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Immune flux

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https://www.readbyqxmd.com/read/28534248/immune-checkpoint-inhibitor-therapy-what-line-of-therapy-and-how-to-choose
#1
REVIEW
Chethan Ramamurthy, James L Godwin, Hossein Borghaei
Immunotherapy is now an established part of the treatment paradigm for advanced non-small cell lung cancer (NSCLC), but the line of therapy and the sequence of agents are still in flux. In this time when much is to be learned, the optimal therapy for most patients in both the first-line and previously treated settings is in the context of a clinical trial. For standard therapy, however, there are good data to support the practice of programmed death-ligand 1 (PD-L1) testing in the front-line advanced setting and to use pembrolizumab as first-line therapy for those with ≥50% PD-L1 expression...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28533780/innate-immune-function-of-mitochondrial-metabolism
#2
REVIEW
David Sancho, Michel Enamorado, Johan Garaude
Sensing of microbe-associated molecular patterns or danger signals by innate immune receptors drives a complex exchange of information. Innate receptor signaling not only triggers transcriptional events but also induces profound changes in metabolic fluxes, redox balance, and metabolite abundance thereby influencing immune cell function. Mitochondria are at the core of metabolic adaptation to the changing environment. The close interaction between mitochondrial metabolism and immune signaling has emerged as a central regulator of innate sensing...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28530276/focus-a-metaheuristic-algorithm-for-computing-knockouts-from-genome-scale-models-for-strain-optimization
#3
Sarma Mutturi
Although handful tools are available for constraint-based flux analysis to generate knockout strains, most of these are either based on bilevel-MIP or its modifications. However, metaheuristic approaches that are known for their flexibility and scalability have been less studied. Moreover, in the existing tools, sectioning of search space to find optimal knocks has not been considered. Herein, a novel computational procedure, termed as FOCuS (Flower-pOllination coupled Clonal Selection algorithm), was developed to find the optimal reaction knockouts from a metabolic network to maximize the production of specific metabolites...
May 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28518216/queen-presence-mediates-the-relationship-between-collective-behavior-and-disease-susceptibility-in-ant-colonies
#4
Carl N Keiser, Svjetlana Vojvodic, Imani O Butler, Elizabeth Sartain, Volker H W Rudolf, Julia B Saltz
The success of social living can be explained, in part, by a group's ability to execute collective behaviors unachievable by solitary individuals. However, groups vary in their ability to execute these complex behaviors, often because they vary in their phenotypic composition. Group membership changes over time due to mortality or emigration, potentially leaving groups vulnerable to ecological challenges in times of flux. In some societies, the loss of important individuals (e.g., leaders, elites, queens) may have an especially detrimental effect on groups' ability to deal with these challenges...
May 18, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28513846/a-calmodulin-like-protein-regulates-plasmodesmal-closure-during-bacterial-immune-responses
#5
Bo Xu, Cécilia Cheval, Anuphon Laohavisit, Bradleigh Hocking, David Chiasson, Tjelvar S G Olsson, Ken Shirasu, Christine Faulkner, Matthew Gilliham
Plants sense microbial signatures via activation of pattern recognition receptors (PPRs), which trigger a range of cellular defences. One response is the closure of plasmodesmata, which reduces symplastic connectivity and the capacity for direct molecular exchange between host cells. Plasmodesmal flux is regulated by a variety of environmental cues but the downstream signalling pathways are poorly defined, especially the way in which calcium regulates plasmodesmal closure. Here, we identify that closure of plasmodesmata in response to bacterial flagellin, but not fungal chitin, is mediated by a plasmodesmal-localized Ca(2+) -binding protein Calmodulin-like 41 (CML41)...
May 17, 2017: New Phytologist
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#6
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28480159/tracing-insights-into-human-metabolism-using-chemical-engineering-approaches
#7
Thekla Cordes, Christian M Metallo
Metabolism coordinates the conversion of available nutrients toward energy, biosynthetic intermediates, and signaling molecules to mediate virtually all biological functions. Dysregulation of metabolic pathways contributes to many diseases, so a detailed understanding of human metabolism has significant therapeutic implications. Over the last decade major technological advances in the areas of analytical chemistry, computational estimation of intracellular fluxes, and biological engineering have improved our ability to observe and engineer metabolic pathways...
