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1.
Phys Chem Chem Phys ; 24(19): 11898-11909, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35510687

RESUMO

The magnetic properties of cobalt metal nanowires grown by electrodeposition in porous membranes depend largely on the synthesis conditions. Here, we focus on the role of electrolyte additives on the magnetic anisotropy of the electrodeposited nanowires. Through magnetometry and internal field nuclear magnetic resonance (IF NMR) studies, we compared both the magnetic and crystalline structures of 50 and 200 nm diameter Co nanowires synthesized in the presence or absence of organic additives. The spectral characteristics of IF NMR were compared structurally to X-ray diffraction patterns, and the anisotropy of the NMR enhancement factor in ferromagnetic multidomain structures to magnetometry results. While the magnetic behavior of the 50 nm nanowires was dominated, as expected, by shape anisotropy with magnetic domains oriented on axis, the analysis of the 200 nm proved to be more complex. 59Co IF NMR revealed that the determining difference between the samples electrodeposited in the presence or in absence of organic additives was not the dominant crystalline system (fcc or hcp) but the coherent domain sizes and boundaries. In the presence of organic additives, the cobalt crystal domains are smaller and with defective grain boundaries, as revealed by resonances below 210 MHz. This prevented the development in the Co hcp part of the sample of the strong magnetocrystalline anisotropy that was observed in the absence of organic additives. In the presence of organic additives, even in nanowires as wide as 200 nm, the magnetic behavior remained determined by the shape anisotropy with a positive effective magnetic anisotropy and strong anisotropy of the NMR enhancement factor.

2.
Angew Chem Int Ed Engl ; 61(18): e202117851, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35199437

RESUMO

Carbon hydrogasification is the slowest reaction among all carbon-involved small-molecule transformations. Here, we demonstrate a mechanochemical method that results in both a faster reaction rate and a new synthesis route. The reaction rate was dramatically enhanced by up to 4 orders of magnitude compared to the traditional thermal method. Simultaneously, the reaction exhibited very high selectivity (99.8 % CH4 , versus 80 % under thermal conditions) with a cobalt catalyst. Our study demonstrated that this extreme increase in reaction rate originates from the continuous activation of reactive carbon species via mechanochemistry. The high selectivity is intimately related to the activation at low temperature, at which higher hydrocarbons are difficult to form. This work is expected to advance studies of carbon hydrogasification, and other solid-gas reactions.

3.
Muscle Nerve ; 52(6): 1078-87, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24777698

RESUMO

INTRODUCTION: Clenbuterol has been used to alleviate chronic obstructive pulmonary disease and elicit an anabolic response in muscles. The aim of this study was to determine the influence of muscle mass variation on physical capacities in rats. METHODS: The left hindlimbs of Wistar rats were immobilized for 20 days in plantarflexion with a splint and then remobilized for 16 days. The effect of a non-myotoxic dose of clenbuterol during the immobilization period was evaluated. Physical capacities were coordination, free locomotion, grip strength, and bilateral deficit. RESULTS: Immobilization induced a loss of muscle mass, coordination, and strength without any effect on free locomotion. The positive anabolic effect of clenbuterol did not prevent a loss of physical capacities resulting from immobilization. CONCLUSIONS: Muscle mass correlated strongly with coordination and isometric strength in untreated rats. Anabolic effect, fiber phenotype modification, and perturbation in neuromuscular communication with clenbuterol improved muscle mass, but it altered physical capacities.


