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1.
Se Pu ; 37(11): 1157-1161, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642267

RESUMO

A method using ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the determination of nine B vitamins in peptone. The samples were extracted with water. The analytes were separated on a Syncronis C18 column (100 mm×2.1 mm, 1.7 µm). The nine B vitamins were detected by ESI-MS/MS under the multiple reaction monitoring (MRM) mode, and the analysis was completed in 8 min. Quantification analysis was performed by using the external standard method. The correlation coefficients (R2) of the nine B vitamins in their linear ranges were greater than 0.999. The limits of detection were 0.09-1.67 µg/L. The relative standard deviations of the method were less than 3% (n=6). The mean recoveries of the nine B vitamins were 80.2%-103.9% at different spiked levels. The method is simple, accurate and sensitive, and is suitable for the determination of the nine B vitamins in peptone.


Assuntos
Peptonas/química , Complexo Vitamínico B/análise , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem
2.
Nat Commun ; 7: 13564, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27976669

RESUMO

A grand challenge in material science is to understand the correlation between intrinsic properties and defect dynamics. Radiation tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Unlike traditional approaches that rely on microstructural and nanoscale features to mitigate radiation damage, this study demonstrates enhancement of radiation tolerance with the suppression of void formation by two orders magnitude at elevated temperatures in equiatomic single-phase concentrated solid solution alloys, and more importantly, reveals its controlling mechanism through a detailed analysis of the depth distribution of defect clusters and an atomistic computer simulation. The enhanced swelling resistance is attributed to the tailored interstitial defect cluster motion in the alloys from a long-range one-dimensional mode to a short-range three-dimensional mode, which leads to enhanced point defect recombination. The results suggest design criteria for next generation radiation tolerant structural alloys.

3.
Nat Commun ; 7: 11225, 2016 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-27071458

RESUMO

The large fraction of material residing at grain boundaries in nanocrystalline metals and alloys is responsible for their ultrahigh strength, but also undesirable microstructural instability under thermal and mechanical loads. However, the underlying mechanism of stress-driven microstructural evolution is still poorly understood and precludes rational alloy design. Here we combine quantitative in situ electron microscopy with three-dimensional atom-probe tomography to directly link the mechanics and kinetics of grain boundary migration in nanocrystalline Al films with the excess of O atoms at the boundaries. Site-specific nanoindentation leads to grain growth that is retarded by impurities, and enables quantification of the critical stress for the onset of grain boundary migration. Our results show that a critical excess of impurities is required to stabilize interfaces in nanocrystalline materials against mechanical driving forces, providing new insights to guide control of deformation mechanisms and tailoring of mechanical properties apart from grain size alone.

4.
Artigo em Inglês | MEDLINE | ID: mdl-28050194

RESUMO

Objective. Insomnia is one of the most common sleep disorders. Hypnotics have poor long-term efficacy. Mongolian medical warm acupuncture has significant efficacy in treating insomnia. The paper evaluates the role of Mongolian medical warm acupuncture in treating insomnia by investigating the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index, and polysomnography indexes. Method. The patients were diagnosed in accordance with International Classification of Sleep Disorders (ICSD-2). The insomnia patients were divided into the acupuncture group (40 cases) and the estazolam group (40 cases). The patients underwent intervention of Mongolian medical warm acupuncture and estazolam. The indicators of the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index (PSQI), and polysomnography indexes (PSG) have been detected. Result. Based on the comparison of the Mongolian medicine syndrome scores between the warm acupuncture group and the drug treatment group, the result indicated P < 0.01. The clinical efficacy result showed that the effective rate (85%) in the warm acupuncture group was higher than that (70%) in the drug group. The total scores of PSQI of both groups were approximated. The sleep quality indexes of both groups decreased significantly (P < 0.05). The sleep quality index in the Mongolian medical warm acupuncture group decreased significantly (P < 0.01) and was better than that in the estazolam group. The sleep efficiency and daytime functions of the patients in the Mongolian medical warm acupuncture group improved significantly (P < 0.01). The sleep time was significantly extended (P < 0.01) in the Mongolian medical warm acupuncture group following PSG intervention. The sleep time during NREM in the Mongolian warm acupuncture group increased significantly (P < 0.01). The sleep time exhibited a decreasing trend during REM and it decreased significantly in the Mongolian warm acupuncture group (P < 0.01). The percentage of sleep time in the total sleep time during NREM3+4 in the Mongolian medical warm acupuncture group increased significantly. Conclusion. Mongolian medical warm acupuncture is efficient and safe in treating insomnia. It is able to better improve the patients' sleep time and daytime functions. It is better than that in the estazolam group following drug withdrawal in terms of improving the sleep time. It is more effective in helping the insomnia patients than hypnotics.

