bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Community Composition Reveals Spatial Variation and Distinctive Core Microbiome of the Weaver Ant Oecophylla smaragdina in Malaysia
Authors: Chua Kah-Ooi , Song Sze-Looi , Yong Hoi-Sen , See-Too Wah-Seng , Yin Wai-Fong , Chan Kok-Gan
Published: July 2018

The weaver antOecophylla smaragdinais an aggressive predator of other arthropods and has been employed as a biological control agent against many insect pests in plantations. Despite playing important roles in pest management, information about the microbiota ofO.smaragdinais limited. In this work, a number ofO.smaragdinacolonies (n = 12) from Malaysia had been studied on their microbiome profile using Illumina 16S rRNA gene amplicon sequencing. We characterized the core microbiota associated with theseO.smaragdinaand investigated variation between colonies from different environments. Across all 12 samples, 97.8% of the sequences were assigned to eight bacterial families and most communities were dominated by families Acetobacteraceae and Lactobacillaceae. Comparison among colonies revealed predominance of Acetobacteraceae inO.smaragdinafrom forest areas but reduced abundance was observed in colonies from urban areas. In addition, our findings also revealed distinctive community composition inO.smaragdinashowing little taxonomic overlap with previously reported ant microbiota. In summary, our work provides information regarding microbiome ofO.smaragdinawhich is essential for establishing healthy colonies. This study also forms the basis for further study on microbiome ofO.smaragdinafrom other regions.
Stress related epigenetic changes may explain opportunistic success in biological invasions in Antipode mussels
Authors: Ardura Alba , Clusa Laura , Zaiko Anastasija , Garcia-Vazquez Eva , Miralles Laura
Published: July 2018

Different environmental factors could induce epigenetic changes, which are likely involved in the biological invasion process. Some of these factors are driven by humans as, for example, the pollution and deliberate or accidental introductions and others are due to natural conditions such as salinity. In this study, we have analysed the relationship between different stress factors: time in the new location, pollution and salinity with the methylation changes that could be involved in the invasive species tolerance to new environments. For this purpose, we have analysed two different mussels’ species, reciprocally introduced in antipode areas: the Mediterranean blue musselMytilus galloprovincialisand the New Zealand pygmy musselXenostrobus securis, widely recognized invaders outside their native distribution ranges. The demetylathion was higher in more stressed population, supporting the idea of epigenetic is involved in plasticity process. These results can open a new management protocols, using the epigenetic signals as potential pollution monitoring tool. We could use these epigenetic marks to recognise the invasive status in a population and determine potential biopollutants.
Tobacco biomarkers and genetic/epigenetic analysis to investigate ethnic/racial differences in lung cancer risk among smokers
Authors: Murphy Sharon E. , Park Sungshim Lani , Balbo Silvia , Haiman Christopher A. , Hatsukami Dorothy K. , Patel Yesha , Peterson Lisa A. , Stepanov Irina , Stram Daniel O. , Tretyakova Natalia , Hecht Stephen S. , Le Marchand Loïc
Published: July 2018

The Multiethnic Cohort Study has demonstrated that African Americans and Native Hawaiians have a higher risk for lung cancer due to cigarette smoking than Whites while Latinos and Japanese Americans have a lower risk. These findings are consistent with other epidemiologic studies in the literature. In this review, we summarize tobacco carcinogen and toxicant biomarker studies and genetic analyses which partially explain these differences. As determined by measurement of total nicotine equivalents in urine, which account for about 85% of the nicotine dose, African Americans take up greater amounts of nicotine than Whites per cigarette while Japanese Americans take up less. There are corresponding differences in the uptake of tobacco smoke carcinogens such as tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, 1,3-butadiene, and other toxic volatiles. The lower nicotine uptake of Japanese Americans is clearly linked to the preponderance of low activity forms of the primary nicotine metabolizing enzyme CYP2A6 in this ethnic group, leading to more unchanged nicotine in the body and thus lower smoking intensity. But the relatively high risk of Native Hawaiians and the low risk of Latino smokers for lung cancer are not explained by these factors. The possible role of epigenetics in modifying lung cancer risk among smokers is also discussed here. The results of these published studies may lead to a better understanding of susceptibility factors for lung cancer in cigarette smokers thus potentially identifying biomarkers that can detect those individuals at highest risk so that preventive approaches can be initiated at an early stage of the lung cancer development process.
Determination of chirality and density control of Néel-type skyrmions with in-plane magnetic field
Authors: Zhang Senfu , Zhang Junwei , Wen Yan , Chudnovsky Eugene M. , Zhang Xixiang
Published: July 2018

Magnetic skyrmions are topologically protected nanoscale spin textures exhibiting fascinating physical behaviors. Recent observations of room temperature Néel-type skyrmions in magnetic multilayer films are an important step towards their use in ultra-low power devices. Here, we investigate the magnetization reversal in [Pt/Co/Ta]n multilayer samples under a tilted magnetic field using in-situ Lorentz transmission electron microscopy. On decreasing the magnetic field, individual skyrmions appear to subsequently evolve into snake-like structures growing in the direction opposite to the in-plane magnetic field. We show that this unusual relation between the velocity vector and the magnetic field is dominated by the chirality of the Néel-type skyrmions. It allows one to extract the sign of the Dzyaloshinskii–Moriya constant. We also demonstrate that high concentration of skyrmions can be achieved on increasing the in-plane component of the field or increasing the disorder of the film. Our micromagnetic simulations agree with our experimental results.
A new diphosphine-carbonyl complex of ruthenium: an efficient precursor for C–C and C–N bond coupling catalysis
Authors: Mukherjee Aparajita , Hrovat David A. , Richmond Michael G. , Bhattacharya Samaresh
Published: July 2018

