bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial Results of Concomitant Cryoplasty After Remote Endarterectomy of the Superficial Femoral Artery: A Feasibility Study (Cryoplasty Following Remote Endarterectomy)
Authors: Gisbertz Suzanne S. , de Borst Gert-Jan , Overtoom Tim Th. C. , Moll Frans L. , de Vries Jean-Paul P.M. 
Published: October 2009

Objective: Remote endarterectomy is a less invasive technique compared with supragenicular bypass surgery for superficial femoral artery (SFA) occlusive disease. Early restenosis remains one of the drawbacks of this procedure. To prevent restenosis following remote endarterectomy, concomitant cryoplasty of the desobstruct SFA was introduced. Methods: A prospective cohort study was initiated with 17 patients treated with cryoplasty of the SFA after remote endarterectomy. Indications for surgery were claudication (n = 12), rest pain (n = 3), or tissue loss (n = 2). Results: There were no technical failures. The Kaplan-Meier estimate of the primary and assisted primary patency rate after 1 year of follow-up was 74%. Secondary patency was 89%. Limb salvage was 100%. No aneurysmal degeneration and no other adverse events occurred during the follow-up. Conclusions: This pilot study showed that cryoplasty after remote SFA endarterectomy is a safe procedure, with promising patency rates.
Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation
Authors: Funderburg Nicholas T. , Mayne Elizabeth , Sieg Scott F. , Asaad Robert , Jiang Wei , Kalinowska Magdalena , Luciano Angel A. , Stevens Wendy , Rodriguez Benigno , Brenchley Jason M. , Douek Daniel C. , Lederman Michael M. 
Published: October 2009

Abstract
HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV+ patients was related to plasma levels of interleukin-6 and to D-dimer products of fibrinolysis. We provide evidence that this elevated risk for coagulation may be related to increased proportions of monocytes expressing cell surface tissue factor (TF, thromboplastin) in persons with HIV infection. Monocyte TF expression could be induced in vitro by lipopolysaccharide and flagellin, but not by interleukin-6. Monocyte expression of TF was correlated with HIV levels in plasma, with indices of immune activation, and with plasma levels of soluble CD14, a marker of in vivo lipopolysaccharide exposure. TF levels also correlated with plasma levels of D-dimers, reflective of in vivo clot formation and fibrinolysis. Thus, drivers of immune activation in HIV disease, such as HIV replication, and potentially, microbial translocation, may activate clotting cascades and contribute to thrombus formation and cardiovascular morbidities in HIV infection.
Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium
Authors: Pham Tho , Gregg Christopher J. , Karp Felix , Chow Renee , Padler-Karavani Vered , Cao Hongzhi , Chen Xi , Witztum Joseph L. , Varki Nissi M. , Varki Ajit 
Published: October 2009

AbstractHumans are genetically unable to synthesize the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc). However, Neu5Gc can be metabolically incorporated and covalently expressed on cultured human cell surfaces. Meanwhile, humans express varying and sometimes high titers of polyclonal anti-Neu5Gc antibodies. Here, a survey of human tissues by immunohistochemistry with both a monospecific chicken anti-Neu5Gc antibody and with affinity-purified human anti-Neu5Gc antibodies demonstrates endothelial expression of Neu5Gc, likely originating from Neu5Gc-rich foods like red meats. We hypothesized that the combination of Neu5Gc incorporation and anti-Neu5Gc antibodies can induce endothelial activation. Indeed, the incubation of high-titer human sera with Neu5Gc-fed endothelial cells led to Neu5Gc-dependent antibody binding, complement deposition, endothelial activation, selectin expression, increased cytokine secretion, and monocyte binding. The proinflammatory cytokine tumor necrosis factor-α also selectively enhanced human anti-Neu5Gc antibody reactivity. Anti-Neu5Gc antibodies affinity-purified from human serum also directed Neu5Gc-dependent complement deposition onto cultured endothelial cells. These data indicate a novel human-specific mechanism in which Neu5Gc-rich foods deliver immunogenic Neu5Gc to the endothelium, giving anti-Neu5Gc antibody- and complement-dependent activation, and potentially contributing to human vascular pathologies. In the case of atherosclerosis, Neu5Gc is present both in endothelium overlying plaques and in subendothelial regions, providing multiple pathways for accelerating inflammation in this disease.
Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells
Authors: Wang Yongchao , Fiskus Warren , Chong Daniel G. , Buckley Kathleen M. , Natarajan Kavita , Rao Rekha , Joshi Atul , Balusu Ramesh , Koul Sanjay , Chen Jianguang , Savoie Andrew , Ustun Celalettin , Jillella Anand P. , Atadja Peter , Levine Ross L. , Bhalla Kapil N. 
Published: October 2009

