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1.
Vaccine ; 42(3): 608-619, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38142216

RESUMO

In this study, we evaluated the immunogenicity and protective immunity of in vitro transcribed Venezuelan equine encephalitis virus (VEEV TC-83 strain) self-amplifying RNA (saRNA) encoding the SARS-CoV-2 spike (S) protein in wild type (S-WT) and stabilized pre-fusion conformations (S-PP). Immunization with S-WT and S-PP saRNA induced specific neutralizing antibody responses in both K18-Tg hACE2 (K18) and BALB/c mice, as assessed using SARS-CoV-2 pseudotyped viruses. Protective immunity was assessed in challenge experiments. Two immunizations with S-WT and S-PP induced protective immunity, evidenced by lower mortality, lower weight loss and more than one log10 lower subgenomic virus RNA titers in the upper and lower respiratory tracts in both K18 and BALB/c mice. Histopathologic examination of lungs post-challenge showed that immunization with S-WT and S-PP resulted in a higher degree of immune cell infiltration and inflammatory changes, compared with control mice, characterized by high levels of T- and B-cell infiltration. No substantial differences were found in the presence and localization of eosinophils, macrophages, neutrophils, and natural killer cells. CD4 and CD8 T-cell depletion post immunization resulted in reduced lung inflammation post challenge but also prolonged virus clearance. These data indicate that immunization with saRNA encoding the SARS-CoV-2 S protein induces immune responses that are protective following challenge, that virus clearance is associated with pulmonary changes caused by T-cell and B-cell infiltration in the lungs, but that this T and B-cell infiltration plays an important role in viral clearance.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas Virais , gama-Globulinas , Animais , Humanos , Camundongos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Imunização , Glicoproteína da Espícula de Coronavírus/genética
2.
Organometallics ; 42(12): 1331-1338, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37915831

RESUMO

Ti-catalyzed oxidative alkyne carboamination with alkenes and azo compounds can yield either α,ß-unsaturated imines or cyclopropyl imines through a common azatitanacyclohexene intermediate. Herein, we report the synthesis of a model azatitanacyclohexene complex (3) through the ring-opening of a cyclopropyl imine with Cp2Ti(BTMSA) (BTMSA = bis(trimethylsilyl)acetylene). 3 readily undergoes thermal or reductant-catalyzed ring contraction to an azatitanacyclopentene (4), analogous to the proposed mechanism for forming α,ß-unsaturated imines in the catalytic reaction. A cyclopropyl imine or an α,ß-unsaturated imine could be liberated via the oxidation of 3 or 4 with azobenzene, respectively, further implicating the role of these metallacycles in the Ti-catalyzed carboamination reaction.

3.
Elife ; 122023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37589453

RESUMO

Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes in circulating cells and their relationships to gene regulation are unknown. We identified age-associated DNA methylation sites in six purified blood-borne immune cell types (naive B, naive CD4+ and CD8+ T cells, granulocytes, monocytes, and NK cells) collected from healthy individuals interspersed over a wide age range. Of the thousands of age-associated sites, only 350 sites were differentially methylated in the same direction in all cell types and validated in an independent longitudinal cohort. Genes close to age-associated hypomethylated sites were enriched for collagen biosynthesis and complement cascade pathways, while genes close to hypermethylated sites mapped to neuronal pathways. In silico analyses showed that in most cell types, the age-associated hypo- and hypermethylated sites were enriched for ARNT (HIF1ß) and REST transcription factor (TF) motifs, respectively, which are both master regulators of hypoxia response. To conclude, despite spatial heterogeneity, there is a commonality in the putative regulatory role with respect to TF motifs and histone modifications at and around these sites. These features suggest that DNA methylation changes in healthy aging may be adaptive responses to fluctuations of oxygen availability.


Assuntos
Envelhecimento , Linfócitos T CD8-Positivos , Humanos , Envelhecimento/genética , Ativação do Complemento , Metilação de DNA , Epigênese Genética
4.
J Virol ; 96(18): e0116621, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36069549

