bluuebunny/crossref_metadata_2025_split huggingface dataset:
The central proline rich region of POB1/REPS2 plays a regulatory role in epidermal growth factor receptor endocytosis by binding to 14-3-3 and SH3 domain-containing proteins
Authors: Tomassi Laura , Costantini Anna , Corallino Salvatore , Santonico Elena , Carducci Martina , Cesareni Gianni , Castagnoli Luisa 
Published: July 2008

Abstract

Background
The human POB1/REPS2 (Partner of RalBP1) protein is highly conserved in mammals where it has been suggested to function as a molecular scaffold recruiting proteins involved in vesicular traffic and linking them to the actin cytoskeleton remodeling machinery. More recently POB1/REPS2 was found highly expressed in androgen-dependent prostate cancer cell lines, while one of its isoforms (isoform 2) is down regulated during prostate cancer progression.

Results
In this report we characterize the central proline rich domain of POB1/REPS2 and we describe for the first time its functional role in receptor endocytosis. We show that the ectopic expression of this domain has a dominant negative effect on the endocytosis of activated epidermal growth factor receptor (EGFR) while leaving transferrin receptor endocytosis unaffected. By a combination of different approaches (phage display, bioinformatics predictions, peptide arrays, mutagenic analysis, in vivo co-immunoprecipitation), we have identified two closely spaced binding motifs for 14-3-3 and for the SH3 of the proteins Amphiphysin II and Grb2. Differently from wild type, proline rich domains that are altered in these motifs do not inhibit EGFR endocytosis, suggesting that these binding motifs play a functional role in this process.

Conclusion
Our findings are relevant to the characterization of the molecular mechanism underlying the involvement of POB1/REPS2, SH3 and 14-3-3 proteins in receptor endocytosis, suggesting that 14-3-3 could work by bridging the EGF receptor and the scaffold protein POB1/REPS2.
Assessing probe-specific dye and slide biases in two-color microarray data
Authors: Lu Ruixiao , Lee Geun-Cheol , Shultz Michael , Dardick Chris , Jung Kihong , Phetsom Jirapa , Jia Yi , Rice Robert H , Goldberg Zelanna , Schnable Patrick S , Ronald Pamela , Rocke David M 
Published: July 2008

Abstract

Background
A primary reason for using two-color microarrays is that the use of two samples labeled with different dyes on the same slide, that bind to probes on the same spot, is supposed to adjust for many factors that introduce noise and errors into the analysis. Most users assume that any differences between the dyes can be adjusted out by standard methods of normalization, so that measures such as log ratios on the same slide are reliable measures of comparative expression. However, even after the normalization, there are still probe specific dye and slide variation among the data. We define a method to quantify the amount of the dye-by-probe and slide-by-probe interaction. This serves as a diagnostic, both visual and numeric, of the existence of probe-specific dye bias. We show how this improved the performance of two-color array analysis for arrays for genomic analysis of biological samples ranging from rice to human tissue.

Results
We develop a procedure for quantifying the extent of probe-specific dye and slide bias in two-color microarrays. The primary output is a graphical diagnostic of the extent of the bias which called ECDF (Empirical Cumulative Distribution Function), though numerical results are also obtained.

Conclusion
We show that the dye and slide biases were high for human and rice genomic arrays in two gene expression facilities, even after the standard intensity-based normalization, and describe how this diagnostic allowed the problems causing the probe-specific bias to be addressed, and resulted in important improvements in performance. The R package LMGene which contains the method described in this paper has been available to download from Bioconductor.
Parallel and serial computing tools for testing single-locus and epistatic SNP effects of quantitative traits in genome-wide association studies
Authors: Ma Li , Runesha H Birali , Dvorkin Daniel , Garbe John R , Da Yang 
Published: July 2008

Abstract

Background
Genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) markers provide opportunities to detect epistatic SNPs associated with quantitative traits and to detect the exact mode of an epistasis effect. Computational difficulty is the main bottleneck for epistasis testing in large scale GWAS.

