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https://www.readbyqxmd.com/read/28079137/x-ray-structure-and-enzymatic-activity-profile-of-a-core-papain-like-protease-of-mers-coronavirus-with-utility-for-structure-based-drug-design
#1
Jozlyn R Clasman, Yahira M Báez-Santos, Robert C Mettelman, Amornrat O'Brien, Susan C Baker, Andrew D Mesecar
Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057356/cell-wall-synthesis-and-central-carbohydrate-metabolism-are-interconnected-by-the-snf1-mig1-pathway-in-kluyveromyces-lactis
#2
Dorthe Rippert, Katja Backhaus, Rosaura Rodicio, Jürgen J Heinisch
The trimeric AMP-activated kinase complex (AMPK) is conserved from yeast to humans and is best known for its role in balancing energy metabolism. Additional functions, including the regulation of cell wall biosynthesis, have been proposed for the SNF1 complex, the baker's yeast homolog of AMPK. We here demonstrate that this function is conserved in the Crabtree-negative milk yeast Kluyveromyces lactis. Deletion mutants in the genes encoding the subunits of the trimeric complex (Klsnf1, Klgal83, Klsnf4) displayed increased sensitivities towards cell wall stress agents and a mutant lacking the kinase subunit had a thinner cell wall in transmission electron micrographs as compared to wild type...
December 28, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28050879/using-critical-consciousness-to-inform-health-professions-education-a%C3%A2-literature-review
#3
REVIEW
Mark Halman, Lindsay Baker, Stella Ng
PURPOSE: To explore how, in health professions education (HPE), the concept of critical consciousness has been defined and discussed, and to consider and suggest how critical pedagogy could be applied in practice. This exploration responds to increasing calls in the literature for HPE to foster compassionate care and social consciousness through the social sciences and humanities. METHOD: The authors searched Medline/PubMed, ERIC and Web of Science for articles focusing on critical consciousness and/or critical pedagogy involving health professions...
January 3, 2017: Perspectives on Medical Education
https://www.readbyqxmd.com/read/28028742/growth-enzymatic-glutathione-peroxidase-activity-and-biochemical-status-of-juvenile-barramundi-lates-calcarifer-fed-dietary-fermented-soybean-meal-and-organic-selenium
#4
I Ilham, Ravi Fotedar
Solvent-extracted soybean meal (SBM) was fermented using baker's yeast Saccharomyces cerevisae at 30 °C for 5 days. Four isonitrogenous and isocaloric diets containing 75% SBM protein, either fermented or non-fermented (SBM and FSBM), and supplemented or not with organic Se (OS) (SBMOS and FSBMOS), were fed to triplicate groups of juvenile barramundi (Lates calcarifer) (initial weight of 5 g) for 75 days. A fishmeal (FM)-based diet formulated for juvenile barramundi was used as a reference diet. The growth of fish was significantly affected by either the interaction of SBM type or by the OS level...
December 27, 2016: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28025774/-they-treat-you-a-different-way-public-insurance-stigma-and-the-challenge-to-quality-health-care
#5
Anna C Martinez-Hume, Allison M Baker, Hannah S Bell, Isabel Montemayor, Kristan Elwell, Linda M Hunt
Under the Affordable Care Act, Medicaid Expansion programs are extending Medicaid eligibility and increasing access to care. However, stigma associated with public insurance coverage may importantly affect the nature and content of the health care beneficiaries receive. In this paper, we examine the health care stigma experiences described by a group of low-income public insurance beneficiaries. They perceive stigma as manifest in poor quality care and negative interpersonal interactions in the health care setting...
