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https://www.readbyqxmd.com/read/29891009/dexamethasone-induced-immunosuppression-mechanisms-and-implications-for-immunotherapy
#1
Amber J Giles, Marsha-Kay N D Hutchinson, Heather M Sonnemann, Jinkyu Jung, Peter E Fecci, Nivedita M Ratnam, Wei Zhang, Hua Song, Rolanda Bailey, Dionne Davis, Caitlin M Reid, Deric M Park, Mark R Gilbert
BACKGROUND: Corticosteroids are routinely utilized to alleviate edema in patients with intracranial lesions and are first-line agents to combat immune-related adverse events (irAEs) that arise with immune checkpoint blockade treatment. However, it is not known if or when corticosteroids can be administered without abrogating the efforts of immunotherapy. The purpose of this study was to evaluate the impact of dexamethasone on lymphocyte activation and proliferation during checkpoint blockade to provide guidance for corticosteroid use while immunotherapy is being implemented as a cancer treatment...
June 11, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29889086/a-feasibility-study-of-combined-intermittent-theta-burst-stimulation-and-modified-constraint-induced-aphasia-therapy-in-chronic-post-stroke-aphasia
#2
Jerzy P Szaflarski, Joseph Griffis, Jennifer Vannest, Jane B Allendorfer, Rodolphe Nenert, Amy W Amara, Victor Sung, Harrison C Walker, Amber N Martin, Victor W Mark, Xiaohua Zhou
PURPOSE: The purpose of this feasibility study was to assess whether combined intermittent theta burst suppression (iTBS) applied to the ipsilesional hemisphere and modified constraint-induced aphasia therapy (mCIAT) are safe and logistically feasible within the time interval associated with iTBS induced long-term potentiation in patients with post-stroke aphasia. We also wanted to determine whether combining priming with iTBS and CIAT improves language functions after treatment. METHODS: Twelve participants received fMRI (semantic decision/tone decision task) and neuropsychological testing of language skills at three time points - before starting the iTBS/mCIAT intervention (T1), immediately after completing 2-week long course of intervention (T2), and at 3-months follow-up (T3)...
June 6, 2018: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#3
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29764837/il22-promotes-kras-mutant-lung-cancer-by-induction-of-a-pro-tumor-immune-response-and-protection-of-stemness-properties
#4
Nasim Khosravi, Mauricio S Caetano, Amber M Cumpian, Nese Unver, Cynthia De la Garza Ramos, Oscar Noble, Soudabeh Daliri, Belinda J Hernandez, Berenice A Gutierrez, Scott E Evans, Samir Hanash, Andrei M Alekseev, Yi Yang, Seon Hee Chang, Roza Nurieva, Humam Kadara, Jichao Chen, Edwin J Ostrin, Seyed Javad Moghaddam
Somatic KRAS mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a Kras-induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-kB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4+ T-helper cell response. IL22 is an effector molecule secreted by CD4+ and γδ T cells that we previously found to be expressed in CC-LR mice. IL22 mostly signals through the STAT3 pathway and is thought to act exclusively on non-hematopoietic cells with basal IL22 receptor (IL22R) expression on epithelial cells...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29763307/genetic-code-expansion-in-rhodobacter-sphaeroides-to-incorporate-non-canonical-amino-acids-into-photosynthetic-reaction-centers
#5
Jared Weaver, Steven G Boxer
Photosynthetic reaction centers (RCs) are the membrane proteins responsible for the initial charge separation steps central to photosynthesis. As a complex and spectroscopically complicated membrane protein, the RC (and other associated photosynthetic proteins) would benefit greatly from the insight offered by site-specifically encoded non-canonical amino acids in the form of probes and an increased chemical range in key amino acid analogues. Towards that goal, we developed a method to transfer amber codon suppression machinery developed for E...
May 15, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29722167/artificial-light-pollution-shifting-spectral-wavelengths-to-mitigate-physiological-and-health-consequences-in-a-nocturnal-marsupial-mammal
#6
Alicia M Dimovski, Kylie A Robert
The focus of sustainable lighting tends to be on reduced CO2 emissions and cost savings, but not on the wider environmental effects. Ironically, the introduction of energy-efficient lighting, such as light emitting diodes (LEDs), may be having a great impact on the health of wildlife. These white LEDs are generated with a high content of short-wavelength 'blue' light. While light of any kind can suppress melatonin and the physiological processes it regulates, these short wavelengths are potent suppressors of melatonin...
