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https://www.readbyqxmd.com/read/28635271/emerging-chemistry-strategies-for-engineering-native-chromatin
#1
Yael David, Tom W Muir
Chromosomes present one of most challenging of all substrates for biochemical study. This is because genomic DNA is physically associated with an astonishing collection of nuclear factors, which serve to both store the nucleic acid in a stable form, but also grant access to the information it encodes when needed. Understanding this complex molecular choreography is central to the field of epigenetics. One of the great challenges in this area is to move beyond correlative type information, which is now in abundant supply, to the point where we can truly connect the dots at the molecular level...
June 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28633678/variation-in-empiric-coverage-versus-detection-of-methicillin-resistant-staphylococcus-aureus-and-pseudomonas-aeruginosa-in-hospitalizations-for-community-onset-pneumonia-across-128-us-veterans-affairs-medical-centers
#2
Barbara E Jones, Kevin Antoine Brown, Makoto M Jones, Benedikt D Huttner, Tom Greene, Brian C Sauer, Karl Madaras-Kelly, Michael A Rubin, Matthew Bidwell Goetz, Matthew H Samore
OBJECTIVE To examine variation in antibiotic coverage and detection of resistant pathogens in community-onset pneumonia. DESIGN Cross-sectional study. SETTING A total of 128 hospitals in the Veterans Affairs health system. PARTICIPANTS Hospitalizations with a principal diagnosis of pneumonia from 2009 through 2010. METHODS We examined proportions of hospitalizations with empiric antibiotic coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAER) and with initial detection in blood or respiratory cultures...
June 21, 2017: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/28628782/incorporation-of-a-health-economic-modelling-tool-into-public-health-commissioning-evidence-use-in-a-politicised-context
#3
Tom Sanders, Amy Grove, Sarah Salway, Susan Hampshaw, Elizabeth Goyder
This paper explores how commissioners working in an English local government authority (LA) viewed a health economic decision tool for planning services in relation to diabetes. We conducted 15 interviews and 2 focus groups between July 2015 and February 2016, with commissioners (including public health managers, data analysts and council members). Two overlapping themes were identified explaining the obstacles and enablers of using such a tool in commissioning: a) evidence cultures, and b) system interdependency...
June 12, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28617516/incorporation-of-native-antibodies-and-fc-fusion-proteins-on-dna-nanostructures-via-a-modular-conjugation-strategy
#4
Bas J H M Rosier, Glenn A O Cremers, Wouter Engelen, Maarten Merkx, Luc Brunsveld, Tom F A de Greef
A photocrosslinkable protein G variant was used as an adapter protein to covalently and site-specifically conjugate an antibody and an Fc-fusion protein to an oligonucleotide. This modular approach enables straightforward decoration of DNA nanostructures with complex native proteins while retaining their innate binding affinity, allowing precise control over the nanoscale spatial organization of such proteins for in vitro and in vivo biomedical applications.
June 15, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28615137/stress-measurement-in-surgeons-and-residents-using-a-smart-patch
#5
Mariska Weenk, Alexander P B Alken, Lucien J L P G Engelen, Sebastian J H Bredie, Tom H van de Belt, Harry van Goor
BACKGROUND: Stress may negatively affect surgeons' performance during surgical procedures, jeopardizing patient safety. For measuring stress, complex methods are used that cannot record stress real time. This study reports stress measurements in surgeons and residents using a novel patch sensor to identify activities and risk factors of stress. METHODS: In this explorative study, surgeons and residents wore the HealthPatch™ during all daily activities for 2-3 days...
June 6, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28614749/plant-nitrogen-nutrition-sensing-and-signaling
#6
REVIEW
Wei Xuan, Tom Beeckman, Guohua Xu
In response to external fluctuations of nitrogen (N) supplies, plants can activate complex regulatory networks for optimizing N uptake and utilization. In this review, we highlight novel N-responsive sensors, transporters, and signaling molecules recently identified in the dicot Arabidopsis and the monocot rice, and discuss their potential roles in N sensing and signaling. Furthermore, over the last couple of years, N sensing has been shown to be affected by multiple external factors, which act as local signals to trigger systemic signaling coordinated by long-distance mobile signals...
