bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphisms of the Beta Fibrinogen Gene and Plasma Fibrinogen Concentration in Caucasian and Japanese Population Samples
Authors: Iso Hiroyasu , Folsom Aaron R , Winkelmann John C , Koike Kazuko , Harada Shoji , Greenberg Beryl , Sato Shinichi , Shimamoto Takashi , lida Minoru , Komachi Yoshio 
Published: July 2018

SummaryWe reported previously that plasma fibrinogen was significantly higher in U.S. Caucasians than in Japanese, which may contribute to the higher mortality rate of coronary heart disease in the United States than in Japan. To examine the contribution of genetic variations to the race difference in plasma fibrinogen levels, restriction fragment length polymorphisms (RFLPs) of the beta fibrinogen gene were examined in 293 nonsmoking Caucasians and Japanese men and women aged 47-69 years. Three RFLPs were detected by digestion of genomic DNA using the BclI restriction enzyme, polymerase chain reaction (PCR) products using HaeIII and HindIII. The alleles B2 (4.2 kb, BclI digestion), H2 (957 b, HaeIII) and Hd2 (465 b, HindIII) were associated with higher fibrinogen concentrations in previous studies. Because of a strong linkage disequilibrium between HaeIII and HindIII polymorphisms, the data of HindIII was presented. The frequency of the B2 allele was 22% (95% Cl: 17-27%) for Caucasians and 13% (10-17%) for Japanese (the difference: p <0.01). The respective frequency of the Hd2 allele was 26% (21-31%) and 12% (8-16%) (p <0.001). After controlling for age, body mass index, alcohol intake, triglycerides, fish intake, and for women, menopausal status and hormone replacement therapy, the adjusted mean fibrinogen level among Caucasians was 289 mg/dl for genotype B1B1 and 301 mg/dl for genotype B1B2 or B2B2 combined (p = 0.18), and 285 mg/dl for Hd1Hd1 and 306 mg/dl for Hd1Hd2 or Hd2Hd2 combined (p = 0.03). The respective mean values among Japanese were 251 mg/dl for B1B1 and 257 mg/dl for B1B2 or B2B2 combined (p = 0.37), 248 mg/dl for Hd1Hd1 and 259 mg/dl for Hd1Hd2 or Hd2Hd2 combined (p = 0.16). These polymorphisms had a similar effect on plasma fibrinogen concentrations for both men and women. The results suggest that a genetic difference may partly explain the higher plasma fibrinogen in Caucasians than in Japanese.
The Effect of Insulin-Induced Hypoglycaemia on Factor VIII: C Concentrations and Thrombin Activity in Subjects with Type 1 (Insulin-Dependent) Diabetes
Authors: Ibbotson Sally H , Catto Andrew , Davies Andrew , Grant Peter J 
Published: July 2018

SummaryThe effect of insulin-induced hypoglycaemia on plasma coagulant activity was studied in 11 subjects with well-controlled, uncomplicated type 1 diabetes. Thrombin generation was determined in plasma by a computer ex-vivo assisted chromogenic method and by the activated partial thromboplastin time (APTT). In addition, factor VIII :C, thrombin-antithrombin III (TAT) complex and fibrindpeptide A (FPA) levels were measured. Hypoglycaemia induced a rise in mean (SD) factor VIII: C concentrations from a baseline level of 1.13 (0.32) IU/ml to a peak 15 min after onset of symptoms and they remained increased at 90 min [1.54 (0.57) and 1.5 (0.54) IU/ml, p <;0.001 respectively]. A corresponding reduction in time to generate 50% maximal thrombin activity occurred from a pre-insulin value of 56 (6) s to a minimum reading of 46 (7) s at 15 min (p <;0.001) and remained low at 90 min [48 (6) s, p <;0.001]. APTT shortened from 43.3 (4.8) s to 40.1 (4.6) s at 30 min (p <;0.001) but did not fall below the normal range (37.6-42.7 s) and no significant changes in TAT or FPA levels were noted. Factor VIII: C correlated inversely with time to generate 50% maximal thrombin activity and APTT (r = -0.580, p <;0.001; r = -0.673, p <;0.001, n = 66, respectively). The results show that the rise in plasma factor VIII: C levels induced by hypoglycaemia is accompanied by accelerated rates of generation of thrombin in contact-activated plasma, though concentrations of FPA and TAT remain unchanged, although TAT complexes are not a sensitive marker of in vivo thrombin generation.
Glycoprotein Ib Can Mediate Endothelial Cell Attachment to a von Willebrand Factor Substratum
Authors: Beacham Dorothy A , Cruz Miguel A , Handin Robert I 
Published: July 2018

