bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human memory B cells originate from three distinct germinal center-dependent and -independent maturation pathways
Authors: Berkowska Magdalena A. , Driessen Gertjan J. A. , Bikos Vasilis , Grosserichter-Wagener Christina , Stamatopoulos Kostas , Cerutti Andrea , He Bing , Biermann Katharina , Lange Johan F. , van der Burg Mirjam , van Dongen Jacques J. M. , van Zelm Menno C. 
Published: June 2011

AbstractMultiple distinct memory B-cell subsets have been identified in humans, but it remains unclear how their phenotypic diversity corresponds to the type of responses from which they originate. Especially, the contribution of germinal center-independent responses in humans remains controversial. We defined 6 memory B-cell subsets based on their antigen-experienced phenotype and differential expression of CD27 and IgH isotypes. Molecular characterization of their replication history, Ig somatic hypermutation, and class-switch profiles demonstrated their origin from 3 different pathways. CD27−IgG+ and CD27+IgM+ B cells are derived from primary germinal center reactions, and CD27+IgA+ and CD27+IgG+ B cells are from consecutive germinal center responses (pathway 1). In contrast, natural effector and CD27−IgA+ memory B cells have limited proliferation and are also present in CD40L-deficient patients, reflecting a germinal center-independent origin. Natural effector cells at least in part originate from systemic responses in the splenic marginal zone (pathway 2). CD27−IgA+ cells share low replication history and dominant Igλ and IgA2 use with gut lamina propria IgA+ B cells, suggesting their common origin from local germinal center-independent responses (pathway 3). Our findings shed light on human germinal center-dependent and -independent B-cell memory formation and provide new opportunities to study these processes in immunologic diseases.
Mapping quantitative trait loci (QTL) in sheep. IV. Analysis of lactation persistency and extended lactation traits in sheep
Authors: Jonas Elisabeth , Thomson Peter C , Hall Evelyn JS , McGill David , Lam Mary K , Raadsma Herman W 
Published: June 2011

Abstract

Background
In sheep dairy production, total lactation performance, and length of lactation of lactation are of economic significance. A more persistent lactation has been associated with improved udder health. An extended lactation is defined by a longer period of milkability. This study is the first investigation to examine the presence of quantitative trait loci (QTL) for extended lactation and lactation persistency in sheep.

Methods
An (Awassi × Merino) × Merino single-sire backcross family with 172 ewes was used to map QTL for lactation persistency and extended lactation traits on a framework map of 189 loci across all autosomes. The Wood model was fitted to data from multiple lactations to estimate parameters of ovine lactation curves, and these estimates were used to derive measures of lactation persistency and extended lactation traits of milk, protein, fat, lactose, useful yield, and somatic cell score. These derived traits were subjected to QTL analyses using maximum likelihood estimation and regression analysis.

Results
Overall, one highly significant (LOD > 3.0), four significant (2.0 < LOD < 3.0) and five suggestive (1.7 < LOD < 2.0) QTL were detected across all traits in common by both mapping methods. One additional suggestive QTL was identified using maximum likelihood estimation, and four suggestive (0.01 < P < 0.05) and two significant (P < 0.01) QTL using the regression approach only. All detected QTL had effect sizes in the range of 0.48 to 0.64 SD, corresponding to QTL heritabilities of 3.1 to 8.9%. The comparison of the detected QTL with results in cattle showed conserved linkage regions. Most of the QTL identified for lactation persistency and extended lactation did not coincide. This suggests that persistency and extended lactation for the same as well as different milk yield and component traits are not controlled by the same genes.

Conclusion
This study identified ten novel QTL for lactation persistency and extended lactation in sheep, but results suggest that lactation persistency and extended lactation do not have a major gene in common. These results provide a basis for further validation in extended families and other breeds as well as targeting regions for genome-wide association mapping using high-density SNP arrays.
PhyloMap: an algorithm for visualizing relationships of large sequence data sets and its application to the influenza A virus genome
Authors: Zhang Jiajie , Mamlouk Amir Madany , Martinetz Thomas , Chang Suhua , Wang Jing , Hilgenfeld Rolf 
Published: June 2011

Abstract

Background
Results of phylogenetic analysis are often visualized as phylogenetic trees. Such a tree can typically only include up to a few hundred sequences. When more than a few thousand sequences are to be included, analyzing the phylogenetic relationships among them becomes a challenging task. The recent frequent outbreaks of influenza A viruses have resulted in the rapid accumulation of corresponding genome sequences. Currently, there are more than 7500 influenza A virus genomes in the database. There are no efficient ways of representing this huge data set as a whole, thus preventing a further understanding of the diversity of the influenza A virus genome.