June 11, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28610663/eculizumab-c5-complexes-express-a-c5a-neoepitope-in-vivo-consequences-for-interpretation-of-patient-complement-analyses
#7
Per H Nilsson, Anub Mathew Thomas, Grethe Bergseth, Alice Gustavsen, Elena B Volokhina, Lambertus P van den Heuvel, Andreas Barratt-Due, Tom E Mollnes
The complement system has obtained renewed clinical focus due to increasing number of patients treated with eculizumab, a monoclonal antibody inhibiting cleavage of C5 into C5a and C5b. The FDA approved indications are paroxysmal nocturnal haemoglobinuria and atypical haemolytic uremic syndrome, but many other diseases are candidates for complement inhibition. It has been postulated that eculizumab does not inhibit C5a formation in vivo, in contrast to what would be expected since it blocks C5 cleavage. We recently revealed that this finding was due to a false positive reaction in a C5a assay...
June 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28597142/simple-mindreading-abilities-predict-complex-theory-of-mind-developmental-delay-in-autism-spectrum-disorders
#8
Maria Chiara Pino, Monica Mazza, Melania Mariano, Sara Peretti, Dagmara Dimitriou, Francesco Masedu, Marco Valenti, Fabia Franco
Theory of mind (ToM) is impaired in individuals with autism spectrum disorders (ASD). The aims of this study were to: (i) examine the developmental trajectories of ToM abilities in two different mentalizing tasks in children with ASD compared to TD children; and (ii) to assess if a ToM simple test known as eyes-test could predict performance on the more advanced ToM task, i.e. comic strip test. Based on a sample of 37 children with ASD and 55 TD children, our results revealed slower development at varying rates in all ToM measures in children with ASD, with delayed onset compared to TD children...
June 9, 2017: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/28596542/leukocyte-bim-deficiency-does-not-impact-atherogenesis-in-ldlr-mice-despite-a-pronounced-induction-of-autoimmune-inflammation
#9
Lieve Temmerman, Marijke M Westra, Ilze Bot, Bart J M van Vlijmen, Niek Van Bree, Martine Bot, Kim L L Habets, Tom G H Keulers, Johan van der Vlag, Thomas G Cotter, Theo J C van Berkel, Erik A L Biessen
Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim (-/-) or wild type bone marrow transplanted ldlr (-/-) mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592527/zika-virus-hijacks-stress-granule-proteins-and-modulates-the-host-stress-response
#10
Shangmei Hou, Anil Kumar, Zaikun Xu, Adriana M Airo, Iryna Stryapunina, Cheung Pang Wong, William Branton, Egor Tchesnokov, Matthias Götte, Christopher Power, Tom C Hobman
Zika virus (ZIKV), a member of the Flaviviridae family, has recently emerged as an important human pathogen with increasing economic and health impact worldwide. Because of its teratogenic nature and association with the serious neurological condition Guillain-Barré syndrome, a tremendous amount of effort has focused on understanding ZIKV pathogenesis. To gain further insights into ZIKV interaction with host cells, we investigated how this pathogen affects stress response pathways. While ZIKV infection induces stress signaling that leads to phosphorylation of eIF2α and cellular translational arrest, stress granule (SG) formation was inhibited...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28587856/optimization-and-characterization-of-a-murine-lung-infection-model-for-the-evaluation-of-novel-therapeutics-against-burkholderia-cenocepacia
#11
Bieke Vanhoutte, Davie Cappoen, Bidart de Macedo Maira, Freya Cools, Eveline Torfs, Tom Coenye, Wim Martinet, Guy Caljon, Louis Maes, Peter Delputte, Paul Cos
Several B. cenocepacia mouse models are available to study the pulmonary infection by this Burkholderia cepacia complex (BCC) species. However, a characterized B. cenocepacia mouse model to evaluate the efficacy of potential new antibacterial therapies is not yet described. Therefore, we optimized and validated the course of infection (i.e. bacterial proliferation in lung, liver and spleen) and the efficacy of a reference antibiotic, tobramycin (TOB), in a mouse lung infection model. Furthermore, the local immune response and histological changes in lung tissue were studied during infection and treatment...
