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Anna Kutschenko, Marie-Christine Reinert, Nadja Krez, David Liebetanz, Andreas Rummel
The highly potent Botulinum neurotoxins (BoNT) are successful drugs to treat neuromuscular disorders. Efforts are being made to further reduce the injected BoNT dose and to lengthen the interval between treatments. Detailed knowledge of the BoNT structure-activity relationship (SAR) allows combining the best features of the different BoNT serotypes. Of all seven BoNT serotypes A-G, BoNT/A displays the highest potency despite low neuronal binding affinity, while BoNT/B exhibits much higher affinity. Recently, a new BoNT/AB hybrid (AABB) was constructed comprising the catalytic and translocation domain of BoNT/A and the 50kDa cell binding domain of BoNT/B...
December 30, 2016: Neurotoxicology
Changwon Yang, Manho Lim, Eunae Kim, Youngshang Pak
We proposed a simple van der Waals backbone correction (O2' and OP) to the AMBER ff12 force field in conjunction with the OPC water via an unequal Lorentz-Berthelot combination rule. As tested on four different tetranuceotides such as r(GACC), r(CCCC), r(AAAA), and r(CAAU), this new force field correctly captured each native fold as the largest population. For a RNA tetraloop (UUCG) tested, the stability of its native fold is substantially improved.
January 3, 2017: Journal of Chemical Theory and Computation
Kim Newton, Katherine E Wickliffe, Allie Maltzman, Debra L Dugger, Andreas Strasser, Victoria C Pham, Jennie R Lill, Merone Roose-Girma, Søren Warming, Margaret Solon, Hai Ngu, Joshua D Webster, Vishva M Dixit
Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival-mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis. However, mice expressing catalytically inactive RIPK1 are viable, and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL...
December 1, 2016: Nature
Chiao-Ling Hung, Chung-Ju Huang, Yu-Jung Tsai, Yu-Kai Chang, Tsung-Min Hung
The main purpose of this two-part study was to examine the effects of acute, moderate intensity exercise on task switching in children with attention-deficit/hyperactivity disorder (ADHD). In Study 1, we compared the task switching performance of children with and without ADHD. Twenty children with ADHD and 20 matched controls performed the task switching paradigm, in which the behavioral indices and P3 component of event-related potentials elicited by task-switching were assessed simultaneously. The amplitude and latency of P3 reflected the amount of attention resource allocated to task-relevant stimulus in the environment and the efficiency of stimulus detection and evaluation, respectively...
2016: Frontiers in Psychology
Prashant Kumar, Anisha Ashokan, Gopala Krishna Aradhyam
BACKGROUND: Human APJ receptor (APJR), a rhodopsin family G-Protein Coupled Receptor (GPCR), activated by isoforms of peptide ligand apelin causing potent inotropic effect, is involved in cardiac function, angiogenesis and maintenance of fluid homeostasis. APJR is expressed in various organs e.g., heart, brain, kidney, muscles, etc. Hence, problems in APJR signaling lead to severe dysregulation in the pathophysiology of an organism. METHODS: Based on multiple sequence alignment of receptors from various organisms, we observe a large number of conserved residues in the extracellular side...
December 2016: Biochimica et Biophysica Acta
Almut Hesse, Michael G Weller
Amino acid analysis is considered to be the gold standard for quantitative peptide and protein analysis. Here, we would like to propose a simple HPLC/UV method based on a reversed-phase separation of the aromatic amino acids tyrosine (Tyr), phenylalanine (Phe), and optionally tryptophan (Trp) without any derivatization. The hydrolysis of the proteins and peptides was performed by an accelerated microwave technique, which needs only 30 minutes. Two internal standard compounds, homotyrosine (HTyr) and 4-fluorophenylalanine (FPhe) were used for calibration...
2016: Journal of Amino Acids
Jonathan K Kleen, Markus E Testorf, David W Roberts, Rod C Scott, Barbara J Jobst, Gregory L Holmes, Pierre-Pascal Lenck-Santini
In working memory tasks, stimulus presentation induces a resetting of intracranial temporal lobe oscillations in multiple frequency bands. To further understand the functional relevance of this phenomenon, we investigated whether working memory performance depends on the phase precision of ongoing oscillations in the hippocampus. We recorded intra-hippocampal local field potentials in individuals performing a working memory task. Two types of trials were administered. For high memory trials presentation of a list of four letters ("List") was followed by a single letter memory probe ("Test")...