December 26, 2016: Culture, Medicine and Psychiatry
https://www.readbyqxmd.com/read/28013504/macromolecule-biosynthesis-assay-and-fluorescence-spectroscopy-methods-to-explore-antimicrobial-peptide-mode-s-of-action
#6
Bimal Jana, Kristin Renee Baker, Luca Guardabassi
Antimicrobial peptides (AMPs) are viable alternatives to the currently available antimicrobials, and numerous studies have investigated their possible use as therapeutic agents for specific clinical applications. AMPs are a diverse class of antimicrobials that often act upon the bacterial cell membrane but may exhibit additional modes of action. Identification of the multiple modes of action requires a comprehensive study at subinhibitory concentrations and careful data analysis since additional modes of action can be eclipsed by AMP action on the cell membrane...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28009518/measurement-of-in-vivo-gastrointestinal-release-and-dissolution-of-three-locally-acting-mesalamine-formulations-in-regions-of-the-human-gastrointestinal-tract
#7
Alex Yu, Jason R Baker, Ann F Fioritto, Ying Wang, Ruijuan Luo, Siwei Li, Bo Wen, Michael Bly, Yasuhiro Tsume, Mark J Koenigsknecht, Xinyuan Zhang, Robert Lionberger, Gordon L Amidon, William L Hasler, Duxin Sun
As an orally administered, locally acting gastrointestinal drug, mesalamine products are designed to achieve high local drug concentration in the gastrointestinal (GI) tract for the treatment of ulcerative colitis. The aim of this study was to directly measure and compare drug dissolution of three mesalamine formulations in human GI tract and to correlate their GI concentration with drug concentration in plasma. Healthy human subjects were orally administered Pentasa, Apriso, or Lialda. GI fluids were aspirated from stomach, duodenum, proximal jejunum, mid jejunum, and distal jejunum regions...
December 23, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27986800/a-matter-of-life-and-death-controversy-at-the-interface-between-clinical-and-legal-decision-making-in-prolonged-disorders-of-consciousness
#8
Lynne Turner-Stokes
Best interests decision-making and end-of-life care for patients in permanent vegetative or minimally conscious states (VS/MCS) is a complex area of clinical and legal practice, which is poorly understood by most clinicians, lawyers and members of the public. In recent weeks, the Oxford Shrieval lecture by Mr Justice Baker ('A Matter of Life and Death', 11 October 2016) and its subsequent reporting in the public press has sparked debate on the respective roles of clinicians, the Court of Protection and the Mental Capacity Act 2005 in decisions to withhold or withdraw life-sustaining treatments from patients with disorders of consciousness...
December 16, 2016: Journal of Medical Ethics
https://www.readbyqxmd.com/read/27986569/backbone-engineering-within-a-latent-%C3%AE-hairpin-structure-to-design-inhibitors-of-polyglutamine-amyloid-formation
#9
Karunakar Kar, Matthew A Baker, George A Lengyel, Cody L Hoop, Ravindra Kodali, In-Ja Byeon, W Seth Horne, Patrick C A van der Wel, Ronald Wetzel
Candidates for the toxic molecular species in the expanded polyglutamine (polyQ) repeat diseases range from various types of aggregates to "misfolded" monomers. One way to vet these candidates is to develop mutants that restrict conformational landscapes. Previously, we inserted two self-complementary β-hairpin enhancing motifs into a short polyQ sequence to generate a mutant, here called "βHP," that exhibits greatly improved amyloid nucleation without measurably enhancing β-structure in the monomer ensemble...
December 13, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27936070/attraction-oviposition-and-larval-survival-of-the-fungus-gnat-lycoriella-ingenua-on-fungal-species-isolated-from-adults-larvae-and-mushroom-compost
#10
Kevin R Cloonan, Stefanos S Andreadis, Haibin Chen, Nina E Jenkins, Thomas C Baker
We previously showed that the females of the mushroom sciarid, Lycoriella ingenua (Dufour, 1839) (Diptera: Sciaridae), one of the most severe pests of the cultivated white button mushroom, Agaricus bisporus (J.E. Lange) Emil J. Imbach (Agaricales: Agaricaceae), are attracted to the mushroom compost that mushrooms are grown on and not to the mushrooms themselves. We also showed that females are attracted to the parasitic green mold, Trichoderma aggressivum. In an attempt to identify what is in the mushroom compost that attracts female L...
