bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges and promises for the development of donor-independent platelet transfusions
Authors: Lambert Michele P. , Sullivan Spencer K. , Fuentes Rudy , French Deborah L. , Poncz Mortimer 
Published: January 2013

Abstract
Platelet transfusions are often a life-saving intervention, and the use of platelet transfusions has been increasing. Donor-derived platelet availability can be challenging. Compounding this concern are additional limitations of donor-derived platelets, including variability in product unit quality and quantity, limited shelf life and the risks of product bacterial contamination, other transfusion-transmitted infections, and immunologic reactions. Because of these issues, there has been an effort to develop strategies to generate platelets from exogenously generated precursor cells. If successful, such platelets have the potential to be a safer, more consistent platelet product, while reducing the necessity for human donations. Moreover, ex vivo–generated autologous platelets or precursors may be beneficial for patients who are refractory to allogeneic platelets. For patients with inherited platelet disorders, ex vivo–generated platelets offer the promise of a treatment via the generation of autologous gene-corrected platelets. Theoretically, ex vivo–generated platelets also offer targeted delivery of ectopic proteins to sites of vascular injury. This review summarizes the current, state-of-the-art methodologies in delivering a clinically relevant ex vivo–derived platelet product, and it discusses significant challenges that must be overcome for this approach to become a clinical reality.
Cophenetic metrics for phylogenetic trees, after Sokal and Rohlf
Authors: Cardona Gabriel , Mir Arnau , Rosselló Francesc , Rotger Lucía , Sánchez David 
Published: January 2013

AbstractBackgroundPhylogenetic tree comparison metrics are an important tool in the study of evolution, and hence the definition of such metrics is an interesting problem in phylogenetics. In a paper in Taxon fifty years ago, Sokal and Rohlf proposed to measure quantitatively the difference between a pair of phylogenetic trees by first encoding them by means of their half-matrices of cophenetic values, and then comparing these matrices. This idea has been used several times since then to define dissimilarity measures between phylogenetic trees but, to our knowledge, no proper metric on weighted phylogenetic trees with nested taxa based on this idea has been formally defined and studied yet. Actually, the cophenetic values of pairs of different taxa alone are not enough to single out phylogenetic trees with weighted arcs or nested taxa.ResultsFor every (rooted) phylogenetic treeT, let itscophenetic vectorφ(T) consist of all pairs of cophenetic values between pairs of taxa inTand all depths of taxa inT. It turns out that these cophenetic vectors single out weighted phylogenetic trees with nested taxa. We then define a family of cophenetic metricsdφ,pby comparing these cophenetic vectors by means ofLpnorms, and we study, either analytically or numerically, some of their basic properties: neighbors, diameter, distribution, and their rank correlation with each other and with other metrics.ConclusionsThe cophenetic metrics can be safely used on weighted phylogenetic trees with nested taxa and no restriction on degrees, and they can be computed inO(n2) time, wherenstands for the number of taxa. The metricsdφ,1anddφ,2have positive skewed distributions, and they show a low rank correlation with the Robinson-Foulds metric and the nodal metrics, and a very high correlation with each other and with the splitted nodal metrics. The diameter ofdφ,p, forp⩾1, is inO(n(p+2)/p), and thus for lowpthey are more discriminative, having a wider range of values.
RNA-Seq analysis reveals new gene models and alternative splicing in the fungal pathogen Fusarium graminearum
Authors: Zhao Chunzhao , Waalwijk Cees , de Wit Pierre J G M , Tang Dingzhong , van der Lee Theo 
Published: January 2013

Abstract

Background
The genome of Fusarium graminearum has been sequenced and annotated previously, but correct gene annotation remains a challenge. In addition, posttranscriptional regulations, such as alternative splicing and RNA editing, are poorly understood in F. graminearum. Here we took advantage of RNA-Seq to improve gene annotations and to identify alternative splicing and RNA editing in F. graminearum.

