bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mast Cell Inhibition Attenuates Myocardial Damage, Adverse Remodeling, and Dysfunction During Fulminant Myocarditis in the Rat
Authors: Mina Yair , Rinkevich-Shop Shunit , Konen Eli , Goitein Orly , Kushnir Tammar , Epstein Frederick H. , Feinberg Micha S. , Leor Jonathan , Landa-Rouben Natalie 
Published: November 2012

Background: Myocarditis is a life-threatening heart disease characterized by myocardial inflammation, necrosis, and chronic fibrosis. While mast cell inhibition has been suggested to prevent fibrosis in rat myocarditis, little is known about its effectiveness in attenuating cardiac remodeling and dysfunction in myocarditis. Thus, we sought to test the hypothesis that mast cell inhibition will attenuate the inflammatory reaction and associated left ventricular (LV) remodeling and dysfunction after fulminant autoimmune myocarditis. Methods and Results: To induce experimental autoimmune myocarditis, we immunized 30 rats with porcine cardiac myosin (PCM) twice at a 7-day interval. On day 8 animals were randomized into treatment with either an intraperitoneal (IP) injection of 25mg/kg of cromolyn sodium (n = 13) or an equivalent volume (∼0.5 mL IP) of normal saline (n = 11). All animals were scanned by serial echocardiography studies before treatment (baseline echocardiogram) and after 20 days of cromolyn sodium (28 days after immunization). Furthermore, serial cardiac magnetic resonance was performed in a subgroup of 12 animals. After 20 days of treatment (28 days from first immunization), hearts were harvested for histopathological analysis. By echocardiography, cromolyn sodium prevented LV dilatation and attenuated LV dysfunction, compared with controls. Postmortem analysis of hearts showed that cromolyn sodium reduced myocardial fibrosis, as well as the number and size of cardiac mast cells in the inflamed myocardium, compared with controls. Conclusions: Our study suggests that mast cell inhibition with cromolyn sodium attenuates adverse LV remodeling and dysfunction in myocarditis. This mechanism-based therapy is clinically relevant and could improve the outcome of patients at risk for inflammatory cardiomyopathy and heart failure.
Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study
Authors: Saleh Mansoor N. , Bussel James B. , Cheng Gregory , Meyer Oliver , Bailey Christine K. , Arning Michael , Brainsky Andres 
Published: November 2012

Abstract
Patients with chronic immune thrombocytopenia may have bleeding resulting from low platelet counts. Eltrombopag increases and maintains hemostatic platelet counts; however, to date, outcome has been reported only for treatment lasting ≤ 6 months. This interim analysis of the ongoing open-label EXTEND (Eltrombopag eXTENded Dosing) study evaluates the safety and efficacy of eltrombopag in 299 patients treated up to 3 years. Splenectomized and nonsplenectomized patients achieved platelets ≥ 50 000/μL at least once (80% and 88%, respectively). Platelets ≥ 50 000/μL and 2 × baseline were maintained for a median of 73 of 104 and 109 of 156 cumulative study weeks, respectively. Bleeding symptoms (World Health Organization Grades 1-4) decreased from 56% of patients at baseline to 20% at 2 years and 11% at 3 years. One hundred (33%) patients were receiving concomitant treatments at study entry, 69 of whom attempted to reduce them; 65% (45 of 69) had a sustained reduction or permanently stopped ≥ 1 concomitant treatment. Thirty-eight patients (13%) experienced ≥ 1 adverse events leading to study withdrawal, including patients meeting protocol-defined withdrawal criteria (11 [4%] thromboembolic events, 5 [2%] exceeding liver enzyme thresholds). No new or increased incidence of safety issues was identified. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts in the desired range. This study is registered at www.clinicaltrials.gov as NCT00351468.
A novel function for FOXP3 in humans: intrinsic regulation of conventional T cells
Authors: McMurchy Alicia N. , Gillies Jana , Gizzi Maria Concetta , Riba Michela , Garcia-Manteiga Jose Manuel , Cittaro Davide , Lazarevic Dejan , Di Nunzio Sara , Piras Ignazio S. , Bulfone Alessandro , Roncarolo Maria Grazia , Stupka Elia , Bacchetta Rosa , Levings Megan K. 
Published: November 2012

