bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoglin expression in the endothelium is regulated by Fli-1, Erg, and Elf-1 acting on the promoter and a –8-kb enhancer
Authors: Pimanda John E. , Chan W.Y. Iris , Donaldson Ian J. , Bowen Mark , Green Anthony R. , Göttgens Berthold 
Published: February 2006

AbstractAngiogenesis is critical to the growth and regeneration of tissue but is also a key component of tumor growth and chronic inflammatory disorders. Endoglin plays a key role in angiogenesis by modulating cellular responses to transforming growth factor-β (TGF-β) signaling and is upregulated in proliferating endothelial cells. To gain insights into the transcriptional hierarchies that govern endoglin expression, we used a combination of comparative genomic, biochemical, and transgenic approaches. Both the promoter and a region 8 kb upstream of exon 1 were active in transfection assays in endothelial cells. In transgenic mice, the promoter directed low-level expression to a subset of endothelial cells. By contrast, inclusion of the –8 enhancer resulted in robust endothelial activity with additional staining in developing ear mesenchyme. Subsequent molecular analysis demonstrated that both the –8 enhancer and the promoter depend on conserved Ets sites, which were bound in endothelial cells in vivo by Fli-1, Erg, and Elf-1. This study therefore establishes the transcriptional framework within which endoglin functions during angiogenesis.
Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation
Authors: Nguyen Nguyet M , Pulkkinen Leena , Schlueter Jessica A , Meneguzzi Guerrino , Uitto Jouni , Senior Robert M 
Published: February 2006

Abstract

Background
Laminin γ2 (Lamc2), one of the polypeptides in laminin-332 (laminin-5), is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive.

Methods
Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical and immunofluorescence staining.

Results
Compared to littermate controls, Lamc2-/- lungs were similar in morphology during embryonic life. At post-natal day 1–2, distal saccules were mildly dilated by chord length measurements. Epithelial differentiation as evaluated by immunohistochemical staining for markers of ciliated cells, Clara cells, alveolar type I cells and alveolar type II cells did not reveal a difference between Lamc2-/- and littermate control lungs. Likewise, vascular development, smooth muscle cell differentiation, and elastic fiber formation looked similar, as did airway basement membrane ultrastructure. Branching morphogenesis by lung bud culture was similar in Lamc2-/- and littermate control lungs. Since laminin-332 is important for hemidesmosome formation, we examined the structure of tracheal hemidesmosomes by transmission electron microscopy. Compared to littermate controls, Lamc2-/- tracheal hemidesmosomes were less organized and lacked the increased electron density associated with the basement membrane abutting the hemidesmosome.

Conclusion
These findings indicate that laminin γ2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage.
Computational models with thermodynamic and composition features improve siRNA design
Authors: Shabalina Svetlana A , Spiridonov Alexey N , Ogurtsov Aleksey Y 
Published: February 2006

Abstract

Background
Small interfering RNAs (siRNAs) have become an important tool in cell and molecular biology. Reliable design of siRNA molecules is essential for the needs of large functional genomics projects.

Results
To improve the design of efficient siRNA molecules, we performed a comparative, thermodynamic and correlation analysis on a heterogeneous set of 653 siRNAs collected from the literature. We used this training set to select siRNA features and optimize computational models. We identified 18 parameters that correlate significantly with silencing efficiency. Some of these parameters characterize only the siRNA sequence, while others involve the whole mRNA. Most importantly, we derived an siRNA position-dependent consensus, and optimized the free-energy difference of the 5' and 3' terminal dinucleotides of the siRNA antisense strand. The position-dependent consensus is based on correlation and t-test analyses of the training set, and accounts for both significantly preferred and avoided nucleotides in all sequence positions. On the training set, the two parameters' correlation with silencing efficiency was 0.5 and 0.36, respectively. Among other features, a dinucleotide content index and the frequency of potential targets for siRNA in the mRNA added predictive power to our model (R = 0.55). We showed that our model is effective for predicting the efficiency of siRNAs at different concentrations.
We optimized a neural network model on our training set using three parameters characterizing the siRNA sequence, and predicted efficiencies for the test siRNA dataset recently published by Novartis. On this validation set, the correlation coefficient between predicted and observed efficiency was 0.75. Using the same model, we performed a transcriptome-wide analysis of optimal siRNA targets for 22,600 human mRNAs.