June 3, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28586827/genome-wide-pleiotropy-between-parkinson-disease-and-autoimmune-diseases
#12
Aree Witoelar, Iris E Jansen, Yunpeng Wang, Rahul S Desikan, J Raphael Gibbs, Cornelis Blauwendraat, Wesley K Thompson, Dena G Hernandez, Srdjan Djurovic, Andrew J Schork, Francesco Bettella, David Ellinghaus, Andre Franke, Benedicte A Lie, Linda K McEvoy, Tom H Karlsen, Suzanne Lesage, Huw R Morris, Alexis Brice, Nicholas W Wood, Peter Heutink, John Hardy, Andrew B Singleton, Anders M Dale, Thomas Gasser, Ole A Andreassen, Manu Sharma
Importance: Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. Objectives: To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach...
June 5, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28576471/connection-of-protein-transport-and-organelle-contact-sites-in-mitochondria
#13
REVIEW
Lars Ellenrieder, Heike Rampelt, Thomas Becker
Mitochondrial biogenesis and function depend on the intensive exchange of molecules with other cellular compartments. The mitochondrial outer membrane plays a central role in this communication process. It is equipped with a number of specific protein machineries that enable the transport of proteins and metabolites. Furthermore, the outer membrane forms molecular contact sites with other cell organelles like the endoplasmic reticulum (ER), thus integrating mitochondrial function in cellular physiology. The best-studied mitochondrial organelle contact site, the ER-mitochondria encounter structure (ERMES) has been linked to many vital processes including mitochondrial division, inheritance, mitophagy and phospholipid transport...
May 30, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28570533/a-real-world-what-where-when-memory-test
#14
Tom V Smulders, Amber Black-Dominique, Tahsina S Choudhury, Simona E Constantinescu, Kyriaki Foka, Tom J Walker, Kevin Dick, Stephen Bradwel, R Hamish McAllister-Williams, Peter Gallagher
Episodic memory is a complex memory system which allows recall and mental re-experience of previous episodes from one's own life. Real-life episodic memories are about events in their spatiotemporal context and are typically visuospatial, rather than verbal. Yet often, tests of episodic memory use verbal material to be recalled (word lists, stories). The Real-World What-Where-When memory test requires participants to hide a total of 16 different objects in 16 different locations over two temporal occasions, 2 h apart...
May 16, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28566107/comparison-of-outcomes-in-australian-indigenous-and-non-indigenous-children-and-adolescents-undergoing-cardiac-surgery
#15
Edward R Justo, Benjamin M Reeves, Robert S Ware, Janelle C Johnson, Tom R Karl, Nelson D Alphonso, Robert N Justo
BACKGROUND: Population-based registries report 95% 5-year survival for children undergoing surgery for CHD. This study investigated paediatric cardiac surgical outcomes in the Australian indigenous population. METHODS: All children who underwent cardiac surgery between May, 2008 and August, 2014 were studied. Demographic information including socio-economic status, diagnoses and co-morbidities, and treatment and outcome data were collected at time of surgery and at last follow-up...
June 1, 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/28564595/structural-basis-for-regulation-of-escrt-iii-complexes-by-lgd
#16
Brian J McMillan, Christine Tibbe, Andrew A Drabek, Tom C M Seegar, Stephen C Blacklow, Thomas Klein
The ESCRT-III complex induces outward membrane budding and fission through homotypic polymerization of its core component Shrub/CHMP4B. Shrub activity is regulated by its direct interaction with a protein called Lgd in flies, or CC2D1A or B in humans. Here, we report the structural basis for this interaction and propose a mechanism for regulation of polymer assembly. The isolated third DM14 repeat of Lgd binds Shrub, and an Lgd fragment containing only this DM14 repeat and its C-terminal C2 domain is sufficient for in vivo function...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28562644/a-quantitative-indicator-diagram-for-lytic-polysaccharide-monooxygenases-reveals-the-role-of-aromatic-surface-residues-in-hjlpmo9a-regioselectivity
#17
Barbara Danneels, Magali Tanghe, Henk-Jan Joosten, Thomas Gundinger, Oliver Spadiut, Ingeborg Stals, Tom Desmet
Lytic polysaccharide monooxygenases (LPMOs) have changed our understanding of lignocellulosic degradation dramatically over the last years. These metalloproteins catalyze oxidative cleavage of recalcitrant polysaccharides and can act on the C1 and/or C4 position of glycosidic bonds. Structural data have led to several hypotheses, but we are still a long way from reaching complete understanding of the factors that determine their divergent regioselectivity. Site-directed mutagenesis enables the investigation of structure-function relationship in enzymes and will be of major importance in unraveling this intriguing matter...
2017: PloS One
https://www.readbyqxmd.com/read/28561022/il-17-induced-notch1-activation-in-oligodendrocyte-progenitor-cells-enhances-proliferation-and-inflammatory-gene-expression
#18
Chenhui Wang, Cun-Jin Zhang, Bradley N Martin, Katarzyna Bulek, Zizhen Kang, Junjie Zhao, Guanglin Bian, Julie A Carman, Ji Gao, Ashok Dongre, Haibo Xue, Stephen D Miller, Youcun Qian, Dolores Hambardzumyan, Tom Hamilton, Richard M Ransohoff, Xiaoxia Li
NOTCH1 signalling contributes to defective remyelination by impairing differentiation of oligodendrocyte progenitor cells (OPCs). Here we report that IL-17 stimulation induces NOTCH1 activation in OPCs, contributing to Th17-mediated demyelinating disease. Mechanistically, IL-17R interacts with NOTCH1 via the extracellular domain, which facilitates the cleavage of NOTHC1 intracellular domain (NICD1). IL-17-induced NOTCH1 activation results in the interaction of IL-17R adaptor Act1 with NICD1, followed by the translocation of the Act1-NICD1 complex into the nucleus...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28559564/efficient-generation-of-bispecific-murine-antibodies-for-pre-clinical-investigations-in-syngeneic-rodent-models
#19
Aran F Labrijn, Joyce I Meesters, Matthew Bunce, Anthony A Armstrong, Sandeep Somani, Tom C Nesspor, Mark L Chiu, Işil Altintaş, Sandra Verploegen, Janine Schuurman, Paul W H I Parren
Therapeutic concepts exploiting tumor-specific antibodies are often established in pre-clinical xenograft models using immuno-deficient mice. More complex therapeutic paradigms, however, warrant the use of immuno-competent mice, that more accurately capture the relevant biology that is being exploited. These models require the use of (surrogate) mouse or rat antibodies to enable optimal interactions with murine effector molecules. Immunogenicity is furthermore decreased, allowing longer-term treatment. We recently described controlled Fab-arm exchange (cFAE) as an easy-to-use method for the generation of therapeutic human IgG1 bispecific antibodies (bsAb)...
May 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28557792/the-approximate-entropy-concept-extended-to-three-dimensions-for-calibrated-single-parameter-structural-complexity-interrogation-of-volumetric-images
#20
Christopher J Moore, Tom Marchant
Reconstructive volumetric imaging permeates medical practice because of its apparently clear depiction of anatomy. However, the tell tale signs of abnormality and its delineation for treatment demand experts work at the threshold of visibility for hints of structure. Hitherto, a suitable assistive metric that chimes with clinical experience has been absent. This paper develops the complexity measure approximate entropy (ApEn) from its one-dimensional physiological origin into a three-dimensional (3D) algorithm to fill this gap...
May 30, 2017: Physics in Medicine and Biology
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