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Strain TC023T, a Gram-positive, long, rod-shaped, spore-forming anaerobe, was isolated from the faeces of a heart failure mouse model. The strain formed greyish-white coloured colonies with a convex elevation on brain-heart infusion medium supplemented with 0.1â% sodium taurocholate, incubated at 37â°C for 2 days. Taxonomic analysis based on the 16S rRNA gene sequence showed that TC023T belonged to the genus Turicibacter, and was closely related to Turicibacter bilis MMM721T (97.6â%) and Turicibacter sanguinis MOL361T (97.4â%). The whole genome of the strain has a G+C content of 37.3âmol%. The average nucleotide identity and genome-to-genome distance between TC023T and Turicibacter bilis MMM721T were 77.6â% and 24.3â%, respectively, and those with Turicibacter sanguinis MOL361T were 75.4â% and 24.3â%, respectively. These genotypic, phenotypic, and biochemical analyses indicated that the isolate represents a novel species in the genus Turicibacter, and the name Turicibacter faecis sp. nov. is proposed. The type strain is TC023T (RIMD 2002001T=TSD 372T).
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Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Modelos Animales de Enfermedad , Heces , Insuficiencia Cardíaca , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Animales , ARN Ribosómico 16S/genética , Heces/microbiología , Ratones , ADN Bacteriano/genética , Insuficiencia Cardíaca/microbiología , Genoma Bacteriano , Masculino , Ácidos GrasosRESUMEN
How deregulation of chromatin modifiers causes malignancies is of general interest. Here, we show that histone H2A T120 is phosphorylated in human cancer cell lines and demonstrate that this phosphorylation is catalyzed by hVRK1. Cyclin D1 was one of ten genes downregulated upon VRK1 knockdown in two different cell lines and showed loss of H2A T120 phosphorylation and increased H2A K119 ubiquitylation of its promoter region, resulting in impaired cell growth. In vitro, H2A T120 phosphorylation and H2A K119 ubiquitylation are mutually inhibitory, suggesting that histone phosphorylation indirectly activates chromatin. Furthermore, expression of a phosphomimetic H2A T120D increased H3 K4 methylation. Finally, both VRK1 and the H2A T120D mutant histone transformed NIH/3T3 cells. These results suggest that histone H2A T120 phosphorylation by hVRK1 causes inappropriate gene expression, including upregulated cyclin D1, which promotes oncogenic transformation.
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Transformación Celular Neoplásica/genética , Ciclina D1/genética , Regulación Neoplásica de la Expresión Génica , Histonas/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas/genética , Secuencia de Aminoácidos , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Cromatina/química , Cromatina/metabolismo , Ciclina D1/metabolismo , Proteínas de Drosophila , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Células HeLa , Histonas/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Metilación , Ratones , Oligopéptidos/genética , Oligopéptidos/metabolismo , Fosforilación , Protamina Quinasa/genética , Protamina Quinasa/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Transducción de Señal , Treonina/metabolismo , UbiquitinaciónRESUMEN
BACKGROUND: In 2014, the World Health Organization (WHO) released a classification system introducing neuroendocrine neoplasms (NENs) of the female reproductive tract, excluding the ovaries. This study aimed to evaluate whether retrospective adaption of the gastroenteropancreatic (GEP)-NEN classification is feasible for ovarian NENs (O-NENs) and correlates with prognosis. METHODS: Sixty-eight patients diagnosed with carcinoid, small cell carcinoma (pulmonary type), paraganglioma, non-small/large cell neuroendocrine carcinoma (NEC), mixed NEC, or undifferentiated carcinomas at 20 institutions in Japan were included in this retrospective cross-sectional study. We identified O-NENs through central pathological review using a common slide set, followed by reclassification according to WHO 2010 guidelines for GEP-NENs. A proportional hazards model was used to assess the association of prognostic factors (age, stage, performance status, histology, and residual disease) with overall survival (OS) and progression-free survival (PFS). RESULTS: Of the 68 enrolled patients, 48 were eligible for analysis. All carcinoids (n = 32) were reclassified as NET G1/G2, whereas 14 of 16 carcinomas were reclassified as NEC/mixed adeno-NEC (MANEC) (Fisher's exact test; p < 0.01). The OS/PFS was 49.0/42.5 months and 6.5/3.9 months for NET G1/G2 and NEC/MANEC, respectively. Histology revealed that NEC/MANEC was associated with increased risk of death (HR = 48.0; 95% CI, 3.93-586; p < 0.01) and disease progression (HR = 51.6; 95% CI, 5.54-480; p < 0.01). CONCLUSION: Retrospective adaption of GEP-NEN classification to O-NENs is feasible and correlates well with the prognosis of O-NENs. This classification could be introduced for ovarian tumors.
