bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of China rabies virus vaccine strain
Authors: Jiao Wenqiang , Yin Xiangping , Li Zhiyong , Lan Xi , Li Xuerui , Tian Xiaoting , Li Baoyu , Yang Bin , Zhang Yun , Liu Jixing 
Published: November 2011

Abstract

Background
Rabies virus (RV), the agent of rabies, can cause a severe encephalomyelitis in several species of mammals, including humans. As a human rabies vaccine strain employed in China, the genetic knowledge of the aG strain has not been fully studied. The main goal of the present study is to amplify the whole genome of aG strain, and genetic relationships between other vaccine strains and wild strains were analyzed.

Results
The entire genome of human rabies virus vaccine strain aG employed in China was sequenced; this is the second rabies virus vaccine strain from China to be fully characterized. The overall organization and the length of the genome were similar to that of other lyssaviruses. The length of aG strain was 11925nt, comprising a leader sequence of 58nt, nucleoprotein (N) gene of 1353nt, phosphoprotein (P) gene of 894 nt, matrix protein (M) gene of 609nt, glycoprotein (G) gene of 1575nt, RNA-dependent RNA polymerase (RdRp,L) gene of 6384nt, and a trailer region of 70 nt. There was TGAAAAAAA (TGA7) consensus sequence in the end of each gene, except AGA7 at the end of G gene. There was AACAYYYCT consensus start signal at the beginning of each gene.

Conclusions
In this report, we analyzed the full genome of China human rabies vaccine strain aG. Our studies indicated that the genome of aG retained the basic characteristics of RV. At gene level, N was the most conserved among the five coding genes, indicating this gene is the most appropriate for quantitative genotype definition. The phylogenetic analysis of the N indicated the aG strain clustered most closely with Japanese and Russian rabies vaccine strains, suggesting that they may share the same ancestor; also, the aG strain did not share high homology with wild strains isolated from China, making it may not be the best vaccine strain, more research is needed to elucidate the genetic relationship among the RV circulating in China.
An efficient procedure for plant organellar genome assembly, based on whole genome data from the 454 GS FLX sequencing platform
Authors: Zhang Tongwu , Zhang Xiaowei , Hu Songnian , Yu Jun 
Published: November 2011

Abstract

Motivation
Complete organellar genome sequences (chloroplasts and mitochondria) provide valuable resources and information for studying plant molecular ecology and evolution. As high-throughput sequencing technology advances, it becomes the norm that a shotgun approach is used to obtain complete genome sequences. Therefore, to assemble organellar sequences from the whole genome, shotgun reads are inevitable. However, associated techniques are often cumbersome, time-consuming, and difficult, because true organellar DNA is difficult to separate efficiently from nuclear copies, which have been transferred to the nucleus through the course of evolution.

Results
We report a new, rapid procedure for plant chloroplast and mitochondrial genome sequencing and assembly using the Roche/454 GS FLX platform. Plant cells can contain multiple copies of the organellar genomes, and there is a significant correlation between the depth of sequence reads in contigs and the number of copies of the genome. Without isolating organellar DNA from the mixture of nuclear and organellar DNA for sequencing, we retrospectively extracted assembled contigs of either chloroplast or mitochondrial sequences from the whole genome shotgun data. Moreover, the contig connection graph property of Newbler (a platform-specific sequence assembler) ensures an efficient final assembly. Using this procedure, we assembled both chloroplast and mitochondrial genomes of a resurrection plant, Boea hygrometrica, with high fidelity. We also present information and a minimal sequence dataset as a reference for the assembly of other plant organellar genomes.
Serological testing of cattle experimentally infected with Mycoplasma mycoides subsp. mycoides Small Colony using four different tests reveals a variety of seroconversion patterns
Authors: Schubert Evelyn , Sachse Konrad , Jores Jörg , Heller Martin 
Published: November 2011

Abstract

Background
To study the specific antibody response to infection with Mycoplasma mycoides subsp. mycoides Small Colony (MmmSC), the agent of Contagious Bovine Pleuropneumonia (CBPP), we examined three panels of sera collected during three experimental infection trials in African cattle. The methods used included an in-house complement fixation test (CFT), a commercially available CFT, a competitive antibody ELISA (cELISA) and the immunoblotting test (IBT). In addition, lung tissue samples were examined by culture.

Results
A total of 89% (51/59) of all experimentally infected animals tested positive on at least one of the serological tests throughout the trial. The specific antibody titres to the MmmSC infection became positive first by CFT (6 to 9 days post infection [dpi]), followed by IBT (9 to 13 dpi) and cELISA (13 to 16 dpi). Individual animals were found to display remarkably distinct seroconversion patterns, which allowed their classification into i) early high responders, ii) late high responders, and iii) low responders. In accordance with other studies, none of the present serological tests was capable of detecting all CBPP infected animals.

