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Butyricin 7423 and the Membrane H + -ATPase of Clostridum pasteurianum
No full textAbstract. The bacteriocin butyricin 7423 inhibited the activity of the membrane H+-ATPase (BF,F,) of vegetative cells of Clostridium pasteurianum but. not that of its soluble BF, component. In vitro studies with the Ht-ATPases of mutant strains selected for diminished sensitivity (a) to butyricin 7423 and (b) to dicyclohexylcarbodi-imide, confirmed that butyricin 7423 interacts with the BF, component of this enzyme complex. Even so, certain other mutant strains displaying decreased sensitivity to butyricin 7423 possessed H fATPases which in vitro showed undiminished sensitivity to inhibition by the bacteriocin. Furthermore, from the changes in intracellular ATP concentration and in the rates and net pasteurianum It is the chiefpurpose of this communication to report that whilst the ability of butyricin 7423 to interact specifically with the BF, component of the membrane Hf-ATPase of the sensitive target cell is possibly an essential prelude to its action, the lethality of the bacteriocin is not attributable merely to its in vitro ability to inhibit this enzyme complex. Kev words: Bacteriocin -Butvricin 7423 -Clostridium incubated anaerobically at 37" C under N, : CO, (1 9 : 1). pasteurianum -Membrane H C -A T P~~~ -Adenosine triphosphatase Butyricin 7423 is a bacteriocin produced by Clostridiunz butyricum NCIB 7423 which is lethal to several other species of Clostridium including Cl. pasteurianum Offprint requests to: J . Gareth Morris Non-standard abbreviatiolzs: H+-ATPase = proton translocating adenosine 5'-triphosphatase (EC 3.6.1.3); DCCD = dicyclohexylcarbodiimide Isolation of Mutants. Petri plates containing agar (2 2)-solidified glucose minimal medium supplemented with DCCD (80 pM) were overlaid with 3 ml of the same medium (but with 0.9 % agar) seeded with approx. 3 x lo7 cells of CI. pasteurianum 601 3 taken from a late exponential phase batch culture. A small quantity (approx. 0.5 mg) of N-methy1-N'-nitro-N-nitrosoguanidine (NTG) was placed on the plate at three widely separated sites. After anaerobic incubation at 37" C for 3 days, single colonies were selected and the isolates purified by sequential streaking on freshly prepared agarsolidified medium containing 80 yM DCCD. The final isolates were maintained as sporulated cultures on slopes of this medium. Mutants displaying diminished sensitivity to butyricin 7423 were obtained in a similar manner save that the bacteriocin was introduced into wells punched out of the seeded plate at suitable distances from the applied mutagen. Following isolation and purification on agar-solidified medium containing butyricin 7423, the selected mutant strains were stored as lyophilised cultures. Preparation and Assay of Butyricin 7423. Butyricin 7423 was obtained from culture supernatant of Clostridium butyricum NCIB 7423 and was purified essentially by the procedure previously reported b
Inhibition of cell proliferation by DS-7423 and rapamycin.
No full text<p>(A) Cell viability for each cell line was analyzed using the methyl thiazolyl tetrazolium (MTT) assay 72 h after treatment with DS-7423 or rapamycin at the doses indicated. The data were normalized relative to the value of the control cells. In all nine cell lines, DS-7423 suppressed cell proliferation more robustly than rapamycin when both were used at higher doses. (B) IC<sub>50</sub> values for DS-7423 in seven ovarian serous adenocarcinoma (OSA) cell lines (left) were compared with those of nine OCCA cells (right). Four of seven OSA cells had IC<sub>50</sub> values >100 nM, which is higher than that of any OCCA cells.</p
Linked collectors and determiners for: University of British Columbia Botanical Garden Collections (UBCBG).
No full textNatural history specimen data linked to collectors and determiners held within, "University of British Columbia Botanical Garden Collections (UBCBG)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/c5da77b7-7423-49a4-a379-f423ea0f07b8">https://bionomia.net/dataset/c5da77b7-7423-49a4-a379-f423ea0f07b8</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/c5da77b7-7423-49a4-a379-f423ea0f07b8">https://gbif.org/dataset/c5da77b7-7423-49a4-a379-f423ea0f07b8</a>. Formatted as a Frictionless Data package
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Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423
No full textDS-7423, a novel, small-molecule dual inhibitor of phosphatidylinositol-3- kinase (PI3K) and mammalian target of rapamycin (mTOR), is currently in phase I clinical trials for solid tumors. Although DS-7423 potently inhibits PI3Kα (IC50 = 15.6 nM) and mTO
Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423.
No full textDS-7423, a novel, small-molecule dual inhibitor of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), is currently in phase I clinical trials for solid tumors. Although DS-7423 potently inhibits PI3Kα (IC50 = 15.6 nM) and mTOR (IC50 = 34.9 nM), it also inhibits other isoforms of class I PI3K (IC50 values: PI3Kβ = 1,143 nM; PI3Kγ = 249 nM; PI3Kδ = 262 nM). The PI3K/mTOR pathway is frequently activated in ovarian clear cell adenocarcinomas (OCCA) through various mutations that activate PI3K-AKT signaling. Here, we describe the anti-tumor effect of DS-7423 on a panel of nine OCCA cell lines. IC50 values for DS-7423 were <75 nM in all the lines, regardless of the mutational status of PIK3CA. In mouse xenograft models, DS-7423 suppressed the tumor growth of OCCA in a dose-dependent manner. Flow cytometry analysis revealed a decrease in S-phase cell populations in all the cell lines and an increase in sub-G1 cell populations following treatment with DS-7423 in six of the nine OCCA cell lines tested. DS-7423-mediated apoptosis was induced more effectively in the six cell lines without TP53 mutations than in the three cell lines with TP53 mutations. Concomitantly with the decreased phosphorylation level of MDM2 (mouse double minute 2 homolog), the level of phosphorylation of TP53 at Ser46 was increased by DS-7423 in the six cell lines with wild-type TP53, with induction of genes that mediate TP53-dependent apoptosis, including p53AIP1 and PUMA at 39 nM or higher doses. Our data suggest that the dual PI3K/mTOR inhibitor DS-7423 may constitute a promising molecular targeted therapy for OCCA, and that its antitumor effect might be partly obtained by induction of TP53-dependent apoptosis in TP53 wild-type OCCAs
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
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Flow cytometric analysis of the cell cycle in cancer cells treated with DS-7423, and <i>in vivo</i> demonstration of the anti-tumor effect of DS-7423 in nude mice.
No full text<p>(A) Cells (5×10<sup>5</sup>) were seeded in the presence of 10% serum and treated with DS-7423 for 48 h at doses of 9.8 nM, 256 nM, or 2,500 nM. DS-7423 blocked OCCA cell cycle progression into the S phase in a dose-dependent manner. The relative size of the sub-G1 population was increased in six of the cell lines (left) but was not affected in the remaining three cell lines (right). (B) Subcutaneous xenograft tumors in athymic BALB/c mice were established following the injection of OCCA cells of either the TOV-21G (left) or RMG-I (right) cell lines. Mice were treated daily (5–7 days per week) at the indicated doses of DS-7423 (1.5, 3, or 6 mg/kg, 8–10 days). Each treatment group contained five mice. Estimated tumor volumes (upper graphs) and body weight losses (BWL) (lower graphs) were shown in the two OCCA cells. Tumor volumes were calculated by the formula {(major axis)*(minor axis)<sup>2</sup>/2} mm<sup>3</sup>. Groups were compared at the end of treatment. Points, mean; bars, standard deviation (SD); *p<0.05.</p
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