Selective use of the primary literature transforms the classroom into a virtual laboratory

CREATE (consider, read, elucidate hypotheses, analyze and interpret the data, and think of the next experiment) is a new method for teaching science and the nature of science through primary literature. CREATE uses a unique combination of novel pedagogical tools to guide undergraduates through analysis of journal articles, highlighting the evolution of scientific ideas by focusing on a module of four articles from the same laboratory. Students become fluent in the universal language of data analysis as they decipher the figures, interpret the findings, and propose and defend further experiments to test their own hypotheses about the system under study. At the end of the course students gain insight into the individual experiences of article authors by reading authors' responses to an e-mail questionnaire generated by CREATE students. Assessment data indicate that CREATE students gain in ability to read and critically analyze scientific data, as well as in their understanding of, and interest in, research and researchers. The CREATE approach demystifies the process of reading a scientific article and at the same time humanizes scientists. The positive response of students to this method suggests that it could make a significant contribution to retaining undergraduates as science majors.     

The hedgehog receptor patched is involved in cholesterol transport

Background

Sonic hedgehog (Shh) signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.

Methodology/Principal Findings

Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol) from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.

Conclusion/Significance

Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.     

What Do Experts and Novices ��See�� in Evolutionary Problems?

Considerable research has focused on differences in expert and novice problem representation and performance within physics, chemistry, and genetics. Here, we examine whether models of problem solving based on this work are useful within the domain of evolutionary biology. We utilized card sort tasks, interviews, and paper-and-pencil tests to: (1) delineate problem categorization rules, (2) quantify problem solving success, and (3) measure the relationships between the composition, structure, and coherence of problem solutions. We found that experts and novices perceived different item features to be of significance in card sort tasks, and that sensitivity to item surface features was adversely associated with problem solving success. As in other science domains, evolutionary problem representation and problem solving performance were tightly coupled. Explanatory coherence and the absence of cognitive biases were distinguishing features of evolutionary expertise. We discuss the implications of these findings for biology teaching and learning.     

Does the Segregation of Evolution in Biology Textbooks and Introductory Courses Reinforce Students’ Faulty Mental Models of Biology and Evolution?

The well-established finding that substantial confusion and misconceptions about evolution and natural selection persist after college instruction suggests that these courses neither foster accurate mental models of evolution’s mechanisms nor instill an appreciation of evolution’s centrality to an understanding of the living world. Our essay explores the roles that introductory biology courses and textbooks may play in reinforcing undergraduates’ pre-existing, faulty mental models of the place of evolution in the biological sciences. Our content analyses of the three best-selling introductory biology textbooks for majors revealed the conceptual segregation of evolutionary information. The vast majority of the evolutionary terms and concepts in each book were isolated in sections about evolution and diversity, while remarkably few were employed in other sections of the books. Standardizing the data by number of pages per unit did not alter this pattern. Students may fail to grasp that evolution is the unifying theme of biology because introductory courses and textbooks reinforce such isolation. Two goals are central to resolving this problem: the desegregation of evolution as separate “units” or chapters and the active integration of evolutionary concepts at all levels and across all domains of introductory biology.     

Cell cycle kinetics of regenerating urothelial cells of the rat urinary bladder after partial cystectomy

The cell cycle kinetics of bladder urothelial cells regenerating after partial cystectomy were investigated in 96 female Wistar rats using the percentage labelled mitoses method. In the area of resection a mean cell cycle time (TC) of 15 h was determined. The DNA synthesis phase (TS) lasted 6 h and the premitotic-postsynthetic phase together with the mitosis phase (TG2 + M) 1.5 h, thus giving a presynthetic-postmiotic phase (TG1) of 7.5 h. Similar values were found for the urothelial cells in the stump: the mean cycle time measured 14 h, the TS-phase 6 h, the TG6 + M-phase 2 h and the TG1-phase 6 h. These data are discussed with respect to known cell cycle parameters of bladder urothelium regenerating in response to cytotoxic agents and of neoplastic urothelial cells. The reported findings provide a basis for further investigations using weak carcinogens and threshold doses of potent carcinogens to test the working hypothesis that stimulation of proliferation following partial cystectomy is capable of initiating, accelerating and/or potentiating carcinogenic cell transformation in the urinary bladder.     

Kinetic theory of hyaluronan cleavage by bovine testicular hyaluronidase in standard and crowded environments

In this paper, we introduce a comprehensive kinetic model describing the enzymatic cleavage of hyaluronan (HA) by bovine testicular hyaluronidase (BTH). Our theory focuses specifically on the late stage of the hydrolysis, where the concentrations of a limited number of oligomers may be determined experimentally with accuracy as functions of time.The present model was applied to fit different experimental sets of kinetic data collected by capillary electrophoresis at two HA concentrations and three concentrations of PEG crowder (0, 10, 17% w/w). Our theory seems to apply universally, irrespective of HA concentration and crowding conditions, reproducing to an excellent extent the time evolution of the individual molar fractions of oligomers. Remarkably, we found that the reaction mechanism in the late degradation stage essentially reduces to the cleavage or transfer of active dimers. While the recombination of dimers is the fastest reaction, the rate-limiting step turns out to be invariably the hydrolysis of hexamers. Crowding, HA itself or other inert, volume-excluding agents, clearly boosts recombination events and concomitantly slows down all fragmentation pathways.Overall, our results bring a novel and comprehensive quantitative insight into the complex reaction mechanism underlying enzymatic HA degradation. Importantly, rationalizing the effect of crowding not only brings the intricate conditions of in-vivo settings a little closer, but also emerges as a powerful tool to help pinpointing relevant kinetic pathways in complex systems.