Results
We identified and revised 655 incorrectly predicted gene models, including revisions of intron predictions, intron splice sites and prediction of novel introns. 231 genes were identified with two or more alternative splice variants, mostly due to intron retention. Interestingly, the expression ratios between different transcript isoforms appeared to be developmentally regulated. Surprisingly, no RNA editing was identified in F. graminearum. Moreover, 2459 novel transcriptionally active regions (nTARs) were identified and our analysis indicates that many of these could be missed genes. Finally, we identified the 5′ UTR and/or 3′ UTR sequences of 7666 genes. A number of representative novel gene models and alternatively spliced genes were validated by reverse transcription polymerase chain reaction and sequencing of the generated amplicons.

Conclusions
We have developed novel and efficient strategies to identify alternatively spliced genes and incorrect gene models based on RNA-Seq data. Our study identified hundreds of alternatively spliced genes in F. graminearum and for the first time indicated that alternative splicing is developmentally regulated in filamentous fungi. In addition, hundreds of incorrect predicted gene models were identified and revised and thousands of nTARs were discovered in our study, which will be helpful for the future genomic and transcriptomic studies in F. graminearum.
Multilevel comparative analysis of the contributions of genome reduction and heat shock to the Escherichia colitranscriptome
Authors: Ying Bei-Wen , Seno Shigeto , Kaneko Fuyuro , Matsuda Hideo , Yomo Tetsuya 
Published: January 2013

AbstractBackgroundBoth large deletions in genome and heat shock stress would lead to alterations in the gene expression profile; however, whether there is any potential linkage between these disturbances to the transcriptome have not been discovered. Here, the relationship between the genomic and environmental contributions to the transcriptome was analyzed by comparing the transcriptomes of the bacteriumEscherichia coli(strain MG1655 and its extensive genomic deletion derivative, MDS42) grown in regular and transient heat shock conditions.ResultsThe transcriptome analysis showed the following: (i) there was a reorganization of the transcriptome in accordance with preferred chromosomal periodicity upon genomic or heat shock perturbation; (ii) there was a considerable overlap between the perturbed regulatory networks and the categories enriched for differentially expressed genes (DEGs) following genome reduction and heat shock; (iii) the genes sensitive to genome reduction tended to be located close to genomic scars, and some were also highly responsive to heat shock; and (iv) the genomic and environmental contributions to the transcriptome displayed not only a positive correlation but also a negatively compensated relationship (i.e., antagonistic epistasis).ConclusionThe contributions of genome reduction and heat shock to theEscherichia colitranscriptome were evaluated at multiple levels. The observations of overlapping perturbed networks, directional similarity in transcriptional changes, positive correlation and epistatic nature linked the two contributions and suggest somehow a crosstalk guiding transcriptional reorganization in response to both genetic and environmental disturbances in bacteriumE.coli.
Adjustment method for microarray data generated using two-cycle RNA labeling protocol
Authors: Wang Fugui , Chen Rui , Ji Dong , Bai Shunong , Qian Minping , Deng Minghua 
Published: January 2013

Abstract

Background
Microarray technology is widely utilized for monitoring the expression changes of thousands of genes simultaneously. However, the requirement of relatively large amount of RNA for labeling and hybridization makes it difficult to perform microarray experiments with limited biological materials, thus leads to the development of many methods for preparing and amplifying mRNA. It is addressed that amplification methods usually bring bias, which may strongly hamper the following interpretation of the results. A big challenge is how to correct for the bias before further analysis.

Results
In this article, we observed the bias in rice gene expression microarray data generated with the Affymetrix one-cycle, two-cycle RNA labeling protocols, followed by validation with Real Time PCR. Based on these data, we proposed a statistical framework to model the processes of mRNA two-cycle linear amplification, and established a linear model for probe level correction. Maximum Likelihood Estimation (MLE) was applied to perform robust estimation of the Retaining Rate for each probe. After bias correction, some known pre-processing methods, such as PDNN, could be combined to finish preprocessing. Then, we evaluated our model and the results suggest that our model can effectively increase the quality of the microarray raw data: (i) Decrease the Coefficient of Variation for PM intensities of probe sets; (ii) Distinguish the microarray samples of five stages for rice stamen development more clearly; (iii) Improve the correlation coefficients among stamen microarray samples. We also discussed the necessity of model adjustment by comparing with another simple adjustment method.

