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91.
Constantina Papatriantafyllopoulou Catherine P. Raptopoulou Spyros P. Perlepes John C. Plakatouras 《Inorganica chimica acta》2009,362(7):2361-478
The reactions of methyl 2-pyridyl ketone oxime, (py)C(Me)NOH, with MSO4 · xH2O (M = Zn, x = 7; M = Cd, x = 8/3), in the absence of an external base, have been investigated. The synthetic study has led to the two new complexes [Zn(SO4){(py)C(Me)NOH}(H2O)3] · H2O (1 · H2O) and [Zn2(SO4)2{(py)C(Me)NOH}4] · (py)C(Me)NOH [2 · (py)C(Me)NOH], and the coordination polymer [Cd(SO4){(py)C(Me)NOH}(H2O)]n · [Cd(SO4){(py)C(Me)NOH}(H2O)2]n (3). In the three complexes the organic ligand chelates through its nitrogen atoms. The sulfate anion in 1 · H2O is monodentate; the complex molecule is the mer isomer considering the positions of the aqua ligands. The ZnII centers in 2 · (py)C(Me)NOH are bridged by two syn, anti η1:η1:μ2 ligands; each metal ion has the cis-cis-trans disposition of the coordinated sulfate oxygen, pyridyl nitrogen and oxime nitrogens, respectively. The molecular structure of 3 is unique consisting of two different linear and ladder - type chains. π-π stacking interactions and/or hydrogen bonds lead to the formation of interesting supramolecular architectures in the three complexes. The thermal decomposition of complex 3 has been studied. Characteristic vibrational (IR, Raman) bands are discussed in terms of the nature of bonding and the structures of the three complexes. 相似文献
92.
This paper investigates the effectiveness of spiking agents when trained with reinforcement learning (RL) in a challenging multiagent task. In particular, it explores learning through reward-modulated spike-timing dependent plasticity (STDP) and compares it to reinforcement of stochastic synaptic transmission in the general-sum game of the Iterated Prisoner's Dilemma (IPD). More specifically, a computational model is developed where we implement two spiking neural networks as two "selfish" agents learning simultaneously but independently, competing in the IPD game. The purpose of our system (or collective) is to maximise its accumulated reward in the presence of reward-driven competing agents within the collective. This can only be achieved when the agents engage in a behaviour of mutual cooperation during the IPD. Previously, we successfully applied reinforcement of stochastic synaptic transmission to the IPD game. The current study utilises reward-modulated STDP with eligibility trace and results show that the system managed to exhibit the desired behaviour by establishing mutual cooperation between the agents. It is noted that the cooperative outcome was attained after a relatively short learning period which enhanced the accumulation of reward by the system. As in our previous implementation, the successful application of the learning algorithm to the IPD becomes possible only after we extended it with additional global reinforcement signals in order to enhance competition at the neuronal level. Moreover it is also shown that learning is enhanced (as indicated by an increased IPD cooperative outcome) through: (i) strong memory for each agent (regulated by a high eligibility trace time constant) and (ii) firing irregularity produced by equipping the agents' LIF neurons with a partial somatic reset mechanism. 相似文献
93.
Debanu Das Robert D. Finn Polat Abdubek Tamara Astakhova Herbert L. Axelrod Constantina Bakolitsa Xiaohui Cai Dennis Carlton Connie Chen Hsiu‐Ju Chiu Michelle Chiu Thomas Clayton Marc C. Deller Lian Duan Kyle Ellrott Carol L. Farr Julie Feuerhelm Joanna C. Grant Anna Grzechnik Gye Won Han Lukasz Jaroszewski Kevin K. Jin Heath E. Klock Mark W. Knuth Piotr Kozbial S. Sri Krishna Abhinav Kumar Winnie W. Lam David Marciano Mitchell D. Miller Andrew T. Morse Edward Nigoghossian Amanda Nopakun Linda Okach Christina Puckett Ron Reyes Henry J. Tien Christine B. Trame Henry van den Bedem Dana Weekes Tiffany Wooten Qingping Xu Andrew Yeh Jiadong Zhou Keith O. Hodgson John Wooley Marc‐André Elsliger Ashley M. Deacon Adam Godzik Scott A. Lesley Ian A. Wilson 《Protein science : a publication of the Protein Society》2010,19(11):2131-2140
Sufu (Suppressor of Fused), a two‐domain protein, plays a critical role in regulating Hedgehog signaling and is conserved from flies to humans. A few bacterial Sufu‐like proteins have previously been identified based on sequence similarity to the N‐terminal domain of eukaryotic Sufu proteins, but none have been structurally or biochemically characterized and their function in bacteria is unknown. We have determined the crystal structure of a more distantly related Sufu‐like homolog, NGO1391 from Neisseria gonorrhoeae, at 1.4 Å resolution, which provides the first biophysical characterization of a bacterial Sufu‐like protein. The structure revealed a striking similarity to the N‐terminal domain of human Sufu (r.m.s.d. of 2.6 Å over 93% of the NGO1391 protein), despite an extremely low sequence identity of ~15%. Subsequent sequence analysis revealed that NGO1391 defines a new subset of smaller, Sufu‐like proteins that are present in ~200 bacterial species and has resulted in expansion of the SUFU (PF05076) family in Pfam. 相似文献
94.
