bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial cell biology: An update
Authors: Breier Georg , Morawietz Henning 
Published: May 2006

SummaryThe 5th International Symposium on the Biology of Endothelial Cells was held in Dresden, Germany. The meeting included sessions on endothelial cell differentiation, tumor and lymph angiogenesis, endothelial cell junctions and barrier function, biomechanical control of endothelial function, oxidative stress and endothelial dysfunction, hypoxia and VEGF-induced signaling, inflammation and angiogenesis. This report summarizes the key findings of the platform presentations of the meeting.
Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study
Authors: Wallace Alison M , He Jian-Qing , Burkett Kelly M , Ruan Jian , Connett John E , Anthonisen Nicholas R , Paré Peter D , Sandford Andrew J 
Published: May 2006

Abstract

Background
Alpha-defensins, which are major constituents of neutrophil azurophilic granules, and beta-defensins, which are expressed in airway epithelial cells, could contribute to the pathogenesis of chronic obstructive pulmonary disease by amplifying cigarette smoke-induced and infection-induced inflammatory reactions leading to lung injury. In Japanese and Chinese populations, two different beta-defensin-1 polymorphisms have been associated with chronic obstructive pulmonary disease phenotypes. We conducted population-based association studies to test whether alpha-defensin and beta-defensin polymorphisms influenced smokers' susceptibility to lung function decline and susceptibility to lower respiratory infection in two groups of white participants in the Lung Health Study (275 = fast decline in lung function and 304 = no decline in lung function).

Methods
Subjects were genotyped for the alpha-defensin-1/alpha-defensin-3 copy number polymorphism and four beta-defensin-1 polymorphisms (G-20A, C-44G, G-52A and Val38Ile).

Results
There were no associations between individual polymorphisms or imputed haplotypes and rate of decline in lung function or susceptibility to infection.

Conclusion
These findings suggest that, in a white population, the defensin polymorphisms tested may not be of importance in determining who develops abnormally rapid lung function decline or is susceptible to developing lower respiratory infections.
Bounded search for de novo identification of degenerate cis-regulatory elements
Authors: Carlson Jonathan M , Chakravarty Arijit , Khetani Radhika S , Gross Robert H 
Published: May 2006

Abstract

Background
The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach.

Results
In this paper, we report PRISM, a degenerate motif finder that leverages the relationship between the statistical significance of a set of binding sites and that of the individual binding sites. PRISM first identifies overrepresented, non-degenerate consensus motifs, then iteratively relaxes each one into a high-scoring degenerate motif. This approach requires no tunable parameters, thereby lending itself to unbiased performance comparisons. We therefore compare PRISM's performance against nine popular motif finders on 28 well-characterized S. cerevisiae regulons. PRISM consistently outperforms all other programs. Finally, we use PRISM to predict the binding sites of uncharacterized regulons. Our results support a proposed mechanism of action for the yeast cell-cycle transcription factor Stb1, whose binding site has not been determined experimentally.

Conclusion
The relationship between statistical measures of the binding sites and the set as a whole leads to a simple means of identifying the diverse range of cis-regulatory elements to which a protein binds. This approach leverages the advantages of word-counting, in that position dependencies are implicitly accounted for and local optima are more easily avoided. While we sacrifice guaranteed optimality to prevent the exponential blowup of exhaustive search, we prove that the error is bounded and experimentally show that the performance is superior to other methods. A Java implementation of this algorithm can be downloaded from our web server at http://genie.dartmouth.edu/prism.
Prediction of amphipathic in-plane membrane anchors in monotopic proteins using a SVM classifier
Authors: Sapay Nicolas , Guermeur Yann , Deléage Gilbert 
Published: May 2006