Conclusion
We conclude that the adjustment model is necessary and could effectively increase the quality of estimation for gene expression from the microarray raw data.
RNAi phenotypes are influenced by the genetic background of the injected strain
Authors: Kitzmann Peter , Schwirz Jonas , Schmitt-Engel Christian , Bucher Gregor 
Published: January 2013

Abstract

Background
RNA interference (RNAi) is a powerful tool to study gene function in organisms that are not amenable to classical forward genetics. Hence, together with the ease of comprehensively identifying genes by new generation sequencing, RNAi is expanding the scope of animal species and questions that can be addressed in terms of gene function. In the case of genetic mutants, the genetic background of the strains used is known to influence the phenotype while this has not been described for RNAi experiments.

Results
Here we show in the red flour beetle Tribolium castaneum that RNAi against Tc-importin α1 leads to different phenotypes depending on the injected strain. We rule out off target effects and show that sequence divergence does not account for this difference. By quantitatively comparing phenotypes elicited by RNAi knockdown of four different genes we show that there is no general difference in RNAi sensitivity between these strains. Finally, we show that in case of Tc-importin α1 the difference depends on the maternal genotype.

Conclusions
These results show that in RNAi experiments strain specific differences have to be considered and that a proper documentation of the injected strain is required. This is especially important for the increasing number of emerging model organisms that are being functionally investigated using RNAi. In addition, our work shows that RNAi is suitable to systematically identify the differences in the gene regulatory networks present in populations of the same species, which will allow novel insights into the evolution of animal diversity.
Functional analysis of the ATP-binding cassette (ABC) transporter gene family of Tribolium castaneum
Authors: Broehan Gunnar , Kroeger Tobias , Lorenzen Marcé , Merzendorfer Hans 
Published: January 2013

AbstractBackgroundThe ATP-binding cassette (ABC) transporters belong to a large superfamily of proteins that have important physiological functions in all living organisms. Most are integral membrane proteins that transport a broad spectrum of substrates across lipid membranes. In insects, ABC transporters are of special interest because of their role in insecticide resistance.ResultsWe have identified 73 ABC transporter genes in the genome ofT. castaneum, which group into eight subfamilies (ABCA-H). This coleopteran ABC family is significantly larger than those reported for insects in other taxonomic groups. Phylogenetic analysis revealed that this increase is due to gene expansion within a single clade of subfamily ABCC. We performed an RNA interference (RNAi) screen to study the function of ABC transporters during development. In ten cases, injection of double-stranded RNA (dsRNA) into larvae caused developmental phenotypes, which included growth arrest and localized melanization, eye pigmentation defects, abnormal cuticle formation, egg-laying and egg-hatching defects, and mortality due to abortive molting and desiccation. Some of the ABC transporters we studied in closer detail to examine their role in lipid, ecdysteroid and eye pigment transport.ConclusionsThe results from our study provide new insights into the physiological function of ABC transporters inT. castaneum,and may help to establish new target sites for insect control.
A new computational approach redefines the subtelomeric vir superfamily of Plasmodium vivax
Authors: Lopez Francisco Javier , Bernabeu Maria , Fernandez-Becerra Carmen , del Portillo Hernando A 
Published: January 2013

Abstract

Background
Subtelomeric multigene families of malaria parasites encode virulent determinants. The published genome sequence of Plasmodium vivax revealed the largest subtelomeric multigene family of human malaria parasites, the vir super-family, presently composed of 346 vir genes subdivided into 12 different subfamilies based on sequence homologies detected by BLAST.

Results
A novel computational approach was used to redefine vir genes. First, a protein-weighted graph was built based on BLAST alignments. This graph was processed to ensure that edge weights are not exclusively based on the BLAST score between the two corresponding proteins, but strongly dependant on their graph neighbours and their associations. Then the Markov Clustering Algorithm was applied to the protein graph. Next, the Homology Block concept was used to further validate this clustering approach. Finally, proteome-wide analysis was carried out to predict new VIR members. Results showed that (i) three previous subfamilies cannot longer be classified as vir genes; (ii) most previously unclustered vir genes were clustered into vir subfamilies; (iii) 39 hypothetical proteins were predicted as VIR proteins; (iv) many of these findings are supported by a number of structural and functional evidences, sub-cellular localization studies, gene expression analysis and chromosome localization (v) this approach can be used to study other multigene families in malaria.

