Basal Quality Research Articles

Against Universalism in Biosemiotic Theories

Abstract The frontiers of biosemiotics are inconspicuously blurry. This is a feature and not a bug of the discipline in that it allows us to ask questions beyond certain boundaries, enriching both our knowledge beyond semiotic theories and the possibility of covering new ground through them. Yet, explanatory power should be something of a concern for biosemioticians looking to plant flags around different heights. The paths cleared by backwoodsmen should hold up to scrutiny, and in order for biosemioticians to examine these paths, some of the features of semiotic theory should work as reminders of what the aim of semiotic theory is. This paper will explore one particular issue when it comes to building biosemiotic theories, namely, the idea that the semiotic comprises a universal and basal quality in a hierarchy of elements assumed to give rise to other, more complex things. The metatheoretical problem at its core will be defined as the unnecessary expansion of semiotic attributes in order to give them enough explanatory power to either provide semiotic theories of everything or give a semiotic basis to theories that do not, in principle, require it.

Abstract 1002: Molecular characterization of aggresome formation in choroid plexus carcinoma

Abstract Our long-term goal is to define and characterize the mechanisms underlying aggresome formation in choroid plexus carcinoma a rare pediatric tumor. Protein misfolding is inevitable, 30% of newly synthesized polypeptides can end up misfolded, such proteins are either refolded or eliminated by cellular quality control pathways which include the ubquitin proteosome system and autophagy. In recent years, protein misfolding has been implicated in the pathophysiology of many diseases such as diabetes, neurological disorders and cancer. Studies from our laboratory have shown that choroid plexus carcinoma tumors are characterized by the formation of aggresomes at the microtubules organizing centers (MTOC) in FFPE tumor tissues. This was further conformed by the development of choroid plexus carcinoma cell line (CPC-45) which was characterized by the constitutive formation of aggresomes at MTOC. When examining the soluble and insoluble fractions, vimentin was only identified in the insoluble fraction. These results were further confirmed using electron microscopy. Aggresome formation implies presence of toxic protein over load and/or defective autophagy. CPC-45 cells displayed normal LC3B (an indicator of autophagosome) expression and regulation upon nutrient deprivation. To further monitor autophagy, CPC-45 and SHY-5Y cells were infected with the dual Tandem Sensor RFP-GFP-LC3B to label autophagosome and its maturation to autolysosome. While SHY-5Y displayed both green and red fluorescence upon infection, CPC-45 was only positive after serum starvation thus confirming the targeting of aggresomes by LC3B mediated autophagy. Recently, the LC3B paralog LC3AV1 was found to be silenced by DNA methylation in several cancer cell lines and reported as major player in autophagy and as a potential tumor suppressor. To further explore the role of LC3A in aggresome formation, CPC-45 cells were transfected with either GFP empty vector or LC3AV1-GFP construct. Only LC3A-GFP transfected cells were positive for aggresome formation while in GFP transfected we did not observe any signal. Consistent with previous reports that over expression of GFP results in protein accumulation at the aggresomes. Our results suggest that LC3A is the mediator of the basal quality control function of autophagy which is different from the stress induced autophagy mediated by LC3B. Based on our findings, we propose that perturbation in the autophagic pathway due lack of LC3Av1 expression lead to a failure in the aggresome degradation process and hence provide an advantage to tumor cells to overcome protein misfold overload thus contributing to the tumorigenicity of the disease. Citation Format: Heba Samaha, Marwa Nassar, Myret Ghabriel, Maha Yehia, Hala Taha, Dina Yassin, Sherine Salem, Khaled Shaaban, Mariem Omar, Shahenda M. El-Naggar. Molecular characterization of aggresome formation in choroid plexus carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1002. doi:10.1158/1538-7445.AM2015-1002