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Michael Richardson

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https://www.readbyqxmd.com/read/29775310/fragment-based-discovery-of-a-potent-orally-bioavailable-inhibitor-which-modulates-the-phosphorylation-and-catalytic-activity-of-erk1-2
#1
Tom D Heightman, Valerio Berdini, Hannah Braithwaite, Ildiko Maria Buck, Megan Cassidy, Juan Castro, Aurelie Courtin, James E H Day, Charlotte East, Lynsey Fazal, Brent Graham, Charlotte M Griffiths-Jones, John F Lyons, Vanessa Martins, Sandra Muench, Joanne M Munck, David Norton, Marc O'Reilly, Nick Palmer, Puja Pathuri, Michael Reader, David C Rees, Sharna J Rich, Caroline Richardson, Harpreet Saini, Neil T Thompson, Nicola G Wallis, Hugh Walton, Nicola E Wilsher, Alison J-A Woolford, Michael Cooke, David Cousin, Stuart Onions, Jonathan Shannon, John Watts, Christopher W Murray
Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signalling through ERK1/2. Here we describe the fragment based generation of ERK1/2 inhibitors which block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29751860/teaching-radiology-physics-interactively-with-scientific-notebook-software
#2
Michael L Richardson, Behrang Amini
RATIONALE AND OBJECTIVES: The goal of this study is to demonstrate how the teaching of radiology physics can be enhanced with the use of interactive scientific notebook software. METHODS: We used the scientific notebook software known as Project Jupyter, which is free, open-source, and available for the Macintosh, Windows, and Linux operating systems. RESULTS: We have created a scientific notebook that demonstrates multiple interactive teaching modules we have written for our residents using the Jupyter notebook system...
June 2018: Academic Radiology
https://www.readbyqxmd.com/read/29750518/altered-microbiome-leads-to-significant-phenotypic-and-transcriptomic-differences-in-a-lipid-accumulating-chlorophyte
#3
Lubna Richter, Cresten B Mansfeldt, Michael M Kuan, Alexandra Cesare, Stephen T Menefee, Ruth E Richardson, Beth A Ahner
Given the challenges facing the economically favorable production of products from microalgae, understanding factors that might impact productivity rates including growth rates and accumulation of desired products, e.g., triacylglycerols (TAG) for biodiesel feedstock, remains critical. Although operational parameters such as media composition and reactor design can clearly effect growth rates, the role of microbe-microbe interactions is just beginning to be elucidated. In this study an oleaginous marine algae Chlorella spp...
May 11, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29744843/biogelx-cell-culture-on-self-assembling-peptide-gels
#4
Mhairi M Harper, Michael L Connolly, Laura Goldie, Eleanore J Irvine, Joshua E Shaw, Vineetha Jayawarna, Stephen M Richardson, Matthew J Dalby, David Lightbody, Rein V Ulijn
Aromatic peptide amphiphiles can form self-supporting nanostructured hydrogels with tunable mechanical properties and chemical compositions. These hydrogels are increasingly applied in two-dimensional (2D) and three-dimensional (3D) cell culture, where there is a rapidly growing need to store, grow, proliferate, and manipulate naturally derived cells within a hydrated, 3D matrix. Biogelx Limited is a biomaterials company, created to commercialize these bio-inspired hydrogels to cell biologists for a range of cell culture applications...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29716742/climate-velocity-can-inform-conservation-in-a-warming-world
#5
REVIEW
Isaac Brito-Morales, Jorge García Molinos, David S Schoeman, Michael T Burrows, Elvira S Poloczanska, Christopher J Brown, Simon Ferrier, Tom D Harwood, Carissa J Klein, Eve McDonald-Madden, Pippa J Moore, John M Pandolfi, James E M Watson, Amelia S Wenger, Anthony J Richardson
Climate change is shifting the ranges of species. Simple predictive metrics of range shifts such as climate velocity, that do not require extensive knowledge or data on individual species, could help to guide conservation. We review research on climate velocity, describing the theory underpinning the concept and its assumptions. We highlight how climate velocity has already been applied in conservation-related research, including climate residence time, climate refugia, endemism, historic and projected range shifts, exposure to climate change, and climate connectivity...