Reaction of 1,2-bis(diphenylphosphino)benzene (dppbz) with [{Ru(CO)2Cl2}n] affords [Ru(dppbz)(CO)2Cl2], which serves as an excellent pre-catalyst for Suzuki-type C–C coupling and Buchwald-type C–N coupling reactions.
Oxidatively stable ferrocenyl-π-bridge-titanocene D–π-A complexes: an electrochemical and spectroscopic investigation of the mixed-valent states
Authors: Pienkos Jared A. , Webster Alexander B. , Piechota Eric J. , Agakidou A. Danai , McMillen Colin D. , Pritchett David Y. , Meyer Gerald J. , Wagenknecht Paul S.
Published: July 2018

Coordination of CuI into RCp2Ti(C2Fc)2 compounds results in well-separated FeIII/II couples and mixed-valent states with distinct spectroscopic signatures.
Ferritin encapsulation of artificial metalloenzymes: engineering a tertiary coordination sphere for an artificial transfer hydrogenase
Authors: Hestericová Martina , Heinisch Tillmann , Lenz Markus , Ward Thomas R.
Published: July 2018

Creating a tertiary coordination sphere around a transition metal catalyst incorporated within a protein affects its catalytic turnover and enantioselectivity.
Octacyanometallate qubit candidates
Authors: Pearson Tyler J. , Laorenza Daniel W. , Krzyaniak Matthew D. , Wasielewski Michael R. , Freedman Danna E.
Published: July 2018

Cyanometallates are excellent building blocks for networks, we demonstrate counterintuitively long spin–lattice relaxation times in two heavy octacyanometalltes.
Modelling mass balance of cadmium in paddy soils under long term control scenarios
Authors: Feng Wenli , Guo Zhaohui , Peng Chi , Xiao Xiyuan , Shi Lei , Han Xiaoqing , Ran Hongzhen
Published: July 2018

A simple mass balance model was developed for the change of Cd content in soils under long-term control scenarios.
Laurus nobilis(laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice
Authors: Medeiros-Fonseca B. , Mestre V. F. , Colaço B. , Pires M. J. , Martins T. , Gil da Costa R. M. , Neuparth M. J. , Medeiros R. , Moutinho Magda S. S. , Dias Maria Inês , Barros Lillian , Bastos M. M. S. M. , Félix L. , Venâncio C. , Ferreira Isabel C. F. R. , Antunes L. M. , Oliveira P. A.
Published: July 2018

Cancers induced by HPV remain a significant public health threat, fueling the study of new therapies.
Performance-improved Li-O2 batteries by tailoring the phases of MoxC porous nanorods as an efficient cathode
Authors: Yu Hong , Dinh Khang Ngoc , Sun Yuanmiao , Fan Haosen , Wang Yonghui , Jing Yao , Li Shuzhou , Srinivasan Madhavi , Yan Qingyu
Published: July 2018

By tailoring the phases of MoxC, α-MoC1−x exhibits better Li-O2 battery performance than β-Mo2C with a lower charge-transfer resistance and better O2 adsorption.
Acetic acid lignins from Chinese quince fruit (Chaenomeles sinensis): effect of pretreatment on their structural features and antioxidant activities
Authors: Qin Zhao , Zhang Zhao-Guo , Liu Hua-Min , Qin Guang-Yong , Wang Xue-De
Published: July 2018

Three pretreatments, including sugar removal, dephenolization and multiple processes, are applied on the lignin extraction from Chinese quince fruits.
Three-dimensional water evaporation on a macroporous vertically aligned graphene pillar array under one sun
Authors: Zhang Panpan , Liao Qihua , Yao Houze , Cheng Huhu , Huang Yaxin , Yang Ce , Jiang Lan , Qu Liangti
Published: July 2018

Three-dimensional water evaporation is proposed based on highly vertically ordered pillar array of graphene-assembled framework (HOPGF). A high evaporation rate of 2.10 kg m−2 h−1 is achieved (1 sun). This efficient SSG system has been applied to wastewater purification, solar water heater and housing self-supply water system.
Correlating nano black spots and optical stability in mixed halide perovskite quantum dots
Authors: Ko Yun-Hyuk , Prabhakaran Prem , Jalalah Mohammed , Lee Seung-Jae , Lee Kwang-Sup , Park Jea-Gun
Published: July 2018

We correlate appearance of nano black spots (NBSs), optical stability and Goldschmidt tolerance factor (t) in mixed halide perovskite QDs.
Effect of fluorine substitution of the β-ketoiminate ancillary ligand on photophysical properties and electroluminescence ability of new iridium(iii) complexes
Authors: Witkowska Ewelina , Wiosna-Salyga Gabriela , Glowacki Ireneusz , Orwat Bartosz , Oh Myong-joon , Kownacki Ireneusz , Kubicki Maciej , Gierczyk Blazej , Dutkiewicz Michal , Cieszko Pawel , Luszczynska Beata , Ulanski Jacek , Grzelak Izabela , Hoffmann Marcin , Ledwon Przemyslaw , Lapkowski Mieczyslaw
Published: July 2018

The influence and emissive properties of N,O-donating ligands with fluorinatedN-aryl moieties on the electronic structure of complexes of the formula [Ir(bzq)2(O∧N)] are reported.
Disentangling the AGN and star formation connection using XMM-Newton
Authors: Masoura V. A. , Mountrichas G. , Georgantopoulos I. , Ruiz A. , Magdis G. , Plionis M.
Published: July 2018

