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1.
PLoS Pathog ; 17(3): e1009399, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33720977

RESUMO

Trypanosoma cruzi is a protist parasite and the causative agent of American trypanosomiasis or Chagas disease. The parasite life cycle in its mammalian host includes an intracellular stage, and glycosylated proteins play a key role in host-parasite interaction facilitating adhesion, invasion and immune evasion. Here, we report that a Golgi-localized Mn2+-Ca2+/H+ exchanger of T. cruzi (TcGDT1) is required for efficient protein glycosylation, host cell invasion, and intracellular replication. The Golgi localization was determined by immunofluorescence and electron microscopy assays. TcGDT1 was able to complement the growth defect of Saccharomyces cerevisiae null mutants of its ortholog ScGDT1 but ablation of TcGDT1 by CRISPR/Cas9 did not affect the growth of the insect stage of the parasite. The defect in protein glycosylation was rescued by Mn2+ supplementation to the growth medium, underscoring the importance of this transition metal for Golgi glycosylation of proteins.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Doença de Chagas/metabolismo , Interações Hospedeiro-Parasita/fisiologia , Manganês/metabolismo , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/fisiologia , Animais , Chlorocebus aethiops , Glicosilação , Complexo de Golgi/metabolismo , Células Vero , Internalização do Vírus , Replicação Viral/fisiologia
2.
Inorg Chem ; 62(49): 19856-19870, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38031668

RESUMO

The reactions of amide functionalized bisphosphine, o-Ph2PC6H4C-(O)N(H)C6H4PPh2-o (1) (BalaHariPhos), with copper salts is described. Treatment of 1 with CuX in a 1:1 molar ratio yielded chelate complexes of the type [CuX{(o-Ph2PC6H4C(O)N(H)C6H4PPh2-o)}-κ2-P,P] (X = Cl, 2; Br, 3; and I, 4), which on subsequent treatment with KOtBu resulted in a dimeric complex [Cu(o-Ph2PC6H4C(O)(N)C6H4PPh2-o)]2 (5). Interestingly, complexes 2-4 showed weak N-H···Cu interactions. These weak H-bonding interactions are studied in detail both experimentally and computationally. Also, CuI complexes 2-5 were employed in the oxidative dehydrogenative carboxylation (ODC) of unactivated cycloalkanes in the presence of carboxylic acids to form the corresponding allylic esters. Among complexes 2-5, halide-free dimeric CuI complex 5 showed excellent metal-ligand cooperativity in the oxidative dehydrogenative carboxylation (ODC) in the presence of carboxylic acids to form the corresponding allylic esters through C(sp3)-H bond activation of unactivated cycloalkanes. Mechanistic details of the catalytic process were established by isolating the precatalyst [Cu{(o-Ph2PC6H4C(O)(NH)C6H4PPh2-o)-κ2-P,P}(OOCPh)] (6) and fully characterized by mass spectrometry, NMR data, and single-crystal X-ray analysis. Density functional theory-based calculations further provided a quantitative understanding of the energetics of a series of H atom transfer steps occurring in the catalytic cycle.

3.
FASEB J ; 35(6): e21641, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34041791

RESUMO

The bloodstream stage of Trypanosoma brucei, the causative agent of African trypanosomiasis, is characterized by its high rate of endocytosis, which is involved in remodeling of its surface coat. Here we present evidence that RNAi-mediated expression down-regulation of vacuolar protein sorting 41 (Vps41), a component of the homotypic fusion and vacuole protein sorting (HOPS) complex, leads to a strong inhibition of endocytosis, vesicle accumulation, enlargement of the flagellar pocket ("big eye" phenotype), and dramatic effect on cell growth. Unexpectedly, other functions described for Vps41 in mammalian cells and yeasts, such as delivery of proteins to lysosomes, and lysosome-related organelles (acidocalcisomes) were unaffected, indicating that in trypanosomes post-Golgi trafficking is distinct from that of mammalian cells and yeasts. The essentiality of TbVps41 suggests that it is a potential drug target.


