bluuebunny/crossref_metadata_2025_split huggingface dataset:
AltTrans: Transcript pattern variants annotated for both alternative splicing and alternative polyadenylation
Authors: Le Texier Vincent , Riethoven Jean-Jack , Kumanduri Vasudev , Gopalakrishnan Chellappa , Lopez Fabrice , Gautheret Daniel , Thanaraj Thangavel Alphonse 
Published: April 2006

Abstract

Background
The three major mechanisms that regulate transcript formation involve the selection of alternative sites for transcription start (TS), splicing, and polyadenylation. Currently there are efforts that collect data & annotation individually for each of these variants. It is important to take an integrated view of these data sets and to derive a data set of alternate transcripts along with consolidated annotation. We have been developing in the past computational pipelines that generate value-added data at genome-scale on individual variant types; these include AltSplice on splicing and AltPAS on polyadenylation. We now extend these pipelines and integrate the resultant data sets to facilitate an integrated view of the contributions from splicing and polyadenylation in the formation of transcript variants.

Description
The AltSplice pipeline examines gene-transcript alignments and delineates alternative splice events and splice patterns; this pipeline is extended as AltTrans to delineate isoform transcript patterns for each of which both introns/exons and 'terminating' polyA site are delineated; EST/mRNA sequences that qualify the transcript pattern confirm both the underlying splicing and polyadenylation. The AltPAS pipeline examines gene-transcript alignments and delineates all potential polyA sites irrespective of underlying splicing patterns. Resultant polyA sites from both AltTrans and AltPAS are merged. The generated database reports data on alternative splicing, alternative polyadenylation and the resultant alternate transcript patterns; the basal data is annotated for various biological features. The data (named as integrated AltTrans data) generated for both the organisms of human and mouse is made available through the Alternate Transcript Diversity web site at http://www.ebi.ac.uk/atd/.

Conclusion
The reported data set presents alternate transcript patterns that are annotated for both alternative splicing and alternative polyadenylation. Results based on current transcriptome data indicate that the contribution of alternative splicing is larger than that of alternative polyadenylation.
Automatic pathway building in biological association networks
Authors: Yuryev Anton , Mulyukov Zufar , Kotelnikova Ekaterina , Maslov Sergei , Egorov Sergei , Nikitin Alexander , Daraselia Nikolai , Mazo Ilya 
Published: April 2006

Abstract

Background
Scientific literature is a source of the most reliable and comprehensive knowledge about molecular interaction networks. Formalization of this knowledge is necessary for computational analysis and is achieved by automatic fact extraction using various text-mining algorithms. Most of these techniques suffer from high false positive rates and redundancy of the extracted information. The extracted facts form a large network with no pathways defined.

Results
We describe the methodology for automatic curation of Biological Association Networks (BANs) derived by a natural language processing technology called Medscan. The curated data is used for automatic pathway reconstruction. The algorithm for the reconstruction of signaling pathways is also described and validated by comparison with manually curated pathways and tissue-specific gene expression profiles.

Conclusion
Biological Association Networks extracted by MedScan technology contain sufficient information for constructing thousands of mammalian signaling pathways for multiple tissues. The automatically curated MedScan data is adequate for automatic generation of good quality signaling networks. The automatically generated Regulome pathways and manually curated pathways used for their validation are available free in the ResNetCore database from Ariadne Genomics, Inc. [1]. The pathways can be viewed and analyzed through the use of a free demo version of PathwayStudio software. The Medscan technology is also available for evaluation using the free demo version of PathwayStudio software.
The Gaggle: An open-source software system for integrating bioinformatics software and data sources
Authors: Shannon Paul T , Reiss David J , Bonneau Richard , Baliga Nitin S 
Published: April 2006