Results
The EPISNPmpi and EPISNP computer programs were developed for testing single-locus and epistatic SNP effects on quantitative traits in GWAS, including tests of three single-locus effects for each SNP (SNP genotypic effect, additive and dominance effects) and five epistasis effects for each pair of SNPs (two-locus interaction, additive × additive, additive × dominance, dominance × additive, and dominance × dominance) based on the extended Kempthorne model. EPISNPmpi is the parallel computing program for epistasis testing in large scale GWAS and achieved excellent scalability for large scale analysis and portability for various parallel computing platforms. EPISNP is the serial computing program based on the EPISNPmpi code for epistasis testing in small scale GWAS using commonly available operating systems and computer hardware. Three serial computing utility programs were developed for graphical viewing of test results and epistasis networks, and for estimating CPU time and disk space requirements.

Conclusion
The EPISNPmpi parallel computing program provides an effective computing tool for epistasis testing in large scale GWAS, and the epiSNP serial computing programs are convenient tools for epistasis analysis in small scale GWAS using commonly available computer hardware.
Genetic origin, admixture, and asymmetry in maternal and paternal human lineages in Cuba
Authors: Mendizabal Isabel , Sandoval Karla , Berniell-Lee Gemma , Calafell Francesc , Salas Antonio , Martínez-Fuentes Antonio , Comas David 
Published: July 2008

Abstract

Background
Before the arrival of Europeans to Cuba, the island was inhabited by two Native American groups, the Tainos and the Ciboneys. Most of the present archaeological, linguistic and ancient DNA evidence indicates a South American origin for these populations. In colonial times, Cuban Native American people were replaced by European settlers and slaves from Africa. It is still unknown however, to what extent their genetic pool intermingled with and was 'diluted' by the arrival of newcomers. In order to investigate the demographic processes that gave rise to the current Cuban population, we analyzed the hypervariable region I (HVS-I) and five single nucleotide polymorphisms (SNPs) in the mitochondrial DNA (mtDNA) coding region in 245 individuals, and 40 Y-chromosome SNPs in 132 male individuals.

Results
The Native American contribution to present-day Cubans accounted for 33% of the maternal lineages, whereas Africa and Eurasia contributed 45% and 22% of the lineages, respectively. This Native American substrate in Cuba cannot be traced back to a single origin within the American continent, as previously suggested by ancient DNA analyses. Strikingly, no Native American lineages were found for the Y-chromosome, for which the Eurasian and African contributions were around 80% and 20%, respectively.

Conclusion
While the ancestral Native American substrate is still appreciable in the maternal lineages, the extensive process of population admixture in Cuba has left no trace of the paternal Native American lineages, mirroring the strong sexual bias in the admixture processes taking place during colonial times.
Decision maker views on priority setting in the Vancouver Island Health Authority
Authors: Dionne Francois , Mitton Craig , Smith Neale , Donaldson Cam 
Published: July 2008

Abstract

Background
Decisions regarding the allocation of available resources are a source of growing dissatisfaction for healthcare decision-makers. This dissatisfaction has led to increased interest in research on evidence-based resource allocation processes. An emerging area of interest has been the empirical analysis of the characteristics of existing and desired priority setting processes from the perspective of decision-makers.

Methods
We conducted in-depth, face-to-face interviews with 18 senior managers and medical directors with the Vancouver Island Health Authority, an integrated health care provider in British Columbia responsible for a population of approximately 730,000. Interviews were transcribed and content-analyzed, and major themes and sub-themes were identified and reported.

Results
Respondents identified nine key features of a desirable priority setting process: inclusion of baseline assessment, use of best evidence, clarity, consistency, clear and measurable criteria, dissemination of information, fair representation, alignment with the strategic direction and evaluation of results. Existing priority setting processes were found to be lacking on most of these desired features. In addition, respondents identified and explicated several factors that influence resource allocation, including political considerations and organizational culture and capacity.

