bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of adaptive evolution between wheat and rice as deduced from full-length common wheat cDNA sequence data and expression patterns
Authors: Kawaura Kanako , Mochida Keiichi , Enju Akiko , Totoki Yasushi , Toyoda Atsushi , Sakaki Yoshiyuki , Kai Chikatoshi , Kawai Jun , Hayashizaki Yoshihide , Seki Motoaki , Shinozaki Kazuo , Ogihara Yasunari 
Published: June 2009

Abstract

Background
Wheat is an allopolyploid plant that harbors a huge, complex genome. Therefore, accumulation of expressed sequence tags (ESTs) for wheat is becoming particularly important for functional genomics and molecular breeding. We prepared a comprehensive collection of ESTs from the various tissues that develop during the wheat life cycle and from tissues subjected to stress. We also examined their expression profiles in silico. As full-length cDNAs are indispensable to certify the collected ESTs and annotate the genes in the wheat genome, we performed a systematic survey and sequencing of the full-length cDNA clones. This sequence information is a valuable genetic resource for functional genomics and will enable carrying out comparative genomics in cereals.

Results
As part of the functional genomics and development of genomic wheat resources, we have generated a collection of full-length cDNAs from common wheat. By grouping the ESTs of recombinant clones randomly selected from the full-length cDNA library, we were able to sequence 6,162 independent clones with high accuracy. About 10% of the clones were wheat-unique genes, without any counterparts within the DNA database. Wheat clones that showed high homology to those of rice were selected in order to investigate their expression patterns in various tissues throughout the wheat life cycle and in response to abiotic-stress treatments. To assess the variability of genes that have evolved differently in wheat and rice, we calculated the substitution rate (Ka/Ks) of the counterparts in wheat and rice. Genes that were preferentially expressed in certain tissues or treatments had higher Ka/Ks values than those in other tissues and treatments, which suggests that the genes with the higher variability expressed in these tissues is under adaptive selection.

Conclusion
We have generated a high-quality full-length cDNA resource for common wheat, which is essential for continuation of the ongoing curation and annotation of the wheat genome. The data for each clone's expression in various tissues and stress treatments and its variability in wheat and rice as a result of their diversification are valuable tools for functional genomics in wheat and for comparative genomics in cereals.
Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine
Authors: Rong Yefei , Jin Dayong , Wu Wenchuan , Lou Wenhui , Wang Danshong , Kuang Tiantao , Ni Xiaoling , Qin Xinyu 
Published: June 2009

Abstract

Background
Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer.

Methods
MUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups.

Results
The DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (P < 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (P < 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (P < 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells.

Conclusion
The MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer.
Triple negative breast carcinoma is a prognostic factor in Taiwanese women
Authors: Lin Che , Chien Su-Yu , Chen Li-Sheng , Kuo Shou-Jen , Chang Tsai-Wang , Chen Dar-Ren 
Published: June 2009

Abstract

Background
Currently, there is a debate as to whether triple negative breast carcinoma (TNBC) has a worse prognosis than non-TNBC. Our aim was to determine whether TNBC is a prognostic factor for survival.

Methods
We identified 1,048 Taiwanese breast carcinoma patients, of whom 167 (15.9%) had TNBC. Data used for analysis were derived from our cancer registry database for women with breast cancer who were diagnosed between 2002 January and 2006 December.

Results
In the Kaplan-Meier analysis, tumor subgroup (TNBC vs. non-TNBC) was a prognosis factor related to 5-year overall survival. In the univariate analysis, tumor subgroup (TNBC vs. non-TNBC) was a significant factor related to 5-year overall survival, in addition to age, tumor size, lymph node, metastasis, grade, stage, estrogen receptor status, progesterone receptor status, and HER2 overexpression status. In the multivariate analysis, tumor subgroup was not a significant factor related to 5-year disease-free survival (DFS). In node-positive patients, tumor subgroup was a significant factor related to 5-year overall survival, in addition to age, tumor size, metastasis, and grade. In node-negative patients, tumor subgroup was not a significant factor related to 5-year disease-free survival and 5-year overall survival.

Conclusion
Our results indicated that TNBC patients in Taiwan have worse 5-year overall survival than non-TNBC patients. Notably, in node-positive patients, TNBC played a prognostic role in 5-year overall survival.
CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma
Authors: McRonald Fiona E , Morris Mark R , Gentle Dean , Winchester Laura , Baban Dilair , Ragoussis Jiannis , Clarke Noel W , Brown Michael D , Kishida Takeshi , Yao Masahiro , Latif Farida , Maher Eamonn R 
Published: June 2009

Abstract

Background
Renal cell carcinoma (RCC) is histopathologically heterogeneous with clear cell and papillary the most common subtypes. The most frequent molecular abnormality in clear cell RCC is VHL inactivation but promoter methylation of tumour suppressor genes is common in both subtypes of RCC. To investigate whether RCC CpG methylation status was influenced by histopathology and VHL status we performed high-throughput epigenetic profiling using the Illumina Goldengate Methylation Array in 62 RCC (29 RCC from von Hippel-Lindau (VHL) disease patients, 20 sporadic clear cell RCC with wild type VHL and 13 sporadic papillary RCC).