AbstractBackgroundSystems biologists work with many kinds of data, from many different sources, using a variety of software tools. Each of these tools typically excels at one type of analysis, such as of microarrays, of metabolic networks and of predicted protein structure. A crucial challenge is to combine the capabilities of these (and other forthcoming) data resources and tools to create a data exploration and analysis environment that does justice to the variety and complexity of systems biology data sets. A solution to this problem should recognize that data types, formats and software in this high throughput age of biology are constantly changing.ResultsIn this paper we describe the Gaggle -a simple, open-source Java software environment that helps to solve the problem of software and database integration. Guided by the classic software engineering strategy ofseparation of concernsand a policy ofsemantic flexibility, it integrates existing popular programs and web resources into a user-friendly, easily-extended environment.We demonstrate that four simple data types (names, matrices, networks, and associative arrays) are sufficient to bring together diverse databases and software. We highlight some capabilities of the Gaggle with an exploration ofHelicobacter pyloripathogenesis genes, in which we identify a putative ricin-like protein -a discovery made possible by simultaneous data exploration using a wide range of publicly available data and a variety of popular bioinformatics software tools.ConclusionWe have integrated diverse databases (for example, KEGG, BioCyc, String) and software (Cytoscape, DataMatrixViewer, R statistical environment, and TIGR Microarray Expression Viewer). Through this loose coupling of diverse software and databases the Gaggle enables simultaneous exploration of experimental data (mRNA and protein abundance, protein-protein and protein-DNA interactions), functional associations (operon, chromosomal proximity, phylogenetic pattern), metabolic pathways (KEGG) and Pubmed abstracts (STRING web resource), creating an exploratory environment useful to 'web browser and spreadsheet biologists', to statistically savvy computational biologists, and those in between. The Gaggle uses Java RMI and Java Web Start technologies and can be found athttp://gaggle.systemsbiology.net.
Highly sensitive and specific bioassay for measuring bioactive TGF-β
Authors: Tesseur Ina , Zou Kun , Berber Elisabeth , Zhang Hui , Wyss-Coray Tony 
Published: April 2006

AbstractBackgroundTransforming Growth Factor-β (TGF-β) regulates key biological processes during development and in adult tissues and has been implicated in many diseases. To study the biological functions of TGF-β, sensitive, specific, and convenient bioassays are necessary. Here we describe a new cell-based bioassay that fulfills these requirements.ResultsEmbryonic fibroblasts fromTgfb1-/-mice were stably transfected with a reporter plasmid consisting of TGF-β responsive Smad-binding elements coupled to a secreted alkaline phosphatase reporter gene (SBE-SEAP). Clone MFB-F11 showed more than 1000-fold induction after stimulation with 1 ng/ml TGF-β1, and detected as little as 1 pg/ml TGF-β1. MFB-F11 cells were highly induced by TGF-β1, TGF-β2 and TGF-β3, but did not show induction with related family members activin, nodal, BMP-2 and BMP-6 or with trophic factors bFGF and BDNF. MFB-F11 cells can detect and quantify TGF-β in biological samples without prior enrichment of TGF-βs, and can detect biologically activated TGF-β in a cell co-culture system.ConclusionMFB-F11 cells can be used to rapidly and specifically measure TGF-β with high sensitivity.
Notch signaling through Tramtrack bypasses the mitosis promoting activity of the JNK pathway in the mitotic-to-endocycle transition of Drosophila follicle cells
Authors: Jordan Katherine C , Schaeffer Valerie , Fischer Karin A , Gray Elizabeth E , Ruohola-Baker Hannele 
Published: April 2006

Abstract

Background
The follicle cells of the Drosophila egg chamber provide an excellent model in which to study modulation of the cell cycle. During mid-oogenesis, the follicle cells undergo a variation of the cell cycle, endocycle, in which the cells replicate their DNA, but do not go through mitosis. Previously, we showed that Notch signaling is required for the mitotic-to-endocycle transition, through downregulating String/Cdc25, and Dacapo/p21 and upregulating Fizzy-related/Cdh1.

Results
In this paper, we show that Notch signaling is modulated by Shaggy and temporally induced by the ligand Delta, at the mitotic-to-endocycle transition. In addition, a downstream target of Notch, tramtrack, acts at the mitotic-to-endocycle transition. We also demonstrate that the JNK pathway is required to promote mitosis prior to the transition, independent of the cell cycle components acted on by the Notch pathway.

