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https://www.readbyqxmd.com/read/29054108/increase-in-pro-apoptotic-activity-of-inhibitory-pas-domain-protein-via-phosphorylation-by-mk2
#1
Shuya Kasai, Mary Jane Elizabeth Richardson, Satoru Torii, Ken-Ichi Yasumoto, Hiroki Shima, Kazuhiko Igarashi, Ken Itoh, Kazuhiro Sogawa, Kazutaka Murayama
Inhibitory PAS domain protein (IPAS) is a bifunctional protein that downregulates hypoxic gene expression and exerts pro-apoptotic activity by preventing pro-survival activity of Bcl-xL and its related factors. Pro-apoptotic activity of IPAS is attenuated by the activation of the PINK1-Parkin pathway, and involved in neuronal degeneration in an experimental mouse model of Parkinson's disease. The current study shows that phosphorylation of IPAS at Ser184 by MAPK-activated protein kinase 2 (MK2 or MAPKAPK2) enhances the pro-apoptotic function of IPAS...
October 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29054097/dynamic-characteristics-of-a-flagellar-motor-protein-analyzed-using-an-elastic-network-model
#2
Moon-Ki Choi, Soojin Jo, Byung Ho Lee, Min Hyeok Kim, Jae Boong Choi, Kyunghoon Kim, Moon Ki Kim
At the base of a flagellar motor, its rotational direction and speed are regulated by the interaction between rotor and stator proteins. A switching event occurs when the cytoplasmic rotor protein, called C-ring, changes its conformation in response to binding of the CheY signal protein. The C-ring structure consists of FliG, FliM, and FliN proteins and its conformational changes in FliM and FliG including HelixMC play an important role in switching the motor direction. Therefore, clarifying their dynamic properties as well as conformational changes is a key to understanding the switching mechanism of the motor protein...
October 5, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29054096/simplified-autodock-force-field-for-hydrated-binding-sites
#3
Marek Wojciechowski
A set of high quality structures of protein-ligand complexes with experimentally determined binding affinities has been extracted from the Protein Data Bank and used to test and recalibrate AutoDock force field. Since for some binding sites water molecules are crucial for bridging the receptor-ligand interactions, they have to be included in the analysis. To simplify the process of incorporating water molecules into the binding sites and make it less ambiguous, new simple water model was created. After recalibration of the force field on the new dataset much better correlation between the computed and experimentally determined binding affinities was achieved and the quality of pose prediction improved even more...
September 23, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29054054/conformational-analysis-of-the-human-chemokine-receptor-cxcr3
#4
Raffaele Raucci, Andrea Polo, Alfredo Budillon, Giovanni Colonna, Susan Costantini
In the last years, some studies showed the patho-genetic role of CXCR3 bound to its ligands in many human inflammatory diseases and cancers. Thus, the blockage of the CXCR3 interaction site to its ligands is seen as a possible therapeutic target for the treatment of cancer. The presence of flexible regions in the chemokine receptors determines their capability to develop specific mechanisms of action. We have recently focused on the features of the N-terminal region of human CXCR3 free in solution, where we demonstrate the presence of numerous conformational ensembles, dynamically stabilized by H-bonds...
October 17, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29054053/leptin-reduces-microrna-122-level-in-hepatic-stellate-cells-in-vitro-and-in-vivo
#5
Xuguang Zhai, Fangyun Cheng, Li Ji, Xiaofei Zhu, Qing Cao, Yali Zhang, Xin Jia, Qian Zhou, Wei Guan, Yajun Zhou
Obese patients, often accompanied by hyperleptinemia, are more likely to develop liver fibrosis. Leptin, an adipocyte-derived hormone, augments inflammatory in liver and promotes hepatic stellate cell (HSC) activation (a key step for liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and can attenuate liver fibrosis. This study examined the effect of leptin on miR-122 level in HSCs in vivo and in vitro. Results demonstrated that leptin reduced the levels of both miR-122 (mature miR-122) and primary miR-122 (pri-miR-122)...
