bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of Platelet Function by Radical Species Produced During Irradiation of Oxygenated Water
Authors: Krinsky Norman I , Sladdin Danielle G , Levine Peter H , Taub Irwin A , Simic Michael G 
Published: July 2018

SummaryGel-filtered platelets in neutral, oxygen-containing solutions irradiated to a dose of 10 krad with γ-rays display a significant inhibition of ADP-induced aggregation. Though the superoxide anion radical (O-
2) and H2O2 are generated in water irradiated under these conditions, only catalase, but not superoxide dismutase (SOD), conveyed protection against this inhibition of platelet function. When the platelets are in the presence of 10-3 M sodium formate, which converts the majority of the radical species formed to O-
2, inhibition of aggregation was again observed. Under these circumstances, the addition of catalase significantly decreased this inhibition, whereas the addition of SOD was without effect.In order to separate the platelet-inhibition effects of the radical species generated in the medium from a direct effect of irradiation on platelet components, relatively stable quantities of O-
2. were produced in alkaline solutions and reacted with gel-filtered platelets. Again, an inhibition of ADP-induced aggregation was observed. This inhibition was not significantly altered by the addition of SOD, but was abolished by the addition of catalase, either with or without SOD.Our observation would indicate that O-
2.is without direct effect on platelet function, but serves as the precursor of H2O2, which can inhibit platelet reactions.
Diversity of Primary Structures of the Carboxy-terminal Regions of Mammalian Fibrinogen Aα-Chains
Authors: Murakawa Masahiro , Okamura Takashi , Kamura Takumi , Shibuya Tsunefumi , Harada Mine , Niho Yoshiyuki 
Published: July 2018

SummaryThe partial amino acid sequences of fibrinogen Aα-chains from five mammalian species have been inferred by means of the polymerase chain reaction (PCR). From the genomic DNA of the rhesus monkey, pig, dog, mouse and Syrian hamster, the DNA fragments coding for α-C domains in the Aα-chains were amplified and sequenced. In all species examined, four cysteine residues were always conserved at the homologous positions. The carboxy- and amino-terminal portions of the α-C domains showed a considerable homology among the species. However, the sizes of the middle portions, which corresponded to the internal repeat structures, showed an apparent variability because of several insertions and/or deletions. In the rhesus monkey, pig, mouse and Syrian hamster, 13 amino acid tandem repeats fundamentally similar to those in humans and the rat were identified. In the dog, however, tandem repeats were found to consist of 18 amino acids, suggesting an independent multiplication of the canine repeats. The sites of the α-chain cross-linking acceptor and α2-plasmin inhibitor cross-linking donor were not always evolutionally conserved. The arginyl-glycyl-aspartic acid (RGD) sequence was not found in the amplified region of either the rhesus monkey or the pig. In the canine α-C domain, two RGD sequences were identified at the homologous positions to both rat and human RGD S. In the Syrian hamster, a single RGD sequence was found at the same position to that of the rat. Triplication of the RGD sequences was seen in the murine fibrinogen α-C domain around the homologous site to the rat RGDS sequence. These findings are of some interest from the point of view of structure-function and evolutionary relationships in the mammalian fibrinogen Aα-chains.
Recombinant Pro-Urokinase Requires Heparin for Optimal Clot Lysis and Restoration of Blood Flow in a Canine Femoral Artery Thrombosis Model
Authors: Burke Sandra E , Lubbers Nathan L , Nelson Richard A , Henkin Jack 
Published: July 2018

SummaryHeparin is often used as an adjunct to thrombolytic therapy in order to prevent reocclusion of the patent vessels in patients with thrombotic disease. Controversy exists as to whether heparin is required for effective clot lysis with tissue-type plasminogen activator, while in vitro data and small scale clinical trials have suggested an enhancement of pro-urokinase efficacy by heparin. The present study was conducted to determine whether heparin pre-treatment is required to produce optimal clot lysis and blood flow restoration in response to recombinant pro-urokinase (r-proUK). In four groups of dogs, blood clots labelled with 125Iodine were formed in the femoral artery and were monitored continuously for loss of counts as an indicator of clot lysis. Femoral artery blood flow was measured simultaneously. Group 1 received vehicle (n = 5), while group 2 was given vehicle + heparin (n = 6; 500 U bolus + 350 U/h). This dose of heparin increased the activated partial thromboplastin time (APTT) by at least 1.5 times the control level for the 4 h observation period. Group 3 received r-proUK alone at a dose of 100,000 U/kg (50% given as a 1-min bolus injection, 50% as a 30 min infusion) (n = 8), while group 4 was treated with the same dose of r-proUK in the presence of heparin as described (n = 8). Clot lysis at 4 h in groups 1 and 2 was 26 ± 3% and 28 ± 5%, respectively; flow was not restored in either group. In group 3, clot lysis was 50 ± 4% while group 4 showed lysis of 85 ± 5% (p <0.05). However, flow was not restored in any dog in group 3, while five of eight dogs in group 4 showed complete restoration of blood flow. In the remaining three dogs, flow was restored to 70–91% of control levels. The data suggest that a regimen of heparin pretreatment with continued infusion markedly increases the efficacy of r-proUK in this model and results in significant restoration of blood flow.
Subunit A of Factor XIII Regulates Subunit B Plasma Concentration
Authors: Rodeghiero F , Morbin M , Barbui T 
Published: July 2018

