Community Landscapes: An Integrative Approach to Determine Overlapping Network Module Hierarchy,Identify Key Nodes and Predict Network Dynamics

Background

Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult.

Methodology/Principal Findings

Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1) determine pervasively overlapping modules with high resolution; (2) uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3) allow the determination of key network nodes and (4) help to predict network dynamics.

Conclusions/Significance

The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction.     

The Embryo Project: An Integrated Approach to History,Practices, and Social Contexts of Embryo Research

This essay describes the approach and early results of the collaborative Embryo Project and its on-line encyclopedia (). The project is based on a relational database that allows federated searches and inclusion of multiple types of objects targeted for multiple user groups. The emphasis is on the history and varied contexts of developmental biology, focusing on people, places, institutions, techniques, literature, images, and other aspects of study of embryos. This essay introduces the ways of working as well as the long-term goals of the project. We invite others to join the effort, both in this particular project and in joining together in digital collection, archiving, and knowledge generation at the borders of biology and history.     

An Integrative Approach Combining Noncovalent Mass Spectrometry, Enzyme Kinetics and X-ray Crystallography to Decipher Tgt Protein-Protein and Protein-RNA Interaction

The tRNA-modifying enzyme tRNA-guanine transglycosylase (Tgt) is a putative target for new selective antibiotics against Shigella bacteria. The formation of a Tgt homodimer was suggested on the basis of several crystal structures of Tgt in complex with RNA. In the present study, noncovalent mass spectrometry was used (i) to confirm the dimeric oligomerization state of Tgt in solution and (ii) to evidence the binding stoichiometry of the complex formed between Tgt and its full-length substrate tRNA. To further investigate the importance of Tgt protein-protein interaction, point mutations were introduced into the dimer interface in order to study their influence on the formation of the catalytically active complex. Enzyme kinetics revealed a reduced catalytic activity of these mutated variants, which could be related to a destabilization of the dimer formation as evidenced by both noncovalent mass spectrometry and X-ray crystallography. Finally, the effect of inhibitor binding was investigated by noncovalent mass spectrometry, thus providing the binding stoichiometries of Tgt:inhibitor complexes and showing competitive interactions in the presence of tRNA. Inhibitors that display an influence on the formation of the dimer interface in the crystal structure are promising candidates to alter the protein-protein interaction, which could provide a new way to inhibit Tgt.     

From Recombination Dynamics to Device Performance: Quantifying the Efficiency of Exciton Dissociation,Charge Separation,and Extraction in Bulk Heterojunction Solar Cells with Fluorine‐Substituted Polymer Donors

An original set of experimental and modeling tools is used to quantify the yield of each of the physical processes leading to photocurrent generation in organic bulk heterojunction solar cells, enabling evaluation of materials and processing condition beyond the trivial comparison of device performances. Transient absorption spectroscopy, “the” technique to monitor all intermediate states over the entire relevant timescale, is combined with time‐delayed collection field experiments, transfer matrix simulations, spectral deconvolution, and parametrization of the charge carrier recombination by a two‐pool model, allowing quantification of densities of excitons and charges and extrapolation of their kinetics to device‐relevant conditions. Photon absorption, charge transfer, charge separation, and charge extraction are all quantified for two recently developed wide‐bandgap donor polymers: poly(4,8‐bis((2‐ethylhexyl)oxy)benzo[1,2‐b:4,5‐b′]dithiophene‐3,4‐difluorothiophene) (PBDT[2F]T) and its nonfluorinated counterpart poly(4,8‐bis((2‐ethylhexyl)oxy)benzo[1,2‐b:4,5‐b′]dithiophene‐3,4‐thiophene) (PBDT[2H]T) combined with PC₇₁BM in bulk heterojunctions. The product of these yields is shown to agree well with the devices' external quantum efficiency. This methodology elucidates in the specific case studied here the origin of improved photocurrents obtained when using PBDT[2F]T instead of PBDT[2H]T as well as upon using solvent additives. Furthermore, a higher charge transfer (CT)‐state energy is shown to lead to significantly lower energy losses (resulting in higher V_OC) during charge generation compared to P3HT:PCBM.     