Assuntos
Endocitose , Lisossomos/metabolismo , Organelas/metabolismo , Proteínas de Protozoários/metabolismo , Trypanosoma brucei brucei/fisiologia , Tripanossomíase/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Transporte Proteico , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/genética , Interferência de RNA , Tripanossomíase/parasitologia , Proteínas de Transporte Vesicular/antagonistas & inibidores , Proteínas de Transporte Vesicular/genética
4.
J Chem Inf Model ; 61(8): 4058-4067, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297570

RESUMO

The COVID-19 pandemic has motivated researchers all over the world in trying to find effective drugs and therapeutics for treating this disease. To save time, much effort has focused on repurposing drugs known for treating other diseases than COVID-19. To support these drug repurposing efforts, we built the CAS Biomedical Knowledge Graph and identified 1350 small molecules as potentially repurposable drugs that target host proteins and disease processes involved in COVID-19. A computer algorithm-driven drug-ranking method was developed to prioritize those identified small molecules. The top 50 molecules were analyzed according to their molecular functions and included 11 drugs in clinical trials for treating COVID-19 and new candidates that may be of interest for clinical investigation. The CAS Biomedical Knowledge Graph provides researchers an opportunity to accelerate innovation and streamline the investigative process not just for COVID-19 but also in many other diseases.


Assuntos
COVID-19 , Reposicionamento de Medicamentos , Antivirais , Humanos , Pandemias , Reconhecimento Automatizado de Padrão , SARS-CoV-2
5.
J Am Chem Soc ; 142(18): 8160-8173, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32271552

RESUMO

Cathodes based on layered LiMO2 are the limiting components in the path toward Li-ion batteries with energy densities suitable for electric vehicles. Introducing an overstoichiometry of Li increases storage capacity beyond a conventional mechanism of formal transition metal redox. However, the role and fate of the oxide ligands in such intriguing additional capacity remain unclear. This reactivity was predicted in Li3RuO4, making it a valuable model system. A comprehensive analysis of the redox activity of both Ru and O under different electrochemical conditions was carried out, and the effect of Li/Ru ordering was evaluated. Li3RuO4 displays highly reversible Li intercalation to Li4RuO4 below 2.5 V vs Li+/Li0, with conventional reactivity through the formal Ru5+-Ru4+ couple. In turn, it can also undergo anodic Li extraction at 3.9 V, which involves O states to a much greater extent than Ru. This reaction competes with side processes such as electrolyte decomposition and, to a much lesser extent, oxygen loss. Although the associated capacity is reversible, reintercalation unlocks a different, conventional pathway also involving the formal Ru5+-Ru4+ couple despite operating above 2.5 V, leading to chemical hysteresis. This new pathway is both chemically and electrochemically reversible in subsequent cycles. This work exemplifies both the challenge of stabilizing highly depleted O states, even with 4d metals, and the ability of solids to access the same redox couple at two very different potential windows depending on the underlying structural changes. It highlights the importance of properly defining the covalency of oxides when defining charge compensation in view of the design of materials with high capacity for Li storage.

6.
J Am Chem Soc ; 142(18): 8522-8531, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32271554

RESUMO

Layered Li-rich Ni, Mn, Co (NMC) oxide cathodes in Li-ion batteries provide high specific capacities (>250 mAh/g) via O-redox at high voltages. However, associated high-voltage interfacial degradation processes require strategies for effective electrode surface passivation. Here, we show that an acidic surface treatment of a Li-rich NMC layered oxide cathode material leads to a substantial suppression of CO2 and O2 evolution, ∼90% and ∼100% respectively, during the first charge up to 4.8 V vs Li+/0. CO2 suppression is related to Li2CO3 removal as well as effective surface passivation against electrolyte degradation. This treatment does not result in any loss of discharge capacity and provides superior long-term cycling and rate performance in comparison to as-received, untreated materials. We also quantify the extent of lattice oxygen participation in charge compensation ("O-redox") during Li+ removal by a novel ex situ acid titration. Our results indicate that the peroxo-like species resulting from O-redox originate on the surface at least 300 mV earlier than the activation plateau region at around 4.5 V. X-ray photoelectron spectra and Mn L-edge X-ray absorption spectra of the cathode powders reveal a Li+ deficiency and a partial reduction of Mn ions on the surface of the acid-treated material. More interestingly, although the irreversible oxygen evolution is greatly suppressed through the surface treatment, O K-edge resonant inelastic X-ray scattering shows that the lattice O-redox behavior is largely sustained. The acidic treatment, therefore, only optimizes the surface of the Li-rich material and almost eliminates the irreversible gas evolution, leading to improved cycling and rate performance. This work therefore presents a simple yet effective approach to passivate cathode surfaces against interfacial instabilities during high-voltage battery operation.