SummarySubunit a of Factor XIII is found absent in homozygotes and reduced in heterozygotes. Since a concomitant reduction of subunit b occurs in these cases, an interaction between the loci controlling the synthesis of the two subunits was suggested. However in the present study we have shown that the administration of subunit a in two totally devoid homozygotes produced an increase of subunit b, reaching the maximum concentration five days after infusion. This strongly suggests that subunit b plasma level is regulated on the subunit a plasma amount.
Rabbit Antibodies Against the Procoagulant Activity (VIII:C) of Human Factor VIII
Authors: Tran T H , Marbet G A , Duckert F 
Published: July 2018

SummaryThe procoagulant activity VIII:C was separated from factor VIII antigen (VIIIR:Ag) by gel filtration in the presence of 0.25 mol/l calcium chloride. Antibodies (anti-VIII:C) were obtained by immunization of rabbits with VIII:C. The last step of the purification procedure of antibodies consists of an adsorption on VIIIR:Ag-Sepharose 2 BCL as immunoadsorbent to remove contaminating traces of antibodies against VIIIR:Ag. The anti- VIII:C titer remains unchanged during this adsorption (29 Bethesda units per mg). In solution, anti-VIII:C neutralies factor VIII activity (in plasma, cryoprecipitate or in purified form) and the fragment VIII:C without reacting with VIIIR:Ag. Once immobilized on a solid matrix, i.e.2% agarose, it loses over 95% of its inhibitory capacity. The immobilized anti-VIIIR:Ag binds stoichiometrically the antigen and the activity of plasma factor VIII. These results together suggest that factor VIII is composed of 2 different entities, but undissociated under physiological conditions. Immunophysical analyses as a function of pH and temperature of anti-VIII:C and its complex with factor VIII show properties similar to those of homologous antibodies. The antigen determinants of VIII:C (VIII:CAg) are destroyed at low pHs or high temperatures, and VIII:C can no more form a complex with anti-VIII:C. Purified anti-VIII:C is also used in a two-stage assay to detect VIII:CAg or cross-reacting material in some severe haemophiliacs.
Fibrinopeptide A (FPA) Level and Fibrinogen Kinetics in Patients with Malignant Disease
Authors: Yoda Yasuhiro , Abe Tsukasa 
Published: July 2018

SummaryFPA level, fibrinogen turnover rate, and fibrinolytic activity were studied on 18 patients with malignant disease. It was found that the FPA levels were significantly elevated and were correlated with fibrinogen turnover rate (r=0.74, p<0.001) and FDP (r = 0.58, p<0.02). Estimated FPA turnover rate was also correlated with fibrinogen turnover rate (r = 0.70, p<0.001). These results suggest that fibrinogen catabolism in patients with malignant disease is related with thrombin proteolysis. However, ratios of 1/2 FPA turnover rate to fibrinogen turnover rate suggest that intravascular thrombin proteolysis is not the major determinant of fibrinogen catabolism. It is suspected that extravascular thrombin proteolysis is responsible for the elevation of plasma FPA level which is correlated with acceleration of fibrinogen catabolism.
Prothrombin-Activator (Thromboplastin) Generation in the Blood of Water Snake (Natrix piscator)
Authors: Srivastava V M , Dube B , Dube R K , Agarwal G P 
Published: July 2018

SummaryThe generation of prothrombin-activator (thromboplastin) in water snake (Natrix piscator) is clearly delayed, Compared to a mammalian system, but the final activity is well comparable to that in man, when homologous sources of “phospholipid” (erythrocyte-lysate) and of substrate plasma are employed in one stage “thromboplastin generation test”. The use of heterologous source of either of the above reagents resulted in significantly longer clotting times; hence the need for homologous source of above reagents in the test is emphasized for comparative studies on animal haemostasis.
Delayed Elimination of Fibrin from the Lungs in Rats Given α2-Antiplasmin
Authors: Carlin G , Einarsson M , Saldeen T 
Published: July 2018

SummaryInjection of human α2–antiplasmin resulted in delayed elimination of fibrin from the lungs in rats with thrombin–induced intravascular coagulation. The amount of α2–antiplasmin injected was chosen so as to simulate the posttraumatic increase of this inhibitor in man. By injecting trace amounts only of radiolabelled α2–antiplasmin a specific uptake of this protein in the lungs was noted after the thrombin-induced coagulation. The results may indicate that the posttraumatic increase in α2–antiplasmin is of significance for the delayed elimination of fibrin seen in patients following trauma.
Personalized disease signatures through information-theoretic compaction of big cancer data
Authors: Vasudevan Swetha , Flashner-Abramson Efrat , Remacle F. , Levine R. D. , Kravchenko-Balasha Nataly 
Published: July 2018

Significance
Accurate cancer diagnostics is a prerequisite for optimal personalized cancer medicine. We propose an information-theoretic cancer diagnosis that identifies signatures comprising patient-specific oncogenic processes rather than cancer type-specific biomarkers. Such comprehensive transcriptional signatures should allow for more accurate classification of cancer patients and better patient-specific diagnostics. The approach that we describe herein allows decoding of large-scale molecular-level information and elucidating patient-specific transcriptional altered network structures. Thereby, we move from cancer type-associated biomarkers to unbiased patient-specific unbalanced oncogenic processes.
Characterization of a novel hydroxynitrile lyase from Nandina domestica Thunb
Authors: Isobe Kimiyasu , Kitagawa Asuka , Kanamori Kazuma , Kashiwagi Nozomi , Matsui Daisuke , Yamaguchi Takuya , Fuhshuku Ken-ichi , Semba Hisashi , Asano Yasuhisa 
Published: July 2018

ABSTRACT
The leaves of Nandina domestica Thunb. exhibited high hydroxynitrile lyase (HNL) activity in (R)-mandelonitrile synthesis. The specific activity of young leaves was significantly higher than that of mature leaves. We isolated two HNLs with molecular mass of 24.9 kDa (NdHNL-S) and 28.0 kDa (NdHNL-L) from the young leaves. Both NdHNLs were composed of two identical subunits, without FAD and carbohydrates. We purified NdHNL-L and revealed its enzymatic properties. The whole deduced amino acid sequence of NdHNL-L was not homologous to any other HNLs, and the specific activity for mandelonitrile synthesis by NdHNL-L was higher than that by other plant HNLs. The enzyme catalyzed enantioselective synthesis of (R)-cyanohydrins, exhibited high activity at pH 4.0, and high stability in the pH range of 3.5–8.0 and below 55°C. Thus, NdHNL-L is a novel HNL with novel amino acid sequence and has a potential for the efficient production of (R)-cyanohydrins.
Contextual factors on physical demands in professional women's soccer: Female Athletes in Motion study
Authors: Vescovi Jason D. , Falenchuk Olesya 
Published: July 2018

AbstractThe aim of this study was to examine the impact of contextual factors on relative locomotor and metabolic power distances during professional female soccer matches. Twenty‐eight players (forwards, n = 4; midfielders, n = 12; defenders, n = 12) that competed in a 90‐min home and away match (regular season only). The generalised estimating equations (GEE) was used to evaluate relative locomotor and metabolic power distances for three contextual factors: location (home vs. away), type of turf (natural vs. artificial), and match outcome (win, loss and draw). No differences were observed for home vs. away matches. Moderate‐intensity running (20.0 ± 1.0 m min−1 and 16.4 ± 0.9 m min−1), high‐intensity running (8.6 ± 0.4 m min−1 and 7.3 ± 0.4 m min−1) and high‐metabolic power (16.3 ± 0.5 m min−1 and 14.4 ± 0.5 m min−1) distances were elevated on artificial turf compared to natural grass, respectively. Relative sprint distance was greater during losses compared with draws (4.3 ± 0.4 m min−1 and 3.4 ± 0.3 m min−1). Overall physical demands of professional women's soccer were not impacted by match location. However, the elevation of moderate and high‐intensity demands while playing on artificial turf may have implications on match preparations as well as recovery strategies.
Deficits in context-dependent adaptive coding in early psychosis and healthy individuals with schizotypal personality traits
Authors: Kirschner Matthias , Haugg Amelie , Manoliu Andrei , Simon Joe J , Huys Quentin J M , Seifritz Erich , Tobler Philippe N , Kaiser Stefan 
Published: July 2018

