bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flanking HS-62.5 and 3′ HS1, and regions upstream of the LCR, are not required for β-globin transcription
Authors: Bender M. A. , Byron Rachel , Ragoczy Tobias , Telling Agnes , Bulger Michael , Groudine Mark 
Published: April 2006

Abstract
The locus control region (LCR) was thought to be necessary and sufficient for establishing and maintaining an open β-globin locus chromatin domain in the repressive environment of the developing erythrocyte. However, deletion of the LCR from the endogenous locus had no significant effect on chromatin structure and did not silence transcription. Thus, the cis-regulatory elements that confer the open domain remain unidentified. The conserved DNaseI hypersensitivity sites (HSs) HS-62.5 and 3′HS1 that flank the locus, and the region upstream of the LCR have been implicated in globin gene regulation. The flanking HSs bind CCCTC binding factor (CTCF) and are thought to interact with the LCR to form a “chromatin hub” involved in β-globin gene activation. Hispanic thalassemia, a deletion of the LCR and 27 kb upstream, leads to heterochromatinization and silencing of the locus. Thus, the region upstream of the LCR deleted in Hispanic thalassemia (upstream Hispanic region [UHR]) may be required for expression. To determine the importance of the UHR and flanking HSs for β-globin expression, we generated and analyzed mice with targeted deletions of these elements. We demonstrate deletion of these regions alone, and in combination, do not affect transcription, bringing into question current models for the regulation of the β-globin locus.
Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung
Authors: André E. , Stoeger T. , Takenaka S. , Bahnweg M. , Ritter B. , Karg E. , Lentner B. , Reinhard C. , Schulz H. , Wjst M. 
Published: April 2006

High levels of particulate matter in ambient air are associated with increased respiratory and cardiovascular health problems. It has been hypothesised that it is the ultrafine particle fraction (diameter <100 nm) that is largely responsible for these effects. To evaluate the associated mechanisms on a molecular level, the current authors applied an expression profiling approach.Healthy mice were exposed to either ultrafine carbon particles (UFCPs; mass concentration 380 µg·m-3) or filtered air for 4 and 24 h. Histology of the lungs did not indicate any pathomorphological changes after inhalation.Examination of the bronchoalveolar lavage fluid revealed a small increase in polymorphonuclear cell number (ranging 0.6–1%) after UFCP inhalation, compared with clean air controls, suggesting a minor inflammatory response. However, DNA microarray profile analysis revealed a clearly biphasic response to particle exposure. After 4 h of inhalation, mainly heat shock proteins were induced, whereas after 24 h, different immunomodulatory proteins (osteopontin, galectin-3 and lipocalin-2) were upregulated in alveolar macrophages and septal cells.In conclusion, these data indicate that inhalation of ultrafine carbon particles triggers a biphasic pro-inflammatory process in the lung, involving the activation of macrophages and the upregulation of immunomodulatory proteins.
Effect of smoking on exhaled nitric oxide and flow-independent nitric oxide exchange parameters
Authors: Malinovschi A. , Janson C. , Holmkvist T. , Norbäck D. , Meriläinen P. , Högman M. 
Published: April 2006

