bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Wind Stress Feedback on the Stability of the Atlantic Meridional Overturning Circulation
Authors: Arzel Olivier , England Matthew H. , Saenko Oleg A. 
Published: June 2010

Abstract
Recent results based on models using prescribed surface wind stress forcing have suggested that the net freshwater transport Σ by the Atlantic meridional overturning circulation (MOC) into the Atlantic basin is a good indicator of the multiple-equilibria regime. By means of a coupled climate model of intermediate complexity, this study shows that this scalar Σ cannot capture the connection between the properties of the steady state and the impact of the wind stress feedback on the evolution of perturbations. This implies that, when interpreting the observed value of Σ, the position of the present-day climate is systematically biased toward the multiple-equilibria regime. The results show, however, that the stabilizing influence of the wind stress feedback on the MOC is restricted to a narrow window of freshwater fluxes, located in the vicinity of the state characterized by a zero freshwater flux divergence over the Atlantic basin. If the position of the present-day climate is farther away from this state, then wind stress feedbacks are unable to exert a persistent effect on the modern MOC. This is because the stabilizing influence of the shallow reverse cell situated south of the equator during the off state rapidly dominates over the destabilizing influence of the wind stress feedback when the freshwater forcing gets stronger. Under glacial climate conditions by contrast, a weaker sensitivity with an opposite effect is found. This is ultimately due to the relatively large sea ice extent of the glacial climate, which implies that, during the off state, the horizontal redistribution of fresh waters by the subpolar gyre does not favor the development of a thermally direct MOC as opposed to the modern case.
Revisiting the Influence of the Quasi-Biennial Oscillation on Tropical Cyclone Activity
Authors: Camargo Suzana J. , Sobel Adam H. 
Published: June 2010

AbstractThe statistical relationship between the quasi-biennial oscillation (QBO) and tropical cyclone (TC) activity is explored, with a focus on the North Atlantic. Although there is a statistically significant relationship between the QBO and TCs in the Atlantic from the 1950s to the 1980s, as found by previous studies, that relationship is no longer present in later years. Several possibilities for this change are explored, including the interaction with ENSO, volcanoes, QBO decadal variability, and interactions with solar forcing. None provides a completely satisfying explanation. In the other basins, the relationship is weaker than in the Atlantic, even in the early record.
Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia
Authors: Shehata Medhat , Schnabl Susanne , Demirtas Dita , Hilgarth Martin , Hubmann Rainer , Ponath Elena , Badrnya Sigrun , Lehner Claudia , Hoelbl Andrea , Duechler Markus , Gaiger Alexander , Zielinski Christoph , Schwarzmeier Josef D. , Jaeger Ulrich 
Published: June 2010

Abstract
Evidence suggests that tumor microenvironment is critically involved in supporting survival of chronic lymphocytic leukemia (CLL) cells. However, the molecular mechanisms of this effect and the clinical significance are not fully understood. We applied a microenvironment model to explore the interaction between CLL cells and stromal cells and to elucidate the role of phosphatidylinositol 3 kinase (PI3-K)/Akt/phosphatase and tensin homolog detected on chromosome 10 (PTEN) cascade in this process and its in vivo relevance. Primary human stromal cells from bone marrow, lymph nodes, and spleen significantly inhibited spontaneous apoptosis of CLL cells. Pan–PI3-K inhibitors (LY294002, wortmannin, PI-103), isotype-specific inhibitors of p110α, p110β, p110γ, and small interfering RNA against PI3-K and Akt1 counteracted the antiapoptotic effect of the stromal cells. Induction of apoptosis was associated with a decrease in phosphatidylinositol-3,4,5-triphosphate, PI3-K–p85, and dephosphorylation of phosphatidylinositol-dependent kinase-1 (PDK-1), Akt1, and PTEN. Freshly isolated peripheral blood mononuclear cells from patients with CLL (n = 44) showed significantly higher levels of phosphorylated Akt1, PDK-1, PTEN, and CK2 than healthy persons (n = 8). CK2 inhibitors (4,5,6,7-tetrabromo-1H-benzotriazole, apigenin, and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazol) decreased phosphorylation of PTEN and Akt, induced apoptosis in CLL cells, and enhanced the response to fludarabine. In conclusion, bone marrow microenvironment modulates the PI3-K/Akt/PTEN cascade and prevents apoptosis of CLL cells. Combined inhibition of PI3-K/Akt and recovery of PTEN activity may represent a novel therapeutic concept for CLL.
A semi-supervised learning approach to predict synthetic genetic interactions by combining functional and topological properties of functional gene network
Authors: You Zhu-Hong , Yin Zheng , Han Kyungsook , Huang De-Shuang , Zhou Xiaobo 
Published: June 2010

Abstract

Background
Genetic interaction profiles are highly informative and helpful for understanding the functional linkages between genes, and therefore have been extensively exploited for annotating gene functions and dissecting specific pathway structures. However, our understanding is rather limited to the relationship between double concurrent perturbation and various higher level phenotypic changes, e.g. those in cells, tissues or organs. Modifier screens, such as synthetic genetic arrays (SGA) can help us to understand the phenotype caused by combined gene mutations. Unfortunately, exhaustive tests on all possible combined mutations in any genome are vulnerable to combinatorial explosion and are infeasible either technically or financially. Therefore, an accurate computational approach to predict genetic interaction is highly desirable, and such methods have the potential of alleviating the bottleneck on experiment design.