Conclusion
Comparison of the assays' performance in terms of sensitivity and specificity raises serious questions as to their reliability for identification of infected individuals in the field. In view of these limitations, a combination of CFT and cELISA can markedly improve CBPP diagnosis at single-animal level.
Accountability and pediatric physician-researchers: are theoretical models compatible with Canadian lived experience?
Authors: Czoli Christine , Da Silva Michael , Zlotnik Shaul Randi , d'Agincourt-Canning Lori , Simpson Christy , Boydell Katherine , Rashkovan Natalie , Vanin Sharon 
Published: November 2011

AbstractPhysician-researchers are bound by professional obligations stemming from both the role of the physician and the role of the researcher. Currently, the dominant models for understanding the relationship between physician-researchers' clinical duties and research duties fit into three categories: the similarity position, the difference position and the middle ground. The law may be said to offer a fourth "model" that is independent from these three categories.These models frame the expectations placed upon physician-researchers by colleagues, regulators, patients and research participants. This paper examines the extent to which the data from semi-structured interviews with 30 physician-researchers at three major pediatric hospitals in Canada reflect these traditional models. It seeks to determine the extent to which existing models align with the described lived experience of the pediatric physician-researchers interviewed.Ultimately, we find that although some physician-researchers make references to something like the weak version of the similarity position, the pediatric-researchers interviewed in this study did not describe their dual roles in a way that tightly mirrors any of the existing theoretical frameworks. We thus conclude that either physician-researchers are in need of better training regarding the nature of the accountability relationships that flow from their dual roles or that models setting out these roles and relationships must be altered to better reflect what we can reasonably expect of physician-researchers in a real-world environment.
Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration
Authors: Gozal Yair M , Seyfried Nicholas T , Gearing Marla , Glass Jonathan D , Heilman Craig J , Wuu Joanne , Duong Duc M , Cheng Dongmei , Xia Qiangwei , Rees Howard D , Fritz Jason J , Cooper Deborah S , Peng Junmin , Levey Allan I , Lah James J 
Published: November 2011

Abstract

Background
Detergent-insoluble protein accumulation and aggregation in the brain is one of the pathological hallmarks of neurodegenerative diseases. Here, we describe the identification of septin 11 (SEPT11), an enriched component of detergent-resistant fractions in frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions (FTLD-U), using large-scale unbiased proteomics approaches.

Results
We developed and applied orthogonal quantitative proteomic strategies for the unbiased identification of disease-associated proteins in FTLD-U. Using these approaches, we proteomically profiled detergent-insoluble protein extracts prepared from frontal cortex of FTLD-U cases, unaffected controls, or neurologic controls (i.e. Alzheimer's disease; AD). Among the proteins altered specifically in FTLD-U, we identified TAR DNA binding protein-43 (TDP-43), a known component of ubiquitinated inclusions. Moreover, we identified additional proteins enriched in detergent-resistant fractions in FTLD-U, and characterized one of them, SEPT11, in detail. Using independent highly sensitive targeted proteomics approaches, we confirmed the enrichment of SEPT11 in FTLD-U extracts. We further showed that SEPT11 is proteolytically cleaved into N-terminal fragments and, in addition to its prominent glial localization in normal brain, accumulates in thread-like pathology in affected cortex of FTLD-U patients.

Conclusions
The proteomic discovery of insoluble SEPT11 accumulation in FTLD-U, along with novel pathological associations, highlights a role for this cytoskeleton-associated protein in the pathogenesis of this complex disorder.
Pathway-based joint effects analysis of rare genetic variants using Genetic Analysis Workshop 17 exon sequence data
Authors: Hu Pingzhao , Xu Wei , Cheng Lu , Xing Xiang , Paterson Andrew D 
Published: November 2011

Abstract
Pathway-based analysis has been recently used in joint tests of association between disease and a group of common genetic variants. Here we explore this idea for the joint effects analysis of rare genetic variants and their association with quantitative traits and disease. We accumulate multiple rare minor alleles in a genetic risk score for each individual in a given pathway; this score is then used to assess association with quantitative phenotypes and disease. We demonstrate that this approach may be better than studying single rare variants or a gene risk score for identifying individuals with significantly greater risk.
Chemical and morphological characterization of sugarcane bagasse submitted to a delignification process for enhanced enzymatic digestibility
Authors: Rezende Camila Alves , de Lima Marisa Aparecida , Maziero Priscila , deAzevedo Eduardo Ribeiro , Garcia Wanius , Polikarpov Igor 
Published: November 2011

