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https://www.readbyqxmd.com/read/28103901/pathogenic-lrrk2-variants-are-gain-of-function-mutations-that-enhance-lrrk2-mediated-repression-of-%C3%AE-catenin-signaling
#1
Daniel C Berwick, Behzad Javaheri, Andrea Wetzel, Mark Hopkinson, Jonathon Nixon-Abell, Simone Grannò, Andrew A Pitsillides, Kirsten Harvey
BACKGROUND: LRRK2 mutations and risk variants increase susceptibility to inherited and idiopathic Parkinson's disease, while recent studies have identified potential protective variants. This, and the fact that LRRK2 mutation carriers develop symptoms and brain pathology almost indistinguishable from idiopathic Parkinson's disease, has led to enormous interest in this protein. LRRK2 has been implicated in a range of cellular events, but key among them is canonical Wnt signalling, which results in increased levels of transcriptionally active β-catenin...
January 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28097047/quantifying-the-on-and-off-contributions-to-the-flash-erg-with-the-discrete-wavelet-transform
#2
Mathieu Gauvin, Maja Sustar, John M Little, Jelka Brecelj, Jean-Marc Lina, Pierre Lachapelle
PURPOSE: Discrete wavelet transform (DWT) analyses suggest that the 20- and 40-Hz components of the short-flash photopic electroretinogram (ERG) are closely related to the ON and OFF pathways, respectively. With the DWT, we examined how the ERG ON and OFF components are modulated by the stimulus intensity and/or duration. METHODS: Discrete wavelet transform descriptors (20, 40 Hz and 40:20-Hz ratio) were extracted from ERGs evoked to 25 combinations of flash durations (150-5 ms) and strengths (0...
January 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28094991/polarization-mediated-modulation-of-electronic-and-transport-properties-of-hybrid-mos2-batio3-srruo3-tunnel-junctions
#3
Tao Li, Pankaj Sharma, Alexey Lipatov, Hyungwoo Lee, Jung-Woo Lee, Mikhail Y Zhuravlev, Tula R Paudel, Yuri A Genenko, Chang-Beom Eom, Evgeny Y Tsymbal, Alexander Sinitskii, Alexei Gruverman
Hybrid structures composed of ferroelectric thin films and functional two-dimensional (2D) materials may exhibit unique characteristics and reveal new phenomena due to the cross-interface coupling between their intrinsic properties. In this report, we demonstrate a symbiotic interplay between spontaneous polarization of the ultrathin BaTiO3 ferroelectric film and conductivity of the adjacent molybdenum disulfide (MoS2) layer, a 2D narrow-band semiconductor. Polarization-induced modulation of the electronic properties of MoS2 results in a giant tunneling electroresistance effect in the hybrid MoS2/BaTiO3/SrRuO3 ferroelectric tunnel junctions (FTJs) with an OFF/ON resistance ratio as high as 104 - a 50-fold increase in comparison with the same type of FTJs with metal electrodes...
January 17, 2017: Nano Letters
https://www.readbyqxmd.com/read/28091822/does-the-growth-differentiation-balance-hypothesis-explain-allocation-to-secondary-metabolites-in-combretum-apiculatum-an-african-savanna-woody-species
#4
Dawood Hattas, Peter F Scogings, Riitta Julkunen-Tiitto
The growth differentiation balance hypothesis (GDBH) provides a framework that predicts a trade-off between costs of secondary metabolites (SMs) relative to the demand for photosynthate by growth. However, this hypothesis was developed using empirical evidence from plant species in northern boreal and temperate systems, leaving its applicability to species under different abiotic and biotic conditions questionable and generalizations problematic. The objective of this study was to investigate whether the GDBH explains allocation to SMs in the deciduous African savanna woody species C...
January 14, 2017: Journal of Chemical Ecology
https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#5
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28087445/distinct-subcomponents-of-mouse-retinal-ganglion-cell-receptive-fields-are-differentially-altered-by-light-adaptation
#6
C S Cowan, J Sabharwal, R L Seilheimer, S M Wu
The remarkable dynamic range of vision is facilitated by adaptation of retinal sensitivity to ambient lighting conditions. An important mechanism of sensitivity adaptation is control of the spatial and temporal window over which light is integrated. The retina accomplishes this by switching between parallel synaptic pathways with differing kinetics and degrees of synaptic convergence. However, the relative shifts in spatial and temporal integration are not well understood - particularly in the context of the antagonistic spatial surround...
