text:
Supplementary Materialsoncotarget-09-26130-s001
Supplementary Materialsoncotarget-09-26130-s001. rather elevated expression of green fluorescence protein transduced by the same Ad vector. These data collectively indicated that an HSP90 inhibitor SQ22536 possessed a divalent action on p53 expression, as an activator for endogenous wild-type p53 through inhibited ubiquitination and a negative regulator of exogenously over-expressed p53 through the proteasome pathway. and the genes, but possessed the wild-type gene [3]. Deletion of p16 expression increases cyclin-dependent kinase 4/6 activities and subsequently phosphorylates pRb, which induces uninhibited cell cycle progression. In addition, p14 deficiency augments MDM2 activities that promote p53 ubiquitination and degradation, and consequently decreases p53 expression levels. The genetic defect in the INK4A/ARF locus thus leads to dysfunction of both pRb and p53 with tumor suppressive activities. Up-regulation of p53 in mesothelioma not only restores the suppressed p53 functions but dephosphorylates pRb since p21 induced by p53 blocks cyclin-dependent kinase 2 activities. Induction of p53 expression is therefore a direct way to reconstitute the tumor suppressor functions and can be a therapeutic strategy for mesothelioma [4]. We in fact showed that transduction of mesothelioma with adenoviruses (Ad) expressing the wild-type gene (Ad-p53) decreased the viability and increased susceptibility to cisplatin- or pemetrexed-mediated cytotoxicity [5]. SQ22536 Warmth shock protein (HSP) 90 is a molecular chaperon and functions to maintain a number of client proteins in order to deal with cellular stresses and to mediate cellular homeostasis [6]. The HSP90 expression is often up-regulated in a variety of cancer and the client proteins with oncogenic potential are therefore constitutively activated to support cancer cell survival. An inhibitor for HSP90 disrupts actions of the oncoproteins and produces cytotoxic effects on tumor cells which are frequently addicted to oncogenic processes [7]. The inhibitors also suppress growth signaling activities and have been investigated for anti-tumor effects in clinical trials [7, 8]. Moreover, HSP90 inhibitors can augment p53 expression through inhibiting functions of MDM4 which constitutes a heterodimeric structure with MDM2 [9, 10]. A degradation procedure for p53 is certainly mediated with the ubiquitination-proteasome pathway mainly, and MDM2 with an ubiquitin ligase function regulates p53 expression through facilitating the proteasome-mediated degradation [11] negatively. HSP90 inhibitors as a result increase p53 appearance by suppressing the MDM2-mediated p53 degradation through MDM4. The inhibitors can as a result be a applicant agent for therapy of mesothelioma that is sensitive to p53-mediated growth inhibition. Geldanamycin derivatives, 17-allylamino-17-demetheoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG), are a prototype of the HSP90 inhibitor but have not been well investigated for the cytotoxic activity in mesothelioma. With this study we examined whether HSP90 inhibitors produced anti-tumor effects on mesothelioma and accomplished combinatory effects with Ad-p53 by inhibiting a degradation process of transduced p53. We found that the HSP90 inhibitors augmented endogenous wild-type p53 manifestation but rather down-regulated the p53 level induced Rabbit Polyclonal to ARFGEF2 by Ad-p53. RESULTS Cytotoxic activity of HSP90 inhibitors to mesothelioma We examined cytotoxic effects of 17-AAG and 17-DMAG with human being mesothelioma cells and immortalized cells of mesothelium source with the WST assay (Number ?(Figure1A).1A). Relative viabilities of the cells were examined with different doses of the HSP90 inhibitors. The HSP90 inhibitors suppressed viability of these SQ22536 cells and 17-DMAG was more cytotoxic than 17-AAG. We then examined a possible relation between the susceptibility and the p53 practical status. We classified NCI-H2452 (truncated p53 protein), Met-5A (SV40 T antigen indicated), JMN-1B and EHMES-1 cells (mutated genotype) like a nonfunctional along with other 5 cells.
This entry was posted in Guanylyl Cyclase on March 10, 2021 by bioxorio.
Non-small cell lung cancers (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio-resistance
Non-small cell lung cancers (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio-resistance. region, leading to an increased mRNA expression, therefore efficiently inhibited the transcription of Nrf2 to the nucleus, which suppressed the Nrf2-dependent antioxidant and resulted in the upregulation of ROS. Importantly, when combined with radiation, genistein further improved the ROS levels in A549 cells whereas reducing the radiation-induced oxidative stress in MRC-5 cells, probably via increasing the manifestation levels of Nrf2, GSH and HO-1. Moreover, radiation combined with genistein significantly improved cell apoptosis in A549 but not MRC-5 cells. Together, the results herein show the intrinsic difference in the redox status of A549 and MRC-5 cells could be the target for genistein to selectively sensitize A549 cells to radiation, leading to a rise in radiosensitivity for A549 cells thereby. reported which the promoter area of Keap1 is normally aberrantly AZD5423 hypermethylated and Keap1 mRNA appearance amounts are lower in some lung cancers cell lines and lung cancers tissues; however, Keap1 is expressed in BEAS-2B individual normal bronchial epithelial cells [17] highly. Genistein is an all natural isoflavone numerous biological actions. Xie recommended that genistein includes a significant inhibitory influence on global DNA methylation amounts in breast cancer tumor cells [18]. Furthermore, several research [19, 20] possess demonstrated that genistein can invert hypermethylation and reactivate many TSGs in cancers cells. Nevertheless, whether genistein regulates the methylation degree of the Keap1 promoter area and the next appearance of Keap1 haven't been elucidated however. The purpose of this research was to research how genistein in different ways modulates the intracellular redox position in individual non-small cell lung cancers A549 AZD5423 cells and individual regular lung fibroblast MRC-5 cells, recognize the goals of genistein within the Nrf2-Keap1 pathway, and measure the radiosensitizing aftereffect of genistein on A549 cells. Outcomes The radiosensitizing aftereffect of genistein was selective for A549 cells rather than MRC-5 cells First of all, a MTT was performed by us assay beneath the development condition to supply cell viability. MRC-5 cells had been found to become more resistant to the genistein-induced cytotoxicity weighed against A549 cells (Amount ?(Figure1A).1A). The subcytotoxic dose of genistein (10 M) was chosen to study the combined effect of genistein and radiation on cell radiosensitivity. Comparisons of the growth curves and survival fractions for the two cell lines indicated a selectively radiosensitizing effect of genistein on A549 cells. For example, in Figure ?Number1D,1D, genistein alone decreased the number of A549 cells in growth rate by 24.2 1.5%, but increased the number of MRC-5 cells in growth rate by 16.0 1.3%. Radiation (4 Gy) decreased the cell growth rate by 11.0 1.0% in A549 cells and by 31.6 2.9% in MRC-5 cells. Interestingly, the growth rate in the combined treatment group was almost the same as AZD5423 the control group for MRC-5 cells, but decreased by 59.2 3.9% in A549 cells. Related results were produced from the clonogenic success data as proven in Amount ?Figure1E1E. Open up in another window Amount 1 The radiosensitizing aftereffect of genistein was selective for A549 cells however, not for MRC-5 cells(A) MTT assay. Cell viability was assessed after 48 h of genistein treatment. (B) and (C) cell development curves. Cell quantities were plotted on the log-linear scale. The info points of the very first 2 times had been excluded in the info fitting. Equations produced from the exponential development curve suit [Y = begin exp ( = 0.05, ** 0.01 0.01) and in MRC-5 cells ( 0.05). Nevertheless, genistein by itself elicited a rise from the ROS level in A549 cells instead of in MRC-5 cells. When coupled with rays, genistein elevated the mobile ROS level in A549 cells additional, marketing the cell-killing influence thereby. Significantly, in AZD5423 MRC-5 cells, genistein reduced the radiation-induced ROS level, recommending an antioxidant response by genistein. Open up in another window Amount 2 Genistein induced oxidative tension and oxidative harm in A549 instead of in MRC-5 cells(A) DCFH-DA assay. Cells had been treated with 10 M genistein for 48 AZD5423 h after that with or without irradiation; (B) PCO; (C) MDA and (D) 8-OHdG levels. * GCSF 0.05, ** 0.01, *** 0.001 0.01) and in MRC-5 cells ( 0.05). However, in the combined treatment group, the PCO and MDA material increased significantly ( 0.001) in A549 cells but not in MRC-5 cells. Simultaneously, DNA oxidative damage was studied.
This entry was posted in Heparanase on March 10, 2021 by bioxorio.
Supplementary MaterialsFIG?S1
Supplementary MaterialsFIG?S1. red). Nuclei had been stained with DAPI (blue). Club, 20 m. (C) Dimension from the TEER of Calu-3 cell level cultured in AIC using 0.4-m-pore membrane or 3-m-pore membrane, with or minus the addition of 5 ng/ml IL-4 or IL-13 for 24 h. TEER was portrayed as mean ohms cm2??SEM. Statistical evaluation was performed by one way-ANOVA (for 0.4- versus 3- m-pore membrane, three filters; for control versus IL-4 or IL-13 treated, four filter systems from two indie experiments). Values which are statistically considerably different are indicated by asterisks the following: ***, 0.01. Download FIG?S3, TIF file, 1.1 MB. Copyright ? 2019 Audry et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. FIG?S4. Coculture of with in broth. ELF2 BHI broth cultures with ((alone were produced for 24 h, and CFUs were determined. The number of meningococci after 24 h of growth was expressed as mean percentage of the value for the control experiment SEM. Peucedanol The control was meningococci produced in monoculture. Statistical analysis was performed by Students test on four wells from two impartial experiments. Values that are statistically Peucedanol significantly different are indicated by asterisks as follows: ****, 0.0001; **, 0.01. Download FIG?S4, TIF file, 0.2 MB. Copyright ? 2019 Audry et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. TABLE?S1. Oligosaccharides recognized on Calu-3 mucins. Download Table?S1, DOCX file, 0.1 MB. Copyright ? 2019 Audry et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. TABLE?S2. Sialylated oligosaccharides and their nonsialylated forms recognized on Calu-3 mucins or human nasal mucins. Download Table?S2, DOCX file, 0.04 MB. Copyright ? 2019 Audry et al. This content is distributed under the conditions of the Innovative Commons Attribution 4.0 International permit. TABLE?S3. Primers found in this scholarly research. Download Desk?S3, DOCX document, 0.02 MB. Copyright ? 2019 Audry et al. This article is distributed beneath the conditions of the Innovative Commons Attribution 4.0 International permit. ABSTRACT can be an inhabitant from the nasopharynx, that it really is transmitted from person to disseminates or person in bloodstream and becomes a harmful pathogen. In this ongoing work, we attended to colonization from the nasopharyngeal specific niche market by concentrating on the interplay between meningococci as well as the airway mucus that lines the mucosa from the web host. Using Calu-3 cells harvested in air user interface culture (cells harvested using the apical area facing surroundings), we examined meningococcal colonization from the mucus as well as the web host response. Our outcomes recommended that behaved like commensal bacterias in mucus, without getting together with individual cells or Peucedanol transmigrating with the cell level actively. As a total result, type IV pili usually do not are likely involved within this model, and meningococci didn't trigger a solid innate immune system response in the Calu-3 cells. Finally, we've shown that model would work for studying relationship of with various other bacteria surviving in the nasopharynx which is sent from individual to individual by aerosol droplets made by respiration, talking, or hacking and coughing or by immediate connection with a polluted fluid. The organic reservoir of may be the individual nasopharynx mucosa, located on the relative back again of the nose area and over the oropharynx. The means where meningococci combination the nasopharyngeal wall structure is certainly under issue still, because of the absence of another and convenient super model tiffany livingston mimicking the nasopharyngeal specific niche market. Here, we required advantage of Calu-3 cells produced in air interface culture to study how meningococci colonize the nasopharyngeal niche. We report that this airway mucus is usually both a niche for meningococcal growth and a protective barrier against contamination. As such, behaves like commensal bacteria and is unlikely to induce contamination without an external trigger. (meningococcus) is a Gram-negative bacterium that normally resides asymptomatically in the human nasopharynx. For unknown reasons, it may.
