bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation
Authors: Rettinger Eva , Willasch Andre M. , Kreyenberg Hermann , Borkhardt Arndt , Holter Wolfgang , Kremens Bernhard , Strahm Brigitte , Woessmann Wilhelm , Mauz-Koerholz Christine , Gruhn Bernd , Burdach Stefan , Albert Michael H. , Schlegel Paul-Gerhardt , Klingebiel Thomas , Bader Peter 
Published: September 2011

AbstractPrevious studies have shown that children with acute myeloid leukemia (AML) who developed mixed chimerism (MC) were at high risk for relapse after allogeneic stem-cell transplantation (allo-SCT). We investigated the feasibility of intensified preemptive immunotherapy in children receiving allo-SCT for AML. Eighty-four children were registered in our trial from May 2005 to April 2009; of these, 71 fulfilled the inclusion criteria and were treated according to the study protocol. Serial and semiquantitative analyses of posttransplantation chimerism were performed. Defined immunotherapy approaches were considered in MC patients. Continuous complete chimerism (CC) was observed in 51 of 71 patients. MC was detected in 20 patients and was followed by immunotherapy in 13. Six of 13 MC patients returned to CC without toxicity and remained in long-term remission. Overall, the probability of event-free survival (pEFS) was 66% (95% confidence interval [95% CI] = 53%-76%) for all patients and 46% (95% CI = 19%-70%) in MC patients with intervention; however, this number increased to 71% (95% CI = 26%-92%) in 7 of 13 MC patients on immunotherapy who were in remission at the time of transplantation. All MC patients without intervention relapsed. These results suggest that MC is a prognostic factor for impending relapse in childhood AML, and that preemptive immunotherapy may improve the outcome in defined high-risk patients after transplantation.
Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade
Authors: Ikebuchi Ryoyo , Konnai Satoru , Shirai Tatsuya , Sunden Yuji , Murata Shiro , Onuma Misao , Ohashi Kazuhiko 
Published: September 2011

Abstract
The inhibitory receptor programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV) infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.
Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase
Authors: Qi Feng , Pradhan Ranjan K , Dash Ranjan K , Beard Daniel A 
Published: September 2011

Abstract

Background
Mitochondrial 2-oxoglutarate (α-ketoglutarate) dehydrogenase complex (OGDHC), a key regulatory point of tricarboxylic acid (TCA) cycle, plays vital roles in multiple pathways of energy metabolism and biosynthesis. The catalytic mechanism and allosteric regulation of this large enzyme complex are not fully understood. Here computer simulation is used to test possible catalytic mechanisms and mechanisms of allosteric regulation of the enzyme by nucleotides (ATP, ADP), pH, and metal ion cofactors (Ca2+ and Mg2+).

Results
A model was developed based on an ordered ter-ter enzyme kinetic mechanism combined with con-formational changes that involve rotation of one lipoic acid between three catalytic sites inside the enzyme complex. The model was parameterized using a large number of kinetic data sets on the activity of OGDHC, and validated by comparison of model predictions to independent data.

Conclusions
The developed model suggests a hybrid rapid-equilibrium ping-pong random mechanism for the kinetics of OGDHC, consistent with previously reported mechanisms, and accurately describes the experimentally observed regulatory effects of cofactors on the OGDHC activity. This analysis provides a single consistent theoretical explanation for a number of apparently contradictory results on the roles of phosphorylation potential, NAD (H) oxidation-reduction state ratio, as well as the regulatory effects of metal ions on ODGHC function.
Prediction of protein-binding areas by small-world residue networks and application to docking
Authors: Pons Carles , Glaser Fabian , Fernandez-Recio Juan 
Published: September 2011

Abstract

Background
Protein-protein interactions are involved in most cellular processes, and their detailed physico-chemical and structural characterization is needed in order to understand their function at the molecular level. In-silico docking tools can complement experimental techniques, providing three-dimensional structural models of such interactions at atomic resolution. In several recent studies, protein structures have been modeled as networks (or graphs), where the nodes represent residues and the connecting edges their interactions. From such networks, it is possible to calculate different topology-based values for each of the nodes, and to identify protein regions with high centrality scores, which are known to positively correlate with key functional residues, hot spots, and protein-protein interfaces.