RESUMO

Studies on Ebola virus disease (EVD) survivors and clinical studies on Ebola virus (EBOV) vaccine candidates have pinpointed the importance of a strong antibody response in protection and survival from EBOV infection. However, little is known about the T cell responses to EBOV or EBOV vaccines. We used HLA-A*02:01 (HLA-A2) transgenic mice to study HLA-A2-specific T cell responses elicited following vaccination with EBOV glycoprotein (EBOV-GP) presented with three different systems: (i) recombinant protein (rEBOV-GP), (ii) vesicular stomatitis replication-competent recombinant virus (VSV-EBOV-GP), and (iii) modified vaccinia Ankara virus recombinant (MVA-EBOV-GP). T cells from immunized animals were analyzed using peptide pools representing the entire GP region and individual peptides. Regardless of the vaccine formulation, we identified a minimal 9mer epitope containing an HLA-A2 motif (FLDPATTS), which was confirmed through HLA-A2 binding affinity and immunization studies. Using binding prediction software, we identified substitutions surrounding position 9 (S9V, P10V, and Q11V) that predicted enhanced binding to the HLA-A2 molecule. This enhanced binding was confirmed through in vitro binding studies and enhanced potency was shown with in vivo immunization studies using the enhanced sequences and the wild-type sequence. Of note, in silico studies predicted the enhanced 9mer epitope carrying the S9V substitution as the best overall HLA-A2 epitope for the full-length EBOV-GP. These results suggest that EBOV-GP-S9V and EBOV-GP-P10V represent more potent in vivo immunogens. Identification and enhancement of EBOV-specific human HLA epitopes could lead to the development of tools and reagents to induce more robust T cell responses in human subjects. IMPORTANCE Vaccine efficacy and immunity to viral infection are often measured by neutralizing antibody titers. T cells are specialized subsets of immune cells with antiviral activity, but this response is variable and difficult to track. We showed that the HLA-A2-specific T cell response to the Ebola virus glycoprotein can be enhanced significantly by a single residue substitution designed to improve an epitope binding affinity to one of the most frequent MHC alleles in the human population. This strategy could be applied to improve T cell responses to Ebola vaccines designed to elicit antibodies and adapted to target MHC alleles of populations in regions where endemic infections, like Ebola virus disease, are still causing outbreaks with concerning pandemic potential.


Assuntos
Aminoácidos , Ebolavirus , Epitopos de Linfócito T , Glicoproteínas , Doença pelo Vírus Ebola , Aminoácidos/metabolismo , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra Ebola/genética , Ebolavirus/genética , Epitopos de Linfócito T/metabolismo , Antígeno HLA-A2/genética , Antígeno HLA-A2/metabolismo , Humanos , Camundongos , Proteínas Recombinantes , Vírus Vaccinia , Vesiculovirus
6.
Int J Mol Sci ; 23(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35457082

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative motor disorder without an available therapeutic to halt the formation of Lewy bodies for preventing dopaminergic neuronal loss in the nigrostriatal pathway. Since oxidative-stress-mediated damage has been commonly reported as one of the main pathological mechanisms in PD, we assessed the efficacy of a novel NOX inhibitor from AptaBio Therapeutics (C-6) in dopaminergic cells and PD mouse models. The compound reduced the cytotoxicity and enhanced the cell viability at various concentrations against MPP+ and α-synuclein preformed fibrils (PFFs). Further, the levels of ROS and protein aggregation were significantly reduced at the optimal concentration (1 µM). Using two different mouse models, we gavaged C-6 at two different doses to the PD sign-displaying transgenic mice for 2 weeks and stereotaxically PFF-injected mice for 5 weeks. Our results demonstrated that both C-6-treated mouse models showed alleviated motor deficits in pole test, hindlimb clasping, crossbeam, rotarod, grooming, and nesting analyses. We also confirmed that the compound treatment reduced the levels of protein aggregation, along with phosphorylated-α-synuclein, in the striatum and ventral midbrain and further dopaminergic neuronal loss. Taken together, our results strongly suggest that NOX inhibition can be a potential therapeutic target for PD.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Camundongos , Camundongos Transgênicos , Degeneração Neural/patologia , Doença de Parkinson/metabolismo , Agregados Proteicos , alfa-Sinucleína/metabolismo
7.
Front Immunol ; 13: 1095140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36741385

