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https://www.readbyqxmd.com/read/28811106/questiomycin-a-stimulates-sorafenib-induced-cell-death-via-suppression-of-glucose-regulated-protein-78
#1
Kayo Machihara, Hidenori Tanaka, Yoshihiro Hayashi, Ichiro Murakami, Takushi Namba
Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat owing to the lack of effective chemotherapeutic methods. Sorafenib, the first-line and only available treatment for HCC, extends patient overall survival by several months, with a response rate below 10%. Thus, the identification of an agent that enhances the anticancer effect of sorafenib is critical for the development of therapeutic options for HCC. Endoplasmic reticulum (ER) stress response is one of the methods of sorafenib-induced cell death...
August 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28749938/the-mecillinam-resistome-reveals-a-role-for-peptidoglycan-endopeptidases-in-stimulating-cell-wall-synthesis-in-escherichia-coli
#2
Ghee Chuan Lai, Hongbaek Cho, Thomas G Bernhardt
Bacterial cells are typically surrounded by an net-like macromolecule called the cell wall constructed from the heteropolymer peptidoglycan (PG). Biogenesis of this matrix is the target of penicillin and related beta-lactams. These drugs inhibit the transpeptidase activity of PG synthases called penicillin-binding proteins (PBPs), preventing the crosslinking of nascent wall material into the existing network. The beta-lactam mecillinam specifically targets the PBP2 enzyme in the cell elongation machinery of Escherichia coli...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28720467/intradermal-immunization-with-raav1-vector-induces-robust-memory-cd8-t-cell-responses-independently-of-transgene-expression-in-dcs
#3
Alexandre Ghenassia, David-Alexandre Gross, Stéphanie Lorain, Fabiola Tros, Dominique Urbain, Sofia Benkhelifa-Ziyyat, Alain Charbit, Jean Davoust, Pascal Chappert
Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8(+) T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8(+) T cell responses...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28706238/freezing-response-independent-facilitation-of-fear-extinction-memory-in-the-prefrontal-cortex
#4
Jiso Hong, Daesoo Kim
The infralimbic cortex (IL) is known to facilitate the formation of extinction memory through reciprocal interactions with the amygdala, which produces fear responses such as freezing. Thus, whether presynaptic input from the amygdala and post-synaptic output of IL neurons are functionally dissociated in extinction memory formation remains unclear. Here, we demonstrated that photostimulation of IL inputs from BLA did not change freezing responses to conditioned stimuli (CS) during training, but did facilitate extinction memory, measured as a reduction in freezing responses to the CS 1 day later...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696913/linking-physiological-parameters-to-perturbations-in-the-human-exposome-environmental-exposures-modify-blood-pressure-and-lung-function-via-inflammatory-cytokine-pathway
#5
Matthew A Stiegel, Joachim D Pleil, Jon R Sobus, Tina Stevens, Michael C Madden
Human biomonitoring is an indispensable tool for evaluating the systemic effects derived from external stressors including environmental pollutants, chemicals from consumer products, and pharmaceuticals. The aim of this study was to explore consequences of environmental exposures to diesel exhaust (DE) and ozone (O3) and ultimately to interpret these parameters from the perspective of in vitro to in vivo extrapolation. In particular, the objective was to use cytokine expression at the cellular level as a biomarker for physiological systemic responses such as blood pressure and lung function at the systemic level...
July 11, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28692049/mdm2-selectively-suppresses-dna-damage-arising-from-inhibition-of-topoisomerase-ii-independent-of-p53
#6
J C Senturk, S Bohlman, J J Manfredi
Mdm2 is often overexpressed in tumors that retain wild-type TP53 but may affect therapeutic response independently of p53. Herein is shown that tumor cells with MDM2 amplification are selectively resistant to treatment with topoisomerase II poisons but not other DNA damaging agents. Tumor cells that overexpress Mdm2 have reduced DNA double-strand breaks in response to doxorubicin or etoposide. This latter result is not due to altered drug uptake. The selective attenuation of DNA damage in response to these agents is dependent on both Mdm2 levels and an intact ubiquitin ligase function...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28652400/activation-of-human-basophils-by-a549-lung-epithelial-cells-reveals-a-novel-ige-dependent-response-independent-of-allergen
#7
John T Schroeder, Anja P Bieneman
Evidence for epithelial cell (EC)-derived cytokines (e.g., thymic stromal lymphopoietin [TSLP]) activating human basophils remains controversial. We therefore hypothesize that ECs can directly activate basophils via cell-to-cell interaction. Basophils in medium alone or with IL-3 ± anti-IgE were coincubated with TSLP, IL-33, or IL-25. Analogous experiments cocultured basophils (1-72 h) directly with EC lines. Supernatants were tested for mediators and cytokines. Abs targeting receptors were tested for neutralizing effects...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28610902/post-stimulus-fmri-and-eeg-responses-evidence-for-a-neuronal-origin-hypothesised-to-be-inhibitory
#8
K J Mullinger, M T Cherukara, R B Buxton, S T Francis, S D Mayhew
Post-stimulus undershoots, negative responses following cessation of stimulation, are widely observed in functional magnetic resonance (fMRI) blood oxygenation level dependent (BOLD) data. However, the debate surrounding whether the origin of this response phase is neuronal or vascular, and whether it provides functionally relevant information, that is additional to what is contained in the primary response, means that undershoots are widely overlooked. We simultaneously recorded electroencephalography (EEG), BOLD and cerebral blood-flow (CBF) [obtained from arterial spin labelled (ASL) fMRI] fMRI responses to hemifield checkerboard stimulation to test the potential neural origin of the fMRI post-stimulus undershoot...
