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Brian smith

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https://www.readbyqxmd.com/read/29149594/conversion-of-bim-bh3-from-activator-to-inhibitor-of-bak-through-structure-based-design
#1
Jason M Brouwer, Ping Lan, Angus D Cowan, Jonathan P Bernardini, Richard W Birkinshaw, Mark F van Delft, Brad E Sleebs, Adeline Y Robin, Ahmad Wardak, Iris K Tan, Boris Reljic, Erinna F Lee, W Douglas Fairlie, Melissa J Call, Brian J Smith, Grant Dewson, Guillaume Lessene, Peter M Colman, Peter E Czabotar
Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29131367/influence-of-the-neural-microenvironment-on-prostate-cancer
#2
Christian Coarfa, Diego Florentin, NagiReddy Putluri, Yi Ding, Jason Au, Dandan He, Ahmed Ragheb, Anna Frolov, George Michailidis, MinJae Lee, Dov Kadmon, Brian Miles, Christopher Smith, Michael Ittmann, David Rowley, Arun Sreekumar, Chad J Creighton, Gustavo Ayala
BACKGROUND: Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. METHOD: We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy...
November 13, 2017: Prostate
https://www.readbyqxmd.com/read/29130597/co-occurring-medical-conditions-in-adults-with-down-syndrome-a-systematic-review-toward-the-development-of-health-care-guidelines
#3
REVIEW
George T Capone, Brian Chicoine, Peter Bulova, Mary Stephens, Sarah Hart, Blythe Crissman, Andrea Videlefsky, Katherine Myers, Nancy Roizen, Anna Esbensen, Moya Peterson, Stephanie Santoro, Jason Woodward, Barry Martin, David Smith
Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. The United States Preventive Service Task Force (USPSTF) has developed criteria for prioritizing conditions of public health importance with the potential for providing screening recommendations to improve clinical care. The quality of existing evidence needed to inform clinical guidelines has not been previously reviewed. Using the National Library of Medicine (NLM) database PubMed, we first identified 18 peer reviewed articles that addressed co-occurring medical conditions in adults with DS...
November 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29129718/lessons-in-protac-design-from-selective-degradation-with-a-promiscuous-warhead
#4
Daniel P Bondeson, Blake E Smith, George M Burslem, Alexandru D Buhimschi, John Hines, Saul Jaime-Figueroa, Jing Wang, Brian D Hamman, Alexey Ishchenko, Craig M Crews
Inhibiting protein function selectively is a major goal of modern drug discovery. Here, we report a previously understudied benefit of small molecule proteolysis-targeting chimeras (PROTACs) that recruit E3 ubiquitin ligases to target proteins for their ubiquitination and subsequent proteasome-mediated degradation. Using promiscuous CRBN- and VHL-recruiting PROTACs that bind >50 kinases, we show that only a subset of bound targets is degraded. The basis of this selectivity relies on protein-protein interactions between the E3 ubiquitin ligase and the target protein, as illustrated by engaged proteins that are not degraded as a result of unstable ternary complexes with PROTAC-recruited E3 ligases...
October 31, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29129177/copd-x-australian-and-new-zealand-guidelines-for-the-diagnosis-and-management-of-chronic-obstructive-pulmonary-disease-2017-update
#5
Ian A Yang, Juliet L Brown, Johnson George, Sue Jenkins, Christine F McDonald, Vanessa M McDonald, Kirsten Phillips, Brian J Smith, Nicholas A Zwar, Eli Dabscheck
Chronic obstructive pulmonary disease (COPD) is characterised by persistent respiratory symptoms and chronic airflow limitation, and is associated with exacerbations and comorbidities. Advances in the management of COPD are updated quarterly in the national COPD guidelines, the COPD-X plan, published by Lung Foundation Australia in conjunction with the Thoracic Society of Australia and New Zealand and available at http://copdx.org.au. Main recommendations: Spirometry detects persistent airflow limitation (post-bronchodilator FEV1/FVC < 0...
November 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/29129157/thrombectomy-6-to-24-hours-after-stroke-with-a-mismatch-between-deficit-and-infarct
#6
Raul G Nogueira, Ashutosh P Jadhav, Diogo C Haussen, Alain Bonafe, Ronald F Budzik, Parita Bhuva, Dileep R Yavagal, Marc Ribo, Christophe Cognard, Ricardo A Hanel, Cathy A Sila, Ameer E Hassan, Monica Millan, Elad I Levy, Peter Mitchell, Michael Chen, Joey D English, Qaisar A Shah, Frank L Silver, Vitor M Pereira, Brijesh P Mehta, Blaise W Baxter, Michael G Abraham, Pedro Cardona, Erol Veznedaroglu, Frank R Hellinger, Lei Feng, Jawad F Kirmani, Demetrius K Lopes, Brian T Jankowitz, Michael R Frankel, Vincent Costalat, Nirav A Vora, Albert J Yoo, Amer M Malik, Anthony J Furlan, Marta Rubiera, Amin Aghaebrahim, Jean-Marc Olivot, Wondwossen G Tekle, Ryan Shields, Todd Graves, Roger J Lewis, Wade S Smith, David S Liebeskind, Jeffrey L Saver, Tudor G Jovin
Background The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. Methods We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years)...