Conclusions
This methodology, resource and new classification of vir genes will contribute to a new structural framing of this multigene family and other multigene families of malaria parasites, facilitating the design of experiments to understand their role in pathology, which in turn may help furthering vaccine development.
Identification of miRNAs and their targets using high-throughput sequencing and degradome analysis in cytoplasmic male-sterile and its maintainer fertile lines of Brassica juncea
Authors: Yang Jinghua , Liu Xunyan , Xu Baochen , Zhao Na , Yang Xiaodong , Zhang Mingfang 
Published: January 2013

Abstract

Background
Regulatory network of cytoplasmic male sterility (CMS) occurrence is still largely unknown in plants, although numerous researches have been attempted to isolate genes involved in CMS. Here, we employed high-throughput sequencing and degradome analysis to identify microRNAs and their targets using high-throughput sequencing in CMS and its maintainer fertile (MF) lines of Brassica juncea.

Results
We identified 197 known and 78 new candidate microRNAs during reproductive development of B. juncea. A total of 47 differentially expressed microRNAs between CMS and its MF lines were discovered, according to their sequencing reads number. Different expression levels of selected microRNAs were confirmed by using real-time quantitative PCR between CMS and MF lines. Furthermore, we observed that the transcriptional patterns of these microRNAs could be mimicked by artificially inhibiting mitochondrial F1F0-ATPase activity and its function in MF line by using treatment with oligomycin. Targeted genes of the microRNAs were identified by high-throughput sequencing and degradome approaches, including auxin response factor, NAC (No Apical Meristem) domain transcription factor, GRAS family transcription factor, MYB transcription factor, squamosa promoter binding protein, AP2-type transcription factor, homeobox/homeobox-leucine zipper family and TCP family transcription factors, which were observed to be differentially expressed between CMS and MF.

Conclusion
Taken together, from these findings we suggested microRNA might participate in the regulatory network of CMS by tuning fork in gene expressions in CMS B. juncea. The differential expression of miRNAs observed between CMS and MF lines suggested that biogenesis of miRNAs could be influenced in the CMS.
The impact of MFG-E8 in chronic pancreatitis: potential for future immunotherapy?
Authors: D’Haese Jan G , Demir Ihsan Ekin , Kehl Timo , Winckler Jannik , Giese Nathalia A , Bergmann Frank , Giese Thomas , Büchler Markus W , Friess Helmut , Hartel Mark , Ceyhan Güralp O 
Published: January 2013

Abstract

Background
The glycoprotein MFG-E8 mediates phagocytic clearance of apoptotic cells and influences the pathogenesis and progression of inflammatory diseases. MFG-E8 was shown to attenuate the progression of inflammation and to improve survival in septic rats. Accumulating evidence suggests an immunomodulatory link between MFG-E8 and the pro-inflammatory chemokine fractalkine, which may determine the severity of pain, fibrosis, and inflammation in chronic pancreatitis (CP).

Methods
The expression and localization of MFG-E8 was investigated in CP (n = 62), and normal pancreas (NP; n = 34) by QRT-PCR, Western-blot and immunohistochemistry analyses. Results were correlated with mRNA expression of fractalkine, CX3CR1, and with the presence and degree of pain and fibrosis. Human pancreatic stellate cells (hPSCs) were isolated from CP tissues and evaluated for MFG-E8 mRNA expression after fractalkine stimulation.

Results
MFG-E8-mRNA was significantly overexpressed in CP and isolated hPSCs when compared to NP. Western-blot and immunohistochemistry analysis confirmed accumulation of MFG-E8 in CP, with noticeably increased MFG-E8 immunoreactivity in tubular complexes. MFG-E8 expression correlated significantly with fractalkine expression, severe fibrosis, and the presence of pain in CP patients. Stimulation of hPSCs with fractalkine led to a significant increase in MFG-E8 expression.

