RNA editing occurs in the endosymbiont organelles of higher plants as C-to-U conversions of defined nucleotides. The availability of large quantities of RNA sequencing data makes it possible to ...identify RNA editing sites and to quantify their editing extent. We have investigated RNA editing in 34 protein-coding mitochondrial transcripts of four
species, a genus noteworthy for its remarkably small number of RNA editing sites compared to other angiosperms. 27 of these transcripts were subject to RNA editing in at least one species. In total, 355 RNA editing sites were identified with high confidence, their editing extents ranging from 10 to 100%. The most heavily edited transcripts were
with the highest density of RNA editing sites (53.7 sites / kb) and
with the highest number of sites (39 sites). Most of the editing events are at position 1 or 2 of the codons, usually altering the encoded amino acid, and are highly conserved among the species, also with regard to their editing extent. However, one SNP was found in the newly sequenced and annotated mitochondrial genome of
resulting in the loss of an RNA editing site compared to
and
This SNP causes a C-to-T transition and an amino acid exchange from Ser to Phe, highlighting the widely discussed role of RNA editing in compensating mutations.
RNA editing occurs in the endosymbiont organelles of higher plants as C-to-U conversions of defined nucleotides. The availability of large quantities of RNA sequencing data makes it possible to ...identify RNA editing sites and to quantify their editing extent. We have investigated RNA editing in 34 protein-coding mitochondrial transcripts of four Populus species, a genus noteworthy for its remarkably small number of RNA editing sites compared to other angiosperms. 27 of these transcripts were subject to RNA editing in at least one species. In total, 355 RNA editing sites were identified with high confidence, their editing extents ranging from 10 to 100%. The most heavily edited transcripts were ccmB with the highest density of RNA editing sites (53.7 sites / kb) and ccmFn with the highest number of sites (39 sites). Most of the editing events are at position 1 or 2 of the codons, usually altering the encoded amino acid, and are highly conserved among the species, also with regard to their editing extent. However, one SNP was found in the newly sequenced and annotated mitochondrial genome of P. alba resulting in the loss of an RNA editing site compared to P. tremula and P. davidiana. This SNP causes a C-to-T transition and an amino acid exchange from Ser to Phe, highlighting the widely discussed role of RNA editing in compensating mutations.
Based on empirical evidence, we argue that recent declines in the basic skills of German pupils are highly concerning from a labour market policy perspective. High-quality schooling is crucial for ...meeting the demands of a changing labour market, as it provides new cohorts of workers with basic and self-productive skills and facilitates the acquisition of more complex skills and lifelong meta-competences. Therefore, education policy must be seen as an integral part of labour market policy. However, there is a distinct lack of communication and coordination between labour and education policy in Germany, due to misaligned incentives and fragmented responsibilities. Recent reforms provide hope that the necessary capacity building can be achieved.
In mediatisierten Gesellschaften ist der Zugang zu und die Nutzung von Medien eine bedeutsame Voraussetzung für gesellschaftliche Zugehörigkeit und Teilhabe. Der Zugang zu und die Nutzung von Medien ...ist oft durch soziale Barrieren und Mechanismen des sozialen Ausschlusses geprägt, welche sich an Merkmalen wie soziale und/oder kulturelle Herkunft, Geschlecht, Behinderung etc. anhaften. Vor diesem Hintergrund umreißt und begründet das Handbuch Potentiale und Rahmenbedingungen von Medienbildung für inklusive Settings und die Zusammenhänge von Medien, Bildung und sozialen Differenzlinien. Das E-Book ist barrierefrei.
Please cite this paper as: Bruns, Watanpour, Gebhard, Flechtenmacher, Galli, Schulze‐Bergkamen, Zorn, Büchler and Schemmer (2011). Glycine and Taurine Equally Prevent Fatty Livers from Kupffer ...Cell‐Dependent Injury: An In Vivo Microscopy Study. Microcirculation 18(3), 205–213.
Background: IRI still is a major problem in liver surgery due to warm ischemia and organ manipulation. Steatosis is not only induced by diabetes, hyperalimentation, alcohol and toxins, but also chemotherapy given before resection. Since steatotic livers are prone to Kupffer cell‐dependent IRI, protection of steatotic livers is of special interest. This study was designed to compare the effect of taurine and glycine on IRI in steatotic livers.
Materials and Methods: Steatosis was induced with ethanol (7 g/kg b.w.; p.o.) in female SD rats. Ten minutes after inactivation of Kupffer cells with taurine or glycine (300 mM; i.v.), left liver lobes underwent 60 minutes of warm ischemia. Controls received the same volume of valine (300 mM; i.v.) or normal saline. After reperfusion, white blood cell‐endothelial interactions and latex‐bead phagocytosis by Kupffer cells were investigated. Liver enzymes were measured to estimate injury. For statistical analysis, ANOVA and Student’s t‐test were used.