November 11, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29124114/impact-of-programs-to-reduce-antipsychotic-and-anticholinergic-use-in-nursing-homes
#7
Ryan M Carnahan, Grant D Brown, Elena M Letuchy, Linda M Rubenstein, Brian M Gryzlak, Marianne Smith, Jeffrey C Reist, Michael W Kelly, Susan K Schultz, Michelle T Weckmann, Elizabeth A Chrischilles
Introduction: Antipsychotics are used for managing behavioral and psychological symptoms of dementia (BPSD) but have risks. Anticholinergics can worsen outcomes in dementia. The Improving Antipsychotic Appropriateness in Dementia Patients educational program (IA-ADAPT) and Centers for Medicare and Medicaid Services Partnership to Improve Dementia Care (CMS Partnership) promote improved care for BPSD. The purpose of this study was to evaluate the impact of these programs on medication use and BPSD among nursing home residents...
November 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29124092/dataset-of-the-livability-performance-of-the-city-of-birmingham-uk-as-measured-by-its-citizen-wellbeing-resource-security-resource-efficiency-and-carbon-emissions
#8
Joanne M Leach, Susan E Lee, Christopher T Boyko, Claire J Coulton, Rachel Cooper, Nicholas Smith, Hélène Joffe, Milena Büchs, James D Hale, Jonathan P Sadler, Peter A Braithwaite, Luke S Blunden, Valeria De Laurentiis, Dexter V L Hunt, AbuBakr S Bahaj, Katie Barnes, Christopher J Bouch, Leonidas Bourikas, Marianna Cavada, Andrew Chilvers, Stephen J Clune, Brian Collins, Ellie Cosgrave, Nick Dunn, Jane Falkingham, Patrick James, Corina Kwami, Martin Locret-Collet, Francesca Medda, Adriana Ortegon, Serena Pollastri, Cosmin Popan, Katerina Psarikidou, Nick Tyler, John Urry, Yue Wu, Victoria Zeeb, Chris D F Rogers
This data article presents the UK City LIFE1 data set for the city of Birmingham, UK. UK City LIFE1 is a new, comprehensive and holistic method for measuring the livable sustainability performance of UK cities. The Birmingham data set comprises 346 indicators structured simultaneously (1) within a four-tier, outcome-based framework in order to aid in their interpretation (e.g., promote healthy living and healthy long lives, minimize energy use, uncouple economic vitality from CO2 emissions) and (2) thematically in order to complement government and disciplinary siloes (e...
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29119553/innovation-in-the-design-of-clinical-trials-necessary-for-innovation-in-medicine
#9
EDITORIAL
Brian Smith, Oliver Sander
No abstract text is available yet for this article.
December 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29118166/laboratory-focus-on-improving-the-culture-of-biosafety-statewide-risk-assessment-of-clinical-laboratories-that-process-specimens-for-microbiologic-analysis
#10
Erik Munson, Erin J Bowles, Richard Dern, Eric Beck, Raymond P Podzorski, Allen C Bateman, Timothy K Block, Joshua L Kropp, Tyler Radke, Karen Siebers, Brian Simmons, Mary A Smith, Frances Spray-Larson, David M Warshauer
The Wisconsin State Laboratory of Hygiene challenged Wisconsin laboratories to examine their biosafety practices and improve their culture of biosafety. 103 clinical and public health laboratories completed a questionnaire-based, microbiology-focused biosafety risk assessment. Greater than 96% of respondents performed activities related to specimen processing, direct microscopic examination, and rapid non-molecular testing, while approximately 60% performed culture interpretation. Although important to assessing risk, data specific to patient occupation, symptoms, and travel history were often unavailable to the laboratory and, therefore, less contributory to microbiology biosafety risk assessment than information relative to specimen source and test requisition...
