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https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#1
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28923407/an-automated-toolchain-for-the-data-driven-and-dynamical-modeling-of-combined-sewer-systems
#2
Sara C Troutman, Nathaniel Schambach, Nancy G Love, Branko Kerkez
The recent availability and affordability of sensors and wireless communications is poised to transform our understanding and management of water systems. This will enable a new generation of adaptive water models that can ingest large quantities of sensor feeds and provide the best possible estimates of current and future conditions. To that end, this paper presents a novel data-driven identification/learning toolchain for combined sewer and stormwater systems. The toolchain uses Gaussian Processes to model dry-weather flows (domestic wastewater) and dynamical System Identification to represent wet-weather flows (rainfall runoff)...
September 3, 2017: Water Research
https://www.readbyqxmd.com/read/28921983/the-first-state-in-the-catalytic-cycle-of-the-water-oxidizing-enzyme-identification-of-a-water-derived-%C3%AE-hydroxo-bridge
#3
Thomas Lohmiller, Vera Krewald, Arezki Sedoud, A William Rutherford, Frank Neese, Wolfgang Lubitz, Dimitrios A Pantazis, Nicholas Cox
Nature's water splitting catalyst, an oxygen-bridged tetra-manganese calcium (Mn4O5Ca) complex, sequentially activates two substrate water molecules generating molecular O2. Its reaction cycle is composed of five intermediate (Si) states, where the index i indicates the number of oxidizing equivalents stored by the cofactor. After formation of the S4 state, the product dioxygen is released and the cofactor returns to its lowest oxidation state, S0. Membrane-inlet mass spectrometry measurements suggest that at least one substrate is bound throughout the catalytic cycle, as the rate of (18)O-labeled water incorporation into the product O2 is slow, on a millisecond to second timescale depending on the S state...
September 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28918898/endoplasmic-reticulum-transport-of-glutathione-by-sec61-is-regulated-by-ero1-and-bip
#4
Alise J Ponsero, Aeid Igbaria, Maxwell A Darch, Samia Miled, Caryn E Outten, Jakob R Winther, Gael Palais, Benoit D'Autréaux, Agnès Delaunay-Moisan, Michel B Toledano
In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport...
September 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28906341/the-neurophysiology-of-paediatric-movement-disorders
#5
Verity M McClelland
PURPOSE OF REVIEW: To demonstrate how neurophysiological tools have advanced our understanding of the pathophysiology of paediatric movement disorders, and of neuroplasticity in the developing brain. RECENT FINDINGS: Delineation of corticospinal tract connectivity using transcranial magnetic stimulation (TMS) is being investigated as a potential biomarker for response to therapy. TMS measures of cortical excitability and neuroplasticity are also being used to investigate the effects of therapy, demonstrating neuroplastic changes that relate to functional improvements...
September 12, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28902700/effectiveness-of-collaboration-between-emergency-department-and-intensive-care-unit-teams-on-mortality-rates-of-patients-presenting-with-critical-illness-a-systematic-review
#6
Kerchelle McDowald, Svetlana Direktor, Elizabeth A Hynes, Anna Sahadeo, Margaret E Rogers
BACKGROUND: The increasing volume of adult patients with critical illness entering emergency departments (EDs) burdens the resources of EDs worldwide. This subpopulation faces a high risk of mortality because they require specialized care which many EDs are not yet poised to deliver. An element crucial to delivering care and decreasing the mortality of critically ill patients in the ED is expert collaborative practice across disciplines. Several ED and intensive care unit (ICU) collaborative models exist including: emergency department intensive care units (EDICU) and medical emergency teams (MET)...
September 2017: JBI Database of Systematic Reviews and Implementation Reports
https://www.readbyqxmd.com/read/28902199/tuning-the-electronic-structure-in-stanene-graphene-bilayers-using-strain-and-gas-adsorption
#7
Frank F Yun, D L Cortie, X L Wang
Epitaxial growth of stanene monolayers on graphene substrates is an attractive synthesis route for atomically-thin electronic components, however, it remains unclear how such composites will tolerate lattice strain and exposure to ambient atmosphere. Using density functional theory, we identified several epitaxial configurations for the stanene-graphene bilayer system and determined the effect of strain and water adsorption. In addition to previously reported co-aligned bilayers, we identify a second family of low energy structures involving rotation of one layer by thirty degrees...
September 13, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28898361/expanded-tissue-samples-poised-to-assist-pathologists
#8
Jennifer Abbasi
No abstract text is available yet for this article.
