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https://www.readbyqxmd.com/read/28926243/are-we-there-yet-applying-thermodynamic-and-kinetic-profiling-on-embryonic-ectoderm-development-eed-hit-to-lead-program
#1
Ying Wang, Rohinton P Edalji, Sanjay C Panchal, Chaohong C Sun, Stevan W Djuric, Anil Vasudevan
It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (koff) of the lead compounds were observed as the program progressed...
September 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28899895/biomechanical-and-hemodynamic-measures-of-right-ventricular-diastolic-function-translating-tissue-biomechanics-to-clinical-relevance
#2
Sae Jang, Rebecca R Vanderpool, Reza Avazmohammadi, Eugene Lapshin, Timothy N Bachman, Michael Sacks, Marc A Simon
BACKGROUND: Right ventricular (RV) diastolic function has been associated with outcomes for patients with pulmonary hypertension; however, the relationship between biomechanics and hemodynamics in the right ventricle has not been studied. METHODS AND RESULTS: Rat models of RV pressure overload were obtained via pulmonary artery banding (PAB; control, n=7; PAB, n=5). At 3 weeks after banding, RV hemodynamics were measured using a conductance catheter. Biaxial mechanical properties of the RV free wall myocardium were obtained to extrapolate longitudinal and circumferential elastic modulus in low and high strain regions (E1 and E2, respectively)...
September 12, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28898989/role-of-histone-h3k27-trimethylation-loss-as-a-marker-for-malignant-peripheral-nerve-sheath-tumor-in-fine-needle-aspiration-and-small-biopsy-specimens
#3
Jeffrey K Mito, Xiaohua Qian, Leona A Doyle, Jason L Hornick, Vickie Y Jo
Objectives: Accurate diagnosis of malignant peripheral nerve sheath tumor (MPNST) is often challenging on fine-needle aspiration (FNA) or core needle biopsy. Recurrent mutations in EED and SUZ12, which encode subunits of polycomb repressive complex 2 (PRC2), have been identified in 70% to 92% of MPNSTs; PRC2 inactivation leads to loss of trimethylation of lysine 27 of histone H3 (H3K27me3). We evaluated the utility of H3K27me3 immunohistochemistry for distinguishing MPNST from its cytomorphologic mimics...
August 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28892846/caffeine-and-paraxanthine-in-aquatic-systems-global-exposure-distributions-and-probabilistic-risk-assessment
#4
J L Rodríguez-Gil, N Cáceres, R Dafouz, Y Valcárcel
This study presents one of the most complete applications of probabilistic methodologies to the risk assessment of emerging contaminants. Perhaps the most data-rich of these compounds, caffeine, as well as its main metabolite (paraxanthine), were selected for this study. Information for a total of 29,132 individual caffeine and 7442 paraxanthine samples was compiled, including samples where the compounds were not detected. The inclusion of non-detect samples (as censored data) in the estimation of environmental exposure distributions (EEDs) allowed for a realistic characterization of the global presence of these compounds in aquatic systems...
September 6, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28870443/light-at-night-as-an-environmental-endocrine-disruptor
#5
REVIEW
Kathryn L G Russart, Randy J Nelson
Environmental endocrine disruptors (EEDs) are often consequences of human activity; however, the effects of EEDs are not limited to humans. A primary focus over the past ∼30years has been on chemical EEDs, but the repercussions of non-chemical EEDs, such as artificial light at night (LAN), are of increasing interest. The sensitivity of the circadian system to light and the influence of circadian organization on overall physiology and behavior make the system a target for disruption with widespread effects...
