bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minority Group Opinion in the U.S. States
Authors: Norrander Barbara , Manzano Sylvia 
Published: January 2011

AbstractAs numerous pieces of past research have shown, the opinions of state residents significantly influence the politics and policies of the 50 U.S. states. This type of research flourished when aggregate-level indicators of overall state ideology and partisanship were devised from pooled national public opinion polls. This article provides an extension of such research by devising, from state surveys, aggregate-level measures of the ideological and partisan orientations of racial and ethnic minority voters, as well as that of white voters. These new data demonstrate that the opinions of African Americans, Latinos, and Asian Americans vary across the states, and in many cases, significantly alter the political orientations of a state's citizenry. These data will facilitate research that incorporates racial and ethnic diversity in the study of public opinion, U.S. state politics, and policy.
The future of anti-CD20 monoclonal antibodies: are we making progress?
Authors: Alduaij Waleed , Illidge Tim M. 
Published: January 2011

AbstractThe anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell malignancies. This unprecedented success has not only substantially changed the mindset of the clinical community about the ability of mAb to improve outcomes but has catalyzed the interest in the pharmaceutical industry to develop the next generation of anti-CD20 mAbs. Since the introduction of rituximab 15 years ago, we have learned much about the potential mechanisms underlying the therapeutic efficacy of anti-CD20 mAbs. In parallel, many novel anti-CD20 mAbs have entered the clinic, each designed with modifications to structure aimed at further improving efficacy. On review of the newer generation of anti-CD20 mAbs entering clinical trials, it appears that the link between the novel mechanistic insights and the development of these next-generation anti-CD20 mAbs is unclear. As we move into an era of personalized medicine, it will become increasingly important for us to develop closer links between the emerging mechanistic insights and the clinical development, to further enhance the potency of anti-CD20 mAbs beyond that achieved with rituximab.
High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade
Authors: Kießling Michael K. , Oberholzer Patrick A. , Mondal Chandrani , Karpova Maria B. , Zipser Marie C. , Lin William M. , Girardi Michael , MacConaill Laura E. , Kehoe Sarah M. , Hatton Charlie , French Lars E. , Garraway Levi A. , Polier Gernot , Süss Dorothee , Klemke Claus-Detlev , Krammer Peter H. , Gülow Karsten , Dummer Reinhard 
Published: January 2011

Abstract
Cutaneous T-cell lymphomas (CTCLs) are malignancies of skin-homing lymphoid cells, which have so far not been investigated thoroughly for common oncogenic mutations. We screened 90 biopsy specimens from CTCL patients (41 mycosis fungoides, 36 Sézary syndrome, and 13 non–mycosis fungoides/Sézary syndrome CTCL) for somatic mutations using OncoMap technology. We detected oncogenic mutations for the RAS pathway in 4 of 90 samples. One mycosis fungoides and one pleomorphic CTCL harbored a KRASG13D mutation; one Sézary syndrome and one CD30+ CTCL harbored a NRASQ61K amino acid change. All mutations were found in stage IV patients (4 of 42) who showed significantly decreased overall survival compared with stage IV patients without mutations (P = .04). In addition, we detected a NRASQ61K mutation in the CTCL cell line Hut78. Knockdown of NRAS by siRNA induced apoptosis in mutant Hut78 cells but not in CTCL cell lines lacking RAS mutations. The NRASQ61K mutation sensitized Hut78 cells toward growth inhibition by the MEK inhibitors U0126, AZD6244, and PD0325901. Furthermore, we found that MEK inhibitors exclusively induce apoptosis in Hut78 cells. Taken together, we conclude that RAS mutations are rare events at a late stage of CTCL, and our preclinical results suggest that such late-stage patients profit from MEK inhibitors.
ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes
Authors: Mazan-Mamczarz Krystyna , Hagner Patrick R. , Zhang Yongqing , Dai Bojie , Lehrmann Elin , Becker Kevin G. , Keene Jack D. , Gorospe Myriam , Liu Zhenqui , Gartenhaus Ronald B. 
Published: January 2011

Abstract
Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell-cycle checkpoints and DNA repair after DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression posttranscriptionally. Dysregulation of this DNA damage response RNA operon is probably relevant to lymphoma development in ataxia-telangiectasia persons. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.
Extending pathways and processes using molecular interaction networks to analyse cancer genome data
Authors: Glaab Enrico , Baudot Anaïs , Krasnogor Natalio , Valencia Alfonso 
Published: January 2011

AbstractBackgroundCellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways.ResultsWe present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyse their enrichment in pancreatic mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes.ConclusionsThe proposed method for extending cellular pathways helps to explain the functions of cancer mutated genes by exploiting the synergies of canonical knowledge and large-scale interaction data.
IPRStats: visualization of the functional potential of an InterProScan run
Authors: Kelly Ryan J , Vincent David E , Friedberg Iddo 
Published: January 2011

Abstract

Background
InterPro is a collection of protein signatures for the classification and automated annotation of proteins. Interproscan is a software tool that scans protein sequences against Interpro member databases using a variety of profile-based, hidden markov model and positional specific score matrix methods. It not only combines a set of analysis tools, but also performs data look-up from various sources, as well as some redundancy removal. Interproscan is robust and scalable, able to perform on any machine from a netbook to a large cluster. However, when performing whole-genome or metagenome analysis, there is a need for a fast statistical visualization of the results to have good initial grasp on the functional potential of the sequences in the analyzed data set. This is especially important when analyzing and comparing metagenomic or metaproteomic data-sets.

Results
IPRStats is a tool for the visualization of Interproscan results. Interproscan results are parsed from the Interproscan XML or EBIXML file into an SQLite or MySQL database. The results for each signature database scan are read and displayed as pie-charts or bar charts as summary statistics. A table is also provided, where each entry is a signature (e.g. a Pfam entry) accompanied by one or more Gene Ontology terms, if Interproscan was run using the Gene Ontology option.

Conclusions
We present an platform-independent, open source licensed tool that is useful for Interproscan users who wish to view the summary of their results in a rapid and concise fashion.
Systematic evaluation of genome-wide methylated DNA enrichment using a CpG island array
Authors: Yang Liu , Zhang Kunlin , Dai Wei , He Ximiao , Zhao Qian , Wang Jing , Sun Zhong Sheng 
Published: January 2011

Abstract

Background
Recent progress in high-throughput technologies has greatly contributed to the development of DNA methylation profiling. Although there are several reports that describe methylome detection of whole genome bisulfite sequencing, the high cost and heavy demand on bioinformatics analysis prevents its extensive application. Thus, current strategies for the study of mammalian DNA methylomes is still based primarily on genome-wide methylated DNA enrichment combined with DNA microarray detection or sequencing. Methylated DNA enrichment is a key step in a microarray based genome-wide methylation profiling study, and even for future high-throughput sequencing based methylome analysis.

Results
In order to evaluate the sensitivity and accuracy of methylated DNA enrichment, we investigated and optimized a number of important parameters to improve the performance of several enrichment assays, including differential methylation hybridization (DMH), microarray-based methylation assessment of single samples (MMASS), and methylated DNA immunoprecipitation (MeDIP). With advantages and disadvantages unique to each approach, we found that assays based on methylation-sensitive enzyme digestion and those based on immunoprecipitation detected different methylated DNA fragments, indicating that they are complementary in their relative ability to detect methylation differences.

Conclusions
Our study provides the first comprehensive evaluation for widely used methodologies for methylated DNA enrichment, and could be helpful for developing a cost effective approach for DNA methylation profiling.
The genome sequence of E. coli W (ATCC 9637): comparative genome analysis and an improved genome-scale reconstruction of E. coli
Authors: Archer Colin T , Kim Jihyun F , Jeong Haeyoung , Park Jin Hwan , Vickers Claudia E , Lee Sang Yup , Nielsen Lars K 
Published: January 2011

Abstract

Background

Escherichia coli is a model prokaryote, an important pathogen, and a key organism for industrial biotechnology. E. coli W (ATCC 9637), one of four strains designated as safe for laboratory purposes, has not been sequenced. E. coli W is a fast-growing strain and is the only safe strain that can utilize sucrose as a carbon source. Lifecycle analysis has demonstrated that sucrose from sugarcane is a preferred carbon source for industrial bioprocesses.

Results
We have sequenced and annotated the genome of E. coli W. The chromosome is 4,900,968 bp and encodes 4,764 ORFs. Two plasmids, pRK1 (102,536 bp) and pRK2 (5,360 bp), are also present. W has unique features relative to other sequenced laboratory strains (K-12, B and Crooks): it has a larger genome and belongs to phylogroup B1 rather than A. W also grows on a much broader range of carbon sources than does K-12. A genome-scale reconstruction was developed and validated in order to interrogate metabolic properties.

