290 research outputs found

    The inner kinetochore architecture and its role in error correction

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    The inner kinetochore architecture and its role in error correction

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    Verlust und Bewahrung der Sprache der österreichischen Roma

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    This study deals with maintenance and loss of Romani, or romani čhib, according to shifts in the collective repertoire, attempting to explain these phenomena from the socio- -historical situation of each individual Austrian Roma group. In the process, the question of whether Romani is consciously perceived as a factor of identity by the various groups will be of importance.Ova studija bavi se očuvanjem i gubitkom romskoga jezika (romani čhib), s obzirom na pomake u kolektivnom repertoaru, te pokušava objasniti te pojave temeljem društveno- povijesnoga stanja svake pojedine austrijske romske skupine. U tom procesu važno je pitanje percipiraju li svjesno različite skupine Roma romski jezik kao čimbenik identiteta.Die vorliegende Studie beschäftigt sich mit dem drohenden Verlust der Sprache, mit dem die österreichischen Roma angesichts der Abweichungen innerhalb des Kollektivrepertoires konfrontiert sind. Der Verfasser berichtet über Bemühungen zur Bewahrung dieser Sprache (Romani ^hib) und versucht, diese Erscheinung anhand der gesellschaftlichgeschichtlichen Lage jeder einzelnen in Österreich lebenden Gruppe von Roma zu erklären. Hierbei ist eine ganz wesentliche Frage, ob die verschiedenen Roma-Bevölkerungsgruppen selbst die Sprache als einen Identitätsfaktor wahrnehmen oder nicht

    Plasma free DNA: Evaluation of temperature-associated storage effects observed for Roche Cell-Free DNA collection tubes

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    Introduction: Standardized pre-analytical blood sample procedures for the analysis of circulating cell-free DNA (ccfDNA) are still not available. Therefore, the present study aimed at evaluating the impact of storage conditions related to different times (24 and 48 h) and temperatures (room temperature (RT) and 4 - 8 °C) on the plasma ccfDNA concentration of blood samples drawn into Cell-Free DNA collection tubes (Roche Diagnostics GmbH, Mannheim, Germany). Materials and methods: Venous blood from 30 healthy individuals was collected into five 8.5 mL Cell-Free DNA Collection Tubes (Roche Diagnostics GmbH) each. Plasma samples were processed at time point of blood collection (tube 1), and after storage under the following conditions: 24 h at RT (tube 2) or 4-8 °C (tube 3), and 48 h at RT (tube 4) or 4 - 8 °C (tube 5). Circulating cell-free DNA concentrations were determined by EvaGreen chemistry-based droplet digital PCR (ddPCR). Results: No statistically significant differences between median (interquartile range) plasma ccfDNA concentrations (ng/mL) at time point of blood collection (3.17 (2.13 – 3.76)) and after storage for 24 h (RT: 3.02 (2.41 – 3.68); 4-8 °C: 3.21 (2.19 – 3.46)) and 48 h (RT: 3.13 (2.10 – 3.76); 4-8 °C: 3.09 (2.19 – 3.50)) were observed (P values from 0.102 – 0.975). Conclusions: No unwanted release of genomic DNA from white blood cells could be detected in plasma samples after tube storage for 24 and 48 h regardless of storage temperature

    Subcellular localization and distribution of the reduced folate carrier in normal rat tissues

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    The reduced folate carrier (Rfc1; Slc19a1) mediated transport of reduced folates and antifolate drugs such as methotrexate (MTX) play an essential role in physiological folate homeostasis and MTX cancer chemotherapy. As no systematic reports are as yet available correlating Rfc1 gene expression and protein levels in all tissues crucial for folate and antifolate uptake, storage or elimination, we investigated gene and protein expression of rat Rfc1 (rRfc1) in selected tissues. This included the generation of a specific anti-rRfc1 antibody. Rabbits were immunised with isolated rRfc1 peptides producing specific anti-rRfc1 antiserum targeted to the intracellular C-terminus of the carrier. Using RT-PCR analysis, high rRfc1 transcript levels were detected in colon, kidney, brain, thymus, and spleen. Moderate rRfc1 gene expression was observed in small intestine, liver, bone marrow, lung, and testes whereas transcript levels were negligible in heart, skeletal muscle or leukocytes. Immunohistochemical analyses revealed strong carrier expression in the apical membrane of tunica mucosa epithelial cells of small intestine and colon, in the brush-border membrane of choroid plexus epithelial cells or in endothelial cells of small vessels in brain and heart. Additionally, high rRfc1 protein levels were localized in the basolateral membrane of renal tubular epithelial cells, in the plasma membrane of periportal hepatocytes, and sertoli cells of the testes. Taken together, our results demonstrated that rRfc1 is expressed almost ubiquitously but to very different levels. The predominant tissue distribution supports the essential role of Rfc1 in physiological folate homeostasis. Moreover, our results may contribute to understand antifolate pharmacokinetics and selected organ toxicity associated with MTX chemotherapy

    Regulation des Reduced Folate Carrier (RFC1) in HPCT-1E3-Ratten-Hepatocytoma-Zellen durch Cytochrom P450-Induktoren vom Phenobarbital-Typ

