bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pylori Infection and Gastric Cancer Risk: Evaluation of 15 H. pylori Proteins Determined by Novel Multiplex Serology
Authors: Gao Lei , Michel Angelika , Weck Melanie N. , Arndt Volker , Pawlita Michael , Brenner Hermann 
Published: July 2009

Abstract
Infection with Helicobacter pylori is a major cause of gastric cancer (GC). The association likely has been underestimated in the past due to disease-related clearance of the infection. On the other hand, only a minority of the infected individuals develop GC, and better risk stratification is therefore highly desirable. We aimed to assess the association of GC with antibodies to 15 individual H. pylori proteins, determined by novel multiplex serology, to identify potentially relevant risk markers. This analysis was based on 123 GC cases aged 50 to 74 years and 492 age-matched and sex-matched controls from Saarland, Germany. Eight of the antibodies were significantly associated with noncardia GC and seven of them were significantly related to GC at any site. More pronounced associations were observed for noncardia GC; adjusted odds ratios (95% confidence intervals) ranged from 1.60 (1.01–2.54) for HyuA to 5.63 (3.20–9.91) for cytotoxin-associated antigen A (CagA). A dose-response relationship was found between the number of seropositivities and GC (P &lt; 0.001). The seropositivities of CagA and GroEL were found to be independent predictors of GC, which were strongly related to GC risk in a dose-response manner (P &lt; 0.001). In conclusion, GroEL was identified as a new independent risk marker that may contribute to enhanced quantification of H. pylori–related GC risk. [Cancer Res 2009;69(15):6164–70]
3-Phosphoinositide–Dependent Kinase 1 Potentiates Upstream Lesions on the Phosphatidylinositol 3-Kinase Pathway in Breast Carcinoma
Authors: Maurer Matthew , Su Tao , Saal Lao H. , Koujak Susan , Hopkins Benjamin D. , Barkley Christina R. , Wu Jiaping , Nandula Subhadra , Dutta Bhaskar , Xie Yuli , Chin Y. Rebecca , Kim Da-In , Ferris Jennifer S. , Gruvberger-Saal Sofia K. , Laakso Mervi , Wang Xiaomei , Memeo Lorenzo , Rojtman Albert , Matos Tulio , Yu Jennifer S. , Cordon-Cardo Carlos , Isola Jorma , Terry Mary Beth , Toker Alex , Mills Gordon B. , Zhao Jean J. , Murty Vundavalli V.V.S. , Hibshoosh Hanina , Parsons Ramon 
Published: July 2009

Abstract
Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels of phosphatidylinositol-3,4,5-triphosphate (PIP3). 3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT. PIP3 recruits PDK1 and AKT to the cell membrane through interactions with their pleckstrin homology domains, allowing PDK1 to activate AKT by phosphorylating it at residue threonine-308. We show that total PDK1 protein and mRNA were overexpressed in a majority of human breast cancers and that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We found that increased PDPK1 copy number was associated with upstream pathway lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient survival. Examination of an independent set of breast cancers and tumor cell lines derived from multiple forms of human cancers also found increased PDK1 protein levels associated with such upstream pathway lesions. In human mammary cells, PDK1 enhanced the ability of upstream lesions to signal to AKT, stimulate cell growth and migration, and rendered cells more resistant to PDK1 and PI3K inhibition. After orthotopic transplantation, PDK1 overexpression was not oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our studies argue that PDK1 overexpression and increased PDPK1 copy number are common occurrences in cancer that potentiate the oncogenic effect of upstream lesions on the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer. [Cancer Res 2009;69(15):6299–306]
Functional Unresponsiveness and Replicative Senescence of Myeloid Leukemia Antigen–specific CD8+ T Cells After Allogeneic Stem Cell Transplantation
Authors: Beatty Gregory L. , Smith Jasmine S. , Reshef Ran , Patel Kunal P. , Colligon Theresa A. , Vance Barbara A. , Frey Noelle V. , Johnson F. Brad , Porter David L. , Vonderheide Robert H. 
Published: July 2009

