bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY38-02: Molecular oncogenesis of human T-cell lymphoma: Common features with myeloid malignancies
Authors: Bernard Olivier A. 
Published: August 2012

Abstract
T-cell lymphomas are a heterogeneous group of diseases associated with poor outcome whose molecular bases are ill characterized. Prompted by the effect of Tet2 inactivation in lymphoid differentiation and the co occurrence of lymphoma in patients with myeloid neoplasm with TET2 mutations, we uncovered TET2 mutations in 2% of B-cell lymphoma and 11% of T-cell lymphoma samples. The highest frequency of TET2 mutation in T-cell lymphoma was observed in the ImmunoAngioblastic (AITL) (10/30: 30%) and the Peripheral T-cell lymphoma, Not otherwise specified (PTCL, NOS) (6/30:20%) subtypes. Cellular analyses showed that TET2 mutations in AITL patients may also be observed in CD34+ hematopoietic progenitors able to differentiate along the myeloid lineages, indicating that TET2 mutations may have occurred in an immature progenitor able to differentiate along both lymphoid and myeloid lineages.
Current data indicate that TET2 participate to the control of DNA methylation, through the oxydation of methylcytosine, and therefore the epigenetic control of transcription. Further candidate gene sequencing showed DNMT3A mutations in 11% of T-cell lymphoma samples. In our series, DNMT3A mutations were significantly associated with the presence of TET2 mutations since 8 of the 11 DNMT3A mutated patients also carried a TET2 mutation. In some DNMT3A-mutated-patients, those mutations could be observed during an MDS phase, which had preceded the lymphoma phase. Our data point at transformation pathways common to T-cell lymphoma and myeloid neoplasms. They suggest deregulation of DNA methylation and and provide a further basis for the molecular classification of T-cell lymphomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY38-02. doi:1538-7445.AM2012-SY38-02
Abstract SY39-01: Harnessing cancer genome diversity for intervention target discovery and development
Authors: White Michael A. 
Published: August 2012

Abstract
The diverse assortment of somatic lesions associated with human cancer initiation and progression presents a formidable challenge against efforts to develop molecularly targeted therapeutic interventions. Here we are modeling genetic diversity within lung cancer using a panel of over 100 non small cell lung cancer derived cell lines. Broad-scale parallel testing of genetic and chemical perturbations, together with high-resolution genomic characterization, is being used to parse this panel into subtypes with shared target opportunities and molecular correlates that predict response to target intervention. In this way, we have begun to identify somatic allele combinations that drive sensitivity to selective gene depletions and to synthetic small molecules that target these genes and/or the biological processes they serve.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY39-01. doi:1538-7445.AM2012-SY39-01
GAB2—a Scaffolding Protein in Cancer
Authors: Adams Sarah J. , Aydin Iraz T. , Celebi Julide T. 
Published: August 2012

Abstract
Adaptor or scaffolding proteins mediate protein–protein interactions that drive the formation of protein complexes. Grb2-associated binding protein 2 (GAB2) scaffolding protein is an intermediary molecule that links plasma membrane receptor signaling including receptor tyrosine kinases with the downstream effectors, such as protein tyrosine phosphatase, nonreceptor type 11 (SHP2), p85 subunit of phosphoinositide-3 kinase (PI3-K), phospholipase C-gamma 1 (PLC-γ), v-crk sarcoma virus CT10 (CRK), Src homology 2 domain containing transforming protein 1 (SHC), and SH2 containing inositol phosphatase (SHIP). Although, well described in signal transduction, its role in cancer has recently been emerging especially in leukemia, breast and ovarian cancer, and melanoma. GAB2 is essential for two major signal transduction pathways in cancer, the PI3-K-AKT and extracellular signal-regulated kinase (ERK) signaling pathways, and thus regulates a number of key cellular processes. This review focuses on structure and function of GAB2, its regulatory proteins, emerging role in cancer, and potential as a therapeutic target. Mol Cancer Res; 10(10); 1265–70. ©2012 AACR.
Long-Term Outcome of Stents Versus Bypass Surgery in Diabetic and Nondiabetic Patients With Multivessel or Left Main Coronary Artery Disease
Authors: Park Duk-Woo , Kim Young-Hak , Song Hae Geun , Ahn Jung-Min , Kim Won-Jang , Lee Jong-Young , Kang Soo-Jin , Lee Seung-Whan , Lee Cheol Whan , Park Seong-Wook , Yun Sung-Cheol , Chung Sung-Ho , Choo Suk Jung , Chung Cheol Hyun , Lee Jae-Won , Park Seung-Jung 
Published: August 2012

Background—
Coronary artery bypass grafting and percutaneous coronary intervention (PCI) are alternative treatments for complex multivessel or left main disease. However, the relative treatment effects in diabetic and nondiabetic patients remain uncertain.