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Biomarcadores de Tumor/sangre , Neoplasias Gastrointestinales/clasificación , Tumores Neuroendocrinos/clasificación , Neoplasias Ováricas/sangre , Neoplasias Ováricas/clasificación , Neoplasias Ováricas/diagnóstico , Neoplasias Pancreáticas/clasificación , Guías de Práctica Clínica como Asunto , Anciano , Estudios Transversales , Femenino , Humanos , Japón , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Pronóstico , Estudios Retrospectivos , Organización Mundial de la SaludRESUMEN
Endometriosis is a chronic inflammatory disease. Endometriotic cysts contain hemoglobin (Hb) and infiltrated macrophages, indicating that the metabolism of Hb by macrophages may play an important role in the inflammation of endometriotic cysts. In this study, we investigated the distribution of immune cells and CD163 (Hb receptor)-positive cells in the endometriotic cyst wall using immunohistochemistry. We also examined the role of macrophage activation by Hb on the pathogenesis of endometriotic cysts by measuring the cytokine concentration in the cystic fluids and macrophage-culture supernatant using ELISA. Macrophages were the most prominent immune cells observed in the endometriotic cysts and were differentially distributed in the different histological areas of the cyst wall. The localization of CD163-positive macrophages was restricted to the hemorrhagic and outer areas in the cyst wall. High concentrations of IL-6 and CCL2 were found in the cystic fluids, and inflammatory cytokines (IL-6, TNF-α, and CCL2) were secreted from macrophages on stimulation by Hb. IL-6 is a promotional factor for endometriotic stromal cells and ovarian clear cell carcinoma, the most common histological subtype of endometriosis-related ovarian cancer, hence, the continuous activation of macrophages by Hb could be a potential mechanism underlying endometriosis development and carcinogenesis.
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Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Carcinogénesis , Endometriosis/fisiopatología , Hemoglobinas/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Receptores de Superficie Celular , Adenocarcinoma de Células Claras , Adulto , Citocinas/metabolismo , Endometriosis/inmunología , Femenino , Humanos , Inmunohistoquímica , Macrófagos/inmunología , Persona de Mediana Edad , Neoplasias OváricasRESUMEN
Cells may exchange information with other cells and tissues by exerting forces on the extracellular matrix (ECM). Fibronectin (FN) is an important ECM component that forms fibrils through cell contacts and creates directionally biased geometry. Here, we demonstrate that FN is deposited as pillars between widely separated germ layers, namely the somitic mesoderm and the endoderm, in quail embryos. Alongside the FN pillars, long filopodia protrude from the basal surfaces of somite epithelial cells. Loss-of-function of Ena/VASP, α5ß1-integrins or talin in the somitic cells abolished the FN pillars, indicating that FN pillar formation is dependent on the basal filopodia through these molecules. The basal filopodia and FN pillars are also necessary for proper somite morphogenesis. We identified a new mechanism contributing to FN pillar formation by focusing on cyclic expansion of adjacent dorsal aorta. Maintenance of the directional alignment of the FN pillars depends on pulsatile blood flow through the dorsal aortae. These results suggest that the FN pillars are specifically established through filopodia-mediated and pulsating force-related mechanisms.