SummaryIntroduction of single amino acid substitutions into the C-terminal Arg-Gly-Asp-Ser (RGDS) site of von Willebrand Factor, referred to as RGD mutant vWF, selectively abrogated vWF binding to platelet glycoprotein IIb/IIIa (GpIIb/IIIa, αIIbβ3 and abolished human umbilical vein endothelial cell (HUVEC) spreading, but not attachment, to RGD mutant vWF (Beacham, D. A., Wise, R. J., Turci, S. M. and Handin, R. I. 1992. J. Biol. Chem. 167, 3409-3415). These results suggested that in addition to the vitronectin receptor (VNR, αvβ3), a second endothelial membrane glycoprotein can mediate HUVEC adhesion to vWF. HUVEC attachment to wild-type (WT) and RGD-mutant vWF was reduced by two proteins known to block the vWF-platelet glycoprotein Ib/IX (GpIb/IX) interaction, the monoclonal antibody AS-7 and the recombinant polypeptide, vWF-A1. The addition of cytochalasin B or DNase I to disrupt potential GPIbα-cytoskeletal interactions enhanced the immunoprecipitation of endothelial GPIbα, caused HUVEC to round up, and increased HUVEC adhesion to RGD mutant vWF. These results indicate that while the VNR is the primary adhesion receptor for vWF, endothelial GPIbα can mediate HUVEC attachment to vWF. GpIb-dependent attachment could contribute to HUVEC adhesion under conditions when cell surface expression of the VNR is downregulated, and VNR-dependent adhesion is reduced.
Factor VII Coagulant Activity in Relation to Serum Lipoproteins and Dietary Fat in Middle-aged Men
Authors: Väisänen Sari , Rankinen Tuomo , Penttilä IIkka , Rauramaa Rainer 
Published: July 2018

SummaryThe associations of serum lipoproteins and habitual diet to factor VII coagulant activity (FVIIc) were analysed in 119 middle-aged men. FVIIc was measured by one-stage clotting assay, cholesterol and triglycerides enzymatically, serum apolipoproteins (apo) immunoturbi- dimetrically and habitual diet using four-day food records. ApoB, cholesterol, triglycerides, apoA-II, LDL cholesterol and dietary fat correlated directly to FVIIc (p <0.001). In multivariate analysis apoB, dietary fat and apoA-II explained 35.3% of the variance in FVIIc. In the lowest apoB tertile FVIIc was increased only when fat intake was high (>38 E%), in the middle tertile FVIIc increased gradually from low to high fat intake, whereas in the highest apoB tertile FVIIc was not related to dietary fat (p = 0.038 for age-adjusted interaction). The present data demonstrate a direct relation between apoB and FVIIc in middle-aged men. Low fat diet seem to associate to decreased FVIIc especially in subjects in the lower end of the apoB distribution.
In Vitro Characterization of High Purity Factor IX Concentrates for the Treatment of Hemophilia B
Authors: Limentani Steven A , Gowell Kerry P , Deitcher Steven R 
Published: July 2018

SummaryThis study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor Vila could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected. Prothrombin contaminated all of the products except Mononine. Activation products of prothrombin were identified for three of four lots of Immunine and for one lot of Factor IX VHP. These results thus demonstrate that high purity factor IX concentrates differ substantially in the degree to which they are contaminated by potentially thrombogenic materials.
Quantitative and Qualitative Analysis of Platelet GPIb and von Willebrand Factor in Liver Cirrhosis
Authors: Beer J H , Clerici N , Baillod P , von Felten A , Schlappritzi E , Büchi L 
Published: July 2018

