bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adhesion and Aggregation of Thrombin Prestimulated Human Platelets on Surface-Bound Fibrinogen: Evidence for Involvement of ADP and Arachidonic Acid Pathways
Authors: Feuerstein I A , Dickson V M 
Published: July 2018

SummaryThe purpose of this study was to examine the influence of substances released from human platelets upon their accumulation on human fibrinogen-coated glass tubes. After prestimulation with thrombin for one minute or in the absence of prestimulation, washed human platelets suspended in Eagle’s medium with RBC were drawn through the tubes at 1 ml/min, 80 s-1, for 1, 2 or 6 min. Thrombin prestimulation (0.02,0.05 or 0.25 U/ml) was followed by inactivation with hirudin (0.1, 0.25 or 1.25 U/ml) before flow. Singly adherent platelets were observed in the absence of thrombin or with thrombin for exposure times of 1 and 2 min. At 6 min after at least 0.05 U/ml of thrombin, surface- bound aggregates were observed. The initial rate of adhesion increased with the amount of thrombin used for prestimulation. For adhesion to fibrinogen in the absence of prestimulation, platelet-derived ADP was a stimulator. Adhesion was shown to be independent of the ADP and arachidonic acid pathways in response to prestimulation with a low level of thrombin, 0.02 U/ml. For adhesion and cohesion, aggregation, in the presence of sufficient thrombin for prestimulation, 0.05 U/ml, ADP, serotonin and substances from arachidonic acid metabolism acted jointly to stimulate platelets.
The Effect of a Thromboxane Synthetase Inhibitor, Dazoxiben, and Acetylsalicylic Acid on Platelet Function and Prostaglandin Metabolism
Authors: Dale Jon , Thaulow Erik , Myhre Erik , Parry John 
Published: July 2018

SummaryTwenty-four men received either placebo, 0.1 g of the thromboxane synthetase inhibitor dazoxiben, 0.25 or 1.0 g of acetylsalicylic acid (ASA). Dazoxiben reduced the maximal rate of collagen-induced platelet aggregation, but less than did ASA. ASA abolished secondary, ADP-induced aggregation, dazoxiben not. Both drugs prolonged the bleeding-time.Plasma thromboxane B2 (TxB2) levels did not change significantly after dazoxiben, whereas the prostacyclin metabolite 6-keto-PGF1α rose. The larger dose of ASA reduced both TxB2 and 6-keto-PGF1α in plasma. Whole blood was allowed to clot in order to estimate prostaglandin metabolism. Both drugs prevented thromboxane production effectively. Formation of 6-keto-PGF1α decreased by 95 per cent after ASA but was more than doubled after dazoxiben.Dazoxiben is a selective and effective thromboxane synthetase inhibitor, but has a weaker effect on platelet reactivity than ASA, possibly because endoperoxide formation is not prevented.
An Enzyme Linked Immunosorbent Assay for Determination of Tissue Plasminogen Activator Applied to Patients with Thromboembolic Disease
Authors: Bergsdorf Nils , Nilsson Torbjörn , Wallén Per 
Published: July 2018

SummaryUtilizing the immunoglobulin fraction from a goat antiserum against human uterine tissue plasminogen activator, an enzyme- linked immunoassay for tissue-type plasminogen activator in human plasma has been developed. With the new method, the concentration of t-PA in normal human acidified plasma is found to be 4.0 ± 1.8 (SD) ng/ml. It increases to 12 ng/ml after a tomiquet test, and to 14 ng/ml after strenous physical exercise. In a group of patients with idiopathic thromboembolic disease, the resting t-PA concentration was 5 ng/ml and the post-occlusion value 16 ng/ml. Furthermore, the patients also exhibited a normal post-occlusion rise in the concentration of plasmin-α2-antiplasmin complex. However, in 37% of the post-occlusion patient plasmas, virtually no increase in t-PA could be detected by a specific activity assay. The results indicate that the reason for a defective post-occlusion fibrinolytic activity in a majority of cases may be the presence of increased concentrations of a fast-acting specific t-PA inhibitor.
A Plasma Factor Enhances Activity of Vitamin K-Dependent Coagulation Proteins
Authors: Owens Michael R , Cimino Catherine D 
Published: July 2018

