bluuebunny/crossref_metadata_2025_split huggingface dataset:
One Hundred Million Jobs for the Chinese Workers! Why China’s Current Model of Development Is Unsustainable and How a Progressive Economic Program Can Help the Chinese Workers, the Chinese Economy, and China’s Environment
Authors: Piovani Chiara , Li Minqi 
Published: September 2010

This paper argues that China’s current model of development led by exports and investment is not sustainable for economic, social, and environmental reasons. The accumulation of economic, social, and environmental imbalances could potentially lead to a major crisis for China and the global economy. The paper proposes a progressive economic program that could help China move towards a more equitable and ecologically sustainable model of development. JEL classification: E60, O53, P30
Embryonic stem cell–derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression
Authors: Mazzarella Luca , Jørgensen Helle F. , Soza-Ried Jorge , Terry Anna V. , Pearson Stella , Lacaud Georges , Kouskoff Valerie , Merkenschlager Matthias , Fisher Amanda G. 
Published: September 2010

Abstract
Many lineage-specific developmental regulator genes are transcriptionally primed in embryonic stem (ES) cells; RNA PolII is bound at their promoters but is prevented from productive elongation by the activity of polycomb repressive complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognized by a simultaneous enrichment for trimethylation of lysine 4 and trimethylation of lysine 27 of histone H3 (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate toward blood-forming precursors. Surprisingly however, neural specifying genes, such as Nkx2-2, Nkx2-9, and Sox1, remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.
Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy
Authors: Finn Jonathan D. , Ozelo Margareth C. , Sabatino Denise E. , Franck Helen W. G. , Merricks Elizabeth P. , Crudele Julie M. , Zhou Shangzhen , Kazazian Haig H. , Lillicrap David , Nichols Timothy C. , Arruda Valder R. 
Published: September 2010

Abstract
Inhibitory antibodies to factor VIII (FVIII) are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of patients. Current treatment for inhibitors is based on long-term, daily injections of large amounts of FVIII protein. Liver-directed gene therapy has been used to induce antigen-specific tolerance, but there are no data in hemophilic animals with pre-existing inhibitors. To determine whether sustained endogenous expression of FVIII could eradicate inhibitors, we injected adeno-associated viral vectors encoding canine FVIII (cFVIII) in 2 strains of inhibitor hemophilia A dogs. In 3 dogs, a transient increase in inhibitor titers (up to 7 Bethesda Units [BU]) at 2 weeks was followed by continuous decline to complete disappearance within 4-5 weeks. Subsequently, an increase in cFVIII levels (1.5%-8%), a shortening of clotting times, and a reduction (> 90%) of bleeding episodes were observed. Immune tolerance was confirmed by lack of antibody formation after repeated challenges with cFVIII protein and normal protein half-life. A fourth dog exhibited a strong early anamnestic response (216 BU), with slow decline to 0.8 BU and cFVIII antigen detection by 18 months after vector delivery. These data suggest that liver gene therapy has the potential to eradicate inhibitors and could improve the outcomes of hemophilia A patients.
Phase 1/2 trial of total marrow and lymph node irradiation to augment reduced-intensity transplantation for advanced hematologic malignancies
Authors: Rosenthal Joseph , Wong Jeffrey , Stein Anthony , Qian Dajun , Hitt Debbie , Naeem Hossameldin , Dagis Andrew , Thomas Sandra H. , Forman Stephen 
Published: September 2010

Abstract
This phase 1/2 study assessed the augmentation of reduced-intensity conditioning (RIC) with total marrow and lymph node irradiation (TMLI), for peripheral blood stem cell transplantation, in patients with advanced hematologic disease. The regimen consisted of fludarabine 25 mg/m2 per day for 5 days, melphalan 140 mg/m2 for one day, and TMLI radiation at 150 cGy/fraction in 8 fractions over 4 days. Eligible patients were over 50 years old and/or had compromised organ function. Median age of the 33 evaluable patients was 55.2 years. Eighteen events of nonhematologic grade III or higher toxicities occurred in 9 patients. Day 30 and day 100 mortalities were 3% and 15%, respectively. Patients achieved myeloid and platelet engraftment at a median of 14 days after transplantation. Long-term toxicities occurred in 2 patients: hypokalemia and tremor, both grade III, on days 370 and 361 after transplantation. Fourteen patients died, 7 of relapse-related causes and 7 of non–relapse-related causes. With a median follow-up for living patients of 14.7 months, 1-year overall survival, event-free survival, and non–relapse-related mortality were 75%, 65%, and 19%, respectively. Addition of TMLI to RIC is feasible and safe and could be offered to patients with advanced hematologic malignancies who might not otherwise be candidates for RIC.
Non-coding RNA detection methods combined to improve usability, reproducibility and precision
Authors: Raasch Peter , Schmitz Ulf , Patenge Nadja , Vera Julio , Kreikemeyer Bernd , Wolkenhauer Olaf 
Published: September 2010

