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https://www.readbyqxmd.com/read/29040978/hydrogen-rich-saline-attenuates-brain-injury-induced-by-cardiopulmonary-bypass-and-inhibits-microvascular-endothelial-cell-apoptosis-via-the-pi3k-akt-gsk3%C3%AE-signaling-pathway-in-rats
#1
Keyan Chen, Nan Wang, Yugang Diao, Wanwei Dong, YingJie Sun, Lidan Liu, Xiuying Wu
BACKGROUND/AIMS: Cardiopulmonary bypass (CPB) is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS) can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. METHODS: A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB) was used to assess permeability of the blood-brain barrier (BBB); HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT -PCR analyses of brain tissue and neurons...
October 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29040952/design-synthesis-kinetic-mechanism-and-molecular-docking-studies-of-novel-1-pentanoyl-3-arylthioureas-as-inhibitors-of-mushroom-tyrosinase-and-free-radical-scavengers
#2
Fayaz Ali Larik, Aamer Saeed, Pervaiz Ali Channar, Urooj Muqadar, Qamar Abbas, Mubashir Hassan, Sung-Yum Seo, Michael Bolte
A series of novel 1-pentanoyl-3-arylthioureas was designed as new mushroom tyrosinase inhibitors and free radical scavengers. The title compounds were obtained in excellent yield and characterized by FTIR, (1)H NMR, (13)C NMR and X-ray crystallography in case of compound (4a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 1-Pentanoyl-3-(4-methoxyphenyl) thiourea (4f) showed tyrosinase inhibitory activity (IC50 1.568 ± 0.01 mM) comparable to Kojic acid (IC50 16...
September 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29040752/expansion-of-the-dehydrin-gene-family-in-the-pinaceae-is-associated-with-considerable-structural-diversity-and-drought-responsive-expression
#3
Juliana Stival Sena, Isabelle Giguère, Philippe Rigault, Jean Bousquet, John Mackay
Temperatures are expected to increase over the next century in all terrestrial biomes and particularly in boreal forests, where drought-induced mortality has been predicted to rise. Genomics research is helping to develop hypotheses regarding the molecular basis of drought tolerance and recent work proposed that the osmo-protecting dehydrin proteins have undergone a clade-specific expansion in the Pinaceae, a major group of conifer trees. The objectives of this study were to identify all of the putative members of the gene family, trace their evolutionary origin, examine their structural diversity and test for drought-responsive expression...
October 13, 2017: Tree Physiology
https://www.readbyqxmd.com/read/29040738/nf90-nf45-is-a-selective-rna-chaperone-that-rearranges-viral-and-cellular-riboswitches-biochemical-analysis-of-a-virus-host-factor-activity
#4
Tobias Schmidt, Susann Friedrich, Ralph Peter Golbik, Sven-Erik Behrens
The heterodimer NF90-NF45 is an RNA-binding protein complex that modulates the expression of various cellular mRNAs on the post-transcriptional level. Furthermore, it acts as a host factor that supports the replication of several RNA viruses. The molecular mechanisms underlying these activities have yet to be elucidated. Recently, we showed that the RNA-binding capabilities and binding specificity of NF90 considerably improves when it forms a complex with NF45. Here, we demonstrate that NF90 has a substrate-selective RNA chaperone activity (RCA) involving RNA annealing and strand displacement activities...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040729/csra-maximizes-expression-of-the-acrab-multidrug-resistance-transporter
#5
Vito Ricci, Victoria Attah, Tim Overton, David C Grainger, Laura J V Piddock
Carbon Storage Regulator A (CsrA) is an RNA binding protein that acts as a global regulator of diverse genes. Using a combination of genetics and biochemistry we show that CsrA binds directly to the 5' end of the transcript encoding AcrAB. Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of both AcrA and AcrB. Nucleotide substitutions at the 5' UTR of acrA mRNA that could potentially weaken the inhibitory RNA secondary structure, allow for more efficient translation of the AcrAB proteins...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040720/genome-wide-prediction-of-minor-groove-electrostatic-potential-enables-biophysical-modeling-of-protein-dna-binding
#6
Tsu-Pei Chiu, Satyanarayan Rao, Richard S Mann, Barry Honig, Remo Rohs
Protein-DNA binding is a fundamental component of gene regulatory processes, but it is still not completely understood how proteins recognize their target sites in the genome. Besides hydrogen bonding in the major groove (base readout), proteins recognize minor-groove geometry using positively charged amino acids (shape readout). The underlying mechanism of DNA shape readout involves the correlation between minor-groove width and electrostatic potential (EP). To probe this biophysical effect directly, rather than using minor-groove width as an indirect measure for shape readout, we developed a methodology, DNAphi, for predicting EP in the minor groove and confirmed the direct role of EP in protein-DNA binding using massive sequencing data...
