bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the Child Mealtime Feeding Behavior Questionnaire
Authors: Ainuki Tomomi , Akamatsu Rie
Published: November 2012

It has been suggested that parents’ feeding behaviors are associated with the eating behaviors of their children. The objective of this study was to develop the Child Mealtime Feeding Behavior Questionnaire (CMFBQ) to assess the strategies used by mothers in response to picky eating by their children at meals. The participants, 834 mothers of 3- to 6-year-old children attending kindergartens and nursery schools in Tokyo and Fukui, Japan, completed the self-administered questionnaires. Exploratory and confirmatory factor analyses of data obtained from these participants produced an 18-item scale with 4 subscales: “behavioral strategy,” “passive coercion,” “punishment and reward,” and “permission.” The internal consistency (Cronbach’s α) of these subscales ranged from .65 to .82. Maternal punishment and reward and maternal permission were positively associated with children’s picky eating; however, other behavioral strategies, including passive coercion, were not significantly related to children’s picky eating. The CMFBQ can assess the strategies used by mothers to encourage their children to eat meals. Researchers and health practitioners can use this measure to better understand how mothers motivate their children to eat meals and to consider the implications of these practices for children’s eating behaviors without placing an undue burden on respondents.
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

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 Points

Live 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 Points

Uridine 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

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

Background

Epitope 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.

Results

A 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.

Conclusions

Our 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

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

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

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

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

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

Background

Transition 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.

Results

Deletion 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.

Conclusions

Our results demonstrate that PNPase is necessary to maintain bacterial cells in the planktonic mode through down-regulation ofpgaABCDexpression and PNAG production.
miRNA164-directed cleavage of ZmNAC1 confers lateral root development in maize (Zea maysL.)
Authors: Li Jing , Guo Guanghui , Guo Weiwei , Guo Ganggang , Tong Dan , Ni Zhongfu , Sun Qixin , Yao Yingyin
Published: November 2012

Background

MicroRNAs are a class of small, non-coding RNAs that regulate gene expression by binding target mRNA, which leads to cleavage or translational inhibition. The NAC proteins, which include NAM, ATAF, and CUC, are a plant-specific transcription factor family with diverse roles in development and stress regulation. It has been reported that miR164 negatively regulates NAC1 expression, which in turn affects lateral root development in Arabidopsis; however, little is known about the involvement of the maize NAC family and miR164 in lateral root development.

Results

We collected 175 maize transcripts with NAC domains. Of these, 7 ZmNACs were putative targets for regulation by miR164. We isolated one gene, called TC258020 (designated ZmNAC1) from 2 maize inbred lines, 87-1 and Zong3. ZmNAC1 had a high expression level in roots and showed higher abundance (1.8 fold) in Zong3 relative to 87-1, which had less lateral roots than Zong3. There was a significant correlation between the expression level of ZmNAC1 and the lateral root density in the recombinant inbred line (RIL) population. Transgenic Arabidopsis that overexpressed ZmNAC1 had increased lateral roots in comparison to the wild type. These findings suggest that ZmNAC1 played a significant role in lateral root development. An allelic expression assay showed that trans-regulatory elements were the dominant mediators of ZmNAC1 differential expression in 87-1 and Zong3, and further analysis revealed that miR164 was a trans-element that guided the cleavage of endogenous ZmNAC1 mRNA. Both mature miR164 and miR164 precursors had higher expression in 87-1 than Zong3, which was the opposite of the expression pattern of ZmNAC1. Additionally, the allelic assay showed that the cis-regulatory element most likely affected Zm-miR164b's expression pattern. A β-glucuronidase (GUS) assay showed that the Zm-miR164b promoter had higher GUS activity in 87-1 than in Zong3. In addition, we detected miR164b expression in the RIL population, and the results indicated that miR164b had a higher expression level in the RILs containing 87-1 promoter than those containing Zong3 promoter.

Conclusion

Our results indicate one possible pathway in maize by which differences in miR164b promoter activity resulted in a different expression pattern for mature miR164 which negatively regulates ZmNAC1 expression in 87-1 and Zong3, thereby contributing to a significantly different lateral root phenotype.
Molecular characterization of LMW-GS genes in Brachypodium distachyon L. reveals highly conserved Glu-3 loci in Triticum and relatedspecies
Authors: Wang Shunli , Wang Ke , Chen Guanxing , Lv Dongwen , Han Xiaofeng , Yu Zitong , Li Xiaohui , Ye Xingguo , Hsam SLK , Ma Wujun , Appels Rudi , Yan Yueming
Published: November 2012

Background

Brachypodium distachyon L. is a newly emerging model plant system for temperate cereal crop species. However, its grain protein compositions are still not clear. In the current study, we carried out a detailed proteomics and molecular genetics study on grain glutenin proteins in B. distachyon.