November 2016: Current Opinion in Chemical Engineering
https://www.readbyqxmd.com/read/28469008/the-early-response-during-the-interaction-of-fungal-phytopathogen-and-host-plant
#8
REVIEW
Yilin Shen, Na Liu, Chuang Li, Xin Wang, Xiaomeng Xu, Wan Chen, Guozhen Xing, Wenming Zheng
Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28460464/ppar%C3%AE-activation-by-troglitazone-enhances-human-lung-cancer-cells-to-trail-induced-apoptosis-via-autophagy-flux
#9
Uddin Md Nazim, Ji-Hong Moon, You-Jin Lee, Jae-Won Seol, Sang-Youel Park
Members of the tumor necrosis factor (TNF) transmembrane cytokine superfamily, such as TNFα and Fas ligand (FasL), play crucial roles in inflammation and immunity. TRAIL is a member of this superfamily with the ability to selectively trigger cancer cell death but does not motive cytotoxicity to most normal cells. Troglitazone are used in the cure of type II diabetes to reduce blood glucose levels and improve the sensitivity of an amount of tissues to insulin. In this study, we revealed that troglitazone could trigger TRAIL-mediated apoptotic cell death in human lung adenocarcinoma cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439552/direct-observation-of-chiral-currents-and-magnetic-reflection-in-atomic-flux-lattices
#10
Fangzhao Alex An, Eric J Meier, Bryce Gadway
The prospect of studying topological matter with the precision and control of atomic physics has driven the development of many techniques for engineering artificial magnetic fields and spin-orbit interactions. Recently, the idea of introducing nontrivial topology through the use of internal (or external) atomic states as effective "synthetic dimensions" has garnered attraction for its versatility and possible immunity from heating. We engineer tunable gauge fields through the local control of tunneling phases in an effective two-dimensional manifold of discrete atomic momentum states...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28409633/tunable-nitric-oxide-release-from-s-nitroso-n-acetylpenicillamine-via-catalytic-copper-nanoparticles-for-biomedical-applications
#11
Jitendra Pant, Marcus J Goudie, Sean P Hopkins, Elizabeth J Brisbois, Hitesh Handa
The quest for novel therapies to prevent bacterial infections and blood clots (thrombosis) is of utmost importance in biomedical research due to the exponential growth in the cases of thrombosis and blood infections and the emergence of multi-drug-resistant strains of bacteria. Endogenous nitric oxide (NO) is a cellular signaling molecule that plays a pivotal role in host immunity against pathogens, prevention of clotting, and regulation of systemic blood pressure, among several other biological functions. The physiological effect of NO is dose dependent, which necessitates the study of its tunable release kinetics, which is the objective of this study...
April 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28405704/expression-of-histophilus-somni-ibpa-dr2-protective-antigen-in-the-diatom-thalassiosira-pseudonana
#12
Aubrey Davis, Lauren T Crum, Lynette B Corbeil, Mark Hildebrand
Increasing demand for the low-cost production of valuable proteins has stimulated development of novel expression systems. Many challenges faced by existing technology may be overcome by using unicellular microalgae as an expression platform due to their ability to be cultivated rapidly, inexpensively, and in large scale. Diatoms are a particularly productive type of unicellular algae showing promise as production organisms. Here, we report the development of an expression system in the diatom Thalassiosira pseudonana by expressing the protective IbpA DR2 antigen from Histophilus somni for the production of a vaccine against bovine respiratory disease...
April 12, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28402325/the-bioenergetics-of-inflammation-insights-into-obesity-and-type-2-diabetes
#13
REVIEW
K N Keane, E K Calton, R Carlessi, P H Hart, P Newsholme
Diabetes mellitus is one of the most common chronic metabolic disorders worldwide, and its incidence in Asian countries is alarmingly high. Type 2 diabetes (T2DM) is closely associated with obesity, and the staggering rise in obesity is one of the primary factors related to the increased frequency of T2DM. Low-grade chronic inflammation is also accepted as an integral metabolic adaption in obesity and T2DM, and is believed to be a major player in the onset of insulin resistance. However, the exact mechanism(s) that cause a persistent chronic low-grade infiltration of leukocytes into insulin-target tissues such as adipose, skeletal muscle and liver are not entirely known...
April 12, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28366813/mita-modulated-autophagy-flux-promotes-cell-death-in-breast-cancer-cells
#14
Khyati Bhatelia, Kritarth Singh, Paresh Prajapati, Lakshmi Sripada, Milton Roy, Rajesh Singh
The crosstalk between inflammation and autophagy is an emerging phenomenon observed during tumorigenesis. Activation of NF-κB and IRF3 plays a key role in the regulation of cytokines that are involved in tumor growth and progression. The genes of innate immunity are known to regulate the master transcription factors like NF-κB and IRF3. Innate immunity pathways at the same time regulate the genes of the autophagy pathway which are essential for tumor cell metabolism. In the current study, we studied the role of MITA (Mediator of IRF3 Activation), a regulator of innate immunity, in the regulation of autophagy and its implication in cell death of breast cancer cells...
