bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells
Authors: Basso Katia , Saito Masumichi , Sumazin Pavel , Margolin Adam A. , Wang Kai , Lim Wei-Keat , Kitagawa Yukiko , Schneider Christof , Alvarez Mariano J. , Califano Andrea , Dalla-Favera Riccardo 
Published: December 2009

Abstract
BCL6 is a transcriptional repressor required for mature B-cell germinal center (GC) formation and implicated in lymphomagenesis. BCL6's physiologic function is only partially known because the complete set of its targets in GC B cells has not been identified. To address this issue, we used an integrated biochemical-computational-functional approach to identify BCL6 direct targets in normal GC B cells. This approach includes (1) identification of BCL6-bound promoters by genome-wide chromatin immunoprecipitation, (2) inference of transcriptional relationships by the use of a regulatory network reverse engineering approach (ARACNe), and (3) validation of physiologic relevance of the candidate targets down-regulated in GC B cells. Our approach demonstrated that a large set of promoters (> 4000) is physically bound by BCL6 but that only a fraction of them is repressed in GC B cells. This set of 1207 targets identifies several cellular functions directly controlled by BCL6 during GC development, including activation, survival, DNA-damage response, cell cycle arrest, cytokine signaling, Toll-like receptor signaling, and differentiation. These results define a broad role of BCL6 in preventing centroblasts from responding to signals leading to exit from the GC before they complete the phase of proliferative expansion and of antibody affinity maturaton.
Inferring protein function by domain context similarities in protein-protein interaction networks
Authors: Zhang Song , Chen Hu , Liu Ke , Sun Zhirong 
Published: December 2009

Abstract

Background
Genome sequencing projects generate massive amounts of sequence data but there are still many proteins whose functions remain unknown. The availability of large scale protein-protein interaction data sets makes it possible to develop new function prediction methods based on protein-protein interaction (PPI) networks. Although several existing methods combine multiple information resources, there is no study that integrates protein domain information and PPI networks to predict protein functions.

Results
The domain context similarity can be a useful index to predict protein function similarity. The prediction accuracy of our method in yeast is between 63%-67%, which outperforms the other methods in terms of ROC curves.

Conclusion
This paper presents a novel protein function prediction method that combines protein domain composition information and PPI networks. Performance evaluations show that this method outperforms existing methods.
454 pyrosequencing based transcriptome analysis of Zygaena filipendulae with focus on genes involved in biosynthesis of cyanogenic glucosides
Authors: Zagrobelny Mika , Scheibye-Alsing Karsten , Jensen Niels Bjerg , Møller Birger Lindberg , Gorodkin Jan , Bak Søren 
Published: December 2009

Abstract

Background
An essential driving component in the co-evolution of plants and insects is the ability to produce and handle bioactive compounds. Plants produce bioactive natural products for defense, but some insects detoxify and/or sequester the compounds, opening up for new niches with fewer competitors. To study the molecular mechanism behind the co-adaption in plant-insect interactions, we have investigated the interactions between Lotus corniculatus and Zygaena filipendulae. They both contain cyanogenic glucosides which liberate toxic hydrogen cyanide upon breakdown. Moths belonging to the Zygaena family are the only insects known, able to carry out both de novo biosynthesis and sequestration of the same cyanogenic glucosides as those from their feed plants. The biosynthetic pathway for cyanogenic glucoside biosynthesis in Z. filipendulae proceeds using the same intermediates as in the well known pathway from plants, but none of the enzymes responsible have been identified. A genomics strategy founded on 454 pyrosequencing of the Z. filipendulae transcriptome was undertaken to identify some of these enzymes in Z. filipendulae.

Results
Comparisons of the Z. filipendulae transcriptome with the sequenced genomes of Bombyx mori, Drosophila melanogaster, Tribolium castaneum, Apis mellifera and Anopheles gambiae indicate a high coverage of the Z. filipendulae transcriptome. 11% of the Z. filipendulae transcriptome sequences were assigned to Gene Ontology categories. Candidate genes for enzymes functioning in the biosynthesis of cyanogenic glucosides (cytochrome P450 and family 1 glycosyltransferases) were identified based on sequence length, number of copies and presence/absence of close homologs in D. melanogaster, B. mori and the cyanogenic butterfly Heliconius. Examination of biased codon usage, GC content and selection on gene candidates support the notion of cyanogenesis as an "old" trait within Ditrysia, as well as its origins being convergent between plants and insects.