Results

SDS-PAGE and RP-HPLC analysis of grain proteins showed that Brachypodium has few gliadins and high molecular weight glutenin subunits. In contrast the electrophoretic patterns for the albumin, globulin and low molecular weight glutenin subunit (LMW-GS) fractions of the grain protein were similar to those in wheat. In particular, the LMW-C type subunits in Brachypodium were more abundant than the equivalent proteins in common wheat. Southern blotting analysis confirmed that Brachypodium has 4–5 copies of LMW-GS genes. A total of 18 LMW-GS genes were cloned from Brachypodium by allele specific PCR. LMW-GS and 4 deduced amino acid sequences were further confirmed by using Western-blotting and MALDI-TOF-MS. Phylogenetic analysis indicated that Brachypodium was closer to Ae. markgrafii and Ae. umbellulata than to T. aestivum.

Conclusions

Brachypodium possessed a highly conserved Glu-3 locus that is closely related to Triticum and related species. The presence of LMW-GS in B. distachyon grains indicates that B. distachyon may be used as a model system for studying wheat quality attributes.
Deep-sequencing transcriptome analysis of chilling tolerance mechanisms of a subnival alpine plant, Chorispora bungeana
Authors: Zhao Zhiguang , Tan Lingling , Dang Chunyan , Zhang Hua , Wu Qingbai , An Lizhe
Published: November 2012

Background

The plant tolerance mechanisms to low temperature have been studied extensively in the model plant Arabidopsis at the transcriptional level. However, few studies were carried out in plants with strong inherited cold tolerance.Chorispora bungeanais a subnival alpine plant possessing strong cold tolerance mechanisms. To get a deeper insight into its cold tolerance mechanisms, the transcriptome profiles of chilling-treatedC. bungeanaseedlings were analyzed by Illumina deep-sequencing and compared with Arabidopsis.

Results

Two cDNA libraries constructed from mRNAs of control and chilling-treated seedlings were sequenced by Illumina technology. A total of 54,870 unigenes were obtained byde novoassembly, and 3,484 chilling up-regulated and 4,571 down-regulated unigenes were identified. The expressions of 18 out of top 20 up-regulated unigenes were confirmed by qPCR analysis. Functional network analysis of the up-regulated genes revealed some common biological processes, including cold responses, and molecular functions inC. bungeanaand Arabidopsis responding to chilling. Karrikins were found as new plant growth regulators involved in chilling responses ofC. bungeanaand Arabidopsis. However, genes involved in cold acclimation were enriched in chilling up-regulated genes in Arabidopsis but not inC. bungeana.In addition, although transcription activations were stimulated in bothC. bungeanaand Arabidopsis, noCBFputative ortholog was up-regulated inC. bungeanawhileCBF2andCBF3were chilling up-regulated in Arabidopsis. On the other hand, up-regulated genes related to protein phosphorylation and auto-ubiquitination processes were over-represented inC. bungeanabut not in Arabidopsis.

Conclusions

We conducted the first deep-sequencing transcriptome profiling and chilling stress regulatory network analysis ofC. bungeana, a subnival alpine plant with inherited cold tolerance. Comparative transcriptome analysis suggests that cold acclimation is not a major chilling tolerance mechanism ofC. bungeana. Activation of protein phosphorylation and ubiquitination may confer chilling tolerance toC. bungeanain a more rapid and flexible way than cold acclimation. Such differences may have contributed to the differences in cold tolerance betweenC. bungeanaand Arabidopsis. The results presented in this paper will be informative for gene discovery and the molecular mechanisms related to plant cold tolerance.
Aberrant expression of CD133 in non-small cell lung cancer and its relationship to vasculogenic mimicry
Authors: Wu Shiwu , Yu Lan , Wang Danna , Zhou Lei , Cheng Zenong , Chai Damin , Ma Li , Tao Yisheng
Published: November 2012

Background

To investigate on expressions and clinical significances of CD133 protein and vasculogenic mimicry (VM) in primary non-small cell lung cancer (NSCLC).

Methods

The specimens of NSCLC from 305 Chinese patients with follow-up were analyzed for CD133 protein expression and VM by immunohistochemical and histochemical staining.