AbstractBackgroundMembrane proteins are estimated to represent about 25% of open reading frames in fully sequenced genomes. However, the experimental study of proteins remains difficult. Considerable efforts have thus been made to develop prediction methods. Most of these were conceived to detect transmembrane helices in polytopic proteins. Alternatively, a membrane protein can be monotopic and anchoredviaan amphipathic helix inserted in a parallel way to the membrane interface, so-called in-plane membrane (IPM) anchors. This type of membrane anchor is still poorly understood and no suitable prediction method is currently available.ResultsWe report here the "AmphipaSeeK" method developed to predict IPM anchors. It uses a set of 21 reported examples of IPM anchored proteins. The method is based on a pattern recognition Support Vector Machine with a dedicated kernel.ConclusionAmphipaSeeK was shown to be highly specific, in contrast with classically used methods (e.g. hydrophobic moment). Additionally, it has been able to retrieve IPM anchors in naively tested sets of transmembrane proteins (e.g. PagP). AmphipaSeek and the list of the 21 IPM anchored proteins is available on NPS@, our protein sequence analysis server.
Gene expression alterations in brains of mice infected with three strains of scrapie
Authors: Skinner Pamela J , Abbassi Hayet , Chesebro Bruce , Race Richard E , Reilly Cavan , Haase Ashley T 
Published: May 2006

Abstract

Background
Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative disorders which occur in humans and various animal species. Examples include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer and elk, and scrapie in sheep, and experimental mice. To gain insights into TSE pathogenesis, we made and used cDNA microarrays to identify disease-associated alterations in gene expression. Brain gene expression in scrapie-infected mice was compared to mock-infected mice at pre-symptomatic and symptomatic time points. Three strains of mouse scrapie that show striking differences in neuropathology were studied: ME7, 22L, and Chandler/RML.

Results
In symptomatic mice, over 400 significant gene expression alterations were identified. In contrast, only 22 genes showed significant alteration in the pre-symptomatic animals. We also identified genes that showed significant differences in alterations in gene expression between strains. Genes identified in this study encode proteins that are involved in many cellular processes including protein folding, endosome/lysosome function, immunity, synapse function, metal ion binding, calcium regulation and cytoskeletal function.

Conclusion
These studies shed light on the complex molecular events that occur during prion disease, and identify genes whose further study may yield new insights into strain specific neuropathogenesis and ante-mortem tests for TSEs.
Cell-type specific gene expression profiles of leukocytes in human peripheral blood
Authors: Palmer Chana , Diehn Maximilian , Alizadeh Ash A , Brown Patrick O 
Published: May 2006

AbstractBackgroundBlood is a complex tissue comprising numerous cell types with distinct functions and corresponding gene expression profiles. We attempted to define the cell type specific gene expression patterns for the major constituent cells of blood, including B-cells, CD4+ T-cells, CD8+ T-cells, lymphocytes and granulocytes. We did this by comparing the global gene expression profiles of purified B-cells, CD4+ T-cells, CD8+ T-cells, granulocytes, and lymphocytes using cDNA microarrays.ResultsUnsupervised clustering analysis showed that similar cell populations from different donors share common gene expression profiles. Supervised analyses identified gene expression signatures for B-cells (427 genes), T-cells (222 genes), CD8+ T-cells (23 genes), granulocytes (411 genes), and lymphocytes (67 genes). No statistically significant gene expression signature was identified for CD4+ cells. Genes encoding cell surface proteins were disproportionately represented among the genes that distinguished among the lymphocyte subpopulations. Lymphocytes were distinguishable from granulocytes based on their higher levels of expression of genes encoding ribosomal proteins, while granulocytes exhibited characteristic expression of various cell surface and inflammatory proteins.ConclusionThe genes comprising the cell-type specific signatures encompassed many of the genes already known to be involved in cell-type specific processes, and provided clues that may prove useful in discovering the functions of many still unannotated genes. The most prominent feature of the cell type signature genes was the enrichment of genes encoding cell surface proteins, perhaps reflecting the importance of specialized systems for sensing the environment to the physiology of resting leukocytes.
Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAPgenes
Authors: Norkina Oxana , Graf Rolf , Appenzeller Philippe , De Lisle Robert C 
Published: May 2006

Abstract

Background
The cystic fibrosis (CF) mouse pancreas has constitutively elevated expression of the Reg/PAP cell stress genes (60-fold greater Reg3α, and 10-fold greater PAP/Reg3β and Reg3γ). These genes are suggested to be involved in protection or recovery from pancreatic injury.