AbstractThe mutant JAK2V617F tyrosine kinase (TK) is present in the majority of patients with BCR-ABL–negative myeloproliferative neoplasms (MPNs). JAK2V617F activates downstream signaling through the signal transducers and activators of transcription (STAT), RAS/mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3 (PI3)/AKT pathways, conferring proliferative and survival advantages in the MPN hematopoietic progenitor cells (HPCs). Treatment with the pan-histone deacetylase (HDAC) inhibitor panobinostat (PS) is known to inhibit the chaperone function of heat shock protein 90, as well as induce growth arrest and apoptosis of transformed HPCs. Here, we demonstrate that PS treatment depletes the autophosphorylation, expression, and downstream signaling of JAK2V617F. Treatment with PS also disrupted the chaperone association of JAK2V617F with hsp90, promoting proteasomal degradation of JAK2V617F. PS also induced apoptosis of the cultured JAK2V617F-expressing human erythroleukemia HEL92.1.7 and Ba/F3-JAK2V617F cells. Treatment with the JAK2 TK inhibitor TG101209 attenuated JAK2V617F autophosphorylation and induced apoptosis of HEL92.1.7 and Ba/F3-JAK2V617F cells. Cotreatment with PS and TG101209 further depleted JAK/STAT signaling and synergistically induced apoptosis of HEL92.1.7 and Ba/F3-JAK2V617F cells. Cotreatment with TG101209 and PS exerted greater cytotoxicity against primary CD34+ MPN cells than normal CD34+ HPCs. These in vitro findings suggest combination therapy with HDAC and JAK2V617F inhibitors is of potential value for the treatment of JAK2V617F-positive MPN.
Significant functional heterogeneity among KIR2DL1 alleles and a pivotal role of arginine245
Authors: Bari Rafijul , Bell Teresa , Leung Wai-Hang , Vong Queenie P. , Chan Wing Keung , Das Gupta Neha , Holladay Martha , Rooney Barbara , Leung Wing 
Published: October 2009

AbstractKiller immunoglobulin-like receptors (KIRs) play an essential role in the regulation of natural killer cell functions. KIR genes are highly polymorphic in nature, showing both haplotypic and allelic variations among people. We demonstrated in both in vitro and in vivo models a significant heterogeneity in function among different KIR2DL1 alleles, including their ability to inhibit YT-Indy cells from degranulation, interferon γ production, and cytotoxicity against target cells expressing the HLA-Cw6 ligand. Subsequent experiments showed that the molecular determinant was an arginine residue at position 245 (R245) in its transmembrane domain that mechanistically affects both the efficiency of inhibitory signaling and durability of surface expression. Specifically, in comparison with R245-negative alleles, KIR2DL1 that included R245 recruited more Src-homology-2 domain-containing protein tyrosine phosphatase 2 and β-arrestin 2, showed higher inhibition of lipid raft polarization at immune synapse, and had less down-regulation of cell-surface expression upon interaction with its ligand. Thus, our findings provide novel insights into the molecular determinant of KIR2DL1 and conceivably a fundamental understanding of KIR2DL1 allelic polymorphism in human disease susceptibility, transplant outcome, and donor selection.
T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993)
Authors: Marks David I. , Paietta Elisabeth M. , Moorman Anthony V. , Richards Susan M. , Buck Georgina , DeWald Gordon , Ferrando Adolfo , Fielding Adele K. , Goldstone Anthony H. , Ketterling Rhett P. , Litzow Mark R. , Luger Selina M. , McMillan Andrew K. , Mansour Marc R. , Rowe Jacob M. , Tallman Martin S. , Lazarus Hillard M. 
Published: October 2009