Abstract

Background
In recent years, biorefining of lignocellulosic biomass to produce multi-products such as ethanol and other biomaterials has become a dynamic research area. Pretreatment technologies that fractionate sugarcane bagasse are essential for the successful use of this feedstock in ethanol production. In this paper, we investigate modifications in the morphology and chemical composition of sugarcane bagasse submitted to a two-step treatment, using diluted acid followed by a delignification process with increasing sodium hydroxide concentrations. Detailed chemical and morphological characterization of the samples after each pretreatment condition, studied by high performance liquid chromatography, solid-state nuclear magnetic resonance, diffuse reflectance Fourier transformed infrared spectroscopy and scanning electron microscopy, is reported, together with sample crystallinity and enzymatic digestibility.

Results
Chemical composition analysis performed on samples obtained after different pretreatment conditions showed that up to 96% and 85% of hemicellulose and lignin fractions, respectively, were removed by this two-step method when sodium hydroxide concentrations of 1% (m/v) or higher were used. The efficient lignin removal resulted in an enhanced hydrolysis yield reaching values around 100%. Considering the cellulose loss due to the pretreatment (maximum of 30%, depending on the process), the total cellulose conversion increases significantly from 22.0% (value for the untreated bagasse) to 72.4%. The delignification process, with consequent increase in the cellulose to lignin ratio, is also clearly observed by nuclear magnetic resonance and diffuse reflectance Fourier transformed infrared spectroscopy experiments. We also demonstrated that the morphological changes contributing to this remarkable improvement occur as a consequence of lignin removal from the sample. Bagasse unstructuring is favored by the loss of cohesion between neighboring cell walls, as well as by changes in the inner cell wall structure, such as damaging, hole formation and loss of mechanical resistance, facilitating liquid and enzyme access to crystalline cellulose.

Conclusions
The results presented herewith show the efficiency of the proposed method for improving the enzymatic digestibility of sugarcane bagasse and provide understanding of the pretreatment action mechanism. Combining the different techniques applied in this work warranted thorough information about the undergoing morphological and chemical changes and was an efficient approach to understand the morphological effects resulting from sample delignification and its influence on the enhanced hydrolysis results.
Myc and Miz-1 have coordinate genomic functions including targeting Hox genes in human embryonic stem cells
Authors: Varlakhanova Natalia , Cotterman Rebecca , Bradnam Keith , Korf Ian , Knoepfler Paul S 
Published: November 2011

Abstract

Background
A proposed role for Myc in maintaining mouse embryonic stem (ES) cell pluripotency is transcriptional repression of key differentiation-promoting genes, but detail of the mechanism has remained an important open topic.

Results
To test the hypothesis that the zinc finger protein Miz-1 plays a central role, in the present work we conducted chromatin immunoprecipitation/microarray (ChIP-chip) analysis of Myc and Miz-1 in human ES cells, finding homeobox (Hox) genes as the most significant functional class of Miz-1 direct targets. Miz-1 differentiation-associated target genes specifically lack acetylated lysine 9 and trimethylated lysine 4 of histone H3 (AcH3K9 and H3K4me3) 9 histone marks, consistent with a repressed transcriptional state. Almost 30% of Miz-1 targets are also bound by Myc and these cobound genes are mostly factors that promote differentiation including Hox genes. Knockdown of Myc increased expression of differentiation genes directly bound by Myc and Miz-1, while a subset of the same genes is downregulated by Miz-1 loss-of-function. Myc and Miz-1 proteins interact with each other and associate with several corepressor factors in ES cells, suggesting a mechanism of repression of differentiation genes.

Conclusions
Taken together our data indicate that Miz-1 and Myc maintain human ES cell pluripotency by coordinately suppressing differentiation genes, particularly Hox genes. These data also support a new model of how Myc and Miz-1 function on chromatin.
The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain
Authors: Kim Jae-Sung , Kroin Jeffrey S , Li Xin , An Howard S , Buvanendran Asokumar , Yan Dongyao , Tuman Kenneth J , van Wijnen Andre J , Chen Di , Im Hee-Jeong 
Published: November 2011

Abstract

Introduction

Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats.

Methods

Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model.

Results

After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model.

