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1.
Elife ; 92020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32423531

RESUMO

Fitness effects of mutations depend on environmental parameters. For example, mutations that increase fitness of bacteria at high antibiotic concentration often decrease fitness in the absence of antibiotic, exemplifying a tradeoff between adaptation to environmental extremes. We develop a mathematical model for fitness landscapes generated by such tradeoffs, based on experiments that determine the antibiotic dose-response curves of Escherichia coli strains, and previous observations on antibiotic resistance mutations. Our model generates a succession of landscapes with predictable properties as antibiotic concentration is varied. The landscape is nearly smooth at low and high concentrations, but the tradeoff induces a high ruggedness at intermediate antibiotic concentrations. Despite this high ruggedness, however, all the fitness maxima in the landscapes are evolutionarily accessible from the wild type. This implies that selection for antibiotic resistance in multiple mutational steps is relatively facile despite the complexity of the underlying landscape.

2.
Nat Commun ; 11(1): 2537, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439901

RESUMO

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation. The effects of influenza infection on the upper respiratory tract (URT) microbiome are largely unknown. Here, we report a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes have stable healthy ecostate communities both within and between individuals. In contrast, infected patients and ferrets exhibit large changes in bacterial community composition over time and between individuals. The unhealthy ecostates of infected individuals progress towards the healthy ecostate, coinciding with viral clearance and recovery. Pseudomonadales associate statistically with the disturbed microbiomes of infected individuals. The dynamic and resilient microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 225: 117513, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521000

RESUMO

The use of bioactive flavonoids as drugs has long mesmerized the scientific world. Their small size and planar structure enables them to interact with limitless substrates especially biomolecules. Taxifolin is a flavonoid well known for its anti-oxidizing and metal chelating properties. Its interaction with a few biomolecules has been studied so far to exploit its pharmacological activities. Hemoglobin, an iron containing macromolecule acts as a major carrier protein and is also associated with the occurrence of many diseases. Our present study lays emphasis on the interaction of flavanonol taxifolin with bovine hemoglobin at physiological pH. This was achieved by monitoring the changes in the absorbance, fluorescence, anisotropic, lifetime and circular dichroic spectra. Benesi-Hildebrand plot determined a binding constant value of 20.0 × 103 M-1 at 25 °C. Stern-Volmer quenching studies reveal that the binding is associated with a static mode of quenching. The complexation is thermodynamically favored as indicated by the negative value of enthalpy and positive value of entropy changes seen from the van't Hoff plot. Theoretical DFT calculations were used to find out an optimized geometry and HOMO-LUMO energy gap for taxifolin. Molecular docking studies revealed the location of taxifolin inside the hemoglobin moiety.

4.
Neuron ; 105(1): 122-137.e8, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31784285

RESUMO

Pyramidal tract neurons (PTs) represent the major output cell type of the mammalian neocortex. Here, we report the origins of the PTs' ability to respond to a broad range of stimuli with onset latencies that rival or even precede those of their intracortical input neurons. We find that neurons with extensive horizontally projecting axons cluster around the deep-layer terminal fields of primary thalamocortical axons. The strategic location of these corticocortical neurons results in high convergence of thalamocortical inputs, which drive reliable sensory-evoked responses that precede those in other excitatory cell types. The resultant fast and horizontal stream of excitation provides PTs throughout the cortical area with input that acts to amplify additional inputs from thalamocortical and other intracortical populations. The fast onsets and broadly tuned characteristics of PT responses hence reflect a gating mechanism in the deep layers, which assures that sensory-evoked input can be reliably transformed into cortical output.