Results
Here we show that this correlation can be efficiently used for the scoring of rigid-body docking poses. When integrated into the pyDock energy-based docking method, the new combined scoring function significantly improved the results of the individual components as shown on a standard docking benchmark. This improvement was particularly remarkable for specific protein complexes, depending on the shape, size, type, or flexibility of the proteins involved.

Conclusions
The network-based representation of protein structures can be used to identify protein-protein binding regions and to efficiently score docking poses, complementing energy-based approaches.
iCTNet: A Cytoscape plugin to produce and analyze integrative complex traits networks
Authors: Wang Lili , Khankhanian Pouya , Baranzini Sergio E , Mousavi Parvin 
Published: September 2011

Abstract

Background
The speed at which biological datasets are being accumulated stands in contrast to our ability to integrate them meaningfully. Large-scale biological databases containing datasets of genes, proteins, cells, organs, and diseases are being created but they are not connected. Integration of these vast but heterogeneous sources of information will allow the systematic and comprehensive analysis of molecular and clinical datasets, spanning hundreds of dimensions and thousands of individuals. This integration is essential to capitalize on the value of current and future molecular- and cellular-level data on humans to gain novel insights about health and disease.

Results
We describe a new open-source Cytoscape plugin named iCTNet (i ntegrated C omplex T raits Net works). iCTNet integrates several data sources to allow automated and systematic creation of networks with up to five layers of omics information: phenotype-SNP association, protein-protein interaction, disease-tissue, tissue-gene, and drug-gene relationships. It facilitates the generation of general or specific network views with diverse options for more than 200 diseases. Built-in tools are provided to prioritize candidate genes and create modules of specific phenotypes.

Conclusions
iCTNet provides a user-friendly interface to search, integrate, visualize, and analyze genome-scale biological networks for human complex traits. We argue this tool is a key instrument that facilitates systematic integration of disparate large-scale data through network visualization, ultimately allowing the identification of disease similarities and the design of novel therapeutic approaches.
The online database and Cytoscape plugin are freely available for academic use at: http://www.cs.queensu.ca/ictnet
Widespread Horizontal Gene Transfer from Circular Single-stranded DNA Viruses to Eukaryotic Genomes
Authors: Liu Huiquan , Fu Yanping , Li Bo , Yu Xiao , Xie Jiatao , Cheng Jiasen , Ghabrial Said A , Li Guoqing , Yi Xianhong , Jiang Daohong 
Published: September 2011

Abstract

Background
In addition to vertical transmission, organisms can also acquire genes from other distantly related species or from their extra-chromosomal elements (plasmids and viruses) via horizontal gene transfer (HGT). It has been suggested that phages represent substantial forces in prokaryotic evolution. In eukaryotes, retroviruses, which can integrate into host genome as an obligate step in their replication strategy, comprise approximately 8% of the human genome. Unlike retroviruses, few members of other virus families are known to transfer genes to host genomes.

Results
Here we performed a systematic search for sequences related to circular single-stranded DNA (ssDNA) viruses in publicly available eukaryotic genome databases followed by comprehensive phylogenetic analysis. We conclude that the replication initiation protein (Rep)-related sequences of geminiviruses, nanoviruses and circoviruses have been frequently transferred to a broad range of eukaryotic species, including plants, fungi, animals and protists. Some of the transferred viral genes were conserved and expressed, suggesting that these genes have been coopted to assume cellular functions in the host genomes. We also identified geminivirus-like and parvovirus-like transposable elements in genomes of fungi and lower animals, respectively, and thereby provide direct evidence that eukaryotic transposons could derive from ssDNA viruses.