AbstractThe biology and outcome of adult T-cell acute lymphoblastic leukemia are poorly understood. We present here the clinical and biologic features of 356 patients treated uniformly on the prospective trial (UKALL XII/ECOG 2993) with the aim of describing the outcome and identifying prognostic factors. Complete remission was obtained in 94% of patients, and 48% survived 5 years. Positivity of blasts for CD1a and lack of expression of CD13 were associated with better survival (P = .01 and < .001, respectively). NOTCH1 and CDKN2A mutations were seen in 61% and 42% of those tested. Complex cytogenetic abnormalities were associated with poorer survival (19% vs 51% at 5 years, P = .006). Central nervous system involvement at diagnosis did not affect survival (47% vs 48%, P = not significant). For 99 patients randomized between autograft and chemotherapy, 5-year survival was 51% in each arm. Patients with a matched sibling donor had superior 5-year survival to those without donors (61% vs 46%, χ2, P = .02); this was the result of less relapse (25% vs 51% at 5 years, P < .001). Only 8 of 123 relapsed patients survive. This study provides a baseline for trials of new drugs, such as nelarabine, and may allow risk-adapted therapy in patients with poor-prognosis T-cell ALL.
A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis
Authors: Mumford Andrew D. , Dawood Ban B. , Daly Martina E. , Murden Sherina L. , Williams Michael D. , Protty Majd B. , Spalton Jennifer C. , Wheatley Mark , Mundell Stuart J. , Watson Steve P. 
Published: October 2009

AbstractWe investigated the cause of mild mucocutaneous bleeding in a 14-year-old male patient (P1). Platelet aggregation and ATP secretion induced by arachidonic acid and the thromboxane A2 receptor (TxA2R) agonist U46619 were reduced in P1 compared with controls, whereas the responses to other platelet agonists were retained. P1 was heterozygous for a transversion within the TBXA2R gene predictive of a D304N substitution in the TxA2R. In Chinese hamster ovary-K1 cells expressing the variant D304N TxA2R, U46619 did not increase cytosolic free Ca2+ concentration, indicating loss of receptor function. The TxA2R antagonist [3H]-SQ29548 showed an approximate 50% decrease in binding to platelets from P1 but absent binding to Chinese hamster ovary-K1 cells expressing variant D304N TxA2R. This is the second naturally occurring TxA2R variant to be associated with platelet dysfunction and the first in which loss of receptor function is associated with reduced ligand binding. D304 lies within a conserved NPXXY motif in transmembrane domain 7 of the TxA2R that is a key structural element in family A G protein-coupled receptors. Our demonstration that the D304N substitution causes clinically significant platelet dysfunction by reducing ligand binding establishes the importance of the NPXXY motif for TxA2R function in vivo.
A permutation-based multiple testing method for time-course microarray experiments
Authors: Sohn Insuk , Owzar Kouros , George Stephen L , Kim Sujong , Jung Sin-Ho 
Published: October 2009

