bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD39+Regulatory T cells suppress generation and differentiation of Th17 cells in human malignant pleural effusion via a LAP-dependent mechanism
Authors: Ye Zhi-Jian , Zhou Qiong , Zhang Jian-Chu , Li Xiao , Wu Cong , Qin Shou-Ming , Xin Jian-Bao , Shi Huan-Zhong 
Published: June 2011

AbstractBackgroundBoth regulatory T cells (Tregs) and T helper IL-17-producing cells (Th17 cells) have been found to be involved in human malignancies, however, the possible implication of Tregs in regulating generation and differentiation of Th17 cells in malignant pleural effusion remains to be elucidated.MethodsThe numbers of both CD39+Tregs and Th17 cells in malignant pleural effusion and peripheral blood from patients with lung cancer were determined by flow cytometry. The regulation and mechanism of Tregs on generation and differentiation of Th17 cells were explored.ResultsBoth CD39+Tregs and Th17 cells were increased in malignant pleural effusion when compared with blood, and the numbers of CD39+Tregs were correlated negatively with those of Th17 cells. It was also noted that high levels of IL-1β, IL-6, and TGF-β1 could be observed in malignant pleural effusion when compared the corresponding serum, and that pleural CD39+Tregs could express latency-associated peptide on their surface. When naïve CD4+T cells were cocultured with CD39+Tregs, Th17 cell numbers decreased as CD39+Treg numbers increased, addition of the anti-latency-associated peptide mAb to the coculture reverted the inhibitory effect exerted by CD39+Tregs.ConclusionsTherefore, the above results indicate that CD39+Tregs inhibit generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism.
Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury
Authors: Zhou Fang , Onizawa Shigemitsu , Nagai Atsushi , Aoshiba Kazutetsu 
Published: June 2011

Abstract

Background
Genotoxic stress, such as by exposure to bromodeoxyuridine (BrdU) and cigarette smoke, induces premature cell senescence. Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients. However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown. The present study was designed to test the hypothesis that premature senescence of airway epithelial cells (Clara cells) impairs repair processes and exacerbates inflammation after airway injury.

Methods
C57/BL6J mice were injected with the Clara-cell-specific toxicant naphthalene (NA) on days 0, 7, and 14, and each NA injection was followed by a daily dose of BrdU on each of the following 3 days, during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce. The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose. Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation. NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312. Human lung tissue samples were obtained from COPD patients, asymptomatic smokers, and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients, and if so, whether it is accompanied by p38 MAPK activation.

Results
BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure. However, after repeated NA exposure, BrdU induced epithelial cell (Clara cell) senescence, as demonstrated by a DNA damage response, p21 overexpression, increased senescence-associated β-galactosidase activity, and growth arrest, which resulted in impaired epithelial regeneration. The epithelial senescence was accompanied by p38 MAPK-dependent airway inflammation. Senescent NCI-H441 cells impaired epithelial wound repair and secreted increased amounts of pro-inflammatory cytokines in a p38 MAPK-dependent manner. Clara cell senescence in COPD patients was accelerated and accompanied by p38 MAPK activation.

Conclusions
Senescence of airway epithelial cells impairs repair processes and exacerbates p38 MAPK-dependent inflammation after airway injury, and it may contribute to the pathogenesis of COPD.
PAPC and the Wnt5a/Ror2 pathway control the invagination of the otic placode in Xenopus
Authors: Jung Barbara , Köhler Almut , Schambony Alexandra , Wedlich Doris 
Published: June 2011

Abstract

Background
Paraxial protocadherin (PAPC) plays a crucial role in morphogenetic movements during gastrulation and somitogenesis in mouse, zebrafish and Xenopus. PAPC influences cell-cell adhesion mediated by C-Cadherin. A putative direct adhesion activity of PAPC is discussed. PAPC also promotes cell elongation, tissue separation and coordinates cell mass movements. In these processes the signaling function of PAPC in activating RhoA/JNK and supporting Wnt-11/PCP by binding to frizzled 7 (fz7) is important.