RESUMO

Lysine specific methyltransferase 2D (Kmt2d) catalyzes the mono-methylation of histone 3 lysine 4 (H3K4me1) and plays a critical role in regulatory T cell generation via modulating Foxp3 gene expression. Here we report a role of Kmt2d in naïve CD8+ T cell generation and survival. In the absence of Kmt2d, the number of CD8+ T cells, particularly naïve CD8+ T cells (CD62Lhi/CD44lo), in spleen was greatly decreased and in vitro activation-related death significantly increased from Kmt2d fl/flCD4cre+ (KO) compared to Kmt2d fl/flCD4cre- (WT) mice. Furthermore, analyses by ChIPseq, RNAseq, and scRNAseq showed reduced H3K4me1 levels in enhancers and reduced expression of apoptosis-related genes in activated naïve CD8+ T cells in the absence of Kmt2d. Finally, we confirmed the activation-induced death of antigen-specific naïve CD8+ T cells in vivo in Kmt2d KO mice upon challenge with Listeria monocytogenes infection. These findings reveal that Kmt2d regulates activation-induced naïve CD8+ T cell survival via modulating H3K4me1 levels in enhancer regions of apoptosis and immune function-related genes.


Assuntos
Linfócitos T CD8-Positivos , Histona-Lisina N-Metiltransferase , Lisina , Animais , Camundongos , Biomarcadores , Linfócitos T CD8-Positivos/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Fatores de Transcrição/metabolismo
8.
ACS Omega ; 6(47): 32208-32214, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34870041

RESUMO

While the chemical vapor deposition technique can be used to fabricate 2D materials in a larger area, materials like MoS2 have limited controllability due to their lack of self-controlling nature. This article presents a new technique for synthesizing a void-free millimeter-scale continuous monolayer MoS2 film through the diffusion of a well-controlled Mo, Na, and seeding promoter-based coating under a low-pressure N2 atmosphere. Compared to the conventional method, this technique provides precise control of solid precursors, where MoS2 grows next to the coating. At 800 °C, the synthesized MoS2 showed a uniform single-layer MoS2 film; however, a Na-free coating showed nanoscale voids and poor crystal quality, which are attributed to a higher edge-attachment barrier that slows down the MoS2 lateral growth. The synthesized MoS2 with Na-containing solution showed an intense PL peak with a 1.86 eV band gap. Even at the relatively low temperature of 700 °C, compared to the Na-excluded condition, MoS2 showed almost two times higher area coverage with a comparatively larger crystal size. This finding may assist in the future development of MoS2-based electronic and optoelectronic devices such as transistors and photodetectors.

9.
Immunity ; 54(11): 2465-2480.e5, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34706222

RESUMO

Epigenetic reprogramming underlies specification of immune cell lineages, but patterns that uniquely define immune cell types and the mechanisms by which they are established remain unclear. Here, we identified lineage-specific DNA methylation signatures of six immune cell types from human peripheral blood and determined their relationship to other epigenetic and transcriptomic patterns. Sites of lineage-specific hypomethylation were associated with distinct combinations of transcription factors in each cell type. By contrast, sites of lineage-specific hypermethylation were restricted mostly to adaptive immune cells. PU.1 binding sites were associated with lineage-specific hypo- and hypermethylation in different cell types, suggesting that it regulates DNA methylation in a context-dependent manner. These observations indicate that innate and adaptive immune lineages are specified by distinct epigenetic mechanisms via combinatorial and context-dependent use of key transcription factors. The cell-specific epigenomics and transcriptional patterns identified serve as a foundation for future studies on immune dysregulation in diseases and aging.


Assuntos
Metilação de DNA , Epigênese Genética , Epigenômica , Regulação da Expressão Gênica , Imunidade , Fatores de Transcrição/metabolismo , Transcriptoma , Epigenômica/métodos , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Fatores de Transcrição/genética
10.
Metabolites ; 11(2)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669564

RESUMO

Pilates has been known as exercise intervention that improves the function of pelvic floor muscle (PFM) associated with impacting urinary incontinence (UI). This study investigated the effect of Pilates on UI in Korean women by determining the change in functional movement of PFM (FMP) and metabolic profiles. UI group with Pilates (UIP, n = 13) participated in 8-weeks Oov Pilates program, and 8 subjects were assigned to Control and UI group with no Pilates (UINP), respectively. Before and after 8 weeks, plasma samples were collected from all participants, and ultrasonography was used to measure the functional change of PFM for calculating FMP ratio. Plasma samples were analyzed by mass spectrometry to identify the change of metabolic features. After 8-weeks intervention, FMP ratio was remarkably decreased in UIP (48.1% ↓, p < 0.001), but not in Control and UINP (p > 0.05). In metabolic features, L-Glutamine (m/z: 147.07 [M + H]+), L-Cystathionine (m/z: 240.09 [M + NH4]+), L-Arginine (m/z: 197.1 [M + Na]+), and L-1-Pyrroline-3-hydroxy-5-carboxylate (m/z: 147.07 [M + NH4]+) were significantly elevated solely in UIP (p < 0.001). Our study elucidated that Pilates can ameliorate the FMP and enhance the specific metabolic characteristics, which was potentially associated with invigorated PFM contractility to effectively control the bladder base and continence.

