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Wei-Wen Sun, Jillian Romsdahl, Chun-Jun Guo, Clay C C Wang
Acetylaranotin is an epipolythiodiketopiperazine (ETP) secondary metabolite with a broad range of bioactivities. We demonstrated that ATEG_01465.1 located outside of acetylaranotin gene cluster is responsible for catalyzing the S-methylation of its biosynthetic pathway. Combining the previous characterization of acetylaranotin biosynthetic gene cluster together with the identification of its S-methyltransferase provides a means to obtain second-generation acetylaranotin derivatives previously inaccessible. By permutations of targeted deletions of ATEG_01465...
August 7, 2018: Fungal Genetics and Biology: FG & B
Corinne Cather, Mary F Brunette, Kim T Mueser, Steven F Babbin, Robert Rosenheck, Christoph U Correll, Piper Kalos-Meyer
Lifetime co-occurring substance use disorders are common at the time of presentation for treatment of a first episode of primary psychosis and persistent substance use disorder (SUD) leads to poorer outcomes. We assessed whether the NAVIGATE program, a coordinated specialty care service that includes optional substance abuse content reduced substance use compared to usual care in 404 individuals in the Recovery After Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study. Participants were randomized to two years of NAVIGATE (n = 223) or usual care (n = 181) and assessed monthly for substance use...
July 24, 2018: Psychiatry Research
Julia E Moore, Shusmita Rashid, Jamie S Park, Sobia Khan, Sharon E Straus
BACKGROUND: Few training opportunities are available for implementation practitioners; we designed the Practicing Knowledge Translation (PKT) to address this gap. The goal of PKT is to train practitioners to use evidence and apply implementation science in healthcare settings. The aim of this study was to describe PKT and evaluate participant use of implementation science theories, models, and frameworks (TMFs), knowledge, self-efficacy, and satisfaction and feedback on the course. METHODS: PKT was delivered to implementation practitioners between September 2015 and February 2016 through a 3-day workshop, 11 webinars...
August 6, 2018: Implementation Science: IS
Changshan Wang, Motohiko Oshima, Daisuke Sato, Hirotaka Matsui, Sho Kubota, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Shuhei Koide, Jun Matsubayashi, Makiko Mochizuki-Kashio, Takako Nakano-Yokomizo, Jie Bai, Toshitaka Nagao, Akinori Kanai, Atsushi Iwama, Goro Sashida
Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a new pathological entity with poor outcomes in T cell ALL (T-ALL) that is characterized by a high incidence of loss-of-function mutations in polycomb repressive complex 2 (PRC2) genes. We generated a mouse model of ETP-ALL by deleting Ezh2, one of the PRC2 genes, in p53-null hematopoietic cells. The loss of Ezh2 in p53-null hematopoietic cells impeded the differentiation of ETPs and eventually induced ETP-ALL-like disease in mice, indicating that PRC2 functions as a bona fide tumor suppressor in ETPs...
August 6, 2018: Journal of Clinical Investigation
Qing Wang, Ran Yan, Nancy Pinnell, Anna C McCarter, Yeonjoo Oh, Yiran Liu, Cher Sha, Noah F Garber, Yitong Chen, Qingqing Wu, Chia-Jui Ku, Ivy Tran, Amparo Serna Alarcon, Rork Kuick, James Douglas Engel, Ivan Maillard, Tomasz Cierpicki, Mark Y Chiang
Notch1 signaling must elevate to high levels in order to drive the proliferation of CD4- CD8- double-negative (DN) thymocytes and progression to the CD4+ CD8+ double-positive (DP) stage through beta-selection. During this critical phase of pre-T cell development, which is also known as the DN-DP transition, it is unclear whether the Notch1 transcriptional complex strengthens its signal output as a discrete unit or through cofactors. We previously showed that the protein inhibitor of activated STAT (PIAS)-like coactivator Zmiz1 is a context-dependent cofactor of Notch1 in T-cell leukemia...
August 3, 2018: Blood
Chiara Russo, Marina Isidori, Jessica A Deaver, Helen C Poynton
The use of anticancer drugs in chemotherapy is increasing, leading to growing environmental concentrations of imatinib mesylate (IMA), cisplatinum (CDDP), and etoposide (ETP) in aquatic systems. Previous studies have shown that these anticancer drugs cause DNA damage in the crustacean Daphnia magna at low, environmentally relevant concentrations. To explore the mechanism of action of these compounds and the downstream effects of DNA damage on D. magna growth and development at a sensitive life stage, we exposed neonates to low level concentrations equivalent to those that elicit DNA damage (IMA: 2000 ng/L, ETP: 300 ng/L, CDDP: 10 ng/L) and performed transcriptomic analysis using an RNA-seq approach...