Results
Here we present a new algorithm, "PhyloMap", which combines ordination, vector quantization, and phylogenetic tree construction to give an elegant representation of a large sequence data set. The use of PhyloMap on influenza A virus genome sequences reveals the phylogenetic relationships of the internal genes that cannot be seen when only a subset of sequences are analyzed.

Conclusions
The application of PhyloMap to influenza A virus genome data shows that it is a robust algorithm for analyzing large sequence data sets. It utilizes the entire data set, minimizes bias, and provides intuitive visualization. PhyloMap is implemented in JAVA, and the source code is freely available at http://www.biochem.uni-luebeck.de/public/software/phylomap.html
NORMA-Gene: A simple and robust method for qPCR normalization based on target gene data
Authors: Heckmann Lars-Henrik , Sørensen Peter B , Krogh Paul Henning , Sørensen Jesper G 
Published: June 2011

Abstract

Background
Normalization of target gene expression, measured by real-time quantitative PCR (qPCR), is a requirement for reducing experimental bias and thereby improving data quality. The currently used normalization approach is based on using one or more reference genes. Yet, this approach extends the experimental work load and suffers from assumptions that may be difficult to meet and to validate.

Results
We developed a data driven normalization algorithm (NORMA-Gene). An analysis of the performance of NORMA-Gene compared to reference gene normalization on artificially generated data-sets showed that the NORMA-Gene normalization yielded more precise results under a large range of parameters tested. Furthermore, when tested on three very different real qPCR data-sets NORMA-Gene was shown to be best at reducing variance due to experimental bias in all three data-sets compared to normalization based on the use of reference gene(s).

Conclusions
Here we present the NORMA-Gene algorithm that is applicable to all biological and biomedical qPCR studies, especially those that are based on a limited number of assayed genes. The method is based on a data-driven normalization and is useful for as little as five target genes comprising the data-set. NORMA-Gene does not require the identification and validation of reference genes allowing researchers to focus their efforts on studying target genes of biological relevance.
Determinants of antigenicity and specificity in immune response for protein sequences
Authors: Wang Yulong , Wu Wenjun , Negre Nicolas N , White Kevin P , Li Cheng , Shah Parantu K 
Published: June 2011

Abstract

Background
Target specific antibodies are pivotal for the design of vaccines, immunodiagnostic tests, studies on proteomics for cancer biomarker discovery, identification of protein-DNA and other interactions, and small and large biochemical assays. Therefore, it is important to understand the properties of protein sequences that are important for antigenicity and to identify small peptide epitopes and large regions in the linear sequence of the proteins whose utilization result in specific antibodies.

Results
Our analysis using protein properties suggested that sequence composition combined with evolutionary information and predicted secondary structure, as well as solvent accessibility is sufficient to predict successful peptide epitopes. The antigenicity and the specificity in immune response were also found to depend on the epitope length. We trained the B-Cell Epitope Oracle (BEOracle), a support vector machine (SVM) classifier, for the identification of continuous B-Cell epitopes with these protein properties as learning features. The BEOracle achieved an F1-measure of 81.37% on a large validation set. The BEOracle classifier outperformed the classical methods based on propensity and sophisticated methods like BCPred and Bepipred for B-Cell epitope prediction. The BEOracle classifier also identified peptides for the ChIP-grade antibodies from the modENCODE/ENCODE projects with 96.88% accuracy. High BEOracle score for peptides showed some correlation with the antibody intensity on Immunofluorescence studies done on fly embryos. Finally, a second SVM classifier, the B-Cell Region Oracle (BROracle) was trained with the BEOracle scores as features to predict the performance of antibodies generated with large protein regions with high accuracy. The BROracle classifier achieved accuracies of 75.26-63.88% on a validation set with immunofluorescence, immunohistochemistry, protein arrays and western blot results from Protein Atlas database.