There is growing evidence supporting the coeval growth of galaxies and their resident super-massive black hole (SMBH). Most studies also claim a correlation between the activity of the SMBH and the star formation of the host galaxy. It is unclear, however, whether this correlation extends to all redshifts and X-ray luminosities. Some studies find a weaker dependence at lower luminosities and/or a suppression of the star formation at high luminosities. We here use data from the X-ATLAS and XMM-XXL North fields and compile the largest X-ray sample up to date to investigate how X-ray selected AGN affect the star formation of their host galaxies in a wide redshift and luminosity baseline of 0.03 < z < 3 and log LX(2−10 keV) = (41−45.5) erg s−1. Our sample consists of 3336 AGN. 1872 of our sources have spectroscopic redshifts. For the remaining sources we calculate photometric redshifts using TPZ, a machine-learning algorithm. We estimate stellar masses (M⋆) and star formation rates (SFRs) by applying spectral energy distribution fitting through the CIGALE code, using optical, near-IR, and mid-IR photometry (SDSS, VISTA, and WISE). Of our sources, 608 also have far-IR photometry (Herschel). We use these sources to calibrate the SFR calculations of our remaining X-ray sample. Our results show a correlation between the X-ray luminosity (LX) and the SFR of the host galaxy at all redshifts and luminosities spanned by our sample. We also find a dependence of the specific SFR (sSFR) on redshift, while there are indications that the X-ray luminosity enhances the sSFR even at low redshifts. We then disentangle the effects of stellar mass and redshift on the SFR and again study its dependence on the X-ray luminosity. Towards this end, we estimate the SFR of main-sequence galaxies that have the same stellar mass and redshift as our X-ray AGN and compare them with the SFR of our X-ray AGN. Our analysis reveals that the AGN enhances the star formation of its host galaxy when the galaxy lies below the main sequence and quenches the star formation of the galaxy it lives in when the host lies above the main sequence. Therefore, the effect of AGN on the SFR of the host galaxy depends on the location of the galaxy relative to the main sequence.
Minimum parametric flow in time-dependent dynamic networks
Authors: Parpalea Mircea , Avesalon Nicoleta , Ciurea Eleonor
Published: July 2018

The paper presents a dynamic solution method for the parametric minimum flow in time-dependent, dynamic network. This approach solves the problem for a special parametric dynamic network with linear lower bound functions of a single parameter. Instead of directly working in the original network, the method implements a labelling algorithm which works in the parametric dynamic residual network where repeatedly decreases the flow along quickest dynamic source-sink paths for different subintervals of parameter values, in their increasing order. In each iteration, the algorithm computes both the parametric minimum flow within a certain subinterval, and the new subinterval for which the flow needs to be computed.
Aspects de la complémentation en FLE chez des apprenants hellénophones
Authors: Kakoyianni-Doa Fryni , Loizidou Dora , Monville-Burston Monique
Published: July 2018

Dans les grammaires/manuels du FLE, les sections consacrées aux complétives (autres qu’interrogatives) insistent particulièrement sur trois aspects de ce secteur de la grammaire française : l’emploi du mode (indicatif/subjonctif) dans les complétives parque, l’alternance entre ces complétives et les complétives réduites à l’infinitif et le choix de la préposition introductrice de l’infinitif (de, à, ø). Les apprenants hellénophones, comme les autres apprenants du FLE, achoppent sur ces difficultés, mais sont confrontés en outre à d’autres problèmes dont l’une des sources est leur L1. En effet le grec n’a pas d’infinitif et la nature et les usages de la forme dite ‘subjonctif’ diffèrent significativement de ceux du français. Nous rendons compte dans cet article de la troisième étape d’un projet concernant l’apprentissage/acquisition et l’enseignement de cette zone de la grammaire du français. Un test de jugement de grammaticalité a été administré à deux groupes d’étudiants (première année et avancés). Sur la base des résultats obtenus, nous montrons quelles structures sont problématiques et candidates à la fossilisation, nous discutons des raisons possibles/probables des difficultés rencontrées par les apprenants dans leurs jugements et nous concluons en suggérant des pistes pour un enseignement plus efficace des complétives aux hellénophones.
Finales en sandhi en aquitanopyrénéen Langue de France - Occitan
Authors: Rivière Vincent
Published: July 2018

La forme dels/deus est réalisée indistinctement [des] en occitan dans la zone toulousaine, alors que nous trouvons la forme [del] au singulier côté languedocien et [du] côté gascon. Je pose l’hypothèse suivante : la structure syllabique va conditionner cette réalisation dans le sens où la permissivité de la syllabe dans cette zone ne laisse qu’une position dans laquelle le morphème du pluriel est prioritaire. Gascon oriental et languedocien occidental relèvent d’un modèle où il faut clairement admettre que la finale dépasse la structure syllabique régulière. Cela peut s’expliquer d’une part par des syllabes à noyaux nuls, d’autre part par une conception récursive de la syllabe qui peut être schématisée de la façon suivante : mot = (syllabe)*+ (Consonne facultative). Cela rejoint la formule proposée pour le français dans Dell (1995). Certaines finales sont ainsi des attaques d’une syllabe à noyau nul :

a)[l'up] : (lu)(p0) b) [s'ɛrp] : (sɛr)(p0)

L’hypothèse du noyau nul explique que la particule excédentaire soit une attaque. Il faut cependant limiter les syllabes (C0) aux finales : serps - [s'rs] = (s'r)(s0). Le morphème du pluriel /s/ occupera prioritairementla position d’attaque en finale à la place des autres consonnes. Ce mécanisme sera appliqué à la contraction préposition – article.
Etude de l'interaction chez des sujets somniloques
Authors: Devevey Alain
Published: July 2018

