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https://www.readbyqxmd.com/read/27914063/episweep-computationally-driven-reengineering-of-therapeutic-proteins-to-reduce-immunogenicity-while-maintaining-function
#1
Yoonjoo Choi, Deeptak Verma, Karl E Griswold, Chris Bailey-Kellogg
Therapeutic proteins are yielding ever more advanced and efficacious new drugs, but the biological origins of these highly effective therapeutics render them subject to immune surveillance within the patient's body. When recognized by the immune system as a foreign agent, protein drugs elicit a coordinated response that can manifest a range of clinical complications including rapid drug clearance, loss of functionality and efficacy, delayed infusion-like allergic reactions, more serious anaphylactic shock, and even induced auto-immunity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913667/molecular-basis-for-specificity-of-the-met1-linked-polyubiquitin-signal
#2
REVIEW
Paul R Elliott
The post-translational modification of proteins provides a rapid and versatile system for regulating all signalling pathways. Protein ubiquitination is one such type of post-translational modification involved in controlling numerous cellular processes. The unique ability of ubiquitin to form polyubiquitin chains creates a highly complex code responsible for different subsequent signalling outcomes. Specialised enzymes ('writers') generate the ubiquitin code, whereas other enzymes ('erasers') disassemble it...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913312/crossborder-travel-and-multidrugresistant-tuberculosis-mdrtb-in-europe
#3
Alberto Matteelli, Rosella Centis, Giorgia Sulis, Marina Tadolini
The number of international migrants worldwide has continued to grow rapidly over the past fifteen years and the trend is expected to continue, making the health matters associated with migration a crucial public health challenges faced by governments and societies. Multidrug-resistant tuberculosis is a paradigm of transmissible diseases that do not respect borders and poses a multifaceted and complex challenge on migrant health. The guiding principles for the health response are the respect of equity and human rights as well as the accurate analysis of epidemiological trends and determinants of TB in migrants...
November 29, 2016: Travel Medicine and Infectious Disease
https://www.readbyqxmd.com/read/27913178/estimating-the-material-properties-of-heel-pad-sub-layers-using-inverse-finite-element-analysis
#4
Nafiseh Ahanchian, Christopher J Nester, David Howard, Lei Ren, Daniel Parker
Detailed information about the biomechanical behaviour of plantar heel pad tissue contributes to our understanding of load transfer when the foot impacts the ground. The objective of this work was to obtain the hyperelastic and viscoelastic material properties of heel pad sub-layers (skin, micro-chamber and macro-chamber layers) in-vivo. An anatomically detailed 3D Finite Element model of the human heel was used to derive the sub-layer material properties. A combined ultrasound imaging and motorised platform system was used to compress heel pad and to create input data for the Finite Element model...
November 29, 2016: Medical Engineering & Physics
https://www.readbyqxmd.com/read/27911745/the-role-of-epigenetic-mechanisms-in-the-regulation-of-gene-expression-in-the-nervous-system
#5
Justyna Cholewa-Waclaw, Adrian Bird, Melanie von Schimmelmann, Anne Schaefer, Huimei Yu, Hongjun Song, Ram Madabhushi, Li-Huei Tsai
Neuroepigenetics is a newly emerging field in neurobiology that addresses the epigenetic mechanism of gene expression regulation in various postmitotic neurons, both over time and in response to environmental stimuli. In addition to its fundamental contribution to our understanding of basic neuronal physiology, alterations in these neuroepigenetic mechanisms have been recently linked to numerous neurodevelopmental, psychiatric, and neurodegenerative disorders. This article provides a selective review of the role of DNA and histone modifications in neuronal signal-induced gene expression regulation, plasticity, and survival and how targeting these mechanisms could advance the development of future therapies...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911400/visualizing-stromule-frequency-with-fluorescence-microscopy
#6
Jacob O Brunkard, Anne M Runkel, Patricia Zambryski
Stromules, or "stroma-filled tubules", are narrow, tubular extensions from the surface of the chloroplast that are universally observed in plant cells but whose functions remain mysterious. Alongside growing attention on the role of chloroplasts in coordinating plant responses to stress, interest in stromules and their relationship to chloroplast signaling dynamics has increased in recent years, aided by advances in fluorescence microscopy and protein fluorophores that allow for rapid, accurate visualization of stromule dynamics...