7.
Proc Natl Acad Sci U S A ; 113(16): 4302-7, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27044110

RESUMO

Fatty acylation of cysteine residues provides spatial and temporal control of protein function in cells and regulates important biological pathways in eukaryotes. Although recent methods have improved the detection and proteomic analysis of cysteine fatty (S-fatty) acylated proteins, understanding how specific sites and quantitative levels of this posttranslational modification modulate cellular pathways are still challenging. To analyze the endogenous levels of protein S-fatty acylation in cells, we developed a mass-tag labeling method based on hydroxylamine-sensitivity of thioesters and selective maleimide-modification of cysteines, termed acyl-PEG exchange (APE). We demonstrate that APE enables sensitive detection of protein S-acylation levels and is broadly applicable to different classes of S-palmitoylated membrane proteins. Using APE, we show that endogenous interferon-induced transmembrane protein 3 is S-fatty acylated on three cysteine residues and site-specific modification of highly conserved cysteines are crucial for the antiviral activity of this IFN-stimulated immune effector. APE therefore provides a general and sensitive method for analyzing the endogenous levels of protein S-fatty acylation and should facilitate quantitative studies of this regulated and dynamic lipid modification in biological systems.


Assuntos
Cisteína/metabolismo , Ácidos Graxos/metabolismo , Espectrometria de Massas/métodos , Proteínas de Membrana/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Coloração e Rotulagem/métodos , Acilação , Animais , Camundongos
8.
J Am Chem Soc ; 140(41): 13233-13241, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30285438

RESUMO

Protonation of the Co(I) phenylazopyridine (azpy) complex [CpCo(azpy)] 2 occurs at the azo nitrogen of the 2-phenylazopyridine ligand to generate the cationic Co(I) complex [CpCo(azpyH)]+ 3 with no change in oxidation state at Co. The N-H bond of 3 exhibits diverse hydrogen transfer reactivity, as studies with a variety of organic acceptors demonstrate that 3 can act as a proton, hydrogen atom, and hydride donor. The thermodynamics of all three cleavage modes for the N-H bond (i.e., proton, hydride, and hydrogen atom) were examined both experimentally and computationally. The N-H bond of 3 exhibits a p Ka of 12.1, a hydricity of Δ G°H- = 89 kcal/mol, and a bond dissociation free energy (BDFE) of Δ G°H• = 68 kcal/mol in CD3CN. Hydride transfer from 3 to the trityl cation (Δ G°H- = 99 kcal/mol) is exergonic but takes several hours to reach completion, indicating that 3 is a relatively poor hydride donor, both kinetically and thermodynamically. Hydrogen atom transfer from 3 to 2,6-di- tert-butyl-4-(4'-nitrophenyl)phenoxyl radical (tBu2NPArO·, Δ G°H• = 77.8 kca/mol) occurs rapidly, illustrating the competence of 3 as a hydrogen atom donor.

9.
J Eukaryot Microbiol ; 65(3): 412-421, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29265590

RESUMO

Generation of conditional mutants in Trypanosoma brucei can be done by the use of RNA interference (RNAi). However, RNAi frequently produces off target effects. Here, we present an alternative strategy in which the glmS ribozyme is inserted in the C-terminal region of one allele of a GOI and effectively knocks it down in response to the presence of glucosamine in the culture medium. Using several endogenous genes, we show that the glmS ribozyme cleaves the mRNA in vivo leading to reduction in mRNA and protein expression following glucosamine treatment in both T. brucei procyclic and bloodstream forms. Glucosamine-induced ribozyme activation can be rapidly reversed by removing the inducer. In summary, the glmS ribozyme could be used as a tool to study essential genes in T. brucei.


