bluuebunny/crossref_metadata_2025_split huggingface dataset:
Globular-shaped variable lymphocyte receptors B antibody multimerized by a hydrophobic clustering in hagfish
Authors: Kim Jaesung , Im Se Pyeong , Lee Jung Seok , Lazarte Jassy Mary S. , Kim Si Won , Jung Jae Wook , Kim Jong Yong , Kim Young Rim , Lee Sangmin , Kim Gwang Joong , Jung Hyun Suk , Lee Kyun Oh , Adams Alexandra , Thompson Kim D. , Jung Tae Sung 
Published: July 2018

AbstractIn hagfish and lampreys, two representative jawless vertebrates, the humoral immunity is directly mediated by variable lymphocyte receptors B (VLRBs). Both monomeric VLRBs are structurally and functionally similar, but their C-terminal tails differ: lamprey VLRB has a Cys-rich tail that forms disulfide-linked pentamers of dimers, contributing to its multivalency, whereas hagfish VLRB has a superhydrophobic tail of unknown structure. Here, we reveal that VLRBs obtained from hagfish plasma have a globular-shaped multimerized form (approximately 0.6 to 1.7 MDa) that is generated by hydrophobic clustering instead of covalent linkage. Electron microscopy (EM) and single-particle analysis showed that the multimerized VLRBs form globular-shaped clusters with an average diameter of 28.7 ± 2.2 nm. The presence of VLRBs in the complex was confirmed by immune-EM analysis using an anti-VLRB antibody. Furthermore, the hydrophobic hagfish C-terminus (HC) was capable of triggering multimerization and directing the cellular surface localization via a glycophosphatidylinositol linkage. Our results strongly suggest that the hagfish VLRB forms a previously unknown globular-shaped antibody. This novel identification of a structurally unusual VLRB complex may suggest that the adaptive immune system of hagfish differs from that of lamprey.
Evidence of vitamin D synthesis in insects exposed to UVb light
Authors: Oonincx D. G. A. B. , van Keulen P. , Finke M. D. , Baines F. M. , Vermeulen M. , Bosch G. 
Published: July 2018

AbstractVertebrates obtain the prohormone vitamin D primarily by endogenous cutaneous synthesis under ultraviolet b (UVb) exposure. To date, endogenous synthesis of vitamin D in insects has never been investigated. In an initial experiment, we exposed four insect species which differ in ecology and morphology (migratory locusts, house crickets, yellow mealworms and black soldier fly larvae (BSFL)) to a low irradiance UVb source. In a second experiment we exposed these species to a higher UV irradiance, and in a third we tested the effect of exposure duration on vitamin D concentrations in yellow mealworms. Low irradiance UVb tended to increase vitamin D3 levels in house crickets, vitamin D2 levels in BSFL and vitamin D2 and D3 in yellow mealworms. Higher UVb irradiance increased vitamin D3 levels in all species but BSFL. Both BSFL and migratory locusts had increased vitamin D2 levels. Longer UVb exposure of yellow mealworms increased vitamin D2 and increased vitamin D3 until a plateau was reached at 6400 IU/kg. This study shows that insects can synthesize vitamin D de novo and that the amounts depend on UVb irradiance and exposure duration.
New member candidates of Upper Scorpius from Gaia DR1
Authors: Wilkinson S. , Merín B. , Riviere-Marichalar P. 
Published: July 2018