5.
J Hazard Mater ; 383: 121219, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31546218

RESUMO

Reduced graphene oxide (rGO) as well as graphitic carbon nitride (g-C3N4) catalysts were synthesized and a physical admixture of rGO and g-C3N4 along with TiO2 in the ratio of 1:1:1 by weight was immobilized in a polystyrene film using the facile solvent casting method. An internal loop airlift reactor with a working volume of 1.2 litres incorporating the prepared polymer-based photocatalytic film was designed and tested for the photocatalytic degradation of remazol turquoise blue dye synthetic wastewater. The reactor parameters affecting the photocatalytic activity such as airflow rate and Di/Do (ratio of draft tube diameter to outer tube diameter) were evaluated. The successful operation of the reactor obtained using the ternary immobilized catalyst mixture film gave 92.25% total organic carbon reduction and 94% decolourization within 140 min, compared to 91% decolourization by the slurry form within 40 min. Complete and quicker decolourization of the dye was also demonstrated under the influence of O3 or H2O2. The immobilized catalyst was successfully reused four times. The ternary catalyst admixture employed in this work and the unique design of the photocatalytic reactor helps to increase the degradation rate of toxic textile effluents thus making it suitable for larger scales of treatment.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117411, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31362187

RESUMO

The present study delves into the interaction of a potent cancer-cell photosensitizer Norharmane (NHM) with non-ionic triblock copolymer P123, followed by the assessment of the stability of the formed complex in the presence of ß-cyclodextrin (ß-CD). Spectroscopic results unveil the modulation of the prototropic equilibrium of NHM within the constrained microheterogeneous medium of the copolymer micelle to be favoured towards the neutral species of NHM over the cationic counterpart; which has been aptly rationalized invoking the key role of hydrophobic interaction in the association process and is further reinforced from steady-state and time-resolved spectroscopic measurements. The micropolarity of the probe-binding site has been evaluated by the archetypal ET(30) analysis revealing that the cationic probe remains in the corona region of the micelle instead of penetrating deeper into the micellar core. Moreover, the effect of ß-CD on the stability of the NHM-bound P123 aggregates has also been investigated, revealing that ß-CD can be used as a potential host for the release of the micelle-encapsulated drug through an inclusion complex formation with the P123 monomers. The result is expected to be of potential interest from medical perspective owing to the context of efficient drug release at their potential sites.


Assuntos
Antineoplásicos , Micelas , Fármacos Fotossensibilizantes , beta-Ciclodextrinas/química , Antineoplásicos/análise , Antineoplásicos/química , Antineoplásicos/farmacocinética , Liberação Controlada de Fármacos , Modelos Moleculares , Fármacos Fotossensibilizantes/análise , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Espectrometria de Fluorescência
7.
Microbiol Resour Announc ; 8(45)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699753

RESUMO

Here, we report 17 nearly complete genome sequences of enterovirus D68 (EV-D68) isolated from Kansas City, MO, in 2018. Phylogenetic analysis suggests that these strains belong to subclade B3, similar to the ones that caused the 2016 epidemics in the United States but different from the 2014 outbreak B1 strains.

8.
Microb Genom ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532357

RESUMO

Respiratory syncytial viruses (RSVs) are an important cause of mortality worldwide and a major cause of respiratory tract infections in children, driving development of vaccine candidates. However, there are large gaps in our knowledge of the local evolutionary and transmission dynamics of RSVs, particularly in understudied regions such as the Middle East. To address this gap, we sequenced the complete genomes of 58 RSVA and 27 RSVB samples collected in a paediatric cohort in Amman, Jordan, between 2010 and 2013. RSVA and RSVB co-circulated during each winter epidemic of RSV in Amman, and each epidemic comprised multiple independent viral introductions of RSVA and RSVB. However, RSVA and RSVB alternated in dominance across years, potential evidence of immunological interactions. Children infected with RSVA tended to be older than RSVB-infected children [30 months versus 22.4 months, respectively (P value = 0.02)], and tended to developed bronchopneumonia less frequently than those with RSVB, although the difference was not statistically significant (P value = 0.06). Differences in spatial patterns were investigated, and RSVA lineages were often identified in multiple regions in Amman, whereas RSVB introductions did not spread beyond a single region of the city, although these findings were based on small sample sizes. Multiple RSVA genotypes were identified in Amman, including GA2 viruses as well as three viruses from the ON1 sub-genotype that emerged in 2009 and are now the dominant genotype circulating worldwide. As vaccine development advances, further sequencing of RSV is needed to understand viral ecology and transmission, particularly in under-studied locations.