Results
In this work, we introduce a computational systems biology approach for the accurate prediction of pairwise synthetic genetic interactions (SGI). First, a high-coverage and high-precision functional gene network (FGN) is constructed by integrating protein-protein interaction (PPI), protein complex and gene expression data; then, a graph-based semi-supervised learning (SSL) classifier is utilized to identify SGI, where the topological properties of protein pairs in weighted FGN is used as input features of the classifier. We compare the proposed SSL method with the state-of-the-art supervised classifier, the support vector machines (SVM), on a benchmark dataset in S. cerevisiae to validate our method's ability to distinguish synthetic genetic interactions from non-interaction gene pairs. Experimental results show that the proposed method can accurately predict genetic interactions in S. cerevisiae (with a sensitivity of 92% and specificity of 91%). Noticeably, the SSL method is more efficient than SVM, especially for very small training sets and large test sets.

Conclusions
We developed a graph-based SSL classifier for predicting the SGI. The classifier employs topological properties of weighted FGN as input features and simultaneously employs information induced from labelled and unlabelled data. Our analysis indicates that the topological properties of weighted FGN can be employed to accurately predict SGI. Also, the graph-based SSL method outperforms the traditional standard supervised approach, especially when used with small training sets. The proposed method can alleviate experimental burden of exhaustive test and provide a useful guide for the biologist in narrowing down the candidate gene pairs with SGI. The data and source code implementing the method are available from the website: http://home.ustc.edu.cn/~yzh33108/GeneticInterPred.htm
Predicting nucleosome positioning using a duration Hidden Markov Model
Authors: Xi Liqun , Fondufe-Mittendorf Yvonne , Xia Lei , Flatow Jared , Widom Jonathan , Wang Ji-Ping 
Published: June 2010

Abstract

Background
The nucleosome is the fundamental packing unit of DNAs in eukaryotic cells. Its detailed positioning on the genome is closely related to chromosome functions. Increasing evidence has shown that genomic DNA sequence itself is highly predictive of nucleosome positioning genome-wide. Therefore a fast software tool for predicting nucleosome positioning can help understanding how a genome's nucleosome organization may facilitate genome function.

Results
We present a duration Hidden Markov model for nucleosome positioning prediction by explicitly modeling the linker DNA length. The nucleosome and linker models trained from yeast data are re-scaled when making predictions for other species to adjust for differences in base composition. A software tool named NuPoP is developed in three formats for free download.

Conclusions
Simulation studies show that modeling the linker length distribution and utilizing a base composition re-scaling method both improve the prediction of nucleosome positioning regarding sensitivity and false discovery rate. NuPoP provides a user-friendly software tool for predicting the nucleosome occupancy and the most probable nucleosome positioning map for genomic sequences of any size. When compared with two existing methods, NuPoP shows improved performance in sensitivity.
"Does replication groups scoring reduce false positive rate in SNP interaction discovery?: Response"
Authors: Gayán Javier , González-Pérez Antonio , Ruiz Agustín 
Published: June 2010

Abstract

Abstract
A response to Toplak et al: Does replication groups scoring reduce false positive rate in SNP interaction discovery? BMC Genomics 2010, 11:58.

Background
The genomewide evaluation of genetic epistasis is a computationally demanding task, and a current challenge in Genetics. HFCC (Hypothesis-Free Clinical Cloning) is one of the methods that have been suggested for genomewide epistasis analysis. In order to perform an exhaustive search of epistasis, HFCC has implemented several tools and data filters, such as the use of multiple replication groups, and direction of effect and control filters. A recent article has claimed that the use of multiple replication groups (as implemented in HFCC) does not reduce the false positive rate, and we hereby try to clarify these issues.

Results/Discussion
HFCC uses, as an analysis strategy, the possibility of replicating findings in multiple replication groups, in order to select a liberal subset of preliminary results that are above a statistical criterion and consistent in direction of effect. We show that the use of replication groups and the direction filter reduces the false positive rate of a study, although at the expense of lowering the overall power of the study. A post-hoc analysis of these selected signals in the combined sample could then be performed to select the most promising results.