It is a well-known fact that smoking is associated with a reduction in exhaled nitric oxide (NO) levels. There is, however, limited knowledge relating to the smoking-induced changes in production or exchange of NO in different compartments of the airways.This study comprised 221 adult subjects from the European Community Respiratory Health Survey II, who were investigated in terms of their exhaled NO, lung function, immunoglobulin E sensitisation and smoking habits. The following parameters were determined using extended NO analysis: airway tissue nitric oxide concentration (Caw,NO), airway transfer factor (or diffusing capacity) for nitric oxide (Daw,NO), alveolar nitric oxide concentration (CA,NO) and fractional exhaled nitric oxide concentration at a flow rate of 50 mL·s-1(FeNO,0.05). Maximum total airway nitric oxide flux (J'aw,NO) was calculated fromDaw,NO(Caw,NO–CA,NO).Current smokers (n = 35) exhibited lower (geometric mean)FeNO,0.05(14.0versus22.8 ppb),Caw,NO(79.0;versus126 ppb) andJ'aw,NO(688versus1,153 pL·s-1) than never-smokers (n = 111). Ex-smokers (n = 75) were characterised by lowerFeNO,0.05(17.7versus22.8 ppb) andJaw,NO(858versus1,153 pL·s-1) than never-smokers. These relationships were maintained after adjusting for potential confounders (sex, age, height, immunoglobulin E sensitisation and forced expiratory volume in one second), and, in this analysis, a negative association was found between current smoking andCA,NO. Snus (oral moist snuff) consumption (n = 21) in ex-smokers was associated with an increase inDaw,NOand a reduction inCaw,NO, after adjusting for potential confounders. Passive smoking was associated with a higherCA,NO.Using extended nitric oxide analysis, it was possible to attribute the reduction in exhaled nitric oxide levels seen in ex- and current smokers to a lower total airway nitric oxide flux in ex-smokers and reduced airway and alveolar nitric oxide concentrations in current smokers. The association between snus (oral tobacco) use and reduced nitric oxide concentrations in the airways and increased nitric oxide transfer from the airways warrants further studies.
A stable gene selection in microarray data analysis
Authors: Yang Kun , Cai Zhipeng , Li Jianzhong , Lin Guohui 
Published: April 2006

Abstract

Background
Microarray data analysis is notorious for involving a huge number of genes compared to a relatively small number of samples. Gene selection is to detect the most significantly differentially expressed genes under different conditions, and it has been a central research focus. In general, a better gene selection method can improve the performance of classification significantly. One of the difficulties in gene selection is that the numbers of samples under different conditions vary a lot.

Results
Two novel gene selection methods are proposed in this paper, which are not affected by the unbalanced sample class sizes and do not assume any explicit statistical model on the gene expression values. They were evaluated on eight publicly available microarray datasets, using leave-one-out cross-validation and 5-fold cross-validation. The performance is measured by the classification accuracies using the top ranked genes based on the training datasets.

Conclusion
The experimental results showed that the proposed gene selection methods are efficient, effective, and robust in identifying differentially expressed genes. Adopting the existing SVM-based and KNN-based classifiers, the selected genes by our proposed methods in general give more accurate classification results, typically when the sample class sizes in the training dataset are unbalanced.
Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian gene expression data
Authors: Huber Bertrand R , Bulyk Martha L 
Published: April 2006

AbstractBackgroundA key step in the regulation of gene expression is the sequence-specific binding of transcription factors (TFs) to their DNA recognition sites. However, elucidating TF binding site (TFBS) motifs in higher eukaryotes has been challenging, even when employing cross-species sequence conservation. We hypothesized that for human and mouse, many orthologous genes expressed in a similarly tissue-specific manner in both human and mouse gene expression data, are likely to be co-regulated by orthologous TFs that bind to DNA sequence motifs present within noncoding sequence conserved between these genomes.ResultsWe performed automated motif searching and merging across four different motif finding algorithms, followed by filtering of the resulting motifs for those that contain blocks of information content. Applying this motif finding strategy to conserved noncoding regions surrounding co-expressed tissue-specific human genes allowed us to discover both previously known, and many novel candidate, regulatory DNA motifs in all 18 tissue-specific expression clusters that we examined. For previously known TFBS motifs, we observed that if a TF was expressed in the specified tissue of interest, then in most cases we identified a motif that matched its TRANSFAC motif; conversely, of all those discovered motifs that matched TRANSFAC motifs, most of the corresponding TF transcripts were expressed in the tissue(s) corresponding to the expression cluster for which the motif was found.ConclusionOur results indicate that the integration of the results from multiple motif finding tools identifies and ranks highly more known and novel motifs than does the use of just one of these tools. In addition, we believe that our simultaneous enrichment strategies helped to identify likely humancisregulatory elements. A number of the discovered motifs may correspond to novel binding site motifs for as yet uncharacterized tissue-specific TFs. We expect this strategy to be useful for identifying motifs in other metazoan genomes.
LRTae: improving statistical power for genetic association with case/control data when phenotype and/or genotype misclassification errors are present
Authors: Barral Sandra , Haynes Chad , Stone Millicent , Gordon Derek 
Published: April 2006