Context. Selecting a cluster in proper motion space is an established method for identifying members of a star-forming region. The first data release from Gaia (DR1) provides an extremely large and precise stellar catalogue, which when combined with the Tycho-2 catalogue gives the 2.5 million parallaxes and proper motions contained within the Tycho-Gaia Astrometric Solution (TGAS).
Aims. We aim to identify new member candidates of the nearby Upper Scorpius subgroup of the Scorpius-Centaurus Complex within the TGAS catalogue. In doing so, we also aim to validate the use of a density-based clustering algorithm (DBSCAN) on spatial and kinematic data as a robust member selection method.
Methods. We constructed a method for member selection using a density-based clustering algorithm (DBSCAN) applied over proper motion and distance. We then applied this method to Upper Scorpius and evaluated the results and performance of the method.
Results. We identified 167 member candidates of Upper Scorpius, of which 78 are new, distributed within a 10° radius from its core. These member candidates have a mean distance of 145.6 ± 7.5 pc and a mean proper motion of (−11.4, −23.5) ± (0.7, 0.4) mas yr−1. These values are consistent with measured distances and proper motions of previously identified bona fide members of the Upper Scorpius association.
“Zombie” or active? An alternative explanation to the properties of star-forming galaxies at high redshift
Authors: Saturni F. G. , Mancini M. , Pezzulli E. , Tombesi F. 
Published: July 2018

Context. Star-forming galaxies at high redshift show anomalous values of infrared excess, which can be described only by extremizing the existing relations between the shape of their ultraviolet continuum emission and their infrared-to-ultraviolet luminosity ratio, or by constructing ad hoc models of star formation and dust distribution.
Aims. We present an alternative explanation, based on unveiled AGN activity, of the existence of such galaxies. The scenario of a weak AGN lends itself naturally to explain the observed spectral properties of these high-z objects in terms of a continuum slope distribution and not altered infrared excesses.
Methods. To this end, we directly compare the infrared-to-ultraviolet properties of high-redshift galaxies to those of known categories of AGN (quasars and Seyferts). We also infer the characteristics of their possible X-ray emission.
Results. We find a strong similarity between the spectral shapes and luminosity ratios of AGN with the corresponding properties of such galaxies. In addition, we derive expected X-ray fluxes that are compatible with the energetics from AGN activity.
Conclusions. We conclude that a moderate AGN contribution to the UV emission of such high-z objects is a valid alternative to explain their spectral properties. Even the presence of an active nucleus in each source would not violate the expected quasar statistics. Furthermore, we suggest that the observed similarities between anomalous star-forming galaxies and quasars may provide a benchmark for future theoretical and observational studies on the galaxy population in the early Universe.
Magnesium Inhibits Platelet Activity - an Infusion Study in Healthy Volunteers
Authors: Ravn Hanne Berg , Vissinger Henrik , Kristensen Steen Dalby , Wennmalm Aake , Thygesen Kristian , Husted Steen Elkjcer 
Published: July 2018

SummaryMagnesium (Mg) has shown the ability to inhibit arterial thrombus formation in some experimental animal studies. This effect may be due to an inhibition of platelet reactivity as in vitro studies have demonstrated that Mg inhibits platelet aggregation. In order to evaluate the in vivo effect of Mg in humans measurements of platelet activity, fibrinolytic activity, as well as measurements of prostacyclin (PGI2), and nitric oxide (NO) release were performed after infusion of magnesium sulphate (MgSO4) in healthy volunteers. In a placebo controlled, cross-over study in 14 healthy male subjects, 8 mmol MgSO4 was given as an intravenous bolus over 15 min followed by 3 mmol MgSO4/h.The mean S-Mg concentration increased from 0.85 to 1.50 mM during the Mg infusion period. A transient decrease in blood pressure was observed during the initial bolus infusion of Mg. Haemodynamic parameters were otherwise stable. The bleeding time increased by 48% during the Mg infusion (p <0.005), and in accordance with this, ex vivo platelet aggregation in platelet rich plasma was significantly inhibited, both following collagen (p = 0.02) and ADP (p = 0.04) stimulation. There were no significant changes in plasma beta-thromboglobulin concentration or the excretion of 2,3-dinor-thromboxane B2 in the urine. Neither tissue plasminogen activator (t-PA)activity, tissue plasminogen activator (t-PA)antigen nor plasminogen activator inhibitor (PAI)antigen changed during the Mg infusion period. There was no sign of increased release of PGI2 from the vessel wall as judged by urinary concentration of 2,3-dinor-6-keto-prostaglandin F1α. Nor was there any sustained increase in the release of NO, measured as nitrate concentration in urine. However, a transient increase in NO release was observed during one sample period.In conclusion a reduced platelet activity and increased bleeding time, was found during Mg infusion in healthy volunteers. Fibrinolytic activity showed no changes. An anti-platelet effect may in part be responsible for the beneficial effect of Mg, described in patients with acute myocardial infarction (MI) and preeclampsia.
Serum Thrombopoietin (TPO) Levels in Patients with Amegakaryocytic Thrombocytopenia Are much Higher than those with Immune Thrombocytopenic Purpura
Authors: Mukai Harumi Y , Kojima Hiroshi , Todokoro Kazuo , Tahara Tomoyuki , Kato Takashi , Hasegawa Yuichi , Kobayashi Toshitaka , Ninomiya Haruhiko , Nagasawa Toshiro , Abe Tsukasa 
Published: July 2018