Conclusion
Pyrosequencing is an attractive approach to gain access to genes in the biosynthesis of bio-active natural products from insects and other organisms, for which the genome sequence is not known. Based on analysis of the Z. filipendulae transcriptome, promising gene candidates for biosynthesis of cyanogenic glucosides was identified, and the suitability of Z. filipendulae as a model system for cyanogenesis in insects is evident.
Identification of a novel conserved HLA-A*0201-restricted epitope from the spike protein of SARS-CoV
Authors: Lv Yanbo , Ruan Zhihua , Wang Li , Ni Bing , Wu Yuzhang 
Published: December 2009

AbstractBackgroundThe spike (S) protein is a major structural glycoprotein of coronavirus (CoV), the causal agent of severe acute respiratory syndrome (SARS). The S protein is a potent target for SARS-specific cell-mediated immune responses. However, the mechanism CoV pathogenesis in SARS and the role of special CTLs in virus clearance are still largely uncharacterized. Here, we describe a study that leads to the identification of a novel HLA-A*0201-restricted epitope from conserved regions of S protein.ResultsFirst, different SARS-CoV sequences were analyzed to predict eight candidate peptides from conserved regions of the S protein based upon HLA-A*0201 binding and proteosomal cleavage. Four of eight candidate peptides were tested by HLA-A*0201 binding assays. Among the four candidate peptides, Sp8 (S958-966, VLNDILSRL) induced specific CTLs bothex vivoin PBLs of healthy HLA-A2+donors and in HLA-A2.1/Kbtransgenic mice immunized with a plasmid encoding full-length S protein. The immunized mice released IFN-γ and lysed target cells upon stimulation with Sp8 peptide-pulsed autologous dendritic cells in comparison to other candidates.ConclusionThese results suggest that Sp8 is a naturally processed epitope. We propose that Sp8 epitope should help in the characterization of mechanisms of virus control and immunopathology in SARS-CoV infection.
Allelic diversity and phylogeny of homB, a novel co-virulence marker of Helicobacter pylori
Authors: Oleastro Mónica , Cordeiro Rita , Ménard Armelle , Yamaoka Yoshio , Queiroz Dulciene , Mégraud Francis , Monteiro Lurdes 
Published: December 2009

AbstractBackgroundThehomBgene is aHelicobacter pyloridisease-marker candidate, strongly associated with peptic ulcer disease, whilehomA, its paralogue gene with 90% sequence identity, is correlated with non-ulcer dyspepsia. The HomB encoded outer membrane protein was shown to contribute to the proinflammatory properties ofH. pyloriand also to be involved in bacterial adherence.This study investigated the distribution ofhomBandhomAgenes in 455H. pyloristrains from East Asian and Western countries, and carried out sequence comparison and phylogenetic analyses.ResultsBothhomBandhomAgenes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains.Analysis ofhomBandhomAsequences revealed diversity regarding the number of copies and their genomic localization, with East Asian and Western strains presenting different genotypes. Moreover,homBandhomAsequence analysis suggests regulation by phase variation. It also indicates possible recombination events, leading to gene duplication orhomB/homAconversion which may as well be implicated in the regulation of these genes. Phylogenetic reconstruction ofhomBandhomArevealed clustering according to the geographic origin of strains. Allelic diversity in the middle region of the genes was observed for bothhomBandhomA, although there was no correlation between any allele and disease. For each gene, a dominant worldwide allele was detected, suggesting thathomB/homA allelic variants were independent of the geographical origin of the strain. Moreover, all alleles were demonstrated to be expressedin vivo.ConclusionOverall, these results suggest thathomBandhomAgenes are good candidates to be part of the pool ofH. pyloriOMPs implicated in host-bacteria interface and also contributing to the generation of antigenic variability, and thus involved inH. pyloripersistence.
Falls following discharge after an in-hospital fall
Authors: Davenport Rick D , Vaidean Georgeta D , Jones Carol B , Chandler A Michelle , Kessler Lori A , Mion Lorraine C , Shorr Ronald I 
Published: December 2009

Abstract

Background
Falls are among the most common adverse events reported in hospitalized patients. While there is a growing body of literature on fall prevention in the hospital, the data examining the fall rate and risk factors for falls in the immediate post-hospitalization period has not been well described. The objectives of the present study were to determine the fall rate of in-hospital fallers at home and to explore the risk factors for falls during the immediate post-hospitalization period.