Abstract

Background
In the field of statistical genetics, phenotype and genotype misclassification errors can substantially reduce power to detect association with genetic case/control studies. Misclassification also can bias population frequency parameters such as genotype, haplotype, or multi-locus genotype frequencies. These problems are of particular concern in case/control designs because, short of repeated sampling, there is no way to detect misclassification errors.
We developed a double-sampling procedure for case/control genetic association using a likelihood ratio test framework. Different approaches have been proposed to deal with misclassification errors. We have chosen the likelihood framework because of the ease with which misclassification probabilities may be incorporated into in the statistical framework and hypothesis testing. The statistic is called the Likelihood Ratio Test allowing for errors (LRTae) and is freely available via software download.

Results
We applied our procedure to 10,000 replicates of simulated case/control data in which we introduced phenotype misclassification errors. The phenotype considered is Ankylosing Spondylitis (AS). The LRTae method power was always greater than LRTstd power for the significance levels considered (5%, 1%, 0.1%, 0.01%). Power gains for the LRTae method over the LRTstd method increased as the significance level became more stringent. Multi-locus genotype frequency estimates using LRTae method were more accurate than estimates using LRTstd method.

Conclusion
The LRTae method can be applied to single-locus genotypes, multi-locus genotypes, or multi-locus haplotypes in a case/control framework and can be more powerful to detect association in case/control studies when both genotype and/or phenotype errors are present. Furthermore, the LRTae method provides asymptotically unbiased estimates of case and control genotype frequencies, as well as estimates of phenotype and/or genotype misclassification rates.
Bovine CD2-/NKp46+ cells are fully functional natural killer cells with a high activation status
Authors: Boysen Preben , Olsen Ingrid , Berg Ingvild , Kulberg Siri , Johansen Grethe M , Storset Anne K 
Published: April 2006

AbstractBackgroundNatural killer (NK) cells in the cow have been elusive due to the lack of specific NK cell markers, and various criteria including a CD3-/CD2+phenotype have been used to identify such cells. The recent characterization of the NK-specific NKp46 receptor has allowed a more precise definition of bovine NK cells. NK cells are known as a heterogeneous cell group, and we here report the first functional study of bovine NK cell subsets, based on the expression of CD2.ResultsBovine CD2-NK cells, a minor subset in blood, proliferated more rapidly in the presence of IL-2, dominating the cultures after a few days. Grown separately with IL-2, CD2-and CD2+NK cell subsets did not change CD2 expression for at least two weeks. In blood, CD2-NK cells showed a higher expression of CD44 and CD25, consistent with a high activation status. A higher proportion of CD2-NK cells had intracellular interferon-gamma in the cytoplasm in response to IL-2 and IL-12 stimulation, and the CD2-subset secreted more interferon-gamma when cultured separately. Cytotoxic capacity was similar in both subsets, and both carried transcripts for the NK cell receptors KIR, CD16, CD94 and KLRJ. Ligation by one out of two tested anti-CD2 monoclonal antibodies could trigger interferon-gamma production from NK cells, but neither of them could alter cytotoxicity.ConclusionThese results provide evidence that bovine CD2-as well as CD2+cells of the NKp46+phenotype are fully functional NK cells, the CD2-subset showing signs of being more activated in the circulation.
Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients
Authors: Lorke Dietrich E , Lu Gang , Cho Eric , Yew David T 
Published: April 2006