SummaryNumerous abnormalities of plasmatic coagulation and platelet function may contribute to the bleeding in liver cirrhosis with a defective platelet-von Willebrand factor interaction being a potential mechanism. To analyze GPIb and von Willebrand factor in cirrhosis, we quantified the number of GPIb molecules on the platelet surface by flow cytometry, assessed the total (and indirectly the internal) pool of GPIb by ELISA and measured the circulating amount of glycocalicin in plasma as a measure of proteolytic activity and platelet turnover. Von Willebrand factor was characterized by ELISA, by its ristocetin-cofactor activity and by multimer analysis. Botrocetin-induced agglutination was used for functional analysis.The data from 8 well-characterized cirrhosis patients indicate that total GPIb is insignificantly increased to 46,000 ± 5,000 molecules/P (normal: 39,500 ± 2,000 [SEM]), surface-GPIb is normal with some variability and that the glycocalicin levels are 2-3 times higher than would be expected from the platelet count (= 100 ±5 × 109/1). Von Willebrand factor antigen levels and -activity were 400-500 % of normal with a 22% reduction of the high molecular weight multimers. A significant hyperagglutination response to botrocetin was observed with platelets from both patients and controls using patient plasma as a source of von Willebrand factor. In conclusion, a hyperresponsiveness rather than a defective platelet-von Willebrand factor interaction can be observed in cirrhosis which may compensate for other hemostatic problems and appears to be mediated primarily by increased levels of von Willebrand factor.
Transformation of Cellular Factor XIII into an Active Zymogen Transglutaminase in Thrombin-Stimulated Platelets
Authors: Muszbek László , Haramura Gizella , Polgár János 
Published: July 2018

SummaryThe cellular form of blood coagulation factor XIII (FXIII) is present in platelets, monocytes and macrophages. During long-term stimulation of platelets by thrombin cellular FXIII becomes activated and crosslinks proteins, however, the mechanism of its activation has not been elucidated. It was shown that, contrary to plasma FXIII, the intracellular activation of platelet FXIII does not involve proteolysis. FXIII remained intact in thrombin-activated platelets, i.e., the activation peptide was not removed from the molecule. Part of the zymogen FXIII molecules, however, assumed an active configuration as was demonstrated both by the measurement of transglutaminase activity and by active-site-SH titration. These findings clearly indicate that during platelet activation, when intracellular Ca2+ concentration is raised, a slow non-proteolytic transformation of FXIII zymogen into an active transglutaminase occurs.
Virion structure and genome delivery mechanism of sacbrood honeybee virus
Authors: Procházková Michaela , Füzik Tibor , Škubník Karel , Moravcová Jana , Ubiparip Zorica , Přidal Antonín , Plevka Pavel 
Published: July 2018

Significance
Honey bee pollination is required to sustain the biodiversity of wild flora and for agricultural production; however, honey bee populations in Europe and North America are declining due to virus infections. Sacbrood virus (SBV) infection is lethal to honey bee larvae and decreases the fitness of honey bee colonies. Here we present the structure of the SBV particle and show that it contains 60 copies of a minor capsid protein attached to its surface. No similar minor capsid proteins have been previously observed in any of the related viruses. We also present a structural analysis of the genome release of SBV. The possibility of blocking virus genome delivery may provide a tool to prevent the spread of this honey bee pathogen.
Diffusion in networks and the virtue of burstiness
Authors: Akbarpour Mohammad , Jackson Matthew O. 
Published: July 2018

Significance
The contagion of disease and the diffusion of information depend on personal contact. People are not always available to interact with those around them, and the timing of people’s activities determines whether people have opportunities to meet and transmit a germ, idea, etc., and ultimately whether widespread contagion or diffusion occurs. We show that, in a simple model of contagion or diffusion, the greatest levels of spreading occur when there is heterogeneity in activity patterns: Some people are active for long periods of time and then inactive for long periods, changing their availability only infrequently, while other people alternate frequently between being active and inactive. This observation has policy implications for limiting contagious diseases as well as promoting diffusion of information.
N6-Furfuryladenine is protective in Huntington’s disease models by signaling huntingtin phosphorylation
Authors: Bowie Laura E. , Maiuri Tamara , Alpaugh Melanie , Gabriel Michelle , Arbez Nicolas , Galleguillos Danny , Hung Claudia L. K. , Patel Shreya , Xia Jianrun , Hertz Nicholas T. , Ross Christopher A. , Litchfield David W. , Sipione Simonetta , Truant Ray 
Published: July 2018