10.
Dalton Trans ; 48(31): 11978-11984, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31321393

RESUMO

We report an efficient protocol for the catalytic chemo-selective reduction of tert-amides with pinacolborane (HBpin) to afford the corresponding amines in high yields using aluminium complexes [κ2-{Ph2P(X)NC9H6N}Al(Me)2] [X = S (2a), Se (2b)] as pre-catalysts at room temperature. The aluminium complexes were prepared from the reaction of [Ph2P(X)NC9H6N] [X = S (1a), Se (1b)] and trimethylaluminium in toluene. The solid-state structure of complex 2b is established. Tertiary amides with a wide array of electron-withdrawing and electron-donating functional groups were easily converted to the desired products through the selective cleavage of the amides' C[double bond, length as m-dash]O bond by aluminium hydride as an active species. A kinetic study of the catalytic reaction is also reported.

11.
Int J Biol Macromol ; 138: 57-69, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301395

RESUMO

Chelerythrine (CHL) is a pharmacologically important molecule that appears in positively charged iminium and neutral alkanolamine form on varying the pH. Association of bovine hemoglobin (BHb) with iminium and alkanolamine forms of CHL is explored employing several spectroscopic and theoretical tools. Our results revealed that iminium form of CHL shows greater binding affinity than the neutral alkanolamine form, with nearly one binding site on the protein for both forms. Thermodynamic data showed that the iminium binding to BHb was characterized by negative enthalpy and positive entropy changes while the association of the alkanolamine CHL was accompanied with both positive enthalpy and entropy changes. Both forms of CHL have been found to quench the intrinsic fluorescence of BHb. From Förster's resonance energy transfer (FRET) studies, the binding distance between the energy acceptor (CHL) and donor (ß-Trp 37 of BHb) was found to be optimum for fluorescence quenching to occur. The conformational transformation of BHb induced by CHL complexation showed greater unfolding of the protein architecture for the iminium interaction from CD spectroscopy. Molecular docking study revealed that both iminium and alkanolamine form of CHL reside near ß-Trp 37 at the α1ß2 interface of BHb.


Assuntos
Benzofenantridinas/metabolismo , Hemoglobinas/metabolismo , Simulação de Acoplamento Molecular , Animais , Bovinos , Transferência de Energia , Hemoglobinas/química , Concentração de Íons de Hidrogênio , Ligação Proteica , Conformação Proteica , Termodinâmica
12.
J Biomed Sci ; 26(1): 49, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31266491

RESUMO

BACKGROUND: Human enteroviruses contain over 100 serotypes. We have routinely conducted enterovirus surveillance in northern Taiwan; but about 10% of isolates could not be serotyped using traditional assays. Next-generation sequencing (NGS) is a powerful tool for genome sequencing. METHODS: In this study, we established an NGS platform to conduct genome sequencing for the serologically untypable enterovirus isolates. RESULTS: Among 130 serologically untypable isolates, 121 (93%) of them were classified into 29 serotypes using CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer)-based RT-PCR to amplify VP1 genes (VP1-CODEHOP). We further selected 52 samples for NGS and identified 59 genome sequences from 51 samples, including 8 samples containing two virus genomes. We also detected 23 genome variants (nucleotide identity < 90% compared with genome sequences in the public domain) which were potential genetic recombination, including 9 inter-serotype recombinants and 14 strains with unknown sources of recombination. CONCLUSIONS: We successfully integrated VP1-CODEHOP and NGS techniques to conduct genomic analysis of serologically untypable enteroviruses.


Assuntos
Enterovirus/genética , Genoma Viral , Sorogrupo , Infecções por Enterovirus , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Taiwan
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 223: 117293, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31260885

RESUMO

The association of a putative bioactive alkaloid nitidine (NIT) with blood protein bovine hemoglobin (BHb) was investigated by employing various biophysical and molecular docking techniques. NIT binding to BHb was first characterized by hypochromic effect on the Soret band absorption of BHb from spectrophotometric studies. Spectrofluorimetric titration and unchanged fluorescence lifetime of BHb confirmed ground state complexation followed by the static nature of the emission quenching mechanism of the protein induced by NIT. Substantial conformational changes in the protein structure were established from circular dichroism study. Conformational perturbation results a lowering in the α-helical organization of the tetrameric protein structure. Thermodynamics of the binding suggest that the binding is exothermic with a favourable small positive entropy change and negative enthalpy change making a sense of electrostatic interaction as the major acting force. Experimentally calculated free energy change for the NIT-BHb interaction was found to be -7.50 kcal mol-1 which is in well agreement to the theoretical docking energy value of -6.36 kcal mol-1. AutoDock based molecular docking suggests the internal cavity of BHb as the preferred binding position of NIT. Overall this manuscript depicts consequences on the molecular interaction of NIT with BHb from structural and energetic standpoints providing a profound insight into protein-ligand association.