Results

In NSCLC, positive rates of 48.9% and 35.7% were obtained for CD133 and VM, respectively. The VM and expression of CD133 were significantly higher in carcinoma than in normal. There were a positive relationship between the VM and expression of CD133 and the tumor grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with CD133 and VM positive expression was lower than that of patients with negative expression. Microvessel density (MVD) was positive corresponded with the grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with MVD≥22’s group was shorter than that of patients with MVD<22’s group. Pathological-tumor-node-metastasis (pTNM) stage, positive expression of CD133 and VM, postoperative therapy and MVD were independent prognostic factors of NSCLC (P<0.05). Immunohistochemistry revealed an important intratumoral heterogeneity in all four CD133 expression profiles.

Conclusions

VM, MVD and expression of CD133 are related to differentiation, lymph node metastasis, clinical stage, and prognosis. It is suggested that CD133, VM and MVD should be considered as a potential marker for the prognosis.
Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses
Authors: Anthoney D Alan , Naik Jay , MacPherson Iain RJ , Crawford Donna , Hartley John M , Hartley Janet A , Saito Tomohisa , Abe Masaichi , Jones Keith , Miwa Masanori , Twelves Christopher , Evans TRJ
Published: November 2012

Background

A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011.

Methods

Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs).

Results

32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1–10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion.

Conclusions

TP300 had predictable hematologic toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage.

Trial registration

EU-CTR2006-001345-33
A cluster randomised trial of a school-based resilience intervention to decrease tobacco, alcohol and illicit drug use in secondary school students: study protocol
Authors: Hodder Rebecca K , Freund Megan , Bowman Jenny , Wolfenden Luke , Campbell Elizabeth , Wye Paula , Hazell Trevor , Gillham Karen , Wiggers John
Published: November 2012

Background

Whilst schools provide a potentially appropriate setting for preventing substance use among young people, systematic review evidence suggests that past interventions in this setting have demonstrated limited effectiveness in preventing tobacco, alcohol and other drug use. Interventions that adopt a mental wellbeing approach to prevent substance use offer considerable promise and resilience theory provides one method to impact on adolescent mental well-being. The aim of the proposed study is to examine the efficacy of a resilience intervention in decreasing the tobacco, alcohol and illicit drug use of adolescents.

Methods

A cluster randomised controlled trial with schools as the unit of randomisation will be undertaken. Thirty two schools in disadvantaged areas will be allocated to either an intervention or a control group. A comprehensive resilience intervention will be implemented, inclusive of explicit program adoption strategies. Baseline surveys will be conducted with students in Grade 7 in both groups and again three years later when the student cohort is in Grade 10. The primary outcome measures will include self-reported tobacco, alcohol, marijuana and other illicit drug use. Comparisons will be made post-test between Grade 10 students in intervention and control schools to determine intervention effectiveness across all measures.

Discussion

To the authors’ knowledge this is the first randomised controlled trial to evaluate the effectiveness of a comprehensive school-based resilience intervention, inclusive of explicit adoption strategies, in decreasing tobacco, alcohol and illicit drug use of adolescents attending disadvantaged secondary schools.

Trial registration

ACTRN12611000606987
User fee exemptions and excessive household spending for normal delivery in Burkina Faso: the need for careful implementation
Authors: Ameur Amal Ben , Ridde Valéry , Bado Aristide R , Ingabire Marie-Gloriose , Queuille Ludovic
Published: November 2012

Background

In 2006, the Parliament of Burkina Faso passed a policy to reduce the direct costs of obstetric services and neonatal care in the country’s health centres, aiming to lower the country’s high national maternal mortality and morbidity rates. Implementation was via a “partial exemption” covering 80% of the costs. In 2008 the German NGO HELP launched a pilot project in two health districts to eliminate the remaining 20% of user fees. Regardless of any exemptions, women giving birth in Burkina Faso’s health centres face additional expenses that often represent an additional barrier to accessing health services. We compared the total cost of giving birth in health centres offering partial exemption versus those with full exemption to assess the impact on additional out-of-pocket fees.

Methods

A case–control study was performed to compare medical expenses. Case subjects were women who gave birth in 12 health centres located in the Dori and Sebba districts, where HELP provided full fee exemption for obstetric services and neonatal care. Controls were from six health centres in the neighbouring Djibo district where a partial fee exemption was in place. A random sample of approximately 50 women per health centre was selected for a total of 870 women.

Results

There was an implementation gap regarding the full exemption for obstetric services and neonatal care. Only 1.1% of the sample from Sebba but 17.5% of the group from Dori had excessive spending on birth related costs, indicating that women who delivered in Sebba were much less exposed to excessive medical expenses than women from Dori. Additional out-of-pocket fees in the full exemption health districts took into account household ability to pay, with poorer women generally paying less.

