bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane proteomic analysis of pancreatic cancer cells
Authors: Liu Xiaojun , Zhang Min , Go Vay Liang W , Hu Shen 
Published: September 2010

Abstract

Background
Pancreatic cancer is one of the most aggressive human tumors due to its high potential of local invasion and metastasis. The aim of this study was to characterize the membrane proteomes of pancreatic ductal adenocarcinoma (PDAC) cells of primary and metastatic origins, and to identify potential target proteins related to metastasis of pancreatic cancer.

Methods
Membrane/membrane-associated proteins were isolated from AsPC-1 and BxPC-3 cells and identified with a proteomic approach based on SDS-PAGE, in-gel tryptic digestion and liquid chromatography with tandem mass spectrometry (LC-MS/MS). X! Tandem was used for database searching against the SwissProt human protein database.

Results
We identified 221 & 208 proteins from AsPC-1 and BxPC-3 cells, respectively, most of which are membrane or membrane-associated proteins. A hundred and nine proteins were found in both cell lines while the others were present in either AsPC-1 or BxPC-3 cells. Differentially expressed proteins between two cell lines include modulators of cell adhesion, cell motility or tumor invasion as well as metabolic enzymes involved in glycolysis, tricarboxylic acid cycle, or nucleotide/lipid metabolism.

Conclusion
Membrane proteomes of AsPC-1 (metastatic) and BxPC-3 (primary) cells are remarkably different. The differentially expressed membrane proteins may serve as potential targets for diagnostic and therapeutic interventions.
The Neural/Immune Gene Ontology: clipping the Gene Ontology for neurological and immunological systems
Authors: Geifman Nophar , Monsonego Alon , Rubin Eitan 
Published: September 2010

Abstract

Background
The Gene Ontology (GO) is used to describe genes and gene products from many organisms. When used for functional annotation of microarray data, GO is often slimmed by editing so that only higher level terms remain. This practice is designed to improve the summarizing of experimental results by grouping high level terms and the statistical power of GO term enrichment analysis.
Here, we propose a new approach to editing the gene ontology, clipping, which is the editing of GO according to biological relevance. Creation of a GO subset by clipping is achieved by removing terms (from all hierarchal levels) if they are not functionally relevant to a given domain of interest. Terms that are located in levels higher to relevant terms are kept, thus, biologically irrelevant terms are only removed if they are not parental to terms that are relevant.

Results
Using this approach, we have created the Neural-Immune Gene Ontology (NIGO) subset of GO directed for neurological and immunological systems. We tested the performance of NIGO in extracting knowledge from microarray experiments by conducting functional analysis and comparing the results to those obtained using the full GO and a generic GO slim. NIGO not only improved the statistical scores given to relevant terms, but was also able to retrieve functionally relevant terms that did not pass statistical cutoffs when using the full GO or the slim subset.

Conclusions
Our results validate the pipeline used to generate NIGO, suggesting it is indeed enriched with terms that are specific to the neural/immune domains. The results suggest that NIGO can enhance the analysis of microarray experiments involving neural and/or immune related systems. They also directly demonstrate the potential such a domain-specific GO has in generating meaningful hypotheses.
Comparative study of three commonly used continuous deterministic methods for modeling gene regulation networks
Authors: Swain Martin T , Mandel Johannes J , Dubitzky Werner 
Published: September 2010