Significance
We have discovered a molecule derived from DNA-damage repair that can correct the lack of phosphorylation of mutant huntingtin, the cause of Huntington’s disease (HD). In a mouse model, treatment reverses HD-like disease, and we see the lowering of mutant huntingtin levels to normal. The mechanism of this molecule is that it is processed to make a signal for kinase activity essential for repairing DNA. This mechanism is critical when neurons are stressed and have very low or absent energy levels. We propose that this molecule is a type of signaling from DNA-damage repair that occurs at dangerously low ATP levels.
Recognition of conserved antigens by Th17 cells provides broad protection against pulmonaryHaemophilus influenzaeinfection
Authors: Li Wenchao , Zhang Xinyun , Yang Ying , Yin Qingqin , Wang Yan , Li Yong , Wang Chuan , Wong Sandy M. , Wang Ying , Goldfine Howard , Akerley Brian J. , Shen Hao 
Published: July 2018

SignificanceNontypeableHaemophilus influenzae(NTHi) is a major cause of community acquired pneumonia and exacerbation of chronic obstructive pulmonary disease. Current effort in NTHi vaccine development has focused on generating antibody responses to surface antigens and has had limited success, largely because of antigenic diversity among the numerous circulating NTHi strains. In this study, we have uncovered Th17 responses as the immune mechanism of cross-protection and identified Th17 antigens that are conserved and induce protection against NTHi lung infection, thus making a critical first step toward development of a broadly protective “universal” vaccine—the Holy Grail of vaccine development against respiratory pathogens.
Positional specificity of different transcription factor classes within enhancers
Authors: Grossman Sharon R. , Engreitz Jesse , Ray John P. , Nguyen Tung H. , Hacohen Nir , Lander Eric S. 
Published: July 2018

Significance
Gene expression is controlled by sequence-specific transcription factors (TFs), which bind to regulatory sequences in DNA. The degree to which the arrangement of motif sites within regulatory elements determines their function remains unclear. Here, we show that the positional distribution of TF motif sites within nucleosome-depleted regions of DNA fall into six distinct classes. These patterns are highly consistent across cell types and bring together factors that have similar functional and binding properties. Furthermore, the position of motif sites appears to be related to their known functions. Our results suggest that TFs play distinct roles in forming a functional enhancer, facilitated by their position within a regulatory sequence.
Confinement transition of ℤ
2
gauge theories coupled to massless fermions: Emergent quantum chromodynamics and
SO
(5) symmetry
Authors: Gazit Snir , Assaad Fakher F. , Sachdev Subir , Vishwanath Ashvin , Wang Chong 
Published: July 2018

Significance
Universal properties of quantum (zero-temperature) phase transitions are typically well-described by the classical Landau theory of spontaneous symmetry breaking. A paradigmatic counterexample is deconfined criticality, where quantum interference allows for a direct and continuous transition between states with distinct symmetry-breaking patterns, a phenomenon that is classically forbidden. In this work, we extend the scope of deconfined criticality to a case where breaking of a global symmetry coincides with confinement of a local (gauge) symmetry. Using Monte Carlo simulations, we investigate a lattice realization of this transition. Remarkably, we uncover emergent and enlarged global and gauge symmetries. These findings direct us in constructing a critical field theory description.
Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library
Authors: Merkouris Spyros , Barde Yves-Alain , Binley Kate E. , Allen Nicholas D. , Stepanov Alexey V. , Wu Nicholas C. , Grande Geramie , Lin Chih-Wei , Li Meng , Nan Xinsheng , Chacon-Fernandez Pedro , DiStefano Peter S. , Lindsay Ronald M. , Lerner Richard A. , Xie Jia 
Published: July 2018