Assuntos
Alcaloides/química , Alcaloides/metabolismo , Benzofenantridinas/química , Benzofenantridinas/metabolismo , Hemoglobinas/metabolismo , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , Cinética , Conformação Molecular , Simulação de Acoplamento Molecular , Ligação Proteica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica , Triptofano/química
14.
Virus Evol ; 5(2): vez020, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31341640

RESUMO

Following its introduction into New York State (NYS) in 1999, West Nile virus (WNV; Flavivirus, Flaviviridae) underwent a rapid expansion throughout the USA and into Canada and Latin America. WNV has been characterized as being evolutionarily stable, with weak geographic structure, a dominance of purifying selection and limited adaptive change. We analyzed all available full-genome WNV sequences, focusing on the 543 available sequences from NYS, which included 495 newly sequenced 2000-15 isolates. In addition, we analyzed deep-sequencing data from 317 of these isolates. While our data are generally in agreement with the limited pace of evolutionary change and broad geographic and temporal mixing identified in other studies, we have identified some important exceptions. Most notably, there are 14 codons which demonstrated evidence of positive selection as determined by multiple models, including some positions with evidence of selection in NYS exclusively. Coincident with increased WNV activity, genotypes possessing one or more of these mutations, designated NY01, NY07, and NY10, have increased in prevalence in recent years and displaced historic strains. In addition, we have found a geographical bias with many of these mutations, which suggests selective pressures and adaptations could be regional. Lastly, our deep-sequencing data suggest both increased overall diversity in avian tissue isolates relative to mosquito isolates and multiple non-synonymous minority variants that are both host-specific and retained over time and space. Together, these data provide novel insight into the evolutionary pressures on WNV and the need for continued genetic surveillance and characterization of emergent strains.

15.
Clin Transl Gastroenterol ; 10(6): e00039, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31107724

RESUMO

OBJECTIVES: Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease affecting the esophagus. Although microbial communities may affect the host immune responses, little is known about the role of the microbiome in EoE. We compared the composition of the salivary microbiome in children with EoE with that of non-EoE controls to test the hypotheses that the salivary microbiome is altered in children with EoE and is associated with disease activity. METHODS: Saliva samples were collected from 26 children with EoE and 19 non-EoE controls comparable for age and ethnicity. The salivary microbiome was profiled using 16S rRNA gene sequencing. Disease activity was assessed using the Eosinophilic Esophagitis Endoscopic Reference Score and the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). RESULTS: A trend toward lower microbial richness and alpha diversity was noted in children with EoE. Although the overall salivary microbiome composition was similar between children with and without EoE, specific taxa such as Streptococcus (q value = 0.06) tended to be abundant in children with active EoE compared with non-EoE controls. Haemophilus was significantly abundant in children with active EoE compared with inactive EoE (q value = 0.0008) and increased with the increasing EoEHSS and Eosinophilic Esophagitis Histology Scoring System (q value = 5e-10). In addition, 4 broad salivary microbial communities correlated with the EoEHSS. DISCUSSION: The composition of the salivary microbiome community structure can be altered in children with EoE. A relative abundance of Haemophilus positively correlates with the disease activity. These findings indicate that perturbations in the salivary microbiome may have a role in EoE pathobiology and could serve as a noninvasive marker of disease activity.