Updating Geographic Distribution of Artemia urmiana Günther, 1890 (Branchiopoda: Anostraca) in Europe: An Integrated and Interdisciplinary Approach

Artemia urmiana (a species previously considered endemic of Lake Urmia, NW Iran) has been found in Lake Koyashskoe, a hypersaline lake on the Black Sea coast of the Crimean peninsula (Ukraine). Therefore, this is the first record of A. urmiana in Europe which updates its distribution. The species identification was based on an integrated and interdisciplinary approach using discriminant analysis of the morphometric characters, scanning electron microscopy, and molecular profile analysis. The data derived from the above mentioned approaches converge to significant similarity of the population under investigation with A. urmiana. The updated geographic distribution of the species, deriving from the present report, asks for additional contribution of other disciplines (e.g., avian dispersal of cysts, history of salt trade) to be finally clarified. At present we suggest that the punctuated geographic distribution of A. urmiana is probably linked to its low dispersal capability, and we suppose that its presence in two distant sites could be explained by historical human salt trade between Lake Urmia and the ancient port of Kimmerik, whose remains have been found in the present Lake Koyashskoe. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

An Approach to Integrating Occupational Safety and Health into Life Cycle Assessment: Development and Application of Work Environment Characterization Factors

Integrating occupational safety and health (OSH) into life cycle assessment (LCA) may provide decision makers with insights and opportunities to prevent burden shifting of human health impacts between the nonwork environment and the work environment. We propose an integration approach that uses industry‐level work environment characterization factors (WE‐CFs) to convert industry activity into damage to human health attributable to the work environment, assessed as disability‐adjusted life years (DALYs). WE‐CFs are ratios of work‐related fatal and nonfatal injuries and illnesses occurring in the U.S. worker population to the amount of physical output from U.S. industries; they represent workplace hazards and exposures and are compatible with the life cycle inventory (LCI) structure common to process‐based LCA. A proof of concept demonstrates application of the WE‐CFs in an LCA of municipal solid waste landfill and incineration systems. Results from the proof of concept indicate that estimates of DALYs attributable to the work environment are comparable in magnitude to DALYs attributable to environmental emissions. Construction and infrastructure‐related work processes contributed the most to the work environment DALYs. A sensitivity analysis revealed that uncertainty in the physical output from industries had the most effect on the WE‐CFs. The results encourage implementation of WE‐CFs in future LCA studies, additional refinement of LCI processes to accurately capture industry outputs, and inclusion of infrastructure‐related processes in LCAs that evaluate OSH impacts.     

An Integrated Case Study for Evaluating the Impacts of an Oil Refinery Effluent on Aquatic Biota in the Delaware River: Introduction,Study Approach,and Objectives

This is the first in a series of article presenting results from a case study designed to assess the impacts of an oil refinery effluent [primarily polynuclear aromatic hydrocarbons (PAHs)] on aquatic biota in the Delaware River. During the course of the study, the oil refinery was owned by Motiva Enterprises LLC. This article provides background information on the study area, the study approach and objectives. The specific objectives of this multiyear study were to: (1) measure water column concentrations of PAHs and other contaminants (i.e., metals) in Motiva's effluent and intake canal and selected Delaware River sites; (2) assess fate and transport issues associated with the Refinery effluent; (3) characterize sediment PAHs, total organic carbon (TOC), and grain size distributions in the discharge canal, near-field, mid-field and far-field areas of the Refinery to aid in the selection of Triad sample sites (including reference areas); (4) conduct Triad studies (chemical characterizations, sediment toxicity assessments, and benthic community characterizations) at selected study sites during the spring and summer of 2001 and 2002; (5) perform fingerprinting of PAHs in Motiva's effluent to differentiate Motiva-related PAHs in sediment and biota from other sources; (6) assess bioavailability of PAHs, PCBs, and metals by using resident bivalve studies; (7) conduct long-term coring to determine potential impact of past non-complying discharges; and (8) integrate and analyze all study components to address the research goals. The results from objectives 1, 2, and 3 are briefly summarized in this series of articles whereas the other five objectives are the subject of the various papers presented in this volume.     

dbSWEET: An Integrated Resource for SWEET Superfamily to Understand,Analyze and Predict the Function of Sugar Transporters in Prokaryotes and Eukaryotes