January 10, 2017: Vision Research
https://www.readbyqxmd.com/read/28071740/elucidating-the-modes-of-action-for-bioactive-compounds-in-a-cell-specific-manner-by-large-scale-chemically-induced-transcriptomics
#7
Michio Iwata, Ryusuke Sawada, Hiroaki Iwata, Masaaki Kotera, Yoshihiro Yamanishi
The identification of the modes of action of bioactive compounds is a major challenge in chemical systems biology of diseases. Genome-wide expression profiling of transcriptional responses to compound treatment for human cell lines is a promising unbiased approach for the mode-of-action analysis. Here we developed a novel approach to elucidate the modes of action of bioactive compounds in a cell-specific manner using large-scale chemically-induced transcriptome data acquired from the Library of Integrated Network-based Cellular Signatures (LINCS), and analyzed 16,268 compounds and 68 human cell lines...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070879/a-review-of-pharmacogenetics-of-antimalarials-and-associated-clinical-implications
#8
REVIEW
Hazem Elewa, Kyle John Wilby
Genetic variability in drug-metabolizing enzymes and drug transporters is known to influence the pharmacokinetics of many drugs. Antimalarial drugs are a class of agents known to utilize metabolic and elimination pathways prone to genetic variation. This paper aims to review the genetic variants affecting antimalarial medications and discuss their clinical implications. Data were identified for the genes coding for the cytochrome P450 (CYP) enzymes: CYP2C8, CYP2C19, CYP2A6, CYP2D6, CYP2B6, and the P-glycoprotein drug transporter...
January 9, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28070088/population-and-growth-related-differences-in-helminthic-fauna-of-finless-porpoises-neophocaena-asiaeorientalis-in-five-japanese-populations
#9
Akira Shiozaki, Masao Amano
A survey of helminths and ectoparasites, including epizoits, was conducted in narrow-ridged finless porpoises (Neophocaena asiaeorientalis) from Japanese five populations using dead stranded or incidentally caught animals. In total, 13 helminth species were found (6 nematodes, 4 trematodes, 2 cestodes, and 1 acanthocephalan) in 137 porpoises. A new location record of Stenurus nanjingensis and a new host record of Tetrabothrius sp. were obtained. Eight species of helminth were considered common in the Japanese populations of the finless porpoise: Pharurus sunameri, Pharurus asiaeorientalis, Nasitrema spathulatum, Nasitrema sunameri, Halocercus pingi, Halocercus sunameri, Campula oblonga, and Synthesium elongatum...
January 8, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28069373/memantine-attenuates-cell-apoptosis-by-suppressing-the-calpain-caspase-3-pathway-in-an-experimental-model-of-ischemic-stroke
#10
Bin Chen, Guoxiang Wang, Weiwei Li, Weilin Liu, Ruhui Lin, Jing Tao, Min Jiang, Lidian Chen, Yun Wang
Ischemic stroke, the second leading cause of death worldwide, leads to excessive glutamate release, over-activation of N-methyl-D-aspartate receptor (NMDAR), and massive influx of calcium (Ca(2+)), which may activate calpain and caspase-3, resulting in cellular damage and death. Memantine is an uncompetitive NMDAR antagonist with low-affinity/fast off-rate. We investigated the potential mechanisms through which memantine protects against ischemic stroke in vitro and in vivo. Middle cerebral artery occlusion-reperfusion (MCAO) was performed to establish an experimental model of ischemic stroke...
January 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28065783/mathematical-modeling-of-mutant-transferrin-crm107-molecular-conjugates-for-cancer-therapy
#11
Dennis J Yoon, Kevin Y Chen, André M Lopes, April A Pan, Joseph Shiloach, Anne B Mason, Daniel T Kamei
The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites...
January 6, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28065271/signal-peptidase-enzymology-and-substrate-specificity-profiling
#12
R E Dalbey, D Pei, Ö D Ekici
Signal peptidases are membrane proteases that play crucial roles in the protein transport pathway of bacteria. They cleave off the signal peptide from precursor proteins that are membrane inserted by the SecYEG or Tat translocons. Signal peptide cleavage releases the translocated protein from the inner membrane allowing the protein to be exported to the periplasm, outer membrane, or secreted into the medium. Signal peptidases are very important proteins to study. They are unique serine proteases with a Ser-Lys dyad, catalyze cleavage at the membrane surface, and are promising potential antibacterial drug targets...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28064040/bax-to-basics-how-the-bcl2-gene-family-controls-the-death-of-retinal-ganglion-cells
#13
REVIEW
Margaret E Maes, Cassandra L Schlamp, Robert W Nickells
Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death...