Conclusions
Together our results suggest that antigenicity is a local property of the protein sequences and that protein sequence properties of composition, secondary structure, solvent accessibility and evolutionary conservation are the determinants of antigenicity and specificity in immune response. Moreover, specificity in immune response could also be accurately predicted for large protein regions without the knowledge of the protein tertiary structure or the presence of discontinuous epitopes. The dataset prepared in this work and the classifier models are available for download at https://sites.google.com/site/oracleclassifiers/.
Analysis of expressed sequence tags generated from full-length enriched cDNA libraries of melon
Authors: Clepet Christian , Joobeur Tarek , Zheng Yi , Jublot Delphine , Huang Mingyun , Truniger Veronica , Boualem Adnane , Hernandez-Gonzalez Maria Elena , Dolcet-Sanjuan Ramon , Portnoy Vitaly , Mascarell-Creus Albert , Caño-Delgado Ana I , Katzir Nurit , Bendahmane Abdelhafid , Giovannoni James J , Aranda Miguel A , Garcia-Mas Jordi , Fei Zhangjun 
Published: June 2011

Abstract

Background
Melon (Cucumis melo), an economically important vegetable crop, belongs to the Cucurbitaceae family which includes several other important crops such as watermelon, cucumber, and pumpkin. It has served as a model system for sex determination and vascular biology studies. However, genomic resources currently available for melon are limited.

Result
We constructed eleven full-length enriched and four standard cDNA libraries from fruits, flowers, leaves, roots, cotyledons, and calluses of four different melon genotypes, and generated 71,577 and 22,179 ESTs from full-length enriched and standard cDNA libraries, respectively. These ESTs, together with ~35,000 ESTs available in public domains, were assembled into 24,444 unigenes, which were extensively annotated by comparing their sequences to different protein and functional domain databases, assigning them Gene Ontology (GO) terms, and mapping them onto metabolic pathways. Comparative analysis of melon unigenes and other plant genomes revealed that 75% to 85% of melon unigenes had homologs in other dicot plants, while approximately 70% had homologs in monocot plants. The analysis also identified 6,972 gene families that were conserved across dicot and monocot plants, and 181, 1,192, and 220 gene families specific to fleshy fruit-bearing plants, the Cucurbitaceae family, and melon, respectively. Digital expression analysis identified a total of 175 tissue-specific genes, which provides a valuable gene sequence resource for future genomics and functional studies. Furthermore, we identified 4,068 simple sequence repeats (SSRs) and 3,073 single nucleotide polymorphisms (SNPs) in the melon EST collection. Finally, we obtained a total of 1,382 melon full-length transcripts through the analysis of full-length enriched cDNA clones that were sequenced from both ends. Analysis of these full-length transcripts indicated that sizes of melon 5' and 3' UTRs were similar to those of tomato, but longer than many other dicot plants. Codon usages of melon full-length transcripts were largely similar to those of Arabidopsis coding sequences.

Conclusion
The collection of melon ESTs generated from full-length enriched and standard cDNA libraries is expected to play significant roles in annotating the melon genome. The ESTs and associated analysis results will be useful resources for gene discovery, functional analysis, marker-assisted breeding of melon and closely related species, comparative genomic studies and for gaining insights into gene expression patterns.
Ten-Color flow cytometry reveals distinct patterns of expression of CD124 and CD126 by developing thymocytes
Authors: Tan Chibing , Taylor Ashlee A , Coburn Matthew Z , Marino Julie H , Van De Wiele C Justin , Teague T Kent 
Published: June 2011