Assuntos
Técnicas de Inativação de Genes , RNA Catalítico/genética , RNA Mensageiro/metabolismo , Riboswitch/genética , Trypanosoma brucei brucei/genética , Proteínas de Bactérias/genética , Regulação da Expressão Gênica/genética , Glucosamina/metabolismo , Monoéster Fosfórico Hidrolases/genética , Interferência de RNA , RNA Mensageiro/genética
10.
J Am Chem Soc ; 139(12): 4540-4550, 2017 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-28263588

RESUMO

The dicationic complex [CpCo(azpy)(CH3CN)](ClO4)2 1 (azpy = phenylazopyridine) exhibits a reversible two-electron reduction at a very mild potential (-0.16 V versus Fc0/+) in acetonitrile. This behavior is not observed with the analogous bipyridine and pyrazolylpyridine complexes (3 and 4), which display an electrochemical signature typical of CoIII systems: two sequential one-electron reductions to CoII at -0.4 V and CoI at -1.0 to -1.3 V versus Fc0/+. The doubly reduced, neutral complex [CpCo(azpy)] 2 is isolated as an air-stable, diamagnetic solid via chemical reduction with cobaltocene. Crystallographic and spectroscopic characterization together with experimentally calibrated density functional theory calculations illuminate the key structural and electronic changes that occur upon reduction of 1 to 2. The electrochemical potential inversion observed with 1 is attributed to effective overlap between the metal d and the low-energy azo π* orbitals in the intermediary redox state and additional stabilization of 2 from structural reorganization, leading to a two-electron reduction. This result serves as a key milestone in the quest for two-electron transformations with mononuclear first-row transition metal complexes at mild potentials.

11.
Inorg Chem ; 56(14): 8326-8333, 2017 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-28640601

RESUMO

The one-electron reduction of [CpRu(bpy)NCCH3]PF6 (Cp = cyclopentadienyl; bpy = 2,2'-bipyridine), abbreviated as [Ru-S]+, where S = CH3CN, in CO2-saturated acetonitrile initiates a cascade of rapid electrochemical and chemical steps (ECEC) at an electrode potential of ca. 100 mV positive of the first reduction of the ruthenium complex. The overall two-electron process leads to the generation of a CO-bound ruthenium complex, [Ru-CO]+, and carbonate, as independently confirmed by NMR spectroscopy. Simulations of the cyclic voltammograms using DigiElch together with density functional theory based calculations reveal that the singly reduced ruthenium complex [Ru-S]0 binds CO2 at a rate of ca. 105 M-1 s-1 at almost zero driving force. Subsequent to CO2 binding, all of the steps leading up to deoxygenation are highly exergonic and rapid. A model of the potential energy profile of the CO2 approach to the Ru center in the singly reduced manifold reveals a direct correlation between the reactivity toward CO2 and the nucleophilicity at the metal center influenced by different ligand environments. Through the binding of CO2 after the first reduction, overpotentials associated with consecutive electrochemical reductions are avoided. This work therefore provides an important design principle for engineering transition-metal complexes to activate CO2 under low driving forces.

12.
Mol Microbiol ; 97(1): 64-76, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25825226

RESUMO

Apicomplexa are parasitic protozoa that cause important human diseases including malaria, cryptosporidiosis and toxoplasmosis. The replication of these parasites within their target host cell is dependent on both salvage as well as de novo synthesis of fatty acids. In Toxoplasma gondii, fatty acid synthesis via the apicoplast-localized FASII is essential for pathogenesis, while the role of two other fatty acid biosynthetic complexes remains unclear. Here, we demonstrate that the ER-localized fatty acid elongation (ELO) complexes are essential for parasite growth. Conditional knockdown of the nonredundant hydroxyacyl-CoA dehydratase and enoyl-CoA reductase enzymes in the ELO pathway severely repressed intracellular parasite growth. (13) C-glucose and (13) C-acetate labeling and comprehensive lipidomic analyses of these mutants showed a selective defect in synthesis of unsaturated long and very long-chain fatty acids (LCFAs and VLCFAs) and depletion of phosphatidylinositol and phosphatidylethanolamine species containing unsaturated LCFAs and VLCFAs. This requirement for ELO pathway was bypassed by supplementing the media with specific fatty acids, indicating active but inefficient import of host fatty acids. Our experiments highlight a gap between the fatty acid needs of the parasite and availability of specific fatty acids in the host cell that the parasite has to close using a dedicated synthesis and modification pathway.