AbstractPurpose: The therapeutic effect of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with myeloid malignancies has been attributed in part to a graft-versus-leukemia effect that is dependent on donor T lymphocytes. CD8+ T-cell responses to MHC class I–restricted tumor epitopes, not just allogeneic antigens, may help mediate antileukemia effects after HSCT, but the specificity and function of such cells are not completely understood.Experimental Design: We examined the diversity, phenotype, and functional potential of leukemia-associated antigen-specific CD8+ T cells in patients with myeloid leukemia following allogeneic HSCT. Screening for antigen-specific T cells was accomplished with a peptide/MHC tetramer library.Results: Patients with acute myelogenous leukemia or chronic myelogenous leukemia in remission following HSCT exhibited significant numbers of peripheral blood CD8+ T cells that recognized varying combinations of epitopes derived from leukemia-associated antigens. However, these cells failed to proliferate, release cytokines, or degranulate in response to antigen-specific stimuli. As early as 2 months after HSCT, CD8+ T cells from patients were predominantly CD28− CD57+ and had relatively short telomeres, consistent with cellular senescence.Conclusions: Circulating leukemia-specific CD8+ T cells are prominent in myeloid leukemia patients after HSCT, but such cells are largely functionally unresponsive, most likely due to replicative senescence. These findings carry important implications for the understanding of the graft-versus-leukemia effect and for the rational design of immunotherapeutic strategies for patients with myeloid leukemias.
Human T-cell leukemia virus type 2 produces a spliced antisense transcript encoding a protein that lacks a classic bZIP domain but still inhibits Tax2-mediated transcription
Authors: Halin Marilène , Douceron Estelle , Clerc Isabelle , Journo Chloé , Ko Nga Ling , Landry Sébastien , Murphy Edward L. , Gessain Antoine , Lemasson Isabelle , Mesnard Jean-Michel , Barbeau Benoît , Mahieux Renaud 
Published: July 2009

AbstractHuman T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) retroviruses infect T lymphocytes. The minus strand of the HTLV-1 genome encodes HBZ, a protein that could play a role in the development of leukemia in infected patients. Herein, we demonstrate that the complementary strand of the HTLV-2 genome also encodes a protein that we named APH-2 for “antisense protein of HTLV-2.” APH-2 mRNA is spliced, polyadenylated, and initiates in the 3′-long terminal repeat at different positions. This transcript was detected in all HTLV-2–infected cell lines and short-term culture of lymphocytes obtained from HTLV-2 African patients tested and in 4 of 15 HTLV-2–infected blood donors. The APH-2 protein is 183 amino acids long, is localized in the cell nucleus, and is detected in vivo. Despite the lack of a consensus basic leucine zipper domain, APH-2 interacts with cyclic adenosine monophosphate-response element binding protein (CREB) and represses Tax2-mediated transcription in Tax2-expressing cells and in cells transfected with an HTLV-2 molecular clone. Altogether, our results demonstrate the existence of an antisense strand–encoded protein in HTLV-2, which could represent an important player in the development of disorders, such as lymphocytosis, which is frequently observed in HTLV-2 patients.
First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia
Authors: Eichhorst Barbara F. , Busch Raymonde , Stilgenbauer Stephan , Stauch Martina , Bergmann Manuela A. , Ritgen Matthias , Kranzhöfer Nicole , Rohrberg Robert , Söling Ulrike , Burkhard Oswald , Westermann Anne , Goede Valentin , Schweighofer Carmen D. , Fischer Kirsten , Fink Anna-Maria , Wendtner Clemens M. , Brittinger Günter , Döhner Hartmut , Emmerich Bertold , Hallek Michael ,   the German CLL Study Group (GCLLSG)
Published: July 2009