SignificanceNeurotrophin receptors are a class of receptor tyrosine kinases that couple to signaling pathways critical for neuronal survival and growth. One member, TrkB, is particularly interesting because it plays a role in many severe degenerative neurological diseases. The TrkB natural ligand brain-derived neurotrophic factor (BDNF) is not suitable to be developed as a drug or therapy as proved by previous unsuccessful clinical trials. Here we report a selection method that produced potent full agonist antibodies that mimic BDNF function, yet with better biophysical properties. This study paves the road for the development of agonist antibodies for other receptor tyrosine kinases.
Template and primer requirements for DNA Pol θ-mediated end joining
Authors: He Peng , Yang Wei 
Published: July 2018

Significance
Using oligonucleotides comprised solely of purines or pyrimidines, we find that human Polθ is a bona fide template-dependent DNA polymerase and has no terminal transferase activity under physiological conditions. Polθ requires a minimum of 2 bp and optimally 4 bp between a template/primer pair for efficient and processive DNA synthesis. Polθ polymerase activity is inhibited by a 3′-overhang on the template strand. Consistent with in vivo observations of DNA deletion during TMEJ, 3′-exonucleases or 3′-flap endonucleases are likely recruited to remove such hindrances when microhomology is internal to the 3′ ends. In contrast to a previously report, we observed limited strand displacement activity by Polθ. Because Pol θ lacks a proofreading exonuclease activity and is error prone, minimal strand displacement can be only beneficial for TMEJ.
Deconstructing teleology
Authors: Mithun Marianne 
Published: July 2018

Abstract
A central issue in typology is the role of implicational hierarchies
in shaping individual languages. One view is that the hierarchies
guide language change, or at least constrain it: “Since a hierarchy
constrains what is a possible language, it is also a constraint on
language change, because languages move from one possible state to
another” (Corbett 2011).
Other approaches take a different perspective: “Hierarchies simply
capture the outputs of independent diachronic processes” (Cristofaro & Zúñiga this
volume). Here the relationship between typology and
diachrony is examined with respect to the most frequently-cited
hierarchies, the cluster of Referential/Topicality/Animacy/Empathy
hierarchies. While such hierarchies might appear to drive diachronic
development in some single-step changes, multi-step developments are
a different matter.
The direction(s) of analogical change in direct/inverse
systems
Authors: Jacques Guillaume , Antonov Anton 
Published: July 2018

Abstract
In this chapter, we extract general principles of language change
from the study of the evolution of the conjunct order in various
Algonquian languages, and propose four generalizations concerning
the directionality of the spread of analogy in these systems. These
generalizations are expected to bring insights on the analysis of
data from other language families with direct/inverse marking but
insufficient philological record, such as for instance
Sino-Tibetan.
Extensive stuttering therapy in Turkish children who stutter
Authors: Akin Senkal Ozgul , Ciyiltepe Muzeyyen 
Published: July 2018

Background/aim:
In this study, the immediate and extended outcomes of the stuttering therapy programme were investigated for the first time in Turkey. This paper reports the results of an eight-week extensive stuttering therapy programme for 35 school-aged and adolescents who stutter.

Materials and methods:
Measurements were made immediately before and after the treatment and again during the follow-up period, 6 months’ post-treatment. The measures included percentage of stuttering and syllables spoken per minute.

Results:
Turkish school-aged and adolescent children who stutter showed more within-word dysfluencies than between-word dysfluencies. In addition, stuttering characteristics included (in) audible sound prolongations (24%) and sound/syllable repetition (49%). The results indicated that substantial positive changes occurred and were maintained in speech performance with an eight-week stuttering therapy.

Conclusion:
The present study examined the characteristics of dysfluencies in school-aged and adolescents and then dysfluency characteristics were taken to account before and after stuttering therapy of children and adolescents who stutter at moderate degree in Turkey. Extensive therapy courses were determined for children and adolescents who stutter and their families changed the stuttering behaviour of the participants.