This entry was posted in Hydrogen, Potassium-ATPase on March 9, 2021 by bioxorio.
Planar cell polarity (PCP) requires the asymmetric sorting of unique signaling receptors to proximal and distal areas of polarized epithelial cells
Planar cell polarity (PCP) requires the asymmetric sorting of unique signaling receptors to proximal and distal areas of polarized epithelial cells. the proximal surface area of the polarized epithelial cell. DOI: http://dx.doi.org/10.7554/eLife.00160.001 which were proposed to supply long range patterning cues to modify PCP asymmetry (Bayly and Axelrod, 2011). Extra evidence shows that intracellular trafficking could also donate to the asymmetric localization of PCP signaling receptors (Shimada et al., 2006; Strutt and Strutt, 2008). Coat-protein-mediated cargo proteins sorting on the Golgi network (TGN) can be an important stage of biosynthetic trafficking and regulates concentrating on of a number of transmembrane cargoes with their last places (Rodriguez-Boulan et al., 2005). One of the known vesicle layer protein, clathrin adaptor complexes (AP) have already been proven to mediate sorting of varied transmembrane cargoes on the TGN by straight getting together with tyrosine- or dileucine-based sorting motifs localized inside the cytosolic domains of the transmembrane cargo molecule (Rodriguez-Boulan et al., 2005; Burgos et al., 2010). Lately, AP-1 has been proven to functionally connect to a book Golgi-export motif inside the tertiary framework of Kir2.1 route (Ma et al., 2011). Furthermore to APs, a fresh type of layer proteins complicated, exomer, regulates the transportation of Chs3p and Fus1p in the TGN towards the plasma membrane in candida (Wang et al., 2006; Barfield et al., 2009). Sorting of some soluble secretory cargo in the TGN requires the actin-severing protein ADF/cofilin and the Ca2+ATPase SPCA1 (von Blume et al., 2009, 2011; Curwin et al., 2012). Assembly of coating protein complexes on membranes is initiated by Arf or Arf-like small GTPases that switch between GDP- and GTP-bound Lomustine (CeeNU) claims. Upon GTP binding, Arf proteins expose an N-terminal myristoyl group attached to an amphipathic helix which mediates membrane recruitment and induces membrane curvature (Lee et CSPB al., 2004, 2005; Bielli et al., 2005; Beck et al., 2008). GTP-binding also causes a conformational switch in the switch website of Arf proteins which promotes the membrane recruitment of cytosolic effectors, including coating proteins and lipid changes enzymes (Gillingham and Munro, 2007; Donaldson and Jackson, 2011). Mammalian cells possess 6 Arf proteins and more than 20 Arf-like proteins. The intracellular tasks of the majority of Arf proteins are poorly recognized. A genome-wide RNA interference screen shows that Arf1 and Arfrp1 are required for secretion of recombinant luciferase from S2 cells (Wendler et al., 2010). Arf1 regulates the membrane recruitment of various proteins including coats such as COPI, APs, GGAs and the lipid changes enzymes, phospholipase D and PtdIns 4-kinase (Donaldson and Jackson, 2011). Arfrp1 is essential for survival and has been shown to mediate the trafficking of VSVG, E-cadherin and the glucose transporters GLUT4 and GLUT2 as well as to regulate lipid droplet growth (Shin et al., 2005; Zahn et al., 2008; Nishimoto-Morita et al., 2009; Hesse et al., 2010; Hommel et al., 2010; Hesse et al., 2012) but the molecular mechanisms underlying its intracellular function are unfamiliar. Given the asymmetric distribution of PCP signaling molecules on the surface of epithelial cells, unique sorting or coating protein complexes may be required for their traffic from your TGN. In this study, we focused on identifying the Lomustine (CeeNU) Lomustine (CeeNU) coating proteins that mediate TGN export of a conserved four-transmembrane PCP signaling receptor, Vangl2. In homolog of Vangl2, causes problems in the organization of wing hairs and induces problems in the orientation of attention ommatidia (Taylor et al., 1998; Wolff and Rubin, 1998). In vertebrates, Vangl2 regulates Lomustine (CeeNU) convergent extension (Torban et al., 2004). Mouse Vangl2 looptail mutants, which are defective in ER export, cause severe problems in neural tube closure and disrupt the orientation of stereociliary bundles in mouse cochlea (Kibar et al., 2001a, 2001b; Montcouquiol et al., 2003; Merte et al., 2010). To explore the coating proteins that mediate TGN export of Vangl2, we started by screening the effects on Vangl2 trafficking upon siRNA knockdown of selected Golgi-localized Arf proteins. Our analysis signifies that Arfrp1 regulates TGN export of Vangl2. We discover that AP-1 can be an effector of Arfrp1 which both interact to modify TGN export of Vangl2. Oddly enough, TGN export of 1 various other PCP signaling receptor, Frizzled-6, is normally in addition to the Arfrp1/AP-1 Lomustine (CeeNU) equipment, recommending that differential sorting machineries regulate the TGN export of Frizzled and Vangl2 6, which may donate to their opposing localization over the epithelial cell surface area. Outcomes Knockdown of Arfrp1 accumulates Vangl2 on the TGN To recognize the Arf protein that regulate TGN export of Vangl2, we performed an siRNA knockdown display screen focusing on chosen Golgi-localized Arf protein in HeLa cells stably expressing HA-Vangl2. The display screen indicated that knockdown of Arf1 or Arfrp1 triggered a juxtanuclear accumulation of Vangl2 whereas knockdown of various other Golgi-localized.
This entry was posted in H1 Receptors on March 9, 2021 by bioxorio.
Supplementary MaterialsFigure S1: Appearance levels of endogenous and transfected myc-SNX17 in control and SNX17 silenced cells
Supplementary MaterialsFigure S1: Appearance levels of endogenous and transfected myc-SNX17 in control and SNX17 silenced cells. E, in which the part of SNX17 in the levels of ApoER2-CTF was identified.(TIF) pone.0093672.s001.tif (433K) GUID:?1B6DCDEB-BA28-48BC-9C50-F17CCDA3624B Number S2: SNX17 knockdown does not alter ApoER2 introduction to the early endosome. HeLa pLKO and SNX17 silenced clones were transfected with HA-ApoER2, RAP, and GFP-Rab5. Cells were incubated with anti-HA antibody for 1 h at 4C and then shifted to 37C for 10 min to allow for receptor internalization. After this Mollugin period of time, the antibody remaining at the surface was eliminated by acid wash. Cells were washed, permeabilized, and incubated with Alexa 594-conjugated goat anti-mouse IgG. Images were captured by confocal microscopy, and Mander's colocalization index and Pearson's coefficient were determined in 10 cells for each condition. Bars, 10 m.(TIF) pone.0093672.s002.tif (1.2M) GUID:?9F54322C-E369-4EA7-B886-1CA6AFB47FBE Number S3: The activity of -secretase is not revised in cells with reduced levels of SNX17. Control (pLKO) or SNX17 knockdown N2a cells expressing ApoER2 were lysed in CHAPSO buffer. Measurement of -secretase activity was performed using a fluorogenic substrate assay, which is based on the secretase-dependent cleavage of the -secretase-specific substrate conjugated using a fluorescent molecule.(TIF) pone.0093672.s003.tif (170K) GUID:?4BA1DCBA-9402-4716-A010-680FA768BB48 Figure S4: SNX17 knockdown in neurons. Mouse dissociated cortical neurons had been transfected at DIV Mollugin 5 with GFP as well as the matching shRNA plasmid. After 48 h, cells were analyzed and fixed by immunofluorescence using an anti-SNX17 antibody. The figure implies that when cells are positive for GFP, they're negative for SNX17 within the neurons transfected with SNX17 shRNA also.(TIF) pone.0093672.s004.tif (4.2M) GUID:?4651FF02-2F70-4FB1-8A96-3328D2186DD9 Figure S5: SNX17 knockdown alters the quantity and amount of dendrites induced by reelin. Mouse dissociated hippocampal neurons had been transfected with GFP appearance plasmid as well as the matching shRNA, plasmid. After three times, the neurons had been treated with reelin for 3 times, fixed, and examined by immunofluorescence. Pictures had been captured by confocal microscopy. Quantitative evaluation of the distance and amount of principal and supplementary dendrites was performed by causing specific tracings and utilizing the Neuron J plugin. The measures of principal and supplementary neurites had been decreased upon reelin treatment in SNX17 knockdown neurons considerably, whereas only supplementary neurites had been reduced in quantity within the silenced neurons. *p 0.05; **p 0.01.(TIF) pone.0093672.s005.tif (443K) GUID:?D5E93BA9-CF8A-42B3-B8F7-A5FEA75320DB Strategies S1: SNX17 silencing in neurons. A total of 1105 mouse dissociated cortical neurons Mollugin were transfected at DIV 4 with GFP and the corresponding shRNA plasmid (0.3 g each) using Lipofectamine 2000. After 3 days, the cells were fixed with 4% PFA and 4% sucrose for 20 min and processed for immunofluorescence with a rabbit anti-SNX17 (1250). Later cells were stained with an Alexa 555-conjugated anti-rabbit antibody. Images of individual cells were captured with an inverted LSM 510 Zeiss microscope with a 63 X oil immersion lens, and images were analyzed using ImageJ software.(DOCX) pone.0093672.s006.docx (11K) GUID:?DB4AB492-1A31-45F5-93BD-55950B91F174 Abstract ApoER2 is a member of the low density-lipoprotein receptor (LDL-R) family. As a receptor for reelin, ApoER2 participates in neuronal migration during development as well as synaptic plasticity and survival in the adult brain. A previous yeast two-hybrid screen showed that ApoER2 is a binding partner of sorting nexin 17 (SNX17) – a cytosolic adaptor protein that regulates the trafficking of several membrane proteins IGFBP3 in the endosomal pathway, including LRP1, P-selectin and integrins. However, no further studies have been performed to investigate the role of SNX17 in ApoER2 trafficking and function. In this study, we present evidence based on GST pull-down and inmunoprecipitation assays that the cytoplasmic NPxY endocytosis motif of ApoER2 interacts with the FERM domain of SNX17. SNX17 stimulates ApoER2 recycling in different cell lines including neurons without affecting its endocytic rate and also facilitates the transport of ApoER2 from the early endosomes to the recycling endosomes. The reduction of SNX17 was.
This entry was posted in Hydroxylase, 11-?? on March 8, 2021 by bioxorio.
Data Availability StatementAll data can be obtained and will end up being shared upon demand readily