Conclusion
We demonstrated that the properties of the siRNAs themselves are essential for efficient RNA interference. The 5' ends of antisense strands of efficient siRNAs are U-rich and possess a content similarity to the pyrimidine-rich oligonucleotides interacting with the polypurine RNA tracks that are recognized by RNase H. The advantage of our method over similar methods is the small number of parameters. As a result, our method requires a much smaller training set to produce consistent results. Other mRNA features, though expensive to compute, can slightly improve our model.
GO-Diff: Mining functional differentiation between EST-based transcriptomes
Authors: Chen Zuozhou , Wang Weilin , Ling Xuefeng Bruce , Liu Jane Jijun , Chen Liangbiao 
Published: February 2006

AbstractBackgroundLarge-scale sequencing efforts produced millions of Expressed Sequence Tags (ESTs) collectively representing differentiated biochemical and functional states. Analysis of these EST libraries reveals differential gene expressions, and therefore EST data sets constitute valuable resources for comparative transcriptomics. To translate differentially expressed genes into a better understanding of the underlying biological phenomena, existing microarray analysis approaches usually involve the integration of gene expression with Gene Ontology (GO) databases to derive comparable functional profiles. However, methods are not available yet to process EST-derived transcription maps to enable GO-based global functional profiling for comparative transcriptomics in a high throughput manner.ResultsHere we present GO-Diff, a GO-based functional profiling approach towards high throughput EST-based gene expression analysis and comparative transcriptomics. Utilizing holistic gene expression information, the software converts EST frequencies into EST Coverage Ratios of GO Terms. The ratios are then tested for statistical significances to uncover differentially represented GO terms between the compared transcriptomes, and functional differences are thus inferred. We demonstrated the validity and the utility of this software by identifying differentially represented GO terms in three application cases: intra-species comparison; meta-analysis to test a specific hypothesis; inter-species comparison. GO-Diff findings were consistent with previous knowledge and provided new clues for further discoveries. A comprehensive test on the GO-Diff results using series of comparisons between EST libraries of human and mouse tissues showed acceptable levels of consistency: 61% for human-human; 69% for mouse-mouse; 47% for human-mouse.ConclusionGO-Diff is the first software integrating EST profiles with GO knowledge databases to mine functional differentiation between biological systems, e.g. tissues of the same species or the same tissue cross species. With rapid accumulation of EST resources in the public domain and expanding sequencing effort in individual laboratories, GO-Diff is useful as a screening tool before undertaking serious expression studies.
Detecting overlapping coding sequences in virus genomes
Authors: Firth Andrew E , Brown Chris M 
Published: February 2006

AbstractBackgroundDetecting new coding sequences (CDSs) in viral genomes can be difficult for several reasons. The typically compact genomes often contain a number of overlapping coding and non-coding functional elements, which can result in unusual patterns of codon usage; conservation between related sequences can be difficult to interpret – especially within overlapping genes; and viruses often employ non-canonical translational mechanisms – e.g. frameshifting, stop codon read-through, leaky-scanning and internal ribosome entry sites – which can conceal potentially coding open reading frames (ORFs).ResultsIn a previous paper we introduced a new statistic – MLOGD (Maximum Likelihood Overlapping Gene Detector) – for detecting and analysing overlapping CDSs. Here we present (a) an improved MLOGD statistic, (b) a greatly extended suite of software using MLOGD, (c) a database of results for 640 virus sequence alignments, and (d) a web-interface to the software and database. Tests show that, from an alignment with just 20 mutations, MLOGD can discriminate non-overlapping CDSs from non-coding ORFs with a typical accuracy of up to 98%, and can detect CDSs overlapping known CDSs with a typical accuracy of 90%. In addition, the software produces a variety of statistics and graphics, useful for analysing an input multiple sequence alignment.ConclusionMLOGD is an easy-to-use tool for virus genome annotation, detecting new CDSs – in particular overlapping or short CDSs – and for analysing overlapping CDSs following frameshift sites. The software, web-server, database and supplementary material are available athttp://guinevere.otago.ac.nz/mlogd.html.
Models and partition of variance for quantitative trait loci with epistasis and linkage disequilibrium
Authors: Wang Tao , Zeng Zhao-Bang 
Published: February 2006

Abstract

Background
A genetic model about quantitative trait loci (QTL) provides a basis to interpret the genetic basis of quantitative traits in a study population, such as additive, dominance and epistatic effects of QTL and the partition of genetic variance. The standard quantitative genetics model is based on the least squares partition of genetic effects and also genetic variance in an equilibrium population. However, over years many specialized QTL models have also been proposed for applications in some specific populations. How are these models related? How to analyze and partition a QTL model and genetic variance when both epistasis and linkage disequilibrium are considered?