Conclusions

Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration.
Detection of copeptin in peripheral blood of patients with aneurysmal subarachnoid hemorrhage
Authors: Zhu Xiang-Dong , Chen Jing-Sen , Zhou Feng , Liu Qi-Chang , Chen Gao , Zhang Jian-Min 
Published: November 2011

Abstract
Introduction
Copeptin has been proposed as a prognostic marker in acute illness. This study investigated the ability of copeptin to predict the disease outcome and cerebrovasospasm in the patients with aneurysmal subarachnoid hemorrhage.

Methods
In this retrospective study, 303 consecutive patients were included. Upon admission, plasma copeptin levels were measured by enzyme-linked immunosorbent assay. The end points were mortality after 1 year, in-hospital mortality, cerebrovasospasm and poor functional outcome (Glasgow Outcome Scale score of 1-3) after 1 year.

Results
Upon admission, plasma copeptin level in patients was statistically significantly higher than that in healthy controls. A multivariate analysis showed that plasma copeptin level was an independent predictor of poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm. A receiver operating characteristic curve showed that plasma copeptin level on admission predicted poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm of patients statistically significantly. The area under curve of the copeptin concentration was similar to those of World Federation of Neurological Surgeons (WFNS) score and modified Fisher score for the prediction of poor functional outcome and mortality after 1 year, and in-hospital mortality, but not for the prediction of cerebrovasospasm. In a combined logistic-regression model, copeptin improved the area under curve of WFNS score and modified Fisher score for the prediction of poor functional outcome after 1 year, but not for the prediction of mortality after 1 year, in-hospital mortality, and cerebrovasospasm.

Conclusions
Copeptin level is a useful, complementary tool to predict functional outcome and mortality after aneurysmal subarachnoid hemorrhage.
Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer
Authors: Amir Eitan , Miller Naomi , Geddie William , Freedman Orit , Kassam Farrah , Simmons Christine , Oldfield Maria , Dranitsaris George , Tomlinson George , Laupacis Andreas , Tannock Ian F. , Clemons Mark 
Published: November 2011

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. Results Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. Conclusion Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.
Anthracycline-Related Cardiomyopathy After Childhood Cancer: Role of Polymorphisms in Carbonyl Reductase Genes—A Report From the Children's Oncology Group
Authors: Blanco Javier G. , Sun Can-Lan , Landier Wendy , Chen Lu , Esparza-Duran Diego , Leisenring Wendy , Mays Allison , Friedman Debra L. , Ginsberg Jill P. , Hudson Melissa M. , Neglia Joseph P. , Oeffinger Kevin C. , Ritchey A. Kim , Villaluna Doojduen , Relling Mary V. , Bhatia Smita 
Published: November 2011

Purpose Carbonyl reductases (CBRs) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR1 and CBR3 influence synthesis of these metabolites. We examined whether single nucleotide polymorphisms in CBR1 (CBR1 1096G>A) and/or CBR3 (CBR3 V244M) modified the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors. Patients and Methods One hundred seventy survivors with cardiomyopathy (patient cases) were compared with 317 survivors with no cardiomyopathy (controls; matched on cancer diagnosis, year of diagnosis, length of follow-up, and race/ethnicity) using conditional logistic regression techniques. Results A dose-dependent association was observed between cumulative anthracycline exposure and cardiomyopathy risk (0 mg/m2: reference; 1 to 100 mg/m2: odds ratio [OR], 1.65; 101 to 150 mg/m2: OR, 3.85; 151 to 200 mg/m2: OR, 3.69; 201 to 250 mg/m2: OR, 7.23; 251 to 300 mg/m2: OR, 23.47; > 300 mg/m2: OR, 27.59; Ptrend < .001). Among individuals carrying the variant A allele (CBR1:GA/AA and/or CBR3:GA/AA), exposure to low- to moderate-dose anthracyclines (1 to 250 mg/m2) did not increase the risk of cardiomyopathy. Among individuals with CBR3 V244M homozygous G genotypes (CBR3:GG), exposure to low- to moderate-dose anthracyclines increased cardiomyopathy risk when compared with individuals with CBR3:GA/AA genotypes unexposed to anthracyclines (OR, 5.48; P = .003), as well as exposed to low- to moderate-dose anthracyclines (OR, 3.30; P = .006). High-dose anthracyclines (> 250 mg/m2) were associated with increased cardiomyopathy risk, irrespective of CBR genotype status. Conclusion This study demonstrates increased anthracycline-related cardiomyopathy risk at doses as low as 101 to 150 mg/m2. Homozygosis for G allele in CBR3 contributes to increased cardiomyopathy risk associated with low- to moderate-dose anthracyclines, such that there seems to be no safe dose for patients homozygous for the CBR3 V244M G allele. These results suggest a need for targeted intervention for those at increased risk of cardiomyopathy.