May 2, 2018: Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
https://www.readbyqxmd.com/read/29714012/probing-antibody-binding-sites-on-g-protein-coupled-receptors-using-genetically-encoded-photo-activatable-cross-linkers
#7
Thomas Huber, Thomas P Sakmar
We describe a methodology to map epitopes of monoclonal antibodies that bind to G protein-coupled receptors (GPCRs). The method relies on an amber codon suppression strategy to genetically encode photo-activatable cross-linkers, such as p-azido-L-phenylalanine (azF) or p-benzoly-L-phenylalanine (BzF), in GPCRs expressed in mammalian cells in culture. Individual receptor variants that harbor a site-specific photo-crosslinker residue can be assayed for functional activity in standard cell-based assays. The interaction sites between the receptor variants and an antibody can be mapped by determining which of the azF or BzF residues cross-link to the antibody upon UV irradiation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29694026/directed-evolution-of-heterologous-trnas-leads-to-reduced-dependence-on-post-transcriptional-modifications
#8
Kevin C Baldridge, Manasses Jora, Andre C Maranhao, Matthew M Quick, Balasubrahmanyam Addepalli, Jennifer S Brodbelt, Andrew D Ellington, Patrick A Limbach, Lydia M Contreras
Heterologous tRNA:aminoacyl tRNA synthetase pairs are often employed for noncanonical amino acid incorporation in the quest for an expanded genetic code. In this work, we investigated one possible mechanism by which directed evolution can improve orthogonal behavior for a suite of Methanocaldococcus jannaschii ( Mj) tRNATyr -derived amber suppressor tRNAs. Northern blotting demonstrated that reduced expression of heterologous tRNA variants correlated with improved orthogonality. We suspected that reduced expression likely minimized nonorthogonal interactions with host cell machinery...
May 18, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29688896/nox2-in-regulatory-t-cells-promotes-angiotensin-ii-induced-cardiovascular-remodeling
#9
Amber Emmerson, Silvia Cellone Trevelin, Heloise Mongue-Din, Pablo D Becker, Carla Ortiz, Lesley A Smyth, Qi Peng, Raul Elgueta, Greta Sawyer, Aleksandar Ivetic, Robert I Lechler, Giovanna Lombardi, Ajay M Shah
The superoxide-generating enzyme Nox2 contributes to hypertension and cardiovascular remodeling triggered by activation of the renin-angiotensin system. Multiple Nox2-expressing cells are implicated in angiotensin II-induced (Ang II-induced) pathophysiology, but the importance of Nox2 in leukocyte subsets is poorly understood. Here, we investigated the role of Nox2 in T cells, particularly Tregs. Mice globally deficient in Nox2 displayed increased numbers of Tregs in the heart at baseline, whereas Ang II-induced effector T cell (Teff) infiltration was inhibited...
June 11, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29683855/a-week-48-randomized-phase-3-trial-of-darunavir-cobicistat-emtricitabine-tenofovir-alafenamide-in-treatment-na%C3%A3-ve-hiv-1-patients
#10
Joseph J Eron, Chloe Orkin, Joel Gallant, Jean-Michel Molina, Eugenia Negredo, Andrea Antinori, Anthony Mills, Jacques Reynes, Erika Van Landuyt, Erkki Lathouwers, Veerle Hufkens, John Jezorwski, Simon Vanveggel, Magda Opsomer
OBJECTIVES: To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naïve, HIV-1-infected adults. DESIGN: Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247). METHODS: Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363)...
April 19, 2018: AIDS
https://www.readbyqxmd.com/read/29683449/optimizing-the-genetic-incorporation-of-chemical-probes-into-gpcrs-for-photo-crosslinking-mapping-and-bioorthogonal-chemistry-in-live-mammalian-cells
#11
Robert Serfling, Lisa Seidel, Thore Böttke, Irene Coin
The genetic incorporation of non-canonical amino acids (ncAAs) via amber stop codon suppression is a powerful technique to install artificial probes and reactive moieties onto proteins directly in the live cell. Each ncAA is incorporated by a dedicated orthogonal suppressor-tRNA/amino-acyl-tRNA-synthetase (AARS) pair that is imported into the host organism. The incorporation efficiency of different ncAAs can greatly differ, and be unsatisfactory in some cases. Orthogonal pairs can be improved by manipulating either the AARS or the tRNA...
April 9, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29620688/effects-of-branched-chain-amino-acid-supplementation-on-spontaneous-seizures-and-neuronal-viability-in-a-model-of-mesial-temporal-lobe-epilepsy
#12
Shaun E Gruenbaum, Roni Dhaher, Amedeo Rapuano, Hitten P Zaveri, Amber Tang, Nihal de Lanerolle, Tore Eid
BACKGROUND: The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood. MATERIALS AND METHODS: Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8)...
April 3, 2018: Journal of Neurosurgical Anesthesiology
https://www.readbyqxmd.com/read/29615516/mutant-and-wild-type-p53-form-complexes-with-p73-upon-phosphorylation-by-the-kinase-jnk
#13
Eric R Wolf, Ciarán P McAtarsney, Kristin E Bredhold, Amber M Kline, Lindsey D Mayo
The transcription factors p53 and p73 are critical to the induction of apoptotic cell death, particularly in response to cell stress that activates c-Jun N-terminal kinase (JNK). Mutations in the DNA-binding domain of p53, which are commonly seen in cancers, result in conformational changes that enable p53 to interact with and inhibit p73, thereby suppressing apoptosis. In contrast, wild-type p53 reportedly does not interact with p73. We found that JNK-mediated phosphorylation of Thr81 in the proline-rich domain (PRD) of p53 enabled wild-type p53, as well as mutant p53, to form a complex with p73...
