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TOM complex

Ana Trapero, Angela Pacitto, Vinayak Singh, Mohamad Sabbah, Anthony G Coyne, Valerie Mizrahi, Tom L Blundell, David B Ascher, Chris Abell
Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5´-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible (Mth) IMPDH(ΔCBS) inhibitors identified a low affinity phenylimidazole derivative...
March 16, 2018: Journal of Medicinal Chemistry
Alessandra Livigni, Laura O'Hara, Marta E Polak, Tim Angus, Derek W Wright, Lee B Smith, Tom C Freeman
A major endeavor of systems biology is the construction of graphical and computational models of biological pathways as a means to better understand their structure and function. Here, we present a protocol for a biologist-friendly graphical modeling scheme that facilitates the construction of detailed network diagrams, summarizing the components of a biological pathway (such as proteins and biochemicals) and illustrating how they interact. These diagrams can then be used to simulate activity flow through a pathway, thereby modeling its dynamic behavior...
April 2018: Nature Protocols
He Chen, Jiacheng Yao, Yusi Fu, Yuhong Pang, Jianbin Wang, Yanyi Huang
The next generation sequencing (NGS) technologies have been rapidly evolved and applied to various research fields, but often suffer from losing long-range information due to short library size and read length. Here, we develop a simple, cost-efficient and versatile NGS library preparation method, called tagmentation on microbeads (TOM). This method is capable of recovering long-range information through tagmentation mediated by microbead-immobilized transposomes. Using transposomes with DNA barcodes to identically labeling adjacent sequences during tagmentation, we can restore inter-read connection of each fragment from original DNA molecule by fragment-barcode linkage after sequencing...
March 15, 2018: ACS Applied Materials & Interfaces
Sunewang Wang, Dominic Prieschl, James Mattock, Merle Arrowsmith, Conor Pranckevicius, Tom Stennett, Rian Dewhurst, Alfredo Vargas, Holger Braunschweig
Herein we report the discovery that two bottleable, neutral, base-stabilized diborane(5) compounds are able to bind strongly to a number of copper(I) complexes exclusively through their B-B bond. The resulting complexes represent the first known complexes containing unsupported, neutral σB-B diborane ligands. Single-crystal X-ray analyses of these complexes show that the X-Cu moiety (X = Cl, OTf, C6F5) lies opposite the bridging hydrogen of the diborane and is near perpendicular to the B-B bond, interacting almost equally with both boron atoms and causing a B-B bond elongation...
March 14, 2018: Angewandte Chemie
Christopher A Stevens, Jeroen Daamen, Emma Gaudrain, Tom Renkema, Jakob Dirk Top, Fokie Cnossen, Niels A Taatgen
Training negotiation is difficult because it is a complex, dynamic activity that involves multiple parties. It is often not clear how to create situations in which students can practice negotiation or how to measure students' progress. Some have begun to address these issues by creating artificial software agents with which students can train. These agents have the advantage that they can be "reset," and played against multiple times. This allows students to learn from their mistakes and try different strategies...
2018: Frontiers in Psychology
Theodora A M Claushuis, Annelou I P Van Der Veen, Janneke Horn, Marcus J Schultz, Riekelt H Houtkooper, Cornelis Van 't Veer, Tom Van Der Poll
Platelets and Toll-like receptor (TLR) signalling play a role in the immune response during sepsis. Although preclinical knowledge about the role of platelet TLR signalling is increasing, data during human sepsis are less abundant. Moreover, controversy remains about the effect of the TLR4 agonist lipopolysaccharide (LPS) on platelet activation. We therefore assessed platelet TLR expression during human and murine sepsis. Moreover, we investigated the effect of TLR4 signalling on platelet activation and TLR expression...
March 12, 2018: Platelets
Wei Xuan, Davy Opdenacker, Steffen Vanneste, Tom Beeckman
Plants have an amazing capacity to adjust their growth to environmental limitations. This is particularly relevant for the root system that tunes its developmental pattern to mine the soil for water and nutrients while avoiding patches of soil that contain biotic and abiotic stress agents. Because most developmental processes are taking place gradually while roots are growing, it is often difficult to correlate gene expression events with specific developmental processes that are not necessarily coinciding in time and space...
