bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Inhibition with Antifibrinolytic Agents of Staphylokinase and Streptokinase Induced Clot Lysis
Authors: Lijnen H Roger , Stassen Jean-Marie , Collen Désiré 
Published: July 2018

SummaryThe inhibitory effects of antifibrinolytic amino acids on clot lysis induced with recombinant staphylokinase (SakSTAR) or with streptokinase (SK) were evaluated in a human plasma milieu in vitro and in a hamster pulmonary embolism model in vivo. Addition of tranexamic acid to a system composed of 60 μ1 125I-fibrin-labeled plasma clots submerged in 0.5 ml human plasma, caused dose-dependent inhibition of lysis; complete lysis in 120 min required 30 nM SakSTAR or 100 nM SK and was reduced to 50% with 0.015 mM or with 0.07 mM tranexamic acid, respectively. Aprotinin also produced dose-dependent inhibition; lysis with SakSTAR or with SK was reduced to 50% of the control value with 8 KIU/ml or with 10 KIU/ml aprotinin, respectively. Thus, in human plasma in vitro the antifibrinolytic potency of tranexamic acid was 5-fold higher towards SakSTAR than towards SK, whereas that of aprotinin was comparable towards both agents.In hamsters with pulmonary embolism given 0.063 mg/kg SakSTAR or 0.20 mg/kg SK over 30 min, the antifibrinolytic potency of tranexamic acid, administered as a single bolus injection or as a bolus injection followed by continuous infusion, was 8- to 10-fold higher towards SakSTAR than towards SK (50% reduction of clot lysis with SakSTAR at 12.5 mg/kg, as compared to 100-150 mg/kg with SK). In contrast, aprotinin was equipotent towards SakSTAR and SK (50% reduction of clot lysis with 2,000 to 2,700 KlU/kg).The higher antifibrinolytic potency of tranexamic acid (which prevents binding of plasminogen to fibrin) towards SakSTAR than towards SK is most likely related to the requirement of fibrin-bound plasminogen for efficient fibrinolysis with SakSTAR. Tranexamic acid thus may be a useful and relatively specific antidote to clot lysis with SakSTAR and, at higher concentrations, to clot lysis with SK.
KRDS, a Peptide Derived from Human Lactotransferrin, Inhibits Thrombin-Induced Thromboxane Synthesis by a Cyclooxygenase-Independent Mechanism
Authors: Lévy-Toledano Sylviane , Grelac Françoise , Caen Jacques P , Maclouf Jacques 
Published: July 2018

SummaryKRDS, a tetrapeptide from human lactotransferrin, inhibits thrombin-induced platelet aggregation, secretion and thromboxane (TX) synthesis without interfering with phospholipase C (PLC) β activation, since in previous work we have shown that Ca2+ mobilization and phosphorylation of the myosin light chain kinase (20 kDa) and pleckstrin (47 kDa) were normal. However, the inhibition of arachido- nic acid-induced aggregation in the presence of KRDS is accompanied by normal TX synthesis suggesting that it does not interfere with the cyclooxygenase activity. To elucidate further the mechanisms of action of this peptide we tested its effect on U46619-induced platelet activation. KRDS inhibits U46619-induced platelet aggregation time- and dose-dependently without inhibiting the phosphorylation of pleckstrin. This suggests that the PLC pathway is not affected and that the inhibitory effect of KRDS is not due to an uncoupling of TXA2 from its receptor. In addition to the PLC pathway, protein tyrosine kinases play a major role in platelet signal transduction mechanisms. At least 7 tyrosine-phosphorylated proteins are detected upon stimulation of platelets by thrombin. KRDS strongly inhibits the tyrosine- phosphorylated substrates, in particular two 100-105 kDa substrates which are related to GP Ilb/IIIa activation and platelet aggregation. The absence of TX synthesis observed in the presence of KRDS could be due to the inactivation of cPLA2 since the latter needs tyrosine phosphorylation to be activated, thus explaining the inhibitory action of KRDS on platelet functions.
Sites of Tissue Factor Pathway Inhibitor (TFPI) and Tissue Factor Expression under Physiologic and Pathologic Conditions
Authors: Østerud Bjarne , Bajaj Madhu S , Bajaj Paul S 
Published: July 2018

SummaryUnder normal conditions, TFPI expression is restricted to megakaryocytes and the endothelium of the microvasculature. It is not synthesized by normal hepatocytes or by the endothelium of larger vessels. In contrast, endothelium and peripheral blood cells do not express tissue factor under normal conditions. Expression of tissue factor under normal physiologic conditions is widespread and is localized in areas which are physically separated from the circulating blood. During an inflammatory response, circulating monocytes have been shown to express tissue factor, whereas in general, expression of tissue factor has not been observed in the endothelium. Adherent monocytes/macrophages express both tissue factor and TFPI under pathologic conditions. Whether or not circulating peripheral blood monocytes under inflammatory conditions express TFPI is not known.
Hemostasis at Extremes of Body Weight
Authors: Hunt Beverley 
Published: July 2018

AbstractExtremes of body weight are not uncommon in the modern world and include anorexia nervosa (AN) and obesity. Both conditions are associated with increased morbidity and mortality: AN has the highest mortality rate of all mental illnesses and unfortunately obesity has reached epidemic proportions and is a well-recognized risk factor for cardiovascular disease including venous thromboembolism (VTE). This article summarizes the current understanding of hemostatic changes of these extremes of body weight. The hemostatic changes of AN have not been well described. Severe AN is associated with pancytopenia with decreased bone marrow cellularity, which causes a mild thrombocytopenia. Platelet hyperaggregability has been recognized in AN and has been attributed at least in part to increased adrenoceptor density. Obesity and the metabolic syndrome are associated with prothrombotic changes, which have been well characterized and related to complex adipocyte-induced inflammatory changes, including increased levels of plasminogen activator inhibitor type 1, von Willebrand factor, fibrinogen, and other evidence of increased coagulation and platelet activation. Accumulating evidence suggests a significant role for increased tissue factor expression and signaling in this relationship, with increased tissue factor expression present in adipose and possibly systemic tissues, induced by adipose-generated cytokines. Intriguingly, the hemostatic changes do not seem to increase with increasing BMI, although the risk of VTE increases with BMI, suggesting that decreased venous flow due to venous enlargement may play the most important role in increased VTE risk with obesity.
The Role of Triangular Fibrocartilage Complex in Axial Stability of the Forearm
Authors: Zhu Andy , Burns Geoffrey , Siljander Breana , Waljee Jennifer , Ozer Kagan 
Published: July 2018

Background The triangular fibrocartilage complex (TFCC) provides stability to the wrist and disruption of this complex can result in axial instability which can lead to ulnocarpal abutment.
Purpose This article determines the individual contributions of the volar radioulnar ligament (VRUL), dorsal radioulnar ligament (DRUL), and foveal attachment of the TFCC to longitudinal stability of the forearm under axial load.
Materials and Methods Eighteen cadaveric specimens were randomly assigned into three groups representing the component of the TFCC to be initially transected: VRUL, DRUL, and foveal attachment. Prior to transection, posterioranterior radiographs of the wrist were obtained at 0, 44.5, and 90 N of axial load. Serial transection of the TFCC components were performed with radiographs obtained at each of the aforementioned loads. Ulnar variance was assessed with two-way repeated measures analysis of variance and paired t-tests.
Results Transection of the foveal attachment demonstrated a significant change in ulnar variance of 1.5 and 0.6 mm under 45 and 90 N of load, respectively. At 0 N of load, there was no significant change in ulnar variance between an intact wrist and a wrist with all three ligaments transected; however, a significant change in ulnar variance, 1.0 mm, was observed under 90 N of load.
Conclusion The foveal attachment of the TFCC provides the largest contribution to axial stability.
Clinical Relevance The TFCC provides axial stability to the wrist and disruption of the TFCC may result in change in ulnar variance observed on an axial loaded wrist radiograph.
'A New You, That’s Who': an evaluation of short videos on puberty and human reproduction
Authors: Hurwitz Lisa B. , Lovato Silvia B. , Lauricella Alexis R. , Woodruff Teresa K. , Patrick Eric , Wartella Ellen 
Published: July 2018

AbstractLearning basic information about puberty and human reproduction can alleviate concerns about the transition to adolescence and provide a foundation for later learning about more advanced reproductive health topics, such as family planning. Parents and children alike believe educational videos make these topics more engaging, and socio-cultural theory suggests such videos can effectively promote learning. To that end, we tested the efficacy of a series of reproductive health education videos called 'A New You, That’s Who', with a sample of 80 11-year-old children in a research laboratory setting. The series was designed with socio-cultural theory learning principles in mind and consisted of three 5-min animated music videos focused on puberty, reproductive anatomy, and menstruation. Children were randomly assigned to watch the 'A New You, That’s Who' videos or a control set of videos on the scientific method. Children who watched the treatment videos out-performed peers in the control group on a measure reproductive health knowledge. However, there were no differences in attitudes towards puberty between conditions. The videos provide effective ways to learn factual information about puberty and human reproduction, and may be valuable tools to supplement social-emotional lessons provided at home, at school, or in other real-world settings.
Scleral hypoxia is a target for myopia control
Authors: Wu Hao , Chen Wei , Zhao Fei , Zhou Qingyi , Reinach Peter S. , Deng Lili , Ma Li , Luo Shumeng , Srinivasalu Nethrajeith , Pan Miaozhen , Hu Yang , Pei Xiaomeng , Sun Jing , Ren Ran , Xiong Yinghui , Zhou Zhonglou , Zhang Sen , Tian Geng , Fang Jianhuo , Zhang Lina , Lang Jidong , Wu Deng , Zeng Changqing , Qu Jia , Zhou Xiangtian 
Published: July 2018

Significance
Myopia is the leading cause of visual impairment. Myopic eyes are characterized by scleral extracellular matrix (ECM) remodeling, but the initiators and signaling pathways underlying scleral ECM remodeling in myopia are unknown. In the present study, we found that hypoxia-inducible factor-1α (HIF-1α) signaling promoted myopia through myofibroblast transdifferentiation. Furthermore, antihypoxic treatments prevented the HIF-1α–associated molecular changes, thus suppressing myopia progression. Our findings defined the importance of hypoxia in scleral ECM remodeling and myopia development. The identification of the scleral hypoxia in myopia not only provides a concept for understanding the mechanisms of myopia development but also suggests viable therapeutic approach to control myopia progression in humans.
Dual-process theory of racial isolation, legal cynicism, and reported crime
Authors: Hagan John , McCarthy Bill , Herda Daniel , Cann Chandrasekher Andrea 
Published: July 2018

SignificanceCynicism about lawlessness and police crime prevention and protection efforts is often high in predominately African-American neighborhoods, but residents persist in calling 911 and requesting police assistance. These calls continue to rise in neighborhoods that have recently experienced further increases in racial isolation, incarceration, and home foreclosures. These patterns are independent of statistical controls for an array of potentially confounding variables. The implication is that in the absence of alternatives, and despite past and continuing perceived police ineffectiveness, residents in racially isolated and disadvantaged neighborhoods will continue to call 911, seeking crime prevention and protection by police.
Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle
Authors: Wefers Jakob , van Moorsel Dirk , Hansen Jan , Connell Niels J. , Havekes Bas , Hoeks Joris , van Marken Lichtenbelt Wouter D. , Duez Hélène , Phielix Esther , Kalsbeek Andries , Boekschoten Mark V. , Hooiveld Guido J. , Hesselink Matthijs K. C. , Kersten Sander , Staels Bart , Scheer Frank A. J. L. , Schrauwen Patrick 
Published: July 2018

Significance
Shift workers are affected by circadian misalignment and have an increased risk to develop metabolic diseases such as type 2 diabetes. Here, we show that during simulated short-term night shift work insulin sensitivity at the level of skeletal muscle is decreased in male volunteers, which could contribute to the development of type 2 diabetes in the long term. We also find that the muscle molecular clock does not align rapidly to the new behavioral cycle. Importantly, on the level of the transcriptome, circadian misalignment induced upregulation of fatty acid metabolism pathways, potentially resulting in substrate competition on the cellular level. These findings help to better understand the negative consequences during night shift work.
Monitoring disease activity noninvasively in the
mdx
model of Duchenne muscular dystrophy
Authors: Filareto Antonio , Maguire-Nguyen Katie , Gan Qiang , Aldanondo Garazi , Machado Léo , Chamberlain Jeffrey S. , Rando Thomas A. 
Published: July 2018

Significance
Duchenne muscular dystrophy (DMD) is characterized by a catastrophic progression of muscle degeneration that leads to early death. Currently, there is neither a cure for DMD nor any treatments that effectively halt muscle degeneration. Novel methods that assess disease activity non-invasively would greatly accelerate the development of effective therapies. Here we present a novel preclinical animal model that uses bioluminescence imaging as a read-out of muscle degeneration, therefore constituting a non-invasive method to assess disease progression and response to experimental gene therapy in the mdx model of DMD. This model should be widely applicable for monitoring disease activity and responses to therapy in mouse models of muscular dystrophy.
Urban mobility and neighborhood isolation in America’s 50 largest cities
Authors: Wang Qi , Phillips Nolan Edward , Small Mario L. , Sampson Robert J. 
Published: July 2018

Significance
Living in disadvantaged neighborhoods is widely assumed to undermine life chances because residents are isolated from neighborhoods with greater resources. Yet, residential isolation may be mitigated by individuals spending much of their everyday lives outside their home neighborhoods, a possibility that has been difficult to assess on a large scale. Using new methods to analyze urban mobility in the 50 largest American cities, we find that residents of primarily black and Hispanic neighborhoods—whether poor or not—are far less exposed to either nonpoor or white middle-class neighborhoods than residents of primarily white neighborhoods. Although residents of disadvantaged neighborhoods regularly travel as far and to as many different neighborhoods as those from advantaged neighborhoods, their relative isolation and segregation persist.
Hsp70–Bag3 complex is a hub for proteotoxicity-induced signaling that controls protein aggregation
Authors: Meriin Anatoli B. , Narayanan Arjun , Meng Le , Alexandrov Ilya , Varelas Xaralabos , Cissé Ibrahim I. , Sherman Michael Y. 
Published: July 2018

Significance
This work dissects how cells monitor failure of proteasomes and trigger signaling responses defining whether cells survive proteotoxic stress or undergo apoptosis. The monitoring mechanism involves detection of a buildup of abnormal polypeptides released from ribosomes. Accordingly, the system simultaneously monitors effectiveness of several major processes, including protein synthesis, folding, and degradation. A special scaffold complex composed of heat shock protein 70 (Hsp70) and its cofactor Bcl-2–associated athanogene 3 (Bag3) links accumulation of abnormal polypeptide species with a number of protein kinases involved in various signal-transduction pathways. A startling finding is that an Hsp70–Bag3–regulated kinase, LATS1, regulates very early events of formation of protein aggregates; thus protein aggregation appears to be a tightly regulated process rather than the simple collapse of abnormal proteins.
Subsistence practices, past biodiversity, and anthropogenic impacts revealed by New Zealand-wide ancient DNA survey
Authors: Seersholm Frederik V. , Cole Theresa L. , Grealy Alicia , Rawlence Nicolas J. , Greig Karen , Knapp Michael , Stat Michael , Hansen Anders J. , Easton Luke J. , Shepherd Lara , Tennyson Alan J. D. , Scofield R. Paul , Walter Richard , Bunce Michael 
Published: July 2018

Significance
The mode and tempo of extinctions and extirpations after the first contact phase of human settlements is a widely debated topic. As the last major landmass to be settled by humans, New Zealand offers a unique lens through which to study interactions of people and biota. By analyzing ancient DNA from more than 5,000 nondiagnostic and fragmented bones from 38 subfossil assemblages, we describe species and patterns that have been missed by morphological approaches. We report the identification of five species of whale from an archaeological context in New Zealand and describe the prehistoric kākāpō population structure. Taken together, this study demonstrates insights into subsistence practices and extinction processes and demonstrates the value of genetic analyses of fossil assemblages.
Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence
Authors: Ke Ruian , Li Hui , Wang Shuyi , Ding Wenge , Ribeiro Ruy M. , Giorgi Elena E. , Bhattacharya Tanmoy , Barnard Richard J. O. , Hahn Beatrice H. , Shaw George M. , Perelson Alan S. 
Published: July 2018

Significance
Viral populations exhibit an extraordinary ability to survive abrupt changes in host environment by rapidly generating adaptive mutations. However, our understanding of how viral populations respond to selection pressure and the underlying molecular mechanisms supporting viral adaptation in vivo is limited. Here, we report a set of clinical data sampled from subjects chronically infected by hepatitis C virus (HCV). The data show rapid expansion and turnover of drug-resistant viruses following treatment with an HCV protease inhibitor. By fitting mathematical models to the data, we propose that superinfection and cure of infected cells play critical roles in facilitating the rapid expansion and turnover of viral populations. Our results highlight the importance of considering intracellular viral competition in understanding rapid viral adaptation.
River-discharge effects on United States Atlantic and Gulf coast sea-level changes
Authors: Piecuch Christopher G. , Bittermann Klaus , Kemp Andrew C. , Ponte Rui M. , Little Christopher M. , Engelhart Simon E. , Lentz Steven J. 
Published: July 2018

SignificanceRiver discharge exerts an important influence on coastal ocean circulation but has been overlooked as a driver of historical coastal sea-level change and future coastal flood risk. We explore the relation between observed river discharge and sea level on the United States Atlantic and Gulf coasts over interannual and longer periods. We formulate a theory that predicts the observed correspondence between river discharge and sea level, demonstrating a causal relation between the two variables. Our results highlight a significant but overlooked driver of coastal sea level, indicating the need for (1) improved resolution in remote sensing and modeling of the coastal zone and (2) inclusion of realistic river runoff variability in climate models.
Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes
Authors: Cao Xinyun , Zhu Lei , Song Xuejiao , Hu Zhe , Cronan John E. 
Published: July 2018

SignificanceLipoic acid is an enzyme cofactor found throughout the biological world that is required for key steps in central metabolism. In humans, defective lipoic acid synthesis results in defective energy production, accumulation of toxic levels of certain amino acids, and early death. The different pathways for lipoic acid synthesis put forth have not been validated by direct analysis of the postulated enzyme reactions, excepting a protein called LIPT1. Unfortunately, the enzyme activity reported for LIPT1 is misleading and seems to be an evolutionary remnant. We report that LIPT1 has a second “moonlighting” enzyme activity that fully explains the physiology of individuals lacking LIPT1 activity. We also document the postulated activity of LIPT2, another essential enzyme of the pathway.
Anomalous diffusion, spatial coherence, and viscoelasticity from the energy landscape of human chromosomes
Authors: Di Pierro Michele , Potoyan Davit A. , Wolynes Peter G. , Onuchic José N. 
Published: July 2018

Significance
Several active processes operate on eukaryotic genomes, dictating their three-dimensional arrangement and dynamical properties. The combination of structural organization and dynamics is essential to the proper functioning of the cell. We show that an effective energy landscape model for chromatin provides a unifying description of both the structural and dynamical aspects of the genome, recapitulating many of its features. Using this quasi-equilibrium energy landscape model, we demonstrate that the physical interactions accounting for genome architecture also lead to the nontrivial dynamical behavior of genomes previously described in multiple experimental observations.
Deictic and sociopragmatic effects in Tibeto-Burman SAP
indexation
Authors: DeLancey Scott 
Published: July 2018

Abstract
The study of hierarchical argument indexation systems shows that
while the ranking of both 1st and 2nd person over other arguments is
robust and reliable, it is impossible to find any compelling
crosslinguistic evidence for one or the other ranking of the two
Speech Act Participants, and rare to find a consistent ranking even
within a single language. This paper assembles and reviews
historical changes in the indexation of the “local” categories (1→2
and 2→1) in a number of Tibeto-Burman languages. We see that the
fundamental deictic ranking SAP > 3 is conservative, and inverse
marking to emphasize that ranking has been reinvented several times
in the family. Changes in the marking of local categories are more
diverse, but two phenomena recur independently in different
languages and branches: a tendency for the 1→2 form to be uniquely
marked, sometimes with forms which are not synchronically relatable
to anything else in the paradigm, and a contrasting tendency for the
2→1 form to merge with the marking of 3→1. I propose that these
tendencies reflect what I call sociopragmatic effects, i.e.
the socially delicate nature of any and all natural utterances
involving both the speaker and the addressee.