Conclusion
This work reveals new insights into the regulation of Notch-dependent mitotic-to-endocycle switch.
Evolution of four gene families with patchy phylogenetic distributions: influx of genes into protist genomes
Authors: Andersson Jan O , Hirt Robert P , Foster Peter G , Roger Andrew J 
Published: April 2006

Abstract

Background
Lateral gene transfer (LGT) in eukaryotes from non-organellar sources is a controversial subject in need of further study. Here we present gene distribution and phylogenetic analyses of the genes encoding the hybrid-cluster protein, A-type flavoprotein, glucosamine-6-phosphate isomerase, and alcohol dehydrogenase E. These four genes have a limited distribution among sequenced prokaryotic and eukaryotic genomes and were previously implicated in gene transfer events affecting eukaryotes. If our previous contention that these genes were introduced by LGT independently into the diplomonad and Entamoeba lineages were true, we expect that the number of putative transfers and the phylogenetic signal supporting LGT should be stable or increase, rather than decrease, when novel eukaryotic and prokaryotic homologs are added to the analyses.

Results
The addition of homologs from phagotrophic protists, including several Entamoeba species, the pelobiont Mastigamoeba balamuthi, and the parabasalid Trichomonas vaginalis, and a large quantity of sequences from genome projects resulted in an apparent increase in the number of putative transfer events affecting all three domains of life. Some of the eukaryotic transfers affect a wide range of protists, such as three divergent lineages of Amoebozoa, represented by Entamoeba, Mastigamoeba, and Dictyostelium, while other transfers only affect a limited diversity, for example only the Entamoeba lineage. These observations are consistent with a model where these genes have been introduced into protist genomes independently from various sources over a long evolutionary time.

Conclusion
Phylogenetic analyses of the updated datasets using more sophisticated phylogenetic methods, in combination with the gene distribution analyses, strengthened, rather than weakened, the support for LGT as an important mechanism affecting the evolution of these gene families. Thus, gene transfer seems to be an on-going evolutionary mechanism by which genes are spread between unrelated lineages of all three domains of life, further indicating the importance of LGT from non-organellar sources into eukaryotic genomes.
A simplified explanation for the frameshift mutation that created a novel C-terminal motif in the APETALA3 gene lineage
Authors: Kramer Elena M , Su Huei-Jiun , Wu Cheng-Chiang , Hu Jer-Ming 
Published: April 2006

Abstract

Background
The evolution of type II MADS box genes has been extensively studied in angiosperms. One of the best-understood subfamilies is that of the Arabidopsis gene APETALA3 (AP3). Previous work has demonstrated that the ancestral paleoAP3 lineage was duplicated at some point within the basal eudicots to give rise to the paralogous TM6 and euAP3 lineages. This event was followed in euAP3 orthologs by the replacement of the C-terminal paleoAP3 motif with the derived euAP3 motif. It has been suggested that the new motif was created by an eight-nucleotide insertion that produced a translational frameshift.

Results
The addition of 25 eudicot AP3 homologs to the existing dataset has allowed us to clarify the process by which the euAP3 motif evolved. Phylogenetic analysis indicates that the euAP3/TM6 duplication maps very close to the base of the core eudicots, associated with the families Trochodendraceae and Buxaceae. We demonstrate that although the transformation of paleoAP3 into euAP3 was due to a frameshift mutation, this was the result of a single nucleotide deletion. The use of ancestral character state reconstructions has allowed us to demonstrate that the frameshift was accompanied by few other nucleotide changes. We further confirm that the sequence is evolving as coding region.

Conclusion
This study demonstrates that the simplest of genetic changes can result in the remodeling of protein sequence to produce a kind of molecular 'hopeful monster.' Moreover, such a novel protein motif can become conserved almost immediately on the basis of what appears to be a rapidly generated new function. Given that the existing data on the function of such C-terminal motifs are somewhat disparate and contradictory, we have sought to synthesize previous findings within the context of the current analysis and thereby highlight specific hypotheses that require further investigation before the significance of the euAP3 frameshift event can be fully understood.
"Per cell" normalization method for mRNA measurement by quantitative PCR and microarrays
Authors: Kanno Jun , Aisaki Ken-ichi , Igarashi Katsuhide , Nakatsu Noriyuki , Ono Atsushi , Kodama Yukio , Nagao Taku 
Published: April 2006

Abstract

Background
Transcriptome data from quantitative PCR (Q-PCR) and DNA microarrays are typically obtained from a fixed amount of RNA collected per sample. Therefore, variations in tissue cellularity and RNA yield across samples in an experimental series compromise accurate determination of the absolute level of each mRNA species per cell in any sample. Since mRNAs are copied from genomic DNA, the simplest way to express mRNA level would be as copy number per template DNA, or more practically, as copy number per cell.