June 10, 2017: NeuroImage
https://www.readbyqxmd.com/read/28584876/on-the-nature-of-directed-behavior-to-drug-associated-light-cues-in-rhesus-monkeys-macaca-mulatta
#9
Mark P Reilly, Sonja I Berndt, James H Woods
The present study investigated the role of drug-paired stimuli in controlling the behavior of rhesus monkeys. Systematic observations were made with nine monkeys who had a history of drug self-administration; they had been lever pressing to produce intravenous infusions of various drugs. These observations revealed that the stimulus light co-occurring with drug infusion produced robust and cue-directed behavior such as orienting, touching and biting. Experiment 1 showed that this light-directed behavior would occur in naïve monkeys exposed to a Pavlovian pairing procedure...
November 2016: Behavior Analysis (Washington, D.C.)
https://www.readbyqxmd.com/read/28559819/two-year-complete-remission-of-diffuse-large-b-cell-lymphoma-in-an-immunological-nonresponder-hiv-infected-patient-case-report
#10
Miodrag Vrbic, Ivan Petkovic, Svetislav Vrbic, Maja Jovanovic, Aleksandar Rankovic, Lidija Popovic-Dragonjic, Marina Djordjevic-Spasic
INTRODUCTION: HIV-infected patients are affected significantly more frequently by all types of lymphoma, with diffuse large B-cell lymphoma (DLBCL) as the most prevalent histological type. Since the introduction of combination antiretroviral therapy (cART) morbidity and mortality of DLBCL has been markedly reduced, which is primarily interpreted as a result of the drug-mediated immune reconstitution. CASE REPORT: We present a previously healthy, 44-year-old HIV-infected man with DLBCL of the oral cavity, treated with immunochemotherapy and cART...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28487202/thalamic-mast-cell-activity-is-associated-with-sign-tracking-behavior-in-rats
#11
Christopher J Fitzpatrick, Jonathan D Morrow
Mast cells are resident immune cells in the thalamus that can degranulate and release hundreds of signaling molecules (i.e., monoamines, growth factors, and cytokines) both basally and in response to environmental stimuli. Interestingly, mast cell numbers in the brain show immense individual variation in both rodents and humans. We used a Pavlovian conditioned approach (PCA) procedure to examine whether mast cells are associated with individual variation in the attribution of incentive-motivational value to reward-related cues...
October 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28446868/triggering-avoidance-dissociable-influences-of-aversive-pavlovian-conditioned-stimuli-on-human-instrumental-behavior
#12
Sara Garofalo, Trevor W Robbins
The present study investigates human aversive Pavlovian-to-Instrumental Transfer (PIT) and possible influences of outcome devaluation and instrumental overtraining on this effect. PIT measures the extent to which a Pavlovian conditioned stimulus (CS) can increase instrumental responses independently paired with the same (outcome-specific transfer) or a different (general transfer) reinforcer. Two measures of PIT were obtained: the percentage of instrumental responses and the vigor of such responses. Thirty-eight volunteers performed a standard PIT task sequence...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28418904/a-consensus-hemagglutinin-based-vaccine-delivered-by-an-attenuated-salmonella-mutant-protects-chickens-against-heterologous-h7n1-influenza-virus
#13
Kim Je Hyoung, Irshad Ahmed Hajam, John Hwa Lee
H7N3 and H7N7 are highly pathogenic avian influenza (HPAI) viruses and have posed a great threat not only for the poultry industry but for the human health as well. H7N9, a low pathogenic avian influenza (LPAI) virus, is also highly pathogenic to humans, and there is a great concern that these H7 subtypes would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. A vaccine candidate covering all the three subtypes must, therefore, be an integral part of any pandemic preparedness plan...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28385494/schistosome-induced-pulmonary-b-cells-inhibit-allergic-airway-inflammation-and-display-a-reduced-th2-driving-function
#14
L E P M van der Vlugt, K Obieglo, A Ozir-Fazalalikhan, T Sparwasser, S Haeberlein, H H Smits
Chronic schistosome infections protect against allergic airway inflammation (AAI) via the induction of IL-10-producing splenic regulatory B (Breg) cells. Previous experiments have demonstrated that schistosome-induced pulmonary B cells can also reduce AAI, but act independently of IL-10. We have now further characterized the phenotype and inhibitory activity of these protective pulmonary B cells. We excluded a role for regulatory T (Treg) cell induction as putative AAI-protective mechanisms. Schistosome-induced B cells showed increased CD86 expression and reduced cytokine expression in response to Toll-like receptor (TLR) ligands compared with control B cells...