SummaryWe assayed serum thrombopoietin (TPO) levels in amegakaryocytic thrombocytopenia (AMT) and immune thrombocytopenic purpura (ITP) patients by using a newly established enzyme-linked immunosorbent assay (ELISA). TPO levels in AMT patients were quite high (mean ± SD = 13.7 ± 11.2 fmoles/ml, n = 4), whereas those in ITP patients were only slightly higher (1.25 ± 0.39, n = 12) than those of the healthy donors (0.55 ± 0.2, n = 20). Furthermore, in ITP patients no correlation was observed between platelet counts and serum TPO levels (correlation coefficient = 0.14). We further assayed serum TPO levels sequentially during steroid treatment in patients with AMT and ITP. In one AMT patient serum TPO levels started to decrease in accordance with the increase of megakaryocyte counts, which preceded the increase in platelet counts. However, in ITP patients serum TPO levels did not change significantly throughout the course of the treatment despite the recovery of platelet counts. Based on these findings, we conclude that serum TPO levels may be regulated at least in part by megakaryocyte counts.
Prospective Multicenter Study on Subcutaneous Concentrated Desmopressin for Home Treatment of Patients with von Willebrand Disease and Mild or Moderate Hemophilia A
Authors: Rodeghiero Francesco , Castaman Giancarlo , Mannucci Pier Mannuccio 
Published: July 2018

SummaryDesmopressin is the treatment of choice in most patients with von Willebrand disease (vWD) and mild hemophilia A (HA). Several studies have demonstrated that the intravenous and subcutaneous route of administration are equivalent in terms of pharmacokinetics and clinical efficacy. Home therapy of vWD and mild HA is desirable but so far there have been only a few case reports and no prospective studies. We report the results of a prospective study of home therapy in patients with vWD and mild-moderate HA using concentrated desmopressin self-administered subcutaneously. Clinical efficacy and safety were assessed by the patient using a questionnaire and direct interview. The patients were instructed on self-administration and dosage, reasons for treatment, recognition of side effects and recording clinical efficacy. The study lasted 12 months (range 6-17). During this time, 43/100 (43%) of the enrolled vWD patients (median basal VIII: C 24%, range 9-49) and 36/69 (52%) of HA patients (median basal VIII: C 10%, range 5-34) self-administered the drug. A total of 127 bleeding episodes requiring treatment occurred in patients with vWD and 92 in HA patients. There were 10 treatment failures of which 7 required in-hospital treatment. Overall, in 94% of treatments (excluding menorrhagia) the response was scored as excellent or good. In 86% of treated episodes of menorrhagia the response was scored as excellent or good. According to the patients, 81% of clinical situations would have required in-hospital treatment. Mild flushing, with or without headache, was the only consistent side-effect, reported in about 30% of treatments. In conclusion, home therapy with subcutaneous desmopressin for von Willebrand disease and hemophilia A was well accepted by the patients and proved feasible, efficacious and safe for the prevention or prompt treatment of bleeding.
Depletion of Intravascular Pools of Tissue Factor Pathway Inhibitor (TFPI) during Repeated or Continuous Intravenous Infusion of Heparin in Man
Authors: Hansen John-Bjarne , Sandset Per Morten , Huseby Kirsten Raanaas , Huseby Nils-Erik , Nordøy Arne 
Published: July 2018