Abstract

Background
Non-coding RNAs gain more attention as their diverse roles in many cellular processes are discovered. At the same time, the need for efficient computational prediction of ncRNAs increases with the pace of sequencing technology. Existing tools are based on various approaches and techniques, but none of them provides a reliable ncRNA detector yet. Consequently, a natural approach is to combine existing tools. Due to a lack of standard input and output formats combination and comparison of existing tools is difficult. Also, for genomic scans they often need to be incorporated in detection workflows using custom scripts, which decreases transparency and reproducibility.

Results
We developed a Java-based framework to integrate existing tools and methods for ncRNA detection. This framework enables users to construct transparent detection workflows and to combine and compare different methods efficiently. We demonstrate the effectiveness of combining detection methods in case studies with the small genomes of Escherichia coli, Listeria monocytogenes and Streptococcus pyogenes. With the combined method, we gained 10% to 20% precision for sensitivities from 30% to 80%. Further, we investigated Streptococcus pyogenes for novel ncRNAs. Using multiple methods--integrated by our framework--we determined four highly probable candidates. We verified all four candidates experimentally using RT-PCR.

Conclusions
We have created an extensible framework for practical, transparent and reproducible combination and comparison of ncRNA detection methods. We have proven the effectiveness of this approach in tests and by guiding experiments to find new ncRNAs. The software is freely available under the GNU General Public License (GPL), version 3 at http://www.sbi.uni-rostock.de/moses along with source code, screen shots, examples and tutorial material.
Cell-specific occupancy of an extended repertoire of CREM and CREB binding loci in male germ cells
Authors: Martianov Igor , Choukrallah Mohamed-Amin , Krebs Arnaud , Ye Tao , Legras Stephanie , Rijkers Erikjan , Van Ijcken Wilfred , Jost Bernard , Sassone-Corsi Paolo , Davidson Irwin 
Published: September 2010

Abstract

Background
CREB and CREM are closely related factors that regulate transcription in response to various stress, metabolic and developmental signals. The CREMτ activator isoform is selectively expressed in haploid spermatids and plays an essential role in murine spermiogenesis.

Results
We have used chromatin immunoprecipitation coupled to sequencing (ChIP-seq) to map CREM and CREB target loci in round spermatids from adult mouse testis and spermatogonia derived GC1-spg cells respectively. We identify more than 9000 genomic loci most of which are cell-specifically occupied. Despite the fact that round spermatids correspond to a highly specialised differentiated state, our results show that they have a remarkably accessible chromatin environment as CREM occupies more than 6700 target loci corresponding not only to the promoters of genes selectively expressed in spermiogenesis, but also of genes involved in functions specific to other cell types. The expression of only a small subset of these target genes are affected in the round spermatids of CREM knockout animals. We also identify a set of intergenic binding loci some of which are associated with H3K4 trimethylation and elongating RNA polymerase II suggesting the existence of novel CREB and CREM regulated transcripts.

Conclusions
We demonstrate that CREM and CREB occupy a large number of promoters in highly cell specific manner. This is the first study of CREM target promoters directly in a physiologically relevant tissue in vivo and represents the most comprehensive experimental analysis of CREB/CREM regulatory potential to date.
The core genome of the anaerobic oral pathogenic bacterium Porphyromonas gingivalis
Authors: Brunner Jorg , Wittink Floyd RA , Jonker Martijs J , de Jong Mark , Breit Timo M , Laine Marja L , de Soet Johannes J , Crielaard Wim 
Published: September 2010

