bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remodeling of carotid arteries is associated with increased expression of thrombomodulin in a mouse transverse aortic constriction model
Authors: Hsieh Chung-Yu , Wang Danny , Chung Hsing-Chun , Liu Shu-Lin , Chao Ting-Hsing , Shi Guey-Yueh , Wu Hua-Lin , Li Yi-Heng 
Published: March 2007

SummaryThrombomodulin (TM) is an endothelial glycoprotein that functions as a thrombin cofactor in the activation of protein C. Recent evidence has revealed that TM has unique effects on cellular proliferation, adhesion, and inflammation. We examined TM expression in the arterial remodeling process with different shear conditions. Quantitative real-time reverse transcription- PCR (Q-PCR) revealed that shear stress (25 dyne/cm2 for 6 hours) induced a 2.6 ± 0.4 -fold increase inTM mRNA levels in endothelial cell culture. Adult FVB (Friend leukemia virus B strain) mice underwent transverse aortic constriction (TAC) between the right (RCA) and left carotid artery (LCA). Doppler (n = 8), morphometric (n = 8), and Q-PCR (n = 8 or 10) studies were performed on carotid arteries at different time points. The RCA lumen and media area increased. The LCA wall shear stress decreased after TAC. RCA wall shear stress increased at day 7 followed by a decrease to the baseline at day 28.TM mRNA level in the LCA was decreased by 61% at day 7 after TAC (0.39 ± 0.04; p<0.05 vs. baseline). It progressively returned to the baseline at day 14 (0.85 ± 0.12) and day 28 (1.48 ± 0.05; all p = NS). TM appeared in the media of the RCA;TM mRNA level in the RCA was increased by 11-fold at day 14 after TAC (11.0 ± 0.22) and progressively decreased at day 28 (5.34 ± 0.25, all p<0.05 vs. baseline). Our studies suggested that altered shear stress induced significantTM gene expression changes during the arterial remodeling process.
Mutational screening of six afibrinogenemic patients: Identification and characterization of four novel molecular defects
Authors: Monaldini Luca , Asselta Rosanna , Duga Stefano , Peyvandi Flora , Karimi Mehran , Malcovati Massimo , Tenchini Maria 
Published: March 2007

SummaryCongenital afibrinogenemia (CAF) is a rare coagulation disorder characterized by very low or unmeasurable levels of functional and immunoreactive fibrinogen in plasma, associated with a hemorrhagic phenotype of variable severity. It is transmitted as an autosomal recessive trait (prevalence 1:1,000,000) and is invariantly associated with mutations affecting one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aα, Bβ, and γ chain, respectively). Fibrinogen is secreted by hepatocytes as a hexamer composed of two copies of each chain; the lack of one chain has been demonstrated to prevent its secretion. Most genetic defects causing afibrinogenemia are point mutations, where- as only three large deletions have been identified so far, all affecting the FGA gene. We here report the molecular characterization of six unrelated afibrinogenemic patients leading to the identification of eight different mutations, four hitherto unknown: a 4.1-Kb large deletion involving exon 1 of FGA (AC107385:g. 65682_69828del), two nonsense mutations (p.Trp229X in FGA and p.Trp266X in FGB), and an ins-del mutation (g.1787_ 1789del3ins12) in FGA. The molecular characterization of CAFcausing genetic defects increases our understanding on the genetic basis of this disease and might be helpful for prenatal screening
purposes, as also demonstrated during this study.
Community Attitudes Towards Discriminatory Practice Against People with Severe Mental Illness in Hong Kong
Authors: Chiu Marcus Y.L. , Chan Kenneth K.L. 
Published: March 2007