Conclusions
Our discovery extends the host range of circular ssDNA viruses and sheds light on the origin and evolution of these viruses. It also suggests that ssDNA viruses act as an unforeseen source of genetic innovation in their hosts.
Genome wide gene expression regulation by HIP1 Protein Interactor, HIPPI: Prediction and validation
Authors: Datta Moumita , Choudhury Ananyo , Lahiri Ansuman , Bhattacharyya Nitai P 
Published: September 2011

Abstract

Background
HIP1 Protein Interactor (HIPPI) is a pro-apoptotic protein that induces Caspase8 mediated apoptosis in cell. We have shown earlier that HIPPI could interact with a specific 9 bp sequence motif, defined as the HIPPI binding site (HBS), present in the upstream promoter of Caspase1 gene and regulate its expression. We also have shown that HIPPI, without any known nuclear localization signal, could be transported to the nucleus by HIP1, a NLS containing nucleo-cytoplasmic shuttling protein. Thus our present work aims at the investigation of the role of HIPPI as a global transcription regulator.

Results
We carried out genome wide search for the presence of HBS in the upstream sequences of genes. Our result suggests that HBS was predominantly located within 2 Kb upstream from transcription start site. Transcription factors like CREBP1, TBP, OCT1, EVI1 and P53 half site were significantly enriched in the 100 bp vicinity of HBS indicating that they might co-operate with HIPPI for transcription regulation. To illustrate the role of HIPPI on transcriptome, we performed gene expression profiling by microarray. Exogenous expression of HIPPI in HeLa cells resulted in up-regulation of 580 genes (p < 0.05) while 457 genes were down-regulated. Several transcription factors including CBP, REST, C/EBP beta were altered by HIPPI in this study. HIPPI also interacted with P53 in the protein level. This interaction occurred exclusively in the nuclear compartment and was absent in cells where HIP1 was knocked down. HIPPI-P53 interaction was necessary for HIPPI mediated up-regulation of Caspase1 gene. Finally, we analyzed published microarray data obtained with post mortem brains of Huntington's disease (HD) patients to investigate the possible involvement of HIPPI in HD pathogenesis. We observed that along with the transcription factors like CREB, P300, SREBP1, Sp1 etc. which are already known to be involved in HD, HIPPI binding site was also significantly over-represented in the upstream sequences of genes altered in HD.

Conclusions
Taken together, the results suggest that HIPPI could act as an important transcription regulator in cell regulating a vast array of genes, particularly transcription factors and at least, in part, play a role in transcription deregulation observed in HD.
Analyses of the oligopeptide transporter gene family in poplar and grape
Authors: Cao Jun , Huang Jinling , Yang Yongping , Hu Xiangyang 
Published: September 2011

Abstract

Background
Oligopeptide transporters (OPTs) are a group of membrane-localized proteins that have a broad range of substrate transport capabilities and that are thought to contribute to many biological processes. The OPT proteins belong to a small gene family in plants, which includes about 25 members in Arabidopsis and rice. However, no comprehensive study incorporating phylogeny, chromosomal location, gene structure, expression profiling, functional divergence and selective pressure analysis has been reported thus far for Populus and Vitis.

Results
In the present study, a comprehensive analysis of the OPT gene family in Populus (P. trichocarpa) and Vitis (V. vinifera) was performed. A total of 20 and 18 full-length OPT genes have been identified in Populus and Vitis, respectively. Phylogenetic analyses indicate that these OPT genes consist of two classes that can be further subdivided into 11 groups. Gene structures are considerably conserved among the groups. The distribution of OPT genes was found to be non-random across chromosomes. A high proportion of the genes are preferentially clustered, indicating that tandem duplications may have contributed significantly to the expansion of the OPT gene family. Expression patterns based on our analyses of microarray data suggest that many OPT genes may be important in stress response and functional development of plants. Further analyses of functional divergence and adaptive evolution show that, while purifying selection may have been the main force driving the evolution of the OPTs, some of critical sites responsible for the functional divergence may have been under positive selection.