Results
Here we report a method (designated the "Percellome" method) for normalizing the expression of mRNA values in biological samples. It provides a "per cell" readout in mRNA copy number and is applicable to both quantitative PCR (Q-PCR) and DNA microarray studies. The genomic DNA content of each sample homogenate was measured from a small aliquot to derive the number of cells in the sample. A cocktail of five external spike RNAs admixed in a dose-graded manner (dose-graded spike cocktail; GSC) was prepared and added to each homogenate in proportion to its DNA content. In this way, the spike mRNAs represented absolute copy numbers per cell in the sample. The signals from the five spike mRNAs were used as a dose-response standard curve for each sample, enabling us to convert all the signals measured to copy numbers per cell in an expression profile-independent manner. A series of samples was measured by Q-PCR and Affymetrix GeneChip microarrays using this Percellome method, and the results showed up to 90 % concordance.

Conclusion
Percellome data can be compared directly among samples and among different studies, and between different platforms, without further normalization. Therefore, "percellome" normalization can serve as a standard method for exchanging and comparing data across different platforms and among different laboratories.
A cross sectional survey of urban Canadian family physicians' provision of minor office procedures
Authors: Sempowski Ian P , Rungi Arne A , Seguin Rachelle 
Published: April 2006

Abstract

Background
A discordance exists between the proportion of Canadian family physicians that we expect should be able to perform minor office procedures and the actual provision of care. This pattern has not been extensively studied. The objective of this study was to determine the current patterns and obstacles relating to the provision of four minor office procedures by GP/FPs in a small city in Ontario, Canada. An additional goal was to determine the impact of the remuneration method on the provision of such services.

Methods
A survey was mailed to all GP/FPs practising in Kingston, Ontario. The main outcomes measured in the study were work setting and remuneration method, current procedural practices with respect to four procedures, reasons for not performing procedures, current skill levels, and desire to upgrade.

Results
Surveys were mailed to all 108 GP/FPs in the City of Kingston. Completed surveys were collected for 82 percent (89/108) and 10 were excluded leaving 79 eligible participants. The percentages of GP/FPs who reported performing the procedure were as follows: dermatological excision (63.3%), endometrial biopsy (35.4%), shoulder injection (31.6%), and knee injection (43.0%). The majority of GP/FPs who would not do the procedure themselves would refer to a specialist colleague rather than to another GP/FP. The top reason cited for not performing a specific procedure was "lack of up to date skills" followed by "lack of time". The latter was the only statistically significant difference reported between GP/FPs working in Family Health Networks and GP/FPs working in fee for service settings (26.7% vs 47.0%, χ2 = 4.191 p = 0.041).

Conclusion
A large number of Kingston, Ontario GP/FPs refer patients who require one of four minor office-based procedures for specialist consultation. Referral to other GP/FP colleagues appears underutilized. A perceived lack of up to date skills and a lack of time appear to be concerns. GP/FPs working in Family Health Networks were more likely to perform these procedures themselves. Further studies would clarify the role of changes in medical education, the role of continuing education, and the impact of different remuneration models.
Herpes encephalitis presenting as mild aphasia: Case report
Authors: Khan Omar A , Ramsay Allan 
Published: April 2006

Abstract

Background
Encephalitis presenting as a change in mental status can be challenging to recognize in the primary care setting. However, early detection via a low threshold of suspicion can be useful, leading in turn to early treatment and improved survival.

Case presentation
We present a case which we consider relevant to primary care practitioners. The patient in question presented with relatively mild mental status changes, progressing to confusion, dysnomia and delirium over a period of three days. While infection did not appear to be the leading cause on her differential diagnosis, she was found on extensive workup to have encephalitis caused by Herpes Simplex Virus type 1.