Methods
To test this idea the supramaximal caerulein model was used to induce acute pancreatitis in wild type and CF mice. Serum amylase, pancreatic water content (as a measure of edema), pancreatic myeloperoxidase activity, and Reg/PAP expression were quantified.

Results
In both wild type and CF mice caerulein induced similar elevations in serum amylase (maximal at 12 h), pancreatic edema (maximal at 7 h), and pancreatic myeloperoxidase activity (MPO, a marker of neutrophil infiltration; maximal at 7 h). By immunohistochemistry, Reg3α was strongly expressed in the untreated CF pancreas but not in wild type. During pancreatitis, Reg3α was intensely expressed in foci of inflamed tissue in both wild type and CF.

Conclusion
These data demonstrate that the severity of caerulein-induced pancreatitis is not ameliorated in the CF mouse even though the Reg/PAP stress genes are already highly upregulated. While Reg/PAP may be protective they may also have a negative effect during pancreatitis due to their anti-apoptotic activity, which has been shown to increase the severity of pancreatitis.
Periodontal disease and atherosclerosis from the viewpoint of the relationship between community periodontal index of treatment needs and brachial-ankle pulse wave velocity
Authors: Miyaki Koichi , Masaki Katsunori , Naito Mariko , Naito Toru , Hoshi Keika , Hara Asako , Tohyama Shugo , Nakayama Takeo 
Published: May 2006

AbstractBackgroundIt has been suggested that periodontal disease may be an independent risk factor for the development of atherosclerosis. However, the relationship between periodontal disease and atherosclerosis has not been fully elucidated. This study aimed to assess the effects of periodontal disease on atherosclerosis.MethodsThe study design was a cross-sectional study. Subjects were 291 healthy male workers in Japan. We used the Community Periodontal Index of Treatment Needs (CPITN) score, average probing depth and gingival bleeding index (rate of bleeding gums) to assess the severity of periodontal disease. We also used the Brachial-Ankle Pulse Wave Velocity (baPWV) as the index for the development of atherosclerosis.ResultsThe unadjusted odds ratio (OR) of atherosclerosis in relation to the CPITN score was 1.41 [95% CI: 1.16–1.73]. However, after adjustment for age, systolic blood pressure and smoking, the CPITN score had no relationship with atherosclerosis (adjusted OR: 0.91 [0.68–1.20]).ConclusionOur results show no relationship between mild periodontal disease and atherosclerosis after appropriate adjustments.
Characterization of the family of Mistic homologues
Authors: Roosild Tarmo P , Vega Mark , Castronovo Samantha , Choe Senyon 
Published: May 2006

Abstract

Background
Mistic is a unique Bacillus subtilis protein with virtually no detectable homologues in GenBank, which appears to integrate into the bacterial membrane despite an overall hydrophilic composition. These unusual properties have been shown to be useful for high-yield recombinant expression of other membrane proteins through fusion to the C-terminus of Mistic. To better understand the structure and function of Mistic, we systematically searched for and characterized homologous proteins among closely related bacteria.

Results
Three homologues of Mistic were found with 62% to 93% residue identity, all only 84 residues in length, corresponding to the C-terminal residues of B. subtilis Mistic. In every case, the Mistic gene was found partially overlapping a downstream gene for a K+ channel protein. Residue variation amongst these sequences is restricted to loop regions of the protein's structure, suggesting that secondary structure elements and overall fold have been conserved. Additionally, all three homologues retain the functional ability to chaperone fusion partners to the membrane.