16.
Sci Rep ; 9(1): 7484, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097731

RESUMO

Development of antiviral drug resistance is a continuous concern for viruses with high mutation rates such as influenza. The use of antiviral drugs targeting host proteins required for viral replication is less likely to result in the selection of resistant viruses than treating with direct-acting antivirals. The iminosugar UV-4B is a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II enzymes resulting in improper glycosylation and misfolding of viral glycoproteins. UV-4B has broad-spectrum antiviral activity against diverse viruses including dengue and influenza. To examine the ability of influenza virus to develop resistance against UV-4B, mouse-adapted influenza virus was passaged in mice in the presence or absence of UV-4B and virus isolated from lungs was used to infect the next cohort of mice, for five successive passages. Deep sequencing was performed to identify changes in the viral genome during passaging in the presence or absence of UV-4B. Relatively few minor variants were identified within each virus and the ratio of nonsynonymous to synonymous (dN/dS) substitutions of minor variants confirmed no apparent positive selection following sustained exposure to UV-4B. Three substitutions (one synonymous in PB2, one nonsynonymous in M and PA each) were specifically enriched (>3%) in UV-4B-treated groups at passage five. Recombinant viruses containing each individual or combinations of these nonsynonymous mutations remained sensitive to UV-4B treatment in mice. Overall, these data provide evidence that there is a high genetic barrier to the generation and selection of escape mutants following exposure to host-targeted iminosugar antivirals.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30972302

RESUMO

There is great interest in safe and effective alternative therapies that could benefit patients with inflammatory bowel diseases (IBD). L-arginine (Arg) is a semi-essential amino acid with a variety of physiological effects. In this context, our aim was to investigate the role of dietary Arg in experimental colitis. We used two models of colitis in C57BL/6 mice, the dextran sulfate sodium (DSS) model of injury and repair, and Citrobacter rodentium infection. Animals were given diets containing (1) no Arg (Arg0), 6.4 g/kg (ArgNL), or 24.6 g/kg Arg (ArgHIGH); or (2) the amino acids downstream of Arg: 28 g/kg L-ornithine (OrnHIGH) or 72 g/kg L-proline (ProHIGH). Mice with DSS colitis receiving the ArgHIGH diet had increased levels of Arg, Orn, and Pro in the colon and improved body weight loss, colon length shortening, and histological injury compared to ArgNL and Arg0 diets. Histology was improved in the ArgNL vs. Arg0 group. OrnHIGH or ProHIGH diets did not provide protection. Reduction in colitis with ArgHIGH diet also occurred in C. rodentium-infected mice. Diversity of the intestinal microbiota was significantly enhanced in mice on the ArgHIGH diet compared to the ArgNL or Arg0 diets, with increased abundance of Bacteroidetes and decreased Verrucomicrobia. In conclusion, dietary supplementation of Arg is protective in colitis models. This may occur by restoring overall microbial diversity and Bacteroidetes prevalence. Our data provide a rationale for Arg as an adjunctive therapy in IBD.


Assuntos
Arginina/administração & dosagem , Colite/patologia , Colo/microbiologia , Dieta/métodos , Infecções por Enterobacteriaceae/patologia , Microbioma Gastrointestinal , Animais , Citrobacter rodentium/crescimento & desenvolvimento , Colite/induzido quimicamente , Colo/patologia , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Histocitoquímica , Camundongos Endogâmicos C57BL , Resultado do Tratamento
18.
Am J Trop Med Hyg ; 100(5): 1266-1274, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30860014

RESUMO

Eastern equine encephalitis virus (EEEV) infection results in high mortality in infected horses and humans. Florida has been identified as an important source of EEEV epidemics to other states in the United States. In this study, we further characterized the epidemiological and evolutionary dynamics of EEEV in Florida. Epidemiological analysis of sentinel chicken seroconversion rates to EEEV infections during 2005-2016 suggested significant seasonality of EEEV activity in Florida. We observed significant annual activity of EEEV in the North and North Central regions, with little significant seasonality in the Panhandle region. Phylogenetic analysis of complete EEEV genome sequences from different host sources and regions in Florida during 1986-2014 revealed extensive genetic diversity and spatial dispersal of the virus within Florida and relatively more clustering of the viruses in the Panhandle region. We found no significant association between EEEV genetic variation and host source. Overall, our study revealed a complex epidemiological dynamic of EEEV within Florida, implicating the Panhandle region as a possible source of the virus with sustained year-round transmission. These findings will help in implementing targeted control measures that can have the most impact in reducing or eliminating EEEV and other mosquito-borne viral infections within Florida and in the rest of the United States.