Methods and Results—

We performed a pooled analysis of 5775 patients from 3 clinical studies comparing PCI and coronary artery bypass grafting for multivessel or left main disease and compared adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and repeat revascularization) according to the diabetic status. Over a median follow-up of 5.5 years, risk-adjusted mortality after PCI relative to coronary artery bypass grafting was not different in diabetic (hazard ratio [HR], 1.15; 95% CI, 0.88–1.51) and nondiabetic (HR, 1.15; 95% CI, 0.88–1.50) patients. The adjusted risks of the composite outcome of death, Q-wave myocardial infarction, or stroke were also not different in diabetic (HR, 1.00; 95% CI, 0.79–1.26) and nondiabetic (HR, 0.99; 95% CI, 0.78–1.26) patients. However, PCI was significantly associated with higher risk of repeat revascularization both in diabetic (HR, 3.56; 95% CI, 2.62–4.83) and in nondiabetic (HR, 3.55; 95% CI, 2.61–4.83) patients. Significant interactions were absent between diabetic status and revascularization strategies for death (
P
=0.27), composite outcome of death, Q-wave myocardial infarction, or stroke (
P
=0.97), and repeat revascularization (
P
=0.08).

Conclusions—
For multivessel or left main disease, the long-term risks of mortality and composite serious outcomes were not different between PCI and coronary artery bypass grafting in diabetic and nondiabetic patients, but PCI was associated with higher risk of repeat revascularization. These relative treatment effects were not modified by diabetic status. These results are hypothesis generating and should be addressed in a randomized trial.
Hail in Northeast Italy: A Neural Network Ensemble Forecast Using Sounding-Derived Indices
Authors: Manzato Agostino 
Published: August 2012

Abstract
In a previous work, the hailpad data collected over the plain of the Friuli Venezia Giulia region in northeast Italy during the April–September 1992–2009 period were studied through a bivariate analysis with 52 sounding-derived indices from the Udine–Campoformido station (WMO code 16044). The results showed statistically significant relations but, nevertheless, were not completely satisfactory from a practical point of view. In the current work, a prognostic multivariate analysis is performed, using linear and nonlinear approaches, finding the best results with an ensemble of neural networks. For the hail occurrence–classification problem, a novel method for combining binary classifiers (a variant of the Mojirsheibani major voting algorithm) is introduced. For the hail extension–regression problem the ensemble is built by choosing the members with a bagging algorithm, but combining them with a linear multiregression, in order to increase the forecast variability.
Electromyography and Nerve Conduction Velocity for the Evaluation of the Infraspinatus Muscle and the Suprascapular Nerve in Professional Beach Volleyball Players
Authors: Lajtai Georg , Wieser Karl , Ofner Michael , Raimann Gustav , Aitzetmüller Gernot , Jost Bernhard 
Published: August 2012

Background: Beach volleyball is an overhead sport with a high prevalence of infraspinatus muscle atrophy of the hitting shoulder. Hypothesis: Infraspinatus muscle atrophy seems to be caused by a repetitive traction injury of the suprascapular nerve. Early pathological findings might be assessed with surface electromyography (EMG) and nerve conduction velocity (NCV) measurements. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Fully competitive professional beach volleyball players were assessed with a structured interview, shoulder examination, strength measurements (external rotation and elevation), and neurophysiological examination (surface EMG and NCV of the infraspinatus and supraspinatus muscles and the suprascapular nerve, respectively) during the Beach Volleyball Grand Slam tournament 2010 in Klagenfurt, Austria. Results: Thirty-five men with an average age of 28 years were examined. Visible infraspinatus atrophy was found in 12 players (34%), of which 8 (23%) had slight atrophy and 4 (11%) had severe atrophy. External rotation (90%; P < .006) and elevation strength (93%; P = .03) were significantly lower in the hitting shoulder. Electromyography revealed a higher activation pattern in the infraspinatus muscle of the hitting arm in players with no or slight atrophy ( P = .001) but a significantly lower activation pattern in players with severe atrophy ( P = .013). Nerve conduction velocity measurements showed a significant higher latency and lower amplitude in the hitting shoulder of the total study group and the subgroup with infraspinatus atrophy. Conclusion: Professional beach volleyball players have a high frequency of infraspinatus atrophy (34%) and significantly reduced shoulder strength of the hitting shoulder. These findings are not associated with demographic factors. Electromyography and NCV measurements suggest a suprascapular nerve involvement caused by repetitive strain injuries of the nerve. External rotation strength measurements and NCV measurements can detect a side-to-side difference early, while EMG may show compensation mechanisms for progressive damaging of the suprascapular nerve and, as a result, loss of infraspinatus muscle strength.
Defining new criteria for selection of cell-based intestinal models using publicly available databases
Authors: Christensen Jon , El-Gebali Sara , Natoli Manuela , Sengstag Thierry , Delorenzi Mauro , Bentz Susanne , Bouzourene Hanifa , Rumbo Martin , Felsani Armando , Siissalo Sanna , Hirvonen Jouni , Vila Maya R , Saletti Piercarlo , Aguet Michel , Anderle Pascale 
Published: August 2012

Abstract

Background
The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies.