Conclusion
The functional core of Mistic consists of 84 moderately conserved residues that are sufficient for membrane targeting and integration. Understanding the minimal structural and chemical complexity of Mistic will lead to insights into the mechanistic underpinnings of Mistic-chaperoned membrane integration, as well as how to optimize its use for the recombinant heterologous expression of other integral membrane proteins of interest.
Radiation-induced sterility for pupal and adult stages of the malaria mosquito Anopheles arabiensis
Authors: Helinski Michelle EH , Parker Andrew G , Knols Bart GJ 
Published: May 2006

Abstract

Background
In the context of the Sterile Insect Technique (SIT), radiation-induced sterility in the malaria mosquito Anopheles arabiensis Patton (Diptera: Culicidae) was studied. Male mosquitoes were exposed to gamma rays in the pupal or adult stage and dose-sterility curves were determined.

Methods
Pupae were irradiated shortly before emergence (at 22–26 hrs of age), and adults <24 hrs post emergence. Doses tested ranged between 0 and 100 Gy. The effects of irradiation on adult emergence, male survival, induced sterility and insemination capability were evaluated. Emergence and insemination data were analysed using independent t-tests against the control. Correlation analyses were performed for insemination rate and dose and insemination and fecundity. Male survival was analysed using Kaplan-Meier survival analyses. Finally, the calculated residual fertility values were inverse-normal transformed and linear regression analyses performed.

Results
Irradiation of pupae, for all doses tested, had no effect on adult emergence. Survival curves of males irradiated as pupae or adults were similar or even slightly higher than non-irradiated males. Overall, adults appeared to be slightly more susceptible to irradiation, although no significant differences for individual doses were observed. In the pupal stage, a significant negative correlation was found between insemination and dose, but the correlation-coefficient was associated with less than 25% of the total variation. A review of the literature indicated that An. arabiensis is more radiation resistant than other anopheline mosquitoes.

Conclusion
The optimal dose for male insects to be released in an SIT programme depends on their level of sterility and competitiveness. The use of semi-sterilizing doses to produce more competitive insects is discussed. The most convenient developmental stage for mosquito irradiation on a mass-scale are pupae, but pupal irradiation resulted in a lower insemination rate at the highest dose compared to adult irradiation. On the basis of this study, a suitable dose range that includes semi-sterilizing doses is identified to initiate competitiveness experiments for males irradiated at both developmental stages.
Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression
Authors: Narayan Gopeshwar , Goparaju Chandra , Arias-Pulido Hugo , Kaufmann Andreas M , Schneider Achim , Dürst Matthias , Mansukhani Mahesh , Pothuri Bhavana , Murty Vundavalli V 
Published: May 2006

Abstract

Background
Cervical Cancer (CC) exhibits highly complex genomic alterations. These include hemizygous deletions at 4p15.3, 10q24, 5q35, 3p12.3, and 11q24, the chromosomal sites of Slit-Robo pathway genes. However, no candidate tumor suppressor genes at these regions have been identified so far. Slit family of secreted proteins modulates chemokine-induced cell migration of distinct somatic cell types. Slit genes mediate their effect by binding to its receptor Roundabout (Robo). These genes have shown to be inactivated by promoter hypermethylation in a number of human cancers.

Results
To test whether Slit-Robo pathway genes are targets of inactivation at these sites of deletion, we examined promoter hypermethylation of SLIT1, SLIT2, SLIT3, ROBO1, and ROBO3 genes in invasive CC and its precursor lesions. We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs) in CC cell lines failed to effectively reactivate the down-regulated expression. These results suggest a complex mechanism of inactivation in the Slit-Robo pathway in CC. By analysis of cervical precancerous lesions, we further show that promoter hypermethylation of Slit-Robo pathway occurs early in tumor progression.

Conclusion
Taken together, these findings suggest that epigenetic alterations of Slit-Robo pathway genes (i) play a role in CC development, (ii) further delineation of molecular basis of promoter methylation-mediated gene regulation provides a potential basis for epigenetic-based therapy in advanced stage CC, and (iii) form epigenetic signatures to identify precancerous lesions at risk to progression.
Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells
Authors: Liu Hui , Ippolito Gregory C , Wall Jason K , Niu Teresa , Probst Loren , Lee Baeck-Seung , Pulford Karen , Banham Alison H , Stockwin Luke , Shaffer Arthur L , Staudt Louis M , Das Chhaya , Dyer Martin JS , Tucker Philip W 
Published: May 2006

Abstract

Background
Chromosomal aberrations of BCL11A at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development.