Conclusions

We found that the elimination of fees for facility-based births benefits especially the poorest households. The existence of excessive spending related to direct costs of giving birth is of concern, making it urgent for the government to remove all direct fees for obstetric and neonatal care. However, the policy of completely abolishing user fees is insufficient; the implementation process must have a thorough monitoring system to reduce implementation gaps.
Novel cancerization marker, TP53, and its role in distinguishing normal tissue adjacent to cancerous tissue from normal tissue adjacent to benign tissue
Authors: Liu Guo-Yan , Liu Kun-Hong , Li Yin , Pan Chao , Su Ji-Qin , Liao Hong-Feng , Yv Ren-Xiang , Li Zhao-Hui , Yuan Li , Zhang Huan-Jing , Tzeng Chi-Meng , Xiong Bing
Published: November 2012

Background

The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization.

Methods

We evaluated 15 tumor-related RNA in situ hybridization biomarkers using tumor microarray and samples of seven tumor-adjacent normal tissues from 314 patients. Biomarkers were determined using comprehensive statistical methods (significance of support vector machine-based artificial intelligence and area under curve scoring of classification distribution).

Results

TP53 was found to be a most reliable index (P <10-7; area under curve >87%) for distinguishing NTAC from NTAB, according to the results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53).

Conclusions

The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation.
Prothrombotic gene variants as risk factors of acute myocardial infarction in young women
Authors: Tomaiuolo Rossella , Bellia Chiara , Caruso Antonietta , Di Fiore Rosanna , Quaranta Sandro , Noto Davide , Cefalù Angelo B , Di Micco Pierpaolo , Zarrilli Federica , Castaldo Giuseppe , Averna Maurizio R , Ciaccio Marcello
Published: November 2012

Background

Acute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age.

Methods

We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy).

Results

In young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was significantly higher versus the general population (O.R.: 3.67 for FV Leiden and O.R.: 3.84 for FII G20210A; p<0.001). Among AMI patients we showed only in males that the allelic frequency of the MTHFR C677T variant was significantly higher as compared to the general population. Such difference was due to a significantly higher frequency in AMI males of the MTHFR C677T variant homozygous genotype (O.R. 3.05).

Discussion and conclusion

Our data confirm that young AMI in females is a peculiar phenotype with specific risk factors as the increased plasma procoagulant activity of FV and FII. On the contrary, the homozygous state for the 677T MTHFR variant may cause increased levels of homocysteine and/or an altered folate status and thus an increased risk for AMI, particularly in males. The knowledge of such risk factors (that may be easily identified by molecular analysis) may help to improve prevention strategies for acute coronary diseases in specific risk-group subjects.
Facile synthesis of hollow Cu2O octahedral and spherical nanocrystals and their morphology-dependent photocatalytic properties
Authors: Feng Lili , Zhang Chunlei , Gao Guo , Cui Daxiang
Published: November 2012

Herein, we report that octahedral and spherical Cu2O samples with hollow structures are synthesized in high yield by reducing Cu(EDA)2
2+ complex with hydrazine. A series of experiments are carried out to investigate the factors which impact on the morphology of the Cu2O samples. It is observed that ethylenediamine (EDA) serves as a molecular template in the formation of hollow structure. Octahedral Cu2O with solid structure is prepared without EDA. When EDA is added, Cu2O sample with hollow structure is formed. Different morphologies of Cu2O such as spherical and octahedral could be obtained by adjusting the concentration of EDA and NaOH. The temporal crystal growth mechanism is proposed. Furthermore, the photocatalytic activities of the as-prepared Cu2O nanoparticles are evaluated by monitoring two dyes (methyl orange and congo red) using UV-visible spectrophotometer. Results show that the order of photocatalytic activity of Cu2O with different morphologies is as follows: hollow octahedral morphology > hollow sphere morphology > solid octahedral morphology. The hollow octahedral Cu2O nanoparticles would be a promising material on applications for photocatalytic degradation of organic pollutants.
Synthesis and characterization of titanium complex with a dithiolate ligand for green LCD color filter dyes
Authors: Shin Hwangyu , Park Youngil , Kim Seungho , An Byeong-Kwan , Park Jongwook
Published: November 2012

