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https://www.readbyqxmd.com/read/28642865/spinal-muscular-atrophy-from-defective-chaperoning-of-snrnp-assembly-to-neuromuscular-dysfunction
#1
REVIEW
Maia Lanfranco, Neville Vassallo, Ruben J Cauchi
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN) protein. SMN is part of a multiprotein complex that also includes Gemins 2-8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5) complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs) to generate small nuclear ribonucleoproteins (snRNPs), which are the operating components of the spliceosome...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28632940/characterization-of-the-i4399m-variant-of-apolipoprotein-a-implications-for-altered-prothrombotic-properties-of-lipoprotein-a
#2
Corey A Scipione, Jackson T McAiney, Daniel J Simard, Zainab A Bazzi, Matthew Gemin, Rocco Romagnuolo, Fraser L Macrae, Robert A Ariëns, Robert A Hegele, Janeen Auld, James W Gauld, Michael B Boffa, Marlys L Koschinsky
BACKGROUND: Lipoprotein(a) (Lp(a)) is a causal risk factor for a variety of cardiovascular diseases. Apolipoprotein(a) (apo(a)), the distinguishing component of Lp(a), is homologous to plasminogen, suggesting that Lp(a) can interfere with the normal fibrinolytic functions of plasminogen. This has implications for the persistence of fibrin clots in the vasculature and hence to atherothrombotic diseases. A single nucleotide polymorphism (rs3798220) in the gene encoding apo(a) has been reported that results in an Ile to Met substitution in the protease-like domain (I4399M variant)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28628737/analysis-of-structure-activity-relationships-based-on-the-hcv-sliib-ires-rna-targeting-gghyrfk-cu-complex
#3
Martin J Ross, Insiya Fidai, James Allan Cowan
New therapeutics for the targeting of the hepatitis C virus have been released in recent years. Although these therapies are less prone to resistance, they are still administered in cocktails as a combination of drugs targeting various aspects of the viral life cycle. Herein, we aim to contribute to an arsenal of new HCV therapeutics by targeting HCV internal ribosomal entry sequence (IRES) RNA via development of catalytic metallodrugs that function to degrade rather than inhibit the target molecule. Based on a previously characterized HCV IRES stem-loop IIb RNA-targeting metallopeptide Cu-GGHYrFK (1-Cu), an all L-analogue (3-Cu) and a series of additional complexes with single alanine substitutions in the targeting domain were prepared and screened to determine the influence each amino acid side-chain on RNA localization and recognition, and catalytic reactivity toward the RNA...
June 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28605914/transition-metal-free-homologative-cross-coupling-of-aldehydes-and-ketones-with-geminal-bis-boron-compounds
#4
Thomas C Stephens, Graham Pattison
We report a transition-metal-free coupling of aldehydes and ketones with geminal bis(boron) building blocks which provides the coupled, homologated carbonyl compound upon oxidation. This reaction not only extends an alkyl chain containing a carbonyl group, it also simultaneously introduces a new carbonyl substituent. We demonstrate that enantiopure aldehydes with an enolizable stereogenic center undergo this reaction with complete retention of stereochemistry.
June 13, 2017: Organic Letters
https://www.readbyqxmd.com/read/28598178/multidisciplinary-approach-to-the-treatment-of-double-bilateral-upper-permanent-incisors-in-a-young-boy
#5
G F Ferrazzano, P Festa, T Cantile, V D'Antò, A Ingenito, R Martina
BACKGROUND: A double tooth is a rare developmental anomaly referring to the fusion of two adjacent tooth buds or the gemination of a single bud. CASE REPORT: This case report describes the multidisciplinary approach to an 11-year-old patient with two double upper permanent incisors. The clinical intraoral examination showed a mixed dentition with bilateral double maxillary central incisors, molar Class I malocclusion and palatal ectopy of two lateral upper incisors...
June 2017: European Journal of Paediatric Dentistry: Official Journal of European Academy of Paediatric Dentistry
https://www.readbyqxmd.com/read/28585086/a-mechanistic-study-of-geminal-dicationic-ionic-liquids-as-mobile-phase-additives-for-improving-the-separation-performance-of-high-performance-liquid-chromatography
#6
Guanglong Ding, Wenbing Zhang, Zhaopeng Zhang, Dong Guo, Gang Tang, Yanran Li, Jianqiang Li, Yongsong Cao
Due to the acidity and strong polarity of auxinic herbicides, separation of these compounds in food and environmental samples is a great challenge. In this study, 12 geminal dicationic ionic liquids (GDILs) were synthesized and used as mobile phase additives to separate six auxinic herbicides. The effects of the kind of dication, the length of linkage chain, the kind of anion, the concentration of GDILs, and the pH of mobile phase for the separation were investigated in detail. Compared with [C4MIm][BF4], GDILs ([C8(MIm)2][BF4]2) showed higher resolution, better peak shape, and lower retention factor...