October 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040713/human-argonaute3-has-slicer-activity
#7
Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H Hinckley, James A Brackbill, Vicki H Wysocki, Kotaro Nakanishi
Of the four human Argonaute (AGO) paralogs, only AGO2 has been shown to have slicer activity. The others (AGO1, AGO3 and AGO4) have been thought to assemble with microRNAs to form slicer-independent effector complexes that bind target mRNAs and silence gene expression through translational repression and deadenylation but not cleavage. Here, we report that recombinant AGO3 loaded with miR-20a cleaves complementary target RNAs, whereas AGO3 loaded with let-7a, miR-19b or miR-16 does not, indicating that AGO3 has slicer activity but that this activity depends on the guide RNA...
October 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040693/amypro-a-database-of-proteins-with-validated-amyloidogenic-regions
#8
Mihaly Varadi, Greet De Baets, Wim F Vranken, Peter Tompa, Rita Pancsa
Soluble functional proteins may transform into insoluble amyloid fibrils that deposit in a variety of tissues. Amyloid formation is a hallmark of age-related degenerative disorders. Perhaps surprisingly, amyloid fibrils can also be beneficial and are frequently exploited for diverse functional roles in organisms. Here we introduce AmyPro, an open-access database providing a comprehensive, carefully curated collection of validated amyloid fibril-forming proteins from all kingdoms of life classified into broad functional categories (http://amypro...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040689/regulatory-dynamics-in-the-ternary-dnaa-complex-for-initiation-of-chromosomal-replication-in-escherichia-coli
#9
Yukari Sakiyama, Kazutoshi Kasho, Yasunori Noguchi, Hironori Kawakami, Tsutomu Katayama
In Escherichia coli, the level of the ATP-DnaA initiator is increased temporarily at the time of replication initiation. The replication origin, oriC, contains a duplex-unwinding element (DUE) flanking a DnaA-oligomerization region (DOR), which includes twelve DnaA-binding sites (DnaA boxes) and the DNA-bending protein IHF-binding site (IBS). Although complexes of IHF and ATP-DnaA assembly on the DOR unwind the DUE, the configuration of the crucial nucleoprotein complexes remains elusive. To resolve this, we analyzed individual DnaA protomers in the complex and here demonstrate that the DUE-DnaA-box-R1-IBS-DnaA-box-R5M region is essential for DUE unwinding...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040668/aurora-kinase-b-a-novel-regulator-of-terf1-binding-and-telomeric-integrity
#10
Foong Lyn Chan, Benjamin Vinod, Karel Novy, Ralf B Schittenhelm, Cheng Huang, Maheshi Udugama, Juan Nunez-Iglesias, Jane I Lin, Linda Hii, Julie Chan, Hilda A Pickett, Roger J Daly, Lee H Wong
AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040665/systematic-classification-of-the-his-me-finger-superfamily
#11
Jagoda Jablonska, Dorota Matelska, Kamil Steczkiewicz, Krzysztof Ginalski
The His-Me finger endonucleases, also known as HNH or ββα-metal endonucleases, form a large and diverse protein superfamily. The His-Me finger domain can be found in proteins that play an essential role in cells, including genome maintenance, intron homing, host defense and target offense. Its overall structural compactness and non-specificity make it a perfectly-tailored pathogenic module that participates on both sides of inter- and intra-organismal competition. An extremely low sequence similarity across the superfamily makes it difficult to identify and classify new His-Me fingers...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040648/molecular-basis-for-asymmetry-sensing-of-sirnas-by-the-drosophila-loqs-pd-dcr-2-complex-in-rna-interference