Methods
We identified patients who sustained a fall on one of 16 medical/surgical nursing units during an inpatient admission to an urban community teaching hospital. After discharge, falls were ascertained using weekly telephone surveillance for 4 weeks post-discharge. Patients were followed until death, loss to follow up or end of study (four weeks). Time spent rehospitalized or institutionalized was censored in rate calculations.

Results
Of 95 hospitalized patients who fell during recruitment, 65 (68%) met inclusion criteria and agreed to participate. These subjects contributed 1498 person-days to the study (mean duration of follow-up = 23 days). Seventy-five percent were African-American and 43% were women. Sixteen patients (25%) had multiple falls during hospitalization and 23 patients (35%) suffered a fall-related injury during hospitalization. Nineteen patients (29%) experienced 38 falls at their homes, yielding a fall rate of 25.4/1,000 person-days (95% CI: 17.3-33.4). Twenty-three patients (35%) were readmitted and 3(5%) died. One patient experienced a hip fracture. In exploratory univariate analysis, persons who were likely to fall at home were those who sustained multiple falls in the hospital (p = 0.008).

Conclusion
Patients who fall during hospitalization, especially on more than one occasion, are at high risk for falling at home following hospital discharge. Interventions to reduce falls would be appropriate to test in this high-risk population.
Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia
Authors: Zhou Li , Rua Rejane , Ng Thomas , Vongrad Valentina , Ho Yung S , Geczy Carolyn , Hsu Kenneth , Brew Bruce J , Saksena Nitin K 
Published: December 2009

AbstractBackgroundHIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.MethodsTo study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.ResultsOverall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.ConclusionStrong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.
Ertapenem versus piperacillin/tazobactam for the treatment of complicated infections: a meta-analysis of randomized controlled trials
Authors: An Mao Mao , Zou Zui , Shen Hui , Zhang Jun Dong , Chen Meng Li , Liu Ping , Wang Rui , Jiang Yuan Ying 
Published: December 2009

Abstract

Background
Ertapenem, a new carbapenem with a favorable pharmacokinetic profile, has been approved for the treatment of complicated intra-abdominal Infections (cIAIs), acute pelvic infections (APIs) and complicated skin and skin-structure infections (cSSSIs). The aim of this study is to compare the efficacy and safety of ertapenem with piperacillin/tazobactam, which has been reported to possess good efficacy for the treatment of these complicated infections.

Methods
We performed a meta-analysis of randomized controlled trials identified in PubMed, Cochrane library and Embase that compared the efficacy and safety of ertapenem with piperacillin/tazobactam for the treatment of complicated infections including cIAIs, APIs, cSSSIs. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure visit. The primary safety outcome was drug related clinical and laboratory adverse events occurred during the treatment and the post-treatment period.

Result
Six RCTs, involving 3161 patients, were included in our meta-analysis. Ertapenem was associated similar clinical treatment success with piperacillin/tazobactam for complicated infections treatment (clinically evaluable population, 1937 patients, odds ratios: 1.15, 95% confidence intervals: 0.89-1.49; modified intention to treat population, 2855 patients, odds ratios: 1.03, 95% confidence intervals: 0.87-1.22). All of secondary efficacy outcomes analysis obtained similar findings with clinical treatment success. No difference was found about the incidence of drug related adverse events between ertapenem and piperacillin/tazobactam groups.