January 4, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28062648/dual-chemistry-catalyzed-by-human-acireductone-dioxygenase
#14
Aditi R Deshpande, Thomas C Pochapsky, Gregory A Petsko, Dagmar Ringe
Acireductone dioxygenase (ARD) from the methionine salvage pathway of Klebsiella oxytoca is the only known naturally occurring metalloenzyme that catalyzes different reactions in vivo based solely on the identity of the divalent transition metal ion (Fe(2+) or Ni(2+)) bound in the active site. The iron-containing isozyme catalyzes the cleavage of substrate 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, whereas the nickel-containing isozyme uses the same substrates to catalyze an off-pathway shunt to form methylthiopropionate, carbon monoxide and formate...
January 5, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28060952/trim25-enhances-the-antiviral-action-of-zinc-finger-antiviral-protein-zap
#15
Melody M H Li, Zerlina Lau, Pamela Cheung, Eduardo G Aguilar, William M Schneider, Leonia Bozzacco, Henrik Molina, Eugen Buehler, Akinori Takaoka, Charles M Rice, Dan P Felsenfeld, Margaret R MacDonald
The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28059150/core-shell-structured-titanium-nitrogen-alloys-with-high-strength-high-thermal-stability-and-good-plasticity
#16
Y S Zhang, Y H Zhao, W Zhang, J W Lu, J J Hu, W T Huo, P X Zhang
Multifunctional materials with more than two good properties are widely required in modern industries. However, some properties are often trade-off with each other by single microstructural designation. For example, nanostructured materials have high strength, but low ductility and thermal stability. Here by means of spark plasma sintering (SPS) of nitrided Ti particles, we synthesized bulk core-shell structured Ti alloys with isolated soft coarse-grained Ti cores and hard Ti-N solid solution shells. The core-shell Ti alloys exhibit a high yield strength (~1...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28057832/modification-of-feeding-circuits-in-the-evolution-of-social-behavior
#17
REVIEW
Eva K Fischer, Lauren A O'Connell
Adaptive trade-offs between foraging and social behavior intuitively explain many aspects of individual decision-making. Given the intimate connection between social behavior and feeding/foraging at the behavioral level, we propose that social behaviors are linked to foraging on a mechanistic level, and that modifications of feeding circuits are crucial in the evolution of complex social behaviors. In this Review, we first highlight the overlap between mechanisms underlying foraging and parental care and then expand this argument to consider the manipulation of feeding-related pathways in the evolution of other complex social behaviors...
January 1, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28057004/gene-profile-of-fibroblasts-identify-relation-of-ccl8-with-idiopathic-pulmonary-fibrosis
#18
Jong-Uk Lee, Hyun Sub Cheong, Eun-Young Shim, Da-Jeong Bae, Hun Soo Chang, Soo-Taek Uh, Young Hoon Kim, Jong-Sook Park, Bora Lee, Hyoung Doo Shin, Choon-Sik Park
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by the complex interaction of cells involved in chronic inflammation and fibrosis. Global gene expression of a homogenous cell population will identify novel candidate genes. METHODS: Gene expression of fibroblasts derived from lung tissues (8 IPF and 4 controls) was profiled, and ontology and functional pathway were analyzed in the genes exhibiting >2 absolute fold changes with p-values < 0...
January 5, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28056782/predicting-potential-drug-drug-interactions-by-integrating-chemical-biological-phenotypic-and-network-data
#19
Wen Zhang, Yanlin Chen, Feng Liu, Fei Luo, Gang Tian, Xiaohong Li
BACKGROUND: Drug-drug interactions (DDIs) are one of the major concerns in drug discovery. Accurate prediction of potential DDIs can help to reduce unexpected interactions in the entire lifecycle of drugs, and are important for the drug safety surveillance. RESULTS: Since many DDIs are not detected or observed in clinical trials, this work is aimed to predict unobserved or undetected DDIs. In this paper, we collect a variety of drug data that may influence drug-drug interactions, i...
January 5, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28053243/descending-antinociception-induced-by-secondary-somatosensory-cortex-stimulation-in-experimental-neuropathy-role-of-the-medullospinal-serotonergic-pathway
#20
Boriss Sagalajev, Hanna Viisanen, Hong Wei, Antti Pertovaara
Stimulation of the secondary somatosensory cortex (S2) has attenuated pain in humans and inflammatory nociception in animals. Here we studied S2 stimulation-induced antinociception and its underlying mechanisms in an experimental animal model of neuropathy induced by spinal nerve ligation (SNL). Effect of S2 stimulation on heat-evoked limb withdrawal latency was assessed in lightly anesthetized rats that were divided into three groups based on prior surgery and monofilament testing before induction of anesthesia: i) Sham operated group, ii-iii) (mechanically) hypersensitive and non-hypersensitive SNL groups...
January 4, 2017: Journal of Neurophysiology
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