Results
43 genes were methylated in >20% of primary RCC (range 20–45%) and most (37/43) of these had not been reported previously to be methylated in RCC. The distribution of the number of methylated CpGs in individual tumours differed from the expected Poisson distribution (p < 0.00001; log-likelihood G test) suggesting that a subset of RCC displayed a CpG Island Methylator Phenotype. Comparison of RCC subtypes revealed that, on average, tumour specific CpG methylation was most prevalent in papillary RCC and least in VHL RCC. Many of the genes preferentially methylated in pRCC were linked to TGFβ or ERK/Akt signalling.

Conclusion
These findings demonstrate differing patterns of tumour-specific CpG methylation in VHL and non VHL clear cell RCC and papillary RCC, and identify multiple novel potential CpG methylation biomarkers for RCC.
Molecular analysis of the apoptotic effects of BPA in acute myeloid leukemia cells
Authors: Bontempo Paola , Mita Luigi , Doto Antonella , Miceli Marco , Nebbioso Angela , Lepore Ilaria , Franci GianLuigi , Menafra Roberta , Carafa Vincenzo , Conte Mariarosaria , De Bellis Floriana , Manzo Fabio , Di Cerbo Vincenzo , Benedetti Rosaria , D'Amato Loredana , Marino Maria , Bolli Alessandro , Del Pozzo Giovanna , Diano Nadia , Portaccio Marianna , Mita Gustavo D , Vietri Maria Teresa , Cioffi Michele , Nola Ernesto , Dell'Aversana Carmela , Sica Vincenzo , Molinari Anna Maria , Altucci Lucia 
Published: June 2009

Abstract

Background:
BPA (bisphenol A or 2,2-bis(4-hydroxy-phenol)propane) is present in the manufacture of polycarbonate plastic and epoxy resins, which can be used in impact-resistant safety equipment and baby bottles, as protective coatings inside metal food containers, and as composites and sealants in dentistry. Recently, attention has focused on the estrogen-like and carcinogenic adverse effects of BPA. Thus, it is necessary to investigate the cytotoxicity and apoptosis-inducing activity of this compound.

Methods:
Cell cycle, apoptosis and differentiation analyses; western blots.

Results:
BPA is able to induce cell cycle arrest and apoptosis in three different acute myeloid leukemias. Although some granulocytic differentiation concomitantly occurred in NB4 cells upon BPA treatment, the major action was the induction of apoptosis. BPA mediated apoptosis was caspase dependent and occurred by activation of extrinsic and intrinsic cell death pathways modulating both FAS and TRAIL and by inducing BAD phosphorylation in NB4 cells. Finally, also non genomic actions such as the early decrease of both ERK and AKT phosphorylation were induced by BPA thus indicating that a complex intersection of regulations occur for the apoptotic action of BPA.

Conclusion:
BPA is able to induce apoptosis in leukemia cells via caspase activation and involvement of both intrinsic and extrinsic pathways of apoptosis.
SELDI-TOF MS profiling of serum for detection of nasopharyngeal carcinoma
Authors: Huang Yuan-Jiao , Xuan Chao , Zhang Bei-Bei , Liao Ming , Deng Kai-Feng , He Min , Zhao Jin-Min 
Published: June 2009

Abstract

Background
No satisfactory biomarkers are currently available to screen for nasopharyngeal carcinoma (NPC). We have developed and evaluated surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) for detection and analysis of multiple proteins for distinguishing individuals with NPC from control individuals.

Methods
A preliminary learning set and a classification tree of spectra derived from 24 patients with NPC and a group of 24 noncancer controls were used to develop a proteomic model that discriminated cancer from noncancer effectively. Then, the validity of the classification tree was challenged with a blind test set, which included another 20 patients with NPC and 12 noncancer controls.

Results
A panel of 3 biomarkers ranging m/z 3–20 k was selected to establish Decision Tree model by BPS with sensitivity of 91.66% and specificity of 95.83%. The ability to detect NPC patients was evaluated, a sensitivity of 95.0% and specificity of 83.33% were validated in blind testing set.