AbstractBackgroundWe have developed a 12-parameter/10-color flow cytometric staining method for the simultaneous detection and characterization of 21 mouse thymocyte subpopulations that represent discreet stages of T cell development. To demonstrate the utility of this method, we assessed cytokine receptor expression on mouse thymocyte subsets. These experiments revealed distinct patterns of surface expression of receptors for the cytokines IL-4 and IL-6.ResultsThe IL-4 receptor α chain (CD124) was highly expressed on the earliest thymocyte subsets, then downregulated prior to T cell receptor β-selection and finally upregulated in the CD4/CD8 double positive cells prior to positive selection. The IL-6 receptor α chain (CD126) showed a different pattern of expression. It was expressed on the most mature subsets within the CD4 and CD8 single positive (SP) compartments and was absent on all other thymocytes with the exception of a very small cKit-CD4-CD8-population. Intracellular staining of SP thymocytes for phosphorylated STAT-1 demonstrated that IL-6 signaling was confined to the most mature SP subsets.ConclusionsThis 12-parameter staining methodology uses only commercially available fluorochrome-coupled monoclonal antibodies and therefore could be employed by any investigator with access to a 4-laser flow cytometer. This novel staining scheme allowed us to easily phenotype thymocyte subpopulations that span across development, from the early thymic progenitors (ETPs) to the most mature subsets of the CD4 and CD8 single positive populations.
The non-motile phenotype of Salmonella hha ydgT mutants is mediated through PefI-SrgD
Authors: Wallar Lauren E , Bysice Andrew M , Coombes Brian K 
Published: June 2011

AbstractBackgroundTwo ancestral nucleoid-associated proteins called Hha and YdgT contribute to the negative regulation of several virulence-associated genes inSalmonella entericaserovar Typhimurium. Our previous work showed that Hha and YdgT proteins are required for negative regulation ofSalmonellaPathogenicity Island-2 and thathha ydgTdouble mutants are attenuated for murine infection. Interestingly,hha ydgTmutant bacteria exhibited a non-motile phenotype suggesting that Hha and YdgT have a role in flagellar regulation.ResultsIn this study we show that the non-motile phenotype ofhha ydgTmutants is due to decreased levels of the master transcriptional regulator FlhD4C2resulting in down-regulation of class II/III and class III flagellar promoters and lack of surface flagella on these cells. The horizontally acquiredpefI-srgDregion was found to be partially responsible for this phenotype since deletion ofpefI-srgDin ahha ydgTdeletion background resulted in transient restoration of class II/III and III transcription, expression of surface flagella, and motility in the quadruple mutant.ConclusionThese data extend our current understanding of the mechanisms through which Hha and YdgT regulate flagellar biosynthesis and further describe howS. Typhimurium has integrated horizontal gene acquisitions into ancestral regulatory networks.
The Arabidopsis translocator protein (AtTSPO) is regulated at multiple levels in response to salt stress and perturbations in tetrapyrrole metabolism
Authors: Balsemão-Pires Emilia , Jaillais Yvon , Olson Bradley JSC , Andrade Leonardo R , Umen James G , Chory Joanne , Sachetto-Martins Gilberto 
Published: June 2011

Abstract

Background
The translocator protein 18 kDa (TSPO), previously known as the peripheral-type benzodiazepine receptor (PBR), is important for many cellular functions in mammals and bacteria, such as steroid biosynthesis, cellular respiration, cell proliferation, apoptosis, immunomodulation, transport of porphyrins and anions. Arabidopsis thaliana contains a single TSPO/PBR-related gene with a 40 amino acid N-terminal extension compared to its homologs in bacteria or mammals suggesting it might be chloroplast or mitochondrial localized.

Results
To test if the TSPO N-terminal extension targets it to organelles, we fused three potential translational start sites in the TSPO cDNA to the N-terminus of GFP (AtTSPO:eGFP). The location of the AtTSPO:eGFP fusion protein was found to depend on the translational start position and the conditions under which plants were grown. Full-length AtTSPO:eGFP fusion protein was found in the endoplasmic reticulum and in vesicles of unknown identity when plants were grown in standard conditions. However, full length AtTSPO:eGFP localized to chloroplasts when grown in the presence of 150 mM NaCl, conditions of salt stress. In contrast, when AtTSPO:eGFP was truncated to the second or third start codon at amino acid position 21 or 42, the fusion protein co-localized with a mitochondrial marker in standard conditions. Using promoter GUS fusions, qRT-PCR, fluorescent protein tagging, and chloroplast fractionation approaches, we demonstrate that AtTSPO levels are regulated at the transcriptional, post-transcriptional and post-translational levels in response to abiotic stress conditions. Salt-responsive genes are increased in a tspo-1 knock-down mutant compared to wild type under conditions of salt stress, while they are decreased when AtTSPO is overexpressed. Mutations in tetrapyrrole biosynthesis genes and the application of chlorophyll or carotenoid biosynthesis inhibitors also affect AtTSPO expression.