September 12, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28893290/evasion-of-adaptive-immunity-by-hiv-through-the-action-of-host-apobec3g-f-enzymes
#9
REVIEW
Michael Grant, Mani Larijani
APOBEC3G (A3G) and APOBEC3F (A3F) are DNA-mutating enzymes expressed in T cells, dendritic cells and macrophages. A3G/F have been considered innate immune host factors, based on reports that they lethally mutate the HIV genome in vitro. In vivo, A3G/F effectiveness is limited by viral proteins, entrapment in inactive complexes and filtration of mutations during viral life cycle. We hypothesized that the impact of sub-lethal A3G/F action could extend beyond the realm of innate immunity confined to the cytoplasm of infected cells...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28892759/bioelectrochemical-sulphate-reduction-on-batch-reactors-effect-of-inoculum-type-and-applied-potential-on-sulphate-consumption-and-ph
#10
Manuel A Gacitúa, Enyelbert Muñoz, Bernardo González
Microbial electrolysis batch reactor systems were studied employing different conditions, paying attention on the effect that biocathode potential has on pH and system performance, with the overall aim to distinguish sulphate reduction from H2 evolution. Inocula from pure strains (Desulfovibrio paquesii and Desulfobacter halotolerans) were compared to a natural source conditioned inoculum. The natural inoculum possess the potential for sulphate reduction on serum bottles experiments due to the activity of mutualistic bacteria (Sedimentibacter sp...
August 25, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28892294/nuclease-activity-gives-an-edge-to-host-defense-peptide-piscidin-3-over-piscidin-1-rendering-it-more-effective-against-persisters-and-biofilms
#11
M Daben J Libardo, Ali Adem Bahar, Buyong Ma, Riqiang Fu, Laura E McCormick, Jun Zhao, Scott A McCallum, Ruth Nussinov, Dacheng Ren, Alfredo M Angeles-Boza, Myriam L Cotten
Host defense peptides (HDPs) feature evolution-tested potency against life-threatening pathogens. While piscidin 1 (p1) and piscidin 3 (p3) are homologous and potent fish HDPs, only p1 is strongly membranolytic. Here, we hypothesize that another mechanism imparts p3 strong potency. We demonstrate that the N-termini of both peptides coordinate Cu(2+) and p3-Cu cleaves isolated DNA at a rate on par with free Cu(2+) but significantly faster than p1-Cu. On planktonic bacteria, p1 is more antimicrobial but only p3 features copper-dependent DNA cleavage...
September 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#12
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28885765/reducing-hospital-acquired-pressure-ulcers-using-bundle-methodology-in-pediatric-and-neonatal-patients-receiving-extracorporeal-membrane-oxygenation-therapy-an-integrative-review-and-call-to-action
#13
Suzanne E Courtwright, Kari A Mastro, Christa Preuster, Navid Dardashti, Sandra McGill, Myrlene Madelon, Donna Johnson
PURPOSE: This review focuses on identifying (1) evidence of the effectiveness of care bundle methodology to reduce hospital-acquired pressure ulcers (HAPUs) in pediatric and neonatal patients receiving extracorporeal membrane oxygenation (ECMO) therapy and (2) barriers to implementing HAPU care bundles in this at-risk population. DESIGN AND METHODS: An integrative review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines...
September 8, 2017: Journal for Specialists in Pediatric Nursing: JSPN
https://www.readbyqxmd.com/read/28883974/the-salivary-gland-as-a-target-for-enhancing-immunization-response
#14
REVIEW
Todd A Ponzio, John W Sanders
BACKGROUND: An organism's immune response to a vaccine is dependent on a number of factors, including the site of immunization. While muscle is the most common site for vaccine administration, other sites, including the salivary gland, are poised to confer stronger and broader immunoprotection. FINDINGS: Studies exploring the salivary gland as an immunization site have involved protein antigens, as well as live pathogens and DNA vaccines. While intraductal instillation of protein antigens into the salivary gland may result in a relatively transient increase in antibody production, DNA or attenuated pathogen vaccination appear to confer a lasting widespread mucosal immune response that includes robust salivary and enteric IgA, as well as high levels of circulating IgG...