AbstractBackgroundThe Gram negative anaerobic bacteriumPorphyromonas gingivalishas long been recognized as a causative agent of periodontitis. Periodontitis is a chronic infectious disease of the tooth supporting tissues eventually leading to tooth-loss. Capsular polysaccharide (CPS) ofP. gingivalishas been shown to be an important virulence determinant. Seven capsular serotypes have been described. Here, we used micro-array based comparative genomic hybridization analysis (CGH) to analyze a representative of each of the capsular serotypes and a non-encapsulated strain against the highly virulent and sequenced W83 strain. We defined absent calls usingArabidopsis thaliananegative control probes, with the aim to distinguish between aberrations due to mutations and gene gain/loss.ResultsOur analyses allowed us to call aberrant genes, absent genes and divergent regions in each of the test strains. A conserved coreP. gingivalisgenome was described, which consists of 80% of the analyzed genes from the sequenced W83 strain. The percentage of aberrant genes between the test strains and control strain W83 was 8.2% to 13.7%. Among the aberrant genes many CPS biosynthesis genes were found. Most other virulence related genes could be found in the conserved core genome. Comparing highly virulent strains with less virulent strains indicates thathmuS,a putative CobN/Mg chelatase involved in heme uptake, may be a more relevant virulence determinant than previously expected. Furthermore, the description of the 39 W83-specific genes could give more insight in why this strain is more virulent than others.ConclusionAnalyses of the genetic content of theP. gingivaliscapsular serotypes allowed the description of aP. gingivaliscore genome. The high resolution data from three types of analysis of triplicate hybridization experiments may explain the higher divergence betweenP. gingivalisstrains than previously recognized.
A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families
Authors: Cuadrado-Corrales Natividad , Sánchez-Jimeno Carolina , García Marta , Escámez María-José , Illera Nuria , Hernández-Martín Ángela , Trujillo-Tiebas María-José , Ayuso Carmen , Del Rio Marcela 
Published: September 2010

Abstract

Background
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis caused by more than 500 different mutations in the COL7A1 gene and characterized by blistering of the skin following a minimal friction or mechanical trauma.
The identification of a cluster of RDEB pedigrees carrying the c.6527insC mutation in a specific area raises the question of the origin of this mutation from a common ancestor or as a result of a hotspot mutation. The aim of this study was to investigate the origin of the c.6527insC mutation.

Methods
Haplotypes were constructed by genotyping nine single nucleotides polymorphisms (SNPs) throughout the COL7A1 gene. Haplotypes were determined in RDEB patients and control samples, both of Spanish origin.

Results
Sixteen different haplotypes were identified in our study. A single haplotype cosegregated with the c.6527insC mutation.

Conclusion
Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (
CCGCTCAAA_6527insC
), thus suggesting the presence of a common ancestor.
MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients
Authors: Niimoto Takuya , Nakasa Tomoyuki , Ishikawa Masakazu , Okuhara Atsushi , Izumi Bunichiro , Deie Masataka , Suzuki Osami , Adachi Nobuo , Ochi Mitsuo 
Published: September 2010

Abstract

Background
Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients.

Methods
IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium.

Results
Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells.

Conclusion
These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.
Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs)
Authors: Upadhyay Swapna , Ganguly Koustav , Stoeger Tobias , Semmler-Bhenke Manuela , Takenaka Shinji , Kreyling Wolfgang G , Pitz Mike , Reitmeir Peter , Peters Annette , Eickelberg Oliver , Wichmann H Erich , Schulz Holger 
Published: September 2010

AbstractRationaleSeveral epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR), a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg.Methods250 μg, 500 μg and 1000 μg of fine ambient particles (aerodynamic diameter <2.5 μm, PM2.5-AB) collected from an urban background site in Augsburg during September and October 2006 (PM2.518.2 μg/m3, 10,802 particles/cm3) were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF), blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed.ResultsExposure to 1000 μg of PM2.5-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP) during 2nd-4thday after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg) and reduced heart rate (HR) on the 3rdday post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm). BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2) from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM2.5-AB instillation results in an activation of endothelin system (endothelin1), renin-angiotensin system (angiotensin converting enzyme) and also coagulation system (tissue factor, plasminogen activator inhibitor-1) in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected.ConclusionsOur data suggests that high concentrations of PM2.5-AB exposure triggers low grade PM mediated inflammatory effects in the lungs but disturbs vascular homeostasis in pulmonary tissues and on a systemic level by affecting the renin angiotensin system, the endothelin system and the coagulation cascade. These findings are indicative for promotion of endothelial dysfunction, atherosclerotic lesions, and thrombogeneis and, thus, provide plausible evidence that susceptible-predisposed individuals may develop acute cardiac events like myocardial infarction when repeatedly exposed to high pollution episodes as observed in epidemiological studies in Augsburg, Germany.
DNA methylation epigenotypes in breast cancer molecular subtypes
Authors: Bediaga Naiara G , Acha-Sagredo Amelia , Guerra Isabel , Viguri Amparo , Albaina Carmen , Ruiz Diaz Irune , Rezola Ricardo , Alberdi María Jesus , Dopazo Joaquín , Montaner David , de Renobales Mertxe , Fernández Agustín F , Field John K , Fraga Mario F , Liloglou Triantafillos , de Pancorbo Marian M 
Published: September 2010

Abstract
Introduction
Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. So far, these epigenetic contributions to sporadic breast cancer subtypes have not been well characterized, and only a limited understanding exists of the epigenetic mechanisms affected in those particular breast cancer subtypes. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes.

Methods
By using a microarray approach, we analyzed DNA methylation in regulatory regions of 806 cancer-related genes in 28 breast cancer paired samples. We subsequently performed substantial technical and biologic validation by pyrosequencing, investigating the top qualifying 19 CpG regions in independent cohorts encompassing 47 basal-like, 44 ERBB2+ overexpressing, 48 luminal A, and 48 luminal B paired breast cancer/adjacent tissues. With the all-subset selection method, we identified the most subtype-predictive methylation profiles in multivariable logistic regression analysis.

Results
The approach efficiently recognized 15 individual CpG loci differentially methylated in breast cancer tumor subtypes. We further identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors.

Conclusions
Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.
Multi-species integrative biclustering
Authors: Waltman Peter , Kacmarczyk Thadeous , Bate Ashley R , Kearns Daniel B , Reiss David J , Eichenberger Patrick , Bonneau Richard 
Published: September 2010

AbstractWe describe an algorithm, multi-species cMonkey, for the simultaneous biclustering of heterogeneous multiple-species data collections and apply the algorithm to a group of bacteria containing Bacillus subtilis, Bacillus anthracis, and Listeria monocytogenes. The algorithm reveals evolutionary insights into the surprisingly high degree of conservation of regulatory modules across these three species and allows data and insights from well-studied organisms to complement the analysis of related but less well studied organisms.
Myocarditis During Lenalidomide Therapy
Authors: Carver Joseph R , Nasta Sunita , Chong Elise A , Stonecypher Mark , Wheeler James E , Ahmadi Tahamtan , Schuster Stephen J 
Published: September 2010

Objective: To report the first case of pathologically confirmed myocarditis in a patient receiving treatment with lenalidomide for non-Hodgkin's lymphoma. Case Summary: An 85-year-old woman with recurrent follicular lymphoma was treated with lenalidomide 10 mg daily and low-dose dexamethasone 8 mg once weekly in a clinical trial. She had a past medical history of hypertension and breast cancer. Within 17 days of starting lenalidomide and dexamethasone, she developed symptoms and signs of congestive heart failure. Despite aggressive supportive care, she had progressive and refractory multiorgan failure and died. Postmortem examination of the heart confirmed the absence of coronary artery disease, and histopathological examination of the myocardium revealed a diffuse lymphocytic/eosinophilic inflammatory infiltrate with associated acute and chronic myocardial injury affecting al 4 chambers of the heart, consistent with myocarditis. Discussion: Lenalidomide is an immunomodulatory agent derived from thalidomide and is approved for the treatment of multiple myeloma and myelodysplastic syndromes. The efficacy of lenalidomide has been reported in B-cell malignancies. Common toxicities are myelosuppression, fatigue, diarrhea, skin rash, venous thromboembolism, peripheral neuropathy, and tumor flare reaction. Cardiovascular toxicity has been limited to atrial fibrillation and an increased risk for venous thromboembolism. Autoimmune hemolytic anemia, pneumonitis, and dermatitis have been described with lenalidomide. We propose an immunological mechanism for myocarditis based on the predominantly T-cell infiltration of the myocardium. Conclusions: Our findings suggest that lenalidomide may be a cause of drug-induced myocarditis. When patients treated with lenalidomide present with signs and symptoms of heart failure in the absence of other obvious causes, lenalidomide hypersensitivity should be considered in the differential diagnosis and a myocardial biopsy should be considered when other common causes of heart failure have been excluded. A reasonable management approach is drug discontinuation and early institution of corticosteroid therapy. An objective causality assessment, using the Naranjo probability scale, revealed that the adverse drug event was probable.