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Vasos Sanguíneos/fisiología , Endodermo/metabolismo , Mesodermo/metabolismo , Seudópodos/fisiología , Codorniz/embriología , Estrés Mecánico , Animales , Animales Modificados Genéticamente , Movimiento Celular , Embrión no Mamífero , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , MorfogénesisRESUMEN
Although first-line chemotherapy has a high rate of complete responses in ovarian cancer patients, the vast majority of patients present with recurrent disease that has become refractory to conventional chemotherapy. Peritoneal dissemination and malignant ascites are the hallmarks of recurrent or advanced ovarian cancer and severely reduce quality of life. Development of therapeutic measures to treat such patients is eagerly anticipated. Macrophage infiltration is observed in various types of cancer including epithelial ovarian cancer. In addition, macrophages are involved in the formation of spheroids in the malignant ascites of ovarian cancer and promote cancer growth. iPS-ML, macrophage-like myelomonocytic cells generated from human induced pluripotent stem (iPS) cells, made close contacts with ovarian cancer cells in vitro. We hypothesized that, if we inoculate iPS-ML-producing IFN-ß (iPS-ML/IFN-ß) into the peritoneal cavity of patients with ovarian cancer, IFN-ß produced by the iPS-ML/IFN-ß would efficiently act on the cancer cells to suppress cancer growth. To evaluate this hypothesis, we injected iPS-ML/IFN-ß into SCID mice bearing peritoneally disseminated human ovarian cancer cells, SKOV3. Immunohistochemical analysis of the intraperitoneal tumors detected iPS-ML/IFN-ß infiltrating into the cancer tissues. Therapy with iPS-ML/IFN-ß significantly suppressed tumor progression. In addition, dramatic reduction of cancer-related ascites was observed. Collectively, it is suggested that iPS-ML/IFN-ß therapy offers a new approach for the treatment of patients with advanced ovarian cancer.
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Ascitis/terapia , Interferón beta/metabolismo , Monocitos/trasplante , Neoplasias Ováricas/terapia , Neoplasias Peritoneales/terapia , Animales , Ascitis/etiología , Línea Celular Tumoral , Técnicas de Cocultivo , Femenino , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/inmunología , Ratones , Ratones SCID , Monocitos/citología , Monocitos/inmunología , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/inmunología , Neoplasias Peritoneales/complicaciones , Neoplasias Peritoneales/inmunología , Resultado del Tratamiento , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The ligand-receptor-mediated intercellular communication system plays important roles in coordinating developmental and physiological events in multicellular organisms. In plants, CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptides and their cognate receptors are thought to be involved in various aspects of the plant life cycle. Although the importance of this communication is broadly recognized, most CLE peptides are yet to be functionally characterized. A major problem in research on small signaling peptide-encoding genes is the limited number of loss-of-function mutants available due to their small gene size. CRISPR/Cas9-mediated gene targeting has the potential to overcome this problem, as it can be used to generate targeted mutations in essentially any gene, regardless of size. Here we generated a series of mutants of CLE-peptide-encoding genes. Newly generated clv3 and cle40 mutants reproduced the expected mutant phenotypes in the shoot apical meristem and root meristem, respectively. Our results show that CRISPR/Cas9-mediated gene targeting is a powerful tool for genetic analyses, even of small genes. We also report a novel mutant for CLE44 [which is thought to encode a tracheary elements differentiation inhibitory factor (TDIF)] and show that CLE44 contributes to vascular development. The bioresources presented here will be a powerful tool for further characterization of CLE peptides.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Sistemas CRISPR-Cas , Marcación de Gen/métodos , Oligopéptidos/genética , Regulación de la Expresión Génica de las Plantas , Meristema/genética , Mutación , Raíces de Plantas/genéticaRESUMEN
The yeast RSC, an ATP-dependent chromatin-remodeling complex, is essential for mitotic and meiotic growth. There are two distinct isoforms of this complex defined by the presence of either Rsc1 or Rsc2; however, the functional differences between these complexes are unclear. Here we show that the RSC complex containing Rsc1, but not Rsc2, functions in autophagy induction. Rsc1 was required not only for full expression of ATG8 mRNA but also for maintenance of Atg8 protein stability. Interestingly, decreased autophagic activity and Atg8 protein stability in rsc1Δ cells, but not the defect in ATG8 mRNA expression, were partially suppressed by deletion of TOR1. In addition, we found that rsc1Δ impaired the binding between the Rho GTPase Rho1 and the TORC1-specific component Kog1, which is required for down-regulation of TORC1 activity. These results suggest that the Rsc1-containing RSC complex plays dual roles in the proper induction of autophagy: 1) the transcriptional activation of autophagy-related genes independent of the TORC1 pathway and 2) the inactivation of TORC1, possibly through enhancement of Rho1-Kog1 binding.
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Proteínas Cromosómicas no Histona/metabolismo , Proteínas de Unión al ADN/metabolismo , Nitrógeno/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional/fisiología , Autofagia/fisiología , Regulación hacia Abajo/fisiología , Saccharomyces cerevisiae/citología , Transducción de Señal/fisiologíaRESUMEN
The hypoxia-inducible factors HIF-1α or HIF-2α form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1α/ARNT and HIF-2α/ARNT complexes activate hypoxia-inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O2 deprivation. HIF-2α is known to regulate the function and/or differentiation of stem cells by activating the POU domain transcription factor Oct4; however, the precise underlying mechanism is unknown. This study examined the role of HIF-2α/ARNT in hair development using conditional-knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild-type mice, HIF-2α and ARNT were highly expressed in the precortex above the hair matrix, an area containing differentiating stem cells. An analysis of hair size and type in these mice showed that loss of ARNT decreased the production of zigzag hairs, corresponding to reduced expression of HIF-2α and induction of the mammalian cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27 (Kip1). The results suggest that the HIF-2α/ARNT complex regulates hair follicle differentiation via induction of p21(Waf1/Cip1) and possibly p27(Kip1), as p27(Kip1) expression was not altered in ARNT knockout mice. The findings provide insight into a possible mechanism underlying hair growth disorders and can be useful for future studies on hair follicle response to insults, such as chemotherapy and ionizing radiation.
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Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Cabello/crecimiento & desarrollo , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Folículo Piloso/citología , Folículo Piloso/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Queratinocitos , Ratones , Ratones NoqueadosAsunto(s)
Ginecología , Obstetricia , Academias e Institutos , Congresos como Asunto , Femenino , Humanos , Embarazo , TennesseeRESUMEN
Maternal immune activation is one of the environmental risk factors for offspring to develop psychiatric disorders. A synthetic viral mimetic immunogen, polyinosinic-polycytidylic acid (poly(I:C)), is used to induce maternal immune activation in animal models of psychiatric disorders. In the mouse poly(I:C) model, the existence of segment filamentous bacteria (SFB) in the maternal intestine has been reported to be important for the induction of ASD-related behavioral alterations as well as atypical cortical development called cortical patches. This study aimed to elucidate the effect of a single poly(I:C) injection during embryonic day (E) 9 to E16 on offspring's behavior in the ensured absence of maternal SFB by vancomycin drinking in C57BL/6N mice. The cortical patches were not found at either injection timings with poly(I:C) or PBS vehicle, tested in male or female offspring at postnatal day 0 or 1. Prepulse inhibition was decreased in male adult offspring most strongly at poly(I:C) injection timings later than E11, whereas a modest but significant decrease was observed in female offspring with an injection during E12 to E15. The decrease in social interaction was observed in female offspring most conspicuously at injection timings later than E11, whereas a significant decrease was observed in male offspring with an injection during E12 to E15. In conclusion, this study indicated that behavioral alterations could be induced without maternal SFB. The effect on behavior was substantially different between males and females.
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Bacterias , Poli I-C , Humanos , Ratones , Adulto , Animales , Femenino , Masculino , Ratones Endogámicos C57BL , Poli I-C/farmacología , Modelos Animales de Enfermedad , CitoesqueletoRESUMEN
Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). Impairment of HIF-1-dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif-1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF-1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF-1α.
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Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , Hipoxia/inmunología , Inmunidad Celular/fisiología , Daño por Reperfusión/inmunología , Linfocitos T/inmunología , Animales , Descubrimiento de Drogas , Humanos , Hipoxia/fisiopatología , Daño por Reperfusión/fisiopatología , Linfocitos T/fisiología , Vasculitis/inmunología , Vasculitis/fisiopatologíaRESUMEN
TP53 mutations in acute myeloid leukemia (AML) are associated with poor outcomes. The number of somatic and/or germline genetic tests for therapy is increasing. Patients with such incidental findings should undergo adequate genetic counseling.