July 19, 2018: Aquatic Toxicology
Daniel H Scharf, Jan D Dworschak, Pranatchareeya Chankhamjon, Kirstin Scherlach, Thorsten Heinekamp, Axel A Brakhage, Christian Hertweck
Gliotoxin is a virulence factor of the human pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. The activity of this metabolite is mediated by a transannular disulfide bond, a hallmark of the epipolythiodiketopiperazine (ETP) family. Through the creation of fungal gene deletion mutants, metabolic profiling and heterologous protein expression, we unveiled the critical role of the cytochrome P450 monooxygenase (CYP450) GliC for the stepwise bishydroxylation of the diketopiperazine (DKP) core...
August 3, 2018: ACS Chemical Biology
Gethin Boyle, Agnieszka Kuffel, Kiran Parmar, Kirsty Gibson, Megan Smith, Aidan Grehan, Beverley J Hunt, David J Chambers
BACKGROUND: Cardiac surgery using cardiopulmonary bypass (CPB) is associated with a coagulopathy due to haemodilution, thrombocytopenia and platelet dysfunction and the activation of coagulation and fibrinolysis, despite the use of large doses of unfractionated heparin. Conventional red cell salvage may exacerbate post-operative bleeding as plasma containing haemostatic factors is discarded. We hypothesized that a novel cell salvage device (HemoSep) may attenuate haemostatic changes associated with red cell salvage...
August 1, 2018: Perfusion
Yoshihiro Sohtome, Tadahiro Shimazu, Joaquin Barjau, Shinya Fujishiro, Mai Akakabe, Naoki Terayama, Kosuke Dodo, Akihiro Ito, Minoru Yoshida, Yoichi Shinkai, Mikiko Sodeoka
We present a chemical methylome analysis platform to evaluate the inhibitory activity of small molecules towards poorly characterized protein methyltransferases (PMTs), facsilitating to identify syn-HyPA-ETP-2 as a non-histone arginine methyltransferase inhibitor.
August 14, 2018: Chemical Communications: Chem Comm
Stanislawa Bazan-Socha, Pawel Kuczia, Daniel P Potaczek, Lucyna Mastalerz, Agnieszka Cybulska, Lech Zareba, Romy Kremers, Coenraad Hemker, Anetta Undas
BACKGROUND: Recently, we have reported that asthma is characterized by prothrombotic blood alterations, which were related to the low-grade inflammatory state. Inflammation, however, may also lead to vascular dysfunction. The aim of this study was to evaluate plasma levels of cellular fibronectin (cFN), a marker of vascular injury in asthmatics, and to analyze their impact on described previously prothrombotic blood alterations. METHODS: In a cross-sectional study, we investigated 164 adult stable asthmatics and 72 matched controls...
August 2018: Respiratory Medicine
Kamil Kucharczyk, Marek Weiss, Katarzyna Jastrzebska, Magdalena Luczak, Arkadiusz Ptak, Maciej Kozak, Andrzej Mackiewicz, Hanna Dams-Kozlowska
Background: Silk is a biocompatible and biodegradable material, able to self-assemble into different morphological structures. Silk structures may be used for many biomedical applications, including carriers for drug delivery. The authors designed a new bioengineered spider silk protein, EMS2, and examined its property as a carrier of chemotherapeutics. Materials and methods: To obtain EMS protein, the MS2 silk monomer (that was based on the MaSp2 spidroin of Nephila clavipes ) was modified by the addition of a glutamic acid residue...
2018: International Journal of Nanomedicine
Eleni Vrigkou, Iraklis Tsangaris, Stefanos Bonovas, Petros Kopterides, Elias Kyriakou, Dimitrios Konstantonis, Athanasios Pappas, Anastasia Anthi, Argyri Gialeraki, Stylianos E Orfanos, Apostolos Armaganidis, Argyrios Tsantes
There is a complex and not fully elucidated association between pulmonary arterial hypertension (PAH) and coagulation disorders. The goal of this study was to evaluate platelet function, coagulation and fibrinolysis in PAH patients at diagnosis, before PAH-specific treatment initiation. We enrolled 20 healthy controls and 30 PAH patients (20 with connective tissue disease (CTD-PAH) and 10 idiopathic (iPAH)). None of the participants was on any antiplatelet or anticoagulation therapy. Blood samples from PAH patients were collected during the initial right heart catheterization...
July 26, 2018: Platelets
Ramin Artang, Maren Anderson, Paul Riley, Jorn D Nielsen
<AbstractText Label="Background" NlmCategory="UNASSIGNED">There are clinical situations where monitoring direct oral anticoagulants (DOACs) may be useful. The clinical application of thrombin generation assay (TGA) in monitoring the effect of DOACs has not been well established. An ex vivo study was performed to systematically evaluate the anticoagulant effect of dabigatran, rivaroxaban and apixaban on each individual TGA parameter through serial measurements over time to assess suitability of these parameters for monitoring the anticoagulant effect of DOACs...