Results
We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics.

Conclusions
This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question.
Transcriptome profiling of resistant and susceptible Cavendish banana roots following inoculation with Fusarium oxysporum f. sp. cubense tropical race 4
Authors: Li Chun-yu , Deng Gui-ming , Yang Jing , Viljoen Altus , Jin Yan , Kuang Rui-bin , Zuo Cun-wu , Lv Zhi-cheng , Yang Qiao-song , Sheng Ou , Wei Yue-rong , Hu Chun-hua , Dong Tao , Yi Gan-jun 
Published: August 2012

AbstractBackgroundFusarium wilt, caused by the fungal pathogenFusarium oxysporumf. sp.cubensetropical race 4 (Foc TR4), is considered the most lethal disease of Cavendish bananas in the world. The disease can be managed in the field by planting resistant Cavendish plants generated by somaclonal variation. However, little information is available on the genetic basis of plant resistance to Foc TR4. To a better understand the defense response of resistant banana plants to the Fusarium wilt pathogen, the transcriptome profiles in roots of resistant and susceptible Cavendish banana challenged with Foc TR4 were compared.ResultsRNA-seq analysis generated more than 103 million 90-bp clean pair end (PE) reads, which were assembled into 88,161 unigenes (mean size = 554 bp). Based on sequence similarity searches, 61,706 (69.99%) genes were identified, among which 21,273 and 50,410 unigenes were assigned to gene ontology (GO) categories and clusters of orthologous groups (COG), respectively. Searches in the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG) mapped 33,243 (37.71%) unigenes to 119 KEGG pathways. A total of 5,008 genes were assigned to plant-pathogen interactions, including disease defense and signal transduction. Digital gene expression (DGE) analysis revealed large differences in the transcriptome profiles of the Foc TR4-resistant somaclonal variant and its susceptible wild-type. Expression patterns of genes involved in pathogen-associated molecular pattern (PAMP) recognition, activation of effector-triggered immunity (ETI), ion influx, and biosynthesis of hormones as well as pathogenesis-related (PR) genes, transcription factors, signaling/regulatory genes, cell wall modification genes and genes with other functions were analyzed and compared. The results indicated that basal defense mechanisms are involved in the recognition of PAMPs, and that high levels of defense-related transcripts may contribute to Foc TR4 resistance in banana.ConclusionsThis study generated a substantial amount of banana transcript sequences and compared the defense responses against Foc TR4 between resistant and susceptible Cavendish bananas. The results contribute to the identification of candidate genes related to plant resistance in a non-model organism, banana, and help to improve the current understanding of host-pathogen interactions.
Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background
Authors: Knapp Bernhard , Fischer Gottfried , Van Hemelen Dries , Fae Ingrid , Maillere Bernard , Ebner Christof , Schreiner Wolfgang , Bohle Barbara , Jahn-Schmid Beatrice 
Published: August 2012

AbstractBackgroundMugwort pollen allergens represent the main cause of pollinosis in late summer. The major allergen, Art v 1, contains only one single immunodominant, solely HLA-DR-restricted T cell epitope (Art v 125-36). The frequency of HLA-DRB1*01 is highly increased in mugwort-allergic individuals and HLA-DR1 serves as restriction element for Art v 125-36. However, Art v 125-36also binds to HLA-DR4 with high affinity and DR1-restricted Art v 125-36-specific T cell receptors can be activated by HLA-DR4 molecules. To understand the predominance of HLA-DR1 in mugwort allergy in spite of the degeneracy in HLA/peptide-binding and TCR-recognition, we investigated the molecular background of Art v 125-36/MHC/TCR interactions in the context of HLA-DR1 compared to -DR4.ResultsThe majority of Art v 125-36-specific T cell lines and clones from HLA-DR1 carrying, mugwort pollen-allergic donors reacted to synthetic and naturally processed Art v 1–peptides when presented by HLA-DR1 or HLA-DR4 expressing antigen presenting cells. However, at limiting peptide concentrations DR1 was more effective in T cell stimulation. In addition, the minimal epitope for 50% of Art v 125-36-specific T cells was shorter for DR1 than for DR4.In vitrobinding assays of Art v 125-36mutant peptides to isolated DR1- and DR4-molecules indicated similar binding capacities and use of the same register.In silicosimulation of Art v 125-36binding to HLA-DR1 and -DR4 suggested similar binding of the central part of the peptide to either molecule, but a higher flexibility of the N- and C-terminal amino acids and detachment at the C-terminus in HLA-DR1.ConclusionsThe predominance of HLA-DR1 in the response to Art v 125-36may be explained by subtle conformation changes of the peptide bound to DR1 compared to DR4. Computer simulation supported our experimental data by demonstrating differences in peptide mobility within the HLA-DR complex that may influence TCR-binding. We suggest that the minor differences observedin vitromay be more relevant in the microenvironmentin vivo, so that only presentation by HLA-DR1, but not -DR4 permits successful T cell activation.
Waist circumference a good indicator of future risk for type 2 diabetes and cardiovascular disease
Authors: Siren Reijo , Eriksson Johan G , Vanhanen Hannu 
Published: August 2012