SummaryA plasma factor, “coagulopoietin”, present in animals with depleted vitamin K-dependent coagulation factors, appears to enhance activity of these factors in normal animals. We have investigated the effects of “coagulopoietin” on synthesis of certain coagulation proteins by the isolated rat liver perfused for eight hours. Liver donor rats received plasma injections from vitamin K-deficient rats or from normal rats 24 hr before sacrifice. Coagulation activity of Factor VII and Factor II in liver perfusate samples was measured with a coagulation assay; Factor II synthesis was also measured by rocket immunoelectrophoresis and by activation with E. carinatus venom. Cumulative hepatic synthesis of. Factor VII coagulation activity was increased by 43% when rat liver donors received vitamin K-deficient rat plasma compared to normal rat plasma. Cumulative synthesis of Factor II coagulation activity was increased by 51%, but synthesis of the protein measured immunologically or by activation with venom was not affected. The “coagulopoietin” factor in these studies appears to increase measurable coagulation factor activity without increasing total protein synthesis.
Protective Effect of Warfarin in Arterial Thrombosis: Evidence from a Vascular Prosthesis Model in Rats
Authors: Reyers Ine , de Gaetano Giovanni , Benedetta Donati Maria 
Published: July 2018

SummaryThree different schedules of treatment with warfarin were studied in rats bearing a polyethylene cannula in their abdominal aorta. The time of occlusion of the vascular prosthesis was significantly prolonged when warfarin was started 24 hr previously, at the time of loop insertion or 24 hr later. When the drug treatment was started 24 hr before insertion of the loop, however, a high degree of toxicity was observed. The animals of this group that died of hemorrhage had significantly lower mean thrombotest levels.On the other hand, the correlation between occlusion of the loop and level of anticoagulation was not as simple as one might anticipate; on the one hand, severe anticoagulation did not protect all of the rats from loop occlusion, but, on the other hand, recovery from hypocoagulability was not always immediately followed by occlusion of the loop.In order to better elucidate the mechanism of the antithrombotic effect of warfarin, we also assessed the effect of the drug on platelet-vessel wall interaction by the template bleeding time. A close association existed between warfarin-induced hypocoagulability and prolongation of the bleeding time.These observations may constitute the experimental basis for a better understanding of the antithrombotic effect of warfarin in some arterial diseases and in myocardial infarction.
75Se-Seleno-Methionine-Actin as a Probe for Determination of Platelet Production Rate
Authors: Cardinaud R , Dassin E , Bourebia J 
Published: July 2018

SummarySynthesis of actin is a reasonably correct representation of the platelet production rate. Measurement of actin production obviates some of the drawbacks encountered in currently available methods. Platelet actin was characterized on polyacrylamide gel electrophoreses using methylated radioactive rabbit actin as a reference. Platelet actin was unambiguously identified by showing that it forms a complex with DNAase-I similar to the complex obtained with pure rabbit actin.Six days after intravenous injection of 75Se-seleno-methionine actin was one of the most highly labelled platelet components. The platelet pellet (one rat per sample) was solubilized with 1% Triton X-100, 0.75 M guanidine-HCl and dialyzed in a medium containing 1% SDS (to eliminate Triton X-100 and guanidine-HCl). A carefully measured aliquot was deposited on a polyacrylamide gel. After electrophoresis in the presence of SDS the radioactivity of the actin band was measured and the ratio of the total actin radioactivity to the injected radioactivity was taken as a measure of platelet production.The validity of the actin probe was tested with populations of normal animals. The specific radioactivity of actin was proportional to the injected dose of 75Se-seleno-methionine up to 1 mCi/ kg animal. A semi-log plot of actin specific radioactivity vs time exhibited a pseudo-first order decrease. Another constituent with a high specific radioactivity (XM) was excluded as a suitable probe because it was shown to be an adsorbed plasma protein.
Platelet Adhesion in Polytetrafluoroethylene (PTFE) Vascular Grafts In Vivo and the Influence of Increased Intramuscular Pressure-An Experimental Model
Authors: Christenson J T , Qvarfordt P , Strand S-E , Arvidsson D , Sjöberg T , Olsson P-I 
Published: July 2018

