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https://www.readbyqxmd.com/read/28548834/subtly-modulating-glycogen-synthase-kinase-3-%C3%AE-allosteric-inhibitors-development-and-their-potential-for-the-treatment-of-chronic-diseases
#1
Valle Palomo, Daniel I Pérez, Carlos Roca, Cara Anderson, Natalia Rodriguez-Muela, Concepción Pérez, Jose A Morales-Garcia, Julio A Reyes, Nuria E Campillo, Ana M Pérez-Castillo, Lee L Rubin, Lubov T Timchenko, Carmen Gil, Ana Martínez
Glycogen synthase kinase 3 β (GSK-3β) is a central target in several unmet diseases. To increase the specificity of GSK-3β inhibitors in chronic treatments we are developing small molecules allowing subtle modulation of GSK-3β activity. Design synthesis, structure-activity relationships and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3β are here presented. Furthermore, we show how allosteric binders may overcome the β-catenin side effects associated to strong GSK-3β inhibition...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28548229/endoplasmic-reticulum-stress-in-the-heart-the-insights-into-mechanisms-and-drug-targets
#2
REVIEW
Shunyao Wang, Pablo Binder, Qiru Fang, Zhenzhong Wang, Wei Xiao, Wei Liu, Xin Wang
The endoplasmic reticulum (ER) serves several essential cellular functions including protein synthesis, protein folding, protein translocation, calcium homoeostasis and lipid biosynthesis. Physiological or pathological stimuli which disrupt ER homoeostasis and disturb its functions lead to an accumulation of misfolded and unfolded proteins, a condition referred to as ER stress. ER stress triggers unfolded protein response (UPR) to restore the homoeostasis of ER through activating transcriptional and translational pathways...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28546908/orientation-and-incorporation-of-photosystem-i-in-bioelectronics-devices-enabled-by-phage-display
#3
Pavlo Gordiichuk, Diego Pesce, Olga E Castañeda Ocampo, Alessio Marcozzi, Gert-Jan A H Wetzelaer, Avishek Paul, Mark Loznik, Ekaterina Gloukhikh, Shachar Richter, Ryan C Chiechi, Andreas Herrmann
Interfacing proteins with electrode surfaces is important for the field of bioelectronics. Here, a general concept based on phage display is presented to evolve small peptide binders for immobilizing and orienting large protein complexes on semiconducting substrates. Employing this method, photosystem I is incorporated into solid-state biophotovoltaic cells.
May 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28545367/targeting-dna-minor-groove-by-hybrid-molecules-as-anticancer-agents
#4
Shalini Nekkanti, Ramya Tokala, Nagula Shankaraiah
Agents which can recognize and bind specific sequences of DNA offer selective therapy through the modulation of specific transcription factors or genes. Recently, there has been renewed interest in the field of anticancer minor groove binders. This may be attributed to the fact that many compounds of this class have demonstrated significant antitumor activity against a wide variety of cancers in recent clinical trials. This review will discuss the recent efforts to overcome the drawbacks of existing minor groove binding anticancer agents through rational drug design based on scaffolds with known antitumor activity...
May 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28544982/an-evaluation-of-minor-groove-binders-as-anti-fungal-and-anti-mycobacterial-therapeutics
#5
Fraser J Scott, Ryan J O Nichol, Abedawn I Khalaf, Federica Giordani, Kirsten Gillingwater, Soumya Ramu, Alysha Elliott, Johannes Zuegg, Paula Duffy, Michael-Jon Rosslee, Lerato Hlaka, Santosh Kumar, Mumin Ozturk, Frank Brombacher, Michael Barrett, Reto Guler, Colin J Suckling
This study details the synthesis and biological evaluation of a collection of 19 structurally related Minor Groove Binders (MGBs), derived from the natural product distamycin, which were designed to probe antifungal and antimycobacterial activity. From this initial set, we report several MGBs that are worth more detailed investigation and optimisation. MGB-4, MGB-317 and MGB-325 have promising MIC80s of 2, 4 and 0.25 μg/mL, respectively, against the fungus C. neoformans.MGB-353 and MGB-354 have MIC99s of 3...