April 28, 2018: Trends in Ecology & Evolution
https://www.readbyqxmd.com/read/29700420/exposure-to-toxic-metals-triggers-unique-responses-from-the-rat-gut-microbiota
#6
Joshua B Richardson, Blair C R Dancy, Cassandra L Horton, Young S Lee, Michael S Madejczyk, Zhenjiang Zech Xu, Gail Ackermann, Gregory Humphrey, Gustavo Palacios, Rob Knight, John A Lewis
Our understanding of the interaction between the gut microbiota and host health has recently improved dramatically. However, the effects of toxic metal exposure on the gut microbiota remain poorly characterized. As this microbiota creates a critical interface between the external environment and the host's cells, it may play an important role in host outcomes during exposure. We therefore used 16S ribosomal RNA (rRNA) gene sequencing to track changes in the gut microbiota composition of rats exposed to heavy metals...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29696791/lifelong-reduction-in-complex-iv-induces-tissue-specific-metabolic-effects-but-does-not-reduce-lifespan-or-healthspan-in-mice
#7
Sathyaseelan S Deepa, Gavin Pharaoh, Michael Kinter, Vivian Diaz, Wilson C Fok, Kaitlyn Riddle, Daniel Pulliam, Shauna Hill, Kathleen E Fischer, Vanessa Soto, Constantin Georgescu, Jonathan D Wren, Carlo Viscomi, Arlan Richardson, Holly Van Remmen
Loss of SURF1, a Complex IV assembly protein, was reported to increase lifespan in mice despite dramatically lower cytochrome oxidase (COX) activity. Consistent with this, our previous studies found advantageous changes in metabolism (reduced adiposity, increased insulin sensitivity, and mitochondrial biogenesis) in Surf1-/- mice. The lack of deleterious phenotypes in Surf1-/- mice is contrary to the hypothesis that mitochondrial dysfunction contributes to aging. We found only a modest (nonsignificant) extension of lifespan (7% median, 16% maximum) and no change in healthspan indices in Surf1-/- vs...
April 25, 2018: Aging Cell
https://www.readbyqxmd.com/read/29682992/higher-periprosthetic-fracture-rate-associated-with-use-of-modern-uncemented-stems-compared-to-cemented-stems-in-femoral-neck-fractures
#8
Jin Soo A Song, Daryl Dillman, Dave Wilson, Michael Dunbar, Glen Richardson
INTRODUCTION: Hemiarthroplasty is the preferred treatment for displaced femoral neck fractures in elderly patients. Recently, short tapered-wedge cementless stems have increasingly been used in this population. However, historic data has consistently shown higher rates of periprosthetic fracture with uncemented stems in hip fracture patients. This study aims to evaluate the rate of periprosthetic fracture requiring re-operation and all-cause mortality between cemented and uncemented femoral stem designs including more recent short tapered-wedge cementless stems in hip fracture patients...
April 1, 2018: Hip International: the Journal of Clinical and Experimental Research on Hip Pathology and Therapy
https://www.readbyqxmd.com/read/29678878/a-bispecific-antibody-that-targets-il-6-receptor-and-il-17a-for-the-potential-therapy-of-patients-with-autoimmune-and-inflammatory-diseases
#9
Michael Lyman, Vincent Lieuw, Robyn Richardson, Anjuli Timmer, Christine Stewart, Steve Granger, Richard Woods, Michela Silacci, Dragan Grabulovski, Roland Newman
Despite the success of current biological therapeutics for rheumatoid arthritis, these therapies, targeting individual cytokines or pathways, produce beneficial responses in only about half of patients. Therefore, better therapeutics are needed. IL-6 and IL-17A are pro-inflammatory cytokines in many autoimmune and inflammatory diseases, and several therapeutics have been developed to specifically inhibit them. However, targeting both of these cytokines with a bispecific therapeutic agent could account for their non-overlapping pro-inflammatory functions and for the fact that IL-6 and IL-17A act in a positive feedback loop...
April 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29660923/haemochromatosis-pathophysiology-and-the-red-blood-cell1
#10
Kieran J Richardson, Antony P McNamee, Michael J Simmonds
Haemochromatosis remains the most prevalent genetic disorder of Caucasian populations in Australia and the United States, occurring in ∼1 of 200 individuals and having a carrier frequency of 10-14%. Hereditary haemochromatosis is an autosomal recessive condition, that is phenotypically characterised by a gradual accumulation of iron, above and beyond that required for biological function. Once the binding capacity of iron carriers reaches saturation, the highly reactive free iron generates radicals that may lead to widespread cellular dysfunction...
