Identification of Previously Unknown Interactions Between G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins. However, the extent of these interactions and their role in regulating GPCR-mediated transmembrane signaling is not well understood. For example, receptor activitymodifying proteins (RAMPs), a family of single transmembrane proteins with only three members, are ubiquitously expressed and have been shown to interact with several different GPCRs. Most research to date has focused on the ability of RAMPs to modulate the function of several GPCRs in the secretin-like GPCR family. GPCR-RAMP interactions were shown to affect the ligand binding affinity of two different secretin-like GPCRs, causing the functional diversity of the GPCRs to be driven by an interacting protein. Yet, potential direct interactions among the three known RAMPs and hundreds of non-olfactory GPCR has never been investigated and whether RAMP-GPCR interactions are widespread remains an open question. To determine the breadth of GPCR-RAMP interactions, we first investigated the global coexpression and coevolution between GPCRs and RAMPs. On the one hand, if many GPCRs interact with RAMPs we would except to see statistically significant coexpression and coevolution in comparison to random gene pairs. On the other hand, if GPCR-RAMP interactions are limited to a small number of genes, then averaged coexpression and coevolution would be similar to that expected by chance. To calculate coexpression, we analyzed an RNASeq database of human transcriptomes across 53 different tissues and found that coexpression between non-olfactory GPCRs and RAMPs is significantly higher than random gene pairs. We also analyzed genomic data from all currently available sequenced organisms to calculate the coevolution between non-olfactory GPCRs and RAMPs. We discovered that GPCRs and RAMPs have a significant percentage of shared species and significantly correlated phylogenetic trees. Our results support the hypothesis that GPCRs interact globally with RAMPs. Only a handful of GPCR-RAMP interactions have been reported to date, but our coexpression and coevolution analysis suggested that additional GPCRs interact with RAMPs. To begin to address the potential for direct interactions among the three known RAMPs and hundreds of GPCRs, we developed a highly multiplexed immunoassay using a suspension bead array (SBA) assay designed to detect RAMP-GPCR complexes. We engineered three epitopetagged RAMPs and 23 epitope-tagged GPCRs, including all members of the secretin-like family of GPCRs, as well as eight other GPCRs. We then used 64 antibodies raised against native RAMPs and GPCRs, along with four antibodies targeting the epitope tags, to multiplex the SBA assay to detect and measure all possible combinations of interaction among the 23 GPCRs and three RAMPs from detergent-solubilized lysates. We also used the epitope-tagged constructs to verify a collection of antibodies that target native GPCRs and RAMPs. We validated nearly all previously reported secretin-like GPCR-RAMP interactions, and also found previously unidentified RAMP interactions with additional secretin-like GPCRs, chemokine receptors, and orphan receptors. Using in situ proximity ligation assay, we verified a subset of these novel GPCR-RAMP interactions in cell membranes. The results of the SBA assay provide a complete interactome of secretin-like GPCRs with RAMPs. GPCR-RAMP interactions are more common than previously appreciated, and the SBA strategy will be useful to search for additional GPCRRAMP complexes and other interacting membrane protein pairs in cell lines and tissues

The Anatomy of the Carpal Tunnel and Hand Function of Musicians

Musicians spend hours perfecting their trade, often leading to overuse injuries of the hand; of specific concern to musicians is carpal tunnel syndrome (CTS). This study evaluated the median nerve cross-sectional area and hand function of musicians and non-musicians. Patients completed the upper extremity and CTS specific function questionnaires. The median nerve cross-sectional area, and the width of the carpal tunnel were measured on ultrasound image. The median nerve cross-sectional area was greater in musicians than the non-musician group. The width of the carpal tunnel did not differ between the groups. Musicians showed higher levels of hand dysfunction than the non-musician. The current research identified between group differences in median nerve cross-sectional area and the level of hand dysfunction of musicians. Understanding the interaction between the anatomy of the wrist and wrist and hand dysfunction will benefit clinicians when evaluating and treating musicians

Micro Methods for Megafauna: Novel Approaches to Late Quaternary Extinctions and Their Contributions to Faunal Conservation in the Anthropocene

Drivers of Late Quaternary megafaunal extinctions are relevant to modern conservation policy in a world of growing human population density, climate change, and faunal decline. Traditional debates tend toward global solutions, blaming either dramatic climate change or dispersals of Homo sapiens to new regions. Inherent limitations to archaeological and paleontological data sets often require reliance on scant, poorly resolved lines of evidence. However, recent developments in scientific technologies allow for more local, context-specific approaches. In the present article, we highlight how developments in five such methodologies (radiocarbon approaches, stable isotope analysis, ancient DNA, ancient proteomics, microscopy) have helped drive detailed analysis of specific megafaunal species, their particular ecological settings, and responses to new competitors or predators, climate change, and other external phenomena. The detailed case studies of faunal community composition, extinction chronologies, and demographic trends enabled by these methods examine megafaunal extinctions at scales appropriate for practical understanding of threats against particular species in their habitats today. </section

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Agronomic evaluation of common and improved dessert banana cultivars at different altitudes across Burundi

Banana is an important crop for food and income in Burundi. However, average annual yields are low (5 t/ha) because of low and declining soil fertility, and pest and disease pressure. To help overcome the challenges to banana production in the Great Lakes region of Central Africa, the Consortium for the Improvement of Agriculture-based Livelihoods in Central Africa (CIALCA) has been promoting and facilitating access to new high-yielding, pest- and disease-resistant improved hybrid banana cultivars with good consumer acceptability. The agronomic performance of the improved hybrid 'FHIA-l7' and six commonly grown dessert banana cultivars was evaluated at six sites with contrasting altitudes across Burundi from 2008 to 2012. The data were analysed using linear mixed-effects modelling. 'FHIA-l7' significantly outperformed the other cultivars as it had the heaviest bunch weight. was in the group of cultivars with the most hands and fruits, and the fruits were long and thick. The cultivars 'ITC0680', 'Gros Michel', 'Prata' and 'Yangambi KmS' had the next best agronomic performance, while the cultivars 'Ikigurube' and 'Kamaramasenge' had the poorest performance. The high agronomic performance of 'FHlA-17' shown in this research demonstrates how its increased cultivation may help to ensure the continued production of dessert types of bananas in Burundi and the food and income security of the population