Conclusions
In the present study, we demonstrated for the first time that MFG-E8 is significantly up-regulated in CP patients and together with fractalkine correlated noticeably with severe fibrosis and the presence of pain. hPSCs overexpress MFG-E8 upon fractalkine stimulation in vitro, which underlines the suggested immunmodulatory link in CP and may be a key mechanism in CP fibrogenesis and pain generation. Taken together, these novel findings suggest that MFG-E8 blockade may be a promising tool for future immunotherapy in CP to attenuate both fibrosis and pain sensation.
Radiofrequency ablation of liver tumors: quantitative assessment of tumor coverage through CT image processing
Authors: Passera Katia , Selvaggi Sabrina , Scaramuzza Davide , Garbagnati Francesco , Vergnaghi Daniele , Mainardi Luca 
Published: January 2013

Abstract

Background
Radiofrequency ablation (RFA) is one of the most promising non-surgical treatments for hepatic tumors. The assessment of the therapeutic efficacy of RFA is usually obtained by visual comparison of pre- and post-treatment CT images, but no numerical quantification is performed.

Methods
In this work, a novel method aiming at providing a more objective tool for the evaluation of RFA coverage is described. Image registration and segmentation techniques were applied to enable the visualization of the tumor and the corresponding post-RFA necrosis in the same framework. In addition, a set of numerical indexes describing tumor/necrosis overlap and their mutual position were computed.

Results
After validation of segmentation step, the method was applied on a dataset composed by 10 tumors, suspected not to be completed treated. Numerical indexes showed that only two tumors were totally treated and the percentage of a residual tumor was in the range of 5.12%-35.92%.

Conclusions
This work represents a first attempt to obtain a quantitative tool aimed to assess the accuracy of RFA treatment. The possibility to visualize the tumor and the correspondent post-RFA necrosis in the same framework and the definition of some synthetic numerical indexes could help clinicians in ameliorating RFA treatment.
Jugular venous reflux and plasma endothelin-1 are associated with cough syncope: a case control pilot study
Authors: Chung Chih-Ping , Cheng Chun-Yu , Zivadinov Robert , Chen Wei-Chih , Sheng Wen-Yung , Lee Yu-Chin , Hu Han-Hwa , Hsu Hung-Yi , Yang Kuang-Yao 
Published: January 2013

Abstract

Background
Jugular venous reflux (JVR) has been reported to cause cough syncope via retrograde-transmitted venous hypertension and consequently decreased cerebral blood flow (CBF). Unmatched frequencies of JVR and cough syncope led us to postulate that there should be additional factors combined with JVR to exaggerate CBF decrement during cough, leading to syncope. The present pilot study tested the hypothesis that JVR, in addition to an increased level of plasma endothelin-1 (ET-1), a potent vasoconstrictor, is involved in the pathophysiology of cough syncope.

Methods
Seventeen patients with cough syncope or pre-syncope (Mean[SD] = 74.63(12.37) years; 15 males) and 51 age/gender-matched controls received color-coded duplex ultrasonography for JVR determination and plasma ET-1 level measurements.

Results
Multivariate logistic analysis showed that the presence of both-side JVR (odds ratio [OR] = 10.77, 95% confident interval [CI] = 2.40-48.35, p = 0.0019) and plasma ET-1 > 3.43 pg/ml (OR = 14.57, 95% CI = 2.95-71.59, p = 0.001) were independently associated with the presence of cough syncope/ pre-syncope respectively. There was less incidence of cough syncope/ pre-syncope in subjects with the absence of both-side JVR and a plasma ET-1 ≦3.43 pg/ml. Presence of both side JVR and plasma ET-1 level of > 3.43 pg/ml, increased risk for cough syncope/pre-syncope (p < 0.001).

Conclusions
JVR and higher plasma levels of ET-1 are associated with cough syncope/ pre-syncope. Although sample size of this study was small, we showed a synergistic effect between JVR and plasma ET-1 levels on the occurrence of cough syncope/pre-syncope. Future studies should confirm our pilot findings.