SummaryTissue factor pathway inhibitor (TFPI) is a potent inhibitor of the extrinsic coagulation system. TFPI is increased several-fold in postheparin plasma and thereby thought to contribute significantly to the antithrombotic action of heparin. The present study was conducted to investigate how repeated (n = 8) and continuous (n = 6) administration of heparin affect plasma TFPI and the inhibition of tissue factor (TF)-induced coagulation ex vivo in humans. Free TFPI antigen (TFPI Ag) increased from 19.2 ± 4.0 ng/ml to 204.7 ± 31.7 ng/ml after intravenous injection of 5000IU of unfractionated heparin. Five repeated injections of 5000 IU of heparin at 4 h intervals caused a progressive decrease (−45 ± 8%, p <0.0001 for time effect) in heparin-releasable TFPI and a progressive shortening of the clotting time as determined in a dilute prothrombin time assay (dPT) (−8.7 ± 6.1 s, p <0.0001). The basal concentration of TFPI Ag in plasma collected immediately before each heparin injection was decreased by 29 ± 15% (p <0.0001), whereas the dPT was decreased by 6.9 ± 3.5 s (p <0.0001). During a 24 h continuous infusion of heparin TFPI Ag decreased from 161.5 ± 26.0 ng/ml to 35.6 ± 4.7 ng/ml (−77.3 ± 5.1%) (p <0.0001). The contribution of TFPI to the inhibition of TF-induced coagulation during heparin infusion was estimated to decrease from 60 ± 15% to 20 ± 10% (p <0.0001). The present data indicate partial depletion of intravascular pools of TFPI by repeated and continuous heparin administration and thereby attenuation of its contribution to the antithrombotic action of heparin.
O-glycosylation of Fibrinogen from Different Mammalian Species as Revealed by the Binding of Escherichia coli Biotinylated Lectins
Authors: L’Hôte Corine , Berger Sylvie , Karamanos Yannis 
Published: July 2018

SummaryAfter the demonstration that neither N-glycans nor neuraminic acid are involved in the binding of K88 lectins to the Bp and y chains of porcine fibrinogen and that their recognition was due to O-glycans (L’Hôte C, Berger S, Bourgerie S, Duval-Iflah Y, Julien R, Karamanos Y. Infect Immun 1995; 63: 1927-1932) it clearly appeared that these lectins could be used as probes to detect O-glycans on fibrinogens of other species. The conclusion of the present study is that many mammalian fibrinogens contain complex O-glycans on βp and γ chains. In addition, the combined use of the biotinylated K99 lectin and the Peanut agglutinin demonstrated the presence of sialylated T-antigens on the A± chains of all the fibrinogens examined. These lectins can now be used to determine differences on the glycosylation status of fibrinogens within one species and also to detect O-glycans on other glycoproteins
Factor VIII Inhibitor Antibodies with C2 Domain Specificity Are Less inhibitory to Factor VIII Complexed with von Willebrand Factor
Authors: Suzuki Suzuki , Arai Morio , Amano Kagehiro , Kagawa Kazuhiko , Fukutake Katsuyuki 
Published: July 2018