Key Points
FOXP3 functions as a negative regulator of T-cell proliferation and cytokine production in human conventional T cells. Expression of FOXP3 in human Th17 cells functions to suppress IFN-γ production.
Human ESC-derived hemogenic endothelial cells undergo distinct waves of endothelial to hematopoietic transition
Authors: Rafii Shahin , Kloss Christopher C. , Butler Jason M. , Ginsberg Michael , Gars Eric , Lis Raphael , Zhan Qiansheng , Josipovic Pavle , Ding Bi-Sen , Xiang Jenny , Elemento Olivier , Zaninovic Nikica , Rosenwaks Zev , Sadelain Michel , Rafii Jeremie A. , James Daylon 
Published: November 2012

Key PointsLive imaging of endothelial to hematopoietic conversion identifies distinct subpopulations of hESC-derived hemogenic endothelium. Expression of the Notch ligand DII4 on vascular ECs drives induction of myeloid fate from hESC-derived hematopoietic progenitors.
Overexpression of uridine diphospho glucuronosyltransferase 2B17 in high-risk chronic lymphocytic leukemia
Authors: Gruber Michaela , Bellemare Judith , Hoermann Gregor , Gleiss Andreas , Porpaczy Edit , Bilban Martin , Le Trang , Zehetmayer Sonja , Mannhalter Christine , Gaiger Alexander , Shehata Medhat , Fleiss Karin , Skrabs Cathrin , Lévesque Éric , Vanura Katrina , Guillemette Chantal , Jaeger Ulrich 
Published: November 2012

Key PointsUridine diphospho glucuronosyltransferase 2B17 (UGT2B17) is overexpressed in poor prognostic chronic lymphocytic leukemia.
SDF-1α upregulation by atorvastatin in rats with acute myocardial infarction via nitric oxide production confers anti-inflammatory and anti-apoptotic effects
Authors: Qiu Ruofeng , Cai Anping , Dong Yugang , Zhou Yingling , Yu Danqing , Huang Yuli , Zheng Dongdan , Rao Shaoqi , Feng Yingqing , Mai Weiyi 
Published: November 2012

Abstract

Background
The effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear. Therefore, our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1α expression in rats with AMI.

Methods
Male Sprague–Dawley rats were underwent permanent coronary artery ligation and randomly assigned into four groups as follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME), and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d body weight) was administrated by gavage to rats in three atorvastatin treated groups, and L-NAME (40mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively.

Results
Comparing with group B, NO production, SDF-1α and CXCR4 expression were significantly up-regulated in three atorvastatin treated groups at the seventh day. However, the increments of SDF-1α and CXCR4 expression in group A+L-NAME were reduced when NO production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects of atorvastatin were offset either by decrease of SDF-1α and CXCR4 expression (by L-NAME) or blockage of SDF-1α coupling with CXCR4 (by AMD3100). Expression of STAT3, a cardioprotective factor mediating SDF-1α/CXCR4 axis induced cardiac protection, was up-regulated most significantly in group A. The effects of atorvastatin therapy on cardiac function were also abrogated either when SDF-1α and CXCR4 expression was diminished or the coupling of SDF-1α with CXCR4 was blocked.

Conclusion
SDF-1α upregulation by atorvastatin in rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF-1α upregulation and SDF-1α coupling with CXCR4 conferred anti-inflammatory and anti-apoptotic effects under AMI setting which we speculated that ultimately contributed to cardiac function improvement.
An assessment on epitope prediction methods for protozoa genomes
Authors: Resende Daniela M , Rezende Antônio M , Oliveira Nesley JD , Batista Izabella CA , Corrêa-Oliveira Rodrigo , Reis Alexandre B , Ruiz Jeronimo C 
Published: November 2012

