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1.
Int J Mol Sci ; 25(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38339006

RESUMO

Climate change adversely affects the water and temperature conditions required for plant growth, leading to a decrease in yield. In high temperatures, oxidative stress causes cellular damage in plant cells, which is a negative factor for crop production. Thioredoxin (Trx) is a small redox protein containing a conserved WC(G/P)PC motif that catalyzes the exchange of disulfide bonds. It is known to play an important role in maintaining cellular redox homeostasis. Trx proteins are widely distributed across various subcellular locations, and they play a crucial role in responding to cellular stresses. In this study, seven CaTrxh-type genes present in pepper were identified and the CaTrxh-type family was classified into three subgroups. CaTrxh genes responded to heat stress. Moreover, subcellular locations of the CaTrxh family exhibited dynamic patterns in normal conditions, and we observed relocalizations in heat stress conditions. Each CaTrxh family protein member formed homo-/heteromeric protein complexes in BiFC assay. Unexpectedly, subgroup III CaTrxh9 and CaTrxh10 can recruit subgroup I and II CaTrxh proteins into the plasma membrane. Thus, the function of the CaTrxh-type family is expected to play a protective role in the cell in response to high-temperature stress via protein complex formations. CaTrxh may have potential applications in the development of crops with enhanced tolerance to oxidative stress.


Assuntos
Capsicum , Capsicum/metabolismo , Temperatura , Proteínas de Plantas/metabolismo , Resposta ao Choque Térmico/genética , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética
2.
Sci Rep ; 12(1): 22382, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572699

RESUMO

We investigated the proportions of immediate sequential bilateral cataract surgery (ISBCS) and unilateral cataract surgery during the coronavirus disease 2019 pandemic and compared visual outcomes between the two groups in a tertiary hospital in South Korea. We reviewed 441 cataract surgeries performed between March 1, 2021, and October 31, 2021, at Korea University Guro Hospital by a single surgeon (J.S.S). Medical records of demographics, preoperative visual acuity, corneal astigmatism, axial length, preoperative spherical equivalent, preoperative target (using Barrett's Universal 2 formula), postoperative visual acuity, postoperative refractive error, and postoperative complications were evaluated. Among all patients, 322 (73.0%) eyes underwent ISBCS, and 119 (27.0%) eyes underwent unilateral cataract surgery. The preoperative corrective distance visual acuity (CDVA) was lower in the unilateral cataract surgery group (0.40 ± 0.45 logMAR) than the ISBCS group (0.28 ± 0.16 logMAR, P = 0.008), whereas there was no significant difference in postoperative CDVA between the two groups (0.06 ± 0.10 logMAR vs. 0.07 ± 0.16 logMAR, P = 0.63). There was also no difference in the absolute refractive error between the two groups (0.46 ± 0.37 diopters [D] vs. 0.42 ± 0.38 D, P = 0.63). The preoperative CDVA (P = 0.000) was the significant factor influencing absolute refractive error (r = 0.191, P < 0.001). There was no difference in complications between the two groups, although two patients in the ISBCS group complained of postoperative strabismus.


Assuntos
COVID-19 , Extração de Catarata , Catarata , Facoemulsificação , Erros de Refração , Humanos , Centros de Atenção Terciária , COVID-19/complicações , Extração de Catarata/efeitos adversos , Erros de Refração/complicações , Catarata/complicações , República da Coreia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Facoemulsificação/efeitos adversos
3.
Plants (Basel) ; 11(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36365311

RESUMO

Autophagy is an evolutionarily well-conserved cellular catabolic pathway in eukaryotic cells and plays an important role in cellular processes. Autophagy is regulated by autophagy-associated (ATG) proteins. Among these ATG proteins, the ubiquitin-like protein ATG8/LC3 is essential for autophagosome formation and function. In this study, the potato StATG8 family showed clade I and clade II with significantly different sequences. Expression of the StATG8 family was also increased in senescence. Interestingly, the expression of the StATG8 and other core StATG genes decreased in potato tubers as the tubers matured. The StATG8 family also responded to a variety of stresses such as heat, wounding, salicylic acid, and salt stress. We also found that some Arabidopsis WRKY transcription factors interacted with the StATG8 protein in planta. Based on group II-a WRKY, StATG8-WRKY interaction is independent of the ATG8 interacting motif (AIM) or LC3 interacting region (LIR) motif. This study showed that the StATG8 family had diverse functions in tuber maturation and multiple stress responses in potatoes. Additionally, StATG8 may have an unrelated autophagy function in the nucleus with the WRKY transcription factor.