AbstractBackgroundIt has been hypothesized that alterations of the serotonergic system contribute to neuropsychiatric symptoms in Alzheimer disease (AD). Cellular expressions of the two serotonergic receptors 5-HT2Aand 5-HT6have therefore been determined by immunohistochemistry in the prefrontal cortex of patients with AD (n=6) and normal age-matched controls (n = 7).ResultsIn normal aging patients, 5-HT2Alabel was mainly observed in large pyramidal cells, but to a lesser extent also in small pyramidal cells and in stellate cells of cortical layers II-VI. In AD, a similar distribution was observed, but density of positive cells was significantly reduced by 33%. In aging control patients, the 5-HT6receptor was expressed by pyramidal cells and occasional stellate cells, not only of layers II-V, but also of layer I, where a distinct label was observed in neurons and surrounding fibers. 5-HT6receptor expression in AD patients had the same pattern, but was significantly decreased by 40%.ConclusionOur results indicate that a decline in neurons expressing 5-HT2A, but also 5-HT6receptors may play a role in the etiopathology of neuropsychiatric symptoms in AD.
Knowledge of modifiable risk factors of heart disease among patients with acute myocardial infarction in Karachi, Pakistan: a cross sectional study
Authors: Khan Muhammad S , Jafary Fahim H , Jafar Tazeen H , Faruqui Azhar M , Rasool Syed I , Hatcher Juanita , Chaturvedi Nish 
Published: April 2006

Abstract

Background
Knowledge is an important pre-requisite for implementing both primary as well as secondary preventive strategies for cardiovascular disease (CVD). There are no estimates of the level of knowledge of risk factor of heart disease in patients with CVD. We estimated the level of knowledge of modifiable risk factors and determined the factors associated with good level of knowledge among patients presenting with their first acute myocardial infarction (AMI) in a tertiary care hospital in Karachi, Pakistan.

Methods
A hospital based cross-sectional study was conducted at the National Institute of Cardiovascular Disease, a major tertiary care hospital in Karachi Pakistan. Patients admitted with their first AMI were eligible to participate. Standard questionnaire was used to interview 720 subjects. Knowledge of four modifiable risk factors of heart disease: fatty food consumption, smoking, obesity and exercise were assessed. The participants knowing three out of four risk factors were regarded as having a good level of knowledge. A multiple logistic regression model was constructed to identify the determinants of good level of knowledge.

Results
The mean age (SD) was 54 (11.66) years. A mere 42% of our study population had a good level of knowledge. In multiple logistic regression analysis, independent predictors of "good" level of knowledge were (odds ratio [95% confidence interval]) more than ten years of schooling were 2.5 [1.30, 4.80] (verses no schooling at all) and nuclear family system (verses extended family system) 2.54 [1.65, 3.89]. In addition, Sindhi ethnicity OR [3.03], higher level of exercise OR [2.76] and non user of tobacco OR [2.53] were also predictors of good level of knowledge.

Conclusion
Our findings highlight the lack of good level of knowledge of modifiable risk factors for heart disease among subjects admitted with AMI in Pakistan. There is urgent need for aggressive and targeted educational strategies in the Pakistani population.
Health inequality in adolescence. Does stratification occur by familial social background, family affluence, or personal social position?
Authors: LK Koivusilta , AH Rimpelä , SM Kautiainen 
Published: April 2006

AbstractBackgroundTwo new sets of stratification indicators – family's material affluence and adolescent's personal social position- were compared with traditional indicators of familial social position based on parental occupation and education for their ability to detect health inequality among adolescents.MethodsSurvey data were collected in the Adolescent Health and Lifestyle Survey in 2003 from nationally representative samples of 12-, 14- and 16-year-old Finns (number of respondents 5394, response rate 71%). Indicators of the familial social position were father's socio-economic status, parents' education, parents' labour market position. Indicators of material affluence were number of cars, vacation travels, and computers in the family, own room and amount of weekly spending money. Adolescent's personal social position was measured as school performance. Measures of health were long-standing illness, overweight, use of mental health services, poor self-rated health and number of weekly health complaints. Ordinal logistic regression analysis was applied to study the associations between stratification indicators and health variables.ResultsAll three groups of indicators of social stratification showed inequality in health, but the strongest associations were observed with the adolescent's personal social position. Health inequality was only partly identifiable by the traditional indicators of familial social position. The direction of the inequality was as expected when using the traditional indicators or personal social position: adolescents from higher social positions were healthier than those from lower positions. The indicators of family's material affluence showed mainly weak or no association with health and some of the indicators were inversely associated, although weakly.ConclusionIn addition to traditional indicators describing the socio-structural influences on the distribution of health among adolescents, indicators of family's material affluence should be further developed. Adolescents' personal social position should be included in the studies of health inequalities.
The prolongation of somatic support in a pregnant woman with brain-death: a case report
Authors: Souza João P , Oliveira-Neto Antonio , Surita Fernanda Garanhani , Cecatti José G , Amaral Eliana , Pinto e Silva João L 
Published: April 2006