AbstractBackgroundA gene-regulatory network (GRN) refers to DNA segments that interact through their RNA and protein products and thereby govern the rates at which genes are transcribed. Creating accurate dynamic models of GRNs is gaining importance in biomedical research and development. To improve our understanding of continuous deterministic modeling methods employed to construct dynamic GRN models, we have carried out a comprehensive comparative study of three commonly used systems of ordinary differential equations: TheS-system (SS), artificial neural networks (ANNs), and the general rate law of transcription (GRLOT)method. These were thoroughly evaluated in terms of their ability to replicate the reference models' regulatory structure and dynamic gene expression behavior under varying conditions.ResultsWhile the ANN and GRLOT methods appeared to produce robust models even when the model parameters deviated considerably from those of the reference models, SS-based models exhibited a notable loss of performance even when the parameters of the reverse-engineered models corresponded closely to those of the reference models: this is due to the high number of power terms in the SS-method, and the manner in which they are combined. In cross-method reverse-engineering experiments the different characteristics, biases and idiosynchracies of the methods were revealed. Based on limited training data, with only one experimental condition, all methods produced dynamic models that were able to reproduce the training data accurately. However, an accurate reproduction of regulatory network features was only possible with training data originating from multiple experiments under varying conditions.ConclusionsThe studied GRN modeling methods produced dynamic GRN models exhibiting marked differences in their ability to replicate the reference models' structure and behavior. Our results suggest that care should be taking when a method is chosen for a particular application. In particular, reliance on only a single method might unduly bias the results.
Relative validation of a food frequency questionnaire for national health and nutrition monitoring
Authors: Haftenberger Marjolein , Heuer Thorsten , Heidemann Christin , Kube Friederike , Krems Carolin , Mensink Gert BM 
Published: September 2010

Abstract

Background
Validation of a food frequency questionnaire (FFQ) is important as incorrect information may lead to biased associations. Therefore the relative validity of an FFQ developed for use in the German Health Examination Survey for Adults 2008-2011 (DEGS) was examined.

Methods
Cross-sectional comparisons of food consumption data from the FFQ and from two 24-hour recalls were made in a sample of 161 participants (aged 18 to 80 years) of an ongoing nationwide survey, the German National Nutrition Monitoring (NEMONIT). The data collection took place from November 2008 to April 2009.

Results
Spearman rank correlations between the FFQ and the 24-hour dietary recalls ranged from 0.15 for pizza to 0.80 for tea, with two third of the correlation coefficients exceeding 0.30. All correlation coefficients were statistically significant except those for pizza and cooked vegetables. The proportion of participants classified into the same or adjacent quartile of intake assessed by both methods varied between 68% for cooked vegetables and 94% for coffee. There were no statistically significant differences in food consumption estimates between both methods for 38% of the food groups. For the other food groups, the estimates of food consumption by the FFQ were not generally higher or lower than estimates from the 24-hour dietary recalls.

Conclusions
The FFQ appears to be reasonably valid in the assessment of food consumption of German adults. For some food groups, such as raw and cooked vegetables, relative risks estimates should be interpreted with caution because of the poor ranking agreement.
Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome
Authors: Hong Ping , Li Jinming , Li Yongzhe 
Published: September 2010

Abstract

Background
Recent controversy has surrounded the question of whether xenotropic murine leukaemia virus-related virus (XMRV) contributes to the pathogenesis of chronic fatigue syndrome (CFS). To investigate the question in a Chinese population, 65 CFS patients and 85 blood donor controls were enrolled and multiplex real-time PCR or reverse transcriptase PCR (RT-PCR) was developed to analyze the XMRV infection status of the study participants. The assay was standardized by constructing plasmid DNAs and armored RNAs as XMRV standards and competitive internal controls (CICs), respectively.

Results
The sensitivities of the multiplex real-time PCR and RT-PCR assays were 20 copies/reaction and 10 IU/ml, respectively, with 100% specificity. The within-run precision coefficient of variation (CV) ranged from 1.76% to 2.80% and 1.70% to 2.59%, while the between-run CV ranged from 1.07% to 2.56% and 1.06% to 2.74%. XMRV was not detected in the 65 CFS patients and 65 normal individuals out of 85 controls.

Conclusions
This study failed to show XMRV in peripheral blood mononuclear cells (PBMCs) and plasma of Chinese patients with CFS. The absence of XMRV nucleic acids does not support an association between XMRV infection and the development of CFS in Chinese.
Semi-supervised drug-protein interaction prediction from heterogeneous biological spaces
Authors: Xia Zheng , Wu Ling-Yun , Zhou Xiaobo , Wong Stephen TC 
Published: September 2010

Abstract

Background
Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data.