AbstractBackgroundTime-course microarray experiments are widely used to study the temporal profiles of gene expression. Storeyet al. (2005) developed a method for analyzing time-course microarray studies that can be applied to discovering genes whose expression trajectories change over time within a single biological group, or those that follow different time trajectories among multiple groups. They estimated the expression trajectories of each gene using natural cubic splines under the null (no time-course) and alternative (time-course) hypotheses, and used a goodness of fit test statistic to quantify the discrepancy. The null distribution of the statistic was approximated through a bootstrap method. Gene expression levels in microarray data are often complicatedly correlated. An accurate type I error control adjusting for multiple testing requires the joint null distribution of test statistics for a large number of genes. For this purpose, permutation methods have been widely used because of computational ease and their intuitive interpretation.ResultsIn this paper, we propose a permutation-based multiple testing procedure based on the test statistic used by Storeyet al. (2005). We also propose an efficient computation algorithm. Extensive simulations are conducted to investigate the performance of the permutation-based multiple testing procedure. The application of the proposed method is illustrated using theCaenorhabditis elegansdauer developmental data.ConclusionOur method is computationally efficient and applicable for identifying genes whose expression levels are time-dependent in a single biological group and for identifying the genes for which the time-profile depends on the group in a multi-group setting.
Analysis and modelling of motility of cell populations with MotoCell
Authors: Cantarella Concita , Sepe Leandra , Fioretti Francesca , Ferrari Maria Carla , Paolella Giovanni 
Published: October 2009

Abstract

Background
Cell motility plays a central role in development, wound-healing and tumour invasion. Cultures of eucariotic cells are a complex system where most cells move according to 'random' patterns, but may also be induced to a more coordinate migration by means of specific stimuli, such as the presence of chemical attractants or the introduction of a mechanical stimulus. Various tools have been developed that work by keeping track of the paths followed by specific objects and by performing statistical analysis on the recorded path data. The available tools include desktop applications or macros running within a commercial package, which address specific aspects of the process.

Results
An online application, MotoCell, was developed to evaluate the motility of cell populations maintained in various experimental conditions. Statistical analysis of cell behaviour consists of the evaluation of descriptive parameters such as average speed and angle, directional persistence, path vector length, calculated for the whole population as well as for each cell and for each step of the migration; in this way the behaviour of a whole cell population may be assessed as a whole or as a sum of individual entities. The directional movement of objects may be studied by eliminating the modulo effect in circular statistics analysis, able to evaluate linear dispersion coefficient (R) and angular dispersion (S) values together with average angles. A case study is provided where the system is used to characterize motility of RasV12 transformed NIH3T3 fibroblasts.

Conclusion
Here we describe a comprehensive tool which takes care of all steps in cell motility analysis, including interactive cell tracking, path editing and statistical analysis of cell movement, all within a freely available online service. Although based on a standard web interface, the program is very fast and interactive and is immediately available to a large number of users, while exploiting the web approach in a very effective way. The ability to evaluate the behaviour of single cells allows to draw the attention on specific correlations, such as linearity of movement and deviation from the expected direction. In addition to population statistics, the analysis of single cells allows to group the cells into subpopulations, or even to evaluate the behaviour of each cell with respect to a variable reference, such as the direction of a wound or the position of the closest cell.
Clinical bioinformatics for complex disorders: a schizophrenia case study
Authors: Schwarz Emanuel , Leweke F Markus , Bahn Sabine , Liò Pietro 
Published: October 2009

AbstractBackgroundIn the diagnosis of complex diseases such as neurological pathologies, a wealth of clinical and molecular information is often available to help the interpretation. Yet, the pieces of information are usually considered in isolation and rarely integrated due to the lack of a sound statistical framework. This lack of integration results in the loss of valuable information about how disease associated factors act synergistically to cause the complex phenotype.ResultsHere, we investigated complex psychiatric diseases as networks. The networks were used to integrate data originating from different profiling platforms. The weighted links in these networks capture the association between the analyzed factors and allow the quantification of their relevance for the pathology. The heterogeneity of the patient population was analyzed by clustering and graph theoretical procedures. We provided an estimate of the heterogeneity of the population of schizophrenia and detected a subgroup of patients featuring remarkable abnormalities in a network of serum primary fatty acid amides. We compared the stability of this molecular network in an extended dataset between schizophrenia and affective disorder patients and found more stable structures in the latter.ConclusionWe quantified robust associations between analytes measured with different profiling platforms as networks. The methodology allows the quantitative evaluation of the complexity of the disease. The identified disease patterns can then be further investigated with regards to their diagnostic utility or help in the prediction of novel therapeutic targets. The applied framework is able to enhance the understanding of complex psychiatric diseases, and may give novel insights into drug development and personalized medicine approaches.
Positive selection for the male functionality of a co-retroposed gene in the hominoids
Authors: Zhang Yong , Lu Shujuan , Zhao Shuqi , Zheng Xiaofeng , Long Manyuan , Wei Liping 
Published: October 2009

