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https://www.readbyqxmd.com/read/28918098/identifying-novel-factor-xiia-inhibitors-with-pca-ga-svm-developed-vhts-models
#1
Jonathan Jun Feng Chen, Donald P Visco
There currently is renewed interest in blood clotting Factor XII as a potential target for thrombosis inhibition. Historically untargeted, there is little drug information with which to start drug candidate searches. Typical high-throughput screening can identify potential drug candidates, but is inefficient. Virtual high-throughput screening can be used to raise efficiency by focusing experimental efforts on compounds predicted to be active and is applied here to identify new Factor XIIa inhibitors. We combine principal component analysis, genetic algorithm and support vector machine to create the models used in the virtual high-throughput screening...
September 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28915237/dna-replication-stress-restricts-ribosomal-dna-copy-number
#2
Devika Salim, William D Bradford, Amy Freeland, Gillian Cady, Jianmin Wang, Steven C Pruitt, Jennifer L Gerton
Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen the yeast conditional temperature-sensitive mutant collection of essential genes...
September 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28912585/matrisome-profiling-during-intervertebral-disc-development-and-ageing
#3
Joana Caldeira, Cátia Santa, Hugo Osório, Maria Molinos, Bruno Manadas, Raquel Gonçalves, Mário Barbosa
Intervertebral disc (IVD) degeneration is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. The changes that occur in the disc with age have been under investigation. However, a thorough study of ECM profiling is needed, to better understand IVD development and age-associated degeneration. As so, iTRAQ LC-MS/MS analysis of foetus, young and old bovine NPs, was performed to define the NP matrisome...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898903/inhibition-of-factors-xi-and-xii-for-prevention-of-thrombosis-induced-by-artificial-surfaces
#4
Benjamin Tillman, David Gailani
No abstract text is available yet for this article.
September 12, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28875494/abundance-of-small-mammals-in-the-atlantic-forest-asmaf-a-data-set-for-analyzing-tropical-community-patterns
#5
Marcos S L Figueiredo, Camila S Barros, Ana C Delciellos, Edú B Guerra, Pedro Cordeiro-Estrela, Maja Kajin, Martin R Alvarez, Paulo H Asfora, Diego Astúa, Helena G Bergallo, Rui Cerqueira, Lena Geise, Rosana Gentile, Carlos Eduardo V Grelle, Gilson E Iack-Ximenes, Leonardo C Oliveira, Marcelo Weksler, Marcus V Vieira
Local abundance results from the interaction between populational and environmental processes. The abundance of the species in a community is also one of the most basic descriptors of its structure. Despite its importance, information about species abundances is fragmentary, creating a knowledge gap about species abundances known as Prestonian Shortfall. Here we present a comprehensive dataset of small mammal abundance in the Atlantic Forest. Data were extracted from 114 published sources and from unpublished data collected by our research groups spanning from 1943 to 2017...
September 6, 2017: Ecology
https://www.readbyqxmd.com/read/28835790/n-acylbenzenesulfonamide-dihydro-1-3-4-oxadiazole-hybrids-seeking-selectivity-toward-carbonic-anhydrase-isoforms
#6
Giulia Bianco, Rita Meleddu, Simona Distinto, Filippo Cottiglia, Marco Gaspari, Claudia Melis, Angela Corona, Rossella Angius, Andrea Angeli, Domenico Taverna, Stefano Alcaro, Janis Leitans, Andris Kazaks, Kaspars Tars, Claudiu T Supuran, Elias Maccioni
A series of N-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids (EMAC8000a-m) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of EMAC8000d racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data...
August 10, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28816340/coagulation-factor-xii-regulates-inflammatory-responses-in-human-lungs
#7
Rosanna Hess, Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Gregor Warnecke, Hans-Gerd Fieguth, Steven de Maat, Coen Maas, Francesco Bonella, Klaus T Preissner, Benjamin Weiss, Liliana Schaefer, Wolfgang M Kuebler, Philipp Markart, Malgorzata Wygrecka
Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array...
August 17, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28808141/a-critical-role-for-plasma-kallikrein-in-the-pathogenesis-of-autoantibody-induced-arthritis
#8
Aizhen Yang, Junsong Zhou, Bo Wang, Jihong Dai, Robert W Colman, Wenchao Song, Yi Wu
The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis...