Assuntos
Ácidos Graxos Insaturados/biossíntese , Interações Hospedeiro-Parasita , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/metabolismo , Animais , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Ácido Graxo Sintase Tipo II/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Complexos Multienzimáticos/metabolismo , Mutação , Toxoplasma/enzimologia , Toxoplasma/genética
13.
Inorg Chem ; 55(4): 1623-32, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26835983

RESUMO

The ruthenium hydride [RuH(CNN)(dppb)] (1; CNN = 2-aminomethyl-6-tolylpyridine, dppb = 1,4-bis(diphenylphosphino)butane) reacts rapidly and irreversibly with CO2 under ambient conditions to yield the corresponding Ru formate complex 2. In contrast, the Ru hydride 1 reacts with acetone reversibly to generate the Ru isopropoxide, with the reaction free energy ΔG°(298 K) = -3.1 kcal/mol measured by (1)H NMR in tetrahydrofuran-d8. Density functional theory (DFT), calibrated to the experimentally measured free energies of ketone insertion, was used to evaluate and compare the mechanism and energetics of insertion of acetone and CO2 into the Ru-hydride bond of 1. The calculated reaction coordinate for acetone insertion involves a stepwise outer-sphere dihydrogen transfer to acetone via hydride transfer from the metal and proton transfer from the N-H group on the CNN ligand. In contrast, the lowest energy pathway calculated for CO2 insertion proceeds by an initial Ru-H hydride transfer to CO2 followed by rotation of the resulting N-H-stabilized formate to a Ru-O-bound formate. DFT calculations were used to evaluate the influence of the ancillary ligands on the thermodynamics of CO2 insertion, revealing that increasing the π acidity of the ligand cis to the hydride ligand and increasing the σ basicity of the ligand trans to it decreases the free energy of CO2 insertion, providing a strategy for the design of metal hydride systems capable of reversible, ergoneutral interconversion of CO2 and formate.

14.
PLoS Pathog ; 9(10): e1003665, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24146616

RESUMO

Intracellular pathogens have complex metabolic interactions with their host cells to ensure a steady supply of energy and anabolic building blocks for rapid growth. Here we use the obligate intracellular parasite Toxoplasma gondii to probe this interaction for isoprenoids, abundant lipidic compounds essential to many cellular processes including signaling, trafficking, energy metabolism, and protein translation. Synthesis of precursors for isoprenoids in Apicomplexa occurs in the apicoplast and is essential. To synthesize longer isoprenoids from these precursors, T. gondii expresses a bifunctional farnesyl diphosphate/geranylgeranyl diphosphate synthase (TgFPPS). In this work we construct and characterize T. gondii null mutants for this enzyme. Surprisingly, these mutants have only a mild growth phenotype and an isoprenoid composition similar to wild type parasites. However, when extracellular, the loss of the enzyme becomes phenotypically apparent. This strongly suggests that intracellular parasite salvage FPP and/or geranylgeranyl diphosphate (GGPP) from the host. We test this hypothesis using inhibitors of host cell isoprenoid synthesis. Mammals use the mevalonate pathway, which is susceptible to statins. We document strong synergy between statin treatment and pharmacological or genetic interference with the parasite isoprenoid pathway. Mice can be cured with atorvastatin (Lipitor) from a lethal infection with the TgFPPs mutant. We propose a double-hit strategy combining inhibitors of host and parasite pathways as a novel therapeutic approach against Apicomplexan parasites.