November 8, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29116144/the-effect-of-artificial-selection-on-phenotypic-plasticity-in-maize
#11
Joseph L Gage, Diego Jarquin, Cinta Romay, Aaron Lorenz, Edward S Buckler, Shawn Kaeppler, Naser Alkhalifah, Martin Bohn, Darwin A Campbell, Jode Edwards, David Ertl, Sherry Flint-Garcia, Jack Gardiner, Byron Good, Candice N Hirsch, Jim Holland, David C Hooker, Joseph Knoll, Judith Kolkman, Greg Kruger, Nick Lauter, Carolyn J Lawrence-Dill, Elizabeth Lee, Jonathan Lynch, Seth C Murray, Rebecca Nelson, Jane Petzoldt, Torbert Rocheford, James Schnable, Patrick S Schnable, Brian Scully, Margaret Smith, Nathan M Springer, Srikant Srinivasan, Renee Walton, Teclemariam Weldekidan, Randall J Wisser, Wenwei Xu, Jianming Yu, Natalia de Leon
Remarkable productivity has been achieved in crop species through artificial selection and adaptation to modern agronomic practices. Whether intensive selection has changed the ability of improved cultivars to maintain high productivity across variable environments is unknown. Understanding the genetic control of phenotypic plasticity and genotype by environment (G × E) interaction will enhance crop performance predictions across diverse environments. Here we use data generated from the Genomes to Fields (G2F) Maize G × E project to assess the effect of selection on G × E variation and characterize polymorphisms associated with plasticity...
November 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29114209/the-biogenic-amine-tyramine-and-its-receptor-amtyr1-in-olfactory-neuropils-in-the-honey-bee-apis-mellifera-brain
#12
Irina T Sinakevitch, Sasha M Daskalova, Brian H Smith
This article describes the cellular sources for tyramine and the cellular targets of tyramine via the Tyramine Receptor 1 (AmTyr1) in the olfactory learning and memory neuropils of the honey bee brain. Clusters of approximately 160 tyramine immunoreactive neurons are the source of tyraminergic fibers with small varicosities in the optic lobes, antennal lobes, lateral protocerebrum, mushroom body (calyces and gamma lobes), tritocerebrum and subesophageal ganglion (SEG). Our tyramine mapping study shows that the primary sources of tyramine in the antennal lobe and calyx of the mushroom body are from at least two Ventral Unpaired Median neurons (VUMmd and VUMmx) with cell bodies in the SEG...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/29114034/solution-structure-of-an-ultra-stable-single-chain-insulin-analog-connects-protein-dynamics-to-a-novel-mechanism-of-receptor-binding
#13
Michael D Glidden, Yanwu Yang, Nicholas A Smith, Nelson B Phillips, Kelley Carr, Nalinda P Wickramasinghe, Faramarz Ismail-Beigi, Michael C Lawrence, Brian J Smith, Michael A Weiss
Domain-minimized insulin receptors (IRs) have enabled crystallographic analysis of insulin-bound "micro-receptors." In such structures the C-terminal segment of the insulin B chain inserts between conserved IR domains, unmasking an invariant receptor-binding surface that spans both insulin A- and B chains. This "open" conformation not only rationalizes the inactivity of single-chain insulin (SCI) analogs (in which the A and B chains are directly linked), but also suggests that connecting (C) domains of sufficient length will bind the IR...
November 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29111725/model-studies-to-access-the-6-7-5-5-core-of-ineleganolide-using-tandem-translactonization-cope-or-cyclopropanation-cope-rearrangements-as-key-steps
#14
Jennifer L Roizen, Amanda C Jones, Russell C Smith, Scott C Virgil, Brian M Stoltz
Recently, we reported a convergent cyclopropanation-Cope approach to the core of ineleganolide, which was the first disclosed synthesis of the core of the norditerpene natural product ineleganolide. In this complementary work, a model system for the core of ineleganolide has been prepared through a series of tandem cyclopropanation-Cope and translactonization-Cope rearrangements. Work with this model system has enriched our understanding of the cyclopropanation-Cope rearrangement sequence. Additionally, research into this model system has driven the development of tandem translactonization-Cope rearrangements...
November 7, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29111381/baseline-lower-urinary-tract-symptoms-in-patients-enrolled-in-the-symptoms-of-lower-urinary-tract-dysfunction-research-network-lurn-a-prospective-observational-cohort-study
#15
Anne P Cameron, Christina Lewicky-Gaupp, Abigail R Smith, Brian T Helfand, John L Gore, J Quentin Clemens, Claire C Yang, Nazema Y Siddiqui, H Henry Lai, James W Griffith, Victor P Andreev, Gang Liu, Kevin Weinfurt, Cindy L Amundsen, Catherine S Bradley, John W Kusek, Ziya Kirkali
PURPOSE: To describe and compare the frequency and type of lower urinary tract symptoms (LUTS) reported by men and women at the time they were recruited from urology and urogynecology clinics into the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) multi-center, prospective, observational cohort study. MATERIALS AND METHODS: Six research sites enrolled treatment-seeking men and women who reported any LUTS at a frequency more than "rarely" during the past month on the LUTS tool...
October 27, 2017: Journal of Urology
https://www.readbyqxmd.com/read/29109458/shifts-in-pore-connectivity-from-precipitation-versus-groundwater-rewetting-increases-soil-carbon-loss-after-drought
#16
A Peyton Smith, Ben Bond-Lamberty, Brian W Benscoter, Malak M Tfaily, C Ross Hinkle, Chongxuan Liu, Vanessa L Bailey
Droughts and other extreme precipitation events are predicted to increase in intensity, duration, and extent, with uncertain implications for terrestrial carbon (C) sequestration. Soil wetting from above (precipitation) results in a characteristically different pattern of pore-filling than wetting from below (groundwater), with larger, well-connected pores filling before finer pore spaces, unlike groundwater rise in which capillary forces saturate the finest pores first. Here we demonstrate that pore-scale wetting patterns interact with antecedent soil moisture conditions to alter pore-scale, core-scale, and field-scale C dynamics...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29107642/linking-epcr-binding-pfemp1-to-brain-swelling-in-pediatric-cerebral-malaria
#17
Anne Kessler, Selasi Dankwa, Maria Bernabeu, Visopo Harawa, Samuel A Danziger, Fergal Duffy, Sam D Kampondeni, Michael J Potchen, Nicholas Dambrauskas, Vladimir Vigdorovich, Brian G Oliver, Sarah E Hochman, Wenzhu B Mowrey, Ian J C MacCormick, Wilson L Mandala, Stephen J Rogerson, D Noah Sather, John D Aitchison, Terrie E Taylor, Karl B Seydel, Joseph D Smith, Kami Kim
Brain swelling is a major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine-learning models of malarial retinopathy and brain swelling. We found that parasite var transcripts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite biomass and low platelet levels, are strong indicators of CM cases with malarial retinopathy...
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29107159/assessment-of-a-novel-adult-cervical-deformity-frailty-index-as-a-component-of-preoperative-risk-stratification
#18
Emily K Miller, Tamir Ailon, Brian J Neuman, Eric O Klineberg, Gregory M Mundis, Daniel M Sciubba, Khaled M Kebaish, Virginie Lafage, Justin K Scheer, Justin S Smith, D Kojo Hamilton, Shay Bess, Christopher I Shaffrey, Christopher P Ames
OBJECTIVE: To determine the value of a novel adult cervical deformity frailty index (CD-FI) in preoperative risk stratification. METHODS: We reviewed a prospective, multicenter database of adults with cervical spine deformity. We selected 40 variables to construct the CD-FI using a validated method. Patients were categorized as not frail (NF) (<0.2), frail (0.2-0.4), or severely frail (SF) (>0.4) based on CD-FI score. We performed multivariate logistic regression to determine the relationships between CD-FI score and incidence of complications, length of hospital stay, and discharge disposition...
October 26, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29097611/trends-in-intravenous-antibiotic-duration-for-urinary-tract-infections-in-young-infants
#19
William W Lewis-de Los Angeles, Cary Thurm, Adam L Hersh, Samir S Shah, Michael J Smith, Jeffrey S Gerber, Sarah K Parker, Jason G Newland, Matthew P Kronman, Brian R Lee, Thomas V Brogan, Joshua D Courter, Alicen Spaulding, Sameer J Patel
OBJECTIVES: To assess trends in the duration of intravenous (IV) antibiotics for urinary tract infections (UTIs) in infants ≤60 days old between 2005 and 2015 and determine if the duration of IV antibiotic treatment is associated with readmission. METHODS: Retrospective analysis of infants ≤60 days old diagnosed with a UTI who were admitted to a children's hospital and received IV antibiotics. Infants were excluded if they had a previous surgery or comorbidities, bacteremia, or admission to the ICU...
November 2, 2017: Pediatrics
https://www.readbyqxmd.com/read/29097366/quantitative-trait-locus-mapping-of-macrophage-cholesterol-metabolism-and-crispr-cas9-editing-implicate-an-acat1-truncation-as-a-causal-modifier-variant
#20
Qimin Hai, Brian Ritchey, Peggy Robinet, Alexander M Alzayed, Greg Brubaker, Jinying Zhang, Jonathan D Smith
OBJECTIVE: Cholesterol metabolism is a dynamic process involving intracellular trafficking, cholesterol esterification, and cholesterol ester hydrolysis. Our objective was to identify genes that regulate macrophage cholesterol metabolism. APPROACHES AND RESULTS: We performed quantitative trait loci mapping of free and esterified cholesterol levels and the ratio of esterified to free cholesterol in acetylated low-density lipoprotein-loaded bone marrow-derived macrophages from an AKR×DBA/2 strain intercross...
November 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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