AbstractBackgroundEpitope prediction using computational methods represents one of the most promising approaches to vaccine development. Reduction of time, cost, and the availability of completely sequenced genomes are key points and highly motivating regarding the use of reverse vaccinology. Parasites of genusLeishmaniaare widely spread and they are the etiologic agents of leishmaniasis. Currently, there is no efficient vaccine against this pathogen and the drug treatment is highly toxic. The lack of sufficiently large datasets of experimentally validated parasites epitopes represents a serious limitation, especially for trypanomatids genomes. In this work we highlight the predictive performances of several algorithms that were evaluated through the development of a MySQL database built with the purpose of: a) evaluating individual algorithms prediction performances and their combination for CD8+ T cell epitopes, B-cell epitopes and subcellular localization by means of AUC (Area Under Curve) performance and a threshold dependent method that employs a confusion matrix; b) integrating data from experimentally validated andin silicopredicted epitopes; and c) integrating the subcellular localization predictions and experimental data. NetCTL, NetMHC, BepiPred, BCPred12, and AAP12 algorithms were used forin silicoepitope prediction and WoLF PSORT, Sigcleave and TargetP forin silicosubcellular localization prediction against trypanosomatid genomes.ResultsA database-driven epitope prediction method was developed with built-in functions that were capable of: a) removing experimental data redundancy; b) parsing algorithms predictions and storage experimental validated and predict data; and c) evaluating algorithm performances. Results show that a better performance is achieved when the combined prediction is considered. This is particularly true for B cell epitope predictors, where the combined prediction of AAP12 and BCPred12 reached an AUC value of 0.77. For T CD8+ epitope predictors, the combined prediction of NetCTL and NetMHC reached an AUC value of 0.64. Finally, regarding the subcellular localization prediction, the best performance is achieved when the combined prediction of Sigcleave, TargetP and WoLF PSORT is used.ConclusionsOur study indicates that the combination of B cells epitope predictors is the best tool for predicting epitopes on protozoan parasites proteins. Regarding subcellular localization, the best result was obtained when the three algorithms predictions were combined. The developed pipeline is available upon request to authors.
Transcriptome analysis reveals unique metabolic features in the Cryptosporidium parvum Oocysts associated with environmental survival and stresses
Authors: Zhang Haili , Guo Fengguang , Zhou Huaijun , Zhu Guan 
Published: November 2012

Abstract

Background

Cryptosporidium parvum is a globally distributed zoonotic parasite and an important opportunistic pathogen in immunocompromised patients. Little is known on the metabolic dynamics of the parasite, and study is hampered by the lack of molecular and genetic tools. Here we report the development of the first Agilent microarray for C. parvum (CpArray15K) that covers all predicted ORFs in the parasite genome. Global transcriptome analysis using CpArray15K coupled with real-time qRT-PCR uncovered a number of unique metabolic features in oocysts, the infectious and environmental stage of the parasite.

Results
Oocyst stage parasites were found to be highly active in protein synthesis, based on the high transcript levels of genes associated with ribosome biogenesis, transcription and translation. The proteasome and ubiquitin associated components were also highly active, implying that oocysts might employ protein degradation pathways to recycle amino acids in order to overcome the inability to synthesize amino acids de novo. Energy metabolism in oocysts was featured by the highest level of expression of lactate dehydrogenase (LDH) gene. We also studied parasite responses to UV-irradiation, and observed complex and dynamic regulations of gene expression. Notable changes included increased transcript levels of genes involved in DNA repair and intracellular trafficking. Among the stress-related genes, TCP-1 family members and some thioredoxin-associated genes appear to play more important roles in the recovery of UV-induced damages in the oocysts. Our observations also suggest that UV irradiation of oocysts results in increased activities in cytoskeletal rearrangement and intracellular membrane trafficking.

Conclusions
CpArray15K is the first microarray chip developed for C. parvum, which provides the Cryptosporidium research community a needed tool to study the parasite transcriptome and functional genomics. CpArray15K has been successfully used in profiling the gene expressions in the parasite oocysts as well as their responses to UV-irradiation. These observations shed light on how the parasite oocysts might adapt and respond to the hostile external environment and associated stress such as UV irradiation.
Exon capture and bulk segregant analysis: rapid discovery of causative mutations using high-throughput sequencing
Authors: del Viso Florencia , Bhattacharya Dipankan , Kong Yong , Gilchrist Michael J , Khokha Mustafa K 
Published: November 2012

Abstract

Background
Exome sequencing has transformed human genetic analysis and may do the same for other vertebrate model systems. However, a major challenge is sifting through the large number of sequence variants to identify the causative mutation for a given phenotype. In models like Xenopus tropicalis, an incomplete and occasionally incorrect genome assembly compounds this problem. To facilitate cloning of X. tropicalis mutants identified in forward genetic screens, we sought to combine bulk segregant analysis and exome sequencing into a single step.