March 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28363762/an-integrated-network-analysis-reveals-that-nitric-oxide-reductase-prevents-metabolic-cycling-of-nitric-oxide-by-pseudomonas-aeruginosa
#15
Jonathan L Robinson, Jacob M Jaslove, Allison M Murawski, Christopher H Fazen, Mark P Brynildsen
Nitric oxide (NO) is a chemical weapon within the arsenal of immune cells, but is also generated endogenously by different bacteria. Pseudomonas aeruginosa are pathogens that contain an NO-generating nitrite (NO2(-)) reductase (NirS), and NO has been shown to influence their virulence. Interestingly, P. aeruginosa also contain NO dioxygenase (Fhp) and nitrate (NO3(-)) reductases, which together with NirS provide the potential for NO to be metabolically cycled (NO→NO3(-)→NO2(-)→NO). Deeper understanding of NO metabolism in P...
March 29, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28349484/in-vitro-and-ex-vivo-models-to-study-t-cell-migration-through-the-human-liver-parenchyma
#16
Benjamin G Wiggins, Konstantinos Aliazis, Scott P Davies, Gideon Hirschfield, Patricia F Lalor, Gary Reynolds, Zania Stamataki
The liver is the largest internal organ and filters around 3 pints of blood per minute. This continuous flux of blood should not be confused with rapid egress of lymphocytes through the liver; this organ has intricate corridors of specialized sinusoidal spaces, ensuring that immune cells decelerate to shear flow rates, and providing ample opportunities to interact with parenchymal cells. Migration has been intricately linked to T cell function; it is therefore important to study liver T cell biology into context within the liver microenvironment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28340358/lysosomal-rupture-induced-by-structurally-distinct-chitosans-either-promotes-a-type-1-ifn-response-or-activates-the-inflammasome-in-macrophages
#17
David Fong, Pascal Grégoire-Gélinas, Alexandre P Cheng, Tal Mezheritsky, Marc Lavertu, Sachiko Sato, Caroline D Hoemann
Chitosan is a family of glucosamine and N-acetyl glucosamine polysaccharides with poorly understood immune modulating properties. Here, functional U937 macrophage responses were analyzed in response to a novel library of twenty chitosans with controlled degree of deacetylation (DDA, 60-98%), molecular weight (1 to >100 kDa), and acetylation pattern (block vs. random). Specific chitosan preparations (10 or 190 kDa 80% block DDA and 3, 5, or 10 kDa 98% DDA) either induced macrophages to release CXCL10 and IL-1ra at 5-50 μg/mL, or activated the inflammasome to release IL-1β and PGE2 at 50-150 μg/mL...
March 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28300333/psychological-stress-induced-colonic-barrier-dysfunction-role-of-immune-mediated-mechanisms
#18
P Hattay, D K Prusator, L Tran, B Greenwood-Van Meerveld
BACKGROUND: Evidence suggests that patients with irritable bowel syndrome (IBS) exhibit increases in gut permeability and alterations in tight junction (TJ) protein expression. Although psychological stress worsens IBS symptoms, the mechanisms by which stress enhances gut permeability and affects TJ protein expression remain to be determined. Here, we test the hypothesis that chronic intermittent psychological stress activates the release of proinflammatory cytokines to alter TJ proteins and promotes increased gut permeability...
March 16, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28289506/regulation-of-mitochondrial-function-and-endoplasmic-reticulum-stress-by-nitric-oxide-in-pluripotent-stem-cells
#19
REVIEW
Estefania Caballano-Infantes, José Terron-Bautista, Amparo Beltrán-Povea, Gladys M Cahuana, Bernat Soria, Hajji Nabil, Francisco J Bedoya, Juan R Tejedo
Mitochondrial dysfunction and endoplasmic reticulum stress (ERS) are global processes that are interrelated and regulated by several stress factors. Nitric oxide (NO) is a multifunctional biomolecule with many varieties of physiological and pathological functions, such as the regulation of cytochrome c inhibition and activation of the immune response, ERS and DNA damage; these actions are dose-dependent. It has been reported that in embryonic stem cells, NO has a dual role, controlling differentiation, survival and pluripotency, but the molecular mechanisms by which it modulates these functions are not yet known...
February 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28274797/polyplex-evolution-understanding-biology-optimizing-performance
#20
REVIEW
Arnaldur Hall, Ulrich Lächelt, Jiri Bartek, Ernst Wagner, Seyed Moein Moghimi
Polyethylenimine (PEI) is a gold standard polycationic transfectant. However, the highly efficient transfecting activity of PEI and many of its derivatives is accompanied by serious cytotoxic complications and safety concerns at innate immune levels, which impedes the development of therapeutic polycationic nucleic acid carriers in general and their clinical applications. In recent years, the dilemma between transfection efficacy and adverse PEI activities has been addressed from in-depth investigations of cellular processes during transfection and elucidation of molecular mechanisms of PEI-mediated toxicity and translation of these integrated events to chemical engineering of novel PEI derivatives with an improved benefit-to-risk ratio...
March 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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