4.
J Craniofac Surg ; 33(4): e427-e429, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36041098

RESUMO

ABSTRACT: The purpose of this study was to investigate the distribution of blowout fracture sites among age groups and compare clinical factors that can affect the fracture site. The authors reviewed 330 cases of blowout fracture surgeries and included 226 eyes of 226 patients aged between 20 and 29 years and between 50 and 59 years who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea University Hospital.Medical records including patient demography, trauma etiology, and preoperative computed tomography image were evaluated. Ethmoidal cell septa and fracture site position were compared between the 2 age groups. The causes of injury were categorized into 3 groups: focal trauma, gross trauma, and other causes. Orbital floor fracture was the most common type (40.00%) in the young group, followed by medial wall fracture (25.33%). in contrast, medial wall fracture accounted for the largest proportion (42.11%) in the older group, and orbital floor fracture accounted for only 26.67%. The major cause of blowout fracture in young patients was focal trauma, whereas gross trauma was the most common cause in the older group. The number of ethmoidal cells was 4.19 ±â€Š0.831 (2-6) in the young group and 3.91 ±â€Š1.022 (2-6) in the old group (P  < 0.05). Distribution of blowout fracture site differed between age groups, and these differences can be explained by cause of injury and number of ethmoidal cells.


Assuntos
Fraturas Múltiplas , Fraturas Orbitárias , Adulto , Idoso , Povo Asiático , Olho , Ossos Faciais , Humanos , Fraturas Orbitárias/diagnóstico por imagem , Fraturas Orbitárias/epidemiologia , Fraturas Orbitárias/etiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
5.
J Craniofac Surg ; 33(4): 1190-1192, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36041113

RESUMO

ABSTRACT: The purpose of this study was to investigate the characteristics of blowout fractures caused by baseball trauma. The authors reviewed 337 cases of blowout fracture surgeries and included 330 eyes of 330 patients who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea university Hospital.Medical records including patient demography, trauma etiology, accompanied ocular disease, and preoperative computed tomography images were evaluated. Patients were categorized into 2 groups: a group with blowout fracture caused by baseball trauma and another group with trauma due to other causes. Two-wall blowout fracture (orbital floor fracture and medial wall fracture) was most common (63.16%) in the baseball group, followed by medial wall fracture (21.05%). In contrast, orbital floor fracture accounted for the largest proportion (42.11%) among other causes, and 2-wall blowout fracture accounted for the second largest proportion (31.83%). The most common accompanied ocular disease was traumatic hyphema and traumatic iridocyclitis (36.84%) in the baseball blowout fracture group. in contrast, subconjunctival hemorrhage was the most common ocular disease in the other-causes group (16.08%). The frequency of traumatic hyphema and irido-cyclitis was significantly different among the 2 groups (P  < 0.05). Distribution of blowout fracture sites and frequent ocular disease differed between baseball blowout fracture patients and other-cause blowout fracture patients.


Assuntos
Beisebol , Traumatismos Oculares , Fraturas Orbitárias , Ossos Faciais , Humanos , Hifema , Fraturas Orbitárias/diagnóstico por imagem , Fraturas Orbitárias/epidemiologia , Fraturas Orbitárias/etiologia , Estudos Retrospectivos
6.
Am J Cancer Res ; 12(3): 1295-1308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35411225