October 17, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29054052/synthesis-and-binding-affinity-analysis-of-%C3%AE-1-2-and-%C3%AE-1-6-o-s-linked-dimannosides-for-the-elucidation-of-sulfur-in-glycosidic-bonds-using-quartz-crystal-microbalance-sensors
#6
Oscar Norberg, Bin Wu, Niranjan Thota, Jian-Tao Ge, Germain Fauquet, Ann-Kathrin Saur, Teodor Aastrup, Hai Dong, Mingdi Yan, Olof Ramström
The role of sulfur in glycosidic bonds has been evaluated using quartz crystal microbalance methodology. Synthetic routes towards α1-2- and α1-6-linked dimannosides with S- or O-glycosidic bonds have been developed, and the recognition properties assessed in competition binding assays with the cognate lectin concanavalin A. Mannose-presenting QCM sensors were produced using photoinitiated, nitrene-mediated immobilization methods, and the subsequent binding study was performed in an automated flow-through instrumentation, and correlated with data from isothermal titration calorimetry...
October 9, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/29054004/adsorption-characteristics-of-charged-and-nonionic-small-molecules-to-colloidal-alumina
#7
Vikram J Pansare, Victoria Hwang, Carlos Figueroa, Robert K Prud'homme
Dense fluorescent pigments used for inkjet printing of UV and IR-readable non-photobleaching security features require stabilizers to prevent aggregation/sedimentation and inkjet head clogging at high resolution. A study of small molecule adsorption to α-alumina, a model system for security pigments, is presented. Alumina is dispersed by two methods yielding different zeta potentials but identical isoelectric points. Essentially complete dispersion is obtained in water at pH 3 but aggregation occurs at pH 6 where the surface charging is lower...
October 6, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29053993/orexin-system-in-swine-ovarian-follicles
#8
R Ciccimarra, S Bussolati, F Grasselli, S Grolli, L Ragionieri, F Ravanetti, M Botti, F Gazza, A Cacchioli, R Di Lecce, A M Cantoni, G Basini
Successful reproduction is strictly linked to metabolic cues. The orexins are a family of hypothalamic neurohormones, well known for their key role in the control of food intake and the involvement in several aspects of the reproductive process. The biological actions of both orexins are carried out through binding to the related Orexin 1 (OX1R) and Orexin 2 (OX2R) G-protein-coupled receptors. The purpose of this study was to investigate the presence of orexin system components in the porcine ovaries, to contribute to expand the knowledge about their pleiotropic role...
September 22, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29053960/a-general-strategy-for-discovery-of-inhibitors-and-activators-of-ring-and-u-box-e3-ligases-with-ubiquitin-variants
#9
Mads Gabrielsen, Lori Buetow, Mark A Nakasone, Syed Feroj Ahmed, Gary J Sibbet, Brian O Smith, Wei Zhang, Sachdev S Sidhu, Danny T Huang
RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2∼Ub binding site...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29053958/structure-of-the-dnmt1-reader-module-complexed-with-a-unique-two-mono-ubiquitin-mark-on-histone-h3-reveals-the-basis-for-dna-methylation-maintenance
#10
Satoshi Ishiyama, Atsuya Nishiyama, Yasushi Saeki, Kei Moritsugu, Daichi Morimoto, Luna Yamaguchi, Naoko Arai, Rumie Matsumura, Toru Kawakami, Yuichi Mishima, Hironobu Hojo, Shintaro Shimamura, Fuyuki Ishikawa, Shoji Tajima, Keiji Tanaka, Mariko Ariyoshi, Masahiro Shirakawa, Mitsunori Ikeguchi, Akinori Kidera, Isao Suetake, Kyohei Arita, Makoto Nakanishi
The proper location and timing of Dnmt1 activation are essential for DNA methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono-ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and activation at DNA methylation sites. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the known ubiquitin-recognition structures. The two ubiquitins are simultaneously bound to the RFTS with a combination of canonical hydrophobic and atypical hydrophilic interactions...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29053956/assembly-of-the-whip-trim14-ppp6c-mitochondrial-complex-promotes-rig-i-mediated-antiviral-signaling
#11
Peng Tan, Lian He, Jun Cui, Chen Qian, Xin Cao, Meng Lin, Qingyuan Zhu, Yinyin Li, Changsheng Xing, Xiao Yu, Helen Y Wang, Rong-Fu Wang
Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29053951/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#12
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
No abstract text is available yet for this article.