Conclusion
The case is instructive for general practitioners and other clinicians to maintain vigilance for central nervous system (CNS) infections which may present atypically.
Characteristics and prevalence of hardcore smokers attending UK general practitioners
Authors: MacIntosh Hannah , Coleman Tim 
Published: April 2006

Abstract

Background
Smoking remains a public health problem and although unsolicited GPs' advice against smoking causes between one and three percent of smokers to stop, a significant proportion of smokers are particularly resistant to the notion of stopping smoking. These resistant smokers have been called "hardcore smokers" and although 16% of smokers in the community are hardcore, little is known about hardcore smokers presenting to primary care physicians. Consequently, this study reports the characteristics and prevalence of hardcore smokers attending UK GPs.

Methods
A cross-sectional survey using data from two different research projects was conducted. Data for this analysis had been collected from surgery consultation sessions with 73 GPs in Leicestershire, England, (42 GPs from one project). Research assistants distributed pre-consultation questionnaires to 4147 adults attending GPs' surgery sessions. Questionnaires identified regular smokers, the proportion of hardcore smokers and their characteristics. Non-hardcore and hardcore smokers' ages, gender and nicotine addiction levels were compared.

Results
1170 regular smokers attended surgery sessions and, 16.1% (95% CI, 14.1 to 18.4) were hardcore smokers. Hardcore smokers had higher levels of nicotine addiction than others (p = 0.000), measured by the Heaviness of Smoking Index and were more likely to be male [50.5% hardcore versus 35.3% non-hardcore, (OR = 1.88, 95% CI = 1.4 to 2.6)] but no age differences were observed between groups.

Conclusion
A significant minority of the smokers who present in general practice are resistant to the notion of smoking cessation and these smokers are more heavily nicotine addicted than others. Although clinical guidelines suggest that GPs should regularly advise all smokers against smoking, it is probable that hardcore smokers do not respond positively to this and help to make up the 97%–99% of smokers who do not quit after being advised to stop smoking by GPs. General practitioners need to find approaches for raising the issue of smoking during consultations in ways that do not reinforce the negative opinions of hardcore smokers concerning smoking cessation.
Analysis of Bordetella pertussis pertactin and pertussis toxin types from Queensland, Australia, 1999–2003
Authors: Byrne Shane , Slack Andrew T 
Published: April 2006

Abstract

Background
In Australia two acellular Bordetella pertussis vaccines have replaced the use of a whole cell vaccine. Both of the licensed acellular vaccines contain the following three components; pertussis toxoid, pertussis filamentous haemagglutinin and the 69 kDa pertactin adhesin. One vaccine also contains pertussis fimbriae 2 and 3. Various researchers have postulated that herd immunity due to high levels of pertussis vaccination might be influencing the makeup of endemic B. pertussis populations by selective pressure for strains possessing variants of these genes, in particular the pertactin gene type. Some publications have suggested that B. pertussis variants may be contributing to a reduced efficacy of the existing vaccines and a concomitant re-emergence of pertussis within vaccinated populations. This study was conducted to survey the pertactin and pertussis toxin subunit 1 types from B. pertussis isolates in Queensland, Australia following the introduction of acellular vaccines.

Methods
Forty-six B. pertussis isolates recovered from Queensland patients between 1999 and 2003 were examined by both DNA sequencing and LightCycler™ real time PCR to determine their pertactin and pertussis toxin subunit 1 genotypes.

Results
Pertactin typing showed that 38 isolates possessed the prn1 allele, 3 possessed the prn2 allele and 5 possessed the prn3 allele. All forty-six isolates possessed the pertussis toxin ptxS1A genotype. Amongst the circulating B. pertussis population in Queensland, 82.5% of the recovered clinical isolates therefore possessed the prn1/ptxS1A genotype.

Conclusion
The results of this study compared to historical research on Queensland isolates suggest that B. pertussis pertactin and pertussis toxin variants are not becoming more prevalent in Queensland since the introduction of the acellular vaccines. Current prevalences of pertactin variants are significantly different to that described in a number of other countries with high vaccine coverage. Relative paucity of recovered isolates compared to notified infections, due primarily to non culture based pertussis diagnostics is however a confounding factor in the assessment of variant prevalence.