Conclusion
Our data suggest that AtTSPO plays a role in the response of Arabidopsis to high salt stress. Salt stress leads to re-localization of the AtTSPO from the ER to chloroplasts through its N-terminal extension. In addition, our results show that AtTSPO is regulated at the transcriptional level in tetrapyrrole biosynthetic mutants. Thus, we propose that AtTSPO may play a role in transporting tetrapyrrole intermediates during salt stress and other conditions in which tetrapyrrole metabolism is compromised.
Concordance of self-reported and medical chart information on cancer diagnosis and treatment
Authors: Gupta Vinay , Gu Kai , Chen Zhi , Lu Wei , Shu Xiao Ou , Zheng Ying 
Published: June 2011

Abstract

Background
Self-reported information is an important tool for collecting clinical information for epidemiologic studies and in clinical settings where electronic medical records are not employed and shared.

Methods
Using data collected from the Shanghai Breast Cancer Survival Study (SBCSS), a population-based, prospective cohort study of 5,042 women diagnosed with breast cancer in Shanghai, China, we compared the concordance of patient questionnaire responses to a survey administered approximately 6 months after cancer diagnosis with medical chart information obtained from the diagnostic hospitals for several disease and treatment-related variables.

Results
Of 5,042 SBCSS participants, medical chart information was available for 4,948 women (98.1%). Concordance between patient self-reported and medical chart information was high for the majority of disease-related variables, including: diagnosing hospital (agreement: 98.7%, kappa: 0.99), type of surgery conducted (94.0%, 0.53), ER/PR status (94.5%, 0.91), and tumor position (98.2%, 0.97), as well as for important calendar dates, such as date of diagnosis, surgery, and first chemotherapy treatment. The 10 most commonly used chemotherapeutic drugs were all reported with agreement rates of at least 82%, with associated kappa values that ranged from 0.41 for calcium folinate to 0.76 for vinorelbine.

Conclusions
Our study found high validity for patient self-reported information for a variety of disease and treatment-related variables, suggesting the utility of self-reports as an important source of clinical information for both epidemiological research and patient care.
Fully covered self-expanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model
Authors: Bakhru Mihir R , Foley Patricia L , Gatesman Jeremy , Schmitt Timothy , Moskaluk Christopher A , Kahaleh Michel 
Published: June 2011

Abstract

Background
Fully covered Self-Expanding metal stents (FCSEMS) have been shown efficacious in palliating malignant biliary obstructions. There is little data analyzing mucosal response to their temporary placement in the bile duct.

Methods
Ten mini pigs underwent endoscopic placement of a FCSEMS (Wallflex, Boston Scientific). FCSEMS were kept in place for three months. At the end of the 3 months, FCSEMS were removed endoscopically. Five pigs were euthanized and their bile ducts harvested. The other five were kept alive for another month post removal. A single pathologist, created a scoring system (to determine degree of inflammation, fibrosis, and epithelial injury), examined all specimens in a blinded fashion.

Results
Four FCSEMS spontaneously migrated in the duodenum. On post mortem examination, mild mucosal thickness was noted in three bile duct specimens while superficial inflammation of the bile duct was noted in five animals. Histologic examination of the bile duct revealed focal acute inflammation in both groups. For the 5 animals euthanized immediately after stent removal, there was a tendency to have superficial mucosal erosion and fibrosis. In contrast, increased chronic inflammation was more commonly seen in the animals 1 month post stent removal, with all animals in this group showing moderate degrees of mononuclear inflammatory cell mucosal infiltrates. No severe inflammatory or fibrotic duct injury was observed in any of the study animals, with degree of injury graded as mild to moderate.

Conclusion
FCSEMS appear to induce minimal tissue overgrowth or fibrosis post placement. Ease of removability and no significant histologic injury are advantages noted with FCSEMS., however, further studies are needed to evaluate treating benign biliary strictures with FCSEMS in humans.