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INTRODUCTION: This study examined the relationship between health literacy (HL), women's health, and work productivity (i.e., absenteeism or presenteeism) among female workers in Japan. METHODS: In February 2018, a web-based, nationwide survey was conducted among registered survey company monitors. The questionnaire included women's HL, absenteeism, presenteeism, health behaviors for menstrual abnormalities and premenstrual syndrome (PMS), and demographic information. Overall, 2,596 monitors were randomly invited, and the survey included the first 2,000 respondents (average age = 35.8 years, SD = 8.1). An analysis of covariance (ANCOVA) was conducted to compare adjusted work productivity between two groups: the low-HL group and the high-HL group. The results were adjusted for age, education, employment status, number of children, and the presence of underlying gynecological diseases. Logistic regression analyses were performed to determine any differences in health behaviors for menstrual abnormalities or PMS between the two groups. The results were adjusted for age, education level, number of children, and employment status. RESULTS: The ANCOVA showed that the high-HL group had significantly less presenteeism and better performance when experiencing PMS (p < 0.001 and p < 0.013, respectively) compared to the low-HL group after adjusting for covariates. However, the results showed no significant differences in absenteeism between the two groups. Logistic regression showed that the high-HL group had a significantly higher odds ratio (OR) than the low-HL group in terms of health behaviors for menstrual abnormalities or PMS (OR 2.82 and 1.86, respectively) after adjusting for covariates. CONCLUSIONS: Women's HL may contribute to decreased presenteeism and better health behaviors regarding the use of medicine or medical services.
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Introduction New-onset systemic lupus erythematosus (SLE) during pregnancy is rare and difficult to diagnose, especially in cases that manifest as preeclampsia. We report a patient with new-onset SLE that manifested as preeclampsia during pregnancy and provide a review of the literature to identify factors for a rapid diagnosis. Case A 32-year-old primigravid Japanese woman was diagnosed with severe preeclampsia and underwent emergent cesarean section at 29 weeks of gestation. Her hypertension and renal disorder gradually improved after the operation, but her thrombocytopenia and anemia worsened. SLE was diagnosed on postoperative day 5 by a comprehensive autoimmune workup. She was discharged on postoperative day 34 with remission. Conclusion Our case and previous reports suggest that distinguishing underlying SLE from preeclampsia in the third trimester is particularly difficult. Helpful factors for diagnosis of suspected SLE in these cases were persistence of symptoms and new atypical symptoms for preeclampsia revealed after delivery (e.g., fever, renal disorder, and thrombocytopenia).
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Histone acetylation plays a pivotal role in transcriptional regulation, and ATP-dependent nucleosome remodeling activity is required for optimal transcription from chromatin. While these two activities have been well characterized, how they are coordinated remains to be determined. We discovered ATP-dependent histone H2A acetylation activity in Drosophila nuclear extracts. This activity was column purified and demonstrated to be composed of the enzymatic activities of CREB-binding protein (CBP) and SMARCAD1, which belongs to the Etl1 subfamily of the Snf2 family of helicase-related proteins. SMARCAD1 enhanced acetylation by CBP of H2A K5 and K8 in nucleosomes in an ATP-dependent fashion. Expression array analysis of S2 cells having ectopically expressed SMARCAD1 revealed up-regulated genes. Using native genome templates of these up-regulated genes, we found that SMARCAD1 activates their transcription in vitro. Knockdown analysis of SMARCAD1 and CBP indicated overlapping gene control, and ChIP-seq analysis of these commonly controlled genes showed that CBP is recruited to the promoter prior to SMARCAD1. Moreover, Drosophila genetic experiments demonstrated interaction between SMARCAD1/Etl1 and CBP/nej during development. The interplay between the remodeling activity of SMARCAD1 and histone acetylation by CBP sheds light on the function of chromatin and the genome-integrity network.
