392 research outputs found

    A remembrance of things (best) forgotten: The 'allegorical past' and the feminist imagination

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    This is the author's PDF version of an article published in Feminist theology© 2012. The definitive version is available at http://fth.sagepub.com/This article discusses the US TV series Mad Men, which is set in an advertising agency in 1960s New York, in relation to two key elements which seem significant for a consideration of the current state of feminism in church and academy, both of which centre around what it means to remember or (not) to forget

    Less than the sum of its parts : the dust-corrected Hα luminosity of star-forming galaxies explored at different spatial resolutions with MaNGA and MUSE

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    Funding: NVA would like to thank the University of St Andrews for providing support during her visit. NVA acknowledges support of the Royal Society and the Newton Fund via the award of a Royal Society–Newton Advanced Fellowship (grant NAF\R1\180403), and of Fundação de Amparo à Pesquisa e Inovação de Santa Catarina (FAPESC) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). AW acknowledges financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2019/01768-6. MG receives funding from the European Research Council (ERC) under the European Union Horizon 2020 research and innovative programme (MagneticYSOs programme, grant agreement Nber 679937). EWP, RSK, SR, SCOG and DR acknowledge funding from the Deutsche Forschungsgemeinschaft (DFG) via the Collaborative Research Center (SFB 881) ‘The Milky Way System (subprojects A1, B1, and B2) and from the Heidelberg Cluster of Excellence STRUCTURES in the framework of Germany’s Excellence Strategy (grant EXC-2181/1- 390900948).The Hα and Hβ emission line luminosities measured in a single integrated spectrum are affected in non-trivial ways by point-to-point variations in dust attenuation in a galaxy. This work investigates the impact of this variation when estimating global Hα luminosities corrected for the presence of dust by a global Balmer decrement. Analytical arguments show that the dust-corrected Hα luminosity is always underestimated when using the global Hα/Hβ flux ratio to correct for dust attenuation. We measure this effect on 156 face-on star-forming galaxies from the Mapping Nearby Galaxies at APO (MaNGA) survey. At 1–2 kpc spatial resolution, the effect is small but systematic, with the integrated dust-corrected Hα luminosity underestimated by 2–4 per cent (and typically not more than by 10 per cent), and depends on the specific star formation rate of the galaxy. Given the spatial resolution of MaNGA, these are lower limits for the effect. From Multi Unit Spectroscopic Explorer (MUSE) observations of NGC 628 with a resolution of 36 pc we find the discrepancy between the globally and the point-by-point dust-corrected Hα luminosity to be 14 ± 1 per cent, which may still underestimate the true effect. We use toy models and simulations to show that the true difference depends strongly on the spatial variance of the Hα/Hβ flux ratio, and on the slope of the relation between Hα luminosity and dust attenuation within a galaxy. Larger samples of higher spatial resolution observations are required to quantify the dependence of this effect as a function of galaxy properties.PostprintPeer reviewe

    First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)—a systematic review and individual patient data meta-analysis

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    Evidence for prognosis and treatment of elderly patient with primary central nervous system is limited. High-dose methotrexate should be applied whenever possible, especially combination with oral alkylating agents is a promising approach. Further combinations with other intravenous drugs do not seem to improve outcome. More prospective trials designed for elderly PCNSL patients are warrante

    Divergent expression of claudin -1, -3, -4, -5 and -7 in developing human lung

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    <p>Abstract</p> <p>Background</p> <p>Claudins are the main components of tight junctions, structures which are associated with cell polarity and permeability. The aim of this study was to analyze the expression of claudins 1, 3, 4, 5, and 7 in developing human lung tissues from 12 to 40 weeks of gestation.</p> <p>Methods</p> <p>47 cases were analyzed by immunohistochemisty for claudins 1, 3, 4, 5 and 7. 23 cases were also investigated by quantitative RT-PCR for claudin-1, -3 and -4.</p> <p>Results</p> <p>Claudin-1 was expressed in epithelium of bronchi and large bronchioles from week 12 onwards but it was not detected in epithelium of developing alveoli. Claudin-3, -4 and -7 were strongly expressed in bronchial epithelium from week 12 to week 40, and they were also expressed in alveoli from week 16 to week 40. Claudin-5 was expressed strongly during all periods in endothelial cells. It was expressed also in epithelium of bronchi from week 12 to week 40, and in alveoli during the canalicular period. RT-PCR analyses revealed detectable amounts of RNAs for claudins 1, 3 and 4 in all cases studied.</p> <p>Conclusion</p> <p>Claudin-1, -3, -4, -5, and -7 are expressed in developing human lung from week 12 to week 40 with distinct locations and in divergent quantities. The expression of claudin-1 was restricted to the bronchial epithelium, whereas claudin-3, -4 and -7 were positive also in alveolar epithelium as well as in the bronchial epithelium. All claudins studied are linked to the development of airways, whereas claudin-3, -4, -5 and -7, but not claudin-1, are involved in the development of acinus and the differentiation of alveolar epithelial cells.</p