November 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27907154/pheromone-recognition-and-selectivity-by-comr-proteins-among-streptococcus-species
#7
Erin Shanker, Donald A Morrison, Antoine Talagas, Sylvie Nessler, Michael J Federle, Gerd Prehna
Natural transformation, or competence, is an ability inherent to bacteria for the uptake of extracellular DNA. This process is central to bacterial evolution and allows for the rapid acquirement of new traits, such as antibiotic resistance in pathogenic microorganisms. For the Gram-positive bacteria genus Streptococcus, genes required for competence are under the regulation of quorum sensing (QS) mediated by peptide pheromones. One such system, ComRS, consists of a peptide (ComS) that is processed (XIP), secreted, and later imported into the cytoplasm, where it binds and activates the transcription factor ComR...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27906513/smartphone-based-portable-wireless-optical-system-for-the-detection-of-target-analytes
#8
Shreedhar Gautam, Bhagwan S Batule, Hyo Yong Kim, Ki Soo Park, Hyun Gyu Park
Rapid and accurate on-site wireless measurement of hazardous molecules or biomarkers is one of the biggest challenges in nanobiotechnology. We herein describe a novel smartphone-based Portable and Wireless Optical System (PAWS) for rapid, quantitative, and on-site analysis of target analytes. As a proof-of-concept, we employed gold nanoparticles (GNP) and an enzyme, horse radish peroxidase (HRP), to generate colorimetric signals in response to two model target molecules, melamine and hydrogen peroxide, respectively...
December 1, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27906487/neutrophil-activation-during-acute-human-anaphylaxis-analysis-of-mpo-and-scd62l
#9
Abbie Francis, Erika Bosio, Shelley F Stone, Daniel M Fatovich, Glenn Arendts, Yusuf Nagree, Stephen P J Macdonald, Hugh Mitenko, Mani Rajee, Sally Burrows, Simon G A Brown
BACKGROUND: The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. OBJECTIVE: To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. METHODS: Patients presenting to the Emergency Department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time points...
December 1, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27906169/automated-identification-of-mouse-visual-areas-with-intrinsic-signal-imaging
#10
Ashley L Juavinett, Ian Nauhaus, Marina E Garrett, Jun Zhuang, Edward M Callaway
Intrinsic signal optical imaging (ISI) is a rapid and noninvasive method for observing brain activity in vivo over a large area of the cortex. Here we describe our protocol for mapping retinotopy to identify mouse visual cortical areas using ISI. First, surgery is performed to attach a head frame to the mouse skull (∼1 h). The next day, intrinsic activity across the visual cortex is recorded during the presentation of a full-field drifting bar in the horizontal and vertical directions (∼2 h). Horizontal and vertical retinotopic maps are generated by analyzing the response of each pixel during the period of the stimulus...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27906055/mesenchymal-stem-cells-multipotent-stromal-cells-mscs-are-glycolytic-and-thus-glucose-is-a-limiting-factor-of-in-vitro-models-of-msc-starvation
#11
Austin Nuschke, Melanie Rodrigues, Albin W Wells, Kyle Sylakowski, Alan Wells
BACKGROUND: Mesenchymal stem/multipotent stromal cells (MSCs) contribute to tissue repair but are challenged during wound healing when the blood supply is disrupted, thereby limiting nutrient delivery. Survival mechanisms against 'starvation' include autophagy, which we previously found to enhance differentiation efficiency. MSC response to models of in vitro nutrient deprivation are of great interest for improving MSC survival and therapeutic efficacy; however, the rate-limiting nutrients are unknown...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27903807/concerted-changes-in-the-phosphoproteome-and-metabolome-under-different-co2-o2-gaseous-conditions-in-arabidopsis-rosettes
#12
Cyril Abadie, Samuel Mainguet, Marlène Davanture, Michael Hodges, Michel Zivy, Guillaume Tcherkez
Considerable efforts are currently devoted to understanding the regulation of primary carbon metabolism in plant leaves, which is known to change dramatically with environmental conditions, e.g. during light/dark transitions. Protein phosphorylation is believed to be a key factor in such a metabolic control. In fact, some studies have suggested modifications in the phosphorylation status of key enzymes in the dark compared with the light, or when photosynthesis varies. However, a general view of the phosphoproteome and reciprocal alterations in both the phosphoproteome and metabolome under a wide spectrum of CO2 and O2 conditions so as to vary both gross photosynthesis and photorespiration is currently lacking...
July 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27903704/semantic-congruence-accelerates-the-onset-of-the-neural-signals-of-successful-memory-encoding
#13
P A Packard, A Rodríguez-Fornells, N Bunzeck, B Nicolás, R de Diego-Balaguer, L Fuentemilla
: As the stream of experience unfolds, our memory system rapidly transforms current inputs into long-lasting meaningful memories. A putative neural mechanism that strongly influences how input elements are transformed into meaningful memory codes relies on the ability to integrate them with existing structures of knowledge or schemas. However, it is not yet clear whether schema-related integration neural mechanisms occur during online encoding. In the current investigation, we examined the encoding-dependent nature of this phenomenon in humans...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903210/resource-use-governance-and-case-load-of-rapid-response-teams-in-australia-and-new-zealand-in-2014
#14
(no author information available yet)
BACKGROUND: Rapid response teams (RRTs) are a mandatory element of Australian national health care policy. However, the uptake, resourcing, case load and funding of RRTs in Australian and New Zealand hospitals remain unknown. AIM: To assess the clinical activity, funding, staffing and governance of RRTs in Australian and New Zealand hospitals. METHODS: Survey of Australian and New Zealand hospitals as part of a biannual audit of intensive care resources and capacity...