October 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29053920/turn-on-fluorene-push-pull-probes-with-high-brightness-and-photostability-for-visualizing-lipid-order-in-biomembranes
#13
Janah Shaya, Mayeul Collot, Frédéric Benailly, Najiba Mahmoud, Yves Mély, Benoît Y Michel, Andrey S Klymchenko, Alain Burger
The rational design of environment-sensitive dyes with superior properties is critical for elucidating the fundamental biological processes and understanding the biophysical behavior of cell membranes. In this study, a novel group of fluorene-based push-pull probes was developed for imaging membrane lipids. The design of these fluorogenic conjugates is based on a propioloyl linker to preserve the required spectroscopic features of the core dye. This versatile linker allowed the introduction of a polar deoxyribosyl head, a lipophilic chain, and an amphiphilic/anchoring group to tune the cell membrane binding and internalization...
October 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29053903/galectin-3-an-emerging-biomarker-in-stroke-and-cerebrovascular-diseases
#14
Anand Venkatraman, Shalaka Hardas, Nirav Patel, Navkaranbir Singh Bajaj, Garima Arora, Pankaj Arora
BACKGROUND: The carbohydrate-binding molecule Galectin-3 has garnered significant attention recently as a biomarker for various conditions ranging from cardiac disease to obesity. Though there have been several recent studies investigating its role in stroke and other cerebrovascular diseases, awareness of this emerging biomarker in the wider neurology community is limited. METHODS: We performed a systematic search in PubMed, EMBASE, Scopus, CINAHL, Clinicaltrials...
October 20, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29053874/tau-pathology-and-neurodegeneration-contribute-to-cognitive-impairment-in-alzheimer-s-disease
#15
Alexandre Bejanin, Daniel R Schonhaut, Renaud La Joie, Joel H Kramer, Suzanne L Baker, Natasha Sosa, Nagehan Ayakta, Averill Cantwell, Mustafa Janabi, Mariella Lauriola, James P O'Neil, Maria L Gorno-Tempini, Zachary A Miller, Howard J Rosen, Bruce L Miller, William J Jagust, Gil D Rabinovici
Neuropathological and in vivo studies have revealed a tight relationship between tau pathology and cognitive impairment across the Alzheimer's disease spectrum. However, tau pathology is also intimately associated with neurodegeneration and amyloid pathology. The aim of the present study was therefore to assess whether grey matter atrophy and amyloid pathology contribute to the relationship between tau pathology, as measured with 18F-AV-1451-PET imaging, and cognitive deficits in Alzheimer's disease. We included 40 amyloid-positive patients meeting criteria for mild cognitive impairment due to Alzheimer's disease (n = 5) or probable Alzheimer's disease dementia (n = 35)...
October 7, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053855/rare-gabra3-variants-are-associated-with-epileptic-seizures-encephalopathy-and-dysmorphic-features
#16
Cristina Elena Niturad, Dorit Lev, Vera M Kalscheuer, Agnieszka Charzewska, Julian Schubert, Tally Lerman-Sagie, Hester Y Kroes, Renske Oegema, Monica Traverso, Nicola Specchio, Maria Lassota, Jamel Chelly, Odeya Bennett-Back, Nirit Carmi, Tal Koffler-Brill, Michele Iacomino, Marina Trivisano, Giuseppe Capovilla, Pasquale Striano, Magdalena Nawara, Sylwia Rzonca, Ute Fischer, Melanie Bienek, Corinna Jensen, Hao Hu, Holger Thiele, Janine Altmüller, Roland Krause, Patrick May, Felicitas Becker, Rudi Balling, Saskia Biskup, Stefan A Haas, Peter Nürnberg, Koen L I van Gassen, Holger Lerche, Federico Zara, Snezana Maljevic, Esther Leshinsky-Silver
Genetic epilepsies are caused by mutations in a range of different genes, many of them encoding ion channels, receptors or transporters. While the number of detected variants and genes increased dramatically in the recent years, pleiotropic effects have also been recognized, revealing that clinical syndromes with various degrees of severity arise from a single gene, a single mutation, or from different mutations showing similar functional defects. Accordingly, several genes coding for GABAA receptor subunits have been linked to a spectrum of benign to severe epileptic disorders and it was shown that a loss of function presents the major correlated pathomechanism...