Three green compounds for color filter dyes based on bis(cyclopentadienyl) titanium complexes including dithiolate ligand were synthesized. Physical properties by the change of the substitution groups of the synthesized materials were systematically examined. UV-visible absorption spectrum of the synthesized materials showed maximum absorbing wavelengths of 427 to 430 nm and 632 to 635 nm in solution state, and 434 to 438 nm and 637 to 651 nm in film state, indicating green and black colors. It was observed that the extinction coefficient values (log ε) of all the synthesized materials are very high at 4.0 or above. In addition, it was shown that since the T
d values of three synthesized materials show thermal stability higher than 240°C, they possess high potential to be applied as dyes for LCD color filter and black matrix addictive.
High-rate systematic recursive convolutional encoders: minimal trellis and code search
Authors: Benchimol Isaac , Pimentel Cecilio , Souza Richard Demo , Uchôa-Filho Bartolomeu F
Published: November 2012

We consider high-rate systematic recursive convolutional encoders to be adopted as constituent encoders in turbo schemes. Douillard and Berrou showed that, despite its complexity, the construction of high-rate turbo codes by means of high-rate constituent encoders is advantageous over the construction based on puncturing rate-1/2 constituent encoders. To reduce the decoding complexity of high-rate codes, we introduce the construction of the minimal trellis for a systematic recursive convolutional encoding matrix. A code search is conducted and examples are provided which indicate that a more finely grained decoding complexity-error performance trade-off is obtained.
Methodological quality of English-language genetic guidelines on hereditary breast-cancer screening and management: an evaluation using the AGREE instrument
Authors: Simone Benedetto , De Feo Emma , Nicolotti Nicola , Ricciardi Walter , Boccia Stefania
Published: November 2012

Background

We examined the methodological quality of guidelines on syndromes conferring genetic susceptibility to breast cancer.

Methods

PubMed, EMBASE, and Google were searched for guidelines published up to October 2010. All guidelines in English were included. The Appraisal of Guidelines, Research and Evaluation (AGREE) instrument was used to assess the quality of the guidelines, and their reported evidence base was evaluated.

Results

Thirteen guidelines were deemed eligible: seven had been developed by independent associations, and the other six had national/state endorsements. Four guidelines performed satisfactorily, achieving a score of greater than 50% in all six AGREE domains. Mean ± SD standardized scores for the six AGREE domains were: 90 ± 9% for 'scope and purpose', 51 ± 18% for 'stakeholder involvement', 55 ± 27% for 'rigour of development', 80 ± 11% for 'clarity and presentation', 37 ± 32% for 'applicability', and 47 ± 38% for 'editorial independence'. Ten of the thirteen guidelines were found to be based on research evidence.

Conclusions

Given the ethical implications and the high costs of genetic testing for hereditary breast cancer, guidelines on this topic should provide clear and evidence-based recommendations. Our analysis shows that there is scope for improving many aspects of the methodological quality of current guidelines. The AGREE instrument is a useful tool, and could be used profitably by guidelines developers to improve the quality of recommendations.
The validation of a three-stage screening methodology for detecting active convulsive epilepsy in population-based studies in health and demographic surveillance systems
Authors: Ngugi Anthony K , Bottomley Christian , Chengo Eddie , Kombe Martha Z , Kazungu Michael , Bauni Evasius , Mbuba Caroline K , Kleinschmidt Immo , Newton Charles R
Published: November 2012

Background

There are few studies on the epidemiology of epilepsy in large populations in Low and Middle Income Countries (LMIC). Most studies in these regions use two-stage population-based screening surveys, which are time-consuming and costly to implement in large populations required to generate accurate estimates. We examined the sensitivity and specificity of a three-stage cross-sectional screening methodology in detecting active convulsive epilepsy (ACE), which can be embedded within on-going census of demographic surveillance systems.

We validated a three-stage cross-sectional screening methodology on a randomly selected sample of participants of a three-stage prevalence survey of epilepsy. Diagnosis of ACE by an experienced clinician was used as ‘gold standard’. We further compared the expenditure of this method with the standard two-stage methodology.

Results

We screened 4442 subjects in the validation and identified 35 cases of ACE. Of these, 18 were identified as false negatives, most of whom (15/18) were missed in the first stage and a few (3/18) in the second stage of the three-stage screening. Overall, this methodology had a sensitivity of 48.6% and a specificity of 100%. It was 37% cheaper than a two-stage survey.

Conclusion

This was the first study to evaluate the performance of a multi-stage screening methodology used to detect epilepsy in demographic surveillance sites. This method had poor sensitivity attributed mainly to stigma-related non-response in the first stage. This method needs to take into consideration the poor sensitivity and the savings in expenditure and time as well as validation in target populations. Our findings suggest the need for continued efforts to develop and improve case-ascertainment methods in population-based epidemiological studies of epilepsy in LMIC.