Data Availability StatementAll data can be obtained and will end up being shared upon demand readily. towards the uncontrollable development in cancer. This review shall compare the mechanisms that drive both cancer progression and placental development. Specifically, this review shall concentrate on the molecular systems that promote cell proliferation, evasion of apoptosis, cell invasion, and angiogenesis. was bought at its highest amounts in early gestational placental tissues whereas was at its highest amounts between 35 and 40?weeks [43]. The writers of this research concluded that within the placenta is vital for cytotrophoblast cell proliferation while most likely is important in terminal differentiation. This conclusion is at least partially supported by another obtaining using stimulation by epidermal growth factor (EGF) to induce differentiation of human primary cytotrophoblast cells towards syncytiotrophoblast fate. Cells were treated with EGF for 40?min pulses and, while both c-jun and jun-B mRNA levels rapidly increased 2C4?h after exposure, EGFs effects on jun-B were the most striking. Jun-B was significantly increased in cytotrophoblast cells differentiating towards syncytiotrophoblast lineage, indicating that EGF and its activation of jun-B is important in the terminal differentiation of cytotrophoblast E3 ligase Ligand 10 cells [44]. Interestingly, the hormone adiponectin has also been implicated as an important regulator for the JUN kinase pathway, with a particular emphasis on c-jun regulation. In normal placentas, adiponectin has an antiproliferative effect. However, in gestation diabetes mellitus (GDM) placentas, adiponectin levels are decreased with an increase in cell proliferation, potentially thought to be a contributor to the macrosomia seen in GDM babies. To test whether adiponectin actually inhibits c-Jun in GDM placentas, the choriocarcinoma cell line, BeWo, was treated with high levels of glucose. These high glucose treated cells had significantly lower levels of adiponectin, leading to increased c-Jun protein and increased cell proliferation. Furthermore, addition of adiponectin to high glucose treated cells inhibited c-Jun activation, suppressing cell proliferation [45]. There are also several oncofetal proteins outside of the family of growth factors that promote cell proliferation. For example, our laboratory studies the LIN28-let7-HMGA2 molecular axis. LIN28 is an RNA binding protein considered to be a key molecular factor that regulates the transition from a pluripotent, highly proliferative state to a terminally differentiated cell [46]. One of the main targets of LIN28 is the let-7 family of miRNAs. When cells are highly proliferative, LIN28 negatively regulates the let-7 family. However, as cells commence to differentiate the allow-7 category of miRNAs is certainly upregulated and will bind towards the 3 UTR of to inhibit its translation into proteins [47]. Because of this harmful reviews loop, LIN28 as well as the allow-7?s are inversely expressed in lots of malignancies [48] often. Furthermore, elevated LIN28 continues to be correlated with aggressive cancers and poor prognosis [49] highly. The allow-7?s control other oncofetal protein including HMGA2 E3 ligase Ligand 10 also, c-Myc, RAS, and VEGF [49]. In placental cells, a knockdown of LIN28A resulted in spontaneous syncytialization and differentiation in individual trophoblast cells [50]. Furthermore, knockdown of LIN28B and knockout of both LIN28A and LIN28B results in trophoblast cells which are powered to differentiate towards just the syncytiotrophoblast lineage, however, not extravillous trophoblast cells [51]. These data claim that Collectively, much like pluripotent cells, LIN28 can be an necessary gatekeeper in trophoblast cell differentiation and proliferation. Cell survival The capability to bypass apoptosis is certainly another hallmark of cancers and is vital during placentation. Once again, the development receptor and receptors tyrosine kinase pathways mentioned previously play a significant function in cell success, iGF-1 E3 ligase Ligand 10 and IGF-2 binding to IGF-1R [38 particularly, 52].The Fgfr1 partnership between IGF-1R as well as the E3 ligase Ligand 10 PI3K/Akt and MAPK pathways has been explained as.
This entry was posted in Heat Shock Protein 70 on March 6, 2021 by bioxorio.
Metastatic cancer cells generally can't be eradicated using traditional medical or chemoradiotherapeutic strategies, and disease recurrence is extremely common following treatment
Metastatic cancer cells generally can't be eradicated using traditional medical or chemoradiotherapeutic strategies, and disease recurrence is extremely common following treatment. stem cells to treat human cancers appears technically feasible, challenges such as treatment durability and tumorigenesis necessitate further study to improve therapeutic performance and applicability. This review focuses on recent progress toward stem cell-based cancer treatments, and summarizes treatment advantages, opportunities, and shortcomings, potentially helping to refine future trials and facilitate the translation from experimental to clinical studies. and, like NSCs, are applied widely in the treatment of different cancers. HSCs HSCs, the most primitive of the blood lineage cells, are predominantly found in bone marrow, and produce mature blood cells through proliferation and differentiation of increasingly lineage-restricted progenitors. Transplantation of HSCs has been employed clinically for over four decades. EPCs EPCs are the primary drivers of vascular regeneration [10]. Asahara, suggest potential utility for EPCs in cancer therapy, following transfection or coupling with antitumor drugs or angiogenesis inhibitors [11]. However, recent advances have shifted the focus to EPC roles in disease pathogenesis and potential benefits as part of therapeutic interventions [10]. Reports on EPCs in cancer therapy are rare. CSCs Based on cell surface markers, CSCs, a stem-like cancer cell subpopulation, are isolated from patient cell and tissues lines of different cancer types. CSCs communicate stemness genes, self-renew, differentiate into additional non-stem tumor cells, and withstand traditional cancer remedies [3]. CSCs most likely initiate many tumor types. Traditional tumor therapies can destroy non-stem tumor cells, but cannot get rid of CSCs. Tumors relapse once the remaining CSCs proliferate and differentiate usually. Therefore, focusing on CSCs may resolve clinical issues like drug resistance and recurrence [12]. STEM CELL PROPERTIES In addition to their self-renewal and differentiation capabilities, stem cells have immunosuppressive, antitumor, and migratory properties. Because stem cells express growth factors and cytokines that regulate host innate and cellular immune pathways [13, 14], they could be manipulated to both get away the host immune act and response as cellular delivery agents. Stem cells can magic formula elements also, such as for example CCL2/MCP-1, and connect to tumor cells literally, changing co-cultured tumor cell phenotypes and exerting intrinsic antitumor results [15]. Significantly, many human Limaprost being stem cells possess intrinsic tumor-tropic properties that result from chemokine-cancer cell relationships. Stem cells 1st exhibited migratory features in xenograft mouse versions, manifested as tumor-homing capabilities [16]. Feasible stem cell migration mechanisms have already been analyzed. NSC migration to tumor foci can be set off by hypoxia, which activates manifestation of chemoattractants [6]. Directional HSC migration depends upon the discussion between chemokine, CXCL12, and its own receptor, CXCR4 [17]. A number of MSC-expressed chemokine and development element receptors may participate in tumor homing [18]. The stromal cell-derived factor 1 (SDF1)/CXCR4 axis plays a major role in the migration of various stem cells [19C21]. To improve directed homing, stem cells have been engineered with higher levels of chemokine receptors, or target tissues have been manipulated to release more chemokines [22]. Park, et al. reported that CXCR4-overexpressing MSCs migrated toward glioma cells more effectively than control MSCs and in a xenografted mouse model of human glioma [20]. Controlled release of a chemokine from various biomaterials enhances recruitment of stem cells towards them. Schantz et al. achieved site-specific homing of MSCs toward a cellular polycaprolactone scaffold, which was constantly releasing SDF-1 with micro delivery device [23]. Thus, these two strategies can be combined to increase homing efficiency and improve treatment outcomes. STEM CELL MODIFICATIONS FOR CANCER THERAPY Stem cells, most commonly NSCs and MSCs, can be modified via multiple mechanisms for potential use in cancer therapies. Common modifications include the therapeutic enzyme/prodrug system, and nanoparticle or oncolytic pathogen delivery in the tumor site. Enzyme/prodrug therapy MSCs and NSCs could be engineered expressing enzymes that convert non-toxic prodrugs into cytotoxic items. When customized stem cells are transplanted into tumor-bearing versions, they localize to tumor cells, where in fact the exogenous enzyme changes the prodrug right into a cytotoxic molecule, harming the tumor cells ultimately. As a total result, the total amount, timing, and area of medication discharge could be controlled. Enzyme/prodrug therapy is named suicide gene therapy, and was the initial engineered NSC healing application and KITH_HHV1 antibody the first ever to enter clinical studies [16, 24]. Cytosine deaminase (Compact disc) is a significant enzyme currently found in enzyme/prodrug therapy. Compact disc changes the prodrug, 5-fluorocytosine (5-FC), in to Limaprost the poisonous variant, 5-fluorouracil. Aboody, reported the fact that mix of CD-bearing mouse NSCs and 5-FC inhibited glioblastoma (GBM) cell development [16]. Limaprost Injecting CD-expressing MSCs in to the human brain with 5-FC suppressed tumor growth [25] also. In another of probably the most utilized cytotoxic remedies frequently, individual HB1.F3 cells are engineered expressing CD (HB1.F3.Compact disc) [26]. With excellent protection and efficiency, HB1.F3.Compact disc/5-FC therapy was recently used in the initial individual scientific trial (ClinicalTrials.gov identifier: "type":"clinical-trial","attrs":"text message":"NCT01172964″,"term_identification":"NCT01172964″NCT01172964), where HB1.F3.CD cells were injected into the cavity wall following.
This entry was posted in hERG Channels on March 6, 2021 by bioxorio.
Supplementary MaterialsS1 Fig: Summary of K5 capsule biosynthesis in Nissle 1917 based on data from Cress strains generating Group 2 polysaccharide capsules
Supplementary MaterialsS1 Fig: Summary of K5 capsule biosynthesis in Nissle 1917 based on data from Cress strains generating Group 2 polysaccharide capsules. S2 Table: Primers used in this study. (PDF) pone.0120430.s003.pdf (91K) GUID:?D286FDE6-E5C4-45F2-96A3-E49DCEFEF0AD Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract Nissle 1917 (EcN) is among the best characterised probiotics, with a proven clinical impact in a range of conditions. Despite this, the mechanisms underlying these "probiotic effects" are not clearly defined. Here we applied random transposon mutagenesis to recognize genes highly relevant to the relationship of EcN with intestinal epithelial cells. This confirmed mutants disrupted within the gene, from the K5 capsule biosynthesis cluster, to become enhanced in attachment to Caco-2 cells considerably. Nevertheless, this phenotype was distinctive from that previously reported for EcN K5 lacking mutants (null mutants), prompting us to explore additional the function of in EcN:Caco-2 relationship. Isogenic mutants with deletions in (EcN(EcNand the EcN wild-type, EcNexhibited significantly higher attachment to Caco-2 cells, as well as apoptotic and cytotoxic effects. In contrast, EcNwas comparable to the wild-type in these assays, but was shown to induce significantly higher COX-2 manifestation Orphenadrine citrate in Caco-2 cells. Distinct differences were also apparent in the pervading cell morphology and cellular aggregation between mutants. Overall, these observations reinforce the importance of the EcN K5 capsule in host-EcN relationships, but demonstrate that loss of unique genes in the K5 pathway can modulate the effect of EcN on epithelial cell health. Intro Due to the romantic part of the gut microbiome in human being health and disease processes, this mainly bacterial community is definitely increasingly considered an important target for the development of novel approaches to diagnose, prevent, or treat a wide range of disorders [1C4]. With this context, probiotics are among the most encouraging tools for manipulation of Orphenadrine citrate the gut microbiome, and have been defined as live microorganisms which when given in adequate amounts confer a health benefit over the web host [5]. Nearly all probiotics are Gram-positive bacterial types, and considerable proof is accumulating concerning the efficacy of the organisms in dealing with or preventing a number of gastrointestinal (GI) illnesses, and in addition extra-intestinal disorders [1C4] potentially. One of the probiotics obtainable presently, Nissle 1917 (EcN; serotype O6:K5:H1) is normally of particular curiosity. Not only is normally this one of the very most thoroughly characterized probiotic microorganisms (with