2016: PloS One
https://www.readbyqxmd.com/read/27927840/%C3%AE-blockers-heart-disease-and-copd-current-controversies-and-uncertainties
#11
Jillian G Baker, Robert G Wilcox
Treating people with cardiovascular disease and COPD causes significant clinician anxiety. β-Blockers save lives in people with heart disease, specifically postinfarction and heart failure. COPD and heart disease frequently coexist and people with both disorders have particularly high cardiovascular mortality. There are concerns about giving β-blockers to people with concomitant COPD that include reduced basal lung function, diminished effectiveness of emergency β-agonist treatments, reduced benefit of long-acting β-agonist treatment and difficulty in discriminating between asthma and COPD...
December 7, 2016: Thorax
https://www.readbyqxmd.com/read/27925187/depletion-of-cd52-positive-cells-inhibits-the-development-of-central-nervous-system-autoimmune-disease-but-deletes-an-immune-tolerance-promoting-cd8-t-cell-population-implications-for-secondary-autoimmunity-of-alemtuzumab-in-multiple-sclerosis
#12
Stephanie von Kutzleben, Gareth Pryce, Gavin Giovannoni, David Baker
The objective was to determine whether CD52 lymphocyte depletion can act to promote immunological tolerance induction by way of intravenous antigen administration such that it could be used to either improve efficiency of multiple sclerosis (MS) inhibition or inhibit secondary autoimmunities that may occur following alemtuzumab use in MS. Relapsing experimental autoimmune encephalomyelitis was induced in ABH mice and immune cell depletion was therapeutically applied using mouse CD52 or CD4 (in conjunction with CD8 or CD20) depleting monoclonal antibodies...
December 7, 2016: Immunology
https://www.readbyqxmd.com/read/27920276/studies-of-recombinant-twa1-reveal-constitutive-dimerisation
#13
Ore Francis, Genevieve E Baker, Paul R Race, Josephine C Adams
The mammalian muskelin/RanBP9/CTLH complex and the S. cerevisiae GID complex are large, multi-protein complexes that each contain a RING E3 ubiquitin ligase. The yeast GID complex acts to degrade a key enzyme of gluconeogenesis, fructose 1,6-bisphosphatase, under conditions of abundant fermentable carbon sources. However, the assembly and functions of the mammalian complex remain poorly understood. A striking feature of these complexes is the presence of multiple proteins that contain contiguous lissencephaly-1 homology (LisH), C-terminal to LisH (CTLH) and C-terminal CT11-RanBP9 (CRA) domains...
December 5, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27906551/ald1613-a-novel-long-acting-monoclonal-antibody-to-control-acth-driven-pharmacology
#14
Andrew L Feldhaus, Katie Anderson, Benjamin Dutzar, Ethan Ojala, Patricia Dianne McNeill, Pei Fan, Jenny Mulligan, Sam Marzolf, Charlie Karasek, Michelle Scalley-Kim, Erica Stewart, Jens Billgren, Vanessa Rubin, Kathleen Schneider, David Jurchen, Kathy Snow, Shaun Barnett, Barbara Bengtsson, Brian Baker, John A Latham, Dan Allison, Leon F Garcia-Martinez
ACTH is the primary regulator of adrenal glucocorticoid production. Elevated levels of ACTH play a critical role in disease progression in several indications including congenital adrenal hyperplasia and Cushing's disease. We have generated a specific, high affinity, neutralizing monoclonal antibody (ALD1613) to ACTH. In vitro, ALD1613 neutralizes ACTH-induced signaling via all five melanocortin receptors and inhibited ACTH-induced cAMP accumulation in a mouse adrenal cell line (Y1). ALD1613 administration to wild-type rats significantly reduced plasma corticosterone levels in a dose dependent manner...