Background: The existing literature on community attitudes towards people with severe mental illness (SMI) tends to be rather general and impressionistic, with apparently conflicting findings which have yet to be adequately understood. Aims: This article undertakes to examine the community's level of tolerance towards discriminatory practice against people with SMI in three domains: family relations, employment and health care. Methods: Structured interviews with a representative sample of 507 citizens were carried out using the computer-assisted telephone interview system (CATI). Results: Our survey reveals some expected common misunderstandings about mental illness, with the older age group showing the greatest toleration towards discrimination. However, respondents showed a strong objection to discriminatory behaviour which people with SMI commonly face in health care and employment, whereas greater toleration towards discrimination was found in the family domain. Conclusions: The coexistence of misunderstandings about mental illness and public rejection of discriminatory practice against people with SMI suggests that community attitudes are multi-dimensional and more amendable than expected. The findings of this study call for target-specific educational strategies for community education, as well as accompanying policy initiatives to end discriminatory practice, if people with SMI are to be truly taken as our fellow citizens.
Prevalence Of Depression And Correlates Of Depressive Symptoms For Residents In The Urban Part Of Jeju Island, Korea
Authors: Kim Moon-Doo , Hong Seong-Chul , Lee Chang-In , Kwak Young-Sook , Shin Tae-Kyun , Jang Yun-Hee , Oh Eun-Hee , Lee Ji-Woong , Jeon Bong-Hee , Hwang Seo-Eun 
Published: March 2007

Aims: This study examined the prevalence of depression and depressive symptoms, and the correlates of depressive symptoms, and proposes some methods for reducing risk of depression in residents of the urban part of Jeju Island in Korea. Methods: In all, 1050 residents were selected using multiphasic cluster sampling to represent each district. Of the 981 respondents, 413 were men and 568 were women. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to evaluate depression (CES-D score over 25) and depressive symptoms (CES-D score over 21). Multiple logistic regression analysis was performed for comparisons. Results: The prevalence of depression in males and females was comparable, at 9.47 and 11.36%, respectively. The prevalence of depressive symptoms in men was 15.01%, while in women the level rose to 18.37%. Those with high self-assessed level of stress scores were significantly more likely to have depressive symptoms than those with low self-assessed level of stress scores (odds ratio (OR) = 5.73 (95% confidence interval (95%CI), 1.29–25.36)). Residents at high risk of problem drinking (CAGE score over 3) were significantly more likely to have depressive symptoms than those with a CAGE score under 1 (OR = 3.43 95%CI, 1.77–6.66). Respondents who slept poorly had more depressive symptoms than respondents who slept well (OR = 2.11 95%CI, 1.37–3.23). Females were significantly more likely to have more depressive symptoms than males (OR = 1.70 95%CI, 1.08–2.68). Conclusions: The prevalence of depression and depressive symptoms in urban Jeju Island is similar to that in a nation-wide sample. By providing intensive mental health services to those who have high stress levels, problem drinking, and poor health behavior, early detection of depressive symptoms in the community will be important for improving general health status.
Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801
Authors: DeAngelo Daniel J. , Yu Daohai , Johnson Jeffrey L. , Coutre Steven E. , Stone Richard M. , Stopeck Alison T. , Gockerman Jon P. , Mitchell Beverly S. , Appelbaum Frederick R. , Larson Richard A. 
Published: March 2007

AbstractNelarabine (506U78) is a soluble pro-drug of 9-β-d-arabinofuranosylguanine (ara-G), a deoxyguanosine derivative. We treated 26 patients with T-cell acute lymphoblastic leukemia (T-ALL) and 13 with T-cell lymphoblastic lymphoma (T-LBL) with nelarabine. All patients were refractory to at least one multiagent regimen or had relapsed after achieving a complete remission. Nelarabine was administered on an alternate day schedule (days 1, 3, and 5) at 1.5 g/m2/day. Cycles were repeated every 22 days. The median age was 34 years (range, 16-66 years); 32 (82%) patients were male. The rate of complete remission was 31% (95% confidence interval [CI], 17%, 48%) and the overall response rate was 41% (95% CI, 26%, 58%). The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively. There was only one grade 4 adverse event of the nervous system, which was a reversible depressed level of consciousness. The median disease-free survival (DFS) was 20 weeks (95% CI, 11, 56), and the median overall survival was 20 weeks (95% CI, 13, 36). The 1-year overall survival was 28% (95% CI, 15%, 43%). Nelarabine is well tolerated and has significant antitumor activity in relapsed or refractory T-ALL and T-LBL.
Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia
Authors: Henter Jan-Inge , Karlén Jonas 
Published: March 2007