Results
Here we report the first use of exon capture sequencing to identify mutations in a non-mammalian, vertebrate model. We demonstrate that bulk segregant analysis coupled with exon capture sequencing is not only able to identify causative mutations but can also generate linkage information, facilitate the assembly of scaffolds, identify misassembles, and discover thousands of SNPs for fine mapping.

Conclusion
Exon capture sequencing and bulk segregant analysis is a rapid, inexpensive method to clone mutants identified in forward genetic screens. With sufficient meioses, this method can be generalized to any model system with a genome assembly, polished or unpolished, and in the latter case, it also provides many critical genomic resources.
De Novo characterization of the banana root transcriptome and analysis of gene expression under Fusarium oxysporum f. sp. Cubense tropical race 4 infection
Authors: Wang Zhuo , Zhang JianBin , Jia CaiHong , Liu JuHua , Li YanQiang , Yin XiaoMin , Xu BiYu , Jin ZhiQiang 
Published: November 2012

Abstract

Background
Bananas and plantains (Musa spp.) are among the most important crops in the world due to their nutritional and export value. However, banana production has been devastated by fungal infestations caused by Fusarium oxysporum f. sp. cubense (Foc), which cannot be effectively prevented or controlled. Since there is very little known about the molecular mechanism of Foc infections; therefore, we aimed to investigate the transcriptional changes induced by Foc in banana roots.

Results
We generated a cDNA library from total RNA isolated from banana roots infected with Foc Tropical Race 4 (Foc TR 4) at days 0, 2, 4, and 6. We generated over 26 million high-quality reads from the cDNA library using deep sequencing and assembled 25,158 distinct gene sequences by de novo assembly and gap-filling. The average distinct gene sequence length was 1,439 base pairs. A total of 21,622 (85.94%) unique sequences were annotated and 11,611 were assigned to specific metabolic pathways using the Kyoto Encyclopedia of Genes and Genomes database. We used digital gene expression (DGE) profiling to investigate the transcriptional changes in the banana root upon Foc TR4 infection. The expression of genes in the Phenylalanine metabolism, phenylpropanoid biosynthesis and alpha-linolenic acid metabolism pathways was affected by Foc TR4 infection.

Conclusion
The combination of RNA-Seq and DGE analysis provides a powerful method for analyzing the banana root transcriptome and investigating the transcriptional changes during the response of banana genes to Foc TR4 infection. The assembled banana transcriptome provides an important resource for future investigations about the banana crop as well as the diseases that plague this valuable staple food.
Genetic linkage maps for Asian and American lotus constructed using novel SSR markers derived from the genome of sequenced cultivar
Authors: Yang Mei , Han Yanni , VanBuren Robert , Ming Ray , Xu Liming , Han Yuepeng , Liu Yanling 
Published: November 2012

Abstract

Background
The genus Nelumbo Adans. comprises two living species, N. nucifera Gaertan. (Asian lotus) and N. lutea Pers. (American lotus). A genetic linkage map is an essential resource for plant genetic studies and crop improvement but has not been generated for Nelumbo. We aimed to develop genomic simple sequence repeat (SSR) markers from the genome sequence and construct two genetic maps for Nelumbo to assist genome assembly and integration of a genetic map with the genome sequence.

Results
A total of 86,089 SSR motifs were identified from the genome sequences. Di- and tri-nucleotide repeat motifs were the most abundant, and accounted for 60.73% and 31.66% of all SSRs, respectively. AG/GA repeats constituted 51.17% of dinucleotide repeat motifs, followed by AT/TA (44.29%). Of 500 SSR primers tested, 386 (77.20%) produced scorable alleles with an average of 2.59 per primer, and 185 (37.00%) showed polymorphism among two parental genotypes, N. nucifera ‘Chinese Antique’ and N. lutea ‘AL1’, and six progenies of their F1 population. The normally segregating markers, which comprised 268 newly developed SSRs, 37 previously published SSRs and 53 sequence-related amplified polymorphism markers, were used for genetic map construction. The map for Asian lotus was 365.67 cM with 47 markers distributed in seven linkage groups. The map for American lotus was 524.51 cM, and contained 177 markers distributed in 11 genetic linkage groups. The number of markers per linkage group ranged from three to 34 with an average genetic distance of 3.97 cM between adjacent markers. Moreover, 171 SSR markers contained in linkage groups were anchored to 97 genomic DNA sequence contigs of ‘Chinese Antique’. The 97 contigs were merged into 60 scaffolds.

