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Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence.
No full textInternational audienceThe triazine derivative 12459 is a potent G-quadruplex interacting agent that inhibits telomerase activity. This agent induces time- and dose-dependent telomere shortening, senescence-like growth arrest and apoptosis in the human A549 tumour cell line. We show here that 12459 induces a delayed apoptosis that activates the mitochondrial pathway. A549 cell lines selected for resistance to 12459 and previously characterized for an altered hTERT expression also showed Bcl-2 overexpression. Transfection of Bcl-2 into A549 cells induced a resistance to the short-term apoptotic effect triggered by 12459, suggesting that Bcl-2 is an important determinant for the activity of 12459. In sharp contrast, the Bcl-2 overexpression was not sufficient to confer resistance to the senescence-like growth arrest induced by prolonged treatment with 12459. We also show that 12459 provokes a rapid degradation of the telomeric G-overhang in conditions that paralleled the apoptosis induction. In contrast, the G-overhang degradation was not observed when apoptosis was induced by camptothecin. Bcl-2 overexpression did not modify the G-overhang degradation, suggesting that this event is an early process uncoupled from the final apoptotic pathway
12459 at Moree, New South Wales November 1940 [picture] /
No full textPart of collection: Buckland collection of railway transport photographs.; Title devised by cataloguer from pencil inscription on verso.; Inscriptions: " 12459 Moree 11/40"--In pencil on verso.; Photographer's stamp on verso.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4367048
( and ) Western blot analysis of PARP cleaved form (89 kDa) protein expression (a) or Caspase 3 cleaved form (17 kDa) protein expression (b) performed in untreated A549, JFD18 or JFD9 cells (0) and in cells treated with 10 μM 12459 for 24 or 48 h
No full text<p><b>Copyright information:</b></p><p>Taken from "Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence"</p><p>Nucleic Acids Research 2005;33(7):2192-2203.</p><p>Published online 14 Apr 2005</p><p>PMCID:PMC1079972.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p> β-actin was used as a control for protein loading. Relative PARP cleavage (a) or Caspase 3 cleavage (b) was measured by densitometry scanning of the films, normalized relative to β-actin protein expression and results were expressed relative to untreated A549 cells defined as 100% for PARP or relative to A549 cells treated for 48 h with 12459 for caspase 3 (see bottom of each panel). () Effect of caspase inhibitors on apoptosis induced by 12459 (10 μM, 48 h) on A549 cells. DEVD-FMK and IETD-FMK at 2 μM were added to 12459 and apoptosis was revealed by Hoechst 33342 staining. () Mitochondrial membrane potential was measured by spectrofluorimetry of the JC1 dye in A549 control cells (0) or in cells treated with 1 μM 12459 for 0, 6, 12 or 24 h or with 10 μM 12459 for 4 or 6 h, as described in Materials and Methods. () ROS were measured by spectrofluorimetry using carboxy fluorescein-AM in A549 control cells (0) or in cells treated with 10 μM 12459 for 2, 4, 6, 8 and 14 h. Results represent the mean ± SM of duplicate determinations
12459 at Moree railway station, New South Wales, November 1940 [picture] /
No full textPart of collection: Buckland collection of railway transport photographs.; Title devised by cataloguer from pencil inscription on verso.; Inscriptions: " 12459 at Moree 11/40"--In pencil on verso.; Photographer's stamp on verso.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4366970
( and ) Western blot analysis of Bcl-2 and Bax protein expression performed in A549, JFD18 or JFD9 control cells (0) or cells treated with 10 μM 12459 for 24 or 48 h, as indicated
No full text<p><b>Copyright information:</b></p><p>Taken from "Overexpression of Bcl-2 is associated with apoptotic resistance to the G-quadruplex ligand 12459 but is not sufficient to confer resistance to long-term senescence"</p><p>Nucleic Acids Research 2005;33(7):2192-2203.</p><p>Published online 14 Apr 2005</p><p>PMCID:PMC1079972.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p> β-actin was used as a control for protein loading. ( and ) Analysis of Bcl-2 and Bax mRNA expression by quantitative RT–PCR in untreated A549 cells (0) and in A549 cells treated with 10 μM 12459 for 24 or 48 h. Results (mean ± SD of triplicates) were normalized relative to 18S ribosomal RNA level, and expressed relative to untreated A549 cells, defined as 100%, as described in Materials and Methods
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Psychological distress in student nurses undertaking an educational programme with professional registration as a nurse: their perceived barriers and facilitators in seeking psychological support
No full textThis is the peer reviewed version of the following article: Mitchell, A. E. P. (2018). Psychological Distress in student nurses undertaking an educational programme with professional registration: their perceived barriers and facilitators in seeking psychological support. Journal of Psychiatric and Mental Health Nursing, 25(4), 258-269. http://dx.doi.org/10.1111/jpm.12459, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jpm.12459/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingIntroduction. The present study adds to the existing international evidence on psychological distress in the student population by focusing on student nurses. It quantitatively assesses psychological distress with comparative norms and investigates service uptake in in a single study. Aim. Investigate the level of psychological distress in students and compare this with population norms and highlight potential facilitators and barriers to help seeking. Methods. This study recruited N=121 student nurses from one university in a cross sectional design. Data were analysed using descriptive statistics, independent t-tests and one-way ANOVA’s. Findings. The key findings show high levels of psychological distress which is above levels seen in the general population. The main barriers to seeking support was fear of disclosure and the perceived impact on their suitability as a student nurse. Discussion. The study highlights that high levels of distress identified in the literature are seen in student nurses and that fear of disclosure may account for some not seeking support. Relevance. The fear of disclosure and low levels of seeking support suggest there is a need for mental health nurses and academics to play a key role in mental health literacy and evidence-based interventions such as mindfulness to combat these issues
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