Two novel, highly potent, cytotoxic macrolides, salicylihalamides A (1) and B (2), were isolated from the sponge Haliclona sp. This new macrolide class incorporates salicylic acid, a 12-membered lactone ring, and an enamide side chain. COMPARE pattern-recognition analyses of the NCI 60-cell mean graph screening profiles of 1 did not reveal any significant correlations to the profiles of known antitumor compounds in the NCI's "standard agent database", thus supporting the conclusion that the salicylihalamides represent a potentially important new class for antitumor lead optimization and in vivo investigations.

Instructor Talk—noncontent language used by instructors in classrooms—is a recently defined and promising variable for better understanding classroom dynamics. Having previously characterized the Instructor Talk framework within the context of a single course, we present here our results surrounding the applicability of the Instructor Talk framework to noncontent language used by instructors in novel course contexts. We analyzed Instructor Talk in eight additional biology courses in their entirety and in 61 biology courses using an emergent sampling strategy. We observed widespread use of Instructor Talk with variation in the amount and category type used. The vast majority of Instructor Talk could be characterized using the originally published Instructor Talk framework, suggesting the robustness of this framework. Additionally, a new form of Instructor Talk—Negatively Phrased Instructor Talk, language that may discourage students or distract from the learning process—was detected in these novel course contexts. Finally, the emergent sampling strategy described here may allow investigation of Instructor Talk in even larger numbers of courses across institutions and disciplines. Given its widespread use, potential influence on students in learning environments, and ability to be sampled, Instructor Talk may be a key variable to consider in future research on teaching and learning in higher education.

No abstract

Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.

Active-learning pedagogies have been repeatedly demonstrated to produce superior learning gains with large effect sizes compared with lecture-based pedagogies. Shifting large numbers of college science, technology, engineering, and mathematics (STEM) faculty to include any active learning in their teaching may retain and more effectively educate far more students than having a few faculty completely transform their teaching, but the extent to which STEM faculty are changing their teaching methods is unclear. Here, we describe the development and application of the machine-learning-derived algorithm Decibel Analysis for Research in Teaching (DART), which can analyze thousands of hours of STEM course audio recordings quickly, with minimal costs, and without need for human observers. DART analyzes the volume and variance of classroom recordings to predict the quantity of time spent on single voice (e.g., lecture), multiple voice (e.g., pair discussion), and no voice (e.g., clicker question thinking) activities. Applying DART to 1,486 recordings of class sessions from 67 courses, a total of 1,720 h of audio, revealed varied patterns of lecture (single voice) and nonlecture activity (multiple and no voice) use. We also found that there was significantly more use of multiple and no voice strategies in courses for STEM majors compared with courses for non-STEM majors, indicating that DART can be used to compare teaching strategies in different types of courses. Therefore, DART has the potential to systematically inventory the presence of active learning with ∼90% accuracy across thousands of courses in diverse settings with minimal effort.active learning | evidence-based teaching | science education | lecture | assessment C urrent college STEM (science, technology, engineering, and mathematics) teaching in the United States continues to be lecture-based and is relatively ineffective in promoting learning (1, 2). Undergraduate instructors continue to struggle to engage, effectively teach, and retain postsecondary students, both generally and particularly among women and students of color (3, 4). Federal analyses suggest that a 10% increase in retention of undergraduate STEM students could address anticipated STEM workforce shortfalls (5). Replacing the standard lecture format with more active teaching strategies has been shown to increase

The relationship between the transition to budding and flowering in Artemisia annua and the production of the antimalarial sesquiterpene, artemisinin (AN), the dynamics of artemisinic metabolite changes, AN-related transcriptional changes, and plant and trichome developmental changes were measured. Maximum production of AN occurs during full flower stage within floral tissues, but that changes in the leafy bracts and nonbolt leaves as the plant shifts from budding to full flower. Expression levels of early pathway genes known to be involved in isopentenyl diphosphate and farnesyl diphosphate biosynthesis leading to AN were not immediately positively correlated with either AN or its precursors. However, we found that the later AN pathway genes, amorpha-4,11-diene synthase (ADS) and the cytochrome P450, CYP71AV1 (CYP), were more highly correlated with AN's immediate precursor, dihydroartemisinic acid, within all leaf tissues tested. In addition, leaf trichome formation throughout the developmental phases of the plant also appears to be more complex than originally thought. Trichome changes correlated closely with the levels of AN but not its precursors. Differences were observed in trichome densities that are dependent both on developmental stage (vegetative, budding, and flowering) and on position (upper and lower leaf tissue). AN levels declined significantly as plants matured, as did ADS and CYP transcripts. Spraying leaves with AN or artemisinic acid inhibited CYP transcription; artemisinic acid also inhibited ADS transcription. These data allow us to present a novel model for the differential control of AN biosynthesis as it relates to developmental stage and trichome maturation and collapse.

The 12-site National Fire and Fire Surrogate study (FFS) was a multivariate experiment that evaluated ecological consequences of alternative fuel-reduction treatments in seasonally dry forests of the US. Each site was a replicated experiment with a common design that compared an un-manipulated control, prescribed fire, mechanical and mechanical + fire treatments. Variables within the vegetation, fuelbed, forest floor and soil, bark beetles, tree diseases and wildlife were measured in 10-ha stands, and ecological response was compared among treatments at the site level, and across sites, to better understand the influence of differential site conditions. For most sites, treated stands were predicted to be more resilient to wildfire if it occurred shortly after treatment, but for most ecological variables, short-term response to treatments was subtle and transient. Strong site-specificity was observed in the response of most ecosystem variables, suggesting that practitioners employ adaptive management at the local scale. Because ecosystem components were tightly linked, adaptive management would need to include monitoring of a carefully chosen set of key variables. Mechanical treatments did not serve as surrogates for fire for most variables, suggesting that fire be maintained whenever possible. Restoration to pre-settlement conditions will require repeated treatments over time, with eastern forests requiring more frequent applications.

The novel phorbol ester 12-deoxyphorbol 13-(3E,5E-decadienoate) [1] was isolated as the anti-HIV principle of Excoecaria agallocha leaves and stems collected in northwest Australia. The structure was determined by spectral means. Compound 1 was also a potent displacer of [3H]-phorbol dibutyrate from rat brain membranes.