metabolisable energy corrected for zero nitrogen (AMEn) at constant body weight. The quantity of excreta relative to feed consumption (CDUDM), the nitrogen and phosphorus excreted, the nitrogen to phosphorus ratio and the water content of excreta were measured, and the consequences of such selection on performance and gastro-intestinal tract (GIT) characteristics estimated. The genetic correlations between excretion, GIT and performance traits were established.

Results
Heritability estimates were high for CDUDM and the nitrogen excretion rate (0.30 and 0.29, respectively). The other excretion measurements showed low to moderate heritability estimates, ranging from 0.10 for excreta water content to 0.22 for the phosphorus excretion rate. Except for the excreta water content, the CDUDM was highly correlated with the excretion traits, ranging from -0.64 to -1.00. The genetic correlations between AMEn or CDUDM and the GIT characteristics were very similar and showed that a decrease in chicken excretion involves an increase in weight of the upper part of the GIT, and a decrease in the weight of the small intestine.

Conclusion
In order to limit the environmental impact of chicken production, AMEn and CDUDM seem to be more suitable criteria to include in selection schemes than feed efficiency traits.
Pattern of BOLD signal in auditory cortex relates acoustic response to perceptual streaming
Authors: Hill Kevin T , Bishop Christopher W , Yadav Deepak , Miller Lee M 
Published: August 2011

Abstract

Background
Segregating auditory scenes into distinct objects or streams is one of our brain's greatest perceptual challenges. Streaming has classically been studied with bistable sound stimuli, perceived alternately as a single group or two separate groups. Throughout the last decade different methodologies have yielded inconsistent evidence about the role of auditory cortex in the maintenance of streams. In particular, studies using functional magnetic resonance imaging (fMRI) have been unable to show persistent activity within auditory cortex (AC) that distinguishes between perceptual states.

Results
We use bistable stimuli, an explicit perceptual categorization task, and a focused region of interest (ROI) analysis to demonstrate an effect of perceptual state within AC. We find that AC has more activity when listeners perceive the split percept rather than the grouped percept. In addition, within this ROI the pattern of acoustic response across voxels is significantly correlated with the pattern of perceptual modulation. In a whole-brain exploratory test, we corroborate previous work showing an effect of perceptual state in the intraparietal sulcus.

Conclusions
Our results show that the maintenance of auditory streams is reflected in AC activity, directly relating sound responses to perception, and that perceptual state is further represented in multiple, higher level cortical regions.
Non-Invasive markers for hepatic fibrosis
Authors: Baranova Ancha , Lal Priyanka , Birerdinc Aybike , Younossi Zobair M 
Published: August 2011

Abstract
With great advancements in the therapeutic modalities used for the treatment of chronic liver diseases, the accurate assessment of liver fibrosis is a vital need for successful individualized management of disease activity in patients. The lack of accurate, reproducible and easily applied methods for fibrosis assessment has been the major limitation in both the clinical management and for research in liver diseases. However, the problem of the development of biomarkers capable of non-invasive staging of fibrosis in the liver is difficult due to the fact that the process of fibrogenesis is a component of the normal healing response to injury, invasion by pathogens, and many other etiologic factors. Current non-invasive methods range from serum biomarker assays to advanced imaging techniques such as transient elastography and magnetic resonance imaging (MRI). Among non-invasive methods that gain strongest clinical foothold are FibroScan elastometry and serum-based APRI and FibroTest. There are many other tests that are not yet widely validated, but are none the less, promising. The rate of adoption of non-invasive diagnostic tests for liver fibrosis differs from country to country, but remains limited. At the present time, use of non-invasive procedures could be recommended as pre-screening that may allow physicians to narrow down the patients' population before definitive testing of liver fibrosis by biopsy of the liver. This review provides a systematic overview of these techniques, as well as both direct and indirect biomarkers based approaches used to stage fibrosis and covers recent developments in this rapidly advancing area.
Real-time PCR detection of Human Herpesvirus 1-5 in patients lacking clinical signs of a viral CNS infection
Authors: Sundén Birgitta , Larsson Marie , Falkeborn Tina , Paues Jakob , Forsum Urban , Lindh Magnus , Ydrenius Liselotte , Åkerlind Britt , Serrander Lena 
Published: August 2011

Abstract

Background
Infections of the central nervous system (CNS) with herpes- or enterovirus can be self-limiting and benign, but occasionally result in severe and fatal disease. The polymerase chain reaction (PCR) has revolutionized the diagnostics of viral pathogens, and by multiple displacement amplification (MDA) prior to real-time PCR the sensitivity might be further enhanced. The aim of this study was to investigate if herpes- or enterovirus can be detected in cerebrospinal fluid (CSF) from patients without symptoms.

Methods
Cerebrospinal fluid (CSF) samples from 373 patients lacking typical symptoms of viral CNS infection were analysed by real-time PCR targeting herpesviruses or enteroviruses with or without prior MDA.

Results
In total, virus was detected in 17 patients (4%). Epstein-Barr virus (EBV) was most commonly detected, in general from patients with other conditions (e.g. infections, cerebral hemorrhage). MDA satisfactorily amplified viral DNA in the absence of human nucleic acids, but showed poor amplification capacity for viral DNA in CSF samples, and did not increase the sensitivity for herpes virus-detection with our methodology.

Conclusions
Viral pathogens are rarely detected in CSF from patients without signs of CNS infection, supporting the view that real-time PCR is a highly specific method to detect symptomatic CNS-infection caused by these viruses. However, EBV may be subclinically reactivated due to other pathological conditions in the CNS.
Downregulation of TFPI in breast cancer cells induces tyrosine phosphorylation signaling and increases metastatic growth by stimulating cell motility
Authors: Stavik Benedicte , Skretting Grethe , Aasheim Hans-Christian , Tinholt Mari , Zernichow Lillian , Sletten Marit , Sandset Per Morten , Iversen Nina 
Published: August 2011

AbstractBackgroundIncreased hemostatic activity is common in many cancer types and often causes additional complications and even death. Circumstantial evidence suggests that tissue factor pathway inhibitor-1 (TFPI) plays a role in cancer development. We recently reported that downregulation of TFPI inhibited apoptosis in a breast cancer cell line. In this study, we investigated the effects of TFPI on self-sustained growth and motility of these cells, and of another invasive breast cancer cell type (MDA-MB-231).MethodsStable cell lines with TFPI (both α and β) and only TFPIβ downregulated were created using RNA interference technology. We investigated the ability of the transduced cells to grow, when seeded at low densities, and to form colonies, along with metastatic characteristics such as adhesion, migration and invasion.ResultsDownregulation of TFPI was associated with increased self-sustained cell growth. An increase in cell attachment and spreading was observed to collagen type I, together with elevated levels of integrin α2. Downregulation of TFPI also stimulated migration and invasion of cells, and elevated MMP activity was involved in the increased invasion observed. Surprisingly, equivalent results were observed when TFPIβ was downregulated, revealing a novel function of this isoform in cancer metastasis.ConclusionsOur results suggest an anti-metastatic effect of TFPI and may provide a novel therapeutic approach in cancer.