Conclusions
Overall, the data obtained from our investigation contribute to a better understanding of the complexity of the Populus and Vitis OPT gene family and of the function and evolution of the OPT gene family in higher plants.
Clinical features of headache associated with mobile phone use: a cross-sectional study in university students
Authors: Chu Min Kyung , Song Hoon Geun , Kim Chulho , Lee Byung Chul 
Published: September 2011

AbstractBackgroundHeadache has been reported to be associated with mobile phone (MP) use in some individuals. The causal relationship between headache associated with MP use (HAMP) and MP use is currently undetermined. Identifying the clinical features of HAMP may help in clarifying the pathophysiology of HAMP and in managing symptoms of individuals with HAMP. The aim of the present study is to describe the clinical features of HAMP.MethodsA 14-item questionnaire investigating MP use and headache was administered to 247 medical students at Hallym University, Korea. Individual telephone interviews were subsequently conducted with those participants who reported HAMP more than 10 times during the last 1 year on the clinical features of HAMP. We defined HAMP as a headache attack during MP use or within 1 hour after MP use.ResultsIn total, 214 (86.6%) students completed and returned the questionnaire. Forty (18.9%) students experienced HAMP more than 10 times during the last 1 year in the questionnaire survey. In subsequent telephone interviews, 37 (97.4%) interviewed participants reported that HAMP was triggered by prolonged MP use. HAMP was usually dull or pressing in quality (30 of 38, 79.0%), localised ipsilateral to the side of MP use (32 of 38, 84.2%), and associated with a burning sensation (24 of 38, 63.2%).ConclusionWe found that HAMP usually showed stereotyped clinical features including mild intensity, a dull or pressing quality, localisation ipsilateral to the side of MP use, provocation by prolonged MP use and often accompanied by a burning sensation.
Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT
Authors: Baldini Enke , Arlot-Bonnemains Yannick , Sorrenti Salvatore , Mian Caterina , Pelizzo Maria R , De Antoni Enrico , Palermo Silvio , Morrone Stefania , Barollo Susi , Nesca Angela , Moretti Costanzo G , D'Armiento Massimino , Ulisse Salvatore 
Published: September 2011

Abstract

Background
The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets.

Methods
The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy.

Results
The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar.

Conclusions
We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment.
Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma
Authors: Wu Song , Wang Yong , Sun Liang , Zhang Zhiling , Jiang Zhimao , Qin Zike , Han Hui , Liu Zhuowei , Li Xianxin , Tang Aifa , Gui Yaoting , Cai Zhiming , Zhou Fangjian 
Published: September 2011

Abstract

Background
The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs.

Methods
The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC.

Results
The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients.

Conclusion
To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC.
The extramural metastasis might be categorized in lymph node staging for colorectal cancer
Authors: Qiu Hai-Bo , Chen Gong , Keshari Rajiv P , Luo Hui-Yan , Fang Wang , Qiu Miao-Zhen , Zhou Zhi-Wei , Xu Rui-Hua 
Published: September 2011

Abstract

Background
The objective of this study is to assess the clinical significance and prognostic impact of extramural metastasis in colorectal carcinoma and establish an optimal categorization in the staging system.

Methods
To determine the frequency and prognostic significance of extramural metastasis, from 2000 to 2005, a total of 1,215 patients with colorectal cancer who underwent surgical resection were recruited into this study. Individual demographic and clinicopathologic data were collected including tumor stage, nodal stage, tumor histology, degree of tumor differentiation, and presence of lymphovascular invasion. After surgery, all patients received standard treatments and follow-up, which were closed in April 2010.

Results
EM was detected in 167 (13.7%) patients and in 230 (1.8%) of the 12,534 nodules retrieved as 'lymph nodes'. The incidence of extramural metastasis was significantly higher in patients with large tumors, deeper invasive depth and more lymph node metastasis (P < 0.001). After curative operation, overall survival was significantly worse for patients with extramural metastasis than those without (P < 0.001). Multivariate analysis identified extramural metastasis as an independent prognostic factor (RR = 2.1, 95%CI:1.5-3.0). By using the Akaike information criterion (AIC), N staging was capable of predicting survival outcome with the highest accuracy when both nodal involvement and extramural metastasis were treated together as N factors(AIC = 1025.3).

Conclusion
Extramural metastasis might be diagnosed as replaced lymph nodes in the process of classification, thus forming a new categorization.