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https://www.readbyqxmd.com/read/29167449/structure-of-human-immunoproteasome-with-a-reversible-and-noncompetitive-inhibitor-that-selectively-inhibits-activated-lymphocytes
#1
Ruda de Luna Almeida Santos, Lin Bai, Pradeep K Singh, Naoka Murakami, Hao Fan, Wenhu Zhan, Yingrong Zhu, Xiuju Jiang, Kaiming Zhang, Jean Pierre Assker, Carl F Nathan, Huilin Li, Jamil Azzi, Gang Lin
Proteasome inhibitors benefit patients with multiple myeloma and B cell-dependent autoimmune disorders but exert toxicity from inhibition of proteasomes in other cells. Toxicity should be minimized by reversible inhibition of the immunoproteasome β5i subunit while sparing the constitutive β5c subunit. Here we report β5i-selective inhibition by asparagine-ethylenediamine (AsnEDA)-based compounds and present the high-resolution cryo-EM structural analysis of the human immunoproteasome. Despite inhibiting noncompetitively, an AsnEDA inhibitor binds the active site...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29167309/visualizing-the-complex-functions-and-mechanisms-of-the-anaphase-promoting-complex-cyclosome-apc-c
#2
REVIEW
Claudio Alfieri, Suyang Zhang, David Barford
The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29167075/provider-beliefs-regarding-early-mobilization-in-the-pediatric-intensive-care-unit
#3
Christine L Joyce, Cosme Taipe, Brittany Sobin, Marissa Spadaro, Batsheva Gutwirth, Larissa Elgin, Gabrielle Silver, Bruce M Greenwald, Chani Traube
PURPOSE: Critically ill patients are at risk for short and long term morbidity. Early mobilization (EM) of critically ill adults is safe and feasible, with improvement in outcomes. There are limited studies evaluating EM in pediatric critical care patients. Provider beliefs and concerns must be evaluated prior to EM implementation in the pediatric intensive care unit (PICU). DESIGN AND METHODS: A survey was distributed to PICU providers assessing beliefs and concerns with regards to EM of PICU patients...
October 14, 2017: Journal of Pediatric Nursing
https://www.readbyqxmd.com/read/29166561/structural-characterization-of-native-and-modified-encapsulins-as-nanoplatforms-for-in-vitro-catalysis-and-cellular-uptake
#4
Rindia M Putri, Carolina Allende-Ballestero, Daniel Luque, Robin Klem, Katerina-Asteria Rousou, Aijie Liu, Christoph H-H Traulsen, W Frederik Rurup, Melissa S T Koay, Jose R Castón, Jeroen J L M Cornelissen
Recent years have witnessed the emergence of bacterial semi-organelle encapsulins as promising platforms for bio-nanotechnology. To advance the development of encapsulins as nanoplatforms, a functional and structural basis of these assemblies is required. Encapsulin from Brevibacterium linens is known to be a protein-based vessel for an enzyme cargo in its cavity, which could be replaced with a foreign cargo resulting in a modified encapsulin. Here, we characterize the native structure of B. linens encapsulins with both native and foreign cargo using cryo-electron microscopy (cryo-EM)...
November 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/29165246/regulatory-coiled-coil-domains-promote-head-to-head-assemblies-of-aaa-chaperones-essential-for-tunable-activity-control
#5
Marta Carroni, Kamila B Franke, Michael Maurer, Jasmin Jäger, Ingo Hantke, Felix Gloge, Daniela Linder, Sebastian Gremer, Kürşad Turgay, Bernd Bukau, Axel Mogk
Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA...
November 22, 2017: ELife
https://www.readbyqxmd.com/read/29165244/the-aaa-atpase-vps4-binds-escrt-iii-substrates-through-a-repeating-array-of-dipeptide-binding-pockets
#6
Han Han, Nicole Monroe, Wesley I Sundquist, Peter S Shen, Christopher P Hill
The hexameric AAA ATPase Vps4 drives membrane fission by remodeling and disassembling ESCRT-III filaments. Building upon our earlier 4.3 Å resolution cryo-EM structure (Monroe, Han et al. 2017), we now report a 3.2 Å structure of Vps4 bound to an ESCRT-III peptide substrate. The new structure reveals that the peptide approximates a b-strand conformation whose helical symmetry matches that of the five Vps4 subunits it contacts directly. Adjacent Vps4 subunits make equivalent interactions with successive substrate dipeptides through two distinct classes of side chain binding pockets formed primarily by Vps4 pore loop 1...