2018: Methods in Molecular Biology
Hok Khim Fam, Kunho Choi, Lauren Fougner, Chinten James Lim, Cornelius F Boerkoel
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a nuclear and mitochondrial protein that in nuclei and in vitro repairs blocked 3' DNA termini such as 3' phosphotyrosine conjugates resulting from stalling of topoisomerase I-DNA intermediates. Its mutation also causes spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1). Because Tdp1 colocalizes with mitochondria following oxidative stress, we hypothesized that Tdp1 repairs mitochondrial DNA (mtDNA) and that mtDNA damage mediates entry of Tdp1 into the mitochondria...
March 9, 2018: Scientific Reports
Anna Zuk, Paul M Palevsky, Linda Fried, Frank E Harrell, Samina Khan, Dianne B McKay, Luke Devey, Lakhmir Chawla, Mark de Caestecker, James S Kaufman, B Taylor Thompson, Anupam Agarwal, Tom Greene, Mark Douglas Okusa, Joseph V Bonventre, Laura M Dember, Kathleen D Liu, Benjamin D Humphreys, Daniel Gossett, Yining Xie, Jenna M Norton, Paul L Kimmel, Robert A Star
AKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the "AKI Outcomes: Overcoming Barriers in AKI" workshop on February 10-12, 2015...
March 9, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Ingmar L Defize, Bernadette Schurink, Teus J Weijs, Tom A P Roeling, Jelle P Ruurda, Richard van Hillegersberg, Ronald L A W Bleys
BACKGROUND: Injury and subsequent leakage of unrecognized thoracic duct tributaries during transthoracic esophagectomy may lead to chylothorax. Therefore, we hypothesized that thoracic duct anatomy at the diaphragm is more complex than currently recognized and aimed to provide a detailed description of the anatomy of the thoracic duct at the diaphragm. BASIC PROCEDURES: The thoracic duct and its tributaries were dissected in 7 (2 male and 5 female) embalmed human cadavers...
March 3, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Keren Baranes-Bachar, Adva Levy-Barda, Judith Oehler, Dylan A Reid, Isabel Soria-Bretones, Ty C Voss, Dudley Chung, Yoon Park, Chao Liu, Jong-Bok Yoon, Wei Li, Graham Dellaire, Tom Misteli, Pablo Huertas, Eli Rothenberg, Kristijan Ramadan, Yael Ziv, Yosef Shiloh
Double-strand breaks (DSBs) are critical DNA lesions that robustly activate the elaborate DNA damage response (DDR) network. We identified a critical player in DDR fine-tuning: the E3/E4 ubiquitin ligase UBE4A. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites...
March 1, 2018: Molecular Cell
Sahadev T Reddy, Ngoc L Thai, Jose Oliva, Kusum B Tom, Michael K Dishart, Mark Doyle, June A Yamrozik, Ronald B Williams, Moneal Shah, Adil Wani, Anil Singh, Rishi Maheswary, Robert W W Biederman
BACKGROUND: The preoperative workup of orthotopic liver transplantation (OLT) patents is practically complex given the need for multiple imaging modalities. We recently demonstrated in our Proof-of-Concept study the value of a One-Stop-Shop approach using Cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of HCC as well as cardiovascular risk assessment is critically important in these patients...
March 2, 2018: Clinical Transplantation
Manu Beerens, Xabier L Aranguren, Benoit Hendrickx, Wouter Dheedene, Tom Dresselaers, Uwe Himmelreich, Catherine Verfaillie, Aernout Luttun
Lymphatic capillary growth is an integral part of wound healing, yet, the combined effectiveness of stem/progenitor cells on lymphatic and blood vascular regeneration in wounds needs further exploration. Stem/progenitor cell transplantation also emerged as an approach to cure lymphedema, a condition caused by lymphatic system deficiency. While lymphedema treatment requires lymphatic system restoration from the capillary to the collector level, it remains undetermined whether stem/progenitor cells support a complex regenerative response across the entire anatomical spectrum of the system...
March 1, 2018: Scientific Reports
Mahta Karimpoor, Nathan W Churchill, Fred Tam, Corinne E Fischer, Tom A Schweizer, Simon J Graham
Handwriting is a complex human activity that engages a blend of cognitive and visual motor skills. Current understanding of the neural correlates of handwriting has largely come from lesion studies of patients with impaired handwriting. Task-based fMRI studies would be useful to supplement this work. To address concerns over ecological validity, previously we developed a fMRI-compatible, computerized tablet system for writing and drawing including visual feedback of hand position and an augmented reality display...