Results: Glycine and taurine significantly decreased leukocyte‐ and platelet‐endothelium interactions and latex‐bead phagocytosis (p < 0.05). Liver enzymes were significantly lower after glycine and taurine (p < 0.05).
Conclusions: This study shows that preconditioning with taurine or glycine is equally effective in preventing injury to fatty livers most likely via Kupffer cell‐dependent mechanisms.
Studies in newly diagnosed multiple myeloma (MM) described a prognostic value of the serum free light chain ratio (sFLCr) on progression free survival (PFS) and overall survival (OS). The GMMG MM5 ...phase III trial compares VCD (bortezomib, cyclophosphamide, dexamethasone) and PAd (bortezomib, adriamycin, dose-reduced dexamethasone) for induction therapy followed by stem cell mobilization and harvest, high-dose therapy and a lenalidomide-based consolidation/maintenance therapy for 2 years vs. lenalidomide until complete response (CR). First primary end point of the ongoing study was response after induction, second primary end point was progression-free survival. To analyse if the sFLCr has a prognostic value on the response after induction therapy with respect to achieve a very good partial response (VGPR) or better, we investigated patients with newly diagnosed MM which were included in the MM5 trial.
504 patients between 18-70 years with newly diagnosed MM were included in the MM5 trial between July 2010 and October 2012. Patient serum samples were collected and sent to a central laboratory for analysis of the free light chains (sFLC) in serum prior to treatment and after induction therapy. For the sFLC measurement the Freelite® assay (The Binding Site) was used.
The analysis was based on the intention-to-treat (ITT) population (502 patients evaluable). The sFLC ratio (sFLCr) was available for n=498 patients at baseline. After induction treatment, there were 179 patients achieving CR and VGPR (VGPR+ group) and 318 patients not achieving at least VGPR (PR- group). There was no significant difference in the response between the PAd and the VCD (reported separately), so we analysed the data irrespective of the treatment arm.
We examined in univariate and multivariate analyses the association of response VGPR+ after induction treatment with clinical variables (age, gender, ISS, CRAB criteria, IgA vs non-IgA type MM, WHO status), LDH measurement, cytogenetic factors (deletion 17p13, gain 1q21, translocation (4;14) ) and sFLCr at baseline. sFLCr was analysed either as categorized factor for values within the range 1/32, 32 or outside this range, as proposed by Snozek et al. (2008), or as continuous factor, where the absolute value of log2 transformed sFLCr is used for analyses. Further, LDH values were log2 transformed for analyses. In univariate analysis, the groups of VGPR+ and PR- showed no significant difference in age, gender, ISS, presence of anemia or bone disease, WHO state or the cytogenetic abnormalities del17p13, gain 1q21 or translocation t(4;14), but were significantly associated with elevated Calcium (p=0.07), renal insufficiency (p=0.004), presence of IgA type MM (p<0.001) and LDH measurement (p<0.001). There was no significant difference between patients with sFLCr at baseline within or outside the range set at 1/32 – 32 in achieving VGPR+ (p=0.23) whereas the absolute value of log2 transformed values was significantly associated with response (p=0.02).
VGPR+ was further analysed by multivariate logistic regression models which were adjusted for the clinical and cytogenetic variables, for LDH and for sFLCr (either as categorical or continuous factor). sFLCr revealed as significant prognostic factor when considered as continuous variable (p = 0.03) but failed significance as categorized factor. Patients with extreme sFLCr values showed a better chance of VGPR+, as did IgA myeloma patients (p=0.03) and patients with renal insufficiency (p=0.04).
Cut point analyses showed that in our trial patients with a baseline sFLCr < 1/1097 and >1097 had a significantly better chance to achieve VGPR+ after induction compared to patients with a sFLCr within this range. There were 44 patients below the range (IgA 22.7%, IgG 34.1%, IgD 6.8%, light chain MM (LCMM) 36.4%), 412 patients in the range (IgA 20.9%,IgG 63.8%, IgD 1%, IgM 0.2%, LCMM 14.1%) and 42 patients above the range (IgA 19.1%, IgG 42.9%, LCMM 38.1%).
In conclusion, the cut point for baseline sFLCr published by Snozek et al. did not define patient groups with significantly different response in the MM5 trial. This cut point was set for the outcome OS and PFS and could not be replicated for response after induction treatment in our trial. The cut point which showed a significant difference in achieving VGPR+ was much higher in our population which might be explained by the higher proportion of light chain MM below and above the cut point range.
Salwender:Janssen Cilag: Honoraria; Celgene: Honoraria. Duerig:Janssen Cilag: Honoraria; Celgene: Honoraria. Schmidt-Wolf:Janssen: Honoraria; Novartis: Honoraria. Weisel:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Scheid:Janssen Cilag: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Goldschmidt:Chugai: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria, Research Funding; The Binding Site: Provision of materials, Provision of materials Other.
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