SummaryIn order to clarify the potential role of von Willebrand factor (vWf) in attenuating the inactivation of factor VIII (fVIII) by those antibodies with C2 domain specificity, we investigated a panel of 14 human antibodies to fVIII. Immunoblotting analysis localized light chain (C2 domain) epitopes for four cases, heavy chain (A2 domain) epitopes in five cases, while the remaining five cases were both light and heavy chains. The inhibitor titer was considerably higher for Kogenate, a recombinant fVIII concentrate, than for Haemate P, a fVIII/vWf complex concentrate, in all inhibitor plasmas that had C2 domain specificity. In five inhibitor plasmas with A2 domain specificity and in five with both A2 and C2 domain specificities, Kogenate gave titers similar to or lower than those with Haemate P. The inhibitory effect of IgG of each inhibitor plasma was then compared with recombinant fVIII and its complex with vWf. When compared to the other 10 inhibitor IgGs, IgG concentration, which inhibited 50% of fVIII activity (IC50), was remarkably higher for the fVIII/vWf complex than for fVIII in all the inhibitor IgGs that had C2 domain reactivity. Competition of inhibitor IgG and vWf for fVIII binding was observed in an ELISA system. In 10 inhibitors that had C2 domain reactivity, the dose dependent inhibition of fVIII-vWf complex formation was observed, while, in the group of inhibitors with A2 domain specificity, there was no inhibition of the complex formation except one case. We conclude that a subset of fVIII inhibitors, those that bind to C2 domain determinants, are less inhibitory to fVIII when it is complexed with vWf that binds to overlapping region in the C2 domain.
Functional Expression of Single Chain Glycoprotein lb Alpha on the Surface of COS Cells and BHK Cells
Authors: Petersen Eefke J , Posthumus Eelke , Sixma Jan J 
Published: July 2018

SummaryThe GpIb-IX complex constitutes the major receptor for von Wille-brand factor (vWF) on the surface of blood platelets. The vWF-binding site has been mapped to one of the three constituent chains, Gplba. Surface expression of Gplba depends on the. correct intracellular assembly with the Gplb(3 and GpIX chains. We have now grafted a portion of the extracellular domain of Gplba containing the vWF binding site onto the transmembrane/intracellular domain of the single chain surface molecule ICAM-1. Transient transfection of this chimeric protein in COS cells resulted in surface expression as assessed by immunostain-ing of live cells. Similar results were obtained after stable transfection into BHK cells. Purified vWF bound to the surface of transfected cells in the presence of ristocetin and botrocetin with a Kd of 52 ng/ml, comparable to the Kd for fixed platelets (65.5 ng/ml). This study indicates that functional expression of the vWF-binding domain of GpIbα on the surface of mammalian cells can be obtained in the absence of GpIbβ and GpIX. Furthermore, this model system simplifies existing methods for the assessment of the functional consequences of mutations in Gplba as found in pseudo-von Willebrand disease and Bemard-Soulier syndrome.
Hyperhomocysteinemia and Deep-Vein Thrombosis A Case-Control Study
Authors: Simioni Paolo , Prandoni Paolo , Burlina Alberto , Tormene Daniela , Sardella Corrado , Ferrari Vanni , Benedetti Lino , Girolami Antonio 
Published: July 2018

SummaryIn a case-control study, fasting total homocysteinemia was determined in 208 consecutive outpatients who underwent phlebography because of the first episode of clinically suspected deep-vein thrombosis (DVT) of lower limbs. Contrast venography confirmed the clinical suspicion in 60 patients (28.8%). Hyperhomocysteinemia was detected in 15 of the 60 patients with DVT (25.0%), and in 17 of the 148 subjects without thrombosis (11.5%; p = 0.025). The OR for having an acute DVT in patients with hyperhomocysteinemia was 2.6 (95% Cl: 1.1-5.9). It is concluded that high plasma homocysteine levels are significantly associated with DVT in symptomatic patients. Further studies are needed to clarify the clinical implications of this association.
Distribution and Activation of cAMP- and cGMP-Dependent Protein Kinases in Highly Purified Human Platelet Plasma and Intracellular Membranes
Authors: El-Daher Samer S , Eigenthaler Martin , Walter Ulrich , Furuichi Teiichi , Miyawaki Atsushi , Mikoshiba Mikoshiba , Kakkar Vijay V , Authi Kalwant S 
Published: July 2018