Results
Here we demonstrate by loss of function experiments in Xenopus embryos that PAPC regulates another type of morphogenetic movement, the invagination of the ear placode. Knockdown of PAPC by antisense morpholinos results in deformation of the otic vesicle without altering otocyst marker expression. Depletion of PAPC could be rescued by full-length PAPC, constitutive active RhoA and by the closely related PCNS but not by classical cadherins. Also the cytoplasmic deletion mutant M-PAPC, which influences cell adhesion, does not rescue the PAPC knockdown. Interestingly, depletion of Wnt5a or Ror2 which are also expressed in the otocyst phenocopies the PAPC morphant phenotype.

Conclusions
PAPC signaling via RhoA and Wnt5a/Ror2 activity are required to keep cells aligned in apical-basal orientation during invagination of the ear placode. Since neither the cytoplasmic deletion mutant M-PAPC nor a classical cadherin is able to rescue loss of PAPC we suggest that the signaling function of the protocadherin rather than its role as modulator of cell-cell adhesion is required during invagination of the ear placode.
Testis-specific glyceraldehyde-3-phosphate dehydrogenase: origin and evolution
Authors: Kuravsky Mikhail L , Aleshin Vladimir V , Frishman Dmitrij , Muronetz Vladimir I 
Published: June 2011

AbstractBackgroundGlyceraldehyde-3-phosphate dehydrogenase (GAPD) catalyses one of the glycolytic reactions and is also involved in a number of non-glycolytic processes, such as endocytosis, DNA excision repair, and induction of apoptosis. Mammals are known to possess two homologous GAPD isoenzymes: GAPD-1, a well-studied protein found in all somatic cells, and GAPD-2, which is expressed solely in testis. GAPD-2 supplies energy required for the movement of spermatozoa and is tightly bound to the sperm tail cytoskeleton by the additional N-terminal proline-rich domain absent in GAPD-1. In this study we investigate the evolutionary history of GAPD and gain some insights into specialization of GAPD-2 as a testis-specific protein.ResultsA dataset of GAPD sequences was assembled from public databases and used for phylogeny reconstruction by means of the Bayesian method. Since resolution in some clades of the obtained tree was too low, syntenic analysis was carried out to define the evolutionary history of GAPD more precisely. The performed selection tests showed that selective pressure varies across lineages and isoenzymes, as well as across different regions of the same sequences.ConclusionsThe obtained results suggest that GAPD-1 and GAPD-2 emerged after duplication during the early evolution of chordates. GAPD-2 was subsequently lost by most lineages except lizards, mammals, as well as cartilaginous and bony fishes. In reptilians and mammals, GAPD-2 specialized to a testis-specific protein and acquired the novel N-terminal proline-rich domain anchoring the protein in the sperm tail cytoskeleton. This domain is likely to have originated by exonization of a microsatellite genomic region. Recognition of the proline-rich domain by cytoskeletal proteins seems to be unspecific. Besides testis, GAPD-2 of lizards was also found in some regenerating tissues, but it lacks the proline-rich domain due to tissue-specific alternative splicing.
A tissue-specific landscape of sense/antisense transcription in the mouse intestine
Authors: Klostermeier Ulrich C , Barann Matthias , Wittig Michael , Häsler Robert , Franke Andre , Gavrilova Olga , Kreck Benjamin , Sina Christian , Schilhabel Markus B , Schreiber Stefan , Rosenstiel Philip 
Published: June 2011

Abstract

Background
The intestinal mucosa is characterized by complex metabolic and immunological processes driven highly dynamic gene expression programs. With the advent of next generation sequencing and its utilization for the analysis of the RNA sequence space, the level of detail on the global architecture of the transcriptome reached a new order of magnitude compared to microarrays.