December 2016: Critical Care and Resuscitation: Journal of the Australasian Academy of Critical Care Medicine
https://www.readbyqxmd.com/read/27902998/autoimmune-cytopenias-diagnosis-management
#15
Christian P Nixon, Joseph D Sweeney
The autoimmune cytopenias are a related group of disorders in which differentiated hematopoietic cells are destroyed by the immune system. Single lineage disease is characterized by the production of autoantibodies against red cells (autoimmune hemolytic anemia [AIHA]), platelets (autoimmune thrombocytopenia [ITP]) and neutrophils (autoimmune neutropenia [AIN]) whereas multilineage disease may include various combinations of these conditions. Central to the genesis of this disease is the breakdown of central and/or peripheral tolerance, and the subsequent production of autoantibodies by both tissue and circulating self-reactive B lymphocytes with support from T helper lymphocytes...
December 1, 2016: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/27901071/staphylococcus-aureus-dependent-septic-arthritis-in-murine-knee-joints-local-immune-response-and-beneficial-effects-of-vaccination
#16
Alessia Corrado, Paolo Donato, Silvia Maccari, Raffaella Cecchi, Tiziana Spadafina, Letizia Arcidiacono, Simona Tavarini, Chiara Sammicheli, Donatello Laera, Andrea Guido Oreste Manetti, Paolo Ruggiero, Bruno Galletti, Sandra Nuti, Ennio De Gregorio, Sylvie Bertholet, Anja Seubert, Fabio Bagnoli, Giuliano Bensi, Emiliano Chiarot
Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899163/human-fetal-and-adult-epicardial-derived-cells-a-novel-model-to-study-their-activation
#17
Asja T Moerkamp, Kirsten Lodder, Tessa van Herwaarden, Esther Dronkers, Calinda K E Dingenouts, Fredrik C Tengström, Thomas J van Brakel, Marie-José Goumans, Anke M Smits
BACKGROUND: The epicardium, a cell layer covering the heart, plays an important role during cardiogenesis providing cardiovascular cell types and instructive signals, but becomes quiescent during adulthood. Upon cardiac injury the epicardium is activated, which includes induction of a developmental gene program, epithelial-to-mesenchymal transition (EMT) and migration. However, the response of the adult epicardium is suboptimal compared to the active contribution of the fetal epicardium to heart development...
November 29, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27898218/global-health-security-building-capacities-for-early-event-detection-epidemiologic-workforce-and-laboratory-response
#18
S Arunmozhi Balajee, Ray Arthur, Anthony W Mounts
The Global Health Security Agenda (GHSA) was launched in February 2014 to bring countries with limited capacity into compliance with the International Health Regulations (IHR) (2005). Recent international public health events, such as the appearance of Middle Eastern respiratory syndrome coronavirus and the reappearance of Ebola in West Africa, have highlighted the importance of early detection of disease events and the interconnectedness of countries. Surveillance systems that allow early detection and recognition of signal events, a public health infrastructure that allows rapid notification and information sharing within countries and across borders, a trained epidemiologic workforce, and a laboratory network that can respond appropriately and rapidly are emerging as critical components of an early warning and response system...
November 29, 2016: Health Security
https://www.readbyqxmd.com/read/27897407/activin-a-induces-skeletal-muscle-catabolism-via-p38%C3%AE-mitogen-activated-protein-kinase
#19
Hui Ding, Guohua Zhang, Ka Wai Thomas Sin, Zhelong Liu, Ren-Kuo Lin, Min Li, Yi-Ping Li
BACKGROUND: Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB-activated muscle catabolism is poorly defined. METHODS: We investigated the role of p38β mitogen-activated protein kinases (MAPK) in mediating ActRIIB ligand activin A-activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically...
September 16, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27897246/rapid-control-of-pandemic-h1n1-influenza-by-targeting-nkt-cells
#20
Bianca L Artiaga, Guan Yang, Tarun E Hutchinson, Julia C Loeb, Jürgen A Richt, John A Lednicky, Shahram Salek-Ardakani, John P Driver
Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses...
November 29, 2016: Scientific Reports
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