L'objet de cette étude est de montrer que le langage ne peut en aucun cas se résumer à un acte singulier (Saussure, 1915) et que la psycholinguistique ne peut permettre d'appréhender, du point de vue cognitif, la production d'un acte de langage dans sa globalité. Il est en effet impossible de concevoir la production d'un acte de langage en étudiant un seul individu : "Pour trouver dans l’ensemble du langage la sphère qui correspond à la langue, il faut se placer devant l’acte individuel qui permet de reconstituer le circuit de la parole. Cet acte suppose au moins deux individus; c’est le minimum exigible pour que le circuit soit complet." (Saussure, op. cit., p. 17). Pour ce faire nous montrerons que les productions verbales du sujet somniloque participent d'un échange verbal, au cours duquel l'alternance des tours de parole est adaptée à un interlocuteur, non accessible à l’observateur.
Les interactions logopédiste-enfant comme lieu d’apprentissage de capacités langagières. L’exemple des séquences potentiellement acquisitionnelles
Authors: Rodi Mireille
Published: July 2018

Notre étude est issue d’une perspective interactionniste, de l’acquisition des compétences langagières (Vygotski, 1934;,Bruner, 1983, 1987; Dolz, Pasquier, … Bronckart, 1993; Py, 1996; Bange, 1992). Elle souligne une dynamique interactionnelle, ayant lieu dans interaction asymétrique à savoir : un locuteur dit, novice, peut réutiliser les matériaux linguistiques produits par son, interlocuteur, dit expert, en les intégrant à son propre système. Un, apprentissage peut se réaliser par un processus dialectique, dominé,par un fonctionnement de reprises alternées : on parle de séquences, potentiellement acquisitionnelles (SPA : de Pietro, Matthey, & Py,1989). Nous nous intéresserons ici à la manière dont un enfant, avec troubles spécifiques du développement du langage (tsdl) peut, ainsi tirer bénéfice d’une interaction avec un adulte spécialiste, dans le domaine de la pathologie du langage1. Plus précisément, notre questionnement concerne comment l’enfant parvient à se, saisir d’offres acquisitionnelles et les stratégies du logopédiste, pour lui permettre de se les approprier.
Therapieresistente Fusarienkeratitis mit intraokularer Beteiligung – potenzielle Quellen für eine persistierende Infektion
Authors: Löffler Karin , Holz Frank , Herwig-Carl Martina
Published: July 2018

Hintergrund Die Pilz-Keratitis zeigt ein klinisch sehr variables Erscheinungsbild und wird nicht zuletzt auch deshalb oft erst spät diagnostiziert. Pilze sind generell sehr resistente Keime, und die Therapie gestaltet sich aufgrund der wenigen und speziell anzufertigenden Medikamente zusätzlich schwierig.

Material und Methoden/Ergebnisse Es wird der besonders ungünstige Verlauf bei einer jungen Patientin mit Fusarien-Keratitis dargestellt, bei der das Auge zuletzt trotz maximaler medikamentöser und auch chirurgischer Therapie entfernt werden musste. Die histologische Aufarbeitung zeigte massive (post-)entzündliche Veränderungen im gesamten vorderen Augenabschnitt, persistierende Pilzelemente aber lediglich in der nach Katarakt-Operation verblieben Linsenkapsel und der peripheren Descemet-Membran.

Schlussfolgerung Pilze als Verursacher einer therapierefraktären Keratitis sollten möglichst rasch in die Differentialdiagnose miteinbezogen werden. Falls chirurgische Maßnahmen notwendig werden, sollte die Keratoplastik so groß wie möglich gewählt und bei einer Katarkat-Operation die Kapsel mitentfernt werden, um potentielle Keimreservoire zu beseitigen.
Lidtumoren: Klinische Aspekte der Ophthalmopathologie
Authors: Herwig-Carl Martina , Löffler Karin
Published: July 2018

Hintergrund Lidtumoren insgesamt weisen ein sehr heterogenes Erscheinungsbild auf. Auch Tumoren, die einige Malignitätskriterien aufweisen, können sich histologisch als entzündliche Läsion ohne Nachweis einer Neoplasie darstellen. Umgekehrt können maligne Tumoren zu einer klinisch im Vordergrund stehenden, zumeist therapieresistenten Entzündungsreaktion führen, die entsprechend diagnostiziert und therapiert werden muss.

Material und Methoden/Ergebnisse Anhand ausgewählter Beispiele von Lidtumoren werden potenzielle Problemfälle sowie klinisch unklare Fälle dargestellt und mit dem histopathologischen Befund korreliert.

Schlussfolgerung Lidtumoren können von verschiedenen Strukturen ausgehen und weisen ein breites Spektrum an klinischen Erscheinungsbildern auf. In unklaren Fällen bzw. bei V. a. einen malignen Tumor ist eine Biopsie/Exzision zur histologischen Diagnosestellung erforderlich. Inadäquat behandelte benigne Läsionen wie z. B. inkomplett exzidierte Nävi oder ein Molluscum contagiosum können zu klinisch relevanten Problemen führen.
Taurine Ameliorates Thyroid Hypofunction and Renal Injury in L-NAME-Induced Hypertensive Rats
Authors: Adedara Isaac , Alake Sanmi , Olajide Laide , Adeyemo Mercy , Ajibade Temitayo , Farombi Ebenezer
Published: July 2018