Conclusion
Replication of results in independent samples is generally used in scientific studies to establish credibility in a finding. Nonetheless, the combined analysis of several datasets is known to be a preferable and more powerful strategy for the selection of top signals. HFCC is a flexible and complete analysis tool, and one of its analysis options combines these two strategies: A preliminary multiple replication group analysis to eliminate inconsistent false positive results, and a post-hoc combined-group analysis to select the top signals.
A short upstream promoter region mediates transcriptional regulation of the mouse doublecortin gene in differentiating neurons
Authors: Piens Marie , Muller Marc , Bodson Morgan , Baudouin Gregory , Plumier Jean-Christophe 
Published: June 2010

Abstract

Background
Doublecortin (Dcx), a MAP (Microtubule-Associated Protein), is transiently expressed in migrating and differentiating neurons and thereby characterizes neuronal precursors and neurogenesis in developing and adult neurogenesis. In addition, reduced Dcx expression during development has been related to appearance of brain pathologies. Here, we attempt to unveil the molecular mechanisms controlling Dcx gene expression by studying its transcriptional regulation during neuronal differentiation.

Results
To determine and analyze important regulatory sequences of the Dcx promoter, we studied a putative regulatory region upstream from the mouse Dcx coding region (pdcx 2kb) and several deletions thereof. These different fragments were used in vitro and in vivo to drive reporter gene expression. We demonstrated, using transient expression experiments, that pdcx 2kb is sufficient to control specific reporter gene expression in cerebellar cells and in the developing brain (E14.5). We determined the temporal profile of Dcx promoter activity during neuronal differentiation of mouse embryonic stem cells (mESC) and found that transcriptional activation of the Dcx gene varies along with neuronal differentiation of mESC. Deletion experiments and sequence comparison of Dcx promoters across rodents, human and chicken revealed the importance of a highly conserved sequence in the proximal region of the promoter required for specific and strong expression in neuronal precursors and young neuronal cells. Further analyses revealed the presence in this short sequence of several conserved, putative transcription factor binding sites: LEF/TCF (Lymphoid Enhancer Factor/T-Cell Factor) which are effectors of the canonical Wnt pathway; HNF6/OC2 (Hepatocyte Nuclear Factor-6/Oncecut-2) members of the ONECUT family and NF-Y/CAAT (Nuclear Factor-Y).

Conclusions
Studies of Dcx gene regulatory sequences using native, deleted and mutated constructs suggest that fragments located upstream of the Dcx coding sequence are sufficient to induce specific Dcx expression in vitro: in heterogeneous differentiated neurons from mESC, in primary mouse cerebellar neurons (PND3) and in organotypic slice cultures. Furthermore, a region in the 3'-end region of the Dcx promoter is highly conserved across several species and exerts positive control on Dcx transcriptional activation. Together, these results indicate that the proximal 3'-end region of the mouse Dcx regulatory sequence is essential for Dcx gene expression during differentiation of neuronal precursors.
Comparison of low molecular weight glutenin subunits identified by SDS-PAGE, 2-DE, MALDI-TOF-MS and PCR in common wheat
Authors: Liu Li , Ikeda Tatsuya M , Branlard Gerard , Peña Roberto J , Rogers William J , Lerner Silvia E , Kolman María A , Xia Xianchun , Wang Linhai , Ma Wujun , Appels Rudi , Yoshida Hisashi , Wang Aili , Yan Yueming , He Zhonghu 
Published: June 2010

Abstract

Background
Low-molecular-weight glutenin subunits (LMW-GS) play a crucial role in determining end-use quality of common wheat by influencing the viscoelastic properties of dough. Four different methods - sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional gel electrophoresis (2-DE, IEF × SDS-PAGE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and polymerase chain reaction (PCR), were used to characterize the LMW-GS composition in 103 cultivars from 12 countries.

Results
At the Glu-A3 locus, all seven alleles could be reliably identified by 2-DE and PCR. However, the alleles Glu-A3e and Glu-A3d could not be routinely distinguished from Glu-A3f and Glu-A3g, respectively, based on SDS-PAGE, and the allele Glu-A3a could not be differentiated from Glu-A3c by MALDI-TOF-MS. At the Glu-B3 locus, alleles Glu-B3a, Glu-B3b, Glu-B3c, Glu-B3g, Glu-B3h and Glu-B3j could be clearly identified by all four methods, whereas Glu-B3ab, Glu-B3ac, Glu-B3ad could only be identified by the 2-DE method. At the Glu-D3 locus, allelic identification was problematic for the electrophoresis based methods and PCR. MALDI-TOF-MS has the potential to reliably identify the Glu-D3 alleles.