October 2017: Research and Practice in Thrombosis and Haemostasis
Cheng-Yen Kao, Jenn-Wei Chen, Tsung-Lin Liu, Jing-Jou Yan, Jiunn-Jong Wu
This study investigates the evolution of an Escherichia coli sequence type 219 clone in a patient with recurrent urinary tract infection, comparing isolate EC974 obtained prior to antibiotic treatment and isolate EC1515 recovered after exposure to several β-lactam antibiotics (ceftriaxone, cefixime, and imipenem). EC974 had a smooth colony morphology, while EC1515 had a rough colony morphology on sheep blood agar. RAPD-PCR analysis suggested that both isolates belonged to the same clone. Antimicrobial susceptibility tests showed that EC1515 was more resistant to piperacillin/tazobactam, cefepime, cefpirome, and ertapenem than EC974...
2018: Frontiers in Microbiology
Stephan Fuhrmann, Richard Schabath, Anja Möricke, Martin Zimmermann, Joachim B Kunz, Andreas E Kulozik, Wolf-Dieter Ludwig, Martin Schrappe, Leonid Karawajew, Richard Ratei
This study reports the prognostic impact of the expression of the natural killer cell marker CD56 in a large series of risk-adapted paediatric patients with T cell acute lymphoblastic leukaemia (T-ALL; n = 493) treated within the ALL-Berlin-Frankfurt-Münster (BFM) 2000 protocol. The immunophenotype was analysed centrally at diagnosis using flow cytometry and correlated with clinical parameters and outcome. CD56 expression was detected in 7·1% and early T-cell precursor (ETP) phenotype in 6·7% of all T-ALL patients...
July 20, 2018: British Journal of Haematology
Jochen Blumberger
I review recent experimental measurements probing electron transfer (ET) and electron transport (ETp) through multi-heme cytochromes (MHCs) as well as their theoretical interpretation. Examples include pump-probe spectroscopy of Ru-labeled MHCs aimed at determining heme-heme ET rates in MHCs and the measurement of the I-V characteristics of MHCs in bioelectronic junctions. While the ET mechanism appears to be well established for MHCs in aqueous solution, the ETp mechanism in bioelectronic junctions such as STM remains elusive partly due to the complexities of the electrode-protein interface...
July 13, 2018: Current Opinion in Chemical Biology
Ina Isabella Høiland, Robin Amanda Liang, Kristian Hindberg, Nadezhda Latysheva, Ole-Lars Brekke, Tom Eirik Mollnes, John-Bjarne Hansen
INTRODUCTION: Deep vein thrombosis (DVT) originates in the valvular sinuses of large veins in a local milieu characterized by stasis and severe hypoxia. This may induce complement- and coagulation activation, which potentially increases the risk of venous thromboembolism (VTE). The aim of the present study was to investigate whether the activity of the complement pathways, the level of mannose-binding lectin (MBL) and tissue-factor (TF) induced thrombin generation were associated with risk of unprovoked VTE...
June 30, 2018: Thrombosis Research
Mayada M Elgohary, Maged W Helmy, Elsayeda-Zeinab A Abdelfattah, Doaa M Ragab, Sana M Mortada, Jia-You Fang, Ahmed O Elzoghby
Etoposide (ETP), as a potential treatment for lung cancer, has limited application due to its poor solubility, and systemic side effects. In the current study, we propose inhalable boronate-targeted HSA nanocomposites for combined delivery of ETP and the herbal drug, berberine (BER) for localized therapy of lung cancer. First, ETP was pre-formulated as phospholipid complex (EPC) to enhance drug solubility and facilitate its encapsulation within the hydrophilic albumin nanoparticles (NPs). Second, EPC and BER were then co-loaded with high efficiency into HSA NPs as a synergistic therapy for lung cancer...
July 24, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Delphine Dardalhon-Cuménal, Jérôme Deraze, Camille A Dupont, Valérie Ribeiro, Anne Coléno-Costes, Juliette Pouch, Stéphane Le Crom, Hélène Thomassin, Vincent Debat, Neel B Randsholt, Frédérique Peronnet
In Drosophila, ubiquitous expression of a short Cyclin G isoform generates extreme developmental noise estimated by fluctuating asymmetry (FA), providing a model to tackle developmental stability. This transcriptional cyclin interacts with chromatin regulators of the Enhancer of Trithorax and Polycomb (ETP) and Polycomb families. This led us to investigate the importance of these interactions in developmental stability. Deregulation of Cyclin G highlights an organ intrinsic control of developmental noise, linked to the ETP-interacting domain, and enhanced by mutations in genes encoding members of the Polycomb Repressive complexes PRC1 and PR-DUB...
July 2018: PLoS Genetics
F Artacho-Cordón, M F Fernández, H Frederiksen, L M Iribarne-Durán, I Jiménez-Díaz, F Vela-Soria, A M Andersson, P Martin-Olmedo, F M Peinado, N Olea, J P Arrebola
Urinary concentrations of non-persistent environmental pollutants (npEPs) are widely assessed in biomonitoring studies under the assumption that they are metabolised and eliminated in urine. However, some of these chemicals are moderately lipophilic, and their presence in other biological matrices should also be evaluated to estimate mid/long-term exposure to npEPs and its impact on human health. The present study aims to explore concentrations and potential determinants of npEPs in adipose tissue from a hospital-based adult cohort (GraMo cohort, Southern Spain)...
June 29, 2018: Environment International
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