There is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, L-NAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.
A3 Domain Is Essential for Interaction of von Willebrand Factor with Collagen Type III
Authors: Lankhof Hanneke L , van Hoeij Maggy , Schiphorst Marion E , Bracke Madelon , Wu Ya-Ping , Ijsseldijk Martin J W , Vink Tom , de Groot Philip G , Sixma Jan J
Published: July 2018

von Willebrand factor (vWF) mediates platelet adhesion at sites of vascular damage. It acts as a bridge between receptors on platelets and collagens present in the connective tissue. Two collagen binding sites have been identified on the A1 and A3 domain of the vWF subunit. To study the functional importance of these binding sites, we have made two deletion mutants that lack the A1 domain (residues 478-716; ΔA1-vWF; Sixma et al. Eur. J. Biochem. 196,369,1991 [1]) or the A3 domain (residues 910-1113; ΔA3-vWF). After transfection in baby hamster kidney cells overexpressing furin, the mutants were processed and secreted efficiently. Ristocetin or botrocetin induced platelet binding was normal for ΔA3-vWF as was binding to heparin and factor VIII. As reported by Sixma et al. (1) ΔAl-vWF still binds to collagen type III, indicating that the A3 domain is sufficient for the interaction. In the current study, we investigated the binding of ΔA3-vWF to collagen type III. When preincubated on collagen type III it did not support platelet adhesion under flow conditions, whereas it was able to support platelet adhesion when coated directly to a glass surface. The binding of 125I-ΔA3-vWF to collagen was specific but maximal binding was about 40 times less compared to 125I-vWF. When added at 25 times excess, ΔA3-vWF did not compete with 125I-vWF for binding to collagen type III, whereas ΔAl-vWF did. The binding of 125I-ΔA3-vWF could be blocked by excess unlabeled vWF but not by ΔA1-vWF. In conclusion, we demonstrate that the A3 domain in vWF contains the major collagen binding site. The major binding site present on the A3 domain and the minor site present on A1 bind to different sites on collagen.
Plasminogen Activation by Invasive Human Pathogens
Authors: Boyle Michael D P , Lottenberg Richard
Published: July 2018

In this review the interaction between invasive human pathogens expressing plasmin(ogen) receptors and/or producing plasminogen activators with the human plasmin(ogen) system is described. Evidence is presented for multiple mechanisms by which human pathogens can acquire a surface bound form of plasmin that cannot be regulated by host serpins. The potential importance of these pathways in providing the organisms with the ability to cross tissue barriers is discussed.
Autoantibodies Against the Protease Inhibitor Calpastatin: A New Risk Factor for Venous Thrombosis?
Authors: Schlosser Udo , Lackner Karl J , Scheckenhofer Christine , Spannagl Michael , Spengel Florentin A , Hahn Gabriele , Lang Bernhard , Schmitz Gerd
Published: July 2018

Autoantibodies reactive against human calpastatin were detected by screening a cDNA expression library with the serum of a 53 year old white female patient with a history of venous thrombosis and suspected antiphospholipid syndrome. When further sera were analyzed it could be shown that >90% of calpastatin autoantibodies, detected by Western blotting against the partial calpastatin clone, react with the C-terminal amino acids of the protein. Therefore, an ELISA based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin was developed and 205 healthy blood donors and 138 random sera from hospital patients were analyzed. A total of 11 sera (3.2%) were positive with no significant difference between the two groups (7/205 and 4/138). In 80 consecutive patients with a history of venous thrombosis 9 positive sera (11.3%; p < 0.01 vs. blood donors, p<0.02 vs. hospital patients) were detected. Our results indicate that autoantibodies against calpastatin may constitute a so far unknown risk factor for venous thrombosis.
Efficacy and Safety of Low Molecular Weight Heparin (Ardeparin Sodium) Compared to Warfarin for the Prevention of Venous Thromboembolism after Total Knee Replacement Surgery: A Double-blind, Dose-ranging Study
Authors: Heit John A , Berkowitz Scott D , Bona Robert , Cabanas Victor , Corson John D , Elliott C Gregory , Lyons Roger ,   (Ardeparin Arthroplasty Study Group)
Published: July 2018

We performed a double-blind, randomized clinical trial to compare the efficacy and safety of three different subcutaneous (SC) low molecular weight heparin doses (ardeparin sodium 25,35, or 50 anti-XaU/kg twice daily [BID]) to adjusted-dose warfarin (international normalized ratio [INR] = 2.0 to 3.0), as venous thromboembolism prophylaxis after total knee replacement surgery. The primary endpoint was total venous thromboembolism prevalence, defined as deep vein thrombosis discovered at postoperative venography of the operated leg, or symptomatic, objectively-documented pulmonary embolism. Of 860 patients randomized, 680 (79%) had an evaluable venogram or pulmonary embolism. The total venous thromboembolism prevalence was significantly greater among patients prophylaxed with warfarin compared to ardeparin 50 BID (38% vs 27%, p = 0.019); the prevalence among ardeparin 25 BID (37%) and 35 BID (28%) patients was similar to warfarin and ardeparin 50 BID patients, respectively. Overt bleeding occurred in 22 (7.9%) ardeparin 50 BID patients compared to 12 (4.4%) warfarin patients (p = 0.08), and in seven ardeparin 25 and 35 BID patients each (5.2% and 5.0%, respectively). Compared to the warfarin group, blood loss was significantly greater in the ardeparin 50 and 25 BID groups, and not different in the ardeparin 35 BID group.