Abstract

Background
Abdominal obesity is a more important risk factor than overall obesity in predicting the development of type 2 diabetes and cardiovascular disease. From a preventive and public health point of view it is crucial that risk factors are identified at an early stage, in order to change and modify behaviour and lifestyle in high risk individuals.

Methods
Data from a community based study was used to assess the risk for type 2 diabetes, cardiovascular disease and prevalence of metabolic syndrome in middle-aged men. In order to identify those with increased risk for type 2 diabetes and/or cardiovascular disease sensitivity and specificity analysis were performed, including calculation of positive and negative predictive values, and corresponding 95% CI for eleven different cut-off points, with 1 cm intervals (92 to 102 cm), for waist circumference.

Results
A waist circumference ≥94 cm in middle-aged men, identified those with increased risk for type 2 diabetes and/or for cardiovascular disease with a sensitivity of 84.4% (95% CI 76.4% to 90.0%), and a specificity of 78.2% (95% CI 68.4% to 85.5%). The positive predictive value was 82.9% (95% CI 74.8% to 88.8%), and negative predictive value 80.0%, respectively (95% CI 70.3% to 87.1%).

Conclusions
Measurement of waist circumference in middle-aged men is a reliable test to identify individuals at increased risk for type 2 diabetes and cardiovascular disease. This measurement should be used more frequently in daily practice in primary care in order to identify individuals at risk and when planning health counselling and interventions.
Peptide binding to HLA-DP proteins at pH 5.0 and pH 7.0: a quantitative molecular docking study
Authors: Patronov Atanas , Dimitrov Ivan , Flower Darren R , Doytchinova Irini 
Published: August 2012

Abstract

Background
HLA-DPs are class II MHC proteins mediating immune responses to many diseases. Peptides bind MHC class II proteins in the acidic environment within endosomes. Acidic pH markedly elevates association rate constants but dissociation rates are almost unchanged in the pH range 5.0 – 7.0. This pH-driven effect can be explained by the protonation/deprotonation states of Histidine, whose imidazole has a pKa of 6.0. At pH 5.0, imidazole ring is protonated, making Histidine positively charged and very hydrophilic, while at pH 7.0 imidazole is unprotonated, making Histidine less hydrophilic. We develop here a method to predict peptide binding to the four most frequent HLA-DP proteins: DP1, DP41, DP42 and DP5, using a molecular docking protocol. Dockings to virtual combinatorial peptide libraries were performed at pH 5.0 and pH 7.0.

Results
The X-ray structure of the peptide – HLA-DP2 protein complex was used as a starting template to model by homology the structure of the four DP proteins. The resulting models were used to produce virtual combinatorial peptide libraries constructed using the single amino acid substitution (SAAS) principle. Peptides were docked into the DP binding site using AutoDock at pH 5.0 and pH 7.0. The resulting scores were normalized and used to generate Docking Score-based Quantitative Matrices (DS-QMs). The predictive ability of these QMs was tested using an external test set of 484 known DP binders. They were also compared to existing servers for DP binding prediction. The models derived at pH 5.0 predict better than those derived at pH 7.0 and showed significantly improved predictions for three of the four DP proteins, when compared to the existing servers. They are able to recognize 50% of the known binders in the top 5% of predicted peptides.

Conclusions
The higher predictive ability of DS-QMs derived at pH 5.0 may be rationalised by the additional hydrogen bond formed between the backbone carbonyl oxygen belonging to the peptide position before p1 (p-1) and the protonated ε-nitrogen of His79β. Additionally, protonated His residues are well accepted at most of the peptide binding core positions which is in a good agreement with the overall negatively charged peptide binding site of most MHC proteins.
Arachidonic acid metabolites in pathogenic yeasts
Authors: Ells Ruan , Kock Johan LF , Albertyn Jacobus , Pohl Carolina H 
Published: August 2012

AbstractAlthough most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2αand prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed.