Summary
ISG15 is an interferon-induced and anti-viral ubiquitin-like protein (Ubl). Herc5, the major E3 enzyme for ISG15, mediates the ISGylation of over 300 proteins in interferon-stimulated cells. In addressing this broad substrate selectivity of Herc5, we found that: 1) the range of substrates extends even further and includes many exogenously expressed foreign proteins, 2) ISG15 conjugation is restricted to newly synthesized pools of proteins, and 3) Herc5 is physically associated with polyribosomes. These results lead to a model for ISGylation in which Herc5 broadly modifies newly synthesized proteins in a co-translational manner. This represents a novel mechanism for conjugation of a Ubl and further suggests that, in the context of an interferon-stimulated cell, newly translated viral proteins may be primary targets of ISG15. Consistent with this, we demonstrate that ISGylation of human papillomavirus (HPV) L1 capsid protein has a dominant-inhibitory effect on the infectivity of HPV16 pseudoviruses.
Fibroblast growth factor binding protein 1 (FGFBP1) is expressed in various tumors and may serve as a diagnostic marker and/or a therapeutic target. Previous studies suggested FGFBP1 functions as an angiogenic switch molecule by regulating the activity of FGF2, and it was later found to associate with a broad spectrum of FGFs. To study FGFBP1, we used zebrafish, in which the function of extracellular matrix protein can be easily studied in intact tissues or organisms. When Fgfbp1 expression was knocked down, morphants manifested massive cell death and structural abnormalities. Cell death was most prominent in the brain and the neural tube, but not limited to those regions. These findings suggest that the primary function of Fgfbp1 may be to sustain cellular survival throughout embryogenesis. For comparison, the expression of fgf2 was limited to the early stage of embryogenesis and fgf2 morphants showed more severe phenotype, with high morbidity before reaching 14-somites. Taken together, our work reveals the physiologic function of Fgfbp1, and that its function could be exerted in a Fgf2-independent manner.
A critical component of teacher effectiveness is how teachers notice students' misconceptions and adjust the instructional approach accordingly. Taking a stance that the teachers' instructional quality is crucial to students' learning, a qualitative international comparison study was performed to examine science teachers' perceptions of and their approaches toward students' misconception on photosynthesis between the United States (US) and South Korea. A web-based on-line survey consisting of open-ended questions was administered to secondary science teachers and 85 and 81 teacher responses were collected from the US and Korea, respectively. Constructed responses were analyzed using the constant comparative method and enumerative approach through which regularities and patterns in the responses emerged. Four categories emerged concerning teacher perceptions of misconceptions: Concept, Knowledge Construction, Curriculum, and Pedagogical. Most teachers employed Concept or Knowledge Construction perspective to identify and reason out student misconceptions in both countries. In respect to instructional strategies, two dominant patterns emerged: content-focused and student-focused strategies. Teachers from both countries demonstrated the most frequent use of contentcentered approaches, although the patterns of the usage in relation to their perceptions towards misconceptions were different to some degree. Possible attributing factors for the observed patterns and some limitations of the study are further discussed.
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