BioNAR: an integrated biological network analysis package in bioconductor.

Motivation: Biological function in protein complexes emerges from more than just the sum of their parts: molecules interact in a range of different sub-complexes and transfer signals/information around internal pathways. Modern proteomic techniques are excellent at producing a parts-list for such complexes, but more detailed analysis demands a network approach linking the molecules together and analysing the emergent architectural properties. Methods developed for the analysis of networks in social sciences have proven very useful for splitting biological networks into communities leading to the discovery of sub-complexes enriched with molecules associated with specific diseases or molecular functions that are not apparent from the constituent components alone. Results: Here, we present the Bioconductor package BioNAR, which supports step-by-step analysis of biological/biomedical networks with the aim of quantifying and ranking each of the network's vertices based on network topology and clustering. Examples demonstrate that while BioNAR is not restricted to proteomic networks, it can predict a protein's impact within multiple complexes, and enables estimation of the co-occurrence of metadata, i.e. diseases and functions across the network, identifying the clusters whose components are likely to share common function and mechanisms. Availability and implementation: The package is available from Bioconductor release 3.17: https://bioconductor.org/packages/release/bioc/html/BioNAR.html.

Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain.

The aim of this study was to develop and refine a heterologous mouse model of endometriosis-associated pain in which non-evoked responses, more relevant to the patient experience, were evaluated. Immunodeficient female mice (N = 24) were each implanted with four endometriotic human lesions (N = 12) or control tissue fat (N = 12) on the abdominal wall using tissue glue. Evoked pain responses were measured biweekly using von Frey filaments. Non-evoked responses were recorded weekly for 8 weeks using a home cage analysis (HCA). Endpoints were distance traveled, social proximity, time spent in the center vs. outer areas of the cage, drinking, and climbing. Significant differences between groups for von Frey response, climbing, and drinking were detected on days 14, 21, and 35 post implanting surgery, respectively, and sustained for the duration of the experiment. In conclusion, a heterologous mouse model of endometriosis-associated evoked a non-evoked pain was developed to improve the relevance of preclinical models to patient experience as a platform for drug testing.

Drosophila circadian rhythms in seminatural environments: Summer afternoon component is not an artifact and requires TrpA1 channels.

Under standard laboratory conditions of rectangular light/dark cycles and constant warm temperature, Drosophila melanogaster show bursts of morning (M) and evening (E) locomotor activity and a "siesta" in the middle of the day. These M and E components have been critical for developing the neuronal dual oscillator model in which clock gene expression in key cells generates the circadian phenotype. However, under natural European summer conditions of cycling temperature and light intensity, an additional prominent afternoon (A) component that replaces the siesta is observed. This component has been described as an "artifact" of the TriKinetics locomotor monitoring system that is used by many circadian laboratories world wide. Using video recordings, we show that the A component is not an artifact, neither in the glass tubes used in TriKinetics monitors nor in open-field arenas. By studying various mutants in the visual and peripheral and internal thermo-sensitive pathways, we reveal that the M component is predominantly dependent on visual input, whereas the A component requires the internal thermo-sensitive channel transient receptor potential A1 (TrpA1). Knockdown of TrpA1 in different neuronal groups reveals that the reported expression of TrpA1 in clock neurons is unlikely to be involved in generating the summer locomotor profile, suggesting that other TrpA1 neurons are responsible for the A component. Studies of circadian rhythms under seminatural conditions therefore provide additional insights into the molecular basis of circadian entrainment that would otherwise be lost under the usual standard laboratory protocols.

Functional dissection of the neural substrates for gravitaxic maze behavior in Drosophila melanogaster.

In animals, sensing gravity is supported by mechanosensory neurons that send information to the central brain for integration along with other modalities. In Drosophila, candidate sensory organs for detecting the gravity vector were predicted from the results of a recent forward genetic screen. This analysis also suggested possible roles for the central complex and antennal system in Drosophila. Using the same vertical maze assay employed in the original screen, we investigated the roles of these candidate neural structures by spatial and temporal inactivation of synaptic transmission with the GAL4/UAS-shibire[ts1] system. We correlate changes in the maze behavior of flies with specific inhibition of synaptic transmission for key brain neuropil that includes the central complex and antenno-glomerular tract. Further, our results point toward a minimal, or nonexistent, role for the mushroom bodies.