5.
Nat Mater ; 14(7): 707-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25985457

RESUMO

Linear defects in crystalline materials, known as dislocations, are central to the understanding of plastic deformation and mechanical strength, as well as control of performance in a variety of electronic and photonic materials. Despite nearly a century of research on dislocation structure and interactions, measurements of the energetics and kinetics of dislocation nucleation have not been possible, as synthesizing and testing pristine crystals absent of defects has been prohibitively challenging. Here, we report experiments that directly measure the surface dislocation nucleation strengths in high-quality 〈110〉 Pd nanowhiskers subjected to uniaxial tension. We find that, whereas nucleation strengths are weakly size- and strain-rate-dependent, a strong temperature dependence is uncovered, corroborating predictions that nucleation is assisted by thermal fluctuations. We measure atomic-scale activation volumes, which explain both the ultrahigh athermal strength as well as the temperature-dependent scatter, evident in our experiments and well captured by a thermal activation model.

6.
J Cell Sci ; 128(6): 1150-65, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25653389

RESUMO

The cadherin-catenin adhesion complex is a key contributor to epithelial tissue stability and dynamic cell movements during development and tissue renewal. How this complex is regulated to accomplish these functions is not fully understood. We identified several phosphorylation sites in mammalian αE-catenin (also known as catenin α-1) and Drosophila α-Catenin within a flexible linker located between the middle (M)-region and the carboxy-terminal actin-binding domain. We show that this phospho-linker (P-linker) is the main phosphorylated region of α-catenin in cells and is sequentially modified at casein kinase 2 and 1 consensus sites. In Drosophila, the P-linker is required for normal α-catenin function during development and collective cell migration, although no obvious defects were found in cadherin-catenin complex assembly or adherens junction formation. In mammalian cells, non-phosphorylatable forms of α-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of α-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the α-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.


Assuntos
Caderinas/metabolismo , Caseína Quinase II/metabolismo , Caseína Quinase I/metabolismo , Adesão Celular , Drosophila melanogaster/metabolismo , alfa Catenina/metabolismo , Actinas/metabolismo , Sequência de Aminoácidos , Animais , Apoptose , Western Blotting , Caderinas/genética , Caseína Quinase I/genética , Caseína Quinase II/genética , Membrana Celular/metabolismo , Movimento Celular , Proliferação de Células , Células Cultivadas , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Cães , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Imunofluorescência , Humanos , Imunoprecipitação , Células Madin Darby de Rim Canino , Dados de Sequência Molecular , Ovário/citologia , Ovário/metabolismo , Fosforilação , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , alfa Catenina/química , alfa Catenina/genética
7.
Nano Lett ; 15(1): 8-15, 2015 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-25427143

RESUMO

The elastic properties of gallium nitride (GaN) nanowires with different structures were investigated by in situ electron microscopy in this work. The electric-field-induced resonance method was utilized to reveal that the single crystalline GaN nanowires, along [120] direction, had the similar Young's modulus as the bulk value at the diameter ranging 92-110 nm. Meanwhile, the elastic behavior of the obtuse-angle twin (OT) GaN nanowires was disclosed both by the in situ SEM resonance technique and in situ transmission electron microscopy tensile test for the first time. Our results showed that the average Young's modulus of these OT nanowires was greatly decreased to about 66 GPa and indicated no size dependence at the diameter ranging 98-171 nm. A quantitative explanation for this phenomenon is proposed based on the rules of mixtures in classical mechanics. It is revealed that the elastic modulus of one-dimensional nanomaterials is dependent on the relative orientations and the volume fractions of the planar defects.


Assuntos
Módulo de Elasticidade , Gálio/química , Nanofios/química
8.
Proc Natl Acad Sci U S A ; 111(47): 16814-9, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25385601

RESUMO

Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of ROCK2, but not ROCK1, significantly diminished STAT3 phosphorylation and binding to IL-17 and IL-21 promoters and reduced IFN regulatory factor 4 and nuclear hormone RAR-related orphan receptor γt protein levels in T cells derived from healthy subjects or rheumatoid arthritis patients. Simultaneously, treatment with KD025 also promotes the suppressive function of regulatory T cells through up-regulation of STAT5 phosphorylation and positive regulation of forkhead box p3 expression. The administration of KD025 in vivo down-regulates the progression of collagen-induced arthritis in mice via targeting of the Th17-mediated pathway. Thus, ROCK2 signaling appears to be instrumental in regulating the balance between proinflammatory and regulatory T-cell subsets. Targeting of ROCK2 in man may therefore restore disrupted immune homeostasis and have a role in the treatment of autoimmunity.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Interleucina-17/metabolismo , Interleucinas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/fisiologia , Quinases Associadas a rho/antagonistas & inibidores , Administração Oral , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Humanos , Interleucina-17/genética , Interleucinas/genética , Fosforilação , Regiões Promotoras Genéticas , Inibidores de Proteínas Quinases/administração & dosagem , Fator de Transcrição STAT3/metabolismo , Transcrição Genética
9.
Mol Biol Cell ; 25(16): 2365-74, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24966173