Conclusion
This study makes a contribution to a growing body of knowledge which provides the type of contextual evidence that is required if priority setting processes are to be used successfully by health care decision-makers.
Expression of frog virus 3 genes is impaired in mammalian cell lines
Authors: Eaton Heather E , Metcalf Julie , Brunetti Craig R 
Published: July 2008

Abstract
Frog virus 3 (FV3) is a large DNA virus that is the prototypic member of the family Iridoviridae. To examine levels of FV3 gene expression we generated a polyclonal antibody against the FV3 protein 75L. Following a FV3 infection in fathead minnow (FHM) cells 75L was found in vesicles throughout the cytoplasm as early as 3 hours post-infection. While 75L expressed strongly in FHM cells, our findings revealed no 75L expression in mammalian cells lines despite evidence of a FV3 infection. One explanation for the lack of gene expression in mammalian cell lines may be inefficient codon usage. As a result, 75L was codon optimized and transfection of the codon optimized construct resulted in detectable expression in mammalian cells. Therefore, although FV3 can infect and replicate in mammalian cell lines, the virus may not express its full complement of genes due to inefficient codon usage in mammalian species.
Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice
Authors: Iida Noriho , Nakamoto Yasunari , Baba Tomohisa , Kakinoki Kaheita , Li Ying-Yi , Wu Yu , Matsushima Kouji , Kaneko Shuichi , Mukaida Naofumi 
Published: July 2008

AbstractThe first step in the generation of tumor immunity is the migration of dendritic cells (DCs) to the apoptotic tumor, which is presumed to be mediated by various chemokines. To clarify the roles of chemokines, we induced apoptosis using suicide gene therapy and investigated the immune responses following tumor apoptosis. We injected mice with a murine hepatoma cell line, BNL 1ME A.7R.1 (BNL), transfected with HSV-thymidine kinase (tk) gene and then treated the animals with ganciclovir (GCV). GCV treatment induced massive tumor cell apoptosis accompanied with intratumoral DC infiltration. Tumor-infiltrating DCs expressed chemokine receptors CCR1 and CCR5, and T cells and macrophages expressed CCL3, a ligand for CCR1 and CCR5. Moreover, tumor apoptosis increased the numbers of DCs migrating into the draining lymph nodes and eventually generated a specific cytotoxic cell population against BNL cells. Although GCV completely eradicated HSV-tk-transfected BNL cells in CCR1-, CCR5-, or CCL3-deficient mice, intratumoral and intranodal DC infiltration and the subsequent cytotoxicity generation were attenuated in these mice. When parental cells were injected again after complete eradication of primary tumors by GCV treatment, the wild-type mice completely rejected the rechallenged cells, but the deficient mice exhibited impairment in rejection. Thus, we provide definitive evidence indicating that CCR1 and CCR5 and their ligand CCL3 play a crucial role in the regulation of intratumoral DC accumulation and the subsequent establishment of tumor immunity following induction of tumor apoptosis by suicide genes.
Finding of Kinase Domain Mutations in Patients With Chronic Phase Chronic Myeloid Leukemia Responding to Imatinib May Identify Those at High Risk of Disease Progression
Authors: Khorashad Jamshid S. , de Lavallade Hugues , Apperley Jane F. , Milojkovic Dragana , Reid Alistair G. , Bua Marco , Szydlo Richard , Olavarria Eduardo , Kaeda Jaspal , Goldman John M. , Marin David 
Published: July 2008

Purpose Kinase domain (KD) mutations in the BCR-ABL gene are associated with resistance to imatinib in chronic myeloid leukemia (CML) but their incidence and prognostic significance in chronic phase (CP) patients without resistance are unclear. Patients and Methods We analyzed outcome for 319 patients with CML-CP who were treated with imatinib; 171 were in early CP (ECP) and 148 were in late CP (LCP). Patients were screened routinely for mutations using direct sequencing regardless of response status. The 5-year cumulative incidence of mutations was 6.6% for ECP and 17% for LCP patients. Results Of the 319 patients, 214 (67%) achieved complete cytogenetic responses (CCyR). The identification of a mutation without other evidence of imatinib resistance was highly predictive for loss of CCyR (RR, 3.8; P = .005) and for progression to advanced phase (RR, 2.3; P = .01), though the intervals from first identification to loss of CCyR and disease progression were relatively long (median, 21 and 16 months, respectively). Mutations in the P-loop (excluding residue 244) were associated with a higher risk of progression than mutations elsewhere. Conclusion We conclude that routine mutation screening of patients who appear to be responding to imatinib may identify those at high risk of disease progression.
Inadequate iodine nutrition of pregnant women from Extremadura (Spain)
Authors: Sánchez-Vega Javier , Escobar del Rey Francisco , Fariñas-Seijas Humberto , Morreale de Escobar Gabriella 
Published: July 2008