Results
Alternative pre-mRNA splicing of BCL11A produces multiple isoforms sharing a common N-terminus. The most abundant isoform we have identified in human lymphoid samples is BCL11A-XL, the longest transcript produced at this locus, and here we report the conservation of this major isoform and its functional characterization. We show that BCL11A-XL is a DNA-sequence-specific transcriptional repressor that associates with itself and with other BCL11A isoforms, as well as with the BCL6 proto-oncogene. Western blot data for BCL11A-XL expression coupled with data previously published for BCL6 indicates that these genes are expressed abundantly in germinal-center-derived B cells but that expression is extinguished upon terminal differentiation to the plasma cell stage. Although BCL11A-XL/BCL6 interaction can modulate BCL6 DNA binding in vitro, their heteromeric association does not alter the homomeric transcriptional properties of either on model reporter activity. BCL11A-XL partitions into the nuclear matrix and colocalizes with BCL6 in nuclear paraspeckles.

Conclusion
We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies.
Comparison of tricuspid inflow and superior vena caval Doppler velocities in acute simulated hypovolemia: new non-invasive indices for evaluating right ventricular preload
Authors: Liu Jie , Cao Tie-Sheng , Yuan Li-Jun , Duan Yun-You , Yang Yi-Lin 
Published: May 2006

Abstract

Background
Assessment of cardiac preload is important for clinical management of some emergencies related to hypovolemia. Effects of acute simulated hypovolemia on Doppler blood flow velocity indices of tricuspid valve (TV) and superior vena cava (SVC) were investigated in order to find sensitive Doppler indices for predicting right ventricular preload.

Methods
Doppler flow patterns of SVC and TV in 12 healthy young men were examined by transthoracic echocardiography (TTE) during graded lower body negative pressure (LBNP) of up to -60 mm Hg which simulated acute hypovolemia. Peak velocities of all waves and their related ratios (SVC S/D and tricuspid E/A) were measured, calculated and statistically analyzed.

Results
Except for the velocity of tricuspid A wave, velocities of all waves and their related ratios declined during volume decentralization. Of all indices measured, the peak velocities of S wave and AR wave in SVC correlated most strongly with levels of LBNP (r = -0.744 and -0.771, p < 0.001).

Conclusion
The S and AR velocities are of good values in assessing right ventricular preload. Monitoring SVC flow may provide a relatively noninvasive means to assess direct changes in right ventricular preload.
Theory and practice – a case study of coordination and ownership in the Bangladesh health SWAp
Authors: Sundewall Jesper , Forsberg Birger Carl , Tomson Göran 
Published: May 2006

Abstract

Background
In the past decade the sector-wide approach (SWAp) model has been promoted by donors and adopted by governments in several countries. The purpose of this study is to look at how partners involved in the health SWAp in Bangladesh define ownership and coordination, in their daily work and to analyse the possible implications of these definitions.

Methodology
The study object was a process of decision-making in the Government of Bangladesh in 2003. Information was collected through participant observations, interviews and document review.

Results
During the study period the Government of Bangladesh decided to reverse a decision to unify the two wings of the Ministry of Health and Family Welfare. The decision led to disagreements with development partners, which had serious implications for cooperation between key actors in the Bangladesh health sector leading to deteriorated relationships and suspension of donor funds. The donor community in itself was also in disagreement which led to inconsistencies in the dialogue between the development partners and the Government of Bangladesh.

Conclusion
The case shows that main actors in the Bangladesh health SWAp interpret ownership and coordination, fundamental aspects of SWAp, differently. As long as work ran smoothly, the different definitions did not create any problems, but when disagreements arose they became an obstacle. It is concluded that partners in development should devote more effort to their working relationships and that responsibilities within a SWAp need to be more clearly delineated.