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https://www.readbyqxmd.com/read/28647672/therapeutic-targeting-of-nuclear-export-inhibition-in-lung-cancer
#1
Arjun Gupta, Jessica M Saltarski, Michael A White, Pier P Scaglioni, David E Gerber
Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic targeting of this process, termed selective inhibition of nuclear export (SINE), has demonstrated anti-tumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1)-which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma (Rb), adenomatous polyposis coli (APC), p53, p73, p21, p27, FOXO, STAT3, IKB, topoisomerase II and PAR-4-is the principal focus of SINE drug development...
June 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28647496/a-comprehensive-complex-systems-approach-to-the-study-and-analysis-of-mammalian-cell-cycle-control-system-in-the-presence-of-dna-damage-stress
#2
Ali Abroudi, Sandhya Samarasinghe, Don Kulasiri
Not many models of mammalian cell cycle system exist due to its complexity. Some models are too complex and hard to understand, while some others are too simple and not comprehensive enough. Moreover, some essential aspects, such as the response of G1-S and G2-M checkpoints to DNA damage as well as the growth factor signalling, have not been investigated from a systems point of view in current mammalian cell cycle models. To address these issues, we bring a holistic perspective to cell cycle by mathematically modelling it as a complex system consisting of important sub-systems that interact with each other...
June 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28647385/hunger-and-disinhibition-but-not-cognitive-restraint-are-associated-with-central-norepinephrine-transporter-availability
#3
A Bresch, M Rullmann, J Luthardt, G A Becker, M Patt, Y-S Ding, A Hilbert, O Sabri, S Hesse
The relationship between food-intake related behaviours measured by the Three-Factor Eating Questionnaire (TFEQ) and in vivo norepinephrine transporter (NET) availability has not been explored yet. We investigated ten obese individuals (body mass index (BMI) 42.4 ± 3.7 kg/m(2)) and ten normal-weight healthy controls (HC, BMI 23.9 ± 2.5 kg/m(2)) with (S,S)-[(11)C]-O-methylreboxetine ([(11)C]MRB) positron emission tomography (PET). All participants completed the TFEQ, which measures cognitive restraint, disinhibition and hunger...
June 21, 2017: Appetite
https://www.readbyqxmd.com/read/28647012/striatal-activation-predicts-differential-therapeutic-responses-to-methylphenidate-and-atomoxetine
#4
Kurt P Schulz, Anne-Claude V Bédard, Jin Fan, Thomas B Hildebrandt, Mark A Stein, Iliyan Ivanov, Jeffrey M Halperin, Jeffrey H Newcorn
OBJECTIVE: Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). METHOD: A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design...
July 2017: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28646714/synthetic-cathinones-and-stereochemistry-s-enantiomer-of-mephedrone-reduces-anxiety-and-depressant-like-effects-in-cocaine-or-mdpv-abstinent-rats
#5
Helene L Philogene-Khalid, Callum Hicks, Allen B Reitz, Lee-Yuan Liu-Chen, Scott M Rawls
BACKGROUND AND PURPOSE: The neuropharmacological profile of the synthetic cathinone mephedrone (MEPH) is influenced by stereochemistry. Both MEPH enantiomers are monoamine transporter substrates, but R-MEPH is primarily responsible for rewarding effects of MEPH as it produces greater locomotor activation and intracranial self-stimulation than S-MEPH. S-MEPH is a 50-fold more potent 5-HT releaser than R-MEPH and does not place preference in rats. MEPH is also structurally similar to the cathinone derivative bupropion, an antidepressant and smoking cessation medication, suggesting MEPH has therapeutic and addictive properties...
June 13, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28646516/tofacitinib-restores-the-inhibition-of-reverse-cholesterol-transport-induced-by-inflammation-understanding-the-lipid-paradox-associated-with-rheumatoid-arthritis
#6
S Pérez-Baos, J I Barrasa, P Gratal, A Larrañaga-Vera, I Prieto-Potin, G Herrero-Beaumont, R Largo
BACKGROUND AND PURPOSE: Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The Janus kinase (Jak) inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analyzed the effect of tofacitinib on the lipid profile of hyperlipidemic rabbits with chronic arthritis (CA) and on the regulation of reverse cholesterol transport (RCT) during chronic inflammation...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646469/the-cathinones-mdpv-and-%C3%AE-pvp-elicit-different-behavioral-and-molecular-effects-following-acute-exposure
#7
Giuseppe Giannotti, Isabella Canazza, Lucia Caffino, Sabrine Bilel, Andrea Ossato, Fabio Fumagalli, Matteo Marti
Since the mid-to-late 2000s, synthetic cathinones have gained popularity among drug users due to their psychostimulant effects greater than those produced by cocaine and amphetamine. Among them, 3,4-methylenedioxypyrovalerone (MDPV) and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PVP) are ones of the most popular cathinones available in the clandestine market as "bath salts" or "fertilizers." Pre-clinical studies indicate that MDPV and α-PVP induced psychomotor stimulation, affected thermoregulation, and promoted reinforcing properties in rodents...