Conclusions
The genome of W is more similar to commensal and pathogenic B1 strains than phylogroup A strains, and therefore has greater utility for comparative analyses with these strains. W should therefore be the strain of choice, or 'type strain' for group B1 comparative analyses. The genome annotation and tools created here are expected to allow further utilization and development of E. coli W as an industrial organism for sucrose-based bioprocesses. Refinements in our E. coli metabolic reconstruction allow it to more accurately define E. coli metabolism relative to previous models.
The exopolyphosphatase TbrPPX1 of Trypanosoma brucei
Authors: Luginbuehl Edith , Kunz Stefan , Wentzinger Laurent , Freimoser Florian , Seebeck Thomas 
Published: January 2011

Abstract

Background
Exopolyphosphatases and pyrophosphatases play important but still incompletely understood roles in energy metabolism, and also in other aspects of cell biology such as osmoregulation or signal transduction. Earlier work has suggested that a human exopolyphosphatase, Prune, might exhibit cyclic nucleotide phosphodiesterase activity.

Results
The kinetoplastida, a large order of unicellular eukaryotes that contains many important pathogens such as Trypanosoma brucei (human sleeping sickness), Trypanosoma cruzi (Chagas disease) or Leishmania ssp (several clinically dinstinct leishmaniases) all contain several exo- and pyrophosphatases. The current study provides a systematic classification of these enzymes, which now allows to situate the information that is already available on some of these enzymes. It then analyses the exopolyphosphatase TbrPPX1 of T. brucei in detail, using RNA interference and genetic knockouts in an attempt to define its function, and immunofluorescence microscopy to study its subcellular localization.
TbrPPX1 is an exopolyphosphatase that does hydrolyze pentasodium triphosphate, but not organic triphosphates such as ATP, pyrophosphate or long-chain polyphosphates. Finally, the study investigates the potential cyclic nucleotide phosphodiesterase activity of TbrPPX1.

Conclusions
All kinetoplastid genomes that are currently available contain genes for an exopolyphosphatase and two classes of pyrophosphatases, one associated with the acidocalcisomes and one cytoplasmic. TbrPPX1 represents the T. brucei exopolyphosphatase. It is located throughout the cytoplasm, and its genetic ablation does not produce a dramatic phenotype. Importantly, TbrPPX1 does not exhibit any cyclic nucleotide specific phosphodiesterase activity, which definitively eliminates it as an additional player in cAMP signalling of the kinetoplastida.
An overview of the Phalaenopsisorchid genome through BAC end sequence analysis
Authors: Hsu Chia-Chi , Chung Yu-Lin , Chen Tien-Chih , Lee Yu-Ling , Kuo Yi-Tzu , Tsai Wen-Chieh , Hsiao Yu-Yun , Chen Yun-Wen , Wu Wen-Luan , Chen Hong-Hwa 
Published: January 2011

AbstractBackgroundPhalaenopsisorchids are popular floral crops, and development of new cultivars is economically important to floricultural industries worldwide. Analysis of orchid genes could facilitate orchid improvement. Bacterial artificial chromosome (BAC) end sequences (BESs) can provide the first glimpses into the sequence composition of a novel genome and can yield molecular markers for use in genetic mapping and breeding.ResultsWe used two BAC libraries (constructed using theBamHI andHindIII restriction enzymes) ofPhalaenopsis equestristo generate pair-end sequences from 2,920 BAC clones (71.4% and 28.6% from theBamHI andHindIII libraries, respectively), at a success rate of 95.7%. A total of 5,535 BESs were generated, representing 4.5 Mb, or about 0.3% of thePhalaenopsisgenome. The trimmed sequences ranged from 123 to 1,397 base pairs (bp) in size, with an average edited read length of 821 bp. When these BESs were subjected to sequence homology searches, it was found that 641 (11.6%) were predicted to represent protein-encoding regions, whereas 1,272 (23.0%) contained repetitive DNA. Most of the repetitive DNA sequences were gypsy- and copia-like retrotransposons (41.9% and 12.8%, respectively), whereas only 10.8% were DNA transposons. Further, 950 potential simple sequence repeats (SSRs) were discovered. Dinucleotides were the most abundant repeat motifs; AT/TA dimer repeats were the most frequent SSRs, representing 253 (26.6%) of all identified SSRs. Microsynteny analysis revealed that more BESs mapped to the whole-genome sequences of poplar than to those of grape orArabidopsis, and even fewer mapped to the rice genome. This work will facilitate analysis of thePhalaenopsisgenome, and will help clarify similarities and differences in genome composition between orchids and other plant species.ConclusionUsing BES analysis, we obtained an overview of thePhalaenopsisgenome in terms of gene abundance, the presence of repetitive DNA and SSR markers, and the extent of microsynteny with other plant species. This work provides a basis for future physical mapping of thePhalaenopsisgenome and advances our knowledge thereof.
The minor C-allele of rs2014355 in ACADSis associated with reduced insulin release following an oral glucose load
Authors: Hornbak Malene , Banasik Karina , Justesen Johanne M , Krarup Nikolaj T , Sandholt Camilla H , Andersson Åsa , Sandbæk Annelli , Lauritzen Torsten , Pisinger Charlotta , Witte Daniel R , Sørensen Thorkild IA , Pedersen Oluf , Hansen Torben 
Published: January 2011