August 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28804834/one-stage-factor-viii-assays
#9
Elizabeth Duncan, Susan Rodgers
Coagulation factor assays using one-stage methodology are widely used to measure factor levels for the purpose of detecting a deficiency, or to monitor replacement therapy. In this chapter, we focus on a method to measure Factor VIII coagulant activity (FVIII:C) by the one-stage assay (FVIII:C-1), with extra information provided to also allow this method to apply to Factor IX (FIX), Factor XI (FXI), and Factor XII (FXII). From the perspective of laboratory testing, these factors are components of the "intrinsic" coagulation pathway and are all measured in test systems based on the correction of the Activated Partial Thromboplastin Time (APTT)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28798744/the-mast-cell-contact-and-coagulation-system-connection-in-anaphylaxis
#10
REVIEW
Mar Guilarte, Anna Sala-Cunill, Olga Luengo, Moisés Labrador-Horrillo, Victoria Cardona
Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28754139/evidence-of-altered-haemostasis-in-an-ovine-model-of-venovenous-extracorporeal-membrane-oxygenation-support
#11
Margaret R Passmore, Yoke L Fung, Gabriela Simonova, Samuel R Foley, Sara D Diab, Kimble R Dunster, Michelle M Spanevello, Charles I McDonald, John-Paul Tung, Natalie M Pecheniuk, Karen Hay, Kiran Shekar, John F Fraser
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving modality used in the management of cardiopulmonary failure that is refractory to conventional medical and surgical therapies. The major problems clinicians face are bleeding and clotting, which can occur simultaneously. To discern the impact of pulmonary injury and ECMO on the host's haemostatic response, we developed an ovine model of smoke-induced acute lung injury (S-ALI) and ECMO. The aims of this study were to determine if the ECMO circuit itself altered haemostasis and if this was augmented in a host with pulmonary injury...
July 29, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28745506/structure-dependent-hematological-effects-of-per-and-polyfluoroalkyl-substances-on-activation-of-plasma-kallikrein-kinin-system-cascade
#12
Qian S Liu, Yuzhen Sun, Guangbo Qu, Yanmin Long, Xingchen Zhao, Aiqian Zhang, Qunfang Zhou, Ligang Hu, Guibin Jiang
Per- and polyfluoroalkyl substances (PFASs) are a global concern because of their ubiquitous occurrence and high persistence in human blood, and increasing amounts of unidentified fluorinated compounds are now becoming new exposure issues. This study aims to investigate the structure-related effects of PFASs on the activation of the plasma kallikrein-kinin system (KKS). The effects of 20 PFASs and the related long-chain aliphatic compounds were screened, and their binding affinities for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were evaluated by molecular docking analysis...
August 15, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28743596/the-plasma-contact-system-a-protease-cascade-at-the-nexus-of-inflammation-coagulation-and-immunity
#13
REVIEW
Henri Weidmann, Laura Heikaus, Andy T Long, Clément Naudin, Hartmut Schlüter, Thomas Renné
The contact system is a potent procoagulant and proinflammatory plasma protease cascade that is initiated by binding ("contact")-induced, auto-activation of factor XII zymogen. Formed active serine protease FXIIa then cleaves plasma prekallikrein to kallikrein that in turn liberates the mediator bradykinin from its precursor high molecular weight kininogen. Bradykinin induces inflammation with implications for host defense and innate immunity. FXIIa also triggers the intrinsic pathway of coagulation that has been shown to critically contribute to thrombosis...
July 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28731874/novel-targets-for-anticoagulants-lacking-bleeding-risk
#14
Julia K Bickmann, Trevor Baglin, Joost C M Meijers, Thomas Renné
PURPOSE OF REVIEW: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites...
September 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28715096/effect-of-avulsion-storage-media-on-periodontal-ligament-fibroblast-differentiation
#15
İrem Bağ, Sibel Yildirim
BACKGROUND/AIM: An avulsed tooth must be stored in a solution which maintains periodontal ligament (PDL) cell viability. The aim of this study was to compare the effects of Hank's balanced salt solution (HBSS) and milk on the differentiation of PDL fibroblasts. MATERIALS AND METHODS: Eighteen extracted third molars, (n = 3 for each group), were immersed in HBSS, milk, and Dulbecco's modified Eagle medium-Ham's F12 (DMEM-F12) at 4°C for 30- to 60 minutes or 12 hours...