Abstract
Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m2 for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.4 mg/kg body weight [BW] with an increase to 0.8 mg/kg, every 15 days, for 12 months). Fludarabine resulted in a significantly higher overall and complete remission rate (72% vs 51%, P = .003; 7% vs 0%, P = .011). Time to treatment failure was significantly shorter in the chlorambucil arm (11 vs 18 months; P = .004), but no difference in progression-free survival time was observed (19 months with fludarabine, 18 months with chlorambucil; P = .7). Moreover, fludarabine did not increase the overall survival time (46 months in the fludarabine vs 64 months in the chlorambucil arm; P = .15). Taken together, the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil. This trial is registered with www.isrctn.org under identifier ISRCTN 36294212.
Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome
Authors: Kayser Sabine , Schlenk Richard F. , Londono Martina Correa , Breitenbuecher Frank , Wittke Kerstin , Du Juan , Groner Silja , Späth Daniela , Krauter Jürgen , Ganser Arnold , Döhner Hartmut , Fischer Thomas , Döhner Konstanze ,   for the German-Austrian AML Study Group (AMLSG)
Published: July 2009

AbstractTo evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD–positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3-ITD–mutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD), n = 148; JMD hinge region, n = 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n = 73; remaining TKD1 region, n = 13. ITD length was strongly correlated with functional regions (P < .001). In multivariable analyses, ITD integration site in the beta1-sheet was identified as an unfavorable prognostic factor for achievement of a complete remission (odds ratio, 0.22; P = .01), relapse-free survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio, 1.59; P = .008). ITD insertion site in the beta1-sheet appears to be an important unfavorable prognostic factor in young adult patients with FLT3-ITD–positive AML. The clinical trials described herein have been registered as follows: AML HD93 (already published in 2003), AML HD98A (NCT00146120; http://www.ClinicalTrials.gov), and AMLSG 07-04 (NCT00151242; http://www.ClinicalTrials.gov).
A compartmentalized approach to the assembly of physical maps
Authors: Bozdag Serdar , Close Timothy J , Lonardi Stefano 
Published: July 2009

Abstract

Background
Physical maps have been historically one of the cornerstones of genome sequencing and map-based cloning strategies. They also support marker assisted breeding and EST mapping. The problem of building a high quality physical map is computationally challenging due to unavoidable noise in the input fingerprint data.

Results
We propose a novel compartmentalized method for the assembly of high quality physical maps from fingerprinted clones. The knowledge of genetic markers enables us to group clones into clusters so that clones in the same cluster are more likely to overlap. For each cluster of clones, a local physical map is first constructed using FingerPrinted Contigs (FPC). Then, all the individual maps are carefully merged into the final physical map. Experimental results on the genomes of rice and barley demonstrate that the compartmentalized assembly produces significantly more accurate maps, and that it can detect and isolate clones that would induce "chimeric" contigs if used in the final assembly.

Conclusion
The software is available for download at http://www.cs.ucr.edu/~sbozdag/assembler/
Phylogenetic analysis of the true water bugs (Insecta: Hemiptera: Heteroptera: Nepomorpha): evidence from mitochondrial genomes
Authors: Hua Jimeng , Li Ming , Dong Pengzhi , Cui Ying , Xie Qiang , Bu Wenjun 
Published: July 2009

AbstractBackgroundThe true water bugs are grouped in infraorder Nepomorpha (Insecta: Hemiptera: Heteroptera) and are of great economic importance. The phylogenetic relationships within Nepomorpha and the taxonomic hierarchies of Pleoidea and Aphelocheiroidea are uncertain. Most of the previous studies were based on morphological characters without algorithmic assessment. In the latest study, the molecular markers employed in phylogenetic analyses were partial sequences of 16S rDNA and 18S rDNA with a total length about 1 kb. Up to now, no mitochondrial genome of the true water bugs has been sequenced, which is one of the largest data sets that could be compared across animal taxa. In this study we analyzed the unresolved problems in Nepomorpha using evidence from mitochondrial genomes.ResultsNine mitochondrial genomes of Nepomorpha and five of other hemipterans were sequenced. These mitochondrial genomes contain the commonly found 37 genes without gene rearrangements. Based on the nucleotide sequences of mt-genomes, Pleoidea is not a member of the Nepomorpha and Aphelocheiroidea should be grouped back into Naucoroidea. Phylogenetic relationships among the superfamilies of Nepomorpha were resolved robustly.ConclusionThe mt-genome is an effective data source for resolving intraordinal phylogenetic problems at the superfamily level within Heteroptera. The mitochondrial genomes of the true water bugs are typical insect mt-genomes. Based on the nucleotide sequences of the mt-genomes, we propose the Pleoidea to be a separate heteropteran infraorder. The infraorder Nepomorpha consists of five superfamilies with the relationships (Corixoidea + ((Naucoroidea + Notonectoidea) + (Ochteroidea + Nepoidea))).
Inconsistencies of genome annotations in apicomplexan parasites revealed by 5'-end-one-pass and full-length sequences of oligo-capped cDNAs
Authors: Wakaguri Hiroyuki , Suzuki Yutaka , Sasaki Masahide , Sugano Sumio , Watanabe Junichi 
Published: July 2009

