A Caenorhabditis elegans genetic-interaction map wiggles into view

Systematic mapping of genetic-interaction networks will provide an essential foundation for understanding complex genetic disorders, mechanisms of genetic buffering and principles of robustness and evolvability. A recent study of signaling pathways in Caenorhabditis elegans lays the next row of bricks in this foundation

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

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

Diverse roles of actin in C. elegans early embryogenesis

<p>Abstract</p> <p>Background</p> <p>The actin cytoskeleton plays critical roles in early development in <it>Caenorhabditis elegans</it>. To further understand the complex roles of actin in early embryogenesis we use RNAi and <it>in vivo </it>imaging of filamentous actin (F-actin) dynamics.</p> <p>Results</p> <p>Using RNAi, we found processes that are differentially sensitive to levels of actin during early embryogenesis. Mild actin depletion shows defects in cortical ruffling, pseudocleavage, and establishment of polarity, while more severe depletion shows defects in polar body extrusion, cytokinesis, chromosome segregation, and eventually, egg production. These defects indicate that actin is required for proper oocyte development, fertilization, and a wide range of important events during early embryogenesis, including proper chromosome segregation. <it>In vivo </it>visualization of the cortical actin cytoskeleton shows dynamics that parallel but are distinct from the previously described myosin dynamics. Two distinct types of actin organization are observed at the cortex. During asymmetric polarization to the anterior, or the establishment phase (Phase I), actin forms a meshwork of microfilaments and focal accumulations throughout the cortex, while during the anterior maintenance phase (Phase II) it undergoes a morphological transition to asymmetrically localized puncta. The proper asymmetric redistribution is dependent on the PAR proteins, while both asymmetric redistribution and morphological transitions are dependent upon PFN-1 and NMY-2. Just before cytokinesis, actin disappears from most of the cortex and is only found around the presumptive cytokinetic furrow. Finally, we describe dynamic actin-enriched comets in the early embryo.</p> <p>Conclusion</p> <p>During early <it>C. elegans </it>embryogenesis actin plays more roles and its organization is more dynamic than previously described. Morphological transitions of F-actin, from meshwork to puncta, as well as asymmetric redistribution, are regulated by the PAR proteins. Results from this study indicate new insights into the cellular and developmental roles of the actin cytoskeleton.</p

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

Dynamics of Electron Transport in Cytochrome P450 Systems Studied at Sub-Zero Temperature

Experimentation in fluid mixed solvents (1 : 1 v/v phosphate buffer ethylene glycol) at sub-zero temperatures has permitted us to record the two univalent reductions of the bacterial cytochrome P450 by the natural electron donor putidaredoxin, without recycling or alternative pathway reactions. Dynamic evidence shows the formation of putidaredoxincytochrome complexes prior to electron transfer. The complex formation is rate limiting in the first reduction and in our experimental conditions. The kinetics of binding between the two oxidized proteins has also been recorded in the same medium under various conditions of concentration, temperature and ionic strength. At very low ionic strength, the rate is limited by electrostatic repulsion between the two negatively charge proteins; above I = 0.03 this effect appears negligible and the affinity seems to be governed by hydrophobic interaction free energy

Dynamics of Electron Transport in Cytochrome P450 Systems Studied at Sub-Zero Temperature

Experimentation in fluid mixed solvents (1 : 1 v/v phosphate buffer ethylene glycol) at sub-zero temperatures has permitted us to record the two univalent reductions of the bacterial cytochrome P450 by the natural electron donor putidaredoxin, without recycling or alternative pathway reactions. Dynamic evidence shows the formation of putidaredoxincytochrome complexes prior to electron transfer. The complex formation is rate limiting in the first reduction and in our experimental conditions. The kinetics of binding between the two oxidized proteins has also been recorded in the same medium under various conditions of concentration, temperature and ionic strength. At very low ionic strength, the rate is limited by electrostatic repulsion between the two negatively charge proteins; above I = 0.03 this effect appears negligible and the affinity seems to be governed by hydrophobic interaction free energy

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

microRNA Target Predictions across Seven Drosophila Species and Comparison to Mammalian Targets

microRNAs are small noncoding genes that regulate the protein production of genes by binding to partially complementary sites in the mRNAs of targeted genes. Here, using our algorithm PicTar, we exploit cross-species comparisons to predict, on average, 54 targeted genes per microRNA above noise in Drosophila melanogaster. Analysis of the functional annotation of target genes furthermore suggests specific biological functions for many microRNAs. We also predict combinatorial targets for clustered microRNAs and find that some clustered microRNAs are likely to coordinately regulate target genes. Furthermore, we compare microRNA regulation between insects and vertebrates. We find that the widespread extent of gene regulation by microRNAs is comparable between flies and mammals but that certain microRNAs may function in clade-specific modes of gene regulation. One of these microRNAs (miR-210) is predicted to contribute to the regulation of fly oogenesis. We also list specific regulatory relationships that appear to be conserved between flies and mammals. Our findings provide the most extensive microRNA target predictions in Drosophila to date, suggest specific functional roles for most microRNAs, indicate the existence of coordinate gene regulation executed by clustered microRNAs, and shed light on the evolution of microRNA function across large evolutionary distances. All predictions are freely accessible at our searchable Web site http://pictar.bio.nyu.edu