Abstract
Adaptive coding of information is a fundamental principle of brain functioning. It allows for efficient representation over a large range of inputs and thereby alleviates the limited coding range of neurons. In the present study, we investigated for the first time potential alterations in context-dependent reward adaptation and its association with symptom dimensions in the schizophrenia spectrum. We studied 27 patients with first-episode psychosis, 26 individuals with schizotypal personality traits and 25 healthy controls. We used functional MRI in combination with a variant of the monetary incentive delay task and assessed adaptive reward coding in two reward conditions with different reward ranges. Compared to healthy controls, patients with first-episode psychosis and healthy individuals with schizotypal personality traits showed a deficit in increasing the blood oxygen level-dependent response slope in the right caudate for the low reward range compared to the high reward range. In other words, the two groups showed inefficient neural adaptation to the current reward context. In addition, we found impaired adaptive coding of reward in the caudate nucleus and putamen to be associated with total symptom severity across the schizophrenia spectrum. Symptom severity was more strongly associated with neural deficits in adaptive coding than with the neural coding of absolute reward outcomes. Deficits in adaptive coding were prominent across the schizophrenia spectrum and even detectable in unmedicated (healthy) individuals with schizotypal personality traits. Furthermore, the association between total symptom severity and impaired adaptive coding in the right caudate and putamen suggests a dimensional mechanism underlying imprecise neural adaptation. Our findings support the idea that impaired adaptive coding may be a general information-processing deficit explaining disturbances within the schizophrenia spectrum over and above a simple model of blunted absolute reward signals.
Revealing a Cortical Circuit Responsive to Predatory Threats and Mediating Contextual Fear Memory
Authors: de Lima Miguel Antonio Xavier , Baldo Marcus Vinicius C , Canteras Newton Sabino 
Published: July 2018

Abstract
The ventral part of the anteromedial thalamic nucleus (AMv) receives substantial inputs from hypothalamic sites that are highly responsive to a live predator or its odor trace and represents an important thalamic hub for conveying predatory threat information to the cerebral cortex. In the present study, we begin by examining the cortico-amygdalar-hippocampal projections of the main AMv cortical targets, namely, the caudal prelimbic, rostral anterior cingulate, and medial visual areas, as well as the rostral part of the ventral retrosplenial area, one of the main targets of the anterior cingulate area. We observed that these areas form a clear cortical network. Next, we revealed that in animals exposed to a live cat, all of the elements of this circuit presented a differential increase in Fos, supporting the idea of a predator threat-responsive cortical network. Finally, we showed that bilateral cytotoxic lesions in each element of this cortical network did not change innate fear responses but drastically reduced contextual conditioning to the predator-associated environment. Overall, the present findings suggest that predator threat has an extensive representation in the cerebral cortex and revealed a cortical network that is responsive to predatory threats and exerts a critical role in processing fear memory.
Antisense lncRNA transcription drives stochastic Protocadherin α promoter choice
Authors: Canzio Daniele , Nwakeze Chiamaka L. , Horta Adan , Rajkumar Sandy M. , Coffey Eliot L. , Duffy Erin E. , Duffié Rachel , Simon Matthew D. , Lomvardas Stavros , Maniatis Tom 
Published: July 2018

SUMMARYStochastic and combinatorial activation of clustered Protocadherin (Pcdh) α, β, and γ gene promoters generates a cell-surface identity code in individual neurons that functions in neural circuit assembly. Here we show that Pcdhα promoter choice requires transcription of a long noncoding RNA (lncRNA) initiated from newly identified promoters located in the protein coding sequence of each Pcdhα exon. Antisense transcription of the lncRNA through the sense promoter results in its activation and in DNA demethylation of the binding sites for the CCCTC-binding protein, CTCF, located in close proximity to both sense and antisense promoters. Increased CTCF binding promotes the assembly of long-range DNA contacts between the activated promoter and a neuron-specific enhancer, thus locking in the epigenetic state of the stochastically chosen Pcdhα promoter. Examination of this hierarchical molecular mechanism in differentiating olfactory sensory neurons, suggests that antisense Pcdhα transcription is a key prerequisite for stochastic Pcdhα promoter choice in vivo.
DEET feet: Aedes aegypti mosquitoes use their tarsi to sense DEET on contact
Authors: Dennis Emily Jane , Vosshall Leslie Birgit 
Published: July 2018