11.
Cell Death Dis ; 11(12): 1044, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298885

RESUMO

Cannabinoid 1 receptor (CB1R) expression is upregulated in the liver with viral hepatitis, cirrhosis, and both alcoholic and non-alcoholic fatty liver disease (FLD), whereas its expression is muted under usual physiological conditions. Inhibiting CB1R has been shown to be beneficial in preserving hepatic function in FLD but it is unclear if inhibiting CB1R during an inflammatory response to an acute hepatic injury, such as toxin-induced injury, would also be beneficial. We found that intrinsic CB1R in hepatocytes regulated liver inflammation-related gene transcription. We tested if nullification of hepatocyte-specific CB1R (hCNR1-/-) in mice protects against concanavalin A (Con A)-induced liver injury. We looked for evidence of liver damage and markers of inflammation in response to Con A by measuring liver enzyme levels and proinflammatory cytokines (e.g., TNF-α, IL-1ß, IL-6, IL-17) in serum collected from hCNR1-/- and control mice. We observed a shift to the right in the dose-response curve for liver injury and inflammation in hCNR1-/- mice. We also found less inflammatory cell infiltration and focal necrosis in livers of hCNR1-/- mice compared to controls, resulting from downregulated apoptotic markers. This anti-apoptotic mechanism results from increased activation of nuclear factor kappa B (NF-κB), especially cAMP-dependent cannabinoid signaling and membrane-bound TNF-α, via downregulated TNF-α receptor 2 (TNFR2) transcription levels. Collectively, these findings provide insight into involvement of CB1R in the pathogenesis of acute liver injury.


Assuntos
Concanavalina A/toxicidade , Hepatócitos/metabolismo , Fígado/metabolismo , Fígado/patologia , NF-kappa B/metabolismo , Receptor CB1 de Canabinoide/deficiência , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Membrana Celular/metabolismo , AMP Cíclico/metabolismo , Hepatócitos/efeitos dos fármacos , Inflamação/patologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Modelos Biológicos , Ligação Proteica , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
12.
Front Immunol ; 10: 1993, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497023

RESUMO

Maintenance of telomeres is essential for preserving T cell proliferative responses yet the precise role of telomerase in human T cell differentiation, function, and aging is not fully understood. Here we analyzed human telomerase reverse transcriptase (hTERT) expression and telomerase activity in six T cell subsets from 111 human adults and found that levels of hTERT mRNA and telomerase activity had an ordered decrease from naïve (TN) to central memory (TCM) to effector memory (TEM) cells and were higher in CD4+ than their corresponding CD8+ subsets. This differentiation-related reduction of hTERT mRNA and telomerase activity was preserved after activation. Furthermore, the levels of hTERT mRNA and telomerase activity were positively correlated with the degree of activation-induced proliferation and survival of T cells in vitro. Partial knockdown of hTERT by an anti-sense oligo in naïve CD4+ cells led to a modest but significant reduction of cell proliferation. Finally, we found that activation-induced levels of telomerase activity in CD4+ TN and TCM cells were significantly lower in old than in young subjects. These findings reveal that hTERT/telomerase expression progressively declines during T cell differentiation and age-associated reduction of activation-induced expression of hTERT/telomerase mainly affects naïve CD4+ T cells and suggest that enhancing telomerase activity could be a strategy to improve T cell function in the elderly.


Assuntos
Linfócitos T/citologia , Linfócitos T/enzimologia , Telomerase/metabolismo , Adulto , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Humanos , Telomerase/genética
13.
Sci Rep ; 9(1): 8027, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142824

RESUMO

The burden of minimal hepatic encephalopathy (MHE) is significant, but no universal criteria for diagnosis have been established. We aimed to validate the Korean Stroop Test for MHE screening. Chronic hepatitis B-related liver cirrhosis patients were recruited prospectively from 13 centers. The Korean Stroop Test consisted of two Stroop-off states (color and word) and two Stroop-on states (inhibition and switching). Accuracy adjusted psychomotor speed (rate correct score) of these tests were analyzed. Sex- and age- adjusted rate correct scores of these tests were rated as the Korean Stroop Score (K-Stroop score). MHE was diagnosed when Portosystemic Encephalopathy Syndrome Test (PHES) scores were below -4. A total of 220 liver cirrhosis patients and 376 healthy controls were enrolled. Prevalence of MHE was 20.6% in cirrhosis patients. Rate correct scores and the K-Stroop score showed significant differences between healthy controls, cirrhosis patients without MHE, and cirrhosis patients with MHE. The rate correct score of the K-Stroop score was 0.74 (95% Confidence Interval: 0.66-0.83, P < 0.001). Female gender and the K-Stroop score were significant for MHE diagnosis. The Korean Stroop Test is simple and valid for screening of MHE.