2018: Frontiers in Human Neuroscience
Anub Mathew Thomas, Camilla Schjalm, Per H Nilsson, Paal H H Lindenskov, Runa Rørtveit, Rønnaug Solberg, Ola Didrik Saugstad, Magnus M Berglund, Patrik Strömberg, Corinna Lau, Terje Espevik, Johan Høgset Jansen, Albert Castellheim, Tom Eirik Mollnes, Andreas Barratt-Due
BACKGROUND: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors. OBJECTIVES: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model...
February 27, 2018: Neonatology
Tom D Bunney, Alison J Inglis, Domenico Sanfelice, Brendan Farrell, Christopher J Kerr, Gary S Thompson, Glenn R Masson, Nethaji Thiyagarajan, Dmitri I Svergun, Roger L Williams, Alexander L Breeze, Matilda Katan
Receptor tyrosine kinase FGFR3 is involved in many signaling networks and is frequently mutated in developmental disorders and cancer. The Hsp90/Cdc37 chaperone system is essential for function of normal and neoplastic cells. Here we uncover the mechanistic inter-relationships between these proteins by combining approaches including NMR, HDX-MS, and SAXS. We show that several disease-linked mutations convert FGFR3 to a stronger client, where the determinant underpinning client strength involves an allosteric network through the N-lobe and at the lobe interface...
February 16, 2018: Structure
Rebecca Troisi, Tone Bjørge, Mika Gissler, Tom Grotmol, Cari M Kitahara, Solbjørg Makalani Myrtveit Saether, Anne Gulbech Ording, Camilla Sköld, Henrik Toft Sørensen, Britton Trabert, Ingrid Glimelius
An understanding of the origin of cancer is critical for cancer prevention and treatment. Complex biological mechanisms promote carcinogenesis, and there is increasing evidence that pregnancy-related exposures influence fetal growth cell division and organ functioning and may have a long-lasting impact on health and disease susceptibility in the mothers and offspring. Nulliparity is an established risk factor for breast, ovarian, endometrial, and possibly pancreatic cancer, while the risk of kidney cancer is elevated in parous compared with nulliparous women...
February 24, 2018: Journal of Internal Medicine
Creina Slator, Zara Molphy, Vickie McKee, Conor Long, Tom Brown, Andrew Kellett
In order to expand the current repertoire of cancer treatments and to help circumvent limitations associated with resistance, the identification of new metallodrugs with high potency and novel mechanisms of action is of significant importance. Here we present a class of di-copper(II) complex based on the synthetic chemical nuclease [Cu(Phen)2]+ (where Phen = 1,10-phenanthroline) that is selective against solid epithelial cancer cells from the National Cancer Institute's 60 human cell line panel (NCI-60). Two metallodrug leads are studied and in each case two [Cu(Phen)2]+ units are bridged by a dicarboxylate linker but the length and rigidity of the linkers differ distinctly...
February 21, 2018: Nucleic Acids Research
Laurie A Graham, Gregory C Finnigan, Patricia M Kane
Tom Stevens' lab has explored the subunit composition and assembly of the yeast V-ATPase for more than 30 years. Early studies helped establish yeast as the predominant model system for study of V-ATPase proton pumps and led to the discovery of protein splicing of the V-ATPase catalytic subunit. The Vma- phenotype, characteristic of loss of V-ATPase activity in yeast was key in determining the enzyme's subunit composition via yeast genetics. V-ATPase subunit composition proved to be highly conserved among eukaryotes...
February 23, 2018: Traffic
Eric Duchaud, Tatiana Rochat, Christophe Habib, Paul Barbier, Valentin Loux, Cyprien Guérin, Inger Dalsgaard, Lone Madsen, Hanne Nilsen, Krister Sundell, Tom Wiklund, Nicole Strepparava, Thomas Wahli, Greta Caburlotto, Amedeo Manfrin, Gregory D Wiens, Erina Fujiwara-Nagata, Ruben Avendaño-Herrera, Jean-François Bernardet, Pierre Nicolas
Flavobacterium psychrophilum , the etiological agent of rainbow trout fry syndrome and bacterial cold-water disease in salmonid fish, is currently one of the main bacterial pathogens hampering the productivity of salmonid farming worldwide. In this study, the genomic diversity of the F. psychrophilum species is analyzed using a set of 41 genomes, including 30 newly sequenced isolates. These were selected on the basis of available MLST data with the two-fold objective of maximizing the coverage of the species diversity and of allowing a focus on the main clonal complex (CC-ST10) infecting farmed rainbow trout ( Oncorhynchus mykiss ) worldwide...
2018: Frontiers in Microbiology
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