December 1, 2016: Endocrinology
https://www.readbyqxmd.com/read/27901466/differentiation-alters-stem-cell-nuclear-architecture-mechanics-and-mechano-sensitivity
#15
Su-Jin Heo, Tristan P Driscoll, Stephen D Thorpe, Nandan L Nerurkar, Brendon M Baker, Michael T Yang, Christopher S Chen, David A Lee, Robert L Mauck
Mesenchymal stem cell (MSC) differentiation is mediated by soluble and physical cues. In this study, we investigated differentiation-induced transformations in MSC cellular and nuclear biophysical properties and queried their role in mechanosensation. Our data show that nuclei in differentiated bovine and human MSCs stiffen and become resistant to deformation. This attenuated nuclear deformation was governed by restructuring of Lamin A/C and increased heterochromatin content. This change in nuclear stiffness sensitized MSCs to mechanical-loading-induced calcium signaling and differentiated marker expression...
November 30, 2016: ELife
https://www.readbyqxmd.com/read/27888437/estimated-budget-impact-of-adopting-the-affordable-care-act-s-required-smoking-cessation-coverage-on-united-states-healthcare-payers
#16
Christine L Baker, Cheryl P Ferrufino, Marianna Bruno, Stacey Kowal
INTRODUCTION: Despite abundant information on the negative impacts of smoking, more than 40 million adult Americans continue to smoke. The Affordable Care Act (ACA) requires tobacco cessation as a preventive service with no patient cost share for all FDA-approved cessation medications. Health plans have a vital role in supporting smoking cessation by managing medication access, but uncertainty remains on the gaps between smoking cessation requirements and what is actually occurring in practice...
January 2017: Advances in Therapy
https://www.readbyqxmd.com/read/27883085/phenotypic-and-functional-characterization-of-the-major-lymphocyte-populations-in-the-fruit-eating-bat-pteropus-alecto
#17
Julia María Martínez Gómez, Pravin Periasamy, Charles-Antoine Dutertre, Aaron Trent Irving, Justin Han Jia Ng, Gary Crameri, Michelle L Baker, Florent Ginhoux, Lin-Fa Wang, Sylvie Alonso
The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat's immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8(+) T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864171/mitochondrial-superoxide-dismutase-and-yap1p-act-as-a-signaling-module-contributing-to-ethanol-tolerance-of-the-yeast-saccharomyces-cerevisiae
#18
Anna N Zyrina, Ekaterina A Smirnova, Olga V Markova, Fedor F Severin, Dmitry A Knorre
: There are two superoxide dismutases in the yeast Saccharomyces cerevisiae-cytoplasmic and mitochondrial enzymes. Inactivation of the cytoplasmic enzyme, Sod1p, renders the cells sensitive to a variety of stresses, while inactivation of the mitochondrial isoform, Sod2p, typically has a weaker effect. One exception is ethanol-induced stress. Here we studied the role of Sod2p in ethanol tolerance of yeast. First, we found that repression of SOD2 prevents ethanol-induced relocalization of yeast hydrogen peroxide-sensing transcription factor Yap1p, one of the key stress resistance proteins...
February 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27857941/septin-organization-and-functions-in-budding-yeast
#19
REVIEW
Oliver Glomb, Thomas Gronemeyer
The septins are a conserved family of GTP-binding proteins present in all eukaryotic cells except plants. They were originally discovered in the baker's yeast Saccharomyces cerevisiae that serves until today as an important model organism for septin research. In yeast, the septins assemble into a highly ordered array of filaments at the mother bud neck. The septins are regulators of spatial compartmentalization in yeast and act as key players in cytokinesis. This minireview summarizes the recent findings about structural features and cell biology of the yeast septins...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27842999/conceptualising-the-public-health-role-of-actors-operating-outside-of-formal-health-systems-the-case-of-social-enterprise
#20
Michael J Roy, Rachel Baker, Susan Kerr
This paper focuses on the role of actors that operate outside formal health systems, but nevertheless have a vital, if often under-recognised, role in supporting public health. The specific example used is the 'social enterprise', an organisation that seeks, through trading, to maximise social returns, rather than the distribution of profits to shareholders or owners. In this paper we advance empirical and theoretical understanding of the causal pathways at work in social enterprises, by considering them as a particularly complex form of public health 'intervention'...
January 2017: Social Science & Medicine
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