May 17, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28544937/recycling-metals-from-lithium-ion-battery-by-mechanical-separation-and-vacuum-metallurgy
#6
Jiefeng Xiao, Jia Li, Zhengming Xu
The large-batch application of lithium ion batteries leads to the mass production of spent batteries. So the enhancement of disposal ability of spent lithium ion batteries is becoming very urgent. This study proposes an integrated process to handle bulk spent lithium manganese (LiMn2O4) batteries to in situ recycle high value-added products without any additives. By mechanical separation, the mixed electrode materials mainly including binder, graphite and LiMn2O4 are firstly obtained from spent batteries. Then, the reaction characteristics for the oxygen-free roasting of mixed electrode materials are analyzed...
May 17, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28544635/a-robust-water-based-functional-binder-framework-for-high-energy-lithium-sulfur-batteries
#7
Matthew James Lacey, Viking Österlund, Fabian Jeschull, Andreas Bergfelt, Tim Bowden, Daniel Brandell
We report here a water-based functional binder framework for the lithium-sulfur battery system, based on the general combination of a polyether and an amide-containing polymer. These binders are applied here to positive electrodes optimised towards high energy electrochemical performance based only on commercially available materials. Electrodes with up to 4 mAh cm-2 capacity and 97 - 98% coulombic efficiency are achievable in electrodes with a 65% total sulfur content and a poly(ethylene oxide):poly(vinylpyrrolidone) (PEO:PVP) binder system...
May 19, 2017: ChemSusChem
https://www.readbyqxmd.com/read/28544567/chemoproteomics-aided-medicinal-chemistry-for-the-discovery-of-epha2-inhibitors
#8
Stephanie Heinzlmeir, Jonas Lohse, Tobias Treiber, Denis Kudlinzki, Verena Linhard, Santosh Lakshmi Gande, Sridhar Sreeramulu, Krishna Saxena, Xiaofeng Liu, Mathias Wilhelm, Harald Schwalbe, Bernhard Kuster, Guillaume Médard
The receptor tyrosine kinase EPHA2 has gained interest as therapeutic drug target in cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small molecule inhibitors. Here, we report on the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor Dasatinib as a lead structure. We designed hybrid structures of Dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955 and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2...
May 24, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28544255/a-new-polyoxometalate-pom-based-composite-%C3%AF-fabrication-through-pom-assisted-polymerization-of-dopamine-and-properties-as-anode-materials-for-high-performance-lithium-ion-battery
#9
Yan-Hong Ding, Jun Peng, Shifa-Ullah Khan, Yue Yuan
Organic substrates are indispensable to fabricate multi-functional polyoxometalate (POM)-based composites for various application fields. A new Molybdovanadophosphoric heteropolyacid (PMo10V2)-based polydopamine (PDA) composite (PMo10V2/PDA) has been firstly synthesized through a facile in-situ polymerization method under hydrothermal conditions without adding extra buffer solution. The obtained PMo10V2/PDA composite shows homogeneous microsphere morphology. By utilizing the adhesive ability of PDA, the composite can be used as an anode material without additional binder for rechargeable lithium ion batteries...