2017: Tropical Diseases, Travel Medicine and Vaccines
https://www.readbyqxmd.com/read/28883433/in-situ-wrapping-of-the-cathode-material-in-lithium-sulfur-batteries
#15
Chenji Hu, Hongwei Chen, Yanbin Shen, Di Lu, Yanfei Zhao, An-Hui Lu, Xiaodong Wu, Wei Lu, Liwei Chen
While lithium-sulfur batteries are poised to be the next-generation high-density energy storage devices, the intrinsic polysulfide shuttle has limited their practical applications. Many recent investigations have focused on the development of methods to wrap the sulfur material with a diffusion barrier layer. However, there is a trade-off between a perfect preassembled wrapping layer and electrolyte infiltration into the wrapped sulfur cathode. Here, we demonstrate an in situ wrapping approach to construct a compact layer on carbon/sulfur composite particles with an imperfect wrapping layer...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28882202/structural-characterization-of-poised-states-in-the-oxygen-sensitive-hydrogenases-and-nitrogenases
#16
Jacob H Artz, Oleg A Zadvornyy, David W Mulder, Paul W King, John W Peters
The crystallization of FeS cluster-containing proteins has been challenging due to their oxygen sensitivity, and yet these enzymes are involved in many critical catalytic reactions. The last few years have seen a wealth of innovative experiments designed to elucidate not just structural but mechanistic insights into FeS cluster enzymes. Here, we focus on the crystallization of hydrogenases, which catalyze the reversible reduction of protons to hydrogen, and nitrogenases, which reduce dinitrogen to ammonia. A specific focus is given to the different experimental parameters and strategies that are used to trap distinct enzyme states, specifically, oxidants, reductants, and gas treatments...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28880717/bivalent-histone-codes-on-wnt5a-during-odontogenic-differentiation
#17
Y Zhou, L Zheng, F Li, M Wan, Y Fan, X Zhou, W Du, C Pi, D Cui, B Zhang, J Sun, X Zhou
Lineage-committed differentiation is an essential biological program during odontogenesis, which is tightly regulated by lineage-specific genes. Some of these genes are modified by colocalization of H3K4me3 and H3K27me3 marks at promoter regions in progenitors. These modifications, named "bivalent domains," maintain genes in a poised state and then resolve for later activation or repression during differentiation. Wnt5a has been reported to promote odontogenic differentiation in dental mesenchyme. However, relatively little is known about the epigenetic modulations on Wnt5a activation during tooth development...
September 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28878429/the-national-programme-to-eliminate-lymphatic-filariasis-from-ethiopia
#18
Belete Mengistu, Kebede Deribe, Fikreab Kebede, Sarah Martindale, Mohammed Hassan, Heven Sime, Charles Mackenzie, Abate Mulugeta, Mossie Tamiru, Mesfin Sileshi, Asrat Hailu, Teshome Gebre, Amha Fentaye, Biruck Kebede
Lymphatic filariasis (LF) is one of the most debilitating and disfiguring diseases common in Ethiopia and is caused by Wuchereria bancrofti. Mapping for LF has shown that 70 woredas (districts) are endemic and 5.9 million people are estimated to be at risk. The national government's LF elimination programme commenced in 2009 in 5 districts integrated with the onchocerciasis programme. The programme developed gradually and has shown significant progress over the past 6 years, reaching 100% geographical coverage for mass drug administration (MDA) by 2016...
2017: Ethiopian Medical Journal
https://www.readbyqxmd.com/read/28874851/progress-towards-the-total-synthesis-of-hamigerans-c-and-d-a-direct-approach-to-an-elaborated-6-7-5-carbocyclic-core
#19
Douglas Charles Duquette, Thomas Jensen, Brian Mark Stoltz
The hamigeran family of natural products has been the target of numerous synthetic efforts because of its biological activity and interesting structural properties. Herein, we disclose our efforts toward the synthesis of hamigerans C and D, unique among the initially isolated members because of their 6-7-5 carbocyclic core. Our approach directly targets this tricyclic motif by sequential Negishi and Heck coupling reactions, yielding an advanced intermediate with all necessary carbons and sufficient functionality poised for completion of the synthesis of these two natural products...
September 6, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28871306/introduction-to-sigma-proteins-evolution-of-the-concept-of-sigma-receptors
#20
Felix J Kim
For over 40 years, scientists have endeavored to understand the so-called sigma receptors. During this time, the concept of sigma receptors has continuously and significantly evolved. With thousands of publications on the subject, these proteins have been implicated in various diseases, disorders, and physiological processes. Nevertheless, we are just beginning to understand what sigma proteins do and how they work. Two subtypes have been identified, Sigma1 and Sigma2. Whereas Sigma1 (also known as sigma-1 receptor, Sig1R, σ1 receptor, and several other names) was cloned over 20 years ago, Sigma2 (sigma-2 receptor, σ2 receptor) was cloned very recently and had remained a pharmacologically defined entity...
September 5, 2017: Handbook of Experimental Pharmacology
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