2016: Frontiers in Human Neuroscience
Mónika Sebestyén, György Kóczán, Ferenc Hudecz
Methotrexate (MTX) conjugates with poly[Lys(DL-Alam)] based polymeric polypeptides are efficient against Leishmania donovani parasite infection, but the mechanism of the effect is not known yet. We prepared therefore the 5(6)-carboxyfluorescein (Cf) labeled oligopeptide [Cf-K(AaAa)] (a: D-alanine, A: L-alanine) and the corresponding MTX conjugates [Cf-K(MTX-AaAa)] as model compounds for structure-activity experiments. The conjugate aimed to be synthesized with solid phase methodology on MBHA resin with Boc strategy, using Fmoc-Lys(Boc)-OH...
November 2016: Amino Acids
Song Chen, Chenran Wang, Syn Yeo, Chun-Chi Liang, Takako Okamoto, Shaogang Sun, Jian Wen, Jun-Lin Guan
Autophagy is an evolutionarily conserved cellular process controlled through a set of essential autophagy genes (Atgs). However, there is increasing evidence that most, if not all, Atgs also possess functions independent of their requirement in canonical autophagy, making it difficult to distinguish the contributions of autophagy-dependent or -independent functions of a particular Atg to various biological processes. To distinguish these functions for FIP200 (FAK family-interacting protein of 200 kDa), an Atg in autophagy induction, we examined FIP200 interaction with its autophagy partner, Atg13...
April 1, 2016: Genes & Development
Jung-Yu Tsao, Jia-Dong Tsai, Chen-I Yang
Three new azide-bridged coordination polymers, [M(N3)(tzbp)]n (M = Cu, 1·Cu; Mn, 2·Mn; Co, 3·Co), were successfully synthesized by the introduction of a bifunctional tetrazolate/2,2′-bipyridine ligand, 6-(1H-tetrazol-5-yl)-2,2′-bipyridine (Htzbp), from the in situ [2 + 3] cycloaddition of 6-cyano-2,2′-bipyridine in the presence of an excess of sodium azide under hydrothermal conditions. Compounds 1·Cu−3·Co were characterized by X-ray crystallography, IR spectroscopy, thermogravimetry, and elemental analysis...
February 28, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Robert G Cook, Muhammad A J Qadri, Ryan Oliveira
Auditory scene analysis is the process by which sounds are separated and identified from each other and from the background to make functional auditory objects. One challenge in making these psychological units is that complex sounds often continuously differ in composition over their duration. Here we examined the acoustic basis of complex sound processing in four pigeons by evaluating their performance in an ongoing same/different (S/D) task. This provided an opportunity to investigate avian auditory processing in a non-vocal learning, non-songbird...
February 2016: Behavioural Processes
Indra Mani, Renu Garg, Kailash N Pandey
Binding of the cardiac hormone atrial natriuretic peptide (ANP) to transmembrane guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), produces the intracellular second messenger cGMP in target cells. To delineate the critical role of an endocytic signal in intracellular sorting of the receptor, we have identified a FQQI (Phe(790), Gln(791), Gln(792), and Ile(793)) motif in the carboxyl-terminal region of NPRA. Mouse mesangial cells (MMCs) were transiently transfected with the enhanced green fluorescence protein (eGFP)-tagged wild-type (WT) and mutant constructs of eGFP-NPRA...
January 1, 2016: American Journal of Physiology. Renal Physiology
David E Condon, Scott D Kennedy, Brendan C Mort, Ryszard Kierzek, Ilyas Yildirim, Douglas H Turner
Molecular dynamics (MD) simulations for RNA tetramers r(AAAA), r(CAAU), r(GACC), and r(UUUU) are benchmarked against (1)H-(1)H NOESY distances and (3) J scalar couplings to test effects of RNA torsion parametrizations. Four different starting structures were used for r(AAAA), r(CAAU), and r(GACC), while five starting structures were used for r(UUUU). On the basis of X-ray structures, criteria are reported for quantifying stacking. The force fields, AMBER ff99, parmbsc0, parm99χ_Yil, ff10, and parmTor, all predict experimentally unobserved stacks and intercalations, e...