Conclusions: Postoperative, unmonitored, fixed-dose ardeparin 50 anti-Xa U/kg SC BID is significantly more effective than adjusted-dose warfarin for this indication. Although overt bleeding among warfarin and ardeparin 50 BID patients did not differ significantly, ardeparin 50 BID patients had significantly greater blood loss. Ardeparin 35 anti-Xa U/kg SC BID may provide efficacy similar to ardeparin 50 anti-Xa U/kg SC BID but with reduced bleeding.
Family History of Coronary Heart Disease and Hemostatic Variables in Middle-Aged Adults
Authors: Pankow James S , Folsom Aaron R , Province Michael A , Rao D C , Eckfeldt John , Heiss Gerardo , Shahar Eyal , Wu Kenneth K ,   on behalf of the Atherosclerosis Risk in Communities Investigators and Family Heart Study Research Group
Published: July 2018

Individuals with a family history of coronary heart disease (CHD) may be predisposed to atherothrombosis. To investigate this hypothesis, a family CHD risk score was computed for approximately 13,000 men and women aged 45 to 64; hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor, antithrombin III, protein C) were also measured in plasma. After adjustment for age and ethnicity, there was a statistically significant, positive association between the family risk score and four of the six hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor) in women and all six hemostatic variables in men. In general, these associations were weak and substantially attenuated after adjustment for constitutional, lifestyle, and biochemical covariates. These results indicate that mean levels of selected hemostatic variables, like traditional CHD risk factors, are higher in individuals with a family history of heart disease.
Rapid Direct Determination of Low and High Molecular Weight Kininogen in Human Plasma by Particle Concentration Fluorescence Immunoassay (PCFIA)
Authors: Scott Cheryl F , Shull Bruce , Müller-Esterl Werner , Colman Robert W
Published: July 2018

In this study, we employed Particle Concentration Fluorescence Immunoassay (PCFIA), for directly measuring both high and low molecular weight kininogens (HK and LK) in human plasma. In 38 normal donors, the mean values for plasma kininogens were 93 mg/ml +/- 19 SD, 82 mg/ml +/- 12 SD, and 175 mg/ml +/- 29 SD, respectively for LK, HK, and TotK (the sum of LK and HK detected by their common heavy chains). Plasma completely deficient in HK and LK was unreactive (<0.25 mg/ml) in all 3 assays whereas plasma from a patient with Fitzgerald Trait had an HK value of 11 mg/ml, an LK value of 36 mg/ml and a TotK value of 59 mg/ml. The reagents can be prepared in advance and all three kininogen determinations can be performed, using the same diluted sample, on 24 plasma samples, in triplicate, or 40 plasma samples, in duplicate, in less than 1 h. By performing all 3 kininogen determinations, it is possible to differentiate cleaved from intact kininogens. This technique will facilitate the widespread screening of kininogen levels in biological fluids of normal humans as well as of patients with various diseases.
Identification of the NO Synthase isoforms Expressed in Human Neutrophil Granulocytes, Megakaryocytes and Platelets
Authors: Wallerath Thomas , Gath Ingolf , Aulitzky Walter E , Pollock Jennifer S , Kleinert Hartmut , Förstermann Ulrich
Published: July 2018

Using Western blot and fluorescent immunocytochemistry, NOS III (or ecNOS) and NOS II (or iNOS), but no NOS I (or ncNOS), were identified in preparations of human platelets. Reverse-transcription polymerase chain reactions (RT-PCR) demonstrated NOS III mRNA, but no NOS II mRNA (which is short-lived) and no NOS I mRNA in platelets. Immunofluorescent staining of human bone marrow smears showed the presence of NOS III, but not NOS I in megakaryocytes. A subpopulation of megakaryocytes also expressed NOS II. In preparations of human neutrophils, immunocytochemistry demonstrated NOS I in all cells, whereas no NOS III was detected. The few NOS II positive cells were characterized as contaminating eosinophils. Similarly, in RT-PCR, transcripts for NOS I and NOS II, but not for NOS III, were identified. Thus, the constitutive NOS isoform in megakaryocytes and platelets is NOS III, whereas neutrophils express NOS I. Some megakaryocytes and eosinophils also express NOS II.
PEGylation of lnterleukin-6 Effectively Increases Its Thrombopoietic Potency
Authors: Tsutsumi Yasuo E , Tsunoda Shin-ichi S , Kamada Haruhiko , Kihira Tetsunari , Kaneda Yoshihisa , Ohsugi Yoshiyuki , Mayumi Tadanori
Published: July 2018

The in vivo thrombopoietic activity of polyethylene glycol-modified interleukin-6 (MPEG-IL-6), in which 54% of the 14 lysine amino groups of IL-6 were coupled with PEG, was compared to that of native IL-6. Native IL-6 and MPEG-IL-6, which showed about 51% of the specific bioactivity of native IL-6, were administered subcutaneously to mice every 2 days for 7 days. Native IL-6 increased not only the peripheral platelet count, but also the plasma-IgGl level in a dose-dependent manner. MPEG-IL-6 showed about 500 times higher thrombopoietic potency than native IL-6. Further, in comparison to native IL-6, MPEG-IL-6 did not enhance IgGl production as much as it enhanced platelet production. MPEG-IL-6 significantly stimulated platelet recovery in mice treated with 5-fluorouracil, whereas the administration of native IL-6 had a negligible effect. The plasma halflife of MPEG-IL-6 was about 100-fold longer than that of native IL-6. The decrease in the plasma clearance of MPEG-IL-6 was thought to be due, in part, to the shielding of the proteolytic sites in the IL-6 molecule by the PEG chain. The uptake of IL-6 by the reticuloendothelial system, such as the liver and spleen, was markedly limited by PEGylation. The PEGylation of IL-6 markedly enhanced the blood-residency of IL-6, resulting in effective augmentation of its thrombopoietic activity and a marked decrease in its side-effects. These findings suggest that MPEG-IL-6 may be a potential candidate for thrombopoietic agent.
Low Prevalence of Factor V:Q506 in 41 Patients with Isolated Pulmonary Embolism
Authors: Martinelli Ida , Cattaneo Marco , Panzeri Daniela , Mannucci Pier Mannuccio
Published: July 2018