April 7, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29624528/lack-of-evidence-for-ceiling-effect-for-buprenorphine-analgesia-in-humans
#11
Michael G Richardson, Britany L Raymond
No abstract text is available yet for this article.
April 5, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29620926/patient-and-facility-correlates-of-racial-differences-in-viral-control-for-black-and-white-veterans-with-hiv-infection-in-the-veterans-administration
#12
Mary S Vaughan Sarrazin, Michael E Ohl, Kelly K Richardson, Steven M Asch, Allen L Gifford, Barbara G Bokhour
Black persons with HIV are less likely than white persons to experience viral control even while in treatment. We sought to understand whether patient characteristics and site of care explain these differences using a cross-sectional analysis of medical records. Our cohort included 8779 black and 7836 white patients in the Veterans Administration (VA) health system with HIV who received antiretroviral medication during 2013. Our primary outcome, viral control, was defined as HIV serum RNA <200 copies/mL...
March 2018: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/29601303/the-opioid-epidemic-and-pregnancy-implications-for-anesthetic-care
#13
Britany L Raymond, Bradley T Kook, Michael G Richardson
PURPOSE OF REVIEW: This review summarizes evolving knowledge regarding adverse maternal, fetal, and neonatal effects of opioid exposure during pregnancy, and current treatment options for opioid use disorder (OUD). Maternal and fetal implications of maternal opioid maintenance with methadone and buprenorphine are described. Finally, acute and chronic pain management strategies in opioid-tolerant parturients are reviewed. RECENT FINDINGS: Opioid use among parturients has risen dramatically, with opioid use during pregnancy as high as 20%...
March 29, 2018: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/29587532/an-audit-of-the-accuracy-of-medication-information-in-electronic-medical-discharge-summaries-linked-to-an-electronic-prescribing-system
#14
Yixin Tan, Rohan A Elliott, Belinda Richardson, Francine E Tanner, Michael I Dorevitch
BACKGROUND: Poor communication of medication information to general practitioners when patients are discharged from hospital is a widely recognised problem. There has been little research exploring the accuracy of medication information in electronic discharge summaries (EDS) linked to hospital e-prescribing systems. OBJECTIVE: To evaluate the accuracy of medication lists and medication change information in EDS produced using an integrated e-prescribing and EDS system (where EDS discharge medication lists were imported from discharge e-prescription records, medication change information was manually entered, and medications were dispensed from paper copies of the patients' e-prescriptions)...
January 1, 2018: Health Information Management: Journal of the Health Information Management Association of Australia
https://www.readbyqxmd.com/read/29574388/formation-of-dbps-and-halogen-specific-tox-in-the-presence-of-iopamidol-and-chlorinated-oxidants
#15
Nana Osei B Ackerson, Edward J Machek, Alexis H Killinger, Elizabeth A Crafton, Pushpita Kumkum, Hannah K Liberatore, Michael J Plewa, Susan D Richardson, Thomas A Ternes, Stephen E Duirk
Iopamidol is a known direct precursor to iodinated and chlorinated DBP formation; however, the influence of iopamidol on both iodo/chloro-DBP formation has yet to be fully investigated. This study investigated the effect of iopamidol on the formation and speciation of halogen-specific total organic halogen (TOX), as well as iodo/chloro-DBPs, in the presence of 3 source waters (SWs) from Northeast Ohio and chlorinated oxidants. Chlorination and chloramination of SWs were carried out at pH 6.5-9.0 and, different iopamidol and dissolved organic carbon (DOC) concentrations...