RESUMO

The protein tyrosine kinase Ephrin type-B receptor 2 (EPHB2) belongs to one of the intestinal stem cell signature genes and plays a crucial role in maintaining the crypt-villous axis. Herein, we aimed to investigate the expression of EPHB2 during gastric carcinogenesis and evaluated its prognostic and functional significance in gastric cancer (GC). EPHB2 expression was upregulated in intestinal metaplasia and GCs compared to normal antral and fundic glands. EPHB2 mRNA levels were strongly correlated with the intestinal stem cell markers OLFM4, LGR5, and EPHB3. Notably, EPHB2 expression was significantly correlated with CDX2 expression, and in vitro studies demonstrated that CDX2 expression increased both EPHB2 transcription and protein levels. In a large cohort of GC patients, EPHB2 positivity was observed in 39% of 704 GCs and was negatively correlated with tumor differentiation, lymphovascular invasion, and tumor-node-metastasis stages. Notably, EPHB2 positivity was associated with better overall survival, and it was an independent prognostic marker in intestinal-type GCs. Overexpression of EPHB2 in GC cell lines, MKN-28 and MKN-74, reduced migration activity by suppressing phosphorylation of focal adhesion kinase, whereas no significant difference was observed in proliferation rates. Thus, we suggest that EPHB2 acts as a tumor suppressor in GCs and can be a prognostic marker in intestinal-type GCs.

7.
J Clin Med ; 11(6)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35329825

RESUMO

We compared the retinal vessel density and inner retinal thickness in patients who had one eye with geographic atrophy (GA) and a fellow eye with intermediate age-related macular degeneration (iAMD). The vessel density from the superficial vascular complex (SVC) and deep vascular complex (DVC) through optical coherence tomography angiography and the thickness of the nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), outer nuclear layer (ONL) on a structural optical coherence tomography thickness map were measured in 28 eyes of 14 GA patients with iAMD in the fellow eye. GA eyes had significantly lower vessel density in the SVC (26.2 ± 3.9% vs. 28.3 ± 4.4%; p = 0.015) and DVC (24.2 ± 2.6% vs. 26.8 ± 1.9%; p = 0.003) than fellow eyes (iAMD). GCIPL and ONL were significantly thinner in GA eyes than in the fellow eyes (p = 0.032 and 0.024 in the foveal areas, p = 0.029 and 0.065 in the parafovea areas, respectively). Twenty-four eyes of 12 patients were followed up for 2 years and seven of the fellow eyes (58.3%) developed GA during the follow-up period and showed reduced vessel density in the SVC (26.4 ± 3.0% vs. 23.8 ± 2.9%; p = 0.087) and DVC (25.8 ± 2.2% vs. 22.4 ± 4.4%; p = 0.047) compared to baseline. Vessel density and GCIPL thickness map measurements are potential GA markers in non-neovascular AMD.

8.
J Craniofac Surg ; 33(4): 1008-1012, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34629380

RESUMO

ABSTRACT: The purpose of this study was to compare the configuration of blowout fracture observed through orbital computed tomography (CT) and endoscopy, then present the effectiveness of using an endoscope in reconstruction surgery of blowout fracture. We retrospectively reviewed the clinical records of 337 patients who underwent reconstruction surgery of blowout fracture between January 2017 and December 2020 in the Department of Ophthalmology at Korea University Guro Hospital. The patients were categorized into 3 groups based on preoperative CT findings as follows: combined orbital medial and floor wall fractures, trapdoor fractures, and large blowout fractures. The images obtained through CT and endoscopy were compared among the 3 groups. Endoscopy helped identify herniated soft tissue and posterior fracture margins, and it also provides better magnification and a brighter view of the posterior aspects of the fracture site. Furthermore, endoscopy can also provide educational opportunities to visualize the fracture site and help trainees understand the surgical procedure approach or orbital anatomy. Based on our results, we suggest using an endoscope during blowout fracture surgery as an effective approach to reduce postoperative complications due to endoscopy's advantages in clear visualization of the fracture site during operation.


Assuntos
Fraturas Orbitárias , Procedimentos de Cirurgia Plástica , Endoscopia/métodos , Humanos , Fraturas Orbitárias/diagnóstico por imagem , Fraturas Orbitárias/etiologia , Fraturas Orbitárias/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/efeitos adversos
9.
Korean J Ophthalmol ; 35(2): 130-135, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33596620