September 6, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28864533/first-critical-repressive-h3k27me3-marks-in-embryonic-stem-cells-identified-using-designed-protein-inhibitor
#6
James D Moody, Shiri Levy, Julie Mathieu, Yalan Xing, Woojin Kim, Cheng Dong, Wolfram Tempel, Aaron M Robitaille, Luke T Dang, Amy Ferreccio, Damien Detraux, Sonia Sidhu, Licheng Zhu, Lauren Carter, Chao Xu, Cristina Valensisi, Yuliang Wang, R David Hawkins, Jinrong Min, Randall T Moon, Stuart H Orkin, David Baker, Hannele Ruohola-Baker
The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms...
September 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28858300/development-of-a-high-throughput-fluorescence-polarization-assay-for-the-discovery-of-ezh2-eed-interaction-inhibitors
#7
Mao-Rong Zhu, Dao-Hai Du, Jun-Chi Hu, Lian-Chun Li, Jing-Qiu Liu, Hong Ding, Xiang-Qian Kong, Hua-Liang Jiang, Kai-Xian Chen, Cheng Luo
Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. The interaction of EZH2 with embryonic ectoderm development (EED) is required for EZH2's catalytic activity. Inhibition of the EZH2-EED complex thus represents a novel strategy for interfering with the oncogenic potentials of EZH2 by targeting both its catalytic and non-catalytic functions. To date, there have been no reported high-throughput screening (HTS) assays for inhibitors acting at the EZH2-EED interface...
August 31, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28853738/erratum-the-eed-protein-protein-interaction-inhibitor-a-395-inactivates-the-prc2-complex
#8
Yupeng He, Sujatha Selvaraju, Michael L Curtin, Clarissa G Jakob, Haizhong Zhu, Kenneth M Comess, Bailin Shaw, Juliana The, Evelyne Lima-Fernandes, Magdalena M Szewczyk, Dong Cheng, Kelly L Klinge, Huan-Qiu Li, Marina Pliushchev, Mikkel A Algire, David Maag, Jun Guo, Justin Dietrich, Sanjay C Panchal, Andrew M Petros, Ramzi F Sweis, Maricel Torrent, Lance J Bigelow, Guillermo Senisterra, Fengling Li, Steven Kennedy, Qin Wu, Donald J Osterling, David J Lindley, Wenqing Gao, Scott Galasinski, Dalia Barsyte-Lovejoy, Masoud Vedadi, Fritz G Buchanan, Cheryl H Arrowsmith, Gary G Chiang, Chaohong Sun, William N Pappano
No abstract text is available yet for this article.
July 18, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28846969/effects-of-maternal-exposure-to-bisphenol-af-on-emotional-behaviors-in-adolescent-mice-offspring
#9
Miao Gong, Ziqing Huai, Han Song, Lingyu Cui, Qingjun Guo, Juan Shao, Yuan Gao, Haishui Shi
Exposure to bisphenol A (BPA), one kind of environmental endocrine disruptors (EEDs), exerted significantly detrimental effects on neuro-endocrinological system and related disorders, such as memory dysfunction and depression. Bisphenol AF (BPAF),a newly introduced chemical structurally related to BPA, is used extensively. BPAF has stronger estrogenic activities than BPA. However, the potential neurotoxicological effects of BPAF are still elusive. The present study aimed to investigate the potential effects of maternal BPAF exposure during pregnancy on emotional behaviors of adolescent mice offspring...
August 25, 2017: Chemosphere
https://www.readbyqxmd.com/read/28827272/radiation-dose-from-common-radiological-investigations-and-cumulative-exposure-in-children-with-cystic-fibrosis-an-observational-study-from-a-single-uk-centre
#10
Rebecca Ward, William D Carroll, Paula Cunningham, Sheng-Ang Ho, Mary Jones, Warren Lenney, David Thompson, Francis J Gilchrist
OBJECTIVES: Cumulative radiation exposure is associated with increased risk of malignancy. This is important in cystic fibrosis (CF) as frequent imaging is required to monitor disease progression and diagnose complications. Previous estimates of cumulative radiation are outdated as the imaging was performed on older equipment likely to deliver higher radiation. Our objectives were to determine the radiation dose delivered to children during common radiological investigations using modern equipment and to identify the number of such investigations performed in a cohort of children with CF to calculate their cumulative radiation exposure...