Abstract

Background
Apicomplexan parasites are causative agents of various diseases including malaria and have been targets of extensive genomic sequencing. We generated 5'-EST collections for six apicomplexa parasites using our full-length oligo-capping cDNA library method. To improve upon the current genome annotations, as well as to validate the importance for physical cDNA clone resources, we generated a large-scale collection of full-length cDNAs for several apicomplexa parasites.

Results
In this study, we used a total of 61,056 5'-end-single-pass cDNA sequences from Plasmodium falciparum, P. vivax, P. yoelii, P. berghei, Cryptosporidium parvum, and Toxoplasma gondii. We compared these partially sequenced cDNA sequences with the currently annotated gene models and observed significant inconsistencies between the two datasets. In particular, we found that on average 14% of the exons in the current gene models were not supported by any cDNA evidence, and that 16% of the current gene models may contain at least one mis-annotation and should be re-evaluated. We also identified a large number of transcripts that had been previously unidentified. For 732 cDNAs in T. gondii, the entire sequences were determined in order to evaluate the annotated gene models at the complete full-length transcript level. We found that 41% of the T. gondii gene models contained at least one inconsistency. We also identified and confirmed by RT-PCR 140 previously unidentified transcripts found in the intergenic regions of the current gene annotations. We show that the majority of these discrepancies are due to questionable predictions of one or two extra exons in the upstream or downstream regions of the genes.

Conclusion
Our data indicates that the current gene models are likely to still be incomplete and have much room for improvement. Our unique full-length cDNA information is especially useful for further refinement of the annotations for the genomes of apicomplexa parasites.
Genomic Resources of Magnaporthe oryzae (GROMO): A comprehensive and integrated database on rice blast fungus
Authors: Thakur Shalabh , Jha Sanjay , Roy-Barman Subhankar , Chattoo Bharat 
Published: July 2009

Abstract

Background

Magnaporthe oryzae, rice blast fungus, is the most devastating pathogen of rice. It has emerged as a model phytopathogen for the study of host-pathogen interactions. A large body of data has been generated on different aspects of biology of this fungus and on host-pathogen interactions. However, most of the data is scattered and is not available as a single resource for researchers in this field.

Description
Genomic Resources of Magnaporthe oyzae (GROMO), is a specialized, and comprehensive database for rice blast fungus, integrating information from several resources. GROMO contains information on genomic sequence, mutants available, gene expression, localization of proteins obtained from a variety of repositories, as primary data. In addition, prediction of domains, pathways, protein-protein interactions, sumolyation sites and biochemical properties that were obtained after computational analysis of protein sequences have also been included as derived data. This database has an intuitive user interface that shall prompt the user to explore various possible information resources available on a given gene or a protein, from a single source.