#12
Jan-Niklas Tants, Stephanie Fesser, Thomas Kern, Ralf Stehle, Arie Geerlof, Christoph Wunderlich, Michael Juen, Christoph Hartlmüller, Romy Böttcher, Stefan Kunzelmann, Oliver Lange, Christoph Kreutz, Klaus Förstemann, Michael Sattler
RNA interference defends against RNA viruses and retro-elements within an organism's genome. It is triggered by duplex siRNAs, of which one strand is selected to confer sequence-specificity to the RNA induced silencing complex (RISC). In Drosophila, Dicer-2 (Dcr-2) and the double-stranded RNA binding domain (dsRBD) protein R2D2 form the RISC loading complex (RLC) and select one strand of exogenous siRNAs according to the relative thermodynamic stability of base-pairing at either end. Through genome editing we demonstrate that Loqs-PD, the Drosophila homolog of human TAR RNA binding protein (TRBP) and a paralog of R2D2, forms an alternative RLC with Dcr-2 that is required for strand choice of endogenous siRNAs in S2 cells...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040642/dynamic-dna-binding-junction-recognition-and-g4-melting-activity-underlie-the-telomeric-and-genome-wide-roles-of-human-cst
#13
Anukana Bhattacharjee, Yongyao Wang, Jiajie Diao, Carolyn M Price
Human CST (CTC1-STN1-TEN1) is a ssDNA-binding complex that helps resolve replication problems both at telomeres and genome-wide. CST resembles Replication Protein A (RPA) in that the two complexes harbor comparable arrays of OB-folds and have structurally similar small subunits. However, the overall architecture and functions of CST and RPA are distinct. Currently, the mechanism underlying CST action at diverse replication issues remains unclear. To clarify CST mechanism, we examined the capacity of CST to bind and resolve DNA structures found at sites of CST activity...
October 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040592/the-association-between-igf-i-and-igfbp-3-and-incident-diabetes-in-an-older-population-of-men-and-women-in-the-cardiovascular-health-study
#14
Chino S Aneke-Nash, Xiaonan Xue, Qibin Qi, Mary L Biggs, Anne Cappola, Lewis Kuller, Michael Pollak, Bruce M Psaty, David Siscovick, Kenneth Mukamal, Howard D Strickler, Robert C Kaplan
Context: Insulin like growth factor-I (IGF-I) has structural/functional similarities with insulin and may play a role in glucose homeostasis, along with IGF binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I. Objective: To assess whether IGF-I and IGFBP-3 are associated with higher risk of incident diabetes in older adults. Design: Participants in the Cardiovascular Health Study (n=3133), a cohort of adults aged ≥65 years, were observed for 16 years (n=3133) for the development of incident diabetes...
October 12, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29040563/ten-years-of-cazypedia-a-living-encyclopedia-of-carbohydrate-active-enzymes
#15
(no author information available yet)
CAZypeia was initiated in 2007 to create a comprehensive, living encyclopedia of the carbohydrate-active enzymes (CAZymes) and associated carbohydrate-binding modules involved in the synthesis, modification, and degradation of complex carbohydrates. CAZypedia is closely connected with the actively-curated CAZy database, which provides a sequence-based foundation for the biochemical, mechanistic, and structural characterization of these diverse proteins. Now celebrating its 10th anniversary online, CAZypedia is a successful example of dynamic, community-driven, and expert-based biocuration...