June 9, 2015: Journal of Chemical Theory and Computation
P Ewen King-Smith
Purpose:a Methods: Results: Conclusions:
February 24, 2015: Investigative Ophthalmology & Visual Science
Kai Guo, Yue-Peng Wang, Zhi-Wen Zhou, Yi-Bo Jiang, Wei Li, Xiao-Meng Chen, Yi-Gang Li
BACKGROUND: Phospholemman (PLM) is an important phosphorylation substrate for protein kinases A and C in the heart. Until now, the association between PLM phosphorylation status and L-type calcium channels (LTCCs) gating has not been fully understood. We investigated the kinetics of LTCCs in HEK 293T cells expressing phosphomimetic or nonphosphorylatable PLM mutants. METHODS: The LTCCs gating was measured in HEK 293T cells transfected with LTCC and wild-type (WT) PLM, phosphomimetic or nonphosphorylatable PLM mutants: 6263AA, 6869AA, AAAA, 6263DD, 6869DD or DDDD...
March 2015: Journal of Cellular and Molecular Medicine
Brett A Simms, Ivana A Souza, Renata Rehak, Gerald W Zamponi
The L-type voltage-gated calcium channel Cav1.2 and the calcium-activated CaM kinase cascade both regulate excitation transcription coupling in the brain. CaM kinase is known to associate with the C terminus of Cav1.2 in a region called the PreIQ-IQ domain, which also binds multiple calmodulin molecules. Here we identify and characterize a second CaMKII binding site in the N terminus of Cav1.2 that is formed by a stretch of four amino residues (cysteine-isoleucine-serine-isoleucine) and which regulates channel expression and function...
April 2015: Pflügers Archiv: European Journal of Physiology
Xing-lin Yang, Zhong-dan Hu, Qian Wu, Xi Liu, Qi-ji Liu, Yuan-chao Zhang, Qing-rui Yang
OBJECTIVES: To investigate the association of the polymorphisms in SPARC and NLRP2 with rheumatoid arthritis (RA) in a Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) covering SPARC and three SNPs covering NLRP2 were investigated in 624 Chinese Han RA patients and 1920 healthy controls. RESULTS: The A allele at SPARC rs3210714, SPARC rs11950384, NLRP2 rs2217659, and NLRP2 rs703468 were linked to reduced risk of RA (p = 0...
January 2015: Modern Rheumatology
Miju Lee, Chul-Hwan Lee, Annie Albert Demin, Palinda Ruvan Munashingha, Tamir Amangyeld, Buki Kwon, Tim Formosa, Yeon-Soo Seo
The correct removal of 5'-flap structures by Rad27 and Dna2 during Okazaki fragment maturation is crucial for the stable maintenance of genetic materials and cell viability. In this study, we identified RAD52, a key recombination protein, as a multicopy suppressor of dna2-K1080E, a lethal helicase-negative mutant allele of DNA2 in yeasts. In contrast, the overexpression of Rad51, which works conjointly with Rad52 in canonical homologous recombination, failed to suppress the growth defect of the dna2-K1080E mutation, indicating that Rad52 plays a unique and distinct role in Okazaki fragment metabolism...
May 23, 2014: Journal of Biological Chemistry
Hideki Kondo, Kazuyuki Maruyama, Sotaro Chiba, Ida Bagus Andika, Nobuhiro Suzuki
The transcriptional strategy of orchid fleck virus (OFV), which has a two-segmented negative-strand RNA genome and resembles plant nucleorhabdoviruses, remains unexplored. In this study, the transcripts of six genes encoded by OFV RNA1 and RNA2 in the poly(A)-enriched RNA fraction from infected plants were molecularly characterized. All of the OFV mRNAs were initiated at a start sequence 3'-UU-5' with one to three non-viral adenine nucleotides which were added at the 5' end of each mRNA, whereas their 3' termini ended with a 5'-AUUUAAA(U/G)AAAA(A)n-3' sequence...
March 2014: Virology
Hannele Lindqvist-Kreuze, Manuel Gastelo, Willmer Perez, Gregory A Forbes, David de Koeyer, Merideth Bonierbale
Potato genotypes from a breeding population adapted to tropical highlands were analyzed for the stability of late blight resistance and also for marker-phenotype association. We harmonized the historical evaluation data, consisting of observations spanning 6 years from two field sites utilizing a resistance scale constructed by comparing the area under the disease progress curve (AUDPC) values of 172 genotypes with that of susceptible control 'Yungay'. In total, 70 potato genotypes had a coefficient of variability <0...
June 2014: Phytopathology
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