Assuntos
Difosfatos/metabolismo , Diterpenos/metabolismo , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fosfatos de Poli-Isoprenil/metabolismo , Pirróis/farmacologia , Sesquiterpenos/metabolismo , Toxoplasma/metabolismo , Toxoplasmose/metabolismo , Animais , Apicoplastos/genética , Apicoplastos/metabolismo , Atorvastatina , Farnesiltranstransferase/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Toxoplasma/genética , Toxoplasmose/tratamento farmacológico , Toxoplasmose/genética
15.
Chem Commun (Camb) ; 60(47): 6055-6058, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38780035

RESUMO

Herein, we present a CuI-dimer, [CuI{Ph2PC6H4C(O)NC6H4PPh2-o}]2, which catalyzed direct C(sp3)-H homocoupling of benzyl and cycloalkane derivatives with excellent yields and regio-selectivity. The method is very simple and tolerates various functionalities. Synergistic metal-ligand cooperativity was observed in Cu-N bond cleavage and protonation of nitrogen, and facilitates a bifunctional pathway, minimising the free energy corrugation for catalytic intermediates.

16.
J Biol Chem ; 287(7): 4957-71, 2012 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-22179608

RESUMO

Apicomplexan parasites are responsible for high impact human diseases such as malaria, toxoplasmosis, and cryptosporidiosis. These obligate intracellular pathogens are dependent on both de novo lipid biosynthesis as well as the uptake of host lipids for biogenesis of parasite membranes. Genome annotations and biochemical studies indicate that apicomplexan parasites can synthesize fatty acids via a number of different biosynthetic pathways that are differentially compartmentalized. However, the relative contribution of each of these biosynthetic pathways to total fatty acid composition of intracellular parasite stages remains poorly defined. Here, we use a combination of genetic, biochemical, and metabolomic approaches to delineate the contribution of fatty acid biosynthetic pathways in Toxoplasma gondii. Metabolic labeling studies with [(13)C]glucose showed that intracellular tachyzoites synthesized a range of long and very long chain fatty acids (C14:0-26:1). Genetic disruption of the apicoplast-localized type II fatty-acid synthase resulted in greatly reduced synthesis of saturated fatty acids up to 18 carbons long. Ablation of type II fatty-acid synthase activity resulted in reduced intracellular growth that was partially restored by addition of long chain fatty acids. In contrast, synthesis of very long chain fatty acids was primarily dependent on a fatty acid elongation system comprising three elongases, two reductases, and a dehydratase that were localized to the endoplasmic reticulum. The function of these enzymes was confirmed by heterologous expression in yeast. This elongase pathway appears to have a unique role in generating very long unsaturated fatty acids (C26:1) that cannot be salvaged from the host.


Assuntos
Retículo Endoplasmático/enzimologia , Ácido Graxo Sintase Tipo II/metabolismo , Ácidos Graxos Insaturados/biossíntese , Proteínas de Protozoários/metabolismo , Toxoplasma/enzimologia , Retículo Endoplasmático/genética , Ácido Graxo Sintase Tipo II/genética , Ácidos Graxos Insaturados/genética , Humanos , Marcação por Isótopo , Metabolômica/métodos , Proteínas de Protozoários/genética , Toxoplasma/genética
17.
Dalton Trans ; 51(17): 6795-6808, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35420618

RESUMO

The synthesis of two new 1,2,3-triazole appended monophosphines [P(Ph){(o-C6H4)(1,2,3-N3C(Ph)CH}2] (1) and [P(Ph){o-C6H4(CCH)(1,2,3-N3-Ph)}2] (2) and their RuII complexes is described. The reactions of 1 and 2 with [Ru(PPh3)3Cl2] in a 1 : 1 molar ratio produced cationic complexes 3 and 4, respectively. Both the complexes showed very high catalytic activity towards transfer hydrogenation, nitro reduction, and α-alkylation reactions and afforded the corresponding products in good to excellent yields. The free energy of ß-hydride elimination from the respective Ru-alkoxide intermediates, a key mechanistic step common to all the three catalytic pathways, was calculated to be close to ergoneutral by density functional theory-based calculations, which is posited to rationalize the catalytic activity of 3. The reduction of aromatic nitro compounds was found to be highly chemoselective and produced the corresponding amines as major products even in the presence of a carbonyl group. The triazolyl-N2 coordinated RuII-NPN complex 3 showed better catalytic activity compared to the triazolyl-N3 coordinated complex 4.