June 23, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28646115/genome-analysis-of-endomicrobium-proavitum-suggests-loss-and-gain-of-relevant-functions-during-the-evolution-of-intracellular-symbionts
#8
Hao Zheng, Carsten Dietrich, Andreas Brune
Bacterial endosymbionts of eukaryotes show progressive genome erosion, but detailed investigations of the evolutionary processes involved in the transition to an intracellular lifestyle are generally hampered by the lack of extant free-living lineages. Here, we characterize the genome of the recently isolated, free-living Endomicrobium proavitum, the second member of the Elusimicrobia phylum brought into pure culture, and compare it to the closely related "Candidatus Endomicrobium trichonymphae" strain Rs-D17, a previously described but uncultured endosymbiont of termite gut flagellates...
June 23, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28646111/a-bacillus-paralicheniformis-iron-containing-urease-reduces-urea-concentrations-in-rice-wine
#9
Qingtao Liu, Yuqi Chen, Minglai Yuan, Guocheng Du, Jian Chen, Zhen Kang
Urease, as a nickel-containing metalloenzyme, was the first enzyme to be crystallized, and it has a prominent position in the history of biochemistry. In the present study, we identified a nickel urease gene cluster, ureABCEFGDH, from Bacillus paralicheniformis ATCC 9945a and characterized it in Escherichia coli Enzymatic assays demonstrate that this oxygen-stable urease is also an iron-containing acid urease. UreH heterologous expression assays suggest that this accessory protein is involved in transmembrane transportation of nickel and iron ions...
June 23, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28646091/stress-specific-p38-map-kinase-activation-is-sufficient-to-drive-egf-receptor-endocytosis-but-not-nuclear-translocation
#10
Alejandra Tomas, Sylwia Jones, Simon O Vaughan, Daniel Hochhauser, Clare E Futter
P38 MAP kinase-dependent EGF receptor (EGFR) endocytosis is induced by stress. Ligand and stresses like X-rays, reportedly promote nuclear traffic of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression and so did not represent nuclear EGFR...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28646031/metabolism-and-acetylation-contribute-to-leucine-mediated-inhibition-of-cardiac-glucose-uptake
#11
Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells suggest that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28645958/factors-predicting-self-reported-medication-low-adherence-in-a-large-sample-of-adults-in-the-us-general-population-a-cross-sectional-study
#12
Michael Feehan, Margaux A Morrison, Casey Tak, Donald E Morisky, Margaret M DeAngelis, Mark A Munger
OBJECTIVES: The study objective was to determine the level and correlates of self-reported medication low adherence in the US general population. SETTING: A 30 min cross-sectional online survey was conducted with a national sample of adults. PARTICIPANTS: 9202 adults (aged 18+) who had filled at least three or more prescriptions at a community pharmacy in the past 12 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Self-reported medication adherence was measured with the 8-item Morisky Medication Adherence Scale...
June 23, 2017: BMJ Open
https://www.readbyqxmd.com/read/28645831/synthesis-and-biological-evaluation-of-jl-a7-derivatives-as-potent-abcb1-inhibitors
#13
Miaobo Pan, Jian Cui, Lei Jiao, Hesham Ghaleb, Chen Liao, Jiaqi Zhou, Mutta Kairuki, Haiyan Lin, Wenlong Huang, Hai Qian
Cancer chemotherapy failure is often due to the overexpression of ATP-binding cassette (ABC) transporters (particularly ABCB1), resulting in a variety of structurally and pharmacologically unrelated drugs efflux. The multidrug resistance (MDR) phenomenon could be reversed by ABCB1 inhibitors. Now, JL-A7 as the lead compound based on a triazol-N-ethyl-tetrahydroisoquinoline scaffold, 18 compounds were designed and synthesized. Substitution in para positions yielded high activities toward ABCB1. Moreover, compound 5 could effectively block the drug efflux function of ABCB1 and increase the accumulation of anti-cancer drugs to achieve effective treatment concentration in MDR cells...
June 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28645377/electrical-probes-of-dna-binding-proteins
#14
Jacqueline K Barton, Phillip L Bartels, Yingxin Deng, Elizabeth O'Brien
A DNA electrochemistry platform has been developed to probe proteins bound to DNA electrically. Here gold electrodes are modified with thiol-modified DNA, and DNA charge transport chemistry is used to probe DNA binding and enzymatic reaction both with redox-silent and redox-active proteins. For redox-active proteins, the electrochemistry permits the determination of redox potentials in the DNA-bound form, where comparisons to DNA-free potentials can be made using graphite electrodes without DNA modification...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645217/microtubule-organizing-centers
#15
Jingchao Wu, Anna Akhmanova
The organization of microtubule networks is crucial for controlling chromosome segregation during cell division, positioning, and transport of different organelles and for cell polarity and morphogenesis. The geometry of microtubule arrays strongly depends on the localization and activity of the sites where microtubules are nucleated and where their minus ends are anchored. Such sites are often clustered into structures known as microtubule-organizing centers, which include the centrosomes in animals and spindle pole bodies in fungi...