August 21, 2017: BMJ Open
https://www.readbyqxmd.com/read/28823111/welfare-to-work-interventions-and-their-effects-on-the-mental-and-physical-health-of-lone-parents-and-their-children
#11
REVIEW
Marcia Gibson, Hilary Thomson, Kasia Banas, Vittoria Lutje, Martin J McKee, Susan P Martin, Candida Fenton, Clare Bambra, Lyndal Bond
BACKGROUND: Lone parents in high-income countries have high rates of poverty (including in-work poverty) and poor health. Employment requirements for these parents are increasingly common. 'Welfare-to-work' (WtW) interventions involving financial sanctions and incentives, training, childcare subsidies and lifetime limits on benefit receipt have been used to support or mandate employment among lone parents. These and other interventions that affect employment and income may also affect people's health, and it is important to understand the available evidence on these effects in lone parents...
August 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28806728/costing-evidence-for-health-care-decision-making-in-austria-a-systematic-review
#12
Susanne Mayer, Noemi Kiss, Agata Łaszewska, Judit Simon
BACKGROUND: With rising healthcare costs comes an increasing demand for evidence-informed resource allocation using economic evaluations worldwide. Furthermore, standardization of costing and reporting methods both at international and national levels are imperative to make economic evaluations a valid tool for decision-making. The aim of this review is to assess the availability and consistency of costing evidence that could be used for decision-making in Austria. It describes systematically the current economic evaluation and costing studies landscape focusing on the applied costing methods and their reporting standards...
2017: PloS One
https://www.readbyqxmd.com/read/28806608/differential-effects-of-childhood-trauma-subtypes-on-fatigue-and-physical-functioning-in-chronic-fatigue-syndrome
#13
Maud De Venter, Jela Illegems, Rita Van Royen, Greta Moorkens, Bernard G C Sabbe, Filip Van Den Eede
OBJECTIVE: There is wide consensus that childhood trauma plays an important role in the aetiology of chronic fatigue syndrome (CFS). The current study examines the differential effects of childhood trauma subtypes on fatigue and physical functioning in individuals suffering from CFS. METHODS: Participants were 155 well-documented adult, predominantly female CFS patients receiving treatment at the outpatient treatment centre for CFS of the Antwerp University Hospital in Belgium...
July 19, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28801442/bangladesh-environmental-enteric-dysfunction-beed-study-protocol-for-a-community-based-intervention-study-to-validate-non-invasive-biomarkers-of-environmental-enteric-dysfunction
#14
Mustafa Mahfuz, Subhasish Das, Ramendra Nath Mazumder, M Masudur Rahman, Rashidul Haque, Md Muzibur Rahman Bhuiyan, Hasina Akhter, Md Shafiqul Alam Sarker, Dinesh Mondal, Syed Shafi Ahmed Muaz, A S M Bazlul Karim, Stephen M Borowitz, Christopher A Moskaluk, Michael J Barratt, William A Petri, Jeffrey I Gordon, Tahmeed Ahmed
INTRODUCTION: Environmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28777522/recurrent-cutaneous-decompression-illness-after-pfo-device-implantation-a-case-report
#15
Martin Vanden EEde
It is well known that patency of the foramen ovale (PFO) is a risk factor for decompression illness (DCI) in scuba divers, even if they adhere to the currently accepted and used decompression tables (termed "an undeserved hit"). The correction of the PFO through percutaneous closure after DCI is an ongoing discussion. We describe a case of a diver who redeveloped a cutaneous DCI due to a recurrent PFO after initial treatment with an occluder device four years earlier.