SummaryPreviously cAMP- and cGMP-dependent protein kinases (cAMP-PK, cGMP-PK) have been found predominantly associated with the particulate fraction in human platelets. We now report the distribution and activation of cAMP-PK and cGMP-PK in highly purified fractions of human platelet plasma (PM) and intracellular membranes (IM) prepared using high voltage free flow electrophoresis. Two non-hydrolys-able analogues of cAMP and cGMP namely Sp-5,6-DCl-cBiMPS and 8-p-CPT-cGMP have been used to activate cAMP-PK and cGMP-PK respectively. Addition of either agonist with [γ32P]ATP stimulated the endogenous activity of cAMP-PK or cGMP-PK in PM but not in IM. With PM Sp-5,6-DCl-cBiMPS stimulated the phosphorylation of protein substrates of Mr 16,22,24,46-50,66,90,160 and 250 kDa. A specific peptide inhibitor of cAMP-PK inhibited the phosphorylation of all of the substrates by Sp-5,6-DCl-cBiMPS. 8-pCPT-cGMP also induced the phosphorylation of a number of substrates particularly 16,22, 46-50, 90 and 250 kDa proteins. Inclusion of the cAMP-PK inhibitor peptide totally blocked the phosphorylation of the 16 and 22 kDa proteins, partially inhibited phosphorylation of 46-50 and 90 kDa proteins and had no effect on the 250 kDa protein indicating the 46-50, 90 and 250 kDa proteins were also cGMP-PK substrates. Western blotting with antibodies to cGMP-PK and the catalytic subunit of cAMP-PK revealed the presence of the kinases to be exclusively associated with PM with no detection in IM.The presence of cAMP-PK substrates in IM was investigated by exogenous addition of catalytic subunit of cAMP-PK. Phosphoproteins of Mr 16, 22, 27, 30,45, 75,116 and 250 kDa were detected. A range of antibodies to cAMP-PK substrates were used to identify and localise the substrates. These antibodies revealed GPIb and VASP to be exclusively associated with PM fractions. Rap IB was also predominantly associated with PM with a small level detected in IM. Antibodies to the IP3 receptor (18A10 and 4C11) revealed the protein to be predominantly associated with IM. Additionally the antibody 4C11 recognised a 230 kDa protein band in PM that was not seen in IM. From the known specificity of these antibodies the results confirm the presence of a type IIP3 receptor in IM and a distinct (possible type III) IP3 receptor with the PM. the 16, 22, 27, 30, 75 and 116 kDa proteins in IM represent nwly detected substartes for camp-pk of presently unknown identity.
Comparison of the Recombinant Escherichia coli-Produced Protease Domain of Tissue-Type Plasminogen Activator with Alteplase, Reteplase and Streptokinase in a Canine Model of Coronary Artery Thrombolysis
Authors: Martin Ulrich , Kohnert Ulrich , Stern Anne , Popp Fritz , Fischer Stephan 
Published: July 2018

SummaryRecent in vitro studies have shown that although recombinant Escherichia coli-produced protease domain of tissue-type plasminogen activator (t-PA) has no appreciable fibrin binding and less plasmin-forming activity compared to the wild-type, it is nevertheless an effective fibrinolytic agent in a dynamic in vitro plasma clot lysis system. The purpose of the present study was to evaluate the pharmacological profile of the protease in a canine model of coronary artery thrombosis. The effects of a single i.v. bolus injection of 1 mg/kg protease were compared with those of alteplase, reteplase and streptokinase at clinically relevant doses and dosing regimens in eight dogs per group. The protease rapidly restored coronary blood flow at 12 ± 1 min in all treated dogs with a significantly higher maximal coronary blood flow than in the reference groups, but was associated with short cycles of reocclusion in 4/8 animals. Overall, the coronary blood flow quality of the protease was not significantly different from that of the reference thrombo-lytics. Although fibrinogen was nearly completely degraded during protease treatment, the bleeding time was not significantly more prolonged than in reference groups. In conclusion, the protease domain is a rapidly acting, effective, bolus-injectable thrombolytic agent associated with a systemic lytic state and does not appear to cause significantly more bleeding than the reference thrombolytic agents.