Assuntos
Encefalopatia Hepática/diagnóstico , Hepatite B Crônica/patologia , Cirrose Hepática/complicações , Programas de Rastreamento/métodos , Teste de Stroop , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Encefalopatia Hepática/etiologia , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Índice de Gravidade de Doença
14.
Nanoscale ; 11(14): 6727-6736, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30901015

RESUMO

The use of next-generation graphene requires the control of the number of deposition layers together with its fast synthesis for its use in advanced and miniaturized devices. Here, this article describes a novel technique for the selective growth of a continuous film of a graphene pattern (controlled monolayer/multilayer design) by the chemical vapor deposition (CVD) method on Cu foils modified by different plasma treatments. Ex situ Ar plasma treatment is the preferred treatment for monolayer graphene (I2D/IG = 1.81) synthesis. Bilayer graphene (I2D/IG = 1.05) growth was influenced by applying an additional oxygen plasma treatment, which led to different morphologies and control of the surface-active nature of Cu. The required design was achieved by a photolithography process. Graphene synthesis was performed by a short annealing process (60 s) followed by a single-step short burst of graphene growth (60 s). Relatively high density graphene nuclei with faster graphene growth resulted in monolayer graphene in the Ar plasma-treated area. Ex situ oxygen plasma treatment in selected areas was capable of controlling the amount of graphene nuclei formation, while the kink structure was capable of bolstering the adsorption of a relatively high amount of carbon adatoms, resulting in bilayer graphene.

15.
Nanotechnology ; 30(4): 045301, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30457976

RESUMO

A low-temperature laser crystallization is newly devised for producing polycrystalline silicon (poly-Si) thin films of low-loss, low surface roughness enough for nanoscale patterning, applicable to practical Si metasurface elements on complementary metal-oxide semiconductor (CMOS) electronic architectures in visible lights. The method is based on dielectric encapsulation of an amorphous Si film and subsequent laser-induced local crystallization. Such poly-Si thin film yields order-of-magnitude smaller surface roughness and grain size than those obtained with the conventional laser annealing processes. The mechanism of the formation of small and uniform crystalline grains during solidification is studied to ensure the smooth surfaces enough for nanoscale patterning. By obtaining root mean square of surface roughness <2.49 nm and extinction coefficient <4.8 × 10-2 at 550 nm, visible metasurface color-filter elements are experimentally demonstrated with the resonant transmission-peak efficiency approaching ∼85%. This low-loss poly-Si metasurface is favorably compatible with embedded CMOS electronic architectures in contrast to the conventional thermal annealing processes that often cause failure of electrical device functionalities due to delamination and material-property degradation problems. The proposed fabrication in this study provides a practical method for further development of various Si metasurfaces in the visible domain and their integration with CMOS electronic devices as well.

16.
Nanomicro Lett ; 10(1): 18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30393667

RESUMO

The combination of graphene with conductive nanoparticles, forming graphene-nanoparticle hybrid materials, offers a number of excellent properties for advanced engineering applications. A novel and simple method was developed to deposit 10 wt% tin-doped indium tin oxide (ITO) nanoparticles on graphene. The method involved a combination of a solution-based environmentally friendly electroless deposition approach and subsequent vacuum annealing. A stable organic-free solution of ITO was prepared from economical salts of In(NO3)3 ·H2O and SnCl4. The obtained ITO nanostructure exhibited a unique architecture, with uniformly dispersed 25-35 nm size ITO nanoparticles, containing only the crystallized In2O3 phase. The synthesized ITO nanoparticles-graphene hybrid exhibited very good and reproducible optical transparency in the visible range (more than 85%) and a 28.2% improvement in electrical conductivity relative to graphene synthesized by chemical vapor deposition. It was observed that the ITO nanoparticles affect the position of the Raman signal of graphene, in which the D, G, and 2D peaks were redshifted by 5.65, 5.69, and 9.74 cm-1, respectively, and the annealing conditions had no significant effect on the Raman signatures of graphene.