April 3, 2018: Science Signaling
https://www.readbyqxmd.com/read/29610342/transcriptional-mutagenesis-mediated-by-8-oxog-induces-translational-errors-in-mammalian-cells
#14
Da-Peng Dai, Wei Gan, Hiroshi Hayakawa, Jia-Lou Zhu, Xiu-Qing Zhang, Guo-Xin Hu, Tao Xu, Zhe-Li Jiang, Li-Qun Zhang, Xue-Da Hu, Ben Nie, Yue Zhou, Jin Li, Xiao-Yang Zhou, Jian Li, Tie-Mei Zhang, Qing He, Dong-Ge Liu, Hai-Bo Chen, Nan Yang, Ping-Ping Zuo, Zhi-Xin Zhang, Huan-Ming Yang, Yao Wang, Samuel H Wilson, Yi-Xin Zeng, Jian-Ye Wang, Mutsuo Sekiguchi, Jian-Ping Cai
Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29603062/peripheral-blood-cell-interactions-of-cancer-derived-exosomes-affect-immune-function
#15
Heather R Ferguson Bennit, Amber Gonda, James R W McMullen, Janviere Kabagwira, Nathan R Wall
Cancer-derived exosomes are constitutively produced and secreted into the blood and biofluids of their host patients providing a liquid biopsy for early detection and diagnosis. Given their ubiquitous nature, cancer exosomes influence biological mechanisms that are beneficial to the tumor cells where they are produced and the microenvironment in which these tumors exist. Accumulating evidence suggests that exosomes transport proteins, lipids, DNA, mRNA, miRNA and long non coding RNA (lncRNA) for the purpose of cell-cell and cell-extracellular communication...
March 30, 2018: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/29570993/a-neural-circuit-for-the-suppression-of-pain-by-a-competing-need-state
#16
Amber L Alhadeff, Zhenwei Su, Elen Hernandez, Michelle L Klima, Sophie Z Phillips, Ruby A Holland, Caiying Guo, Adam W Hantman, Bart C De Jonghe, J Nicholas Betley
Hunger and pain are two competing signals that individuals must resolve to ensure survival. However, the neural processes that prioritize conflicting survival needs are poorly understood. We discovered that hunger attenuates behavioral responses and affective properties of inflammatory pain without altering acute nociceptive responses. This effect is centrally controlled, as activity in hunger-sensitive agouti-related protein (AgRP)-expressing neurons abrogates inflammatory pain. Systematic analysis of AgRP projection subpopulations revealed that the neural processing of hunger and inflammatory pain converge in the hindbrain parabrachial nucleus (PBN)...
March 22, 2018: Cell
https://www.readbyqxmd.com/read/29565959/identifying-levorphanol-ingestion-using-urine-biomarkers-in-health-care-patients
#17
Amber R Watson, Ali Roberts
BACKGROUND: Levorphanol is a long-acting opioid analgesic that is an optical isomer of dextrorphan, a metabolite of the over-the-counter cough suppressant dextromethorphan. Providers prescribing levorphanol for pain management may need to assess compliance through urine drug testing, as this agent is subject to abuse. Therefore, it is important to differentiate between dextromethorphan and levorphanol ingestion. OBJECTIVES: This article is the first to report urine concentrations of levorphanol/dextrorphan and 3-hydroxymorphinan in human urine and assesses the need for an enantiomeric analysis to distinguish between dextromethorphan and levorphanol ingestion...
March 2018: Pain Physician
https://www.readbyqxmd.com/read/29529500/anti-inflammatory-hybrids-of-secondary-amines-and-amide-sulfamide-derivatives
#18
Renren Bai, Jian Sun, Zhongxing Liang, Younghyoun Yoon, Eric Salgado, Amber Feng, Yoonhyeun Oum, Yuanyuan Xie, Hyunsuk Shim
The CXCR4/CXCL12 chemokine axis can chemotactically accumulate inflammatory cells to local tissues and regulate the release of inflammatory factors. Developing novel CXCR4 modulators may provide a desirable strategy to control the development of inflammation. A series of novel hybrids were designed by integrating the key pharmacophores of three CXCR4 modulators. The majority of compounds displayed potent CXCR4 binding affinity. Compound 7a exhibited 1000-fold greater affinity than AMD3100 and significantly inhibited invasion of CXCR4-positive tumor cells...
April 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29528852/fixed-dose-darunavir-boosted-with-cobicistat-combined-with-emtricitabine-and-tenofovir-alafenamide-fumarate
#19
Muge Cevik, Chloe Orkin
PURPOSE OF REVIEW: In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. RECENT FINDINGS: In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes...
March 9, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29517978/trap-seq-identifies-cystine-glutamate-antiporteras-a-driver-of-recovery-from-liver-injury
#20
Amber W Wang, Kirk J Wangensteen, Yue J Wang, Adam M Zahm, Nicholas G Moss, Noam Erez, Klaus H Kaestner
Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the Fah-/- mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We used translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes...
April 30, 2018: Journal of Clinical Investigation
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