Conclusion
Currently, information on M. oryzae is available from different resources like BROAD MIT Magnaporthe database, Agrobacterium tumefaciens-mediated transformation (ATMT) M. oryzae database, Magnaporthe grisea – Oryza sativa (MGOS) and Massive Parallel Signature Sequencing (MPSS) databases. In the GROMO project, an effort has been made to integrate information from all these databases, derive some new data based on the available information analyzed by relevant programs and make more insightful predictions to better understand the biology of M. oryzae. The database is currently available at: http://gromo.msubiotech.ac.in/
Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice
Authors: Sica Monica , Martini Mariangela , Viglietti-Panzica Carla , Panzica GianCarlo 
Published: July 2009

AbstractBackgroundNitric oxide plays an important role in the regulation of male and female sexual behavior in rodents, and the expression of the nitric oxide synthase (NOS) is influenced by testosterone in the male rat, and by estrogens in the female. We have here quantitatively investigated the distribution of nNOS immunoreactive (ir) neurons in the limbic hypothalamic region of intact female mice sacrificed during different phases of estrous cycle.ResultsChanges were observed in the medial preoptic area (MPA) (significantly higher number in estrus) and in the arcuate nucleus (Arc) (significantly higher number in proestrus). In the ventrolateral part of the ventromedial nucleus (VMHvl) and in the bed nucleus of the stria terminalis (BST) no significant changes have been observed. In addition, by comparing males and females, we observed a stable sex dimorphism (males have a higher number of nNOS-ir cells in comparison to almost all the different phases of the estrous cycle) in the VMHvl and in the BST (when considering only the less intensely stained elements). In the MPA and in the Arc sex differences were detected only comparing some phases of the cycle.ConclusionThese data demonstrate that, in mice, the expression of nNOS in some hypothalamic regions involved in the control of reproduction and characterized by a large number of estrogen receptors is under the control of gonadal hormones and may vary according to the rapid variations of hormonal levels that take place during the estrous cycle.
Tissue culture-induced transpositional activity of mPing is correlated with cytosine methylation in rice
Authors: Ngezahayo Frédéric , Xu Chunming , Wang Hongyan , Jiang Lily , Pang Jinsong , Liu Bao 
Published: July 2009

AbstractBackgroundmPingis an endogenous MITE in the rice genome, which is quiescent under normal conditions but can be induced towards mobilization under various stresses. The cellular mechanism responsible for modulating the activity ofmPingremains unknown. Cytosine methylation is a major epigenetic modification in most eukaryotes, and the primary function of which is to serve as a genome defense system including taming activity of transposable elements (TEs). Given that tissue-culture is capable of inducing both methylation alteration andmPingtransposition in certain rice genotypes, it provides a tractable system to investigate the possible relationship between the two phenomena.ResultsmPingtransposition and cytosine methylation alteration were measured in callus and regenerated plants in three rice (ssp.indica) genotypes, V14, V27 and R09. All three genotypes showed transposition ofmPing, though at various frequencies. Cytosine methylation alteration occurred both at themPing-flanks and at random loci sampled globally in callus and regenerated plants of all three genotypes. However, a sharp difference in the changing patterns was noted between themPing-flanks and random genomic loci, with a particular type of methylation modification, i.e., CNG hypermethylation, occurred predominantly at themPing-flanks. Pearson's test on pairwise correlations indicated thatmPingactivity is positively correlated with specific patterns of methylation alteration at random genomic loci, while the element's immobility is positively correlated with methylation levels of themPing's 5'-flanks. Bisulfite sequencing of twomPing-containing loci showed that whereas for the immobile locus loss of CG methylation in the 5'-flank was accompanied by an increase in CHG methylation, together with an overall increase in methylation of all three types (CG, CHG and CHH) in themPing-body region, for the active locus erasure of CG methylation in the 5'-flank was not followed by such a change.ConclusionOur results documented that tissue culture-inducedmPingactivity in rice ssp.indicais correlated with alteration in cytosine methylation patterns at both random genomic loci and the elements' flanks, while the stability ofmPingpositively correlates with enhanced methylation levels of both the flanks and probably the elementsper se. Thus, our results implicate a possible role of cytosine methylation in maintainingmPingstability under normal conditions, and in releasing the element's activity as a consequence of epigenetic perturbation in a locus-specific manner under certain stress conditions.