SummaryThrombogenicity of graft material is involved in early graft failure in small diameter grafts. The frequently seen postoperative swelling of the leg after distal revascularization may cause an increased intramuscular pressure and early graft failure.Pairs of 4 mm polytetrafluoroethylene (PTFE) grafts were implanted. Autologous platelets were labeled with mIn-oxine. Platelet adhesiveness onto the grafts were analyzed from gamma camera images. Intramuscular pressures were measured with wick technique. Blood flow was measured. One graft served as control the other as test graft. Ninety minutes after declamping the i. m. pressure was increased in the test-leg to 30 mmHg, and later to 60 mmHg.In the control-graft platelet uptake increased to a maximum 60 min after declamping. Blood flow and i.m. pressure remained uneffected. The test-grafts were initially similar but when i.m. pressure was increased to 30 mmHg activity in the grafts increased significantly. Blood flow decreased with 12% of initial flow. When i. m. pressure was raised to 60 mmHg platelet uptake continued to increase.An increased intramuscular pressure of 30 mmHg or more significantly increase the amount of platelets adhering onto PTFE grafts, emphasizing the need for measuring intramuscular pressures after lower limb vascular revascularizations.
Glucocorticoids Inhibit Plasminogen Activator Production by Endothelial Cells
Authors: Laug Walter E 
Published: July 2018

SummaryConfluent cultures of bovine aortic endothelial cells (BEC) were found to secrete both tissue type plasminogen activator (t- PA) and urokinase type plasminogen activator (u-PA). Exposure of the cultures to increasing concentrations of dexamethasone resulted in a time and concentration dependent inhibition of cellular and secreted u-PA. Complete inhibition of u-PA production and secretion was found at dexamethasone concentrations of 10-8 molar or higher. Several distinct PA forms with molecular weights ranging from 10,000-20,000 to >200,000 were found in the conditioned medium of untreated BEC cultures. After addition of dexamethasone (10-7 molar) to the culture medium the PAs with molecular weights of 117,000, 58,000,47,000, were absent suggesting that they were u-PAs, whereas the PAs with molecular weights of >200,000 and 75,000 remained unchanged suggesting their t-PA origins. The PAs with lower molecular weights of 35,000, 28,000 and 10,000 to 20,000 were most likely generated from the higher molecular weight forms by limited proteolysis since they were absent when the medium was conditioned in the presence of the protease inhibitor Trasylol.The two PA types may therefore be independently regulated in BEC.
Mechanical Heart Valve Replacement in a Low-Middle Income Region in the Modern Era: Midterm Results from a Sub-Saharan Center
Authors: Mve Mvondo Charles , Pugliese Marta , Ambassa Jean Claude , Giamberti Alessandro , Bovio Emanuele , Dailor Ellen 
Published: July 2018

Abstract
Background The management of patients with mechanical heart valves remains a major concern in populations with limited resources and medical facilities. This study reports the clinical outcomes of patients who underwent mechanical valve implantation in a sub-Saharan center over an 8-year period.
Methods A total of 291 mechanical valves were implanted in 233 patients in our institution between February 2008 and June 2016. A total of 117 patients underwent mitral valve replacement (MVR, 50.2%), 57 had aortic valve replacement (AVR, 24.4%), and 59 underwent both AVR and MVR (double valve replacement [DVR], 25.7%). The mean age at surgery was 27.6 ± 13.4 years (range, 7–62 years). Rheumatic etiology was found in 80.6% of the patients. Hospital mortality, late deaths, and valve-related events were reviewed at follow-up (839 patient-years, range: 1–9.4 years, complete in 93%).
Results The 30-day mortality was 4.7% (11/233). The overall survival at 1 and 6 years for the whole cohort was 88.8 ± 2.1% and 78.7 ± 3.3%, respectively. The 6-year survival for AVR, MVR, and DVR was 89.3 ± 4.8%, 73.2 ± 5.4%, and 79.3 ± 5.8%, respectively (p = 0.15). The freedom from neurologic events and anticoagulation-related bleeding at 6 years was 93.1 ± 2.1% and 78.9 ± 3.7%, respectively. No patient had reoperation at follow-up. No case of prosthetic valve thrombosis was identified. Eight full-term pregnancies were reported.
Conclusion This preliminary experience reports acceptable midterm results after mechanical heart valve implantation in our region. Both accurate surgical evaluation and strategies, either financial or social, facilitating patient's education and medical assistance are crucial to ensure good results. Long-term follow-up and further studies comparing current nonthrombogenic options are warranted to draw reliable conclusions.
Number of Risk Factors in Down Syndrome Pregnancies
Authors: Hussamy Deana , Herrera Christina , Twickler Diane , Mcintire Donald , Dashe Jodi 
Published: July 2018