RESUMO

PURPOSE: The correlation between the existence of the preoperative condition of ≥10 prism diopters (PD) in patients with basic type of intermittent exotropia (IXT) and postoperative outcomes was analyzed. METHODS: The medical records of patients that underwent surgery for IXT were analyzed retrospectively. The analysis was conducted by dividing the patients into a group with change of <10 PD (group 1) and ≥10 PD (group 2) before the time of the surgery. Patients who received at least 6 months of follow-up after surgery were included. The age, sex, angle of deviation and stereoacuity of the patients were studied. Surgical success was defined as exodeviation of <10 PD or esodeviation of <4 PD at the final visit after the surgery. The correlation between clinical factors and surgical success rate was analyzed by using correlative analysis. RESULTS: A total of 129 patients participated in the study. There were 108 (83.7%) and 21 (16.3%) patients in groups 1 and 2, respectively. There were 89 (82.4%) and 17 (80.1%) patients with surgical successes in groups 1 and 2, respectively (p = 0.18). Moreover, 13 (12.0%) patients in group 1 and three (14.3%) patients in group 2 required reoperation, showing no significant difference (p = 0.12). There was no statistically significant correlation between surgical success and preoperative change of angle of deviation <10 PD (odds ratio, 1.78; p = 0.17). CONCLUSIONS: Among the patients with basic type of IXT subjected to the analysis, 16.3% had a change of ≥10 PD before surgery, and there was no significant correlation between surgical success and preoperative change of angle of deviation.


Assuntos
Exotropia , Exotropia/cirurgia , Seguimentos , Humanos , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Estudos Retrospectivos , Resultado do Tratamento , Visão Binocular
10.
Sci Rep ; 10(1): 18268, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106589

RESUMO

To objectively analyze the gas tamponade area in patients with different concentrations of perfluoropropane (C3F8) after pars plana vitrectomy (PPV), retrospective analysis was performed in patients diagnosed with retinal detachment or macular hole and underwent PPV with C3F8 tamponade of two concentrations (14% and 20%). The ultra-widefield fundus (UWF) images at one and 10 days and four weeks postoperatively were corrected using stereographic projection to adjust peripheral distortion. The gas-fluid interface curvatures were delineated using UWF stereographic projection images, and the gas-fluid area ratio and estimated gas area were calculated at each concentration. Among 65 eyes, 30 were in the 14% group and 35 were in the 20% group. The gas-fluid area ratio was 0.71 in the 14% group and 0.83 in the 20% group at 10 days (p = 0.046) and 0.27 and 0.45, respectively, at four weeks postoperatively (p < 0.001). The estimated gas area was 52.56 and 60.82 mm2 at 10 days (p = 0.025) and 19.83 and 33.86 mm2 at four weeks (p < 0.001). The gas tamponade areas were objectively shown to be greater under the 20% concentration than the 14% concentration of C3F8 at 10 days and 4 weeks postoperatively using UWF stereographic projection images.


Assuntos
Fluorocarbonos/administração & dosagem , Descolamento Retiniano/cirurgia , Perfurações Retinianas/cirurgia , Vitrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/diagnóstico por imagem , Perfurações Retinianas/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
11.
Nucleic Acids Res ; 48(17): 9959-9968, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32810226

RESUMO

The CRISPR-Cas system provides adaptive immunity for bacteria and archaea to combat invading phages and plasmids. Phages evolved anti-CRISPR (Acr) proteins to neutralize the host CRISPR-Cas immune system as a counter-defense mechanism. AcrIF7 in Pseudomonas aeruginosa prophages strongly inhibits the type I-F CRISPR-Cas system. Here, we determined the solution structure of AcrIF7 and identified its target, Cas8f of the Csy complex. AcrIF7 adopts a novel ß1ß2α1α2ß3 fold and interacts with the target DNA binding site of Cas8f. Notably, AcrIF7 competes with AcrIF2 for the same binding interface on Cas8f without common structural motifs. AcrIF7 binding to Cas8f is driven mainly by electrostatic interactions that require position-specific surface charges. Our findings suggest that Acrs of divergent origin may have acquired specificity to a common target through convergent evolution of their surface charge configurations.