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ADN Helicasas/metabolismo , Proteínas de Drosophila/metabolismo , Histonas/metabolismo , Procesamiento Proteico-Postraduccional/fisiología , Transcripción Genética/fisiología , Factores de Transcripción p300-CBP/metabolismo , Acetilación , Animales , Línea Celular , ADN Helicasas/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Histonas/genética , Factores de Transcripción p300-CBP/genéticaRESUMEN
Molecular epidemiological investigation was conducted among injecting drug users (IDUs) (n = 11) and heterosexuals (n = 15) in Kunming, Yunnan Province of China. HIV-1 genotypes were determined based on the nucleotide sequences of 2.6-kb gag-RT region. The distribution of genotypes among IDUs was as follows: CRF07_BC (5/11) and CRF08_BC (5/11); subtype B' (1/11). Similarly, a majority of Kunming heterosexuals (14/15) were infected with CRF07_BC (4/15), CRF08_BC (6 /15), or subtype B' (4/15), known to predominate among IDUs in China. This contrasts with trends in the coastal regions of China and surrounding southeastern Asian countries, where CRF01_AE predominates among heterosexuals. The heterosexual HIV-1 epidemic in Kunming thus appears to derive from the local IDU epidemic. Of note, subtype B' was the most prevalent strain among heterosexuals before 1997, while CRF07_BC and CRF08_BC became predominant in 2002, indicating a transition of HIV-1 genotype distribution between the early and the more recent samples from Kunming heterosexuals.
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Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/genética , Epidemiología Molecular , Abuso de Sustancias por Vía Intravenosa/complicaciones , China/epidemiología , Femenino , Genes gag , Genotipo , Infecciones por VIH/epidemiología , Transcriptasa Inversa del VIH/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADNRESUMEN
â¢We report a choriocarcinoma coexisting with an epithelioid trophoblastic tumor.â¢Chemotherapy with methotrexate, etoposide, and actinomycin-D was efficacious.â¢Choriocarcinoma with epithelioid trophoblastic tumor may benefit from chemotherapy.
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Acetylation of nucleosomal histones by diverse histone acetyltransferases (HAT) plays pivotal roles in many cellular events. Discoveries of novel HATs and HAT related factors have provided new insights to understand the roles and mechanisms of histone acetylation. In this study, we identified prominent Histone H3 acetylation activity in vitro and purified its activity, showing that it is composed of the MYST acetyltransferase Chameau and Enhancer of the Acetyltransferase Chameau (EAChm) family. EAChm is a negatively charged acidic protein retaining aspartate and glutamate. Furthermore, we identified that Chameau and EAChm stimulate transcription in vitro together with purified general transcription factors. In addition, RNA-seq analysis of Chameu KD and EAChm KD S2 cells suggest that Chameau and EAChm regulate transcription of common genes in vivo. Our results suggest that EAChm regulates gene transcription in Drosophila embryos by enhancing Acetyltransferase Chameau activity.
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Acetiltransferasas/fisiología , Proteínas de Drosophila/fisiología , Transactivadores/fisiología , Acetiltransferasas/química , Secuencia de Aminoácidos , Animales , Proteínas de Drosophila/química , Datos de Secuencia Molecular , Transactivadores/química , Transcripción Genética/fisiologíaRESUMEN
RSC (Remodel the Structure of Chromatin) is an ATP-dependent chromatin remodeling complex essential for the growth of Saccharomyces cerevisiae. RSC exists as two distinct isoforms that share core subunits including the ATPase subunit Nps1/Sth1 but contain either Rsc1or Rsc2. Using the synthetic genetic array (SGA) of the non-essential null mutation method, we screened for mutations exhibiting synthetic growth defects in combination with the temperature-sensitive mutant, nps1-105, and found connections between mitochondrial function and RSC. rsc mutants, including rsc1Δ, rsc2Δ, and nps1-13, another temperature-sensitive nps1 mutant, exhibited defective respiratory growth; in addition, rsc2Δ and nps1-13 contained aggregated mitochondria. The rsc2Δ phenotypes were relieved by RSC1 overexpression, indicating that the isoforms play a redundant role in respiratory growth. Genome-wide expression analysis in nps1-13 under respiratory conditions suggested that RSC regulates the transcription of some target genes of the HAP complex, a transcriptional activator of respiratory gene expression. Nps1 physically interacted with Hap4, the transcriptional activator moiety of the HAP complex, and overexpression of HAP4 alleviated respiratory defects in nps1-13, suggesting that RSC plays pivotal roles in mitochondrial gene expression and shares a set of target genes with the HAP complex.