regards to phenotype, genotype, and scientific efficacy), but may be the just Gram-negative types used [6] currently. EcN was initially isolated in the faeces of a worldwide globe Battle I soldier who, as opposed to comrades in his trench, had not been BMP7 suffering from an outbreak of dysentery [7]. This gastroprotective stress is the energetic element of Mutaflor (Ardeypharm GmbH, Herdecke, Germany), a microbial medication that's used and marketed in a number of countries. Clinical trials show EcN to work for preserving remission of ulcerative colitis (UC) [8C11], arousal from the disease fighting capability in premature newborns [12], treatment of infectious diarrhoea [13], and security of individual intestinal epithelial cells (IECs) against pathogens [14, 15]. These benefits are related to the immuno-modulatory results elicited by EcN generally, which encompass both adaptive and innate components of the disease fighting capability. For instance, colonisation with EcN continues to be indicated to improve the web host cytokine profile, and chemokine creation in cultured IECs [16C19] also; stimulate the production of mucosal peptide centered defences [20]; influence the clonal development of T-Cell populations, and modulate antibody reactions [12, 21, 22]. Notably, the modulation of T-cell functions mediated by EcN may also lengthen to T-cells, potentially enabling EcN to coordinate modulation of both innate and adaptive reactions [22]. EcN has also been indicated to alter Orphenadrine citrate COX-2 manifestation in intestinal epithelial cells [23], which is an important target in the treatment or prevention of several GI diseases including IBD and colorectal malignancy [24C27]. Although most closely related to uropathogenic strains of (UPEC), EcN is considered non-pathogenic. Genomic characterisation offers highlighted the absence of genes encoding the typical.
This entry was posted in HGFR on March 5, 2021 by bioxorio.
Data Availability StatementThe organic data helping the conclusions of the content will be made available with the writers, without undue booking
Data Availability StatementThe organic data helping the conclusions of the content will be made available with the writers, without undue booking. clinical part, bloodstream for CTC isolation was attracted from 44 sufferers with early and locally advanced breasts cancer ahead of neoadjuvant chemotherapy. Regular Giemsa, Pancytokeratin and Papanicolaou staining was applied. 2.3% of examples contained cells that meet both morphological and immunocytochemical criteria for CTC. In 32.6% of examples, partially degenerated pancytokeratin negative cells with morphological top features of tumor cells were observed. In 65.1% of examples, CTCs weren't found. To conclude, our outcomes demonstrate that unchanged tumor cells could be isolated using MACS technology morphologically. However, morphologically unchanged tumor cells weren't discovered within the medical part of the study. At present, MACS technology does not appear suitable for use in a medical cytopathology laboratory. = 43= 0.092). CTCs were detected more often in HER2 positive individuals than in HER2 bad individuals (50% vs. 28%), but this correlation was not statistically significant (Pearsons Hi-square = 0.148). There was no correlation between age, histology, grade, hormone receptor status, tumor stage, nodal involvement and the presence of CTCs. In 34 individuals treated with neoadjuvant chemotherapy, pCR in the breast was accomplished in 35% of CTC positive and in and 40% of CTC bad samples. In addition, pCR in the lymph nodes was observed GIBH-130 in 50% of CTC positive and CTC bad samples. The presence of CTCs after neoadjuvant chemotherapy was not evaluated. Conversation This study aimed to evaluate the feasibility of the MACS technology for CTC isolation and subsequent cytopathological exam in the routine cytopathological laboratory establishing in early breast cancer. The present study is one of the few published studies within the morphology of breast cancer GIBH-130 GIBH-130 CTCs. It is also one of the few published studies using standard cytopathological techniques for CTC preparation and morphological analysis using light microscopy. The results of this study display that GIBH-130 MACS technology preserves the morphology of breast malignancy cells from MCF7 cell collection, however, this was not observed in CTCs from breast cancer individuals. Based GIBH-130 on the findings of this study, we believe isolation with MACS technology followed by preparation of standard cytological slides is at present not yet suitable for routine CTC diagnostics in early breast cancer individuals. In clinical tests looking at the overall performance of CTC isolation methods by spiking cultured tumor cells to whole blood or peripheral blood mononuclear cell suspensions, the preservation of morphology was usually examined using fluorescent microscopy, assessing fundamental features, such as cell size and N/C percentage (3). In the present study, standard light microscopy was used for such exam. The MCF7 cell collection was chosen as it is definitely canonical for breast cancer and the most commonly used breast cancer cell collection in the literature (48, 49), and because our cytopathological lab provides vast knowledge using its light and planning microscopy evaluation. The sensitivity in our technique as investigated within the preclinical area of the research was found to become lower as previously reported. The recovery prices for positive selection-based isolation strategies attained by spiking cultured breasts cancer tumor cells into entire peripheral blood range between 60 to GDNF 100% (50C52). Among the initial studies analyzing the functionality of immunomagnetic parting using breasts cancer tumor cell lines and spiking 1000, 100, and 10 cells discovered a 75% recovery price, which is greater than the recovery price reported in today's research (34%) (53). Although comprehensive washing to avoid potential cell reduction was applied, the non-automated handling of samples inside our protocol may have led to significant cell reduction. Furthermore, the producers protocol is normally optimized for entire blood examples, which means lower sensitivity may be attributed to the usage of diluted BC examples in preclinical section of this research. Unfortunately, we didn't plan to get whole blood examples from healthful volunteers. The primary challenge we encountered throughout this research was the id of cells that exhibited morphological top features of malignancy while staining detrimental for CK. The criteria that were used to label the study samples were based on the presence of atypical morphology and CK positivity, similar to the criteria used by Tsutsuyama et al. (54). We.
This entry was posted in Human Ether-A-Go-Go Related Gene Channels on March 5, 2021 by bioxorio.
Data Availability StatementAll writers make sure that all data generated or analyzed in this research are one of them published content (and its own supplementary information data files)
Data Availability StatementAll writers make sure that all data generated or analyzed in this research are one of them published content (and its own supplementary information data files). Methods Individual non-small cell lung cancers (NSCLC) cell lines (Computer9, Computer9/gef, A549, and H1975) with different EGFR statuses had TAK-715 been examined by cytotoxicity and proliferation assays after AC-93253 iodide TAK-715 treatment. Src and Src-related proteins appearance in AC-93253 iodide-treated Computer9, Computer9/gef, and A549 cells had been assessed by traditional western blotting. The consequences of AC-93253 iodide on cancers cell colony formation, invasion, and migration had been assessed in Computer9 and PC9/gef cells. The synergistic effects of gefitinib and AC-93253 iodide were evaluated by combination index (CI)-isobologram analysis in gefitinib-resistant cell lines. The efficacy of AC-93253 iodide in vivo was decided using nude mice treated with either the compound or the vehicle. Results Among the compounds, AC-93253 iodide exhibited the most potent dose-independent inhibitory effects on the activity of Src as well as on that of the Src-related proteins EGFR, STAT3, and FAK. Furthermore, AC-93253 iodide significantly suppressed malignancy cell proliferation, colony formation, invasion, and migration in vitro and tumor growth in vivo. AC-93253 iodide sensitized tumor cells to gefitinib treatment regardless of whether the cells were gefitinib-sensitive (PC9) or resistant (H1975 and PC9/gef), indicating that it may exert synergistic effects when used in combination with established therapeutic brokers. Our findings also suggested that this inhibitory effects of AC-93253 iodide on lung malignancy progression may be attributable to its ability to modulate multiple proteins, including Src, PI3K, JNK, Paxillin, p130cas, MEK, ERK, and EGFR. Conclusions Our data suggest that AC-93253 iodide inhibits NSCLC cell growth and motility by regulating multiple Src-related pathways. Our findings may facilitate the development of therapeutic strategies and anti-tumor drugs that may be useful for treating lung malignancy in the future. Electronic supplementary material The online edition of this content (10.1186/s13045-017-0539-3) contains supplementary materials, which is open to authorized users. lab tests or ANOVA (Excel; Microsoft) had been performed to look for the need for the distinctions between groups. beliefs ?0.05 were considered significant statistically. Results Virtual screening process of potential applicant substances in the LOPAC collection Src activity depends upon TAK-715 its phosphorylation condition in addition to by proteinCprotein connections on its SH2 and SH3 domains [25]. The phosphorylation takes place and the proteins connections initiate at tyrosine 418 [26]. You'll be able to inhibit Src appearance and stop lung cancers development by regulating the actions that take place at the website. The structures from the chemical compounds within the LOPAC collection, which comprises 1280 medications, had been docked in to the Src tyrosine 418 site with the LibDock process of Discovery Studio room v3.5, as well as the LibDock interaction and rating force had been calculated in line with the docking poses from the compounds. The interaction drive was adopted because the testing criterion to recognize applicant Src-modulating substances. We ultimately find the 15 substances predicted to really have the most powerful connections with Src, as dependant on the virtual screening process process, as applicant substances, which we tagged L1 to L15 (Extra?file?1: Desk S1). These candidate materials were put through additional screening in following natural Mouse monoclonal to PRDM1 analyses then. During the preliminary screening process, the lung cancers Computer9 cell series was treated with applicant substances at a focus of 10?M for 24?h, and the cell lysates were used to research Src phosphorylation. Dasatinib was utilized as a confident control. The outcomes from the test demonstrated that L1, L3, L4, L10, L13, and L14 could inhibit Src activity (Additional file 1: Number S1). Among these compounds, L3, L4, L10, and L14 were selected for more experiments, in which their inhibitory effects on Src and EGFR activity in the H358 and Personal computer9 cell lines were assessed. The results of those experiments showed that L10 could significantly suppress Src and EGFR phosphorylation in both cell lines (Fig.?1a) and that L10 exhibited moderate inhibitory effects on Src manifestation in both cell lines and significant inhibitory effects on EGFR manifestation in the Personal computer9 cell collection. Thus, substance L10, i.e., AC-93253 iodide, was chosen for subsequent tests designed to investigate the systems root its inhibitory results over the phosphorylation and appearance of Src in addition to those of related signaling effectors needed for tumor cell development and motility. Open up in another window Fig. 1 Ramifications of the applicant materials on EGFR and Src expression and cell viability in various cell lines. a Src and EGFR phosphorylation and appearance in H358 and Computer9 cells treated using the applicant substances for 24?h and analyzed by traditional western blotting. Veh (automobile).
This entry was posted in Hydrolases on March 4, 2021 by bioxorio.


text:
Q: Convertings mills to hh mm ss import java.util.Scanner;

public class Mills {

    public static void main(String[] args) {

    Scanner sc = new Scanner(System.in);

    System.out.println("Enter milliseconds");
    long mills= sc.nextLong();

    System.out.println(convertMillis(mills));

    }

    public static String convertMillis(long millis){

        long s = (millis / 1000) % 60;
        long m = (millis / (1000 * 60)) % 60;
        long h = (millis / (1000 * 60 * 60)) % 24;
        String time = String.format("%02d:%02d:%02d:%d",s,m,h);
        return time;
    }
}

I am stuck, I don't know what to do after.
Exception in thread "main" java.util.MissingFormatArgumentException: Format specifier 'd'
    at java.util.Formatter.format(Unknown Source)
    at java.util.Formatter.format(Unknown Source)
    at java.lang.String.format(Unknown Source)
    at Mills.convertMillis(Mills.java:19)
    at Mills.main(Mills.java:10)

A: You have 4 %d in the String.format() but only 3 values. Remove the last %d or add another value.
String time = String.format("%02d:%02d:%02d", s, m, h); // remove a %d

or
String time = String.format("%02d:%02d:%02d:%d", s, m, h, anotherVal); // add another value

A: You should not have to do this all together!! Just use SimpleDateFormat class Like this:
    long millis = 0;
    Calendar c = Calendar.getInstance();
    c.setTimeInMillis(millis);
    SimpleDateFormat sdf = new SimpleDateFormat("hh:mm:ss");
    System.out.println(sdf.format(c.getTime()));

Just replace the 0 with your millis.

A: You have 4 "%d"s in the format string but provide only 3 arguments... Try removing the last %d
public static String convertMillis(long millis){

    long s = (millis / 1000) % 60;
    long m = (millis / (1000 * 60)) % 60;
    long h = (millis / (1000 * 60 * 60)) % 24;
    String time = String.format("%02d:%02d:%02d",s,m,h);
    return time;
}

redpajama_set_name: RedPajamaStackExchange


text:
Sayuri-san no Imouto wa Tenshi (小百合さんの妹は天使, en español: La hermanita de Sayuri es un ángel) es un manga japonés escrito e ilustrado por Hachi Itou. Fue publicado desde agosto de 2014 hasta julio de 2016 en la revista Monthly Comic Flapper de la editorial Kadokawa Shoten (KADOKAWA).

Es una comedia yuri que retrata el reencuentro de dos hermanas que permanecieron separadas por 13 años.

Sinopsis
Por causa del divorcio de sus padres hace 13 años, Sayuri  vivió con el corazón cerrado y sin recibir el amor de nadie. Mikoto, su hermana menor quien se fue con su padre, y es su única preocupación, aparece ante ella para su encuentro 13 años después, ahora con 17, luciendo una aureola y un par de alas. La menor, empieza a convivir con ella en la misma casa y le expresa su afecto diciéndole: "Yo quiero ser tu amor".

Personajes
Sayuri Kobayashi (小林小百合/Kobayashi Sayuri)

Es la protagonista, de 27 años de ella. Trabaja en una floristería. 13 años atrás, el momento en que se divorciaron sus padres, se quedó viviendo con su madre (su padre la abandonó),  permaneció viviendo con el corazón cerrado al no recibir el amor de nadie.

Mientras convive junto a su hermanita Mikoto, con quien tuvo su reencuentro, va abriendo su corazón de forma gradual.

Mikoto Kobayashi (小林美琴/Kobayashi Mikoto)

La co-protagonista de la obra, de 17 años de edad. Asiste a la secundaria.

Vivió con su padres tras el divorcio, pero aparece de manera súbita ante Sayuri y comienzan a convivir juntas.

Ella ama a Sayuri y siempre le expresa todo su cariño diciéndole frases como: "Yo quiero ser tu amor".

Viste una aureola y un par de alas. Gente como Sayuri y Yūki son las únicas que la pueden ver.

Yūki Oga (男鹿ゆうき/Yūki Oga)

Cursa el 2.º año de universidad, comenzó a laborar junto a Sayuri en la misma floristería como trabajo de medio tiempo.

Es mujer, pero suele ser confundida con un varón por su galante aparencia varonil.

A pesar de que le encantan las cosas bonitas (entre ellas, las lesbianas), considera que eso no va con ella.

Himeko Yamamoto (山本姫子/Yamamoto Himeko)

Tiene 17 años y asiste a la misma escuela que Mikoto.

Le fascinan las cosas adorables como las cintas, los lazos y los tartanes.

Al fijarse en Oga, le miente a sus amigas diciéndoles que tiene un novio, y por dicha mentira, le pide a ella que sea su pareja.

Chihiro Kusanagi (草薙ちひろ/Kusanagi Chihiro)

Tiene 28 años de edad, trabaja como fotógrafa freelance.

Información bibliográfica

 Hachi Itou (Sayuri-san no Imouto wa Tenshi) Kadokawa Shoten (Monthly Comic Flapper), 4 tomos.

Bibilografía

Fuente

Historietas de 2014

Anime y manga yuri

redpajama_set_name: RedPajamaWikipedia


Now, we've posted some of the pictures we showed in the slideshow below Jubilee racetrack 2007 subtab "Gallery". Is this a picture of you or a relative to you that you do not want that we show on the website, Mail webmaster@hotingtravet.com and we will remove it!
Do you have a picture you would like that we publish on our website? Mail it to webmaster@hotingtravet.com so maybe we can outsource it!


text:
Eddie Jaywade heading to Hitachi KTM fuelled by Milwaukee?
Febvre: It's time to move on to a new challenge
Romain Febvre has spent the past five years with the Factory Yamaha team contesting the MXGP World Championship.
The French rider has had a great time with the team even winning the MXGP World Championship as a rookie in 2015.
However, it's been announced that Febvre will be leaving Yamaha at the end of the season.
"I have had some amazing times with Yamaha over the past five years, but now it's time to move on to a new challenge. Thanks Yamaha for believing in me in my rookie season! & also for the years after. I hope we can celebrate some more good times over the next four rounds and of course at the #MXoN. I had some good and bad moments since 2015 but always the people of Yamaha and my Team were there to support! Would like to give a huge thankful to Éric de Seynes, Paolo Pavesio, Erik Eggens, Alexandre Kowalski, Michele Rinaldi and all my team", Febvre commented.
In terms of his plans for 2020, we will have to wait until after the Motocross Des Nations for official news. The word in the paddock is that he'll be heading to Factory Kawasaki alongside Clement Desalle – news we reported back in July here.
"To my fans, unfortunately I can't share the news of my new plans until after the Motocross of Nations. I will let you know as soon as I can", added Febvre.
Pic: Yamaha

redpajama_set_name: RedPajamaCommonCrawl


The September/October issue of Poets & Writers magazine has a wonderful profile of Billy Collins. It doesn't seem to be available online but it's definitely worth checking out the next time you're in the bookstore.
for the one you are not holding in your hand.
but then everyone stopped thinking of him as wise.
Let us be clear about something.
on the wrong side of the bed wearing the emperor's clothes.
feels after it has defeated the sword.
that love is the early bird who is better late than never.
I was going to post the link to the article on Billy Collins here, but you're right, it's not available online-- anymore. I read the article online. I know because I saw the photos that are in the article before I received my issue of P & W. Odd that they would take it off, unless they expect the cover boy to sell a lot of magazines.
His book is already the #1 selling poetry book on Amazon, and the release is more than a week away!
Hi Mom Of 4, thank you for the link. Pretty cool that it's number one already! How funny that P&W had the article up and then took it down.
I am not familiar with Billy Collins although I have heard the name. Hmm. I'm not sure whether I like this piece. Maybe it's too long for me (I like 'em short or spoken). It would be a good poem for group analysis and discussion.
I don't buy P&W on a regular basis but when I saw this issue I HAD to get it! I can't wait until his new book comes out.
Hi Melissa, Most of his that I've read are on the long side so he may not be your cup of tea. Though he is supposed to give very good readings. I hope to see him if he comes through this way.
And Iliana, I got a discount on a subscription to P&W but I don't know if I'll renew it when it's up. Sometimes it just seems like a big catalog of MFA programs. But then they have a great article like this!
Poetry & music. Not always in that order.


I CANNOT believe it's 2018! 2017 was bitter sweet.I started a YouTube channel, changed careers, and tried to work outside of my comfort zone a lot more than I usually would. This year, I'm taking my blog to a new level and this year, I can bring you a lot more unfiltered and insightful content into my fashion journey down river.
So, I've had a lot of people ask me, what is my blog actually about (good question)? Did I finally settle down on what it's all about? I had many iterations but I'm finally settling on outdoors, fashion & beauty. Tag line? Sure, I have one – "High Fashion Down River," (thanks, Chan).
It's quirky, weird, and perfectly me. So, I hope you enjoy.
In Seattle, it's raining, but it must be sunny and not gloomy somewhere. This week, I'm talking about ruffles. While it started in the 16th century with mostly white people who were part of the bourgeois to make themselves look a giant saucer, it's a trend that never quite goes away. Queen Elizabeth wore it, so can I and everyone else who has access to Anthropology (thanks to modern day fast fashion).
So, what you think? Leave a comment and let me know!
Okay, one more exciting news – I thought of starting a brunch club for my YT friends out there (and bloggers are welcome). I love everything about brunch – friends, inappropriate jokes, and a sh*t ton of bacon. So, Want to join? Sign up right up hurr.