July 17, 2017: Dental Traumatology: Official Publication of International Association for Dental Traumatology
https://www.readbyqxmd.com/read/28714475/acylated-heptapeptide-binds-albumin-with-high-affinity-and-application-as-tag-furnishes-long-acting-peptides
#16
Alessandro Zorzi, Simon J Middendorp, Jonas Wilbs, Kaycie Deyle, Christian Heinis
The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment of a broad range of diseases that require prolonged drug half-lives. An intriguing approach for extending peptide circulation times works through a 'piggy-back' strategy in which peptides bind via a ligand to the long-lived serum protein albumin. In accordance with this strategy, we developed an easily synthesized albumin-binding ligand based on a peptide-fatty acid chimera that has a high affinity for human albumin (Kd=39 nM)...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28694557/overexpression-of-mir-24-is-involved-in-the-formation-of-hypocoagulation-state-after-severe-trauma-by-inhibiting-the-synthesis-of-coagulation-factor-x
#17
Lu-Jia Chen, Lian Yang, Xing Cheng, Yin-Kai Xue, Li-Bo Chen
BACKGROUND: Dysregulation of microRNAs may contribute to the progression of trauma-induced coagulopathy (TIC). We aimed to explore the biological function that miRNA-24-3p (miR-24) might have in coagulation factor deficiency after major trauma and TIC. METHODS: 15 healthy volunteers and 36 severe trauma patients (Injury Severity Score ≥ 16 were enrolled. TIC was determined as the initial international normalized ratio >1.5. The miR-24 expression and concentrations of factor X (FX) and factor XII in plasma were measured...
2017: Disease Markers
https://www.readbyqxmd.com/read/28692431/differing-mechanisms-of-thrombin-generation-in-live-haematological-and-solid-cancer-cells-determined-by-calibrated-automated-thrombography
#18
Mufuliat Adeola Adesanya, Anthony Maraveyas, Leigh Madden
: Calibrated automated thrombography (CAT) is emerging as a reliable tool for real-time estimation of thrombin generation potential. There is a clinical need for knowledge about the pathways underlying the thrombotic phenotype of different malignancies. Cells from solid (e.g. pancreatic cancer; n = 7) and malignant haematological cell lines (e.g. multiple myeloma; n = 5) were evaluated for thrombin generation, using CAT, with the addition of control plasma (NormTrol; Helena Biosciences, Gateshead, UK)) or plasma deficient in coagulation factors VII and XII...
July 7, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28688220/assessment-of-the-protein-interaction-between-coagulation-factor%C3%A2-xii-and-corn-trypsin-inhibitor-by-molecular-docking-and-biochemical-validation
#19
B K Hamad, M Pathak, R Manna, P M Fischer, J Emsley, L V Dekker
Essentials Corn Trypsin Inhibitor (CTI) is a selective inhibitor of coagulation Factor XII (FXII). Molecular modelling of the CTI-FXIIa complex suggested a canonical inhibitor binding mode. Mutagenesis revealed the CTI inhibitory loop and helices α1 and α2 mediate the interaction. This confirms that CTI inhibits FXII in canonical fashion and validates the molecular model. SUMMARY: Background Corn trypsin inhibitor (CTI) has selectivity for the serine proteases coagulation factor XII and trypsin...
July 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28661939/interactions-of-%C3%AE-amyloid-peptide-with-fibrinogen-and-coagulation-factor-xii-may-contribute-to-alzheimer-s-disease
#20
Hyung J Ahn, Zu-Lin Chen, Daria Zamolodchikov, Erin H Norris, Sidney Strickland
PURPOSE OF REVIEW: To review the evidence that the Alzheimer peptide β-amyloid interacts with the blood coagulation system and influences the pathophysiology of the disease. RECENT FINDINGS: β-amyloid can interact with fibrinogen and blood coagulation factor XII and trigger ischemia and inflammation. SUMMARY: β-amyloid interacts with fibrinogen and factor XII. These interactions can lead to increased clotting, abnormal clot formation, persistent fibrin deposition, and generation of proinflammatory molecules...
September 2017: Current Opinion in Hematology
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