Assuntos
Bacteriófagos/química , Sistemas CRISPR-Cas , Proteínas Virais/química , Bacteriófagos/genética , Bacteriófagos/patogenicidade , Sítios de Ligação , Proteínas Associadas a CRISPR/química , Proteínas Associadas a CRISPR/metabolismo , Simulação de Acoplamento Molecular , Ligação Proteica , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/virologia , Proteínas Virais/metabolismo
12.
Front Psychol ; 10: 370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863345

RESUMO

Since service providers directly conduct emotional labor to customers, it is important to identify the factors influencing emotional labor of service providers. Even though the studies identifying the predisposing factors influencing emotional labor are taking place, there is no empirical evidence confirming how relationship bonds, which have been established between corporations and service providers, are related to emotional labor. This study examined the influences of relationship bonds on emotional labor through person-organization fit (P-O fit) and the moderating effects of collectivism between P-O fit and emotional labor. Analysis was conducted by performing questionnaire surveys targeting 350 employees in the financial industry. As a result of the analysis, it has been found that financial bonds, social bonds, and structural bonds enhanced P-O fit and P-O fit improved deep acting. In addition, this study identified that collectivism of service providers strengthened the influence of P-O fit toward deep acting. This study not only suggested the empirical evidence identifying the process of relationship bonds influencing emotional labor but also expanded the scope of study by examining moderating roles of collectivism in cultural psychology aspect.

14.
J Biol Chem ; 293(8): 2744-2754, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29348170

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide microbial adaptive immunity against bacteriophages. In type I-F CRISPR-Cas systems, multiple Cas proteins (Csy1-4) compose a surveillance complex (Csy complex) with CRISPR RNA (crRNA) for target recognition. Here, we report the biochemical characterization of the Csy1-Csy2 subcomplex from Xanthomonas albilineans, including the analysis of its interaction with crRNA and AcrF2, an anti-CRISPR (Acr) protein from a phage that infects Pseudomonas aeruginosa The X. albilineans Csy1 and Csy2 proteins (XaCsy1 and XaCsy2, respectively) formed a stable heterodimeric complex that specifically bound the 8-nucleotide (nt) 5'-handle of the crRNA. In contrast, the XaCsy1-XaCsy2 heterodimer exhibited reduced affinity for the 28-nt X. albilineans CRISPR repeat RNA containing the 5'-handle sequence. Chromatographic and calorimetric analyses revealed tight binding between the Acr protein from the P. aeruginosa phage and the heterodimeric subunit of the X. albilineans Csy complex, suggesting that AcrF2 recognizes conserved features of Csy1-Csy2 heterodimers. We found that neither XaCsy1 nor XaCsy2 alone forms a stable complex with AcrF2 and the 5'-handle RNA, indicating that XaCsy1-XaCsy2 heterodimerization is required for binding them. We also solved the crystal structure of AcrF2 to a resolution of 1.34 Å, enabling a more detailed structural analysis of the residues involved in the interactions with the Csy1-Csy2 heterodimer. Our results provide information about the order of events during the formation of the multisubunit crRNA-guided surveillance complex and suggest that the Acr protein inactivating type I-F CRISPR-Cas systems has broad specificity.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas Associadas a CRISPR/metabolismo , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Modelos Moleculares , RNA Bacteriano/metabolismo , Xanthomonas/metabolismo , Substituição de Aminoácidos , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas Associadas a CRISPR/antagonistas & inibidores , Proteínas Associadas a CRISPR/química , Proteínas Associadas a CRISPR/genética , Cristalografia por Raios X , Estabilidade Enzimática , Isoenzimas , Cinética , Mutação , Conformação Proteica , Multimerização Proteica , Estabilidade Proteica , Interferência de RNA , Estabilidade de RNA , RNA Bacteriano/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Especificidade da Espécie , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo , Xanthomonas/enzimologia , Xanthomonas/imunologia
15.
Struct Dyn ; 4(5): 054701, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28612041

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins constitute a microbial, adaptive immune system countering invading nucleic acids. Cas2 is a universal Cas protein found in all types of CRISPR-Cas systems, and its role is implicated in new spacer acquisition into CRISPR loci. In subtype I-C CRISPR-Cas systems, Cas2 proteins are metal-dependent double-stranded DNA (dsDNA) nucleases, and a pH-dependent conformational transition has been proposed as a prerequisite for catalytic action. Here, we report the crystal structure of Xanthomonas albilineans Cas2 (XaCas2) and provide experimental evidence of a pH-dependent conformational change during functional activation. XaCas2 crystallized at an acidic pH represented a catalytically inactive conformational state in which two Asp8 residues were too far apart to coordinate a single catalytic metal ion. Consistently, XaCas2 exhibited dsDNA nuclease activity only under neutral and basic conditions. Despite the overall structural similarity of the two protomers, significant conformational heterogeneity was evident in the putative hinge regions, suggesting that XaCas2 engages in hinge-bending conformational switching. The presence of a Trp residue in the hinge region enabled the investigation of hinge dynamics by fluorescence spectroscopy. The pH dependence of the fluorescence intensity overlapped precisely with that of nuclease activity. Mutational analyses further suggested that conformational activation proceeded via a rigid-body hinge-bending motion as both D8E and hinge mutations significantly reduced nuclease activity. Together, our results reveal strong correlations between the conformational states, catalytic activity, and hinge dynamics of XaCas2, and provide structural and dynamic insights into the conformational activation of the nuclease function of Cas2.