text:
Home/Entertainment/Sting forced to pen 'sorry' note to the family of a dead Italian vineyard duke
Sting forced to pen 'sorry' note to the family of a dead Italian vineyard duke
This is the sort of dispute that might well have been settled with a duel at dawn in a bygone era.
Holding the 'pistol' on one side stands Simone Velluti Zati, the Italian-born Duke of San Clemente.
The honour of his late father, he claims, has been impugned by a 'poisonous slander' that sees him accused of using underhand tactics to dupe an unsuspecting Englishman into buying his Tuscan estate.
Standing on the other side is his father's maligner, his pistol now shamefully lowered. He is a milkman's son from Newcastle called Gordon Matthew Thomas Sumner.
Or Sting as the frontman of The Police is better known.
The duke contends that since purchasing the property, Sting, the new 'Lord of the Manor', has spoken ill of his family's wine while turning the historic property into a 'Palm Beach-style resort' — complete with a yoga studio and pizza restaurant.
Sting has issued an unequivocal private apology to Simone Velluti Zati, the Italian-born Duke of San Clemente who claimed the honour of his late father was impugned by a 'poisonous slander' after the musician accused him of using underhand tactics to dupe him buying his Tuscan estate. Above: Sting with his wife Trudy Styler
'More than anything else, it's important to me to defend the legacy of my father,' the 46-year-old duke said in an impassioned conversation with the Daily Mail last night. 'My father did not deserve this.
He has been a very important man in many ways and touched many lives of people who still remember him today.'
Now the Mail can reveal that Sting has issued an unequivocal private apology for the 'great distress' caused to the former owners of his villa by his 'ironic' comments, after sparking a storm that shows no sign of abating.
A grovelling letter, signed simply 'Sting', on headed paper bearing the same name, says: 'You are right, I owe you an apology. The story as reported was disrespectful to the memory of your distinguished father and, for that, I offer my sincere and unequivocal apologies…
'I recognise and accept that this has caused you and your family great distress for which I am truly sorry. Please rest assured that this will not happen again.'
Yet the duke remains unsatisfied. He is demanding the apology be publicly placed on the villa's website and elsewhere.
But what on Earth did the singer do to raise the Italian aristocrat's hackles?
The story goes back to 1997 when Sting and his actress and TV producer wife Trudie Styler purchased the Villa Il Palagio from the current duke's father, who had the same name as his son, for a reported £3 million.
'We bought it for a song, maybe two songs, I'm not sure!' the 69-year-old singer once joked.
Since then, they have spent millions more expanding the estate and turning it into one of the region's most desirable boltholes.
Sting apologised for causing 'great distress to the former owners of his villa by his 'ironic' comments, after sparking a storm that shows no sign of abating
Today, the villa boasts nine bedrooms and eight bathrooms attended by a staff of 15.
Guests of the couple have included Band Aid supremo Sir Bob Geldof and U.S. actor Dustin Hoffman.
The addition of further annexes and guest houses mean that 50 people can now be accommodated — ideal for those rich enough to rent out the property for weddings.
Landscaped grounds provide plenty of ways to keep everyone occupied.
The estate boasts a life-size chessboard, a treehouse overlooking a lake, a chapel and a statue of Buddha, a fountain that once belonged to actress Sophia Loren, a tennis court and swimming pool.
Eco-friendly honey, virgin olive oil and, of course, wine are all produced on the 900-acre estate.
Having replanted the old vineyards, the estate now produces four of its own wines. A case of 2016 vintage 'Message in a Bottle' red costs £175.
'Il Palagio is more than a vacation home for Trudie and Sting,' the property's website reads. 'It is a passion.
And a sanctuary. It is where they have gone for years to find peace and return to a simpler way of life.'
Yet the contents of an interview Sting gave earlier this month to the Italian newspaper Corriere della Sera's magazine Sette disturbed that peace quite spectacularly.
In the article, the singer spoke about the wines he now produces and the guest houses he rents out. 'We had been looking for a house in Tuscany for years,' he said.
The story goes back to 1997 when Sting and his actress and TV producer wife Trudie Styler purchased the Villa Il Palagio from the current duke's father, who had the same name as his son, for a reported £3 million
Sting claimed that Duke Simone gave him a glass of wine that wasn't local when he ans his wife went to view the property. Above: Sting's own brand of wine
'We had seen places that were full of marble like mausoleums. Then we arrived at Il Palagio. It was run-down, but full of charm. It was 1997.
'From that moment, our new life in the countryside began.'
The singer described how they had renovated the villa. 'It was in bad condition,' he said. 'There was a lot to do. We even brought in electricity. Basically, the house had been neglected for a long time.'
Having completed the villa, the couple's attention turned to the grounds, with old vines uprooted and replanted.
Sting explained how he had been persuaded to buy the vineyard in the first place.
'The former owner, Duke Simone Vincenzo Velluti Zati di San Clemente, offered us a glass of red from a carafe during a visit to Il Palagio,' Sting recalled.
'We were negotiating the purchase — we liked the property very much even though it was almost in ruins.
'The duke asked me if I would like to taste some wine from the estate and I said 'yes'. It was an excellent wine, so he convinced me to buy the vineyards as well.
'Then we realised that the duke had served us a Barolo and not a local wine.'
It was this allegation of duplicity that lies at the heart of the current dispute.
Namely, instead of serving him a glass of locally-grown Chianti, the old duke had swapped it for a glass of much superior wine grown in the north of Italy.
Asked how Sting had worked out what had happened, he said: 'After a while, when we served our guests the estate wine, I saw that someone had emptied their glass into the flower beds.
'So we decided to 'take revenge' and to demonstrate that it was possible to produce excellent wine even from the Palagio vineyards.'
He added with a smile: 'Our whole Tuscan adventure is actually a way of getting our own back.'
Which did not go down at all well with the current duke's family. He has now insisted that Sting stop using his family's crest on his wine bottles.
'He bought the property, not the family,' he said.
'What is most surprising is that, given my father passed away in 2012, Sting had 15 years to make these accusations. Instead, he decided to speak ill of the dead.'
With representatives of the singer declining to comment further on the matter, it seemed that the perceived slight was set to fester further — despite the fact that, until recently, relations between the old and new owners of Il Palagio had been amicable.
Sting and his wife Trudie Styler Sting and wife Trudy Styler Celebrate their Sister Moon Red Wine, Il Palagio, in the Tuscan Hills
'My father sold the property in 1997 because the costs of maintaining it had become too high,' said the duke, who works as a wine consultant and now lives near Barcelona.
'Of course, he was not happy about it but it had to be done and I believe the price paid by Sting was fair.
'I was 21 at the time but did not meet him or speak to him but some family members did and had nothing negative to say.
'My father and mother were invited once to Palagio after the sale to have lunch with Sting and his wife and, again, had no negative comments about them.'
The claims contained within the interview were read by horrified friends and family of the old duke.
'My initial reaction was of shock and then of anger,' his son said.
'To see my father's name in an Italian paper linked to a story which spoke of a personal vendetta by Sting for having been cheated on buying the property and vineyards made me feel a deep sense of injustice.
'Also, the fact that he says that he brought electricity to the property makes no sense at all. Palagio was in need of renovations without any doubts but, I assure you, it was a lovely functioning property.'
Having contacted the newspaper to complain, the duke composed a letter of his own, which was last week published in a different Italian newspaper.
In it, he spelt out his wide-ranging objections to the claims which he described as 'highly damaging' to the memory of his father.
'Ultimately, the interview that Sting gave to Corriere della Sera seems primarily designed to promote his wine and pizzas in what is nothing more than a tacky marketing strategy,' he wrote.
Sting claimed he and wife Trudie Styler got stung when they were tricked into buying a vineyard in Tuscany in 1997 when the owner – the Duke Simone Vincenzo Velluti Zati di San Clemente – gave them a glass of wine to try
'Il Palagio has been transformed into a Palm Beach-style resort.
'An average cultured Tuscan knows that, in this part of our region villas, gardens and the countryside are all connected to each other and part of a single landscape.
'By contrast, Sting's renovation of villa and garden is violently out of context, lacking any connection to that countryside which Sting says he feels part of.'
As for the wine, he criticised Sting for uprooting the old vines despite the estate producing what he described as an 'excellent Chianti'.
But his most vehement criticisms are reserved for the claims about his father — which he describes as a 'poisonous and completely false slander'.
He said: 'My father, Simone di San Clemente, was said to have passed off Barolo as a wine produced on the farm with a tavern-style trick.
'Nothing could be more alien to the character, habits, behaviour — in a word, the spirit — of my father [than] to swindle a guest.
'And it would be a little stupid to think that a well-travelled man like Sting, who was 46 at the time, would confuse Barolo with Chianti.'
He added: 'Throughout this story it is hard to recognise the refined taste that Sting says he has acquired over the years.
'Nor does it appear a decision in good taste to use my family crest on the labels of his wines without any authorisation.
'I hope that the karma that Sting holds so dear does not turn against him and I suggest he reflects on the truth while he meditates.
'In the meantime, I am waiting for Mr Gordon Matthew Thomas Sumner to apologise to me.'
And, sure enough, on August 24 — four days after the publication of that letter — Sting did contact the duke, sending him a letter in English, with an Italian translation, shown to the Mail by his London representative.
It reads: 'You are right, I owe you an apology. The story as reported was disrespectful to the memory of your distinguished father, and for that I offer my sincere and unequivocal apologies.
'Your father was an honourable man who never misled me. The intention of this anecdote was to provide an ironic commentary on my naive assumptions, my inexperience and the embarrassing fact that, 25 years ago, I would have been unable to distinguish a Barolo from a bar of soap.
'I ought to be aware by now that irony is only rarely communicated in print but, nonetheless, I recognise and accept that this has caused you and your family great distress for which I am truly sorry. Please rest assured that this will not happen again.'
It ends with a handwritten signature in the name of Sting.
While clearly the letter was designed to draw a line under the matter, the count believes the apology needs to be made more publicly known.
He believes it should be published on the villa's website and sent to all the media outlets that published the 'original insulting story'.
So far, other than The Daily Mail, the letter has only been shared with the Italian newspaper which published the original interview with Sting.
'You cannot simply wake up one morning and insult someone by creating a story of controversial remarks so that it then becomes viral in English language magazines and papers,' he said.
'I am also in the wine business and I perfectly understand it's not an easy market and it's not enough to be a very famous artist to sell.
'However, this does not excuse this bad taste marketing strategy which clearly insulted me and my family's name.'
Not quite pistols at dawn, perhaps. But a reminder, if nothing else, of how thick blood runs in Italy. Thicker than water — and wine.
Madeline Holtznagel shares rare photos with billionaire boyfriend Justin Hemmes
Sharon Stone continues to keep her chin up in Venice after asking fans to pray for her nephew
Daniel Kaluuya and Fred Hampton Jr. Shared an Emotional Oscars Moment You Didn't See on TV
Top professor reveals Covid will be with us forever however says the worst of Omicron wave is over
Scientists find 27,000 barrels of banned pesticide DDT dumped 10 miles off the Los Angeles coast
Man killed by alligator in Louisiana after warning beasts were lurking in Ida flood waters
NYPD descends in force to Washington Square Park but torrential rain sends revelers home
Swimmers along 14-mile stretch LA beaches from Santa Monica to Malibu levels of bacteria still high
TOWIE's Kelsey Stratford wows in a backless artistic dress
Ryder Cup LIVE: Day Three updates and tee times as Europe attempt miracle comeback
Buy Bitcoin with PayPal ▷ Top 2021 Bitcoin to PayPal Online Casinos
Western Australia junket prohibition for Crown Resorts Limited
WSOP 2021 | How Adrian Mateos Has Achieved So Much So Young! | Interview
Ollie Wines gets call from diehard Port Adelaide fan David 'Kochie' Koch after winning Brownlow
Doctor in charge of treating Putin critic Alexei Navalny after he was poisoned VANISHES
US customs officers seize 500 grams of meth hidden in individual PEANUT SHELLS