November 22, 2017: ELife
https://www.readbyqxmd.com/read/29165068/identifying-candidates-for-breast-cancer-using-interactions-of-chemicals-and-proteins
#7
Jing Lu, Kangle Shang, Yi Bi
Breast cancer is one of the major cause of cancer death in women worldwide. Therefore, it is urgent to discovery novel drugs or design effective treatments for this disease. However, the research and development of drugs by using only experimental methods is always time-consuming and expensive. With the development of computer science, some advanced computational methods can make full use of known knowledge to design candidate drugs, thereby reducing the cost and time of experimental testing. In this study, a computational method was proposed to identify novel candidates for breast cancer...
November 20, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29164840/correlations-between-anterior-wall-motion-velocity-of-ascending-aorta-measured-by-quantitative-tissue-velocity-image-and-left-ventricular-geometry-as-well-as-left-heart-function-in-hypertension-patients
#8
Chunyue Luo, Yan Liu, Zuojia Li, Jianying Lin, Ru Chen, Tieshan Zhang, Ying Hu, Guanxun Cheng
BACKGROUD: This study aimed to analyze the correlations between anterior wall motion velocity of ascending aorta measured by quantitative tissue velocity image (QTVI) technique and left ventricular geometry as well as left heart function to evaluate its value of clinical application. METHODS: 110 hypertension patients and 35 healthy controls were included. left ventricular concentric remodeling group and left ventricular hypertrophy group. The QTVI technique was used to obtain the velocity curve of anterior wall of ascending aorta, the peak systolic velocity (Vs), peak velocity of early diastolic motion (Ve) and peak velocity of late diastolic motion (Va)...
November 22, 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/29164814/a-thrombin-receptor-derived-imaging-agent-detects-subclinical-arthritis-in-mice
#9
Beth Friedman, Michael A Whitney, Elamprakash N Savariar, Christa Caneda, Paul Steinbach, Qing Xiong, Dina V Hingorani, Jessica Crisp, Stephen R Adams, Michael Kenner, Csilla N Lippert, Quyen T Nguyen, Monica Guma, Roger Y Tsien, Maripat Corr
OBJECTIVE: Functional imaging of synovitis could improve both early detection of rheumatoid arthritis (RA) and long-term outcomes. Motivated by the intersection of inflammation with coagulation protease activation, we examine coagulation protease activities in arthritic mice with a dual fluorescent Ratiometric thrombin-Activatable Cell Penetrating Peptide (RACPPNleTPRSFL ). METHOD: Mice with chronic transgenic K/BxN arthritis, or with arthritis on Day 1 of passive serum transfer induced arthritis (STIA), were imaged in vivo for Cy5 em: Cy7 em ratiometric fluorescence from proteolytic cleavage and activation of RACPPNleTPRSFL ...
November 22, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29164449/a-generalized-speed-accuracy-response-model-for-dichotomous-items
#10
Peter W van Rijn, Usama S Ali
We propose a generalization of the speed-accuracy response model (SARM) introduced by Maris and van der Maas (Psychometrika 77:615-633, 2012). In these models, the scores that result from a scoring rule that incorporates both the speed and accuracy of item responses are modeled. Our generalization is similar to that of the one-parameter logistic (or Rasch) model to the two-parameter logistic (or Birnbaum) model in item response theory. An expectation-maximization (EM) algorithm for estimating model parameters and standard errors was developed...
November 21, 2017: Psychometrika
https://www.readbyqxmd.com/read/29164368/3d-reconstruction-of-endoplasmic-reticulum-in-a-hydrocarbon-secreting-green-alga-botryococcus-braunii-race-b
#11
Reiko Suzuki, Ichiro Nishii, Shigeru Okada, Tetsuko Noguchi
Based on 3D sections through cells of Botryococcus braunii, the structure of three domains of endoplasmic reticulum, and their spatial and functional relationships to other organelles are clarified. Oil production by photosynthetic microalgae has attracted attention since these oils can be converted into renewable, carbon-neutral fuels. The green alga B. braunii accumulates large amounts of hydrocarbons, 30-50% of cell dry weight, in extracellular spaces rather than its cytoplasm. To advance the knowledge of hydrocarbon biosynthesis and transport pathways in this alga, we utilized transmission EM combined with rapid freezing and image reconstruction...