Results
We report the ultra-deep characterization of the polyadenylated transcriptome in two closely related, yet distinct regions of the mouse intestinal tract (small intestine and colon). We assessed tissue-specific transcriptomal architecture and the presence of novel transcriptionally active regions (nTARs). In the first step, signatures of 20,541 NCBI RefSeq transcripts could be identified in the intestine (74.1% of annotated genes), thereof 16,742 are common in both tissues. Although the majority of reads could be linked to annotated genes, 27,543 nTARs not consistent with current gene annotations in RefSeq or ENSEMBL were identified. By use of a second independent strand-specific RNA-Seq protocol, 20,966 of these nTARs were confirmed, most of them in vicinity of known genes. We further categorized our findings by their relative adjacency to described exonic elements and investigated regional differences of novel transcribed elements in small intestine and colon.

Conclusions
The current study demonstrates the complexity of an archetypal mammalian intestinal mRNA transcriptome in high resolution and identifies novel transcriptionally active regions at strand-specific, single base resolution. Our analysis for the first time shows a strand-specific comparative picture of nTARs in two tissues and represents a resource for further investigating the transcriptional processes that contribute to tissue identity.
Identification of novel soybean microRNAs involved in abiotic and biotic stresses
Authors: Kulcheski Franceli R , de Oliveira Luiz FV , Molina Lorrayne G , Almerão Maurício P , Rodrigues Fabiana A , Marcolino Juliana , Barbosa Joice F , Stolf-Moreira Renata , Nepomuceno Alexandre L , Marcelino-Guimarães Francismar C , Abdelnoor Ricardo V , Nascimento Leandro C , Carazzolle Marcelo F , Pereira Gonçalo AG , Margis Rogério 
Published: June 2011

Abstract

Background
Small RNAs (19-24 nt) are key regulators of gene expression that guide both transcriptional and post-transcriptional silencing mechanisms in eukaryotes. Current studies have demonstrated that microRNAs (miRNAs) act in several plant pathways associated with tissue proliferation, differentiation, and development and in response to abiotic and biotic stresses. In order to identify new miRNAs in soybean and to verify those that are possibly water deficit and rust-stress regulated, eight libraries of small RNAs were constructed and submitted to Solexa sequencing.

Results
The libraries were developed from drought-sensitive and tolerant seedlings and rust-susceptible and resistant soybeans with or without stressors. Sequencing the library and subsequent analyses detected 256 miRNAs. From this total, we identified 24 families of novel miRNAs that had not been reported before, six families of conserved miRNAs that exist in other plants species, and 22 families previously reported in soybean. We also observed the presence of several isomiRNAs during our analyses. To validate novel miRNAs, we performed RT-qPCR across the eight different libraries. Among the 11 miRNAs analyzed, all showed different expression profiles during biotic and abiotic stresses to soybean. The majority of miRNAs were up-regulated during water deficit stress in the sensitive plants. However, for the tolerant genotype, most of the miRNAs were down regulated. The pattern of miRNAs expression was also different for the distinct genotypes submitted to the pathogen stress. Most miRNAs were down regulated during the fungus infection in the susceptible genotype; however, in the resistant genotype, most miRNAs did not vary during rust attack. A prediction of the putative targets was carried out for conserved and novel miRNAs families.

Conclusions
Validation of our results with quantitative RT-qPCR revealed that Solexa sequencing is a powerful tool for miRNA discovery. The identification of differentially expressed plant miRNAs provides molecular evidence for the possible involvement of miRNAs in the process of water deficit- and rust-stress responses.
A comprehensive transcriptome and immune-gene repertoire of the lepidopteran model host Galleria mellonella
Authors: Vogel Heiko , Altincicek Boran , Glöckner Gernot , Vilcinskas Andreas 
Published: June 2011