October 11, 2017: Glycobiology
https://www.readbyqxmd.com/read/29040533/hippocampal-phosphorylated-tau-induced-cognitive-decline-dendritic-spine-loss-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#16
Ramesh Kandimalla, Maria Manczak, Xiangling Yin, Rui Wang, P Hemachandra Reddy
The purpose of our study was to understand the toxic effects of hippocampal phosphorylated tau in tau mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, measured protein levels of mitochondrial dynamics, MAP2, total & phosphorylated tau, and quantified dendritic spines and mitochondrial number and length in 12-month-old tau mice with P301L mutation. Mitochondrial function was assessed by measuring the levels of H2O2, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP...
October 12, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29040432/machine-learning-accelerates-md-based-binding-pose-prediction-between-ligands-and-proteins
#17
Kei Terayama, Hiroaki Iwata, Mitsugu Araki, Yasushi Okuno, Koji Tsuda
Motivation: Fast and accurate prediction of protein-ligand binding structures is indispensable for structure-based drug design (SBDD) and accurate estimation of binding free energy of drug candidate molecules in drug discovery. Recently, accurate pose prediction methods based on short-MD simulations such as MM-PBSA and MM-GBSA among generated docking poses have been used. Since molecular structures obtained from MD simulation depends on the initial condition, taking the average over different initial conditions leads to better accuracy...
October 11, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29040414/luma-is-not-essential-for-murine-cardiac-development-and-function
#18
Matthew John Stroud, Xi Fang, Jianlin Zhang, Nuno Guimarães-Camboa, Jennifer Veevers, Nancy D Dalton, Yusu Gu, William H Bradford, Kirk L Peterson, Sylvia M Evans, Larry Gerace, Ju Chen
Aims: Luma is a recently discovered, evolutionarily conserved protein expressed in mammalian heart that is associated with the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex. The LINC complex structurally integrates the nucleus and the cytoplasm, and plays a critical role in mechanotransduction across the nuclear envelope. Mutations in several LINC components in both humans and mice result in various cardiomyopathies, implying they play essential, non-redundant roles. A single amino acid substitution of serine 358 to leucine (S358L) in LUMA is the unequivocal cause of a distinct form of arrhythmogenic cardiomyopathy...
October 12, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29040388/rna-structure-interactions-and-ribonucleoprotein-processes-of-the-influenza-a-virus
#19
Wayne K Dawson, Michal Lazniewski, Dariusz Plewczynski
In one more years, we will 'celebrate' an exact centenary of the Spanish flu pandemic. With the rapid evolution of the influenza virus, the possibility of novel pandemic remains ever a concern. This review covers our current knowledge of the influenza A virus: on the role of RNA in translation, replication, what is known of the expressed proteins and the protein products generated from alternative splicing, and on the role of base pairing in RNA structure. We highlight the main events associated with viral entry into the cell, the transcription and replication process, an export of the viral genetic material from the nucleus and the final release of the virus...
October 10, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29040308/thermostable-proteins-bioprocesses-the-activity-of-restriction-endonuclease-methyltransferase-from-thermus-thermophilus-rm-tthhb27i-cloned-in-escherichia-coli-is-critically-affected-by-the-codon-composition-of-the-synthetic-gene
#20
Daria Krefft, Aliaksei Papkov, Agnieszka Zylicz-Stachula, Piotr M Skowron
Obtaining thermostable enzymes (thermozymes) is an important aspect of biotechnology. As thermophiles have adapted their genomes to high temperatures, their cloned genes' expression in mesophiles is problematic. This is mainly due to their high GC content, which leads to the formation of unfavorable secondary mRNA structures and codon usage in Escherichia coli (E. coli). RM.TthHB27I is a member of a family of bifunctional thermozymes, containing a restriction endonuclease (REase) and a methyltransferase (MTase) in a single polypeptide...
2017: PloS One
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