17.
Front Immunol ; 9: 549, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29632530

RESUMO

Transition from resting to cell cycle in response to antigenic stimulation is an essential step for naïve CD8+ T cells to differentiate to effector and memory cells. Leaving the resting state requires dramatic changes of chromatin status in the key cell cycle inhibitors but the details of these concerted events are not fully elucidated. Here, we showed that Ezh2, an enzymatic component of polycomb repressive complex 2 (PRC2) catalyzing the trimethylation of lysine 27 on histone 3 (H3K27me3), regulates activation induced naïve CD8+ T cells proliferation and apoptosis. Upon deletion of Ezh2 during thymocyte development (Ezh2fl/flCd4Cre+ mice), naive CD8+ T cells displayed impaired proliferation and increased apoptosis in response to antigen stimulation. However, naive CD8+ T cells only had impaired proliferation but no increase in apoptosis when Ezh2 was deleted after activation (Ezh2fl/flGzmBCre+ mice), suggesting cell cycle and apoptosis are temporally separable events controlled by Ezh2. We then showed that deletion of Ezh2 resulted in the increase in expression of cyclin-dependent kinase inhibitors Cdkn2a (p16 and Arf) and Cdkn1c (p57) in activated naïve CD8+ T cells as the consequence of reduced levels of H3K27me3 at these two gene loci. Finally, with real time imaging, we observed prolonged cell division times of naïve CD8+ T cells in the absence of Ezh2 post in vitro stimulation. Together, these findings reveal that repression of Cdkn1c and Cdkn2a by Ezh2 plays a critical role in execution of activation-induced CD8+ T cell proliferation.


Assuntos
Linfócitos T CD8-Positivos/fisiologia , Ciclo Celular/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/fisiologia , Inibidor de Quinase Dependente de Ciclina p57/fisiologia , Proteína Potenciadora do Homólogo 2 de Zeste/fisiologia , Animais , Antígenos/imunologia , Apoptose , Proliferação de Células , Listeria monocytogenes , Listeriose/imunologia , Camundongos Knockout , Ovalbumina/imunologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-29641462

RESUMO

Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standar Desviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition.


Assuntos
Envelhecimento/psicologia , Atenção , Percepção Auditiva , Inibição Psicológica , Percepção Visual , Estimulação Acústica , Adulto , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Adulto Jovem
19.
Chem Asian J ; 13(4): 390-394, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29318776

RESUMO

A highly fluorescent (ΦF =0.60) and water-soluble two-dimensional (2D) honeycomb-shaped supramolecular organic framework (SOF) was successfully synthesized in pure aqueous solution via self-assembly of novel cyanostilbene-functionalized trilateral guest molecules and cucurbit[8]uril hosts. The size of this fluorescent 2D SOF was >500 nm in diameter, 1.7 nm in thickness, and 3.9 nm in the honeycomb pore diameter. This 2D SOF holds potential as a new all-organic photosensitizer template for photocatalytic H2 evolution from pure water.

20.
Sci Rep ; 7(1): 17868, 2017 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-29259236

RESUMO

Indium tin oxide (ITO) still remains as the main candidate for high-performance optoelectronic devices, but there is a vital requirement in the development of sol-gel based synthesizing techniques with regards to green environment and higher conductivity. Graphene/ITO transparent bi-film was synthesized by a two-step process: 10 wt. % tin-doped ITO thin films were produced by an environmentally friendly aqueous sol-gel spin coating technique with economical salts of In(NO3)3.H2O and SnCl4, without using organic additives, on surface free energy enhanced (from 53.826 to 97.698 mJm-2) glass substrate by oxygen plasma treatment, which facilitated void-free continuous ITO film due to high surface wetting. The chemical vapor deposited monolayer graphene was transferred onto the synthesized ITO to enhance its electrical properties and it was capable of reducing sheet resistance over 12% while preserving the bi-film surface smoother. The ITO films contain the In2O3 phase only and exhibit the polycrystalline nature of cubic structure with 14.35 ± 0.5 nm crystallite size. The graphene/ITO bi-film exhibits reproducible optical transparency with 88.66% transmittance at 550 nm wavelength, and electrical conductivity with sheet resistance of 117 Ω/sq which is much lower than that of individual sol-gel derived ITO film.

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