Abstract
A 10-year-old girl with steroid-resistent Diamond-Blackfan anemia (DBA) developed agranulocytosis 9 weeks after chelation with deferiprone was initiated (45 mg/kg daily, 60% of recommended dose) in addition to her ordinary deferoxamine therapy. The blood counts, checked weekly, dropped markedly between weeks 8 and 9. She rapidly developed a septicemia and was admitted with high fever (40.9°C), white blood cell count 0.4 × 109/L, absolute neutrophil count 0.1 × 109/L and platelets 114 × 109/L. She was administered broad spectrum antibiotics, G-CSF (10 microgram/kg daily) and corticosteroids but remained neutropenic and died 6 weeks after admission. Bone marrow examination day 23 revealed areas with low cellularity (around 30%), but also areas with infiltrates of T cells; granulopoiesis and erythropoiesis were scarce. We conclude that weekly neutrophil monitoring is not sufficient to avoid fatal agranulocytosis. We suggest that deferiprone not be prescribed to DBA patients unless the clinical indications are particularly strong, and that the risk of agranulocytosis in thalassemia patients be carefully considered.
Orthology prediction at scalable resolution by phylogenetic tree analysis
Authors: van der Heijden René TJM , Snel Berend , van Noort Vera , Huynen Martijn A 
Published: March 2007

Abstract

Background
Orthology is one of the cornerstones of gene function prediction. Dividing the phylogenetic relations between genes into either orthologs or paralogs is however an oversimplification. Already in two-species gene-phylogenies, the complicated, non-transitive nature of phylogenetic relations results in inparalogs and outparalogs. For situations with more than two species we lack semantics to specifically describe the phylogenetic relations, let alone to exploit them. Published procedures to extract orthologous groups from phylogenetic trees do not allow identification of orthology at various levels of resolution, nor do they document the relations between the orthologous groups.

Results
We introduce "levels of orthology" to describe the multi-level nature of gene relations. This is implemented in a program LOFT (Levels of Orthology From Trees) that assigns hierarchical orthology numbers to genes based on a phylogenetic tree. To decide upon speciation and gene duplication events in a tree LOFT can be instructed either to perform classical species-tree reconciliation or to use the species overlap between partitions in the tree. The hierarchical orthology numbers assigned by LOFT effectively summarize the phylogenetic relations between genes. The resulting high-resolution orthologous groups are depicted in colour, facilitating visual inspection of (large) trees. A benchmark for orthology prediction, that takes into account the varying levels of orthology between genes, shows that the phylogeny-based high-resolution orthology assignments made by LOFT are reliable.

Conclusion
The "levels of orthology" concept offers high resolution, reliable orthology, while preserving the relations between orthologous groups. A Windows as well as a preliminary Java version of LOFT is available from the LOFT website http://www.cmbi.ru.nl/LOFT.
On the origin and evolution of biosynthetic pathways: integrating microarray data with structure and organization of the Common Pathway genes
Authors: Fondi Marco , Brilli Matteo , Fani Renato 
Published: March 2007

Abstract

Background
The lysine, threonine, and methionine biosynthetic pathways share the three initial enzymatic steps, which are referred to as the Common Pathway (CP). In Escherichia coli three different aspartokinases (AKI, AKII, AKIII, the products of thrA, metL and lysC, respectively) can perform the first step of the CP. Moreover, two of them (AKI and AKII) are bifunctional, carrying also homoserine dehydrogenasic activity (hom product). The second step of the CP is catalyzed by a single aspartate semialdehyde dehydrogenase (ASDH, the product of asd). Thus, in the CP of E. coli while a single copy of ASDH performs the same reaction for three different metabolic routes, three different AKs perfom a unique step. Why and how such a situation did emerge and maintain? How is it correlated to the different regulatory mechanisms acting on these genes? The aim of this work was to trace the evolutionary pathway leading to the extant scenario in proteobacteria.