Assuntos
Broncodilatadores/uso terapêutico , Clembuterol/uso terapêutico , Atividade Motora/fisiologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/reabilitação , Análise de Variância , Animais , Modelos Animais de Doenças , Comportamento Exploratório , Locomoção , Masculino , Atividade Motora/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Atrofia Muscular/etiologia , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/fisiopatologia , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Ratos , Ratos Wistar , Restrição Física/efeitos adversos , Estatística como Assunto , Fatores de Tempo
4.
PLoS One ; 9(1): e80836, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24454684

RESUMO

PURPOSE: Uveal melanoma (UM) is associated with a high risk of metastases and lack of efficient therapies. Reduced capacity for apoptosis induction by chemotherapies is one obstacle to efficient treatments. Human UM is characterized by high expression of the anti-apoptotic protein Bcl-2. Consequently, regulators of apoptosis such as Bcl-2 family inhibitors may constitute an attractive approach to UM therapeutics. In this aim, we have investigated the efficacy of the Bcl-2/Bcl-XL inhibitor S44563 on 4 UM Patient-Derived Xenografts (PDXs) and derived-cell lines. EXPERIMENTAL DESIGN: Four well characterized UM PDXs were used for in vivo experiments. S44563 was administered alone or combined with fotemustine either concomitantly or after the alkylating agent. Bcl-2, Bcl-XL, and Mcl-1 expressions after S44563 administration were evaluated by immunohistochemistry (IHC). RESULTS: S44563 administered alone by at 50 and 100 mg/kg i.p. induced a significant tumour growth inhibition in only one xenograft model with a clear dose effect. However, when S44563 was concomitantly administered with fotemustine, we observed a synergistic activity in 3 out of the 4 tested models. In addition, S44563 administered after fotemustine induced a tumour growth delay in 2 out of 3 tested xenografts. Finally, IHC analyses showed that Bcl-2, Bcl-XL, and Mcl-1 expression were not modified after S44563 administration. CONCLUSION: The novel anti-apoptotic experimental compound S44563, despite a relative low efficacy when administered alone, increased the efficacy of fotemustine in either concomitant or sequential combinations or indeed subsequent to fotemustine. These data support further exploration of potential therapeutic effect of Bcl-2/Bcl-xl inhibition in human UM.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/farmacologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Melanoma/tratamento farmacológico , Terapia de Alvo Molecular , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Neoplasias Uveais/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína bcl-X/antagonistas & inibidores , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Polarização de Fluorescência , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Imuno-Histoquímica , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Camundongos SCID , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Compostos de Nitrosoureia/farmacologia , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/farmacologia , Compostos Organofosforados/uso terapêutico , Peptídeos/metabolismo , Ligação Proteica/efeitos dos fármacos , Sulfonamidas/administração & dosagem , Análise de Sobrevida , Neoplasias Uveais/metabolismo , Neoplasias Uveais/patologia , Proteína bcl-X/metabolismo
5.
Cancer Res ; 73(2): 813-23, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23144294

RESUMO

Breast cancers are composed of molecularly distinct subtypes with different clinical outcomes and responses to therapy. To discover potential therapeutic targets for the poor prognosis-associated triple-negative breast cancer (TNBC), gene expression profiling was carried out on a cohort of 130 breast cancer samples. Polo-like kinase 1 (PLK1) was found to be significantly overexpressed in TNBC compared with the other breast cancer subtypes. High PLK1 expression was confirmed by reverse phase protein and tissue microarrays. In triple-negative cell lines, RNAi-mediated PLK1 depletion or inhibition of PLK1 activity with a small molecule (BI-2536) induced an increase in phosphorylated H2AX, G(2)-M arrest, and apoptosis. A soft-agar colony assay showed that PLK1 silencing impaired clonogenic potential of TNBC cell lines. When cells were grown in extracellular matrix gels (Matrigel), and exposed to BI-2536, apoptosis was observed specifically in TNBC cancerous cells, and not in a normal cell line. When administrated as a single agent, the PLK1 inhibitor significantly impaired tumor growth in vivo in two xenografts models established from biopsies of patients with TNBC. Most importantly, the administration of BI-2536, in combination with doxorubicin + cyclophosphamide chemotherapy, led to a faster complete response compared with the chemotherapy treatment alone and prevented relapse, which is the major risk associated with TNBC. Altogether, our observations suggest PLK1 inhibition as an attractive therapeutic approach, in association with conventional chemotherapy, for the management of patients with TNBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pteridinas/farmacologia , Animais , Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Quinase 1 Polo-Like
6.
Mol Cell Biol ; 31(18): 3734-44, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21746879