Conclusion
This meta-analysis provides evidence that ertapenem 1 g once a day can be used as effectively and safely as recommended dose of piperacillin/tazobactam, for the treatment of complicated infections, particularly of mild to moderate severity. It is an appealing option for the treatment of these complicated infections.
Analyses of associations between three positionally cloned asthma candidate genes and asthma or asthma-related phenotypes in a Chinese population
Authors: Zhou Huanyu , Hong Xiumei , Jiang Shanqun , Dong Hongxing , Xu Xiping , Xu Xin 
Published: December 2009

Abstract

Background
Six asthma candidate genes, ADAM33, NPSR1, PHF11, DPP10, HLA-G, and CYFIP2, located at different chromosome regions have been positionally cloned following the reported linkage studies. For ADAM33, NPSR1, and CYFIP2, the associations with asthma or asthma-related phenotypes have been studied in East Asian populations such as Chinese and Japanese. However, for PHF11, DPP10, and HLA-G, none of the association studies have been conducted in Asian populations. Therefore, the aim of the present study is to test the associations between these three positionally cloned genes and asthma or asthma-related phenotypes in a Chinese population.

Methods
Two, five, and two single nucleotide polymorphisms (SNPs) in the identified top regions of PHF11, DPP10, and HLA-G, respectively, were genotyped in 1183 independent samples. The study samples were selected based on asthma affectation status and extreme values in at least one of the following three asthma-related phenotypes: total serum immunoglobulin E levels, bronchial responsiveness test, and skin prick test. Both single SNP and haplotype analyses were performed.

Results
We found that DPP10 was significantly associated with bronchial hyperresponsiveness (BHR) and BHR asthma after the adjustment for multiple testing; while the associations of PHF11 with positive skin reactions to antigens and the associations of HLA-G with BHR asthma were only nominally significant.

Conclusion
Our study is the first one to provide additional evidence that supports the roles of DPP10 in influencing asthma or BHR in a Chinese population.
End-stage renal disease in young black males in a black-white population: longitudinal analysis of the Bogalusa Heart Study
Authors: Muntner Paul , Arshad Asghar , Morse Stephen A , Patel Dharmendrakumar A , Manapatra Pronabesh D , Reisin Efrain , Aguilar Erwin A , Chen Wei , Srinivasan Sathanur , Berenson Gerald S 
Published: December 2009

Abstract

Background
Risk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized.

Methods
The current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988.

Results
Through 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p < 0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean = 103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m2 among ESRD cases and 18.6 kg/m2 and 18.9 kg/m2 among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD.

Conclusion
These data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.
ACCISS study rationale and design: activating collaborative cancer information service support for cervical cancer screening
Authors: Cofta-Woerpel Ludmila , Randhawa Veenu , McFadden H Gene , Fought Angela , Bullard Emily , Spring Bonnie 
Published: December 2009

Abstract

Background
High-quality cancer information resources are available but underutilized by the public. Despite greater awareness of the National Cancer Institute's Cancer Information Service among low-income African Americans and Hispanics compared with Caucasians, actual Cancer Information Service usage is lower than expected, paralleling excess cancer-related morbidity and mortality for these subgroups. The proposed research examines how to connect the Cancer Information Service to low-income African-American and Hispanic women and their health care providers. The study will examine whether targeted physician mailing to women scheduled for colposcopy to follow up an abnormal Pap test can increase calls to the Cancer Information Service, enhance appropriate medical follow-up, and improve satisfaction with provider-patient communication.

Methods/Design
The study will be conducted in two clinics in ethnically diverse low-income communities in Chicago. During the formative phase, patients and providers will provide input regarding materials planned for use in the experimental phase of the study. The experimental phase will use a two-group prospective randomized controlled trial design. African American and Hispanic women with an abnormal Pap test will be randomized to Usual Care (routine colposcopy reminder letter) or Intervention (reminder plus provider recommendation to call the Cancer Information Service and sample questions to ask). Primary outcomes will be: 1) calls to the Cancer Information Service; 2) timely medical follow-up, operationalized by whether the patient keeps her colposcopy appointment within six months of the abnormal Pap; and 3) patient satisfaction with provider-patient communication at follow-up.

Discussion
The study examines the effectiveness of a feasible, sustainable, and culturally sensitive strategy to increase awareness and use of the Cancer Information Service among an underserved population. The goal of linking a public service (the Cancer Information Service) with real-life settings of practice (the clinics), and considering input from patients, providers, and Cancer Information Service staff, is to ensure that the intervention, if proven effective, can be incorporated into existing care systems and sustained. The approach to study design and planning is aimed at bridging the gap between research and practice/service.

Trial Registration
NCT00873288