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    The sodium dependent reduced folate carrier (Rfc1; Slc19a1) provides the major route for cellular uptake of antifolate chemotherapeutic drugs such as methotrexate (MTX) and reduced folates into liver, kidneys and other tissues. Despite its essential role in cancer treatment and for the body’s folate homeostasis, little is known about Rfc1 regulation. In rat hepatocytes, the 5´ untranslated region of this carrier exhibits, amongst other regulatory elements, a barbiturate recognition box which as yet has only been found in the promotor region of xenobiotic metabolizing enzymes, particularly those of the CYP450 enzyme family. We have therefore investigated the issue of Rfc1 regulation by phenobarbital (PB)-type CYP450 inducers on the functional, transcriptional and translational level using an adequate in vitro model for rat liver. A significant decrease in Rfc1 activity was observed following treatment (48 h) with 1-10 times therapeutic plasma concentrations of PB-type CYP450 inducers like PB, carbamazepine, chlorpromazine, clotrimazole and with the constitutive androstane receptor agonist TCPOBOP. This was not associated with reduced mRNA and protein levels. Further mechanistic investigations revealed that short-term treatment (2 h) of cells with protein phosphatase 2A inhibitor okadaic acid and proteinkinase C inductor PMA was related to a significant reduction of Rfc1 mediated MTX uptake. Finally, the reduction in Rfc1 activity caused by PB, TCPOBOP and PMA was almost completely reversed by simultaneous incubation with the specific PKC inhibitor bisindolylmaleimide. These results demonstrate, that clinical relevant concentrations of PB-type CYP450 inducers cause a significant PKC-dependent reduction in Rfc1 uptake activity on the posttranscriptional level

    PIH11 SOCIO-ECONOMIC ASPECTS OF THE PRENATAL DIAGNOSIS OF CYTOMEGALOVIRUS (CMV) INFECTION IN GERMANY: A BURDEN OF DISEASE STUDY

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    De-Icing Impacts on the Danforth Campus, Spring 2021

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    De-Icing Impacts on the Danforth Campus, Sustainability Exchange, Washington University in St. Louis, Spring 2021

    AhR-activating pesticides increase the bovine ABCG2 efflux activity in MDCKII-bABCG2 cells

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    In bovine mammary glands, the ABCG2 transporter actively secretes xenobiotics into dairy milk. This can have significant implications when cattle are exposed to pesticide residues in feed. Recent studies indicate that the fungicide prochloraz activates the aryl hydrocarbon receptor (AhR) pathway, increasing bovine ABCG2 (bABCG2) gene expression and efflux activity. This could enhance the accumulation of bABCG2 substrates in dairy milk, impacting pesticide risk assessment. We therefore investigated whether 13 commonly used pesticides in Europe are inducers of AhR and bABCG2 activity. MDCKII cells expressing mammary bABCG2 were incubated with pesticides for up to 72 h. To reflect an in vivo situation, applied pesticide concentrations corresponded to the maximum residue levels (MRLs) permitted in bovine fat or muscle. AhR activation was ascertained through CYP1A mRNA expression and enzyme activity, measured by qPCR and 7-ethoxyresorufin-\u39f-deethylase (EROD) assay, respectively. Pesticide-mediated increase of bABCG2 efflux activity was assessed using the Hoechst 33342 accumulation assay. For all assays, the known AhR-activating pesticide prochloraz served as a positive control, while the non-activating tolclofos-methyl provided the negative control. At 10-fold MRL concentrations, chlorpyrifos-methyl, diflufenican, ioxynil, rimsulfuron, and tebuconazole significantly increased CYP1A1 mRNA levels, CYP1A activity, and bABCG2 efflux activity compared to the vehicle control. In contrast, dimethoate, dimethomorph, glyphosate, iprodione, methiocarb and thiacloprid had no impact on AhR-mediated CYP1A1 mRNA levels, CYP1A activity or bABCG2 efflux. In conclusion, the MDCKII-bABCG2 cell model proved an appropriate tool for identifying AhR- and bABCG2-inducing pesticides. This provides an in vitro approach that could reduce the number of animals required in pesticide approval studies

    Long time blood-transfusion trend in a European general hospital

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    Reports about long-time transfusion trends in Austrian hospitals are rare. In our hospital, we implemented an algorithm of preoperative anemia management as part of a patient blood management (PBM) program in October 2011. Anemic individuals with elective surgery underwent an adequate preoperative anemia classification and treatment with erythropoietin and intravenous iron. The aim of this study was to assess red blood cell (RBC), platelet and plasma transfusions before and after implementation of an anemia management program in a general hospital in Austria. This retrospective study evaluated a 12-year trend (2006 – 2017) of RBC, platelet and plasma transfusions in an Austrian general hospital comprising a 6-year period before (2006 – 2011) and a 6-year period after (2012 – 2017) the implementation of an algorithm-guided anemia management. From overall 49,142 transfused RBC units between 2006 - 2017, 22,745 units were transfused in the post-implementation period compared to 26,397 units before PBM initiation (-13.8 %). The plasma unit use decreased also distinctly (787 vs. 1065 units, - 26.1 %) in the period after PBM implementation, whereas a slight decrease of platelet concentration use (807 vs. 843 units, - 4.3 %) was observed, only. This study demonstrates a 12-year pattern of blood use in an Austrian hospital with a distinct decreasing trend of transfused RBC and plasma units during this period. The implementation of PBM activities decreased the need of blood utilization at our institution. Further initiatives are needed to continue this trend in the next years
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