In 70-80% of cases, pulmonary embolism is the consequence of lower extremity deep vein thrombosis. It has been demonstrated that the most common coagulation defect predisposing to venous thrombosis, resistance to activated protein C (APC), is not associated with an increased risk for pulmonary embolism, but the evidence was based on a functional assay to diagnose APC resistance and no information about concomitant deep vein thrombosis was provided. The aim of our study was to evaluate the prevalence of factor V:Q506, the gene mutation responsible for APC resistance, in patients with symptomatic non-fatal pulmonary embolism, whether or not associated with deep vein thrombosis. Patients with uncomplicated deep vein thrombosis and healthy controls were investigated as comparison groups. The overall prevalence of factor V:Q506 in 106 patients with pulmonary embolism was 12.3%, lower than that found in 106 patients with deep vein thrombosis (22.6%, OR 0.5, 95% Cl 0.2-1.0) but significantly higher than that found in 212 healthy subjects taken as controls (2.8%, OR 4.8,95% Cl 1.8-13.0). In the 41 patients with isolated pulmonary embolism, i.e., without the presence of deep vein thrombosis, the prevalence was 4.9%, similar to that in controls (OR 1.8,95% Cl 0.3-9.6), while in the remaining 65 patients with pulmonary embolism associated with deep vein thrombosis the prevalence was significantly higher (16.9%, OR 5.5, 95% Cl 2.0-15.8). In conclusion, the prevalence of factor V:Q506 is high in patients with pulmonary embolism associated with deep vein thrombosis, whereas in patients with isolated pulmonary embolism it is similar to that found in control subjects. This intriguing finding is of difficult interpretation and needs confirmation by further studies.
Blood Coagulation and Thrombosis in Patients with Ovarian Malignancy
Authors: von Tempelhoff Georg-Friedrich , Dietrich Michael , Niemann Frank , Schneider Dirk , Hommel Gerhard , Heilmann Lothar
Published: July 2018

Ovarian cancer cells appear to be capable of both thrombin formation and induction of fibrin degradation which may be essential prerequisites for the development of deep vein thrombosis (DVT) as well as the spread of malignancy. To study further this coagulation – cancer interaction in 60 patients with untreated ovarian cancer of FIGO stage I-IV the incidence of DVT was recorded pre-operatively, postoperatively on day 1, 3, 5, 7, 10, before each of six cycles of Cisplati- num/Epirubicin/Cyclophosphamide chemotherapy, during follow-up and in the post-operative period of second look surgery. In addition, blood coagulation tests results were determined prospectively. Two patients were excluded from these calculations due to previous DVT 5 to 6 weeks before the diagnosis of ovarian cancer but all patients were eligible for surgery and randomized to receive either daily low molecular weight heparin (LMWH) (n = 28) or unfractionated heparin (UFH) (n = 32) for perioperative thrombosis prophylaxis until the 7th postoperative day. According to the FIGO stage, patients were equally distributed in the 2 heparin treatment groups. The predictive value of pre-operative coagulation test results, clinical parameters, and type of heparin used were tested in univariate and multivariate analysis for development of post-operative DVT and overall patients survival. Impedance plethysmography for DVT screening was used. The presence of DVT was then confirmed by phlebography. Only D-dimer and fibrinogen levels were correlated significantly with the FIGO stage while antithrombin, protein C, and plasminogen activator inhibitor activity were not. The incidence of DVT was 6.7% (4/60) up to the 7th and 8.3% (5/60) between the 8th and 29th post-operative day. DVT occurred in 10.6 % (5/47) during chemotherapy. Pre-operative coagulation test results, the type of heparin used, and clinical parameters were not significant risk factors for post-operative DVT development in univariate analysis. The D-dimer and fibrinogen levels were significant risk factors for reduced overall survival in univariate analysis but only the FIGO stage was an independent predictor (in multivariate analysis). After a median follow up of 26.5 months (min. 8 months, max. 41 months), 21.4% of LMWH treated and 37.5% of UFH-treated patients died of cancer (p = 0.26). Pre-operative test results were neither predictive for DVT nor the outcome of cancer but patients showed an improved though not statistically significant overall survival after LMWH treatment.
Degree of Polymer Organization Decreases the Binding of a Monoclonal Antibody Raised against the β-Chain Amino Terminus of Fibrin
Authors: Morris Timothy A , Marsh James J , Fagnani Roberto , Hagan Michael , Moser Kenneth M
Published: July 2018

Accurate non-invasive diagnosis of deep venous thrombosis and pulmonary embolism remains an elusive goal. Radiolabeled antibodies specific for the epitope exposed on the β-chain of fibrin after fibrino- peptide B release (anti-β) enabled in situ imaging of thrombi in experimental subjects with nuclear medicine techniques. When used in patients anticoagulated for thrombo-embolic disease, however, the antibody was unable to reliably image the thrombi. We postulated that the neoepitope on the β-chain of fibrin is covered up as fibrin organizes into a polymer network and is therefore exposed to the antibody only during active incorporation of fibrin subunits. We determined the equilibrium binding kinetics of an anti-β monoclonal antibody to fibrin in various stages of organization. The concentration of exposed epitopes on immobilized fibrin monomers was equal to the molar concentration of fibrin β-chains. The percentage of β-chains exposed to the antibodies markedly decreased as the fibrin network was allowed to organize, a process catalyzed by calcium. Conclusions: The β-chain amino terminus of fibrin is exposed transiently as subunits are added to the enlarging fibrin network. Anti-β antibodies bind preferentially to actively enlarging fibrin polymers.
Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G Promoter Polymorphism and Levels in Subjects with Cerebrovascular Disease
Authors: Catto Andrew J , Carter Angela M , Stickland Max , Bamford John M , Davies J Andrew , Grant Peter J
Published: July 2018