Results
Starting from the classical description of Cockerham genetic model, we first represent the model in a multiple regression setting by using indicator variables to describe the segregation of QTL alleles. In this setting, the definition of additive, dominance and epistatic effects of QTL and the basis for the partition of genetic variance are elaborated. We then build the connection between this general genetic model and a few specialized models (a haploid model, a diploid F
2 model and a general two-allele model), and derive the genetic effects and partition of genetic variance for multiple QTL with epistasis and linkage disequilibrium for these specialized models.

Conclusion
In this paper, we study extensively the composition and property of the genetic model parameters, such as genetic effects and partition of genetic variance, when both epistasis and linkage disequilibrium are considered. This is the first time that both epistasis and linkage disequilibrium are considered in modeling multiple QTL. This analysis would help us to understand the structure of genetic parameters and relationship of various genetic quantities, such as allelic frequencies and linkage disequilibrium, on the definition of genetic effects, and will also help us to understand and properly interpret estimates of the genetic effects and variance components in a QTL mapping experiment.
CoryneRegNet: An ontology-based data warehouse of corynebacterial transcription factors and regulatory networks
Authors: Baumbach Jan , Brinkrolf Karina , Czaja Lisa F , Rahmann Sven , Tauch Andreas 
Published: February 2006

Abstract

Background
The application of DNA microarray technology in post-genomic analysis of bacterial genome sequences has allowed the generation of huge amounts of data related to regulatory networks. This data along with literature-derived knowledge on regulation of gene expression has opened the way for genome-wide reconstruction of transcriptional regulatory networks. These large-scale reconstructions can be converted into in silico models of bacterial cells that allow a systematic analysis of network behavior in response to changing environmental conditions.

Description
CoryneRegNet was designed to facilitate the genome-wide reconstruction of transcriptional regulatory networks of corynebacteria relevant in biotechnology and human medicine. During the import and integration process of data derived from experimental studies or literature knowledge CoryneRegNet generates links to genome annotations, to identified transcription factors and to the corresponding cis-regulatory elements. CoryneRegNet is based on a multi-layered, hierarchical and modular concept of transcriptional regulation and was implemented by using the relational database management system MySQL and an ontology-based data structure. Reconstructed regulatory networks can be visualized by using the yFiles JAVA graph library. As an application example of CoryneRegNet, we have reconstructed the global transcriptional regulation of a cellular module involved in SOS and stress response of corynebacteria.

Conclusion
CoryneRegNet is an ontology-based data warehouse that allows a pertinent data management of regulatory interactions along with the genome-scale reconstruction of transcriptional regulatory networks. These models can further be combined with metabolic networks to build integrated models of cellular function including both metabolism and its transcriptional regulation.
Errors in fracture diagnoses in the emergency department – characteristics of patients and diurnal variation
Authors: Hallas Peter , Ellingsen Trond 
Published: February 2006

Abstract

Background
Evaluation of the circumstances related to errors in diagnosis of fractures at an Emergency Department may suggest ways to reduce the incidence of such errors.

Methods
Retrospective analysis of all cases during a two year period (2002–2004) where a fracture had been overlooked or an injury had been erroneously diagnosed as a fracture (n = 61). 100 random selected patients with correctly diagnosed fractures served as control group.

Results
In the two year period 5879 patients visited the ED with injuries. 1% of all visits to the ED resulted in an error in fracture diagnosis and 3.1% of all fractures were not diagnosed at the initial visit to the ED. 86% of such errors had consequences for treatment. No patient characteristics could be identified as risk factors for a misdiagnosis of a fracture. There was a peak in errors in fracture diagnoses between 8 pm and 2 am (47% against 20% in controls, p < 0.005).