Results
Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG.

Conclusions
We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs.
Impairment of circulating endothelial progenitors in Down syndrome
Authors: Costa Valerio , Sommese Linda , Casamassimi Amelia , Colicchio Roberta , Angelini Claudia , Marchesano Valentina , Milone Lara , Farzati Bartolomeo , Giovane Alfonso , Fiorito Carmela , Rienzo Monica , Picardi Marco , Avallone Bice , Marco Corsi Massimiliano , Sarubbi Berardo , Calabrò Raffaele , Salvatore Paola , Ciccodicola Alfredo , Napoli Claudio 
Published: September 2010

Abstract

Background
Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.

Methods
Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.

Results
We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.

Conclusions
Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.
Concurrent sexual partnerships do not explain the HIV epidemics in Africa: a systematic review of the evidence
Authors: Sawers Larry , Stillwaggon Eileen 
Published: September 2010

The notion that concurrent sexual partnerships are especially common in sub‐Saharan Africa and explain the region's high HIV prevalence is accepted by many as conventional wisdom. In this paper, we evaluate the quantitative and qualitative evidence offered by the principal proponents of the concurrency hypothesis and analyze the mathematical model they use to establish the plausibility of the hypothesis.We find that research seeking to establish a statistical correlation between concurrency and HIV prevalence either finds no correlation or has important limitations. Furthermore, in order to simulate rapid spread of HIV, mathematical models require unrealistic assumptions about frequency of sexual contact, gender symmetry, levels of concurrency, and per‐act transmission rates. Moreover, quantitative evidence cited by proponents of the concurrency hypothesis is unconvincing since they exclude Demographic and Health Surveys and other data showing that concurrency in Africa is low, make broad statements about non‐African concurrency based on very few surveys, report data incorrectly, report data from studies that have no information about concurrency as though they supported the hypothesis, report incomparable data and cite unpublished or unavailable studies. Qualitative evidence offered by proponents of the hypothesis is irrelevant since, among other reasons, there is no comparison of Africa with other regions.Promoters of the concurrency hypothesis have failed to establish that concurrency is unusually prevalent in Africa or that the kinds of concurrent partnerships found in Africa produce more rapid spread of HIV than other forms of sexual behaviour. Policy makers should turn attention to drivers of African HIV epidemics that are policy sensitive and for which there is substantial epidemiological evidence.
Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mechanisms involved in arthrotropism and sustained therapeutic efficacy
Authors: Quan Ling-dong , Purdue P Edward , Liu Xin-ming , Boska Michael D , Lele Subodh M , Thiele Geoffrey M , Mikuls Ted R , Dou Huanyu , Goldring Steven R , Wang Dong 
Published: September 2010

Abstract
Introduction
The purpose of the present manuscript is to test the hypothesis that arthrotropic localization and synovial cell internalization account for the unique capacity of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex, a macromolecular prodrug of dexamethasone) to induce sustained amelioration of joint inflammation and inhibition of tissue damage in an animal model of inflammatory arthritis.

Methods
Rats with adjuvant-induced arthritis (AA) were treated with P-Dex, free dexamethasone, saline or HPMA homopolymer. To define the biodistribution of P-Dex, conjugates with different imaging labels were given to AA rats and analyzed. Isolated joint tissues were evaluated by fluorescence-activated cell sorting (FACS) and immunohistochemical staining. Cellular uptake of P-Dex and its effects on apoptosis and production of proinflammatory cytokines were examined using human monocyte-macrophages and fibroblasts.