AbstractBackgroundNew genes generated by retroposition are widespread in humans and other mammalian species. Usually, this process copies a single parental gene and inserts it into a distant genomic location. However, retroposition of two adjacent parental genes,i.e. co-retroposition, had not been reported until the hominoid chimeric gene,PIPSL, was identified recently. It was shown how two genes linked in tandem (phosphatidylinositol-4-phosphate 5-kinase, type I, alpha,PIP5K1Aand proteasome 26S subunit, non-ATPase, 4,PSMD4) could be co-retroposed from a single RNA molecule to form this novel chimeric gene. However, understanding of the origination and biological function ofPIPSLrequires determination of the coding potential of this gene as well as the evolutionary forces acting on its hominoid copies.ResultsWe tackled these problems by analyzing the evolutionary signature in both within-species variation and between species divergence in the sequence and structure of the gene. We revealed a significant evolutionary signature: the coding region has significantly lower sequence variation, especially insertions and deletions, suggesting that the human copy may encode a protein. Moreover, a survey across five different hominoid species revealed that all adaptive changes ofPSMD4-derived regions occurred on branches leading to human and chimp rather than other hominoid lineages. Finally, computational analysis suggests testis-specific transcription ofPIPSLis regulated by tissue-dependent methylation rather than some transcriptional leakage.ConclusionTherefore, this set of analyses showed thatPIPSLis an extraordinary co-retroposed protein-coding gene that may participate in the male functions of humans and its close relatives.
Metabolic fluxes in the central carbon metabolism of Dinoroseobacter shibae and Phaeobacter gallaeciensis, two members of the marine Roseobacter clade
Authors: Fürch Tobias , Preusse Matthias , Tomasch Jürgen , Zech Hajo , Wagner-Döbler Irene , Rabus Ralf , Wittmann Christoph 
Published: October 2009

Abstract

Background
In the present work the central carbon metabolism of Dinoroseobacter shibae and Phaeobacter gallaeciensis was studied at the level of metabolic fluxes. These two strains belong to the marine Roseobacter clade, a dominant bacterial group in various marine habitats, and represent surface-associated, biofilm-forming growth (P. gallaeciensis) and symbiotic growth with eukaryotic algae (D. shibae). Based on information from recently sequenced genomes, a rich repertoire of pathways has been identified in the carbon core metabolism of these organisms, but little is known about the actual contribution of the various reactions in vivo.

Results
Using 13C labelling techniques in specifically designed experiments, it could be shown that glucose-grown cells of D. shibae catabolise the carbon source exclusively via the Entner-Doudoroff pathway, whereas alternative routes of glycolysis and the pentose phosphate pathway are obviously utilised for anabolic purposes only. Enzyme assays confirmed this flux pattern and link the lack of glycolytic flux to the absence of phosphofructokinase activity. The previously suggested formation of phosphoenolpyruvate from pyruvate during mixotrophic CO2 assimilation was found to be inactive under the conditions studied. Moreover, it could be shown that pyruvate carboxylase is involved in CO2 assimilation and that the cyclic respiratory mode of the TCA cycle is utilised. Interestingly, the use of intracellular pathways was highly similar for P. gallaeciensis.

Conclusion
The present study reveals the first insight into pathway utilisation within the Roseobacter group. Fluxes through major intracellular pathways of the central carbon metabolism, which are closely linked to the various important traits found for the Roseobacter clade, could be determined. The close similarity of fluxes between the two physiologically rather different species might provide the first indication of more general key properties among members of the Roseobacter clade which may explain their enormous success in the marine realm.