Conclusion
A considerable number of fractures were not correctly diagnosed at the initial ED visit. There was a diurnal variation in the rate of misdiagnosis of fractures with a significant peak from 8 pm to 2 am. Where there was an error in fracture diagnosis, the patients did not appear to have a characteristic profile as regarding e.g. age, sex or capability to communicate with the ED staff. Increased consultancy service in radiology may reduce the frequency of errors in diagnosis, particularly in the evenings between 8 pm and 2 am.
Somatisation: illness perspectives of asylum seeker and refugee patients from the former country of Yugoslavia
Authors: Junod Perron Noelle , Hudelson Patricia 
Published: February 2006

AbstractBackgroundSomatisation is particularly challenging in multicultural contexts where patients and physicians often differ in terms of their illness-related beliefs and practices and health care expectations. This paper reports on a exploratory study aimed at better understanding how asylum seeker and refugee patients from the former country of Yugoslavia who were identified by their physicians as somatising make sense of their suffering.MethodsWe conducted semi-structured interviews with 26 asylum seeker and refugee patients from the former country of Yugoslavia who attended the general medicine outpatient clinic of a Swiss teaching Hospital and were identified as presenting with somatisation. Interviews explored patients' illness perspectives and health care expectations. Interviews were audio taped, transcribed verbatim and analyzed to identify key themes in patients' narratives.ResultsPatients attributed the onset of symptoms to past traumatic experiences and tended to attribute their persistence to current living conditions and uncertain legal status. Patients formulated their suffering in both medical and social/legal terms, and sought help from physicians for both types of problems.ConclusionAwareness of how asylum seeker and refugee patients make sense of their suffering can help physicians to better understand patients' expectations of the clinical encounter, and the particular nature and constraints of the patient-provider relationship in the context of asylum.
Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan
Authors: Chiou Chien-Shun , Liao Jui-Cheng , Liao Tsai-Ling , Li Chun-Chin , Chou Chen-Ying , Chang Hsiu-Li , Yao Shu-Man , Lee Yeong-Sheng 
Published: February 2006

Abstract

Background
Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern.

Methods

Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs).

Results
Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the 30 STs suggested the serogroup B isolates be assigned into 5 clonally related groups/ clonal complexes and 7 unique clones. The ST-41/44 complex/Lineage 3, and the ST-3439 and ST-3200 groups represented 79% of the serogroup B meningococci. In contrast, isolates within serogroups A, serogroup W135 (and C), and serogroup Y, respectively, simply belonged to ST-7, ST-11, and ST-23 clones.

Conclusion
Our data suggested that serogroup B isolates were derived from several distinct lineages, most of which could either be indigenous or were introduced into Taiwan a long time ago. The serogroup A, W135 (and C), and Y isolates, respectively, belonged to the ST-7, ST-11, and ST-23, and the represented clones that are currently the major circulating clones in the world and are introduced into Taiwan more recently. The emergence of serogroup A, C and Y strains contributed partly to the increase in cases of meningococcal disease in 2001–2002.
Combination therapy of disseminated coccidioidomycosis with caspofungin and fluconazole
Authors: Park Dae Won , Sohn Jang Wook , Cheong Hee Jin , Kim Woo Joo , Ja Kim Min , Kim Je Hyeong , Shin Chol 
Published: February 2006

Abstract

Background
The current recommended therapy for diffuse coccidioidal pneumonia involves initial treatment with amphotericin B deoxycholate or high-dose fluconazole, followed by an azole after clinical improvement. Amphotericin B is more frequently used as initial therapy if the patient's deterioration is rapid.

Case presentation
A 31-year-old Korean male with coccidioidomycosis presented to the hospital with miliary infiltrates on chest X-ray (CXR) and skin rash on the face and trunk. Initially, the patient did not respond to amphotericin B deoxycholate therapy. However, following caspofungin and fluconazole combination therapy, the patient showed favourable radiological, serological, and clinical response.

Conclusion
This appears to be the first case of diffuse coccidioidal pneumonia with skin involvement in an immunocompetent patient who was treated successfully with caspofungin and fluconazole. Combination therapy with caspofungin and fluconazole may, therefore, be an alternative treatment for diffuse coccidioidal pneumonia that does not respond to amphotericin B deoxycholate therapy.
The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression
Authors: Dempster Emma L , Mill Jonathan , Craig Ian W , Collier David A 
Published: February 2006

AbstractBackgroundTheCOMTgene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression ofCOMTis altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val158Met polymorphism.MethodIn this study we examined the expression levels ofCOMTmRNA using quantitative RT-PCR in 60post mortemcerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene.ResultsWe found no evidence of alteredCOMTexpression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related toCOMTgene expression, replicating the findings of two previous studies. Specifically, val158met (rs165688; Val allele) rs737865 (G allele) and rs165599 (G allele) all showed reduced expression (P < 0.05). Finally, we observe a strong sexual dimorphism inCOMTexpression, with females exhibiting significantly greater levels ofCOMTmRNA.ConclusionThe expression ofCOMTdoes not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.