Chris Christodoulou Sudhir Agrawal Michael J. Gait 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):341-344
Abstract The 2-(2,4-dinitrobenzenesulphenyloxymethyl)benzoyl (DNBSB) group is proposed as a protecting group for the 5′-position of nucleosides. The DNBSB group may be removed under mild non-acidic conditions and may have potential in solid-phase synthesis of oligoribo- and oligodeoxyribonucleotides. 相似文献
95.
George Pentheroudakis Vassiliki Kotoula Anastasia G. Eleftheraki Eleftheria Tsolaki Ralph M. Wirtz Konstantine T. Kalogeras Anna Batistatou Mattheos Bobos Meletios A. Dimopoulos Eleni Timotheadou Helen Gogas Christos Christodoulou Kyriaki Papadopoulou Ioannis Efstratiou Chrisoula D. Scopa Irene Papaspyrou Dimitrios Vlachodimitropoulos Helena Linardou Epaminontas Samantas Dimitrios Pectasides Nicholas Pavlidis George Fountzilas 《PloS one》2013,8(7)
Background
Discrepant data have been published on the incidence and prognostic significance of ESR1 gene amplification in early breast cancer.Patients and Methods
Formalin-fixed paraffin-embedded tumor blocks were collected from women with early breast cancer participating in two HeCOG adjuvant trials. Messenger RNA was studied by quantitative PCR, ER protein expression was centrally assessed using immunohistochemistry (IHC) and ESR1 gene copy number by dual fluorescent in situ hybridization probes.Results
In a total of 1010 women with resected node-positive early breast adenocarcinoma, the tumoral ESR1/CEP6 gene ratio was suggestive of deletion in 159 (15.7%), gene gain in 551 (54.6%) and amplification in 42 cases (4.2%), with only 30 tumors (3%) harboring five or more ESR1 copies. Gene copy number ratio showed a significant, though weak correlation to mRNA and protein expression (Spearman''s Rho <0.23, p = 0.01). ESR1 clusters were observed in 9.5% (57 gain, 38 amplification) of cases. In contrast to mRNA and protein expression, which were favorable prognosticators, gene copy number changes did not obtain prognostic significance. When ESR1/CEP6 gene ratio was combined with function (as defined by ER protein and mRNA expression) in a molecular classifier, the Gene Functional profile, it was functional status that impacted on prognosis. In univariate analysis, patients with functional tumors (positive ER protein expression and gene ratio normal or gain/amplification) fared better than those with non-functional tumors with ESR1 gain (HR for relapse or death 0.49–0.64, p = 0.003). Significant interactions were observed between gene gain/amplification and paclitaxel therapy (trend for DFS benefit from paclitaxel only in patients with ESR1 gain/amplification, p = 0.066) and Gene Functional profile with HER2 amplification (Gene Functional profile prognostic only in HER2-normal cases, p = 0.029).Conclusions
ESR1 gene deletion and amplification do not constitute per se prognostic markers, instead they can be classified to distinct prognostic groups according to their protein-mediated functional status. 相似文献96.
Michael S. Christodoulou Alessandro Sacchetti Valentina Ronchetti Stefania Caufin Alessandra Silvani Giordano Lesma Gabriele Fontana Fabrizio Minicone Benedetta Riva Micol Ventura Maija Lahtela-Kakkonen Elina Jarho Valentina Zuco Franco Zunino Nadine Martinet Federico Dapiaggi Stefano Pieraccini Maurizio Sironi Daniele Passarella 《Bioorganic & medicinal chemistry》2013,21(22):6920-6928
This paper reports the synthesis of a series of evodiamine derivatives. We assayed the ability to inhibit cell growth on three human tumour cell lines (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the catalytic activity of topoisomerase I both by the relaxation assay and the occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and 3 was investigated. Finally, molecular docking analyses were performed in an attempt to rationalize the biological results. 相似文献
97.
