Polyploidization as a Retraction Force in Plant Genome Evolution: Sequence Rearrangements in Triticale

BACKGROUND: Polyploidization is a major evolutionary process in plants where hybridization and chromosome doubling induce enormous genomic stress and can generate genetic and epigenetic modifications. However, proper evaluation of DNA sequence restructuring events and the precise characterization of sequences involved are still sparse. METHODOLOGY/PRINCIPAL FINDINGS: Inter Retrotransposons Amplified Polymorphism (IRAP), Retrotransposons Microsatellite Amplified Polymorphism (REMAP) and Inter Simple Sequence Repeat (ISSR) largely confirmed the absence of any intraspecific variation in wheat, rye and triticale. The comparative analysis of banding profiles between wheat and rye inbred lines revealed 34% of monomorphic (common to both parental species) bands for the ten different primer combinations used. The analysis of triticale plants uncovered nearly 51% of rearranged bands in the polyploid, being the majority of these modifications, due to the loss of rye bands (83%). Sequence analysis of rye fragments absent in triticale revealed for instance homology with hydroxyproline-rich glycoproteins (HRGP), a protein that belongs to a major family of inducible defence response proteins. Conversely, a wheat-specific band absent in triticale comprises a nested structure of copia-like retrotransposons elements, namely Claudia and Barbara. Sequencing of a polyploid-specific band (absent in both parents) revealed a microsatellite related sequence. Cytological studies using Fluorescent In Situ Hybridization (FISH) with REMAP products revealed a widespread distribution of retrotransposon and/or microsatellite flanking sequences on rye chromosomes, with a preferential accumulation in heterochromatic sub-telomeric domains. CONCLUSIONS/SIGNIFICANCE: Here, we used PCR-based molecular marker techniques involving retrotransposons and microsatellites to uncover polyploidization induced genetic restructuring in triticale. Sequence analysis of rearranged genomic fragments either from rye or wheat origin showed these to be retrotransposon-related as well as coding sequences. Further FISH analysis revealed possible chromosome hotspots for sequence rearrangements. The role of chromatin condensation on the origin of genomic rearrangements mediated by polyploidization in triticale is also discussed

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Kamratbedömning som pedagogiskt verktyg i elevers lärandeprocess och lärarens formativa bedömning

Syftet var att jag skulle undersöka huruvida kamratbedömning kan användas för att främja att elever blir mer delaktiga i bedömningen av sin kunskapsutveckling. Med elevernas lärande i fokus vill jag ge eleverna möjlighet att själva få syn på var de befinner sig i sin utveckling och i interaktionen med läraren och andra elever fördjupa sin förståelse och se möjliga vägar vidare i lärandet. Jag har genomfört klassrumsobservationer som har spelats in, jag har analyserat resultatet och kommit fram till att kamratbedömning hjälper elever dels att förstå var de befinner sig i lärandeprocessen, dels hur de ska arbeta vidare med sina uppgifter och framöver i undervisningen i ämnet. Läraren kan i den inspelade kamratbedömningen få syn på vilka färdigheter som övas och används i elevernas kamratbedömning och använda den för bedömningsarbete och betygsättning

The so called quality literature : A study of language games with the expression quality literature

This masters thesis is a study of how the expression quality literature is used in widespread newspapers and magazines. Wittgensteins idea of language games is used as a theoretical starting point. The analysis of 37 articles draws a picture of five language games that are called; the taking over, the polarising, the example giving, the gender critical and the ironic language game. The expression that quality literature is most often put in relation to is popular literature. The line between the two is sometimes distinctly drawn in the articles and sometimes quite vague. In the articles there are few explicit definitions of literary quality or discussions about the complexity of the expression though the use of expressions like the so called quality literature are examples of what can be seen as signs of awareness of this complexity. The most common way of showing the meaning of the expression is to associate it with other words that have an underlying value, words like serious, complex and non-commercial.Uppsatsnivå:

Kamratbedömning som pedagogiskt verktyg i elevers lärandeprocess och lärarens formativa bedömning

Syftet var att jag skulle undersöka huruvida kamratbedömning kan användas för att främja att elever blir mer delaktiga i bedömningen av sin kunskapsutveckling. Med elevernas lärande i fokus vill jag ge eleverna möjlighet att själva få syn på var de befinner sig i sin utveckling och i interaktionen med läraren och andra elever fördjupa sin förståelse och se möjliga vägar vidare i lärandet. Jag har genomfört klassrumsobservationer som har spelats in, jag har analyserat resultatet och kommit fram till att kamratbedömning hjälper elever dels att förstå var de befinner sig i lärandeprocessen, dels hur de ska arbeta vidare med sina uppgifter och framöver i undervisningen i ämnet. Läraren kan i den inspelade kamratbedömningen få syn på vilka färdigheter som övas och används i elevernas kamratbedömning och använda den för bedömningsarbete och betygsättning

Integrating Prosody into an Account of Discourse Structure

In this thesis a study of discourse segmenting is carried out, which investigates both segment boundaries and segment content. The results are related to discourse theory. We study the questions of how the prosody and the text structure influence subjects' annotations of discourse boundaries and discourse prominence. The hypothesis was that the annotations would be influenced by the discourse type. Two studies were carried out. 1) a study of boundary annotation, 2) a study of prominence annotation. All studies were made on four different discourse types, scripted and spontaneous monologue and scripted and spontaneous dialogue. In addition the annotations were carried out under two different conditions 1) based on transcripts alone and 2) based on transcripts together with access to the speech signal. The results indicate that the boundary annotations were less dependent on the speech signal than the prominence annotations. It seems that subjects have segmented on the basis of the text structure, while prominence to a great extent was annotated on the basis of the prosody. In the case of boundary markings the boundary context in terms of parts of speech differs across speaking styles, which is not the case for the prominences. A separate study of segment intentions was also made, and it was found that the interpretation of a specific intention, questions, seems to be arrived at primarily on the basis of the text structure. However, in some cases also the prosody affects the annotations. The picture that emerges indicates a distribution of labour between text structure and prosody, governed by the principle of economy. In cases where the boundaries were less well definied, as in e.g. spontaneous monologue, the pattern of the prominences was clearer. In cases where the boundaries were more clearly indicated, as in read aloud text, the prominences were less clearly communicated. The findings were interpreted within Grosz and Sidner's (1986) discourse theory. It is suggested that differences in the segmenting strategy originating from the interaction of text structure and prosody can be expressed as differences in the contributions from the different components of discourse suggested in the framework of Grosz and Sidner (1986).För att köpa boken skicka en beställning till [email protected]/ To order the book send an e-mail to [email protected]</p