AbstractBackgroundThe larvae of the greater wax mothGalleria mellonellaare increasingly used (i) as mini-hosts to study pathogenesis and virulence factors of prominent bacterial and fungal human pathogens, (ii) as a whole-animal high throughput infection system for testing pathogen mutant libraries, and (iii) as a reliable host model to evaluate the efficacy of antibiotics against human pathogens. In order to compensate for the lack of genomic information inGalleria, we subjected the transcriptome of different developmental stages and immune-challenged larvae to next generation sequencing.ResultsWe performed aGalleriatranscriptome characterization on the Roche 454-FLX platform combined with traditional Sanger sequencing to obtain a comprehensive transcriptome. To maximize sequence diversity, we pooled RNA extracted from different developmental stages, larval tissues including hemocytes, and from immune-challenged larvae and normalized the cDNA pool. We generated a total of 789,105 pyrosequencing and 12,032 high-quality Sanger EST sequences which clustered into 18,690 contigs with an average length of 1,132 bases. Approximately 40% of the ESTs were significantly similar (E≤ e-03) to proteins of other insects, of which 45% have a reported function. We identified a large number of genes encoding proteins with established functions in immunity related sensing of microbial signatures and signaling, as well as effector molecules such as antimicrobial peptides and inhibitors of microbial proteinases. In addition, we found genes known as mediators of melanization or contributing to stress responses. Using the transcriptomic data, we identified hemolymph peptides and proteins induced upon immune challenge by 2D-gelelectrophoresis combined with mass spectrometric analysis.ConclusionHere, we have developed extensive transcriptomic resources forGalleria. The data obtained is rich in gene transcripts related to immunity, expanding remarkably our knowledge about immune and stress-inducible genes inGalleriaand providing the complete sequences of genes whose primary structure have only partially been characterized using proteomic methods. The generated data provide for the first time access to the genetic architecture of immunity in this model host, allowing us to elucidate the molecular mechanisms underlying pathogen and parasite response and detailed analyses of both its immune responses against human pathogens, and its coevolution with entomopathogens.
Recombination phenotypes of the NCI-60 collection of human cancer cells
Authors: Stults Dawn M , Killen Michael W , Shelton Brent J , Pierce Andrew J 
Published: June 2011

Abstract

Background
The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60.

Results
We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of GCI or were sensitive to hmdUrd. With the exception of the NCI-H23 lung cancer line, these phenotypes were not found to overlap. None of the lines examined in either subset exhibited significant changes in the frequency of sister chromatid exchanges (SCE), neither did any of the lines in either subset exhibit microsatellite instability (MSI) indicative of defects in DNA mismatch repair.

Conclusions
Gene cluster instability, sensitivity to hmdUrd and sister chromatid exchange are mechanistically distinct phenomena. Genomic instability in the NCI-60 appears to involve only one mechanism of instability for each individual cell line.
A molecular epidemiological study of respiratory viruses detected in Japanese children with acute wheezing illness
Authors: Fujitsuka Asako , Tsukagoshi Hiroyuki , Arakawa Mika , Goto-Sugai Kazuko , Ryo Akihide , Okayama Yoshimichi , Mizuta Katsumi , Nishina Atsuyoshi , Yoshizumi Masakazu , Kaburagi Yoichi , Noda Masahiro , Tashiro Masato , Okabe Nobuhiko , Mori Masaaki , Yokota Shumpei , Kimura Hirokazu 
Published: June 2011

