Proposal to the Ethics Education in Science and Engineering Program, National Science Foundation: Role-Play Scenarios for Teaching Responsible Conduct of Research

We propose to develop and assess role-play scenarios to teach central topics in the responsible conduct of research (RCR) to graduate students in science and engineering. Together the scenarios will cover plagiarism, authorship, conflict of interest, interpersonal conflicts in mentoring, and concerns about compliance with research regulations on human participants in research, animal subjects, or hazardous substances. Two scenarios will present potential whistleblowing situations. Intellectual merit: Few previous studies have carefully assessed the effectiveness of role-play in teaching ethics. We will conduct a rigorous, systematic assessment of role-play, using multiple methods, with a diverse group of graduate students. We will examine whether role-play helps students identify moral issues in research, understand multiple perspectives in ethical disputes, and negotiate practical solutions to moral problems. We will document how students’ conceptions of RCR change. We will determine whether students retain their new knowledge and skills. For this project, we will draw on our previous experience in the scholarship of teaching and learning. Broader impacts: Collaborating with both graduate and undergraduate students, we will develop educational materials that can be adopted by graduate programs in all science and engineering departments. These materials will be disseminated through professional meetings and archived online. We believe that by engaging students through the role-play scenarios, we would teach graduate students to handle ethical problems in RCR effectively. As an outcome of this project, we expect to find that long after students have participated in role-play sessions, they will recall the lessons of those sessions, and they will be able to apply those lessons to a wide range of ethical problems that they may encounter in their professional careers

Electronic Structure of Cytochrome P450

The optical properties of P450 have been investigated by means of polarized absorption spectroscopy of single crystals of camphor- bound P450CAM in the oxidized, reduced, and CO-reduced states, and iterative extended Ruckel (IEH) calculations. The heme chromophores are orientated such that transitions polarized in the heme plane (x,y-polarized) can be readily distinguished from transitions polarized perpendicular to the heme plane (z-polarized) . High spin oxidized P450 exhibits two broad z-polarized bands, at 567 and 323 nm. IEH calculations suggest that these bands arise from cysteine mercaptide sulfur-to-iron charge transfer transitions. High spin reduced P450 has no z-polarized bands. IEH calculations suggest that loss of these bands occurs because the cysteine sulfur is protonated to a mercaptan. Low spin CO-P450 has an intense x,y-polarized band at 363 nm. This transition, assigned as a mercaptide sulfur-to-porphyrin charge transfer transition, has the correct symmetry to mix with the Soret and may cause the anomalous red shift of the Soret

New Models of Hybrid Leadership in Global Higher Education

This manuscript highlights the development of a leadership preparation program known as the Nanyang Technological University Leadership Academy (NTULA), exploring the leadership challenges unique to a university undergoing rapid growth in a highly multicultural context, and the hybrid model of leadership it developed in response to globalization. It asks the research question of how the university adapted to a period of accelerated growth and transition by adopting a hybrid approach to academic leadership. The paper uses qualitative methodology to review NTULA’s first cohort, including interviews and participant survey responses. The findings illuminate three key areas of the hybridized leadership model that are challenging to balance, including managing the transition from the leadership style required to drive rapid institutional change to the approach needed to preserve that growth, how leaders reconcile the need to be responsive to both administration and faculty, and how to lead in a highly diverse, multicultural space

Protein components of a cytochrome P-450 linalool 8-methyl hydroxylase

The cytochrome P-450 heme-thiolate monooxygenases that hydroxylate monoterpene hydrocarbon groups are effective models for the cytochrome P-450 family. We have purified and characterized the three proteins from a P-450-dependent linalool 8-methyl hydroxylase in Pseudomonas putida (incognita) strain PpG777. The proteins resemble the camphor 5-exohydroxylase components in chemical and physical properties; however, they show neither immunological cross-reactivity nor catalytic activity in heterogenous recombination. These two systems provide an excellent model to probe more deeply the heme-thiolate reaction center, molecular domains of substrate specificity, redox-pair interactions, and the regulation of the reaction cycle

Electronic Structure of Cytochrome P450

The optical properties of P450 have been investigated by means of polarized absorption spectroscopy of single crystals of camphor- bound P450CAM in the oxidized, reduced, and CO-reduced states, and iterative extended Ruckel (IEH) calculations. The heme chromophores are orientated such that transitions polarized in the heme plane (x,y-polarized) can be readily distinguished from transitions polarized perpendicular to the heme plane (z-polarized) . High spin oxidized P450 exhibits two broad z-polarized bands, at 567 and 323 nm. IEH calculations suggest that these bands arise from cysteine mercaptide sulfur-to-iron charge transfer transitions. High spin reduced P450 has no z-polarized bands. IEH calculations suggest that loss of these bands occurs because the cysteine sulfur is protonated to a mercaptan. Low spin CO-P450 has an intense x,y-polarized band at 363 nm. This transition, assigned as a mercaptide sulfur-to-porphyrin charge transfer transition, has the correct symmetry to mix with the Soret and may cause the anomalous red shift of the Soret

RNAiAtlas: a database for RNAi (siRNA) libraries and their specificity

Large-scale RNA interference (RNAi) experiments, especially the ones based on short-interfering RNA (siRNA) technology became increasingly popular over the past years. For such knock-down/screening purposes, different companies offer sets of oligos/reagents targeting the whole genome or a subset of it for various organisms. Obviously, the sequence (and structure) of the corresponding oligos is a key factor in obtaining reliable results in these large-scale studies and the companies use a variety of (often not fully public) algorithms to design them. Nevertheless, as the genome annotations are still continuously changing, oligos may become obsolete, so siRNA reagents should be periodically re-annotated according to the latest version of the sequence database (which of course has serious consequences also on the interpretation of the screening results). In our article, we would like to introduce a new software/database tool, the RNAiAtlas. It has been created for exploration, analysis and distribution of large scale RNAi libraries (currently limited to the human genome) with their latest annotation (including former history) but in addition it contains also specific on-target analysis results (design quality, side effects, off-targets)

Phenotypic and Physiological Characterization of the Epibiotic Interaction Between TM7x and Its Basibiont Actinomyces

Despite many examples of obligate epibiotic symbiosis (one organism living on the surface of another) in nature, such an interaction has rarely been observed between two bacteria. Here, we further characterize a newly reported interaction between a human oral obligate parasitic bacterium TM7x (cultivated member of Candidatus Saccharimonas formerly Candidate Phylum TM7), and its basibiont Actinomyces odontolyticus species (XH001), providing a model system to study epiparasitic symbiosis in the domain Bacteria. Detailed microscopic studies indicate that both partners display extensive morphological changes during symbiotic growth. XH001 cells manifested as short rods in monoculture, but displayed elongated and hyphal morphology when physically associated with TM7x. Interestingly, these dramatic morphological changes in XH001 were also induced in oxygen-depleted conditions, even in the absence of TM7x. Targeted quantitative real-time PCR (qRT-PCR) analyses revealed that both the physical association with TM7x as well as oxygen depletion triggered up-regulation of key stress response genes in XH001, and in combination, these conditions act in an additive manner. TM7x and XH001 co-exist with relatively uniform cell morphologies under nutrient-replete conditions. However, upon nutrient depletion, TM7x-associated XH001 displayed a variety of cell morphologies, including swollen cell body, clubbed-ends, and even cell lysis, and a large portion of TM7x cells transformed from ultrasmall cocci into elongated cells. Our study demonstrates a highly dynamic interaction between epibiont TM7x and its basibiont XH001 in response to physical association or environmental cues such as oxygen level and nutritional status, as reflected by their morphological and physiological changes during symbiotic growth

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps