Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes.

The eukaryotic cell cycle is controlled by a network of interacting regulatory proteins. We used an interaction mating two-hybrid assay to identify connections within the cell cycle regulatory network in Drosophila. We tested interactions between Drosophila cyclins and a panel of hundreds of previously identified proteins. One of the connections we identified was the interaction between cyclin E and a novel Drosophila protein, Cdi4. Because Cdi4 was originally identified by its ability to interact with a Drosophila cyclin-dependent kinase, the finding that it interacts with cyclin E strengthened the notion that it functions in cell cycle regulation. We show that Cdi4 can inhibit cyclin E function both in a yeast assay and in vitro. In light of these results, our sequence analysis revealed that Cdi4 is a unique member of the p21/p27/p57 family of Cdk inhibitors. Our results demonstrate that interaction mating assays using large informative panels of proteins can aid the analysis of regulatory networks by generating and constraining hypotheses that guide further work

A protein network-guided screen for cell cycle regulators in Drosophila

Background: Large-scale RNAi-based screens are playing a critical role in defining sets of genes that regulate specific cellular processes. Numerous screens have been completed and in some cases more than one screen has examined the same cellular process, enabling a direct comparison of the genes identified in separate screens. Surprisingly, the overlap observed between the results of similar screens is low, suggesting that RNAi screens have relatively high levels of false positives, false negatives, or both

A database and tool, IM Browser, for exploring and integrating emerging gene and protein interaction data for Drosophila

BACKGROUND: Biological processes are mediated by networks of interacting genes and proteins. Efforts to map and understand these networks are resulting in the proliferation of interaction data derived from both experimental and computational techniques for a number of organisms. The volume of this data combined with the variety of specific forms it can take has created a need for comprehensive databases that include all of the available data sets, and for exploration tools to facilitate data integration and analysis. One powerful paradigm for the navigation and analysis of interaction data is an interaction graph or map that represents proteins or genes as nodes linked by interactions. Several programs have been developed for graphical representation and analysis of interaction data, yet there remains a need for alternative programs that can provide casual users with rapid easy access to many existing and emerging data sets. DESCRIPTION: Here we describe a comprehensive database of Drosophila gene and protein interactions collected from a variety of sources, including low and high throughput screens, genetic interactions, and computational predictions. We also present a program for exploring multiple interaction data sets and for combining data from different sources. The program, referred to as the Interaction Map (IM) Browser, is a web-based application for searching and visualizing interaction data stored in a relational database system. Use of the application requires no downloads and minimal user configuration or training, thereby enabling rapid initial access to interaction data. IM Browser was designed to readily accommodate and integrate new types of interaction data as it becomes available. Moreover, all information associated with interaction measurements or predictions and the genes or proteins involved are accessible to the user. This allows combined searches and analyses based on either common or technique-specific attributes. The data can be visualized as an editable graph and all or part of the data can be downloaded for further analysis with other tools for specific applications. The database is available at CONCLUSION: The Drosophila Interactions Database described here places a variety of disparate data into one easily accessible location. The database has a simple structure that maintains all relevant information about how each interaction was determined. The IM Browser provides easy, complete access to this database and could readily be used to publish other sets of interaction data. By providing access to all of the available information from a variety of data types, the program will also facilitate advanced computational analyses

A Drosophila protein-interaction map centered on cell-cycle regulators

BACKGROUND: Maps depicting binary interactions between proteins can be powerful starting points for understanding biological systems. A proven technology for generating such maps is high-throughput yeast two-hybrid screening. In the most extensive screen to date, a Gal4-based two-hybrid system was used recently to detect over 20,000 interactions among Drosophila proteins. Although these data are a valuable resource for insights into protein networks, they cover only a fraction of the expected number of interactions. RESULTS: To complement the Gal4-based interaction data, we used the same set of Drosophila open reading frames to construct arrays for a LexA-based two-hybrid system. We screened the arrays using a novel pooled mating approach, initially focusing on proteins related to cell-cycle regulators. We detected 1,814 reproducible interactions among 488 proteins. The map includes a large number of novel interactions with potential biological significance. Informative regions of the map could be highlighted by searching for paralogous interactions and by clustering proteins on the basis of their interaction profiles. Surprisingly, only 28 interactions were found in common between the LexA- and Gal4-based screens, even though they had similar rates of true positives. CONCLUSIONS: The substantial number of new interactions discovered here supports the conclusion that previous interaction mapping studies were far from complete and that many more interactions remain to be found. Our results indicate that different two-hybrid systems and screening approaches applied to the same proteome can generate more comprehensive datasets with more cross-validated interactions. The cell-cycle map provides a guide for further defining important regulatory networks in Drosophila and other organisms

Measurement of the antineutrino neutral-current elastic differential cross section

arXiv:1309.7257v1 [hep-ex

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest ($K^+ \rightarrow \mu^+ \nu_\mu$) at the NuMI beamline absorber. These signal $\nu_\mu$-carbon events are distinguished from primarily pion decay in flight $\nu_\mu$ and $\overline{\nu}_\mu$ backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9$\sigma$ level. The muon kinetic energy, neutrino-nucleus energy transfer ($\omega=E_\nu-E_\mu$), and total cross section for these events is extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of $\omega$ using neutrinos, a quantity thus far only accessible through electron scattering.Comment: 6 pages, 4 figure

Measurement of inclusive charged current interactions on carbon in a few-GeV neutrino beam

The SciBooNE Collaboration reports a measurement of inclusive charged current interactions of muon neutrinos on carbon with an average energy of 0.8 GeV using the Fermilab Booster Neutrino Beam. We compare our measurement with two neutrino interaction simulations: NEUT and NUANCE. The charged current interaction rates (product of flux and cross section) are extracted by fitting the muon kinematics, with a precision of 6-15% for the energy dependent and 3% for the energy integrated analyses. We also extract CC inclusive interaction cross sections from the observed rates, with a precision of 10-30% for the energy dependent and 8% for the energy integrated analyses. This is the first measurement of the CC inclusive cross section on carbon around 1 GeV. These results can be used to convert previous SciBooNE cross section ratio measurements to absolute cross section values.Comment: 21 pages, 16 figures. Accepted by Phys. Rev. D. Minor revisions to match the accepted versio

Measurement of Muon Neutrino Quasi-Elastic Scattering on Carbon

The observation of neutrino oscillations is clear evidence for physics beyond the standard model. To make precise measurements of this phenomenon, neutrino oscillation experiments, including MiniBooNE, require an accurate description of neutrino charged current quasi-elastic (CCQE) cross sections to predict signal samples. Using a high-statistics sample of muon neutrino CCQE events, MiniBooNE finds that a simple Fermi gas model, with appropriate adjustments, accurately characterizes the CCQE events observed in a carbon-based detector. The extracted parameters include an effective axial mass, M_A^eff = 1.23+/-0.20 GeV, that describes the four-momentum dependence of the axial-vector form factor of the nucleon; and a Pauli-suppression parameter, kappa = 1.019+/-0.011. Such a modified Fermi gas model may also be used by future accelerator-based experiments measuring neutrino oscillations on nuclear targets.Comment: 5 pages, 3 figure

Measurement of the \nu_\mu charged current \pi^+ to quasi-elastic cross section ratio on mineral oil in a 0.8 GeV neutrino beam

Using high statistics samples of charged current $\nu_\mu$ interactions, MiniBooNE reports a measurement of the single charged pion production to quasi-elastic cross section ratio on mineral oil (CH$_2$), both with and without corrections for hadron re-interactions in the target nucleus. The result is provided as a function of neutrino energy in the range 0.4 GeV $< E_\nu <$ 2.4 GeV with 11% precision in the region of highest statistics. The results are consistent with previous measurements and the prediction from historical neutrino calculations.Comment: 4 pages, 2 figure