miR-199a-5p regulates urothelial permeability and may play a role in bladder pain syndrome

Defects in urothelial integrity resulting in leakage and activation of underlying sensory nerves are potential causative factors of bladder pain syndrome, a clinical syndrome of pelvic pain and urinary urgency/frequency in the absence of a specific cause. Herein, we identified the microRNA miR-199a-5p as an important regulator of intercellular junctions. On overexpression in urothelial cells, it impairs correct tight junction formation and leads to increased permeability. miR-199a-5p directly targets mRNAs encoding LIN7C, ARHGAP12, PALS1, RND1, and PVRL1 and attenuates their expression levels to a similar extent. Using laser microdissection, we showed that miR-199a-5p is predominantly expressed in bladder smooth muscle but that it is also detected in mature bladder urothelium and primary urothelial cultures. In the urothelium, its expression can be up-regulated after activation of cAMP signaling pathways. While validating miR-199a-5p targets, we delineated novel functions of LIN7C and ARHGAP12 in urothelial integrity and confirmed the essential role of PALS1 in establishing and maintaining urothelial polarity and junction assembly. The present results point to a possible link between miR-199a-5p expression and the control of urothelial permeability in bladder pain syndrome. Up-regulation of miR-199a-5p and concomitant down-regulation of its multiple targets might be detrimental to the establishment of a tight urothelial barrier, leading to chronic pain.

Videogames and Aggression in Teenagers

Victor Sazonov (Russia). Video Games and Aggression in Teenagers. Mr. Sazonov works as a psychologist at the Obninsk Linguistic College and worked on this research from July 1996 to June 1997. Mr. Sazonov conducted a survey of 200 tenth and eleventh graders in Moscow (94 boys and 106 girls), in which they were asked to estimate the total amount of time they spent playing video games each week and which games were the most popular. Aggression was also assessed using two measures, the first dealing with manifest physical aggression and the second with aggressive behavioural delinquency. The data collected showed that 62% of teenagers spend at least one hour a week playing video games, with 10% spending over seven hours on them. Girls tended to play less than boys (1.6 and 2.8 hours on average respectively). Eight of the ten most popular games require the player to perform acts of a violent nature. Boys also scored higher on the index of aggressive behavioural delinquency, with a mean of 7.0 compared to 4.6 for girls. The results of the correlation analysis between time spent playing video games and measures of aggression were mixed. No relation was found between manifest physical aggression and time spent on the games, although in the case of aggressive behavioural delinquency the link was significant, which seems to indicate that aggressive teenagers spend more time playing video games. While the lack of significant correlations between violent games and aggression suggest that video games may not in fact be as great a menace as their critics suggest, Mr. Sazonov admits that these findings may be influenced by the high number of teenagers who do not play games at all or play relatively little. He also suggests that the abstract nature of the violence in games (often directed against aliens or spaceships) may make it less of a risk than the more realistic violence seen on television. In summary, however, he concludes that his results provide more support for the theories saying that violent video games provide a stimulus to violent action, than for those which suggest that they may help defuse violent tendencies.

Adenosine diphosphate (ADP) and ADP receptor play a major role in platelet activation/aggregation induced by sera from heparin-induced thrombocytopenia patients

The molecular basis for heparin-induced thrombocytopenia (HIT), a relatively common complication of heparin therapy, is not yet fully understood. We found that pretreatment of platelets with AR-C66096 (formerly FPL 66096), a specific platelet adenosine diphosphate (ADP) receptor antagonist, at a concentration of 100 to 200 nmol/L that blocked ADP-dependent platelet aggregation, resulted in complete loss of platelet aggregation responses to HIT sera. AR-C66096 also totally inhibited HIT serum-induced dense granule release, as judged by measurement of adenosine triphosphate (ATP) release. Apyrase, added to platelets at a concentration that had only minor effects on thrombin- or arachidonic acid-induced aggregation, also blocked completely HIT serum-induced platelet aggregation. Furthermore, AR-C66096 inhibited platelet aggregation and ATP release induced by cross-linking Fc gamma RIIA with specific antibodies. These data show that released ADP and the platelet ADP receptor play a pivotal role in HIT serum-induced platelet activation/aggregation. The thromboxane receptor inhibitor, Daltroban, had no effect on HIT serum-induced platelet activation whereas GPIIb-IIIa antagonists blocked platelet aggregation but had only a moderate effect on HIT serum-induced dense granule release. Pretreatment of platelets with chondroitinases but not with heparinases resulted in concentration dependent inhibition of HIT serum-induced platelet aggregation. These novel data relating to the mechanism of platelet activation induced by HIT sera suggest that the possibility should be examined that ADP receptor antagonists or compounds that inhibit ADP release may be effective as therapeutic agents for the prevention or treatment of complications associated with heparin therapy.

Place for video games : a theoretical and pedagogical framework for multiliteracies learning in English studies

Students are now involved in a vastly different textual landscape than many English scholars, one that relies on the “reading” and interpretation of multiple channels of simultaneous information. As a response to these new kinds of literate practices, my dissertation adds to the growing body of research on multimodal literacies, narratology in new media, and rhetoric through an examination of the place of video games in English teaching and research. I describe in this dissertation a hybridized theoretical basis for incorporating video games in English classrooms. This framework for textual analysis includes elements from narrative theory in literary study, rhetorical theory, and literacy theory, and when combined to account for the multiple modalities and complexities of gaming, can provide new insights about those theories and practices across all kinds of media, whether in written texts, films, or video games. In creating this framework, I hope to encourage students to view texts from a meta-level perspective, encompassing textual construction, use, and interpretation. In order to foster meta-level learning in an English course, I use specific theoretical frameworks from the fields of literary studies, narratology, film theory, aural theory, reader-response criticism, game studies, and multiliteracies theory to analyze a particular video game: World of Goo. These theoretical frameworks inform pedagogical practices used in the classroom for textual analysis of multiple media. Examining a video game from these perspectives, I use analytical methods from each, including close reading, explication, textual analysis, and individual elements of multiliteracies theory and pedagogy. In undertaking an in-depth analysis of World of Goo, I demonstrate the possibilities for classroom instruction with a complex blend of theories and pedagogies in English courses. This blend of theories and practices is meant to foster literacy learning across media, helping students develop metaknowledge of their own literate practices in multiple modes. Finally, I outline a design for a multiliteracies course that would allow English scholars to use video games along with other texts to interrogate texts as systems of information. In doing so, students can hopefully view and transform systems in their own lives as audiences, citizens, and workers.