June 6, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28514597/a-blocked-linear-method-for-optimizing-large-parameter-sets-in-variational-monte-carlo
#7
Luning Zhao, Eric Neuscamman
We present a modification to variational Monte Carlo's linear method optimization scheme that addresses a critical memory bottleneck while maintaining compatibility with both the traditional ground state variational principle and our recently introduced variational principle for excited states. For wave function ansatzes with tens of thousands of variables, our modification reduces the required memory per parallel process from tens of gigabytes to hundreds of megabytes, making the methodology a much better fit for modern supercomputer architectures in which data communication and per-process memory consumption are primary concerns...
June 1, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28504532/orthography-affects-second-language-speech-double-letters-and-geminate-production-in-english
#8
Bene Bassetti
Second languages (L2s) are often learned through spoken and written input, and L2 orthographic forms (spellings) can lead to non-native-like pronunciation. The present study investigated whether orthography can lead experienced learners of EnglishL2 to make a phonological contrast in their speech production that does not exist in English. Double consonants represent geminate (long) consonants in Italian but not in English. In Experiment 1, native English speakers and EnglishL2 speakers (Italians) were asked to read aloud English words spelled with a single or double target consonant letter, and consonant duration was compared...
May 15, 2017: Journal of Experimental Psychology. Learning, Memory, and Cognition
https://www.readbyqxmd.com/read/28498379/non-pericyclic-cycloaddition-of-gem-difluorosubstituted-azomethine-ylides-to-the-c-double-bond-length-as-m-dash-o-bond-computational-study-and-synthesis-of-fluorinated-oxazole-derivatives
#9
Karina R Gaisina, Alexander F Khlebnikov, Mikhail S Novikov
The cycloaddition of arenecarbaldehydes and α,α,α-trifluoroacetophenones with gem-difluoro-substituted azomethine ylides, generated from N-benzhydrylideneamines and difluorocarbene, occurs regioselectively to give, after hydrolysis, oxazolidin-4-ones. The primary cycloadducts of trifluoroacetophenones, 4,4-difluoro-5-trifluoromethyloxazolidine derivatives, are sufficiently stable to be isolated in reasonable to excellent yields. The results of correlation analysis and DFT calculations reveal a non-pericyclic step-wise mechanism of the reaction...
May 31, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28488589/quasicrystalline-and-crystalline-types-of-local-protein-order-in-capsids-of-small-viruses
#10
O V Konevtsova, V V Pimonov, V L Lorman, S B Rochal
Like metal alloys and micellar systems in soft matter, the viral capsid structures can be of crystalline and quasicrystalline types. We reveal the local quasicrystalline order of proteins in small spherical viral capsids using their nets of dodecahedral type. We show that the structure of some of the viral shells is well described in terms of a chiral pentagonal tiling, whose nodes coincide with centers of mass of protein molecules. The chiral protein packing found in these capsids originates from the pentagonal Penrose tiling (PPT), due to a specific phason reconstruction needed to fit the protein order at the adjacent dodecahedron faces...
July 19, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28486928/patterns-of-divergence-in-fish-species-separated-by-the-isthmus-of-panama
#11
Christine E Thacker
BACKGROUND: The Pleistocene closure of Isthmus of Panama, separating the basins of the Eastern Pacific and the Caribbean Sea, created a unique natural experiment that reveals how marine faunas respond to environmental change. To explore how fishes have been affected by this tectonic event, I compare transisthmian patterns in phylogeny and morphology for geminate lineages in two families, Eleotridae (sleepers) and Apogonidae (cardinalfishes). RESULTS: Time-calibrated phylogenies for these families show different diversification patterns...
May 10, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28485597/photoaquation-mechanism-of-hexacyanoferrate-ii-ions-ultrafast-2d-uv-and-transient-visible-and-ir-spectroscopies
#12
Marco Reinhard, Gerald Auböck, Nicholas A Besley, Ian P Clark, Gregory M Greetham, Magnus W D Hanson-Heine, Raphael Horvath, Thomas S Murphy, Thomas J Penfold, Michael Towrie, Michael W George, Majed Chergui
Ferrous iron(II) hexacyanide in aqueous solutions is known to undergo photoionization and photoaquation reactions depending on the excitation wavelength. To investigate this wavelength dependence, we implemented ultrafast two-dimensional UV transient absorption spectroscopy, covering a range from 280 to 370 nm in both excitation and probing, along with UV pump/visible probe or time-resolved infrared (TRIR) transient absorption spectroscopy and density functional theory (DFT) calculations. As far as photoaquation is concerned, we find that excitation of the molecule leads to ultrafast intramolecular relaxation to the lowest triplet state of the [Fe(CN)6](4-) complex, followed by its dissociation into CN(-) and [Fe(CN)5](3-) fragments and partial geminate recombination, all within <0...
May 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28481497/charge-transfer-states-in-organic-solar-cells-understanding-the-impact-of-polarization-delocalization-and-disorder
#13
Zilong Zheng, Naga Rajesh Tummala, Yao-Tsung Fu, Veaceslav Coropceanu, Jean-Luc Brédas
We investigate the impact of electronic polarization, charge delocalization, and energetic disorder on the charge-transfer (CT) states formed at a planar C60/pentacene interface. The ability to examine large complexes containing up to seven pentacene molecules and three C60 molecules allows us to take explicitly into account the electronic polarization effects. These complexes are extracted from a bilayer architecture modeled by molecular dynamics simulations and evaluated by means of electronic-structure calculations based on long-range-separated functionals (ωB97XD and BNL) with optimized range-separation parameters...