    Feedback in W49A diagnosed with radio recombination lines and models

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    We present images of radio recombination lines (RRLs) at wavelengths around 17 cm from the star-forming region W49A to determine the kinematics of ionized gas in the THOR survey (The H I/OH/Recombination line survey of the inner Milky Way) at an angular resolution of 16.′′8 x 13.′′8. The distribution of ionized gas appears to be affected by feedback processes from the star clusters in W49A. The velocity structure of the RRLs shows a complex behavior with respect to the molecular gas. We find a shell-like distribution of ionized gas as traced by RRL emission surrounding the central cluster of OB stars in W49A. We describe the evolution of the shell with the recent feedback model code WARPFIELD that includes the important physical processes and has previously been applied to the 30 Doradus region in the Large Magellanic Cloud. The cloud structure and dynamics of W49A are in agreement with a feedback-driven shell that is re-collapsing. The shell may have triggered star formation in other parts of W49A. We suggest that W49A is a potential candidate for star formation regulated by feedback-driven and re-collapsing shells.We would like to thank the referee for the detailed, helpful, and insightful comments, which considerably improved the paper. M.R.R. is a fellow of the International Max Planck Research School for Astronomy and Cosmic Physics (IMPRS) at the University of Heidelberg. H.B., M.R.R., Y.W., J.S. and J.C.M. acknowledge support from the European Research Council under the Horizon 2020 Framework Program via the ERC Consolidator Grant CSF-648505. M.R.R., D.R., H.B., E.W.P., S.C.O.G. and R.S.K. acknowledge support from the Deutsche Forschungsgemeinschaft (DFG) via Sonderforschungsbereich (SFB) 881 “The Milky Way System” (sub-projects B1, B2 and B8). S.C.O.G., E.W.P. and R.S.K. further acknowledge support from the DFG via Priority Program SPP 1573 “Physics of the Interstellar Medium” (grant numbers KL1358/18.1, KL 1358/19.2, and GL 668/2–1) and from the European Research Council via the ERC Advanced Grant STARLIGHT (project number 339177). The research was carried out in part at the Jet Propulsion Laboratory, which is operated forNASA by the California Institute of Technology. R.J.S. acknowledges support from an STFC Ernest Rutherford fellowship. S.E.R. acknowledges support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement # 706390. F.B. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement No 726384 – EMPIRE)

    A Bcl-x(L)-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis

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    Following exocytosis, the rate of recovery of neurotransmitter release is determined by vesicle retrieval from the plasma membrane and by recruitment of vesicles from reserve pools within the synapse, which is dependent on mitochondrial ATP. The anti-apoptotic Bcl-2 family protein Bcl-xL also regulates neurotransmitter release and recovery in part by increasing ATP availability from mitochondria. We now find, that Bcl-xL directly regulates endocytic vesicle retrieval in hippocampal neurons through protein–protein interaction with components of the clathrin complex. Our evidence suggests that, during synaptic stimulation, Bcl-xL translocates to clathrin-coated pits in a calmodulin-dependent manner and forms a complex with the GTPase Drp1, Mff and clathrin. Depletion of Drp1 produces misformed endocytic vesicles. Mutagenesis studies suggest that formation of the Bcl-xL–Drp1 complex is necessary for the enhanced rate of vesicle endocytosis produced by Bcl-xL, thus providing a mechanism for presynaptic plasticity

    The apparent genetic anticipation in PMS2-associated Lynch syndrome families is explained by birth cohort effect