November 2016: Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc
https://www.readbyqxmd.com/read/28776573/pancreatic-intraductal-tubulopapillary-neoplasm-is-genetically-distinct-from-intraductal-papillary-mucinous-neoplasm-and-ductal-adenocarcinoma
#16
Olca Basturk, Michael F Berger, Hiroshi Yamaguchi, Volkan Adsay, Gokce Askan, Umesh K Bhanot, Ahmet Zehir, Fatima Carneiro, Seung-Mo Hong, Giuseppe Zamboni, Esra Dikoglu, Vaidehi Jobanputra, Kazimierz O Wrzeszczynski, Serdar Balci, Peter Allen, Naoki Ikari, Shoko Takeuchi, Hiroyuki Akagawa, Atsushi Kanno, Tooru Shimosegawa, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno, Ryota Higuchi, Masakazu Yamamoto, Kyoko Shimizu, Toru Furukawa, David S Klimstra
Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28762137/a-clinicopathologic-study-of-head-and-neck-malignant-peripheral-nerve-sheath-tumors
#17
Adepitan A Owosho, Cherry L Estilo, Joseph M Huryn, Ping Chi, Cristina R Antonescu
Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST...
July 31, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28752843/loss-of-h3k27-trimethylation-is-not-suitable-for-distinguishing-malignant-peripheral-nerve-sheath-tumor-from-melanoma-a-study-of-387-cases-including-mimicking-lesions
#18
Sophie Le Guellec, Nicolas Macagno, Valérie Velasco, Laurence Lamant, Marick Lae, Thomas Filleron, Nausicaa Malissen, Elisabeth Cassagnau, Philippe Terrier, Christine Chevreau, Dominique Ranchere-Vince, Jean-Michel Coindre
The diagnosis of malignant peripheral nerve sheath tumor remains challenging, especially in the sporadic setting. Malignant peripheral nerve sheath tumor is a rare malignancy, and owing to the lack of specific histological criteria, immunohistochemical and molecular diagnostic markers, several differential diagnoses must be considered, in particular melanoma. Recently, inactivation of the polycomb repressive complex 2 (PRC2), induced by inactivating mutations in two of its critical constituents SUZ12 and EED, was reported in a large subset of malignant peripheral nerve sheath tumors...
July 28, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28709054/probing-the-relationship-between-external-and-internal-human-exposure-of-organophosphate-flame-retardants-using-pharmacokinetic-modelling
#19
Thuy T Bui, Fuchao Xu, Nele Van den Eede, Anna Palm Cousins, Adrian Covaci, Ian T Cousins
Human external exposure (i.e. intake) of organophosphate flame retardants (PFRs) has recently been quantified, but no link has yet been established between external and internal exposure. In this study, we used a pharmacokinetic (PK) model to probe the relationship between external and internal exposure data for three PFRs (EHDPHP, TNBP and TPHP) available for a Norwegian cohort of 61 individuals from 61 different households. Using current literature on metabolism of PFRs, we predicted the metabolite serum/urine concentrations and compared it to measured data from the study population...
November 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28704368/mouse-models-of-17q21-31-microdeletion-and-microduplication-syndromes-highlight-the-importance-of-kansl1-for-cognition
#20
Thomas Arbogast, Giovanni Iacono, Claire Chevalier, Nurudeen O Afinowi, Xander Houbaert, Matthijs C van Eede, Christine Laliberte, Marie-Christine Birling, Katrin Linda, Hamid Meziane, Mohammed Selloum, Tania Sorg, Nael Nadif Kasri, David A Koolen, Henk G Stunnenberg, R Mark Henkelman, Maksym Kopanitsa, Yann Humeau, Bert B A De Vries, Yann Herault
Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants in the KANSL1 gene. The reciprocal 17q21.31 microduplication syndrome is associated with psychomotor delay, and reduced social interaction. To investigate the pathophysiology of 17q21.31 microdeletion and microduplication syndromes, we generated three mouse models: 1) the deletion (Del/+); or 2) the reciprocal duplication (Dup/+) of the 17q21...
July 2017: PLoS Genetics
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