May 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28480917/femtosecond-to-microsecond-observation-of-the-photochemical-reaction-of-1-2-di-quinolin-2-yl-disulfide-with-methyl-methacrylate
#14
Daisuke Koyama, Paul M Donaldson, Andrew J Orr-Ewing
The mechanism of the thiol-ene reaction induced by 330 nm ultraviolet excitation of 1,2-di(quinolin-2-yl)disulfide (QSSQ) in the presence of methyl methacrylate (MMA) is investigated by sub-picosecond to microsecond transient absorption spectroscopy. The measurements, spanning more than seven orders of magnitude of time, directly reveal multiple radical reaction steps. The ground state quinoliene-2-thiyl radical (QS) is formed with a time constant of ∼200 fs by photolysis of QSSQ, followed by (64 ± 1)% decay of the initially formed QS radical because of solvent cage induced geminate recombination and QS dimer formation with a rate coefficient of (3...
May 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28475338/br%C3%A3-nsted-acid-catalyzed-intramolecular-hydroarylation-of-%C3%AE-benzylstyrenes
#15
Xiao Cai, Amir Keshavarz, Justin D Omaque, Benjamin J Stokes
Using triphenylmethylium tetrakis(pentafluorophenyl)borate as a convenient Brønsted acid precatalyst, β-(α,α-dimethylbenzyl)styrenes are shown to cyclize efficiently to afford a variety of new indanes that possess a benzylic quaternary center. The geminal dimethyl-containing quaternary center is proposed to be necessary to arm the substrate for cyclization through steric biasing.
May 5, 2017: Organic Letters
https://www.readbyqxmd.com/read/28451249/geminal-bis-borane-formation-by-borane-lewis-acid-induced-cyclopropyl-rearrangement-and-its-frustrated-lewis-pair-reaction-with-carbon-dioxide
#16
Yun-Lin Liu, Gerald Kehr, Constantin G Daniliuc, Gerhard Erker
Cyclopropylacetylene reacts with two molar equivalents of Piers' borane [HB(C6F5)2] under mild conditions by an addition/rearrangement sequence with cyclopropyl ring opening to give a mixture of two α-B(C6F5)2 substituted tetrahydroboroles. This compound forms an active frustrated Lewis pair with P (t) Bu3 that heterolytically splits dihydrogen and adds carbon dioxide as a geminal chelate bis-boryl component. The respective reactions of the two-fold HB(C6F5)2 addition to Ph-CH2CH2C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 CH were studied as a geminal Lewis acid reference...
February 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28449230/metal-free-arene-and-heteroarene-borylation-catalyzed-by-strongly-electrophilic-bis-boranes
#17
Gerhard Erker, Yun-Lin Liu, Gerald Kehr, Constantin G Daniliuc
The geminal chelate bis-borylalkanes 4 and 5 featuring strongly electrophilic B(C6F5)2 and B(C6F5) groups, respectively, serve as efficient catalysts for the borylation of arenes and heteroarenes. The borylation reactions proceed under mild conditions with liberation of dihydrogen.
April 27, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28399452/design-synthesis-and-evaluation-of-curcumin-derivatives-as-nrf2-activators-and-cytoprotectors-against-oxidative-death
#18
Zhi-Shan Tu, Qi Wang, Dan-Dan Sun, Fang Dai, Bo Zhou
Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells...
April 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28391179/weak-coupling-between-magnetically-inequivalent-spins-the-deceptively-simple-complicated-spectrum-of-a-13-c-labeled-trimethylated-amine
#19
Ulric B le Paige, Bauke Smits, Peter 't Hart, Fons Lefeber, Nathaniel I Martin, Hugo van Ingen
Magnetic inequivalence of nuclear spins is well known to cause additional splittings that complicate spectral analysis. Here, we present an extraordinary case of magnetic inequivalence, manifested in the 13-spin system of a (13)C,(15)N-labeled trimethylated amine. All methyl group protons are chemically equivalent due to the molecular symmetry, but not all are magnetically equivalent as they have different (1)JCH and (3)JCH couplings. In general, spectra of such a large spin system can be expected to be extremely complicated by the presence of hundreds if not thousands of extra lines, caused by the strong coupling between inequivalent nuclei...
May 2017: Journal of Magnetic Resonance
https://www.readbyqxmd.com/read/28386097/phenotypic-variability-and-community-interactions-of-germinating-streptomyces-spores
#20
Ye Xu, Kalin Vetsigian
A case can be made for stochastic germination and interactions among germinating spores as beneficial germination strategies in uncertain environments. However, there is little data on how widespread, species-specific or diverse such phenomena are. Focusing on Streptomycetes, a platform was developed for quantification of germination and early growth within communities of spores. We found that the germination process is stochastic at three levels: spores vary in their germination times, mycelium networks grow at different rates, and a fraction of germlings stall their growth shortly after germination...
April 6, 2017: Scientific Reports
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