L1629: Hallmarked in London, 1911 by William Frederick Williams, this fine George V Antique, Sterling Silver Photograph Frame is of large size and is absolutely plain in style. It has a deep blue velvet easel back and a cream moire lining. The frame measures 12" x 10" (31cm x 26cm) with an aperture of 10" x 8" (25cm x 20cm).


text:
Writing and Revising
Second Edition|©2015 Marcia F. Muth; X. J. Kennedy; Dorothy M. Kennedy
E-book from C$22.99
Paperback C$37.99
Whether you're writing a brief paper or more complicated essay, Writing and Revising serves as a concise and affordable writing guide and reference.
Marcia F. Muth
Marcia F. Muth teaches, writes, and edits. She has taught first-year writing at The Ohio State University and other introductory courses at St. Peter's College (Englewood Cliffs). Her many writing workshops have been sponsored by Fordham University, the University of Colorado Colorado Springs, and currently the School of Education and Human Development at the University of Colorado Denver. She is the author or coauthor of many composition textbooks and ancillaries, including The Bedford Guide for College Writers, The Concise Bedford Guide for Writers, Writing and Revising: A Portable Guide, Researching and Writing: A Portable Guide, and The St. Martin's Pocket Guide to Research and Documentation (all from Bedford/St. Martin's). Her projects as a writer and an editor have included Harold D. Lasswell: An Annotated Bibliography as well as many grant proposals, textbooks, ancillaries, reports, and other publications. She continues to learn how to write clearly and effectively from her students, editors, reviewers, and writing colleagues.
X. J. Kennedy
X. J. Kennedy is an acclaimed poet, children's author, college teacher, and textbook author. He has taught freshman composition at the University of Michigan; the University of North Carolina, Greensboro; and Tufts University. More than 2 million students have used his introductory literature texts and The Bedford Reader, now in its fourteenth edition.
Dorothy M. Kennedy
Dorothy M. Kennedy was a writer and editor whose articles and reviews have appeared in both professional and academic journals. She taught composition at the University of Michigan and Ohio University and, with X. J. Kennedy, was the recipient of the NCTE Teacher's Choice Award for Knock at a Star: A Child's Introduction to Poetry.
Concise but comprehensive guide to writing at a very affordable price


text:
The Hour of Fate è un cortometraggio del 1911. Il nome del regista non viene riportato.

Trama

Produzione
Il film fu prodotto dalla Reliance Film Company.

Distribuzione
Il film, un cortometraggio in una bobina - uscì nelle sale degli Stati Uniti l'11 gennaio 1911, distribuito dalla Motion Picture Distributors and Sales Company.

Collegamenti esterni


"View is great from #5 but beds are uncomfortable and the only way to use wifi is to go to the common room and plug in the electricity!"
"If you wait too long the Fremont Troll will get you 8|"
"They serve Thali meals and tiffin meals ($25 deposit for tiffin box)"
"Have the lamb pide, it is the best item on the menu. But won't feed one person if your hungry."
"The mayorship is hard to steal, don't even try."


text:
CIFF will introduce an area dedicated to sports brands
Sport is again playing a central role in people's lives, and this has inspired the CIFF trade show. The great Danish show detected a growing need, by concept and multi-brand fashion and lifestyle stores, for products that are both technical and fashionable, and announced the introduction from its next edition (from 3rd to 5th February) of a new section labelled 'Performance'.
Autumn-Winter 15/16 collection - Peak Performance
The new area is dedicated to sporting brands that target retailers whose profile is more fashion than sport specialist, and who are oriented to the high-end segment. It is a logical follow-up for the show to its latest introduction of urban and streetwear sections. Technical products will play the starring role in the new section, featuring a selection of outdoor, leisure and pure sport brands.
Like the rest of the show, the Performance area will of course see a prevailing presence of Nordic brands. Notable among them are, for example, Peak Performance, Casall, Tretorn, Scandinavian Edition and Bergans of Norway.


text:
Share this Story: Longtime hockey volunteer presented with Lakers' award
Longtime hockey volunteer presented with Lakers' award
Andy Bader
For more than half of its 20-year existence, Mitchell's Kevin Nicholson has been a part of the Huron-Perth 'AAA' Lakers hockey organization.
Whether it be as assistant coach, trainer, manager, president or head coach – as his current title suggests with the major atoms this upcoming season – Nicholson has been a part of the program he truly believes in.
For that longtime service, Nicholson was presented April 5 with the John O'Keefe Memorial Award which is presented annually to an individual in the Huron-Perth organization who has provided outstanding volunteer work with Lakers' teams and/or the association.
Nicholson just finished his 11th season with the Lakers, beginning as a trainer on his son Wyatt's '98 team. Another former O'Keefe award winner - Jack Chaffe, also of Mitchell - got Nicholson involved on the executive end and over the years he has also been the Alliance league representative with the Ontario Minor Hockey Association (OMHA) as well as the Lakers' head of hockey operations. He's been president for a total of five-and-a-half years during his tenure.
"I think it's a great program," he said, alluding to the amount of practice time the players receive every season, usually one-and-a-half hours twice a week.
"Ice time is the big thing in my mind, plus you get to play with some of the best kids in the area, and against other larger centers' best players," he continued. "Ever since I've been involved it's been about the development of the kids."
Nicholson admits he "fell into" the head coaching job of the 2007 minor atoms this past season, his son Hayden's team, as no other candidate was interested. He will continue as head bench boss this year for the same team in major atom, with tryouts currently underway.
Nicholson said his flexible family life, with wife Michele sharing the load; as well as his place of employment, Thompsons in Mitchell, where he is operations supervisor, makes it easier to juggle his Lakers' responsibilities.
"My first boss Ralph Currie, his son played Lakers, so he knew the program and said 'it's good, take a look at it if you get the opportunity' and we did," he said.
No doubt the Lakers organization is glad he did.
Longtime hockey volunteer presented with Lakers' award Back to video


text:
Will the Castro Theatre remain an LGBTQ landmark as new management takes over?
Tony Bravo February 11, 2022Updated: February 13, 2022, 4:26 pm
Members of the Castro LGBTQ Culture District worry for the future of the beloved Castro Theatre as it is under new management. Photo: Brontë Wittpenn / The Chronicle
The Castro Theatre has been at the center of San Francisco's historically queer Castro neighborhood and an LGBTQ cultural landmark for more than 50 years. Its marquee and neon blade blinking "Castro" have become an abiding symbol of the neighborhood's place in the struggle for gay rights.
The movie house, which marks its centennial in June, has not only hosted LGBTQ-themed films in repertory and festivals such as Frameline — the world's longest-running and largest LGBTQ event of its kind — but also annual concerts by the San Francisco Gay Men's Chorus, conversations with celebrities significant to queer culture and memorial services for people like Pride flag creator Gilbert Baker. Legend has it that famed gay film writer Vito Russo ("The Celluloid Closet") even had his ashes scattered in the auditorium.
"The Castro has been really the Radio City Music Hall for gay people in San Francisco," said filmmaker John Waters, a frequent Castro moviegoer who has also performed on its stage. "It was a cult temple for people who love movies and pageantry. It was a tribe."
It's not surprising, then, that when The Chronicle broke the news last month that the Castro Theatre's management would be taken over by Bay Area concert promoters Another Planet Entertainment, known for producing the San Francisco music festival Outside Lands, reaction was mixed — from optimistic to angry.
Stephen Torres, co-chair of the Castro LGBTQ Cultural District and a former theater employee, said that initially with the theater shuttered as a repertory film house for two years due to the pandemic, "I was thrilled at the prospect of any sort of management after the long closure."
But quickly, reservations about the new management's plans to put a greater emphasis on live events set in for Torres and other members of the Cultural District, as they stated in a letter to APE on Jan. 20. The group specifically cited deep concerns about the potential loss of "the strong LGBTQ programming focus that has been a source of connection, education and delight for many thousands over the decades."
District manager of the Castro LGBTQ Cultural District Tina Aguirre (right) walks with executive co-chair Stephen Torres near the Castro Theatre. Photo: Brontë Wittpenn / The Chronicle
Author and activist Cleve Jones, who has lived in the neighborhood since the 1970s, said that while some change was inevitable, "I hope that these folks understand the extraordinarily unique role that that building has played in what is now called the LGBTQ community of San Francisco and even beyond."
He pointed to a larger issue that has affected San Francisco and other cities with prominent LGBTQ populations: "the demise of the traditional gayborhood," a phenomenon spurred by trends of gentrification, a decentralizing of queer culture by digital media and the closure of legacy LGBTQ businesses, like South of Market's Stud Bar in 2020 and the Mission's Lexington Club in 2015.
Among the concerns is that the neighborhood could potentially lose one of its only all-age venues amid its many 21-and-older bars and nightlife destinations. There are also fears that longtime community partners and independent producers, like "Impresario of Castro Street" Marc Huestis and drag performer Peaches Christ, would be priced out of a venue pivoting to more commercial acts.
But chief among these fears is that queer culture will no longer be a focus. Many are particularly worried about the type of live entertainment that will be booked and whether new audiences will be respectful to the Castro community.
"We don't want people that are going to, let's say, a Dave Chappelle comedy show in the Castro Theatre taking over (bars) 440 or the Edge," said Tina Aguirre, Castro LGBTQ Cultural District manager, referring to the controversial comedian noted for his antagonistic relationship with the transgender community. "We need to have those safe spaces."
Adding to frustrations was that neither APE nor the Castro's longtime owners, the Nasser family, did any outreach to the community or longtime events producers ahead of announcing their partnership and are only now in contact with stakeholders.
Sources have told The Chronicle that this could have been due to the terms of a nondisclosure agreement between the Nasser family and APE. Steven Nasser, whose grandfather built the theater that opened in 1922, did not respond to an email from The Chronicle by publication time, and APE declined to comment.
Event producer Marc Huestis (left) and host Eddie Muller (right) share the stage with Kim Novak during "A Tribute to Living Legend Kim Novak" at the Castro Theatre on May 20, 2018. Photo: Jana Asenbrennerova / Special to The Chronicle
"The rollout could have been a little better," said Mary Conde, APE's senior vice president. But she added that "now that this news is public and we're in the building, now is the time to hit the pavement and go and meet the neighbors, get to know the community groups and address the questions and concerns that folks have. Their concerns are very valid. We want to be good partners to the community, and we want to honor the legacy of the Castro Theatre."
In recent days, Conde has walked the area near the theater, sometimes with former District 8 Supervisor Bevan Dufty, and introduced herself to neighboring businesses. On Feb. 3, Conde met with the Castro Merchants Association on Zoom and listened to concerns ranging from gentrification to fears of major closures of Castro Street, like the one for "The Matrix Resurrections" premiere in December prior to APE taking over management.
APE has also hired veteran public relations professional David Perry to aid in its outreach campaign. Perry, who is gay and co-founded the neighborhood's Rainbow Honor Walk, said that he "would never work with any organization that had anything less than impeccable standards," in terms of its commitment to the LGBTQ community.
This year's Frameline will continue as planned, June 16-26, and Conde confirmed that movie screenings outside of film festival dates will still happen at the Castro, though not with the same frequency. The current staff would also remain employed, and the Castro Theatre's beloved organ will continue to be a fixture at the venue following a temporary closure for upgrades to the building. Additionally, APE is trying to determine how it will work with longtime presenters like Huestis and Peaches Christ on future programming.
"We will be very thoughtful and considerate in how we book this venue," Conde said, "and I can assure you that Dave Chappelle will never perform at the Castro Theatre."
But for many, it isn't just preserving queer programming that's at stake: it's preserving the venue's unique queer audiences.
Performer and filmmaker John Cameron Mitchell, whose film "Hedwig and the Angry Inch" was given a special screening at the theater during the 2001 Frameline festival, called the crowd at the Castro "truly the best audience I've ever experienced in my life. New York certainly doesn't have anything like it anymore. It's a gay cathedral."
Queer scholar and Film Quarterly editor B. Ruby Rich agrees.
"I stood on the stage at the Castro with a full house of dykes jumping to their feet and clapping for me," Rich said, recalling the night she received the Frameline Award during the 2012 festival. "That was a once-in-a-lifetime experience."
Drag performers Peaches Christ and Jinkx Monsoon as Big and Little Edie Beale at a screening of the cult documentary "Grey Gardens" at the Castro Theatre. Photo: Joshua Grannell
Cultural District leaders said while they now feel "cautiously hopeful and optimistic" about APE's involvement at the theater following this month's meeting between the company and the Castro Merchants Association (a second meeting between APE and the Cultural District has been scheduled for Friday, Feb. 11), they know there is still a ways to go to ensure trust between APE and the community.
"APE now has an understanding that cultural humility and openness is what we needed as a part of this process," said Aguirre. "What remains is us actually doing the work of figuring out how to make sure that the Castro can thrive and also maintain LGBTQ culture being centered at the Castro Theatre."
For Peaches Christ, that begins with honoring a contract between her and the Castro for shows rescheduled from 2020. APE has affirmed that commitment and plans to continue discussions about future rental rates for community producers like herself.
"I think they will program appropriately because it's in their own best interests as a business," she said. "They may make mistakes here and there, but I don't think they will intentionally disregard the feelings of the community."
Exclusive: S.F.'s Castro Theatre turning into live events venue featuring music, comedy and more
Castro Theatre will still show movies, new operator Another Planet assures distraught film fanatics
S.F. rally seeks to stop Castro Theatre's conversion to live events venue
Even closed for the pandemic, the Castro Theatre is still columnist's first love
Tony Bravo
Tony Bravo Tony Bravo is a San Francisco Chronicle staff writer. Email: tbravo@sfchronicle.com
Raging Fire
The Spirit of the Beehive