April 4, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28319463/solid-cancer-incidence-among-the-life-span-study-of-atomic-bomb-survivors-1958-2009
#15
Eric J Grant, Alina Brenner, Hiromi Sugiyama, Ritsu Sakata, Atsuko Sadakane, Mai Utada, Elizabeth K Cahoon, Caitlin M Milder, Midori Soda, Harry M Cullings, Dale L Preston, Kiyohiko Mabuchi, Kotaro Ozasa
This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up...
May 2017: Radiation Research
https://www.readbyqxmd.com/read/28263416/the-effect-of-reward-expectation-on-the-time-course-of-perceptual-decisions
#16
Annalisa Tosoni, Giorgia Committeri, Cinzia Calluso, Gaspare Galati
Perceptual discriminations can be strongly biased by the expected reward for a correct decision but the neural mechanisms underlying this influence are still partially unclear. Using functional magnetic resonance imaging (fMRI) during a task requiring to arbitrarily associate a visual stimulus with a specific action, we have recently shown that perceptual decisions are encoded within the same sensory-motor regions responsible for planning and executing specific motor actions. Here we examined whether these regions additionally encode the amount of expected reward for a perceptual decision...
March 6, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28261564/legionella-pneumophila-strain-130b-evades-macrophage-cell-death-independent-of-the-effector-sidf-in-the-absence-of-flagellin
#17
Mary Speir, Adam Vogrin, Azadeh Seidi, Gilu Abraham, Stéphane Hunot, Qingqing Han, Gerald W Dorn, Seth L Masters, Richard A Flavell, James E Vince, Thomas Naderer
The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28242789/tm6sf2-rs58542926-variant-affects-postprandial-lipoprotein-metabolism-and-glucose-homeostasis-in-nafld
#18
Giovanni Musso, Ugo Cipolla, Maurizio Cassader, Silvia Pinach, Francesca Saba, Franco De Michieli, Elena Paschetta, Daria Bongiovanni, Luciana Framarin, Nicola Leone, Mara Berrutti, Floriano Rosina, Stefania Corvisieri, Federica Molinaro, Antonio Sircana, Roberto Gambino
Mechanisms underlying the opposite effects of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C>T polymorphism on liver injury and cardiometabolic risk in nonalcoholic fatty liver disease (NAFLD) are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabolism, glucose homeostasis, and nutrient oxidation in NAFLD. Sixty nonobese nondiabetic normolipidemic biopsy-proven NAFLD patients and 60 matched controls genotyped for TM6SF2 C>T polymorphism underwent: indirect calorimetry; an oral fat tolerance test with measurement of plasma lipoprotein subfractions, adipokines, and incretin glucose-dependent insulinotropic polypeptide (GIP); and an oral glucose tolerance test with minimal model analysis of glucose homeostasis...
June 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28241570/thickness-independent-dynamics-in-cholesteric-liquid-crystals
#19
Yo Inoue, Mayo Hattori, Hiroshi Moritake
We report fast electro-optic response independent of cell thickness in cholesteric liquid crystals (ChLCs). Usually, an electric field normal to the helix axis of ChLCs induces two fast and one slow response components: helical elongation (slow one), helical deformation (fast one), and flexoelectric effect (fast one). In this study, we found that a planarly aligned ChLC applied with an in-plane electric field exhibited only fast response components because the glass substrates suppressed the motion of the helical elongation...
February 20, 2017: Optics Express
https://www.readbyqxmd.com/read/28221370/blunted-ventral-striatal-responses-to-anticipated-rewards-foreshadow-problematic-drug-use-in-novelty-seeking-adolescents
#20
Christian Büchel, Jan Peters, Tobias Banaschewski, Arun L W Bokde, Uli Bromberg, Patricia J Conrod, Herta Flor, Dimitri Papadopoulos, Hugh Garavan, Penny Gowland, Andreas Heinz, Henrik Walter, Bernd Ittermann, Karl Mann, Jean-Luc Martinot, Marie-Laure Paillère-Martinot, Frauke Nees, Tomas Paus, Zdenka Pausova, Luise Poustka, Marcella Rietschel, Trevor W Robbins, Michael N Smolka, Juergen Gallinat, Gunter Schumann, Brian Knutson
Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16...
February 21, 2017: Nature Communications
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