18.
IUCrJ ; 9(Pt 3): 378-385, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35546799

RESUMO

EuAl4 possesses the BaAl4 crystal structure type with tetragonal symmetry I4/mmm. It undergoes a charge density wave (CDW) transition at T CDW = 145 K and features four consecutive antiferromagnetic phase transitions below 16 K. Here we use single-crystal X-ray diffraction to determine the incommensurately modulated crystal structure of EuAl4 in its CDW state. The CDW is shown to be incommensurate with modulation wave vector q = (0,0,0.1781 (3)) at 70 K. The symmetry of the incommensurately modulated crystal structure is orthorhombic with superspace group Fmmm(00σ)s00, where Fmmm is a subgroup of I4/mmm of index 2. Both the lattice and the atomic coordinates of the basic structure remain tetragonal. Symmetry breaking is entirely due to the modulation wave, where atoms Eu and Al1 have displacements exclusively along a, while the fourfold rotation would require equal displacement amplitudes along a and b. The calculated band structure of the basic structure and interatomic distances in the modulated crystal structure both indicate the Al atoms as the location of the CDW. The tem-per-ature dependence of the specific heat reveals an anomaly at T CDW = 145 K of a magnitude similar to canonical CDW systems. The present discovery of orthorhombic symmetry for the CDW state of EuAl4 leads to the suggestion of monoclinic instead of orthorhombic symmetry for the third AFM state.

19.
Curr Med Imaging ; 16(3): 249-261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133955

RESUMO

BACKGROUND: Data mining algorithms are extensively used to classify the data, in which prediction of disease using minimal computation time plays a vital role. OBJECTIVES: The aim of this paper is to develop the classification model from reduced features and instances. METHODS: In this paper we proposed four search algorithms for feature selection the first algorithm is Random Global Optimal (RGO) search algorithm for searching the continuous, global optimal subset of features from the random population. The second is Global and Local Optimal (GLO) search algorithm for searching the global and local optimal subset of features from population. The third one is Random Local Optimal (RLO) search algorithm for generating random, local optimal subset of features from the random population. Finally the Random Global and Optimal (RGLO) search algorithm for searching the continuous, global and local optimal subset of features from the random population. RGLO search algorithm combines the properties of first three stated algorithm. The subsets of features generated from the proposed four search algorithms are evaluated using the consistency based subset evaluation measure. Instance based learning algorithm is applied to the resulting feature dataset to reduce the instances that are redundant or irrelevant for classification. The model developed using naïve Bayesian classifier from the reduced features and instances is validated with the tenfold cross validation. RESULTS: Classification accuracy based on RGLO search algorithm using naïve Bayesian classifier is 94.82% for Breast, 97.4% for DLBCL, 98.83% for SRBCT and 98.89% for Leukemia datasets. CONCLUSION: The RGLO search based reduced features results in the high prediction rate with less computational time when compared with the complete dataset and other proposed subset generation algorithm.


Assuntos
Algoritmos , Mineração de Dados/métodos , Neoplasias/diagnóstico , Teorema de Bayes , Humanos , Reprodutibilidade dos Testes , Máquina de Vetores de Suporte
20.
Healthc Technol Lett ; 6(1): 13-18, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30881694

RESUMO

This Letter proposes a customised approach for attribute selection applied to the fuzzy rough quick reduct algorithm. The unbalanced data is balanced using synthetic minority oversampling technique. The huge dimensionality of the cancer data is reduced using a correlation-based filter. The dimensionality reduced balanced attribute gene subset is used to compute the final minimal reduct set using a customised fuzzy triangular norm operator on the fuzzy rough quick reduct algorithm. The customised fuzzy triangular norm operator is used with a Lukasiewicz fuzzy implicator to compute the fuzzy approximation. The customised operator selects the least number of informative feature genes from the dimensionality reduced datasets. Classification accuracy using leave-one-out cross validation of 94.85, 76.54, 98.11, and 99.13% is obtained using a customised function for Lukasiewicz triangular norm operator on leukemia, central nervous system, lung, and ovarian datasets, respectively. Performance analysis of the conventional fuzzy rough quick reduct and the proposed method are performed using parameters such as classification accuracy, precision, recall, F-measure, scatter plots, receiver operating characteristic area, McNemar test, chi-squared test, Matthew's correlation coefficient and false discovery rate that are used to prove that the proposed approach performs better than available methods in the literature.

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