SWEET (Sweet Will Eventually be Exported Transporter) proteins have been recently discovered and form one of the three major families of sugar transporters. Homologs of SWEET are found in both prokaryotes and eukaryotes. Bacterial SWEET homologs have three transmembrane segments forming a triple-helical bundle and the functional form is dimers. Eukaryotic SWEETs have seven transmembrane helical segments forming two triple-helical bundles with a linker helix. Members of SWEET homologs have been shown to be involved in several important physiological processes in plants. However, not much is known regarding the biological significance of SWEET homologs in prokaryotes and in mammals. We have collected more than 2000 SWEET homologs from both prokaryotes and eukaryotes. For each homolog, we have modeled three different conformational states representing outward open, inward open and occluded states. We have provided details regarding substrate-interacting residues and residues forming the selectivity filter for each SWEET homolog. Several search and analysis options are available. The users can generate a phylogenetic tree and structure-based sequence alignment for selected set of sequences. With no metazoan SWEETs functionally characterized, the features observed in the selectivity filter residues can be used to predict the potential substrates that are likely to be transported across the metazoan SWEETs. We believe that this database will help the researchers to design mutational experiments and simulation studies that will aid to advance our understanding of the physiological role of SWEET homologs. This database is freely available to the scientific community at http://bioinfo.iitk.ac.in/bioinfo/dbSWEET/Home.     

Combining noninvasive genetics and a new mammalian sex‐linked marker provides new tools to investigate population size,structure and individual behaviour: An application to bats

Monitoring wild populations is crucial for their effective management. Noninvasive genetic methods provide robust data from individual free‐ranging animals, which can be used in capture–mark–recapture (CMR) models to estimate demographic parameters without capturing or disturbing them. However, sex‐ and status‐specific behaviour, which may lead to differences in detection probabilities, is rarely considered in monitoring. Here, we investigated population size, sex ratio, sex‐ and status‐related behaviour in 19 Rhinolophus hipposideros maternity colonies (Northern France) with a noninvasive genetic CMR approach (using faeces) combined with parentage assignments. The use of the DDX3X/Y‐Mam sexual marker designed in this study, which shows inter‐ and intrachromosomal length polymorphism across placental mammals, together with eight polymorphic microsatellite markers, produced high‐quality genetic data with limited genotyping errors and allowed us to reliably distinguish different categories of individuals (males, reproductive and nonreproductive females) and to estimate population sizes. We showed that visual counts represent well‐adult female numbers and that population composition in maternity colonies changes dynamically during the summer. Before parturition, colonies mainly harbour pregnant and nonpregnant females with a few visiting males, whereas after parturition, colonies are mainly composed of mothers and their offspring with a few visiting nonmothers and males. Our approach gives deeper insight into sex‐ and status‐specific behaviour, a prerequisite for understanding population dynamics and developing effective monitoring and management strategies. Provided sufficient samples can be obtained, this approach can be readily applied to a wide range of species.     

A Novel Approach to Identify and Map Kitten Clusters Using Geographic Information Systems (GIS): A Case Study From Tompkins County,NY

A retrospective study using a geographic information system (GIS) was conducted to capture, map, and analyze intake data of caregiver (owner)-surrendered kittens (aged 0–6 months) to the Society for the Prevention of Cruelty to Animals (SPCA) of Tompkins County, NY, from 2009 to 2011. Addresses of caregiver-surrendered kittens during the study period were mapped (n = 1,017). Mapping and analysis of the resultant data set revealed that the distribution of kittens was nonrandom. Seventeen statistically significant (p = .001) clusters were identified, 1 of which was the SPCA of Tompkins County (due to anonymously surrendered nonhuman animals). The remaining 16 clusters were composed of 52 homes; 27.5% (280/1,017) of the kittens in the data set originated from these 52 homes. The majority of kittens within clusters were surrendered from high-density residential and manufactured residential home parks. Analyzing such clusters using GIS is a novel approach for targeting spay/neuter and educational programs to areas contributing disproportionately to shelter populations. This method may prove useful to help shelters more effectively allocate their limited resources, but further evaluation of this and other targeted approaches is needed to assess the long-term efficacy of such programs.