Conclusion
This high-flux proteomic classification system will provide a highly accurate and innovative approach for the detection/diagnosis of NPC.
Characterization of the tumor marker muc16 (ca125) expressed by murine ovarian tumor cell lines and identification of a panel of cross-reactive monoclonal antibodies
Authors: Goodell Cara AR , Belisle Jennifer A , Gubbels Jennifer AA , Migneault Martine , Rancourt Claudine , Connor Joseph , Kunnimalaiyaan Muthusamy , Kravitz Rachel , Tucker Ward , Zwick Michael , Patankar Manish S 
Published: June 2009

Abstract

Objectives
The ovarian tumor marker CA125 is expressed on human MUC16, a cell surface bound mucin that is also shed by proteolytic cleavage. Human MUC16 is overexpressed by ovarian cancer cells. MUC16 facilitates the binding of ovarian tumor cells to mesothelial cells lining the peritoneal cavity. Additionally, MUC16 also is a potent inhibitor of natural killer cell mediated anti-tumor cytotoxic responses. Extensive studies using human as well as murine ovarian tumor cell models are required to clearly define the function of MUC16 in the progression of ovarian tumors. The major objective of this study was to determine if the murine ovarian tumor cells, MOVCAR, express Muc16 and to characterize antibodies that recognize this mucin.

Methods
RT-PCR analysis was used for detecting the Muc16 message and size exclusion column chromatography for isolating Muc16 produced by MOVCAR cells. Soluble and cell-associated murine Muc16 were analyzed, respectively, by Western blotting and flow cytometry assays using a new panel of antibodies. The presence of N-linked oligosaccharides on murine Muc16 was determined by ConA chromatography.

Results
We demonstrate that murine Muc16 is expressed by mouse ovarian cancer cells as an ~250 kDa glycoprotein that carries both O-linked and N-linked oligosaccharides. In contrast to human MUC16, the murine ortholog is primarily released from the cells and cannot be detected on the cell surface. Since the released murine Muc16 is not detected by conventional anti-CA125 assays, we have for the first time identified a panel of anti-human MUC16 antibodies that also recognizes the murine counterpart.

Conclusion
The antibodies identified in this study can be used in future purification of murine Muc16 and exhaustive study of its properties. Furthermore, the initial identification and characterization of murine Muc16 is a vital preliminary step in the development of effective murine models of human ovarian cancer. These models will aid in the further elucidation of the role that human MUC16 plays in the etiology and progression of ovarian tumors.
Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study
Authors: Dubin Arnaldo , Pozo Mario O , Casabella Christian A , Pálizas Fernando , Murias Gastón , Moseinco Miriam C , Kanoore Edul Vanina S , Pálizas Fernando , Estenssoro Elisa , Ince Can 
Published: June 2009

Abstract
Introduction
Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation.

Methods
Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (ΔPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated.

Results
Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and ΔPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 ± 0.7, 2.2 ± 0.7, 2.0 ± 0.8) and the percent of perfused capillaries (72 ± 26, 71 ± 27, 67 ± 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 ± 10,17 ± 10,14 ± 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001).

Conclusions
Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.
Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction
Authors: Hofer Stefan , Brenner Thorsten , Bopp Christian , Steppan Jochen , Lichtenstern Christoph , Weitz Jürgen , Bruckner Thomas , Martin Eike , Hoffmann Ursula , Weigand Markus A 
Published: June 2009

Abstract
Introduction
Severe sepsis, septic shock, and resulting organ failure represent the most common cause of death in intensive care medicine, with mortality ranging from 40% to 70%. It is still unclear whether necrosis or apoptosis plays the predominant role in severe sepsis. Determining the prevalent mode of cell death would be valuable, as new therapeutic agents (eg, antiapoptotic drugs such as caspase inhibitors) may improve unsatisfactory outcomes in patients with severe sepsis. Furthermore, the prognostic value of newly developed cell death serum biomarkers is of great interest.

Methods
In total, 147 patients (101 patients with severe sepsis, 28 postoperative patients after major abdominal surgery, 18 healthy volunteers) were enrolled. Baseline and clinical data were evaluated. Blood samples from patients with severe sepsis were collected at the time of sepsis diagnosis, and 48 and 120 hours later; samples from healthy volunteers were collected once, and from postoperative patients, once immediately after surgery. We measured caspase-cleaved and uncleaved cytokeratin-18 (CK-18, intermediate filament protein) as a marker of cell death, isolated CK-18 fragments as a marker of apoptosis, as well as IL-6, soluble vascular cell adhesion molecule, and soluble intercellular adhesion molecule.

Results
Age and sex of patients with severe sepsis and postoperative patients were comparable, whereas healthy volunteers were significantly younger. In healthy volunteers, the mode of cellular turnover was primarily apoptotic cell death. Postoperative patients showed comparable levels of apoptotic activity, but necrotic cell death was markedly increased, probably due to surgical tissue injury. In contrast, patients with severe sepsis, and especially non-survivors of the septic group showed increased levels of markers for both apoptotic and necrotic cell death. In severe septic patients with liver dysfunction, necrosis is increased relative to severe septic patients with intact hepatic function. For severe septic patients with liver dysfunction, a cut-off value for caspase-cleaved and uncleaved cytokeratin-18 could be calculated, in order to identify patients at high risk for death due to severe sepsis.