Abstract

Background
A genome-wide association study (GWAS) using metabolite concentrations as proxies for enzymatic activity, suggested that two variants: rs2014355 in the gene encoding short-chain acyl-coenzyme A dehydrogenase (ACADS) and rs11161510 in the gene encoding medium-chain acyl-coenzyme A dehydrogenase (ACADM) impair fatty acid β-oxidation. Chronic exposure to fatty acids due to an impaired β-oxidation may down-regulate the glucose-stimulated insulin release and result in an increased risk of type 2 diabetes (T2D). We aimed to investigate whether the two variants associate with altered insulin release following an oral glucose load or with T2D.

Methods
The variants were genotyped using KASPar® PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT) in a random sample of middle-aged Danish individuals (n

ACADS
= 4,324; n

ACADM
= 4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (n

ACADS
= 8,313; n

ACADM
= 8,344).

Results
In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (β) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (β = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (β = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (β = 2.9% (0.5%;5.2%), P = 0.02). The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P = 0.21). rs11161510 of ACADM did not associate with any indices of glucose-stimulated insulin release or with T2D.

Conclusions
In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS was associated with reduced measures of glucose-stimulated insulin release during an OGTT, a finding which in part may be mediated through an impaired β-oxidation of fatty acids.
Corticosteroid and antiviral therapy for Bell's palsy: A network meta-analysis
Authors: Numthavaj Pawin , Thakkinstian Ammarin , Dejthevaporn Charungthai , Attia John 
Published: January 2011

Abstract

Background
Previous meta-analyses of treatments for Bell's palsy are still inconclusive due to different comparators, insufficient data, and lack of power. We therefore conducted a network meta-analysis combining direct and indirect comparisons for assessing efficacy of steroids and antiviral treatment (AVT) at 3 and 6 months.

Methods
We searched Medline and EMBASE until September 2010 using PubMed and Elsviere search engines. A network meta-analysis was performed to assess disease recovery using a mixed effects hierarchical model. Goodness of fit of the model was assessed, and the pooled odds ratio (OR) and 95% confidence interval (CI) were estimated.

Results
Six studies (total n = 1805)were eligible and contributed to the network meta-analysis. The pooled ORs for resolution at 3 months were 1.24 (95% CI: 0.79 - 1.94) for Acyclovir plus Prednisolone and 1.02 (95% CI: 0.73 - 1.42) for Valacyclovir plus Prednisolone, versus Prednisolone alone. Either Acyclovir or Valacyclovir singly had significantly lower efficacy than Prednisolone alone, i.e., ORs were 0·44 (95% CI: 0·28 - 0·68) and 0·60 (95% CI: 0·42 - 0·87), respectively. Neither of the antiviral agents was significantly different compared with placebo, with a pooled OR of 1·25 (95% CI: 0·78 - 1·98) for Acyclovir and 0·91 (95% CI: 0·63 - 1·31) for Valacyclovir. Overall, Prednisolone-based treatment increased the chance of recovery 2-fold (95% CI: 1·55 - 2·42) compared to non-Prednisolone-based treatment. To gain 1 extra recovery, 6 and 26 patients need to be treated with Acyclovir and prednisolone compared to placebo and prednisolone alone, respectively.

Conclusions
Our evidence suggests that the current practice of treating Bell's palsy with AVT plus corticosteroid may lead to slightly higher recovery rates compared to treating with prednisone alone but this does not quite reach statistical significance; prednisone remains the best evidence-based treatment.