Conclusion
Genetic mapping of SSR markers derived from sequenced contigs in Nelumbo enabled the associated contigs to be anchored in the linkage map and facilitated assembly of the genome sequences of ‘Chinese Antique’. The present study reports the first construction of genetic linkage maps for Nelumbo, which can serve as reference linkage maps to accelerate characterization germplasm, genetic mapping for traits of economic interest, and molecular breeding with marker-assisted selection.
Decreased miR-192 expression in peripheral blood of asthmatic individuals undergoing an allergen inhalation challenge
Authors: Yamamoto Masatsugu , Singh Amrit , Ruan Jian , Gauvreau Gail M , O'Byrne Paul M , R Carlsten Christopher , FitzGerald J Mark , Boulet Louis-Philippe , Tebbutt Scott J 
Published: November 2012

Abstract

Background
MicroRNAs are small non-coding RNAs that regulate gene expression at the post-transcriptional level. While they have been implicated in various diseases, the profile changes in allergen inhalation challenge are not clarified in human. We aimed to evaluate changes in the microRNA profiles in the peripheral blood of asthmatic subjects undergoing allergen inhalation challenge.

Results
Seven mild asthmatic subjects participated in the allergen inhalation challenge. In addition, four healthy control subjects (HCs) were recruited. MicroRNA profiles in peripheral blood samples (pre-challenge and 2 hours post-challenge) were measured by the NanoString nCounter assay to determine changes in miRNA levels as these asthmatic subjects underwent an allergen inhalation challenge. One common miRNA, miR-192, was significantly expressed in both comparisons; HCs vs. pre-challenge and pre- vs. post-challenge, showing that miR-192 was significantly under-expressed in asthmatics compared to HCs and decreased in post-challenge at an FDR of 1%. Cell-specific statistical deconvolution attributed miR-192 expression in whole blood to PBMCs. MiR-192 was technically validated using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showing that the level in asthmatics (pre-challenge) was significantly lower than HCs and that post-challenge was significantly lower than pre-challenge. The normalized relative miR-192 expression quantified using RT-qPCR specific to PBMCs was also validated. Ontology enrichment and canonical pathway analyses for target genes suggested several functions and pathways involved in immune response and cell cycle.

Conclusions
The miRNA profile in peripheral blood was altered after allergen inhalation challenge. Change in miR-192 levels may be implicated in asthma mechanisms. These results suggest that allergen inhalation challenge is a suitable method to characterize peripheral miRNA profiles and potentially elucidate the mechanism of human asthma.
The RNA processing enzyme polynucleotide phosphorylase negatively controls biofilm formation by repressing poly-N-acetylglucosamine (PNAG) production in Escherichia coli C
Authors: Carzaniga Thomas , Antoniani Davide , Dehò Gianni , Briani Federica , Landini Paolo 
Published: November 2012

AbstractBackgroundTransition from planktonic cells to biofilm is mediated by production of adhesion factors, such as extracellular polysaccharides (EPS), and modulated by complex regulatory networks that, in addition to controlling production of adhesion factors, redirect bacterial cell metabolism to the biofilm mode.ResultsDeletion of thepnpgene, encoding polynucleotide phosphorylase, an RNA processing enzyme and a component of the RNA degradosome, results in increased biofilm formation inEscherichia coli. This effect is particularly pronounced in theE.colistrain C-1a, in which deletion of thepnpgene leads to strong cell aggregation in liquid medium. Cell aggregation is dependent on the EPS poly-N-acetylglucosamine (PNAG), thus suggesting negative regulation of the PNAG biosynthetic operonpgaABCDby PNPase. Indeed,pgaABCDtranscript levels are higher in thepnpmutant. Negative control ofpgaABCDexpression by PNPase takes place at mRNA stability level and involves the 5’-untranslated region of thepgaABCDtranscript, which serves as acis-element regulatingpgaABCDtranscript stability and translatability.ConclusionsOur results demonstrate that PNPase is necessary to maintain bacterial cells in the planktonic mode through down-regulation ofpgaABCDexpression and PNAG production.