RESUMO

E-cadherin is highly phosphorylated within its ß-catenin-binding region, and this phosphorylation increases its affinity for ß-catenin in vitro. However, the identification of key serines responsible for most cadherin phosphorylation and the adhesive consequences of modification at such serines have remained unknown. In this study, we show that as few as three serines in the ß-catenin-binding domain of E-cadherin are responsible for most radioactive phosphate incorporation. These serines are required for binding to ß-catenin and the mutual stability of both E-cadherin and ß-catenin. Cells expressing a phosphodeficient (3S>A) E-cadherin exhibit minimal cell-cell adhesion due to enhanced endocytosis and degradation through a lysosomal compartment. Conversely, negative charge substitution at these serines (3S>D) antagonizes cadherin endocytosis and restores wild-type levels of adhesion. The cadherin kinase is membrane proximal and modifies the cadherin before it reaches the cell surface. Together these data suggest that E-cadherin phosphorylation is largely constitutive and integral to cadherin-catenin complex formation, surface stability, and function.


Assuntos
Caderinas/biossíntese , Adesão Celular , Membrana Celular/metabolismo , Serina/metabolismo , beta Catenina/metabolismo , Animais , Antígenos CD , Células COS , Linhagem Celular , Endocitose , Humanos , Fosforilação , Ligação Proteica
10.
Angew Chem Int Ed Engl ; 51(31): 7744-7, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-22730148

RESUMO

Bistable surface: The reversible phase transition between wurtzite (WZ) and body-centered-tetragonal (BCT) lattice was activated in ZnO(1010) surfaces and directly imaged at atomic scale by using aberration-corrected electron microscopy. A nucleation-growth mechanism for the surface reconstruction is further proposed based on observations and calculations of the WZ-BCT domain boundary.

11.
Nano Lett ; 12(2): 704-8, 2012 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-22214316

RESUMO

Relaxation is a most basic structural behavior of free surfaces, however, direct observation of surface relaxation remains challenging in atomic-scale. Herein, single-crystalline nanoislands formed in situ on ZnO nanowires and nanobelts are characterized using aberration-corrected transmission electron microscopy combined with ab initio calculations. For the first time, displacements of both Zn and O atoms in the fresh (10 ̅10) facets are quantified to accuracies of several picometers and the under-surface distributions of contractions and rotations of Zn-O bonds are directly measured, which unambiguously verify the theoretically predicted relaxation of ZnO (10 ̅10) free surfaces. Finally, the surface relaxation is directly correlated with the size effects of electromechanical properties (e.g., elastic modulus and spontaneous polarization) in ZnO nanowires.


Assuntos
Nanoestruturas/química , Óxido de Zinco/química , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Teoria Quântica , Propriedades de Superfície
12.
PLoS One ; 5(4): e10184, 2010 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-20419129

RESUMO

C. elegans and Drosophila generate distinct signaling and adhesive forms of beta-catenin at the level of gene expression. Whether vertebrates, which rely on a single beta-catenin gene, generate unique adhesive and signaling forms at the level of protein modification remains unresolved. We show that beta-catenin unphosphorylated at serine 37 (S37) and threonine 41 (T41), commonly referred to as transcriptionally Active beta-Catenin (ABC), is a minor nuclear-enriched monomeric form of beta-catenin in SW480 cells, which express low levels of E-cadherin. Despite earlier indications, the superior signaling activity of ABC is not due to reduced cadherin binding, as ABC is readily incorporated into cadherin contacts in E-cadherin-restored cells. Beta-catenin phosphorylated at serine 45 (S45) or threonine 41 (T41) (T41/S45) or along the GSK3 regulatory cassette S33, S37 or T41 (S33/37/T41), however, is largely unable to associate with cadherins. Beta-catenin phosphorylated at T41/S45 and unphosphorylated at S37 and T41 is predominantly nuclear, while beta-catenin phosphorylated at S33/37/T41 is mostly cytoplasmic, suggesting that beta-catenin hypophosphorylated at S37 and T41 may be more active in transcription due to its enhanced nuclear accumulation. Evidence that phosphorylation at T41/S45 can be spatially separated from phosphorylations at S33/37/T41 suggests that these phosphorylations may not always be coupled, raising the possibility that phosphorylation at S45 serves a distinct nuclear function.


Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Transdução de Sinais , beta Catenina/metabolismo , Caderinas , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Humanos , Fosforilação , Serina/metabolismo , Transcrição Genética
13.
J Biol Chem ; 284(41): 28222-31, 2009 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-19706613

RESUMO

Post-translational stabilization of beta-catenin is a key step in Wnt signaling, but the features of beta-catenin required for stabilization are incompletely understood. We show that forms of beta-catenin lacking the unstructured C-terminal domain (CTD) show faster turnover than full-length or minimally truncated beta-catenins. Mutants that exhibit faster turnover show enhanced association with axin in co-transfected cells, and excess CTD polypeptide can compete binding of the beta-catenin armadillo (arm) repeat domain to axin in vitro, indicating that the CTD may restrict beta-catenin binding to the axin-scaffold complex. Fluorescent resonance energy transmission (FRET) analysis of cyan fluorescent protein (CFP)-arm-CTD-yellow fluorescent protein beta-catenin reveals that the CTD of beta-catenin can become spatially close to the N-terminal arm repeat region of beta-catenin. FRET activity is strongly diminished by the coexpression of beta-catenin binding partners, indicating that an unliganded groove is absolutely required for an orientation that allows FRET. Amino acids 733-759 are critical for beta-catenin FRET activity and stability. These data indicate that an N-terminal orientation of the CTD is required for beta-catenin stabilization and suggest a model where the CTD extends toward the N-terminal arm repeats, shielding these repeats from the beta-catenin destruction complex.


Assuntos
Estrutura Terciária de Proteína , Proteínas Repressoras/metabolismo , beta Catenina/química , beta Catenina/metabolismo , Sequência de Aminoácidos , Animais , Proteína Axina , Linhagem Celular , Transferência Ressonante de Energia de Fluorescência , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Repressoras/genética , Transdução de Sinais/fisiologia , Técnicas do Sistema de Duplo-Híbrido , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , beta Catenina/genética
14.
Biochem Biophys Res Commun ; 353(1): 189-94, 2007 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-17174935

RESUMO

To identify estrogen-responsive genes in mammary glands, microarray assays were performed. Twenty genes were found to be up-regulated while 16 genes were repressed in the 9h estrogen treated glands. The induction of GAS6, one of the genes up-regulated by estrogen, was confirmed by RNase protection assay. Furthermore, GAS6 was also demonstrated to be induced by estrogen in ER positive breast cancer cells. Analysis of GAS6 promoter revealed that GAS6 promoter was regulated by estrogen. An estrogen response element (ERE) was identified in the GAS6 promoter. Electrophoretic mobility shift assay revealed that ERalpha interacted with the ERE in the GAS6 promoter. Chromatin immunoprecipitation demonstrated that ERalpha was recruited to the GAS6 promoter upon estrogen stimulation. These results suggested that GAS6 is an estrogen target gene in mammary epithelial cells.


Assuntos
Células Epiteliais/metabolismo , Estrogênios/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Glândulas Mamárias Animais/metabolismo , Receptores Estrogênicos/metabolismo , Animais , Células Epiteliais/efeitos dos fármacos , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
15.
J Biol Chem ; 281(23): 15714-20, 2006 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-16603732

RESUMO

A novel estrogen receptor (ER)alpha coactivator complex, the MLL2 complex, which consists of MLL2, ASH2, RBQ3, and WDR5, was identified. ERalpha directly binds to the MLL2 complex through two LXXLL motifs in a region of MLL2 near the C terminus in a ligand-dependent manner. Disrupting the interaction between ERalpha and the MLL2 complex with small interfering RNAs specific against MLL2 or an MLL2 fragment representing the interacting region with ERalpha significantly inhibited the ERalpha transcription activity. The MLL2 complex was recruited on promoters of ERalpha target genes along with ERalpha upon estrogen stimulation. Inhibition of MLL2 expression decreased the estrogen-induced expression of ERalpha target genes cathepsin D and to a lesser extent pS2. In addition, MCF-7 cell growth was also inhibited by the depletion of MLL2. These results demonstrate that the ERalpha signaling pathway is critically dependent on its direct interaction with the MLL2 complex and suggest a central role for the MLL2 complex in the growth of ERalpha-positive cancer cells.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Receptor alfa de Estrogênio/agonistas , Proteínas de Neoplasias/fisiologia , Sequência de Bases , Linhagem Celular Tumoral , Primers do DNA , Estrogênios/fisiologia , Regulação da Expressão Gênica/fisiologia , Humanos , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , RNA Interferente Pequeno
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