Assuntos
Galinhas/virologia , Encefalomielite Equina do Leste/epidemiologia , Monitoramento Epidemiológico/veterinária , Variação Genética , Estações do Ano , Animais , Anticorpos Antivirais/sangue , Vírus da Encefalite Equina do Leste/genética , Encefalomielite Equina do Leste/sangue , Florida/epidemiologia , Genoma Viral , Geografia , Filogenia , Saúde Pública , Soroconversão
19.
J Immunol ; 202(7): 1949-1961, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30760620

RESUMO

T cells mediate skin immune surveillance by secreting specific cytokines and regulate numerous functions of keratinocytes, including migration during homeostasis and disease pathogenesis. Keratinocyte migration is mediated mainly by proteolytic cleavage of the extracellular matrix and/or by cytoskeleton reorganization. However, the cross-talk between T cell cytokines and actomyosin machinery of human primary keratinocytes (HPKs), which is required for cytoskeleton reorganization and subsequent migration, remains poorly examined. In this study, we describe that IL-9 profoundly reduced the actin stress fibers, inhibited contractility, and reduced the cortical stiffness of HPKs, which resulted in inhibition of the migration potential of HPKs in an adhesion- and MMP-independent manner. Similarly, IL-9 inhibited the IFN-γ-induced migration of HPKs by inhibiting the actomyosin machinery (actin stress fibers, contractility, and stiffness). IL-17A increased the actin stress fibers, promoted cellular contractility, and increased proteolytic collagen degradation, resulting in increased migration potential of HPKs. However, IL-9 inhibited the IL-17A-mediated HPKs migration. Mechanistically, IL-9 inhibited the IFN-γ- and IL-17A-induced phosphorylation of myosin L chain in HPKs, which is a major regulator of the actomyosin cytoskeleton. Finally, in addition to HPKs, IL-9 inhibited the migration of A-431 cells (epidermoid carcinoma cells) induced either by IFN-γ or IL-17A. In conclusion, our data demonstrate the influence of T cell cytokines in differentially regulating the actomyosin cytoskeleton and migration potential of human keratinocytes, which may have critical roles in skin homeostasis and pathogenesis of inflammatory diseases as well as skin malignancies.


Assuntos
Citoesqueleto de Actina/metabolismo , Movimento Celular/fisiologia , Interleucina-17/metabolismo , Interleucina-9/metabolismo , Queratinócitos/metabolismo , Citoesqueleto de Actina/imunologia , Humanos , Interleucina-17/imunologia , Interleucina-9/imunologia , Queratinócitos/imunologia , Pele/imunologia , Pele/metabolismo
20.
Dalton Trans ; 48(21): 7227-7235, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-30688333

RESUMO

We report the catalytic hydroamination of amino acid esters with carbodiimides and isocyanates to furnish corresponding quinazolinone and urea derivatives under mild conditions using two titanium(iv) complexes [(ImRN)2Ti(NMe2)2] (R = tBu, 2a; R = Mes, 2b), which were synthesised by reacting tetrakis(dimethylamido)titanium(iv) [Ti(NMe2)4] with imidazolin-2-imine [ImRNH; R = tert-butyl (tBu) (1a), mesityl (Mes) (1b)] in a 1 : 2 molar ratio in toluene. Furthermore, the reaction of titanium complex 2a with 2,6-diisopropylphenylamine (DippNH2) resulted in the corresponding mixed ligand titanium complex [κ1-(ImtBuN)2Ti(NMe2)(HNDipp)] (3a). In contrast, the reaction of complex 2a with 2,6-dimethyl phenol afforded the mono-imidazolin-2-iminato TiIV phenolate complex [κ1-(ImtBuN)Ti(O-1,6-Me2C6H3)3] (4a). The solid-state structures of complexes 2b, 3a, and 4a, established by single crystal X-ray diffraction analyses, confirmed a very short bond between titanium and imidazolin-2-iminato nitrogen in each case. Titanium complexes 2a and 2b exhibited relatively high conversion, superior selectivity and broad functional group tolerance in both hydroamination reactions under mild conditions. We propose the most plausible mechanism for the guanylation/cyclisation of amino acid esters to carbodiimides on the basis of a number of controlled reactions.

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