Objective The objective of this study was to evaluate risk factor prevalence in pregnancies with fetal Down syndrome, in an effort to characterize efficacy of population-based screening.
Study Design Retrospective review of singleton pregnancies with delivery of live born or stillborn infant with Down syndrome from 2009 through 2015. Risk factor categories included maternal age ≥35 years, abnormal serum screening, identification of ≥1 ultrasound marker at 16 to 22 weeks (nuchal thickness ≥6 mm, echogenic intracardiac focus, echogenic bowel, renal pelvis dilatation, femur length <third percentile), and detection of a major fetal anomaly. Statistical analyses included χ2 test and Mantel–Haenszel χ2 test.
Results Down syndrome infants represented 1:428 singleton births. All risk categories were assessed in 125 pregnancies and included abnormal serum screen in 110 (88%), ≥1 ultrasound marker in 66 (53%), and ≥1 anomaly in 41 (34%). The calculated risk was at least 1:270 in 93% of Down syndrome pregnancies. More pregnancies had multiple risk factors than had a single risk factor, 90 (72%) versus 30 (24%), p < 0.001. An abnormal ultrasound marker or anomaly was identified in >50% of fetuses in women <35 years and in >75% of those 35 years and older.
Conclusion In a population-based cohort, sensitivity of second-trimester Down syndrome screening was 93%, with multiple risk factors present in nearly three-fourths of cases.
Interdelivery Interval and Medically Indicated Preterm Delivery
Authors: Grobman William , Dude Annie 
Published: July 2018

Objective The objective of this study was to examine whether a medically indicated preterm delivery is relatively more likely following longer interdelivery intervals.
Study Design This is a case–control study of women with two consecutive deliveries of a live singleton at the same institution between 2005 and 2015, with the subsequent delivery occurring preterm. Preterm deliveries were classified as spontaneous if women delivered following preterm labor, preterm premature rupture of membranes, or placental abruption. Preterm deliveries were classified as medically indicated if women underwent delivery for fetal or maternal medical indications. Interdelivery interval was categorized as < 18, 18 to 59, and 60 months or more. Characteristics of women who had a medically indicated versus spontaneous preterm delivery were compared.
Results Of the 1,276 women, 25.6% had a medically indicated preterm delivery and 74.4% had a spontaneous preterm delivery. Compared with women with an interdelivery interval of 18 to 59 months (of whom 25.7% had a preterm delivery for medical indications), women with a shorter interdelivery interval were less likely (19.3%), while women with a longer interdelivery interval were more likely (37.4%; p = 0.003) to have a medically indicated preterm delivery. This relationship persisted even when accounting for other factors.
Conclusion Preterm deliveries are more likely to be medically indicated as the interdelivery interval lengthens.
Neutral Spaces and Topological Explanations in Evolutionary Biology: Lessons from Some Landscapes and Mappings
Authors: Huneman Philippe 
Published: July 2018

AbstractI consider recent uses of the notion of neutrality in evolutionary biology and ecology, questioning their relevance to the kind of explanation recently labeled ‘topological explanation’. Focusing on fitness landscapes and genotype-phenotype maps, I explore the explanatory uses of neutral subspaces, as modeled in two perspectives: hyperdimensional fitness landscapes and RNA sequence-structure maps. I argue that topological properties of such spaces account for features of evolutionary systems: respectively, capacity for adaptive evolution toward global optima and mutational robustness of genotypes. Thus many models appealing to “neutral” manifolds provide topological alternatives to hypothetical mechanisms.
SKEMPI 2.0: an updated benchmark of changes in protein–protein binding energy, kinetics and thermodynamics upon mutation
Authors: Jankauskaitė Justina , Jiménez-García Brian , Dapkūnas Justas , Fernández-Recio Juan , Moal Iain H 
Published: July 2018

Abstract

Motivation
Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein–protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering.