Fencing Accessories that we offer are manufactured using highly advanced techniques under the strict vigilance of experts. We conduct stringent quality tests on Fencing Accessories so as to ensure that only the defect-free product reaches the customers' end. We are named among the renowned Manufacturers and Exporters of Fencing Accessories. We have the capability to deliver retail as well as bulk orders for Fencing Accessories within the stipulated time frame.


text:
N.W.T. Elections: Native youth leader speaks out on the future of the N.W.T.
Challenges of developing and inspiring the youth of the N.W.T.
More From Digital Archives/Politics/Provincial and Territorial Politics/Northwest Territories Elections
N.W.T. Elections: Handley acclaimed, twice
944370000 02:22
Elections after the boundary makeover
Elections Canada targets youth in the North
Last election of its kind in Canada's North
N.W.T. Elections: Thinking outside the parliamentary political box
Nellie Cournoyea: First Indigenous woman to head a government in Canada
N.W.T. Elections: Campaigning in Canada's North
Campaigning on brotherly love in the N.W.T
N.W.T. Elections: Consensus government
Richard Nerysoo, first Indigenous government leader of the N.W.T.
N.W.T. Elections: Native people power
N.W.T. Elections: Nick Sibbeston on balancing progress and tradition
Native leaders emerge in the N.W.T.


text:
Home > Courses > Course Search Results > CQUniversity Australia > Bachelor of Arts
CQUniversity Australia
The Bachelor of Arts course will provide students with a multidisciplinary education that will give them the opportunity to gain knowledge in a range of humanities and social science disciplines. Students will experience a variety of perspectives, methodologies and learning styles and explore disciplines that study the way humans recognise, record and debate human practices, meanings and values. Students will benefit from the course's flexible structure and can tailor their own program by choosing from a variety of majors and minors. These include Creative and Professional Writing, English and Cultural Studies, Geography and Environmental Studies, History, Liberal Arts and Social Enquiry. Students may also undertake a professional major in Business, Digital Media, Journalism, Language or Psychology.
International: $89,488
QTAC: English (4, SA), UAC: English (Standard, Band 2), VTAC: Units 3 and 4: a study score of at least 25 in any English. English language requirements apply.
24 units (144 credit points).
Subjects you can Study:
Business; Creative and professional writing; Digital media; English and cultural studies; Geography and environmental studies; History; Journalism; Language; Liberal arts; Psychology; Social enquiry.
Study Pathways:
Interim award: Diploma of Arts; Exit award: Diploma of Arts. Students who complete the Bachelor of Arts and achieve a grade point average of 5.5 can apply to study Bachelor of Arts (Honours). Upon completion of this degree, students may be interested in postgraduate courses including Graduate Certificate in Social Innovation.
Not all majors are available at all locations. To find out more about CQUniversity's English language requirements visit www.cqu.edu.au/elp.
Accepts International Students:
Related Careers:
Big Data Analyst, Business Systems Analyst, Geographic Information Systems Officer, Historian, Illustrator, Indigenous Community Liaison Officer, Journalist, Psychologist, Writer,
ATAR/OP
Mid Year Intake
cquniversity@cqu.edu.au
CQUniversity Rockhampton North No info Yes Full time 3 years
CQUniversity Rockhampton North No info Yes Part time 6 years
Online Study 52.4 Yes Part time 6 years
Online Study 52.4 Yes Full time 3 years
Online Study 52.4 Yes Online
CQUniversity Australia has one of the largest national footprints of any university in Australia, proudly offering a wide variety of TAFE and university qualifications with seamless pathways between short courses, certificates and diplomas through to undergraduate, postgraduate and research higher degrees to help you be what you want to be.
We offer a world-class education, are ranked in the top two per cent of universities worldwide* and are recognised as Australia's first and only Changemaker Campus by social innovation group Ashoka U.
At CQUniversity you have the opportunity to study courses online, on campus or a combination of both. We are a leading distance education provider and one of the first Australian universities to offer flexible, mixed-mode study so you can learn where and how it suits you.
Whether you want to stay close to home or move somewhere new, prefer the bustling city life or the relaxed pace of regional locations, we offer more than 20 study locations including campuses and study centres in Adelaide, Biloela, Brisbane, Bundaberg, Cairns, Emerald, Gladstone, Mackay, Melbourne, Noosa, Perth, Rockhampton, Sydney, Townsville and Yeppoon, and study hubs in Broome, Busselton, Charters Towers, Cooma, Geraldton, Karratha and Port Pirie.
Choose from a wide variety of courses in areas including:
accounting and law
creative, performing and visual arts
education and humanities
engineering and built environment
engineering trades
study and work preparation
information technology and digital media
social work and community services
transport and safety sciences.
We also provide training for apprentices and trainees, and industry-specific courses.
We're rated as conducting world class research in 14 different categories and are well above world standard in Applied Mathematics, Mathematical Sciences, Nursing, Other Medical and Health Services, Other Psychology and Cognitive Sciences, and Psychology and Cognitive Sciences^. Our range of research higher degrees allow you to undertake research focused on a particular area of interest.
Benefit from our award-winning and experienced teaching professionals, as well as our focus on student services and support. Our student body is diverse and comes from both local and global communities. We are committed to providing specialist education and training support and a range of career-orientated services to ensure our graduates are successful.
Our courses are designed alongside industry and many include hands-on, practical learning experiences such as field and laboratory work, project-based learning and work placements. Our commitment to providing up-to-date, real-world knowledge and skills has seen us being awarded five-star ratings for Full-Time Employment, Social Equity and Starting Salary, placing us in the top 20 per cent of universities in Australia in these categories+. No matter whether you're just finishing school or thinking of taking up a new challenge, CQUniversity can help you be what you want to be.
For more information visit our website or submit an enquiry form.
Postgraduate and international applicants can apply directly.
* Times Higher Education World University Rankings 2019. Visit www.cqu.edu.au/reputation.
^2015–2016 State of Australian University Research Volume 1 ERA National Report.
+The Good Universities Guide 2018
Study Mode Part-time internal Full-time internal Online
University of Southern Queensland (USQ)
Bachelor of Fine Arts - Drama
Bachelor of Creative Arts
Australian Catholic University (ACU)
Bachelor of Arts / Bachelor of Global Studies
Bachelor of Digital Media - Interaction Design
Billy Blue College of Design at Torrens University
University of Melbourne, The
Bachelor of Arts / Bachelor of Music
Bachelor of Laws/Bachelor of Arts
Bachelor of Arts - Music Industry
Bachelor of Visual Arts and Design
Bachelor of Arts / Bachelor of Science
Bachelor of Music / Bachelor of Arts
Bachelor of Creative Arts / Bachelor of Communication and Media
Bachelor of Performance (Dramatic Arts)
Australian Institute of Music (AIM), The
Bachelor of Arts / Bachelor of International Studies
University of Adelaide, The
Bachelor of International Relations / Bachelor of Arts
Bachelor of Media / Bachelor of Arts
Bachelor of Media / Bachelor of International Studies
Bachelor of Arts Therapy
IKON Institute of Australia
Bachelor of Arts / Bachelor of Business
Bachelor of Information and Communications Technology / Bachelor of Visual Communication
Bachelor of Arts / Bachelor of Economics
Bachelor of Visual Communication
Bachelor of Arts / Bachelor of Commerce
Bachelor of Communications & Media
The University of Notre Dame Australia
Bachelor of Laws / Bachelor of Arts
Bachelor of Arts - Dance
Bachelor of - Arts, Social Sciences, Business and Science - Flexible Double Degree
Australian National University (ANU)
Bachelor of Primary Education (Creative Arts)
Bachelor of Communication & Media/Bachelor of Laws
Bachelor of Web Design and Production
Bachelor of Design (Visual Communication Design)
Bachelor of Laws/Bachelor of Design
Charles Darwin University (CDU)
Bachelor of Creative Arts and Industries - New Media Design / Bachelor of Information Technology