Conclusions
PCR is the simplest, most accurate, lowest cost, and therefore recommended method for identification of Glu-A3 and Glu-B3 alleles in breeding programs. A combination of methods was required to identify certain alleles, and would be especially useful when characterizing new alleles. A standard set of 30 cultivars for use in future studies was chosen to represent all LMW-GS allelic variants in the collection. Among them, Chinese Spring, Opata 85, Seri 82 and Pavon 76 were recommended as a core set for use in SDS-PAGE gels. Glu-D3c and Glu-D3e are the same allele. Two new alleles, namely, Glu-D3m in cultivar Darius, and Glu-D3n in Fengmai 27, were identified by 2-DE. Utilization of the suggested standard cultivar set, seed of which is available from the CIMMYT and INRA Clermont-Ferrand germplasm collections, should also promote information sharing in the identification of individual LMW-GS and thus provide useful information for quality improvement in common wheat.
Coordination of the maize transcriptome by a conserved circadian clock
Authors: Khan Sadaf , Rowe Scott C , Harmon Frank G 
Published: June 2010

Abstract

Background
The plant circadian clock orchestrates 24-hour rhythms in internal physiological processes to coordinate these activities with daily and seasonal changes in the environment. The circadian clock has a profound impact on many aspects of plant growth and development, including biomass accumulation and flowering time. Despite recent advances in understanding the circadian system of the model plant Arabidopsis thaliana, the contribution of the circadian oscillator to important agronomic traits in Zea mays and other cereals remains poorly defined. To address this deficit, this study investigated the transcriptional landscape of the maize circadian system.

Results
Since transcriptional regulation is a fundamental aspect of circadian systems, genes exhibiting circadian expression were identified in the sequenced maize inbred B73. Of the over 13,000 transcripts examined, approximately 10 percent displayed circadian expression patterns. The majority of cycling genes had peak expression at subjective dawn and dusk, similar to other plant circadian systems. The maize circadian clock organized co-regulation of genes participating in fundamental physiological processes, including photosynthesis, carbohydrate metabolism, cell wall biogenesis, and phytohormone biosynthesis pathways.

Conclusions
Circadian regulation of the maize genome was widespread and key genes in several major metabolic pathways had circadian expression waveforms. The maize circadian clock coordinated transcription to be coincident with oncoming day or night, which was consistent with the circadian oscillator acting to prepare the plant for these major recurring environmental changes. These findings highlighted the multiple processes in maize plants under circadian regulation and, as a result, provided insight into the important contribution this regulatory system makes to agronomic traits in maize and potentially other C4 plant species.
In-hospital complications after invasive strategy for the management of Non STEMI: women fare as well as men
Authors: Berthillot Caroline , Stephan Dominique , Chauvin Michel , Roul Gerald 
Published: June 2010

Abstract

Background
To analyze the in-hospital complication rate in women suffering from non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) compared to men.

Methods
The files of 479 consecutive patients (133 women and 346 men) suffering from a Non STEMI (Non ST-segment elevation myocardial infarction) between the January 1st 2006 and March 21st 2009 were retrospectively analyzed with special attention to every single complication occurring during hospital stay. Data were analyzed using nonparametric tests and are reported as median unless otherwise specified. A p value < .05 was considered significant.

Results
As compared to men, women were significantly older (75.8 vs. 65.2 years; p < .005). All cardiovascular risk factors but tobacco and hypertension were similar between the groups: men were noticeably more often smoker (p < .0001) and women more hypertensive (p < .005). No difference was noticed for pre-hospital cardiovascular drug treatment. However women were slightly more severe at entry (more Killip class IV; p = .0023; higher GRACE score for in-hospital death - p = .008 and CRUSADE score for bleeding - p < .0001). All the patients underwent PCI of the infarct-related artery after 24 or 48 hrs post admission without sex-related difference either for timing of PCI or primary success rate. During hospitalization, 130 complications were recorded. Though the event rate was slightly higher in women (30% vs. 26% - p = NS), no single event was significantly gender related. The logistic regression identified age and CRP concentration as the only predictive variables in the whole group. After splitting for genders, these parameters were still predictive of events in men. In women however, CRP was the only one with a borderline p value.

Conclusions
Our study does not support any gender difference for in-hospital adverse events in patients treated invasively for an acute coronary syndrome without ST-segment elevation and elevated troponin.
Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice
Authors: El Khoury Diala , Destouches Damien , Lengagne Renée , Krust Bernard , Hamma-Kourbali Yamina , Garcette Marylène , Niro Sandra , Kato Masashi , Briand Jean-Paul , Courty José , Hovanessian Ara G , Prévost-Blondel Armelle 
Published: June 2010

Abstract

Background
The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity.

Methods
The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse.

Results
HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice.

Conclusions
Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or as an adjuvant therapy in association with current therapeutic interventions on a virulent cancer like melanoma.