Results
A single systemic administration of P-Dex completely suppressed AA for >20 days. Magnetic resonance imaging demonstrated higher HPMA copolymer influx into the inflamed joints than the normal joints. Immunohistochemistry and FACS analyses of arthritic joints revealed extensive uptake of the polymer conjugate by synovial fibroblasts and myeloid lineage cells. The capacity of P-Dex to suppress inflammation was confirmed in monocyte-macrophage cultures in which P-Dex treatment resulted in suppression of lipopolysaccharide-induced IL-6 and TNFα release. Similarly, TNFα-induced expression of matrix metalloproteinases (MMP1 and MMP3) in synovial fibroblasts from a rheumatoid arthritis patient was suppressed by P-Dex. P-Dex showed no detectable effect on monocyte apoptosis.

Conclusions
P-Dex provides superior and sustained amelioration of AA compared with an equivalent dose of free dexamethasone. The arthrotropism and local retention of P-Dex is attributed to the enhanced vascular permeability in arthritic joints and the internalization of P-Dex by synovial cells. The uptake and processing of P-Dex by macrophages and fibroblasts, and downregulation of proinflammatory mediators, provides an explanation for the sustained anti-inflammatory efficacy of P-Dex in this model of inflammatory arthritis.
Host adaptive immunity deficiency in severe pandemic influenza
Authors: Bermejo-Martin Jesus F , Martin-Loeches Ignacio , Rello Jordi , Antón Andres , Almansa Raquel , Xu Luoling , Lopez-Campos Guillermo , Pumarola Tomás , Ran Longsi , Ramirez Paula , Banner David , Cheuk Ng Derek , Socias Lorenzo , Loza Ana , Andaluz David , Maravi Enrique , Gómez-Sánchez Maria J , Gordón Mónica , Gallegos Maria C , Fernandez Victoria , Aldunate Sara , León Cristobal , Merino Pedro , Blanco Jesús , Martin-Sanchez Fernando , Rico Lucia , Varillas David , Iglesias Veronica , Marcos Maria Ángeles , Gandía Francisco , Bobillo Felipe , Nogueira Begoña , Rojo Silvia , Resino Salvador , Castro Carmen , Ortiz de Lejarazu Raul , Kelvin David 
Published: September 2010

Abstract
Introduction
Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown.

Methods
We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1.

Results
The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum.

Conclusions
Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.
A Phase I Study of Sunitinib Plus Capecitabine in Patients With Advanced Solid Tumors
Authors: Sweeney Christopher J. , Chiorean E. Gabriela , Verschraegen Claire F. , Lee Fa Chyi , Jones Suzanne , Royce Melanie , Tye Lesley , Liau Katherine F. , Bello Akintunde , Chao Richard , Burris Howard A. 
Published: September 2010

Purpose This open-label, phase I, dose-escalation study assessed the maximum-tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib in combination with capecitabine in patients with advanced solid tumors. Patients and Methods Sunitinib (25, 37.5, or 50 mg) was administered orally once daily on three dosing schedules: 4 weeks on treatment, 2 weeks off treatment (Schedule 4/2); 2 weeks on treatment, 1 week off treatment (Schedule 2/1); and continuous daily dosing (CDD schedule). Capecitabine (825, 1,000, or 1,250 mg/m2) was administered orally twice daily on days 1 to 14 every 3 weeks for all patients. Sunitinib and capecitabine doses were escalated in serial patient cohorts. Results Seventy-three patients were treated. Grade 3 adverse events included abdominal pain, mucosal inflammation, fatigue, neutropenia, and hand-foot syndrome. The MTD for Schedule 4/2 and the CDD schedule was sunitinib 37.5 mg/d plus capecitabine 1,000 mg/m2 twice per day; the MTD for Schedule 2/1 was sunitinib 50 mg/d plus capecitabine 1,000 mg/m2 twice per day. There were no clinically significant pharmacokinetic drug-drug interactions. Nine partial responses were confirmed in patients with pancreatic cancer (n = 3) and breast, thyroid, neuroendocrine, bladder, and colorectal cancer, and cholangiocarcinoma (each n = 1). Conclusion The combination of sunitinib and capecitabine resulted in an acceptable safety profile in patients with advanced solid tumors. Further evaluation of sunitinib in combination with capecitabine may be undertaken using the MTD for any of the three treatment schedules.