May 24, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28542067/grb2-associated-binder-1-is-required-for-extrafusal-and-intrafusal-muscle-fiber-development
#10
So Y Park, So Y Jang, Yoon K Shin, Byeol A Yoon, Hye J Lee, Hwan T Park
The neuregulin-1 (NRG1) signaling pathway plays an important role in the development of the peripheral neuromuscular system, including in muscle spindle and postnatal myelination. We previously showed that NRG1 on the axonal membrane regulates peripheral nerve myelination through Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling. Here, we determined the role of Gab1 in the development of muscles and the muscle spindle using muscle-specific conditional Gab1 knockout mice...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28541654/stable-1t-mose2-and-carbon-nanotubes-hybridized-flexible-film-binder-free-and-high-performance-li-ion-anode
#11
Ting Xiang, Shi Tao, Weiyu Xu, Qi Fang, Chuanqiang Wu, Daobin Liu, Yu Zhou, Adnan Khalil, Zahir Muhammad, Wangsheng Chu, Zhonghui Wang, Hongfa Xiang, Qin Liu, Li Song
Two-dimensional stable metallic 1T-MoSe2 with expanded interlayer spacing of 10.0 Å in-situ grown on SWCNTs film is fabricated via a one-step solvothermal method. Combined with X-ray absorption near-edge structures, our characterizations reveals that such 1T-MoSe2 and single-walled carbon nanotubes (abbreviated as 1T-MoSe2/SWCNTs) hybridized structure can provide strong electrical and chemical coupling between 1T-MoSe2 nanosheets and SWCNTs film in a form of C-O-Mo bonding, which is significantly benefiting a high-efficiency electron/ion transport pathway and structural stability, thus directly enabling high performance lithium-storage properties...
May 25, 2017: ACS Nano
https://www.readbyqxmd.com/read/28540928/anxiety-associated-increased-cpg-methylation-in-the-promoter-of-asb1-a-translational-approach-evidenced-by-epidemiological-and-clinical-studies-and-a-murine-model
#12
Rebecca T Emeny, Jens Baumert, Anthony S Zannas, Sonja Kunze, Simone Wahl, Stella Iurato, Janine Arloth, Angelika Erhardt, Georgia Balsevich, Mathias V Schmidt, Peter Weber, Anja Kretschmer, Liliane Pfeiffer, Johannes Kruse, Konstantin Strauch, Michael Roden, Christian Herder, Wolfgang Koenig, Christian Gieger, Melanie Waldenberger, Annette Peters, Elisabeth B Binder, Karl-Heinz Ladwig
Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450 K BeadChip) and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation...
May 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28540887/evaluation-of-medication-use-in-malaysian-predialysis-patients
#13
Muhammad Salman, Amer Hayat Khan, Azreen Syazril Adnan, Syed Azhar Syed Sulaiman, Naureen Shehzadi, Nauman Asif, Khalid Hussain, Fahad Saleem, Muhammed Hussnain Raza, Muhammad Shahid Farooq
Chronic kidney disease (CKD) patients suffer from multiple comorbidities and complications as a cause or consequence of kidney disease. Information regarding medication- prescribing patterns in predialysis patients is sparse. We conducted a retrospective study to evaluate the medication prescription patterns among predialysis patients. Medical records (both paper based and computerized) of patients at CKD Resource Centre, Hospital Universiti Sains Malaysia, were reviewed. A total of 615 eligible cases were included in the study...
May 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28540886/effect-of-hemodialysis-on-oxidants-and-antioxidant-factors-in-chronic-renal-failure
#14
Ramin Tajbakhsh, Mostafa Qorbani, Golbarg Mehrpour, Mitra Rahimzadeh, Mohammad Mehdi Azimzadeh, Hossein Mirmiranpour
The current study was conducted to assess the effect of hemodialysis (HD) on the status of plasma oxidants and antioxidants among patients with end-stage renal disease (ESRD). These parameters can have an influence on the HD process and can also be useful for follow-up of these patients. The participants of this cross-sectional study comprised 91 patients with a mean age of 51.1 ± 8.2 years on chronic HD with kt/v between 1.2 and 1.4. The etiology of ESRD in these patients was as follows: diabetes mellitus in 39, hypertension in 35, and glomerulonephritis in 17 patients...
May 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28540741/fine-grained-parcellation-of-brain-connectivity-improves-differentiation-of-states-of-consciousness-during-graded-propofol-sedation
#15
Xiaolin Liu, Kathryn K Lauer, Doug Ward, Christopher Roberts, Suyan Liu, Gollapudy Suneeta, Robert Rohloff, William Gross, Zhan Xu, Guangyu Chen, Jeff Binder, Shi-Jiang Li, Anthony G Hudetz
Conscious perception relies on interactions between spatially and functionally distinct modules of the brain at various spatiotemporal scales. These interactions are altered by anesthesia - an intervention that leads to fading consciousness. Relatively little is known about brain functional connectivity and its anesthetic modulation at a fine spatial scale. Here, we used functional imaging to examine propofol-induced changes in functional connectivity in brain networks defined at a fine-grained parcellation based on a combination of anatomical and functional features...