Conclusions
The measurement of caspase-cleaved and uncleaved cytokeratin-18 appears to be an early predictor for survival in severe septic patients with hepatic dysfunction. Furthermore, the loss of parenchymal cells due to necrosis may be the primary mode of cell death in these patients. This may limit possible therapeutic options.
Muscular dystrophy begins early in embryonic development deriving from stem cell loss and disrupted skeletal muscle formation
Authors: Merrick Deborah , Stadler Lukas Kurt Josef , Larner Dean , Smith Janet 
Published: June 2009

SUMMARY
Examination of embryonic myogenesis of two distinct, but functionally related, skeletal muscle dystrophy mutants (mdx and cav-3−/−) establishes for the first time that key elements of the pathology of Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy type 1C (LGMD-1c) originate in the disruption of the embryonic cardiac and skeletal muscle patterning processes. Disruption of myogenesis occurs earlier in mdx mutants, which lack a functional form of dystrophin, than in cav-3−/− mutants, which lack the Cav3 gene that encodes the protein caveolin-3; this finding is consistent with the milder phenotype of LGMD-1c, a condition caused by mutations in Cav3, and the earlier [embryonic day (E)9.5] expression of dystrophin. Myogenesis is severely disrupted in mdx embryos, which display developmental delays; myotube morphology and displacement defects; and aberrant stem cell behaviour. In addition, the caveolin-3 protein is elevated in mdx embryos. Both cav-3−/− and mdx mutants (from E15.5 and E11.5, respectively) exhibit hyperproliferation and apoptosis of Myf5-positive embryonic myoblasts; attrition of Pax7-positive myoblasts in situ; and depletion of total Pax7 protein in late gestation. Furthermore, both cav-3−/− and mdx mutants have cardiac defects. In cav-3−/− mutants, there is a more restricted phenotype comprising hypaxial muscle defects, an excess of malformed hypertrophic myotubes, a twofold increase in myonuclei, and reduced fast myosin heavy chain (FMyHC) content. Several mdx mutant embryo pathologies, including myotube hypotrophy, reduced myotube numbers and increased FMyHC, have reciprocity with cav-3−/− mutants. In double mutant (mdxcav-3+/−) embryos that are deficient in dystrophin (mdx) and heterozygous for caveolin-3 (cav-3+/−), whereby caveolin-3 is reduced to 50% of wild-type (WT) levels, these phenotypes are severely exacerbated: intercostal muscle fibre density is reduced by 71%, and Pax7-positive cells are depleted entirely from the lower limbs and severely attenuated elsewhere; these data suggest a compensatory rather than a contributory role for the elevated caveolin-3 levels that are found in mdx embryos. These data establish a key role for dystrophin in early muscle formation and demonstrate that caveolin-3 and dystrophin are essential for correct fibre-type specification and emergent stem cell function. These data plug a significant gap in the natural history of muscular dystrophy and will be invaluable in establishing an earlier diagnosis for DMD/LGMD and in designing earlier treatment protocols, leading to better clinical outcome for these patients.
Haploinsufficiency of the murine polycomb gene Suz12 results in diverse malformations of the brain and neural tube
Authors: Miró Xavier , Zhou Xunlei , Boretius Susann , Michaelis Thomas , Kubisch Christian , Alvarez-Bolado Gonzalo , Gruss Peter 
Published: June 2009

SUMMARY
Polycomb proteins are epigenetic regulators of gene expression. Human central nervous system (CNS) malformations are congenital defects of the brain and spinal cord. One example of a human CNS malformation is Chiari malformation (CM), which presents as abnormal brainstem growth and cerebellar herniation, sometimes accompanied by spina bifida and cortical defects; it can occur in families. Clinically, CM ranges from an asymptomatic condition to one with incapacitating or lethal symptoms, including neural tube defects and hydrocephalus. However, no genes that are causally involved in any manifestation of CM or similar malformations have been identified. Here, we show that a pathway that involves Zac1 (also known as Plagl1 or Lot1) and controls neuronal proliferation is altered in mice that are heterozygous for the polycomb gene Suz12, resulting in a phenotype that overlaps with some clinical manifestations of the CM spectrum. Suz12 heterozygotes show cerebellar herniation and an enlarged brainstem, accompanied by occipital cortical alterations and spina bifida. Downward displacement of the cerebellum causes hydrocephalus in the most severely impaired cases. Although the involvement of polycomb genes in human disease is starting to be recognized, this is the first demonstration of their role in nervous system malformations. Our work strongly suggests that brain malformations such as CM can result from altered epigenetic regulation of genes involved in cell proliferation in the brain.