Results
The analysis of the structure, organization, phylogeny, and distribution of ask and hom genes revealed that the presence of multiple copies of these genes and their fusion events are restricted to the γ-subdivision of proteobacteria. This allowed us to depict a model to explain the evolution of ask and hom according to which the fused genes are the outcome of a cascade of gene duplication and fusion events that can be traced in the ancestor of γ-proteobacteria. Moreover, the appearance of fused genes paralleled the assembly of operons of different sizes, suggesting a strong correlation between the structure and organization of these genes. A statistic analysis of microarray data retrieved from experiments carried out on E. coli and Pseudomonas aeruginosa was also performed.

Conclusion
The integration of data concerning gene structure, organization, phylogeny, distribution, and microarray experiments allowed us to depict a model for the evolution of ask and hom genes in proteobacteria and to suggest a biological significance for the extant scenario.
A global gene evolution analysis on Vibrionaceae family using phylogenetic profile
Authors: Vitulo Nicola , Vezzi Alessandro , Romualdi Chiara , Campanaro Stefano , Valle Giorgio 
Published: March 2007

Abstract

Background

Vibrionaceae represent a significant portion of the cultivable heterotrophic sea bacteria; they strongly affect nutrient cycling and some species are devastating pathogens.
In this work we propose an improved phylogenetic profile analysis on 14 Vibrionaceae genomes, to study the evolution of this family on the basis of gene content.
The phylogenetic profile is based on the observation that genes involved in the same process (e.g. metabolic pathway or structural complex) tend to be concurrently present or absent within different genomes. This allows the prediction of hypothetical functions on the basis of a shared phylogenetic profiles. Moreover this approach is useful to identify putative laterally transferred elements on the basis of their presence on distantly phylogenetically related bacteria.

Results

Vibrionaceae ORFs were aligned against all the available bacterial proteomes. Phylogenetic profile is defined as an array of distances, based on aminoacid substitution matrixes, from single genes to all their orthologues. Final phylogenetic profiles, derived from non-redundant list of all ORFs, was defined as the median of all the profiles belonging to the cluster. The resulting phylogenetic profiles matrix contains gene clusters on the rows and organisms on the columns.
Cluster analysis identified groups of "core genes" with a widespread high similarity across all the organisms and several clusters that contain genes homologous only to a limited set of organisms. On each of these clusters, COG class enrichment has been calculated. The analysis reveals that clusters of core genes have the highest number of enriched classes, while the others are enriched just for few of them like DNA replication, recombination and repair.

Conclusion
We found that mobile elements have heterogeneous profiles not only across the entire set of organisms, but also within Vibrionaceae; this confirms their great influence on bacteria evolution even inside the same family. Furthermore, several hypothetical proteins highly correlate with mobile elements profiles suggesting a possible horizontal transfer mechanism for the evolution of these genes. Finally, we suggested the putative role of some ORFs having an unknown function on the basis of their phylogenetic profile similarity to well characterized genes.
ProtNet: a tool for stochastic simulations of protein interaction networks dynamics
Authors: Bernaschi Massimo , Castiglione Filippo , Ferranti Alessandra , Gavrila Caius , Tinti Michele , Cesareni Gianni 
Published: March 2007

Abstract

Background
Protein interactions support cell organization and mediate its response to any specific stimulus. Recent technological advances have produced large data-sets that aim at describing the cell interactome. These data are usually presented as graphs where proteins (nodes) are linked by edges to their experimentally determined partners. This representation reveals that protein-protein interaction (PPI) networks, like other kinds of complex networks, are not randomly organized and display properties that are typical of "hierarchical" networks, combining modularity and local clustering to scale free topology. However informative, this representation is static and provides no clue about the dynamic nature of protein interactions inside the cell.

Results
To fill this methodological gap, we designed and implemented a computer model that captures the discrete and stochastic nature of protein interactions. In ProtNet, our simplified model, the intracellular space is mapped onto either a two-dimensional or a three-dimensional lattice with each lattice site having a linear size (5 nm) comparable to the diameter of an average globular protein. The protein filled lattice has an occupancy (e.g. 20%) compatible with the estimated crowding of proteins in the cell cytoplasm. Proteins or protein complexes are free to translate and rotate on the lattice that represents a sort of naïve unstructured cell (devoid of compartments). At each time step, molecular entities (proteins or complexes) that happen to be in neighboring cells may interact and form larger complexes or dissociate depending on the interaction rules defined in an experimental protein interaction network. This whole procedure can be seen as a sort of "discrete molecular dynamics" applied to interacting proteins in a cell.
We have tested our model by performing different simulations using as interaction rules those derived from an experimental interactome of Saccharomyces cerevisiae (1378 nodes, 2491 edges) and we have compared the dynamics of complex formation in a two and a three dimensional lattice model.