October 7, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053845/substitution-of-yor1p-nbd1-residues-improves-the-thermal-stability-of-human-cystic-fibrosis-transmembrane-conductance-regulator
#17
B M Xavier, E Hildebrandt, F Jiang, H Ding, J C Kappes, I L Urbatsch
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a plasma membrane chloride channel protein that regulates vertebrate fluid homeostasis. The inefficiency of wild type human CFTR protein folding/trafficking is exacerbated by genetic mutations that can cause protein misfolding in the endoplasmic reticulum (ER) and subsequent degradation. This project investigates small changes in protein sequence that can alter the thermal stability of the large multi-domain CFTR protein. We target a conserved 70-residue α-subdomain located in the first nucleotide-binding domain that hosts the common misfolding mutation ∆F508...
October 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29053827/comparative-evaluation-of-texture-wheat-ingredients-and-soy-proteins-in-the-quality-and-acceptability-of-emulsified-chicken-nuggets
#18
M Yeater, G Casco, R K Miller, C Z Alvarado
Chicken nuggets are commonly made with varying levels of textured vegetable proteins, such as soy and wheat, for their ability to bind water and their meat like conformation. This project compared textured wheat proteins and soy proteins at 10%, 20%, 30%, and 40% in emulsified chicken nuggets. A total of 3,024 chicken nuggets were evaluated in replications for batter breader pickup (%), par fry yield (%), cook loss (%), L*, a*, b* color value, texture profile analysis, and sensory analysis. The analysis was conducted for all 4 concentrations of wheat and soy treatments then compared to each other and an all white meat chicken nugget control...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/29053813/comparative-transcriptomic-analysis-of-high-and-low-egg-producing-duck-ovaries
#19
Z Tao, W Song, C Zhu, W Xu, H Liu, S Zhang, Li Huifang
The egg-laying rate is an important indicator of egg production of laying ducks. Egg production directly impacts the economic benefits of the duck industry. In order to obtain better insight into the molecular mechanisms associated with the process of egg production, comparative transcriptomic analysis of the ovaries of Jinding ducks with high and low egg production was performed using the Illumina HiSeq 2500 system. A total of 843 differentially expressed genes (DEGs) was identified, 367 that were down-regulated and 476 that were up-regulated in high egg production (HEP) ovaries, as compared with low egg production (LEP) ovaries...
October 5, 2017: Poultry Science
https://www.readbyqxmd.com/read/29053759/molecular-dynamic-simulations-reveal-suboptimal-binding-of-salbutamol-in-t164i-variant-of-%C3%AE-2-adrenergic-receptor
#20
Srinivas Bandaru, Mallika Alvala, Anuraj Nayarisseri, Saphy Sharda, Himshikha Goud, Hema Prasad Mundluru, Sanjeev Kumar Singh
The natural variant C491T (rs1800088) in ADRB2 gene substitutes Threonine to Isoleucine at 164th position in β2AR and results in receptor sequestration and altered binding of agonists. Present investigation pursues to identify the effect of T164I variation on function and structure of β2AR through systematic computational approaches. The study, in addition, addresses altered binding of salbutamol in T164I variant through molecular dynamic simulations. Methods involving changes in free energy, solvent accessibility surface area, root mean square deviations and analysis of binding cavity revealed structural perturbations in receptor to incur upon T164I substitution...
2017: PloS One
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