The exact role of the fibrinolytic system in the pathogenesis of stroke remains to be established. Elevated circulating levels of plasminogen activator inhibitor-1, the principle inactivator of the fibrinolytic system, have been related to the development of myocardial infarction. There is evidence that a polymorphism in the promoter region of the PAI-1 gene is associated with circulating PAI-1 levels.

We studied a common single nucleotide insertion/deletion (4G/5G) polymorphism by PCR in 558 patients with stroke, the pathological type of which was established by cranial computed tomography, and in 172 controls. 4G/5G genotype and PAI-1 activity were investigated in relation to 1) stroke type and 2) mortality occurring within four weeks, three months and six months of the stroke.

No difference in genotype frequency was observed when all cases of stroke were compared with controls nor between the clinically determined subtypes of cerebral infarction. PAI-1 activity was significantly higher in patients with stroke (n = 245) both at presentation (11.6 U/ml) and after three months (11.8 U/ml), in paired samples, than in control subjects (8.8 U/ml, p <0.0001). Thirty-seven (6.2%), 86 (14.5%) and 122 (20.5%) patients had died within one, three and six months of admission, respectively. PAI-1 activity was independently associated with all-cause mortality at one and three months after stroke (p = 0.02 and p = 0.03 respectively), but not after six months.

In this population the 4G/5G promoter polymorphism is not associated with an increased risk of stroke. PAI-1 levels were elevated at the time of acute stroke which persisted after three months. PAI-1 level but not genotype was associated with early mortality following stroke.
Inhibition of Leucocyte and Platelet Adhesion Reduces Neointimal Hyperplasia after Arterial Injury
Authors: Golino Paolo , Ambrosio Giuseppe , Ragni Massimo , Cirillo Plinio , Esposito Nicolino , Willerson James T , Rothlein Robert , Petrucci Luisa , Condorelli Mario , Chiariello Massimo , Buja Maximilian L
Published: July 2018

Restenosis following coronary angioplasty is thought to result from migration and proliferation of medial smooth muscle cells. However, the factors that initiate this proliferation are still unknown. In a rabbit model of carotid artery injury, we tested the hypothesis that activated platelets and leucocytes might contribute to the development of neointimal hyperplasia. Following arterial injury, rabbits received either no treatment, R15.7, a monoclonal antibody against the leucocyte CD ll/CD 18 adhesion complex, aurintricarboxylic acid (ATA), a sub stance that inhibits platelet glycoprotein Ib-von Willebrand factor interaction, or the combination of R15.7 and ATA. After 21 days, the extent of neointimal hyperplasia was evaluated by planimetry on histological arterial sections. The area of neointima averaged 0.51 ±0.07 mm2 in control animals and it was significantly reduced by administrationof either R15.7 or ATA alone to 0.12 ± 0.05 and 0.20 ±0.01 mm2, respectively (p <0.05 vs controls for both groups). The animals that received the combination of R15.7 and ATA showed a further reduction in neointimal hyperplasia, as compared to animals that received ATA alone (p <0.05 vs ATA alone). These data indicate that platelets and leucocytes play animportant role in the pathophysi ology of neointimal hyperplasia in this experimental model. Interven tions that reduce platelet and leucocyte adhesion to vessel wall might have beneficial effects in reducing restenosis following coronary angioplasty.
Human Urinary Soluble Thrombomodulin (MR-33) Improves Disseminated Intravascular Coagulation without Affecting Bleeding Time in Rats: Comparison with Low Molecular Weight Heparin
Authors: Takahashi Yasuo , Hosaka Yoshitaka , Imada Kazunori , Adachi Takehiro , Niina Hiromi , Watanabe Mitsutoshi , Mochizuki Hidenori
Published: July 2018

We compared the antithrombotic and hemorrhagic effects of naturally existing human urinary soluble thrombomodulin (MR-33) with those of low molecular weight heparin (LMW-heparin) in rats. In in vitro experiments, MR-33 prolonged APTT in a dose-dependent fashion; its effect in this respect was as potent as that of LMW-heparin, but it was less potent than unfractionated heparin (UF-heparin). MR-33 was effective on endotoxin- or thromboplastin-induced disseminated intravascular coagulation (DIC) in rats. In both DIC models, infusion of MR-33 improved hematological abnormalities compatible with DIC in a dose-dependent fashion without excessive prolongation effect on APTT. Although LMW-heparin and UF-heparin also improved both DIC models, excessive prolongation of APTT was observed at high doses. It is well-known that the excessive prolongation of APTT with antithrombotic drugs like heparins is an index for hemorrhage, which is a major side effect in the treatment of DIC. We therefore further compared the antithrombotic (Benefit: dose required for 50% inhibition of fibrinogen decrease: ED50) and hemorrhagic (Risk: minimum dose required for significant prolongation of bleeding time) effects of MR-33 and LMW-heparin in the thromboplastin-induced DIC model. As a result, Benefit-Risk ratio was 1:27 for MR-33 and 1:3 for LMW heparin. These results indicate that MR-33 may be a clinically useful antithrombotic agent with reduced risk for hemorrhage compared with LMW-heparin.