November 22, 2017: Planta
https://www.readbyqxmd.com/read/29164068/comparative-pan-genome-analysis-of-piscirickettsia-salmonis-reveals-genomic-divergences-within-genogroups
#12
Guillermo Nourdin-Galindo, Patricio Sánchez, Cristian F Molina, Daniela A Espinoza-Rojas, Cristian Oliver, Pamela Ruiz, Luis Vargas-Chacoff, Juan G Cárcamo, Jaime E Figueroa, Marcos Mancilla, Vinicius Maracaja-Coutinho, Alejandro J Yañez
Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis, functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29163452/the-opportunistic-pathogen-vibrio-vulnificus-produces-outer-membrane-vesicles-in-a-spatially-distinct-manner-related-to-capsular-polysaccharide
#13
Cheri M Hampton, Ricardo C Guerrero-Ferreira, Rachel E Storms, Jeannette V Taylor, Hong Yi, Paul A Gulig, Elizabeth R Wright
Vibrio vulnificus, a bacterial species that inhabits brackish waters, is an opportunistic pathogen of humans. V. vulnificus infections can cause acute gastroenteritis, invasive septicemia, tissue necrosis, and potentially death. Virulence factors associated with V. vulnificus include the capsular polysaccharide (CPS), lipopolysaccharide, flagellum, pili, and outer membrane vesicles (OMVs). The aims of this study were to characterize the morphology of V. vulnificus cells and the formation and arrangement of OMVs using cryo-electron microscopy (cryo-EM)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29162558/surgical-interventions-for-the-treatment-of-supracondylar-humerus-fractures-in-children-protocol-of-a-systematic-review
#14
Oreste Lemos Carrazzone, João Carlos Belloti, Fabio Teruo Matsunaga, Nacime Salomão Barbachan Mansur, Marcelo Hide Matsumoto, Flavio Faloppa, Marcel Jun Sugawara Tamaoki
BACKGROUND: The treatment of supracondylar humerus fracture in children (SHFC) is associated with complications such as functional deficit, residual deformity, and iatrogenic neurological damage. The standard treatment is closed reduction and percutaneous Kirschner wire fixation with different configurations. Despite this fact, there is still no consensus on the most effective technique for the treatment of these fractures. OBJECTIVE: The aim of this systematic review will be to evaluate the effect of surgical interventions on the treatment of Gartland type II and III SHFC by assessing function, complications, and error as primary outcomes...
November 21, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/29161204/effect-of-neoadjuvant-chemoradiotherapy-on-health-related-quality-of-life-in-esophageal-or-junctional-cancer-results-from-the-randomized-cross-trial
#15
Bo Jan Noordman, Mathilde G E Verdam, Sjoerd M Lagarde, Maarten C C M Hulshof, Pieter van Hagen, Mark I van Berge Henegouwen, Bas P L Wijnhoven, Hanneke W M van Laarhoven, Grard A P Nieuwenhuijzen, Geke A P Hospers, Johannes J Bonenkamp, Miguel A Cuesta, Reinoud J B Blaisse, Olivier R Busch, Fiebo J W Ten Kate, Geert-Jan M Creemers, Cornelis J A Punt, John Th M Plukker, Henk M W Verheul, Ernst J Spillenaar Bilgen, Herman van Dekken, Maurice J C van der Sangen, Tom Rozema, Katharina Biermann, Jannet C Beukema, Anna H M Piet, Caroline M van Rij, Janny G Reinders, Hugo W Tilanus, Ewout W Steyerberg, Ate van der Gaast, Mirjam A G Sprangers, J Jan B van Lanschot
Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and -Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively...