RESUMO

The multisubunit SAGA coactivator complex facilitates access of general transcription factors to DNA through histone acetylation mediated by GCN5. USP22 (ubiquitin-specific protease 22) was recently described as a subunit of the human SAGA complex that removes ubiquitin from monoubiquitinated histone H2B and H2A in vitro. Here we demonstrate an allosteric regulation of USP22 through multiple interactions with different domains of other subunits of the SAGA deubiquitination module (ATXN7, ATXN7L3, and ENY2). Downregulation of ATXN7L3 by short hairpin RNA (shRNA) specifically inactivated the SAGA deubiquitination activity, leading to a strong increase of global H2B ubiquitination and a moderate increase of H2A ubiquitination. Thus, SAGA is the major H2Bub deubiquitinase in human cells, and this activity cannot be fully compensated by other deubiquitinases. Here we show that the deubiquitination activity of SAGA is required for full activation of SAGA-dependent inducible genes. Interestingly, the reduction of the SAGA deubiquitination activity and the parallel increase in H2B ubiquitation at inducible target genes before activation do not induce aberrant gene expression. Our data together indicate that different dynamic equilibriums of H2B ubiquitination/deubiquitination are established at different gene regulatory elements and that H2B ubiquitination changes are necessary but not sufficient to trigger parallel activation of gene expression.


Assuntos
Proteínas do Tecido Nervoso/metabolismo , Elementos Reguladores de Transcrição , Tioléster Hidrolases/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Regulação Alostérica , Ataxina-7 , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Expressão Gênica , Regulação da Expressão Gênica , Células HeLa , Histonas/genética , Histonas/metabolismo , Humanos , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Ubiquitina Tiolesterase , Ubiquitinação
7.
Mol Cell ; 29(1): 92-101, 2008 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-18206972

RESUMO

Transcriptional activators, several different coactivators, and general transcription factors are necessary to access specific loci in the dense chromatin structure to allow precise initiation of RNA polymerase II (Pol II) transcription. Histone acetyltransferase (HAT) complexes were implicated in loosening the chromatin around promoters and thus in gene activation. Here we demonstrate that the 2 MDa GCN5 HAT-containing metazoan TFTC/STAGA complexes contain a histone H2A and H2B deubiquitinase activity. We have identified three additional subunits of TFTC/STAGA (ATXN7L3, USP22, and ENY2) that form the deubiquitination module. Importantly, we found that this module is an enhancer of position effect variegation in Drosophila. Furthermore, we demonstrate that ATXN7L3, USP22, and ENY2 are required as cofactors for the full transcriptional activity by nuclear receptors. Thus, the deubiquitinase activity of the TFTC/STAGA HAT complex is necessary to counteract heterochromatin silencing and acts as a positive cofactor for activation by nuclear receptors in vivo.


Assuntos
Inativação Gênica , Heterocromatina/genética , Histona Acetiltransferases/fisiologia , Mapeamento de Interação de Proteínas , Receptores Androgênicos/genética , Transativadores/fisiologia , Fatores Genéricos de Transcrição/fisiologia , Transcrição Gênica/genética , Ubiquitinação/fisiologia , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Linhagem Celular , Sequência Conservada , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Endopeptidases/química , Endopeptidases/genética , Endopeptidases/fisiologia , Histona Acetiltransferases/química , Humanos , Dados de Sequência Molecular , Complexos Multiproteicos/química , Complexos Multiproteicos/fisiologia , Regiões Promotoras Genéticas/genética , RNA Polimerase II/fisiologia , Proteínas Recombinantes de Fusão/fisiologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Tioléster Hidrolases/química , Tioléster Hidrolases/fisiologia , Transativadores/química , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Fatores Genéricos de Transcrição/química , Ubiquitina Tiolesterase , Fatores de Transcrição de p300-CBP/química , Fatores de Transcrição de p300-CBP/fisiologia
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