ObjectiveTo evaluate the iodine nutrition of the pregnant women of the Spanish Autonomous Community Extremadura. There are ∼10 000 births per year in Extremadura, which historically contains areas with endemic goiter (Las Hurdes).DesignPopulation study in which a representative sample of pregnant women of the general population was analyzed, along with another sample of pregnant women from traditionally goitrogenic areas. With the collaboration of selected health centers, an additional sample of blood and urine was obtained within the primary health care pregnancy-monitoring program; these samples were sent to a single central laboratory.MethodsBiochemistry: determination of iodine and creatinine in urine, and serum concentrations of thyroxine, free thyroxine, tri-iodothyronine, TSH, thyroglobulin, and two anti-thyroid antibodies. Each parameter was measured by means of a single specific RIA.ResultsChanges between the first trimester and later stages of pregnancy of all biochemical variables studied corresponded with those described for other European areas with a comparable iodine nutrition. Using the urinary iodine concentration value as an indicator of iodine ingestion, it was found that in the first trimester of pregnancy six out of ten women from Extremadura ingested less than the currently recommended amount (250 μg I/day), and approximately three out of ten of these women ingested less than half of this amount.ConclusionsIt is imperative to implement in all Extremadura the generalized and controlled use of complements that contain 200–250 μg I/day throughout pregnancy and, if possible, before.
Liver Tumors in Children
Authors: Litten Jason B. , Tomlinson Gail E. 
Published: July 2008

AbstractLearning ObjectivesAfter completing this course, the reader should be able to: Describe the current epidemiologic trends in hepatoblastoma.Identify the genetic syndromes that are seen in a subset of liver tumors.Assess the need for complete tumor resection in the treatment of liver tumors in children as well as the increasingly important option of liver transplantation for those patients with unresectable tumors.Discuss the impact of the hepatitis vaccine in reducing the incidence of hepatocellular carcinoma.Explain the prognostic impact of different histologic subtypes of hepatoblastoma.Promote the need for future clinical trials in testing new agents for hepatocellular carcinoma in children.Employ the different staging systems used in liver tumors, including the traditional North American postsurgical staging system and the European presurgical staging system using imaging.CME This article is available for continuing medical education credit at CME.TheOncologist.com.Malignant liver tumors account for slightly &gt;1% of all pediatric malignancies, with roughly 150 new cases of liver tumors diagnosed in the U.S. annually. The embryonal tumor, hepatoblastoma, accounts for two thirds of malignant liver tumors in children. Other liver malignancies in children include hepatocellular carcinoma, sarcomas, germ cell tumors, and rhabdoid tumors. Benign tumors of the liver in children include vascular tumors, hamartomas, and adenomas. There is an apparent increase in the incidence of hepatoblastoma with perinatal exposures and decreased premature infant mortality as postulated causes for this increased risk. The known causes and associations of liver tumors in children as well as the approaches to diagnosis and treatment of children are discussed in this review article.
Horizontal Drilling Review
Authors: Pendleton L. E. 
Published: July 2008

Abstract
Horizontal drilling has rapidly come into its own as a viable alternative to conventional exploration and production techniques.
The method has proved its value both for the unprecedented increases in production it has enabled operators to realize, and for its availability to allow those same operators to increase reserves by developing resources that might not otherwise be tapped. Innovative operators are applying horizontal technology to produce oil at current prices, rather than waiting for the market to improve before initiating development. Throughout the world, horizontal drilling is burgeoning, and with it, tremendous opportunities – and challenges – for operators and service companies alike.
For many operators today, the question is not so much whether to drill horizontally, but how.
Evaluating the Opportunities for Horizontal Wells in Oman
Authors: Kharusi M. S. 
Published: July 2008

Abstract
The paper describes the results of a comprehensive campaign to evaluate the applicability of horizontal wells in the concession area of Petroleum Development Oman. Thirty- one horizontal wells have been completed by June 1991 in ten different fields, covering a variety of reservoir conditions. Test wells have covered both clastics and carbonates, thin and thick oil columns, heavy and light oils, high and low watercuts. Productivities vary from mediocre to spectacular, sometimes with wells only a couple of hundred meters apart. The pace of learning has been rapid and conclusions in general very positive.
Fluid Characterization for Compositional Simulation with Application to Endicott Field, Alaska.
Authors: Ali Ansar , Mehta V. , Ogbe D. O. , Kamath V. A. , Patil S. L. 
Published: July 2008

ABSTRACT
In this study a method is presented for fluid characterization of Endicott crude oil for compositional simulation. The proposed method is developed by combining PVT and slim-tube data. Fluid properties are calculated using an equation-of-state PVT simulator, and the results are validated by history matching the data obtained from slim-tube experiments run on Endicott field oil samples. The results of the fluid characterization are used as input to a compositional simulator to study the displacement of Endicott oil by injecting carbon dioxide (CO2) and Prudhoe Bay gas (PBG) and their mixtures with natural gas liquids (NGL) into the reservoir. Fluid injection schemes such as single-slug followed by continuous water injection and multi-slug WAG process are discussed. The recovery performance of various solvent injectants in displacing the oil is determined to evaluate the technical feasibility of applying miscible EOR methods to augment production of the Endicott field.
Extracellular Vesicles from Highly Metastatic Osteosarcoma Cells Induce Pro‐Tumorigenic Macrophage Phenotypes
Authors: Griffin Katherine H. , Mizenko Rachel R. , Arun Vishalakshi , Carney Randy P. , Leach J. Kent 
Published: April 2024

AbstractMetastasis is the principal factor in poor prognosis for individuals with osteosarcoma (OS). Understanding the events that lead to metastasis is critical to develop better interventions for this disease. Alveolar macrophages are potentially involved in priming the lung microenvironment for OS metastasis, yet the mechanisms involved in this process remain unclear. Since extracellular vesicles (EVs) are a known actor in primary tumor development, their potential role in OS metastagenesis through macrophage modulation is explored here. The interaction of EVs isolated from highly metastatic (K7M2) and less metastatic (K12) osteosarcoma cell lines is compared with a peritoneal macrophage cell line. An EV concentration that reproducibly induced macrophage migration is identified first, then used for later experiments. By confocal microscopy, both EV types associated with M0 or M1 macrophages; however, only K7M2‐EVs are associated with M2 macrophages, an interaction that is abrogated by EV pre‐treatment with anti‐CD47 antibody. Interestingly, all interactions appeared to be surface binding, not internalized. In functional studies, K7M2‐EVs polarized fewer macrophages to M1. Together, these data suggest that K7M2‐EVs have unique interactions with macrophages that can contribute to the production of a higher proportion of pro‐tumor type macrophages, thereby accelerating metastasis.
Graphene Quantum Dots Eradicate Resistant and Metastatic Cancer Cells by Enhanced Interfacial Inhibition
Authors: Su Yan , Ye Kai , Hu Jinyan , Zhang Zhenlin , Wang Yang , Geng Bijiang , Pan Dengyu , Shen Longxiang 
Published: April 2024

AbstractDrug‐resistant and metastatic cancer cells such as a small population of cancer stem cells (CSCs) play a crucial role in metastasis and relapse. Conventional small‐molecule chemotherapeutics, however, are unable to eradicate drug‐resistant CSCs owing to limited interface inhibitory effects. Herein, it is reported that enhanced interfacial inhibition leading to eradication of drug‐resistant CSCs can be dramatically induced by self‐insertion of bioactive graphene quantum dots (GQDs) into DNA major groove (MAG) sites in cancer cells. Since transcription factors regulate gene expression at the MAG site, MAG‐targeted GQDs exert greatly enhanced interfacial inhibition, downregulating the expression of a collection of cancer stem genes such as ALDH1, Notch1, and Bmi1. Moreover, the nanoscale interface inhibition mechanism reverses cancer multidrug resistance (MDR) by inhibiting MDR1 gene expression when GQDs are used at a nontoxic concentration (1/4 × half‐maximal inhibitory concentration (IC50)) as the MDR reverser. Given their high efficacy in interfacial inhibition, CSC‐mediated migration, invasion, and metastasis of cancer cells can be substantially blocked by MAG‐targeted GQDs, which can also be harnessed to sensitize clinical cytotoxic agents for improved efficacy in combination chemotherapy. These findings elucidate the inhibitory effects of the enhanced nano–bio interface at the MAG site on eradicating CSCs, thus preventing cancer metastasis and recurrence.