16.
Exp Mol Med ; 48: e252, 2016 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-27515126

RESUMO

Replication-independent incorporation of variant histone H3.3 has a profound impact on chromatin function and numerous cellular processes, including the differentiation of muscle cells. The histone chaperone HIRA and H3.3 have essential roles in MyoD regulation during myoblast differentiation. However, the precise mechanism that determines the onset of H3.3 deposition in response to differentiation signals is unclear. Here we show that HIRA is phosphorylated by Akt kinase, an important signaling modulator in muscle cells. By generating a phosphospecific antibody, we found that a significant amount of HIRA was phosphorylated in myoblasts. The phosphorylation level of HIRA and the occupancy of phosphorylated protein on muscle genes gradually decreased during cellular differentiation. Remarkably, the forced expression of the phosphomimic form of HIRA resulted in reduced H3.3 deposition and suppressed the activation of muscle genes in myotubes. Our data show that HIRA phosphorylation limits the expression of myogenic genes, while the dephosphorylation of HIRA is required for proficient H3.3 deposition and gene activation, demonstrating that the phosphorylation switch is exploited to modulate HIRA/H3.3-mediated muscle gene regulation during myogenesis.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Chaperonas de Histonas/metabolismo , Desenvolvimento Muscular , Mioblastos/citologia , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Humanos , Camundongos , Mioblastos/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ativação Transcricional
17.
BMB Rep ; 48(12): 685-90, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26058396

RESUMO

The eukaryotic genome is packed into chromatin, which is important for the genomic integrity and gene regulation. Chromatin structures are maintained through assembly and disassembly of nucleosomes catalyzed by histone chaperones. Asf1 (anti-silencing function 1) is a highly conserved histone chaperone that mediates histone transfer on/off DNA and promotes histone H3 lysine 56 acetylation at globular core domain of histone H3. To elucidate the role of Asf1 in the modulation of chromatin structure, we screened and identified small molecules that inhibit Asf1 and H3K56 acetylation without affecting other histone modification. These pyrimidine-2,4,6-trione derivative molecules inhibited the nucleosome assembly mediated by Asf1 in vitro, and reduced the H3K56 acetylation in HeLa cells. Furthermore, production of HSV viral particles was reduced by these compounds. As Asf1 is implicated in genome integrity, cell proliferation, and cancer, current Asf1 inhibitor molecules may offer an opportunity for the therapeutic development for treatment of diseases.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Cromatina/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Acetilação , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Histonas/metabolismo , Humanos , Chaperonas Moleculares , Nucleossomos/efeitos dos fármacos , Nucleossomos/metabolismo
18.
J Vet Med Sci ; 69(2): 201-4, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17339766

RESUMO

A 10-year-old Maltese dog was presented with abdominal distention and dyspnea. Cytological examination of pleural and peritoneal effusion was suggestive of malignant effusion of glandular origin. Numerous, multifocal, tan to white nodules were disseminated throughout the surface of the abdominal organs and peritoneum at biopsy. Histologically, the tumors were revealed to be an epithelial type of mesothelioma. Neoplastic cells co-expressed cytokeratin and vimentin. Intravenous administration of cisplatin was chosen as the treatment. During treatment, the dog's overall body condition improved and the clinical signs were relieved without significant side effects. The survival time from diagnosis to sudden death by unknown cause was 153 days.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Doenças do Cão/tratamento farmacológico , Mesotelioma/veterinária , Neoplasias Peritoneais/veterinária , Neoplasias Pleurais/veterinária , Animais , Doenças do Cão/patologia , Cães , Evolução Fatal , Feminino , Histocitoquímica/veterinária , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia
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