Heidebrecht T Christodoulou E Chalmers MJ Jan S Ter Riet B Grover RK Joosten RP Littler D van Luenen H Griffin PR Wentworth P Borst P Perrakis A 《Nucleic acids research》2011,39(13):5715-5728
The J-binding protein 1 (JBP1) is essential for biosynthesis and maintenance of DNA base-J (β-d-glucosyl-hydroxymethyluracil). Base-J and JBP1 are confined to some pathogenic protozoa and are absent from higher eukaryotes, prokaryotes and viruses. We show that JBP1 recognizes J-containing DNA (J-DNA) through a 160-residue domain, DB-JBP1, with 10 000-fold preference over normal DNA. The crystal structure of DB-JBP1 revealed a helix-turn-helix variant fold, a ‘helical bouquet’ with a ‘ribbon’ helix encompassing the amino acids responsible for DNA binding. Mutation of a single residue (Asp525) in the ribbon helix abrogates specificity toward J-DNA. The same mutation renders JBP1 unable to rescue the targeted deletion of endogenous JBP1 genes in Leishmania and changes its distribution in the nucleus. Based on mutational analysis and hydrogen/deuterium-exchange mass-spectrometry data, a model of JBP1 bound to J-DNA was constructed and validated by small-angle X-ray scattering data. Our results open new possibilities for targeted prevention of J-DNA recognition as a therapeutic intervention for parasitic diseases. 相似文献
98.
David K. Miller Minal J. Menezes Cas Simons Lisa G. Riley Sandra T. Cooper Sean M. Grimmond David R. Thorburn John Christodoulou Ryan J. Taft 《PloS one》2014,9(8)
Leigh syndrome (LS) is a rare progressive multi-system neurodegenerative disorder, the genetics of which is frequently difficult to resolve. Rapid determination of the genetic etiology of LS in a 5-year-old girl facilitated inclusion in Edison Pharmaceutical’s phase 2B clinical trial of EPI-743. SNP-arrays and high-coverage whole exome sequencing were performed on the proband, both parents and three unaffected siblings. Subsequent multi-tissue targeted high-depth mitochondrial sequencing was performed using custom long-range PCR amplicons. Tissue-specific mutant load was also assessed by qPCR. Complex I was interrogated by spectrophotometric enzyme assays and Western Blot. No putatively causal mutations were identified in nuclear-encoded genes. Analysis of low-coverage off-target mitochondrial reads revealed a previously unreported mitochondrial mutation in the proband in MT-ND3 (m.10134C>A, p.Q26K), a Complex I mitochondrial gene previously associated with LS. Targeted investigations demonstrated that this mutation was 1% heteroplasmic in the mother’s blood and homoplasmic in the proband’s blood, fibroblasts, liver and muscle. Enzyme assays revealed decreased Complex I activity. The identification of this novel LS MT-ND3 variant, the genomics of which was accomplished in less than 3.5 weeks, indicates that rapid genomic approaches may prove useful in time-sensitive cases with an unresolved genetic diagnosis. 相似文献
99.
George Valiakos Konstantinos Papaspyropoulos Alexios Giannakopoulos Periklis Birtsas Sotirios Tsiodras Michael R. Hutchings Vassiliki Spyrou Danai Pervanidou Labrini V. Athanasiou Nikolaos Papadopoulos Constantina Tsokana Agoritsa Baka Katerina Manolakou Dimitrios Chatzopoulos Marc Artois Lisa Yon Duncan Hannant Liljana Petrovska Christos Hadjichristodoulou Charalambos Billinis 《PloS one》2014,9(5)
West Nile Virus (WNV) is the causative agent of a vector-borne, zoonotic disease with a worldwide distribution. Recent expansion and introduction of WNV into new areas, including southern Europe, has been associated with severe disease in humans and equids, and has increased concerns regarding the need to prevent and control future WNV outbreaks. Since 2010, 524 confirmed human cases of the disease have been reported in Greece with greater than 10% mortality. Infected mosquitoes, wild birds, equids, and chickens have been detected and associated with human disease. The aim of our study was to establish a monitoring system with wild birds and reported human cases data using Geographical Information System (GIS). Potential distribution of WNV was modelled by combining wild bird serological surveillance data with environmental factors (e.g. elevation, slope, land use, vegetation density, temperature, precipitation indices, and population density). Local factors including areas of low altitude and proximity to water were important predictors of appearance of both human and wild bird cases (Odds Ratio = 1,001 95%CI = 0,723–1,386). Using GIS analysis, the identified risk factors were applied across Greece identifying the northern part of Greece (Macedonia, Thrace) western Greece and a number of Greek islands as being at highest risk of future outbreaks. The results of the analysis were evaluated and confirmed using the 161 reported human cases of the 2012 outbreak predicting correctly (Odds = 130/31 = 4,194 95%CI = 2,841–6,189) and more areas were identified for potential dispersion in the following years. Our approach verified that WNV risk can be modelled in a fast cost-effective way indicating high risk areas where prevention measures should be implemented in order to reduce the disease incidence. 相似文献
100.