AbstractBackgroundMedical literature has increasingly reported cases of maternal brain death during pregnancy. This is a rare situation which demands the decision and, depending on the gestational age, the implementation of a set of measures to prolong the homeostasis of the human body after brain death for the purpose of maintaining the foetus alive until its viability.Case presentationA 40 year old woman suffered an intracranial haemorrhage during the 25thweek of pregnancy. Despite neurosurgical drainage of a gross intraparenchymatous haematoma, the patient developed brain death. Upon confirmation of this diagnosis, she received full ventilatory and nutritional support, vasoactive drugs, maintenance of normothermia, hormone replacement and other supportive measures required to prolong gestation and improve the survival prognosis of her foetus. All decisions regarding the patient's treatment were taken in consensus with her family. She also received corticosteroids to accelerate foetal lung maturity. During the twenty-five days of somatic support, the woman's condition remained stable; however, during the last seven days the foetus developed oligohydramnios and brain-sparring, which led the medical team to take the decision to perform a Caesarean section at that moment. After delivery, the patient's organs were removed for donation. The male infant was born weighing 815 g, with an Apgar score of 9 and 10 at the first and fifth minutes, respectively. The infant was admitted to the neonatal intensive care unit, but did not require mechanical ventilation and had no major complications. He was discharged at 40 days of life, with no sequelae and weighing 1850 g.ConclusionThese results are in accordance with findings from previous studies and case reports suggesting the appropriateness and safety of extended somatic support during pregnancy under certain circumstances. They also suggest the need for prompt diagnosis of brain death before the occurrence of physiological degeneration, rapid evaluation of foetal status and the decision of the family together with the medical team to prolong maternal somatic support. The occurrence of maternal brain death is a tragedy, but it may also represent a challenging opportunity to save the life of the foetus and, in addition, permit donation of the maternal organs.
Cartilage-bone mismatch in the dysplastic trochlea
Authors: van Huyssteen A. L. , Hendrix M. R. G. , Barnett A. J. , Wakeley C. J. , Eldridge J. D. J. 
Published: April 2006

Trochlear dysplasia is an important anatomical abnormality in symptomatic patellar instability. Our study assessed the mismatch between the bony and cartilaginous morphology in patients with a dysplastic trochlea compared with a control group. MRI scans of 25 knees in 23 patients with trochlear dysplasia and in 11 patients in a randomly selected control group were reviewed retrospectively in order to assess the morphology of the cartilaginous and bony trochlea. Inter- and intra-observer error was assessed. In the dysplastic group there were 15 women and eight men with a mean age of 20.4 years (14 to 30). The mean bony sulcus angle was 167.9° (141° to 203°), whereas the mean cartilaginous sulcus angle was 186.5° (152° to 214°; p < 0.001). In 74 of 75 axial images (98.7%) the cartilaginous contour was different from the osseous contour on subjective assessment, the cartilage exacerbated the abnormality. Our study shows that the morphology of the cartilaginous trochlea differs markedly from that of the underlying bony trochlea in patients with trochlear dysplasia. MRI is necessary in order to demonstrate the pathology and to facilitate surgical planning.
Neglected trans-scaphoid trans-styloid volar dislocation of the lunate
Authors: Givissis P. , Christodoulou A. , Chalidis B. , Pournaras J. 
Published: April 2006

A rare case of radiocarpal dislocation is presented. The lunate and proximal pole of the scaphoid were displaced in a volar and proximal direction. The injury was missed initially and the patient was subsequently operated on six weeks later. Open reduction and internal fixation of the scaphoid was performed and this was followed by an uneventful postoperative period, with a satisfactory functional outcome at the eight-year follow-up, despite carpal instability non-dissociative-dorsal intercalated segmental instability configuration of the carpus. We believe that although open reduction in neglected cases carries the potential risks of avascular necrosis and nonunion of the affected carpal bones, an attempt should be made to restore the anatomy of the carpus.