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    BACKGROUND: PMS2-associated Lynch syndrome is characterized by a relatively low colorectal cancer penetrance compared with other Lynch syndromes. However, age at colorectal cancer diagnosis varies widely, and a strong genetic anticipation effect has been suggested for PMS2 families. In this study, we examined proposed genetic anticipation in a sample of 152 European PMS2 families. METHODS: The 152 families (637 family members) that were eligible for analysis were mainly clinically ascertained via clinical genetics centers. We used weighted Cox-type random effects model, adjusted by birth cohort and sex, to estimate the generational effect on the age of onset of colorectal cancer. Probands and young birth cohorts were excluded from the analyses. Weights represented mutation probabilities based on kinship coefficients, thus avoiding testing bias. RESULTS: Family data across three generations, including 123 colorectal cancers, were analyzed. When compared with the first generation, the crude HR for anticipation was 2.242 [95% confidence interval (CI), 1.162-4.328] for the second generation and 2.644 (95% CI, 1.082-6.464) for the third generation. However, after correction for birth cohort and sex, the effect vanished [HR = 1.302 (95% CI, 0.648-2.619) and HR = 1.074 (95% CI, 0.406-2.842) for second and third generations, respectively]. CONCLUSIONS: Our study did not confirm previous reports of genetic anticipation in PMS2-associated Lynch syndrome. Birth-cohort effect seems the most likely explanation for observed younger colorectal cancer diagnosis in subsequent generations, particularly because there is currently no commonly accepted biological mechanism that could explain genetic anticipation in Lynch syndrome. IMPACT: This new model for studying genetic anticipation provides a standard for rigorous analysis of families with dominantly inherited cancer predisposition

    Protein Kinase C Activation Has Distinct Effects on the Localization, Phosphorylation and Detergent Solubility of the Claudin Protein Family in Tight and Leaky Epithelial Cells

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    We have previously shown that protein kinase C (PKC) activation has distinct effects on the structure and barrier properties of cultured epithelial cells (HT29 and MDCK I). Since the claudin family of tight junction (TJ)-associated proteins is considered to be crucial for the function of mature TJ, we assessed their expression patterns and cellular destination, detergent solubility and phosphorylation upon PKC stimulation for 2 or 18 h with phorbol myristate acetate (PMA). In HT29 cells, claudins 1, 3, 4 and 5 and possibly claudin 2 were redistributed to apical cell–cell contacts after PKC activation and the amounts of claudins 1, 3 and 5, but not of claudin 2, were increased in cell lysates. By contrast, in MDCK I cells, PMA treatment resulted in redistribution of claudins 1, 3, 4 and 5 from the TJ and in reorganization of the proteins into more insoluble complexes. Claudins 1 and 4 were phosphorylated in both MDCK I and HT29 cells, but PKC-induced changes in claudin phosphorylation state were detected only in MDCK I cells. A major difference between HT29 and MDCK I cells, which have low and high basal transepithelial electrical resistance, respectively, was the absence of claudin 2 in the latter. Our findings show that PKC activation targets in characteristic ways the expression patterns, destination, detergent solubility and phosphorylation state of claudins in epithelial cells with different capacities to form an epithelial barrier

    Identification of claudin-4 as a marker highly overexpressed in both primary and metastatic prostate cancer

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    In the quest for markers of expression and progression for prostate cancer (PCa), the majority of studies have focussed on molecular data exclusively from primary tumours. Although expression in metastases is inferred, a lack of correlation with secondary tumours potentially limits their applicability diagnostically and therapeutically. Molecular targets were identified by examining expression profiles of prostate cell lines using cDNA microarrays. Those genes identified were verified on PCa cell lines and tumour samples from both primary and secondary tumours using real-time RT–PCR, western blotting and immunohistochemistry. Claudin-4, coding for an integral membrane cell-junction protein, was the most significantly (P<0.00001) upregulated marker in both primary and metastatic tumour specimens compared with benign prostatic hyperplasia at both RNA and protein levels. In primary tumours, claudin-4 was more highly expressed in lower grade (Gleason 6) lesions than in higher grade (Gleason ⩾7) cancers. Expression was prominent throughout metastases from a variety of secondary sites in fresh-frozen and formalin-fixed specimens from both androgen-intact and androgen-suppressed patients. As a result of its prominent expression in both primary and secondary PCas, together with its established role as a receptor for Clostridium perfringens enterotoxin, claudin-4 may be useful as a potential marker and therapeutic target for PCa metastases
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