Conclusion
ProtNet is a cellular automaton model, where each protein molecule or complex is explicitly represented and where simple interaction rules are applied to populations of discrete particles. This tool can be used to simulate the dynamics of protein interactions in the cell.
The MEPS server for identifying protein conformational epitopes
Authors: Castrignanò Tiziana , De Meo Paolo D'Onorio , Carrabino Danilo , Orsini Massimilano , Floris Matteo , Tramontano Anna 
Published: March 2007

Abstract

Background
One of the most interesting problems in molecular immunology is epitope mapping, i.e. the identification of the regions of interaction between an antigen and an antibody. The solution to this problem, even if approximate, would help in designing experiments to precisely map the residues involved in the interaction and could be instrumental both in designing peptides able to mimic the interacting surface of the antigen and in understanding where immunologically important regions are located in its three-dimensional structure. From an experimental point of view, both genetically encoded and chemically synthesised peptide libraries can be used to identify sequences recognized by a given antibody. The problem then arises of which region of a folded protein the selected peptides correspond to.

Results
We have developed a method able to find the surface region of a protein that can be effectively mimicked by a peptide, given the structure of the protein and the maximum number of side chains deemed to be required for recognition. The method is implemented as a publicly available server. It can also find and report all peptide sequences of a specified length that can mimic the surface of a given protein and store them in a database.
The immediate application of the server is the mapping of antibody epitopes, however the system is sufficiently flexible for allowing other questions to be asked, for example one can compare the peptides representing the surface of two proteins known to interact with the same macromolecule to find which is the most likely interacting region.

Conclusion
We believe that the MEPS server, available at http://www.caspur.it/meps, will be a useful tool for immunologists and structural and computational biologists. We plan to use it ourselves to implement a database of "surface mimicking peptides" for all proteins of known structure and proteins that can be reliably modelled by comparative modelling.
A Grid-based solution for management and analysis of microarrays in distributed experiments
Authors: Porro Ivan , Torterolo Livia , Corradi Luca , Fato Marco , Papadimitropoulos Adam , Scaglione Silvia , Schenone Andrea , Viti Federica 
Published: March 2007

Abstract
Several systems have been presented in the last years in order to manage the complexity of large microarray experiments. Although good results have been achieved, most systems tend to lack in one or more fields. A Grid based approach may provide a shared, standardized and reliable solution for storage and analysis of biological data, in order to maximize the results of experimental efforts. A Grid framework has been therefore adopted due to the necessity of remotely accessing large amounts of distributed data as well as to scale computational performances for terabyte datasets. Two different biological studies have been planned in order to highlight the benefits that can emerge from our Grid based platform. The described environment relies on storage services and computational services provided by the gLite Grid middleware. The Grid environment is also able to exploit the added value of metadata in order to let users better classify and search experiments. A state-of-art Grid portal has been implemented in order to hide the complexity of framework from end users and to make them able to easily access available services and data. The functional architecture of the portal is described. As a first test of the system performances, a gene expression analysis has been performed on a dataset of Affymetrix GeneChip® Rat Expression Array RAE230A, from the ArrayExpress database. The sequence of analysis includes three steps: (i) group opening and image set uploading, (ii) normalization, and (iii) model based gene expression (based on PM/MM difference model). Two different Linux versions (sequential and parallel) of the dChip software have been developed to implement the analysis and have been tested on a cluster. From results, it emerges that the parallelization of the analysis process and the execution of parallel jobs on distributed computational resources actually improve the performances. Moreover, the Grid environment have been tested both against the possibility of uploading and accessing distributed datasets through the Grid middleware and against its ability in managing the execution of jobs on distributed computational resources. Results from the Grid test will be discussed in a further paper.