November 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29160573/activation-of-voltage-dependent-k-channels-strongly-limits-hypoxia-induced-elevation-of-ca-2-i-in-rat-carotid-body-glomus-cells
#16
Jiaju Wang, Donghee Kim
Large-conductance KCa (BK) and other voltage-dependent K(+) channels (Kv) are highly expressed in carotid body (CB) glomus cells, but their role in hypoxia-induced excitation is still not well defined and remains controversial. We addressed this issue by studying the effects of inhibitors of BK (IBTX) and BK/Kv (TEA/4-AP) on [Ca(2+) ]i responses to a wide range of hypoxia at different levels of resting cell Em. IBTX and TEA/4-AP did not affect the basal [Ca(2+) ]i in isolated glomus cells bathed in 5 mm KClo , but elicited transient increases in [Ca(2+) ]i in cells that were moderately depolarized (11-20 mV) by elevation of [KCl]o (12-20 mm)...
November 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29158713/formulation-and-characterization-of-novel-soft-nanovesicles-for-enhanced-transdermal-delivery-of-eprosartan-mesylate
#17
Abdul Ahad, Abdulmohsen A Al-Saleh, Abdullah M Al-Mohizea, Fahad I Al-Jenoobi, Mohammad Raish, Alaa Eldeen B Yassin, Mohd Aftab Alam
The objective of the present work was to formulate, optimize and evaluate the potential of novel soft nanovesicles i.e. nano-transfersomes, containing eprosartan mesylate (EM) for transdermal delivery. Nano-transfersomes of EM were developed using Phospholipon 90G, Span 80 (SP) and sodium deoxycholate (SDC) and characterized for vesicle size, shape, entrapment efficiency, in vitro skin permeation study and confocal laser scanning microscopy. The optimized nano-transfersomes formulation showed vesicles size of 108...
November 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/29156216/covert-retrieval-in-working-memory-impacts-the-phenomenological-characteristics-remembered-during-episodic-memory
#18
Vanessa M Loaiza, Borislava M Borovanska
Much research has investigated the qualitative experience of retrieving events from episodic memory (EM). The present study investigated whether covert retrieval in WM increases the phenomenological characteristics that participants find memorable in EM using tasks that distract attention from the maintenance of memoranda (i.e., complex span; Experiment 1) relative to tasks that do not (i.e., short or long list lengths of simple span; Experiments 1 and 2). Participants rated the quality of the phonological, semantic, and temporal-contextual characteristics remembered during a delayed memory characteristics questionnaire (MCQ)...
November 17, 2017: Consciousness and Cognition
https://www.readbyqxmd.com/read/29155690/cryo-em-structure-of-a-late-pre-40s-ribosomal-subunit-from-saccharomyces-cerevisiae
#19
André Heuer, Emma Thomson, Christian Schmidt, Otto Berninghausen, Thomas Becker, Ed Hurt, Roland Beckmann
Mechanistic understanding of eukaryotic ribosome formation requires a detailed structural knowledge of the numerous assembly intermediates, generated along a complex pathway. Here, we present the structure of a late pre-40S particle at 3.6 Å resolution, revealing in molecular detail how assembly factors regulate the timely folding of pre-18S rRNA. The structure shows that, rather than sterically blocking 40S translational active sites, the associated assembly factors Tsr1, Enp1, Rio2 and Pno1 collectively preclude their final maturation, thereby preventing untimely tRNA and mRNA binding and error prone translation...
November 20, 2017: ELife
https://www.readbyqxmd.com/read/29154724/understanding-how-a-palliative-specific-patient-reported-outcome-intervention-works-to-facilitate-patient-centred-care-in-advanced-heart-failure-a-qualitative-study
#20
Pauline M Kane, Clare I Ellis-Smith, Barbara A Daveson, Karen Ryan, Niall G Mahon, Brendan McAdam, Regina McQuillan, Cecelia Tracey, Christine Howley, Geraldine O'Gara, Caroline Raleigh, Irene J Higginson, Fliss Em Murtagh, Jonathan Koffman
BACKGROUND: Palliative care needs of patients with chronic heart failure are poorly recognised. Policy makers advise a patient-centred approach to holistically assess patients' needs and care goals. Patient-reported outcome measures are proposed to facilitate patient-centred care. AIM: To explore whether and how a palliative care-specific patient-reported outcome intervention involving the Integrated Palliative care Outcome Scale influences patients' experience of patient-centred care in nurse-led chronic heart failure disease management clinics...
November 1, 2017: Palliative Medicine
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