March 16, 2018: Chemosphere
https://www.readbyqxmd.com/read/29557329/food-insecurity-as-a-risk-factor-for-outcomes-related-to-ebola-virus-disease-in-kono-district-sierra-leone-a-cross-sectional-study
#16
J Daniel Kelly, Eugene T Richardson, Michael Drasher, M Bailor Barrie, Sahr Karku, Mohamed Kamara, Katrina Hann, Kerry Dierberg, Allan Hubbard, Christina P Lindan, Paul E Farmer, George W Rutherford, Sheri D Weiser
Studies have shown that people suffering from food insecurity are at higher risk for infectious and noncommunicable diseases and have poorer health outcomes. No study, however, has examined the association between food insecurity and outcomes related to Ebola virus disease (EVD). We conducted a cross-sectional study in two Ebola-affected communities in Kono district, Sierra Leone, from November 2015 to September 2016. We enrolled persons who were determined to have been exposed to Ebola virus. We assessed the association of food insecurity, using an adapted version of the Household Food Insecurity Access Scale, a nine-item scale well validated across Africa, with having been diagnosed with EVD and having died of EVD, using logistic regression models with cluster-adjusted standard errors...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29548320/total-rna-extraction-from-tissues-for-microrna-and-target-gene-expression-analysis-not-all-kits-are-created-equal
#17
Rikki A M Brown, Michael R Epis, Jessica L Horsham, Tasnuva D Kabir, Kirsty L Richardson, Peter J Leedman
BACKGROUND: microRNAs (miRNAs) are short non-coding RNAs that fine-tune gene expression. The aberrant expression of miRNAs is associated with many diseases and they have both therapeutic and biomarker potential. However, our understanding of their usefulness is dependent on the tools we have to study them. Previous studies have identified the need to optimise and standardise RNA extraction methods in order to avoid biased results. Herein, we extracted RNA from murine lung, liver and brain tissues using five commercially available total RNA extraction methods...
March 16, 2018: BMC Biotechnology
https://www.readbyqxmd.com/read/29533239/model-validation-local-diagnosis-correction-and-when-to-quit
#18
Jane S Richardson, Christopher J Williams, Bradley J Hintze, Vincent B Chen, Michael G Prisant, Lizbeth L Videau, David C Richardson
Traditionally, validation was considered to be a final gatekeeping function, but refinement is smoother and results are better if model validation actively guides corrections throughout structure solution. This shifts emphasis from global to local measures: primarily geometry, conformations and sterics. A fit into the wrong local minimum conformation usually produces outliers in multiple measures. Moving to the right local minimum should be prioritized, rather than small shifts across arbitrary borderlines...
February 1, 2018: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/29532541/a-screening-algorithm-for-early-detection-of-major-depressive-disorder-in-head-and-neck-cancer-patients-post-treatment-longitudinal-study
#19
Melissa Henry, Zeev Rosberger, Lola E Ianovski, Michael Hier, Anthony Zeitouni, Karen Kost, Alex Mlynarek, Martin Black, Christina MacDonald, Keith Richardson, Xun Zhang, Fabienne Fuhrmann, Gabrielle Chartier, Saul Frenkiel
OBJECTIVE: The primary purpose of this study was to identify predictors of Major Depressive Disorder in head and neck cancer (HNC) patients in the immediate post-treatment period (ie, at 3 months post-diagnosis), with a focus on previously unexamined historical and contextual factors. METHODS: Prospective longitudinal study of 223 consecutive adults (72% participation) newly diagnosed with a first occurrence of primary HNC, including validated psychometric measures, Structured Clinical Interviews for DSM Disorders, and medical chart reviews...
March 13, 2018: Psycho-oncology
https://www.readbyqxmd.com/read/29526588/rapid-global-spread-of-wri-like-wolbachia-across-multiple-drosophila
#20
Michael Turelli, Brandon S Cooper, Kelly M Richardson, Paul S Ginsberg, Brooke Peckenpaugh, Chenling X Antelope, Kevin J Kim, Michael R May, Antoine Abrieux, Derek A Wilson, Michael J Bronski, Brian R Moore, Jian-Jun Gao, Michael B Eisen, Joanna C Chiu, William R Conner, Ary A Hoffmann
Maternally transmitted Wolbachia, Spiroplasma, and Cardinium bacteria are common in insects [1], but their interspecific spread is poorly understood. Endosymbionts can spread rapidly within host species by manipulating host reproduction, as typified by the global spread of wRi Wolbachia observed in Drosophila simulans [2, 3]. However, because Wolbachia cannot survive outside host cells, spread between distantly related host species requires horizontal transfers that are presumably rare [4-7]. Here, we document spread of wRi-like Wolbachia among eight highly diverged Drosophila hosts (10-50 million years) over only about 14,000 years (5,000-27,000)...
March 19, 2018: Current Biology: CB
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