SummaryDEET (N, N-diethyl-meta-toluamide) is the most effective and broadly used insect repellent, but its mechanism of action is both complex and controversial [1]. Previous work demonstrated that DEET acts both on insect smell [2-6] and taste [7-11] systems. Its olfactory mode of action requires the odorant co-receptor orco [2, 3, 6], while its gustatory repellency is mediated by activation of bitter taste receptors and neurons in the proboscis upon ingestion [8]. Together, these data have led to the assumption that DEET acts only on olfactory and gustatory pathways. We previously observed that orco mutant female Aedes aegypti mosquitoes are strongly attracted to humans even in the presence of DEET, but are rapidly repelled after contacting DEET-treated skin [6]. To understand the basis of this contact chemorepellency, we carried out a series of behavioral experiments and discovered that DEET acts in three distinct ways: through smell, taste, and contact. DEET and bitter tastants are feeding deterrents when ingested, but only DEET is capable of mediating contact repellency on human skin. We show that the repellent touch of DEET is mediated by the tarsal segments of the legs, and not gustatory neurons in the proboscis as previously believed. This work establishes mosquito leg appendages as the actual sensors of DEET, and highlights the existence of an unknown sensory pathway that is independent of bitter taste. These results will inform the search for novel contact-based insect repellents.HighlightsDEET and bitters are both repellent when ingested by Aedes aegypti female mosquitoesOnly DEET is additionally repellent upon contactRepellency of DEET on skin is mediated solely by the legsAny of the three pairs of legs can sense DEET and prevent mosquitoes from biting
DNMT3A-NPM1 mutated acute myeloid leukaemia shows sensitivity to a PARP1 inhibitor combined with daunorubicin in an in vitro model
Authors: Gafencu Grigore , Pileczki Valentina , Jurj Ancuta , Magdo Lorand , Selicean Cristina , Ola Roxana , Ghiaur Gabriel , Berindan-Neagoe Ioana , Tomuleasa Ciprian 
Published: July 2018

SummaryAcute myeloid leukaemia is a neoplasia in need of new treatment approaches. PARP inhibitors are a class of targeted therapeutics for cancer that disrupts dysfunctional DNA damage response in various neoplasia. MLL-AF9 mutated leukaemias are sensitive to combinations of PARP inhibitors and cytotoxic drugs. Moreover, DNMT3A and NPM1 mutations are linked to dysfunctions in DNA damage response. Therefore, we investigated if DNMT3A-NPM1 mutated AML cell line is sensible to PARP inhibitors combined with anthracyclines. Our results show that DNMT3A-NPM1 mutated AML is as sensible to combinations of PARP inhibitors and anthracyclines as MLL-AF9 mutated leukaemias, in an in vitro setting.
Therapeutic gene editing in hematopoietic progenitor cells from a mouse model of Fanconi anemia
Authors: Pino-Barrio MJ , Gimenez Y , Villanueva M , Hildenbeutel M , Sánchez-Dominguez R , Rodriguez-Perales S , Pujol R , Surrallés J , Rio P , Cathomen T , Mussolino C , Bueren JA , Navarro S 
Published: July 2018

ABSTRACTThe promising ability to genetically modify hematopoietic stem and progenitor cells (HSPCs) by precise gene editing remains challenging due to their sensitivity and poor permissiveness. This represents the first evidence of implementing a gene editing strategy in a murinesafe harborlocus that phenotypically corrects primary cells derived from a mouse model of Fanconi anemia (FA).By co-delivering TALENs and a donor therapeuticFANCAcassette template to theMbs85locus (ortholog of the hAAVS1 safe harborlocus), we achieved efficient gene targeting (23%) in FA mouse embryonic fibroblasts (MEFs). This resulted in the phenotypic correction of these cells, as revealed by the improvement of their hypersensitivity to mitomycinC. Moreover, robust evidence of targeted integration was observed in murine WT and FA-A hematopoietic progenitor cells (HPC) reaching mean targeted integration values of 20.98% and 16.33% respectively, with phenotypic correction of FA HPCs. Overall, our results demonstrate the feasibility of implementing a therapeutic targeted integration strategy in a murinesafe harborlocus, such as theMbs85gene, of MEFs and murine HPC from a FA mouse model.