May 25, 2017: Brain Connectivity
https://www.readbyqxmd.com/read/28539100/production-of-thermal-insulation-blocks-from-bottom-ash-of-fluidized-bed-combustion-system
#16
A K Mandal, O P Sinha
The issues of disposal and environmental problems are increased by the generation of bottom ash from the thermal power plants day by day; hence, its recycling is required. The present study aimed to make thermal insulation blocks using as raw material bottom ash and iron ore slime as a binder and to characterize their engineering properties. Two different fineness values of bottom ash were considered with varying amounts of iron ore slime (0-10%) to make the blocks. Blocks were dried followed by firing at 1000, 1100 and 1200°C, respectively...
May 1, 2017: Waste Management & Research
https://www.readbyqxmd.com/read/28535954/sol-gel-derived-bioactive-glass-nanoparticle-incorporated-glass-ionomer-cement-with-or-without-chitosan-for-enhanced-mechanical-and-biomineralization-properties
#17
Dong-Ae Kim, Jung-Hwan Lee, Soo-Kyung Jun, Hae-Won Kim, Mohamed Eltohamy, Hae-Hyoung Lee
OBJECTIVE: This study investigated the mechanical and in vitro biological properties (in immortalized human dental pulp stem cells (ihDPSCs)) of bioactive glass nanoparticle (BGN)-incorporated glass ionomer cement (GIC) with or without chitosan as a binder. METHODS: After the BGNs were synthesized and characterized, three experimental GICs and a control (conventional GIC) that differed in the additive incorporated into a commercial GIC liquid (Hy-bond, Shofu, Japan) were produced: BG5 (5wt% of BGNs), CL0...
May 20, 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/28535354/high-capacity-and-ultrafast-na-ion-storage-of-self-supported-3d-porous-antimony-persulfide-graphene-foam-architecture
#18
Yanying Lu, Ning Zhang, Shuang Jiang, Yudong Zhang, Meng Zhou, Zhanliang Tao, Lynden A Archer, Jun Chen
The key challenge for high performance sodium-ion batteries is the exploitation of appropriate electrode materials with long cycling stability and high rate capability. Here, we report Sb2S5 nanoparticles (~ 5 nm) uniformly encapsulated in three-dimensional (3D) porous graphene foam, which were fabricated by a facile hydrothermal co-assembly strategy, as a high-performance anode material for sodium-ion batteries. The as-prepared composite can be directly used as electrodes without adding binder or current collector, exhibiting outstanding electrochemical performance with high reversible capacity (845 mAh g-1 at 0...
May 23, 2017: Nano Letters
https://www.readbyqxmd.com/read/28535344/clarifying-the-controversial-catalytic-performance-of-co-oh-2-and-co3o4-for-oxygen-reduction-evolution-reactions-toward-efficient-zn-air-batteries
#19
Zhishuang Song, Xiaopeng Han, Yida Deng, Naiqin Zhao, Wenbin Hu, Cheng Zhong
Cobalt-based nanomaterials have been widely studied as catalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) due to their remarkable bifunctional catalytic activity, low cost and easy available. However, controversial results concerning OER/ORR performance exist between different types of cobalt-based catalysts, especially for Co(OH)2 and Co3O4. To address this issue, we develop a facile electrochemical deposition method to grow Co(OH)2 directly on the skeleton of carbon cloth, and further Co3O4 was obtained by post thermal treatment...
May 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28532952/april-consultation-6
#20
Perry S Binder
No abstract text is available yet for this article.
April 2017: Journal of Cataract and Refractive Surgery
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