Results
We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein–protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding.

Availability and implementation
The database is available as supplementary data and at https://life.bsc.es/pid/skempi2/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Heritability estimation and differential analysis of count data with generalized linear mixed models in genomic sequencing studies
Authors: Sun Shiquan , Zhu Jiaqiang , Mozaffari Sahar , Ober Carole , Chen Mengjie , Zhou Xiang 
Published: July 2018

AbstractMotivationGenomic sequencing studies, including RNA sequencing and bisulfite sequencing studies, are becoming increasingly common and increasingly large. Large genomic sequencing studies open doors for accurate molecular trait heritability estimation and powerful differential analysis. Heritability estimation and differential analysis in sequencing studies requires the development of statistical methods that can properly account for the count nature of the sequencing data and that are computationally efficient for large datasets.ResultsHere, we develop such a method, PQLseq (Penalized Quasi-Likelihood for sequencing count data), to enable effective and efficient heritability estimation and differential analysis using the generalized linear mixed model framework. With extensive simulations and comparisons to previous methods, we show that PQLseq is the only method currently available that can produce unbiased heritability estimates for sequencing count data. In addition, we show that PQLseq is well suited for differential analysis in large sequencing studies, providing calibrated type I error control and more power compared to the standard linear mixed model methods. Finally, we apply PQLseq to perform gene expression heritability estimation and differential expression analysis in a large RNA sequencing study in the Hutterites.Availability and implementationPQLseq is implemented as an R package with source code freely available at www.xzlab.org/software.html and https://cran.r-project.org/web/packages/PQLseq/index.html.Supplementary informationSupplementary data are available at Bioinformatics online.
BIPSPI: a method for the prediction of partner-specific protein–protein interfaces
Authors: Sanchez-Garcia Ruben , Sorzano C O S , Carazo J M , Segura Joan 
Published: July 2018

AbstractMotivationProtein–Protein Interactions (PPI) are essentials for most cellular processes and thus, unveiling how proteins interact is a crucial question that can be better understood by identifying which residues are responsible for the interaction. Computational approaches are orders of magnitude cheaper and faster than experimental ones, leading to proliferation of multiple methods aimed to predict which residues belong to the interface of an interaction.ResultsWe present BIPSPI, a new machine learning-based method for the prediction of partner-specific PPI sites. Contrary to most binding site prediction methods, the proposed approach takes into account a pair of interacting proteins rather than a single one in order to predict partner-specific binding sites. BIPSPI has been trained employing sequence-based and structural features from both protein partners of each complex compiled in the Protein–Protein Docking Benchmark version 5.0 and in an additional set independently compiled. Also, a version trained only on sequences has been developed. The performance of our approach has been assessed by a leave-one-out cross-validation over different benchmarks, outperforming state-of-the-art methods.Availability and implementationBIPSPI web server is freely available at http://bipspi.cnb.csic.es. BIPSPI code is available at https://github.com/bioinsilico/BIPSPI. Docker image is available at https://hub.docker.com/r/bioinsilico/bipspi/.Supplementary informationSupplementary data are available at Bioinformatics online.
Scaling read aligners to hundreds of threads on general-purpose processors
Authors: Langmead Ben , Wilks Christopher , Antonescu Valentin , Charles Rone 
Published: July 2018

Abstract

Motivation
General-purpose processors can now contain many dozens of processor cores and support hundreds of simultaneous threads of execution. To make best use of these threads, genomics software must contend with new and subtle computer architecture issues. We discuss some of these and propose methods for improving thread scaling in tools that analyze each read independently, such as read aligners.

Results
We implement these methods in new versions of Bowtie, Bowtie 2 and HISAT. We greatly improve thread scaling in many scenarios, including on the recent Intel Xeon Phi architecture. We also highlight how bottlenecks are exacerbated by variable-record-length file formats like FASTQ and suggest changes that enable superior scaling.

Availability and implementation
Experiments for this study: https://github.com/BenLangmead/bowtie-scaling.

Bowtie
http://bowtie-bio.sourceforge.net .

Bowtie 2
http://bowtie-bio.sourceforge.net/bowtie2 .

HISAT
http://www.ccb.jhu.edu/software/hisat

Supplementary information
Supplementary data are available at Bioinformatics online.