AbstractBackgroundRecent studies strongly suggest that some respiratory viruses are associated with the induction of acute wheezing and/or exacerbation of bronchial asthma. However, molecular epidemiology of these viruses is not exactly known.MethodsUsing PCR technology, we attempted to detect various respiratory viruses from 115 Japanese children. Furthermore, the detected viruses were subjected to homology, pairwise distance, and phylogenetic analysis.ResultsViruses were detected from 99 (86.1%) patients. Respiratory syncytial virus (RSV) alone and human rhinovirus (HRV) alone were detected in 47 (40.9%) and 36 (31.3%) patients, respectively. Both RSV and HRV were detected in 14 (12.2%) patients. Human metapneumovirus (HMPV) alone and human parainfluenza virus (HPIV) alone were detected in 1 (0.9%) patient each, respectively. Homology and phylogenetic analyses showed that the RSV and HRV strains were classified into genetically diverse species or subgroups. In addition, RSV was the dominant virus detected in patients with no history of wheezing, whereas HRV was dominant in patients with a history of wheezing.ConclusionsThe results suggested that these genetically diverse respiratory viruses, especially RSV and HRV, might be associated with wheezing in Japanese children.
Duration and determinants of birth interval among women of child bearing age in Southern Ethiopia
Authors: Yohannes Samuel , Wondafrash Mekitie , Abera Mulumebet , Girma Eshetu 
Published: June 2011

Abstract

Background
Longer intervals between consecutive births decrease the number of children a woman can have. This results in beneficial effects on population size and on the health status of mothers and children. Therefore, understanding the practice of birth interval and its determinants is helpful to design evidence based strategies for interventions. The objective of this study was to determine duration and determinants of birth interval among women of child bearing age in Lemo district, southern Ethiopia in March 2010.

Methods
A community based cross sectional study design with stratified multistage sampling technique was employed. A sample of 844 women of child bearing age were selected by using simple random sampling technique after complete census was conducted in selected kebeles prior to data collection. Structured interviewer administered questionnaire was used for data collection. Actual birth interval was measured with the respondents' memory since majority of the women or their children in the area had no birth certificate.

Results
Majority (57%) of women were practicing short birth interval length with the median birth interval length of 33 months. Actual birth interval length is significantly shorter than preferred birth interval length. Birth interval showed significant variation by contraceptive use, residence, wealth index, breast feeding and occupation of husbands.

Conclusion
low proportion of optimal birth spacing practices with short actual birth interval length and longer preferred birth interval lengths were evident among the study subjects. Hence interventions to enhance contraceptive utilization behaviors among women in Lemo district would be helpful to narrow the gap between optimal and actual birth spacing.
Thymidine Phosphorylase/β-tubulin III expressions predict the response in Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel
Authors: Gao Jing , Lu Ming , Yu Jing-wei , Li Yan-yan , Shen Lin 
Published: June 2011

AbstractBackgroundTo assess the role of Thymidine Phosphorylase and β-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.MethodsThe clinical data and tumor biopsies prior treatment from 33 advanced gastric cancer patients receiving capecitabine plus paclitaxel (cohort 1, experimental group) and 18 patients receiving capecitabine plus cisplatin (cohort 2, control group) in Beijing Cancer Hospital from July 2003 to December 2008 were retrospectively collected and analyzed for Thymidine Phosphorylase and β-tubulin III expressions by immunohistochemistry. The relationships between expressions of biomarkers and response or survival were determined by statistical analysis.ResultsThe median age of 51 patients was 57 years (range, 27-75) with male 34 and female 17, and the response rate, median progression-free survival and overall survival were 43.1%, 120d and 265d. Among cohort 1, the response rate, median progression-free survival and overall survival in β-tubulin III positive (n = 22) and negative patients (n = 11) were 36.4%/72.7% (positive vs negative,P= 0.049), 86d/237d (P= 0.046) and 201d/388d (P= 0.029), respectively; the response rate (87.5% vs 14.3%,P= 0.01) and median progression-free survival (251d vs 84d,P= 0.003) in Thymidine Phosphorylase positive & β-tubulin III negative patients (n = 8) were also significantly higher than those in Thymidine Phosphorylase negative & β-tubulin III positive patients (n = 7). There was no correlation between β-tubulin III expression and response or survival among cohort 2 (n = 18).ConclusionsIn Chinese advanced gastric cancer, Thymidine Phosphorylase positive & β-tubulin III negative might predict response and prognosis to capecitabine plus paclitaxel chemotherapy. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.