June 23, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28645090/the-impact-of-tidal-and-mesoscale-eddy-advection-on-the-long-term-dispersion-of-99-tc-from-sellafield
#16
Magne Simonsen, Øyvind Saetra, Pål Erik Isachsen, Ole Christian Lind, Hilde Kristin Skjerdal, Brit Salbu, Hilde Elise Heldal, Justin P Gwynn
In the present work, numerical models are used to study the fate of the (99)Tc discharges from Sellafield with a specific focus on the role of mesoscale eddy and tidal advection on the transport and dispersion of this radionuclide. Transport estimates are made with an ocean model that resolves a large part of the ocean mesoscale eddy field and also includes tides. Equivalent estimates are also computed with another model in which these processes are either absent or parametrized. Comparison with field observations shows that the coarse-resolution model can reproduce the general features of the observed time-space (99)Tc distribution if the diffusivity in its eddy parametrization scheme is suitably chosen...
June 20, 2017: Journal of Environmental Radioactivity
https://www.readbyqxmd.com/read/28645067/using-a-detailed-inventory-of-a-large-wastewater-treatment-plant-to-estimate-the-relative-importance-of-construction-to-the-overall-environmental-impacts
#17
Serni Morera, Lluís Corominas, Miquel Rigola, Manel Poch, Joaquim Comas
The aim of this work is to quantify the relative contribution to the overall environmental impact of the construction phase compared to the operational phase for a large conventional activated sludge wastewater treatment plant (WWTP). To estimate these environmental impacts, a systematic procedure was designed to obtain the detailed Life Cycle Inventories (LCI) for civil works and equipment, taking as starting point the construction project budget and the list of equipment installed at the Girona WWTP, which are the most reliable information sources of materials and resources used during the construction phase...
June 2, 2017: Water Research
https://www.readbyqxmd.com/read/28645051/enantioselective-disturbance-of-chiral-herbicide-dichlorprop-to-nitrogen-metabolism-of-arabidopsis-thaliana-regular-analysis-and-stable-isotope-attempt
#18
Zunwei Chen, Jia Wang, Siyu Chen, Yuezhong Wen
As the most essential element, nitrogen play a pivotal role in plant physiological process, which is susceptible to contaminants. However, the enantioselective effects of chiral herbicides on nitrogen metabolism have not been comprehensively understood. In this study, effects of chiral herbicide dichlorprop (DCPP) on the nitrogen behaviors in Arabidopsis thaliana were investigated. The results revealed that the uptakes of inorganic nitrogen (NO3(-) and NH4(+)) were preferentially impacted by herbicidal active (R)-DCPP, where the transportation of beneficial NO3(-) was inhibited but the toxic NH4(+) was accumulated...
June 20, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28644754/expression-of-enzymes-related-to-glucose-metabolism-in-non-small-cell-lung-cancer-and-prognosis
#19
Alexandra Giatromanolaki, Efthimios Sivridis, Stella Arelaki, Michael I Koukourakis
Purpose/Aim: Cancer cells are addicted to glycolytic anaerobic pathways, in presence or in absence of a functional Krebs' cycle (phenomenon Warburg). This metabolic predilection relies on both extracellular (impaired vascularization and oxygenation) and intracellular (oncogenic activation of genes) causes. MATERIALS AND METHODS: We investigated the expression and prognostic relevance of enzymes involved in the glucose absorption and metabolism, monocarboxylate transporter (MCT) expression, MCT1 and MCT2, pentose pathway (Glucose-6-phospahte dehydrogenase G6PD), glycogene synthesis (glycogene synthase GYS1), glycolysis (Hexokinase HXKII, phosphofructokinase PFK1, fructose biphosphate aldolase), fate of pyruvate (pyruvate dehydrogenase PDH, phosphorylated pPDH, PDH kinase PDK1, lactate dehydrogenase LDH5 and LDH1) and key Kreb's cycle enzymes (citrate synthase CSynth and isocitrate dehydrogenase IDH)...
June 23, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28644714/genome-mining-in-silico-validation-and-phase-selection-of-a-novel-aldo-keto-reductase-from-candida-glabratea-for-biotransformation
#20
Souvik Basak, Nanda Gopal Sahoo, Angayar K Pavanasam
Previously, we published cloning, over-expression, characterization and subsequent exploitation of a carbonyl reductase (cr) gene, belonging to general family aldo-keto reductase from Candida glabrata CBS138 to convert keto ester (COBE) to a chiral alcohol (ethyl-4-chloro-3-hydroxybutanoate or CHBE). Exploiting global transcription factor CRP, rDNA and transporter engineering, we have improved batch production of CHBE by trinomial bioengineering. Herein, we present the exploration of cr gene in Candida glabrata CBS138 through genome miningapproach, in silico validation of its activity and selection of its biocatalytic phase...
June 23, 2017: Bioengineered
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