Deductive and Analogical Reasoning on a Semantically Embedded Knowledge Graph

Representing knowledge as high-dimensional vectors in a continuous semantic vector space can help overcome the brittleness and incompleteness of traditional knowledge bases. We present a method for performing deductive reasoning directly in such a vector space, combining analogy, association, and deduction in a straightforward way at each step in a chain of reasoning, drawing on knowledge from diverse sources and ontologies.Comment: AGI 201

Walk with Me: a protocol for a pilot RCT of a peer-led walking programme to increase physical activity in inactive older adults

Background: Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those from lower socio-economic position, are also the most inactive. Increasing physical activity levels, particularly among those most inactive, is a public health priority. Peer-led physical activity interventions may offer a model to increase physical activity in the older adult population. This study aims to test the feasibility of a peer-led, multicomponent physical activity intervention in socio-economically disadvantaged community dwelling older adults. Methods: The Medical Research Council framework for developing and evaluating complex interventions will be used to design and test the feasibility of a randomised controlled trial (RCT) of a multicomponent peer-led physical activity intervention. Data will be collected at baseline, immediately after the intervention (12 weeks) and 6 months after baseline measures. The pilot RCT will provide information on recruitment of peer mentors and participants and attrition rates, intervention fidelity, and data on the variability of the primary outcome (minutes of moderate to vigorous physical activity measured with an accelerometer). The pilot trail will also assess the acceptability of the intervention and identify potential resources needed to undertake a definitive study. Data analyses will be descriptive and include an evaluation of eligibility, recruitment, and retention rates. The findings will be used to estimate the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders to identify areas of success and necessary improvements. Discussion: This paper describes the protocol for the ‘Walk with Me’ pilot RCT which will provide the information necessary to inform the design and delivery of a fully powered trial should the Walk with Me intervention prove feasible

The FGLamide-Allatostatins Influence Foraging Behavior in Drosophila melanogaster

Allatostatins (ASTs) are multifunctional neuropeptides that generally act in an inhibitory fashion. ASTs were identified as inhibitors of juvenile hormone biosynthesis. Juvenile hormone regulates insect metamorphosis, reproduction, food intake, growth, and development. Drosophila melanogaster RNAi lines of PheGlyLeu-amide-ASTs (FGLa/ASTs) and their cognate receptor, Dar-1, were used to characterize roles these neuropeptides and their respective receptor may play in behavior and physiology. Dar-1 and FGLa/AST RNAi lines showed a significant reduction in larval foraging in the presence of food. The larval foraging defect is not observed in the absence of food. These RNAi lines have decreased for transcript levels which encodes cGMP- dependent protein kinase. A reduction in the for transcript is known to be associated with a naturally occuring allelic variation that creates a sitter phenotype in contrast to the rover phenotype which is caused by a for allele associated with increased for activity. The sitting phenotype of FGLa/AST and Dar-1 RNAi lines is similar to the phenotype of a deletion mutant of an AST/galanin-like receptor (NPR-9) in Caenorhabditis elegans. Associated with the foraging defect in C. elegans npr-9 mutants is accumulation of intestinal lipid. Lipid accumulation was not a phenotype associated with the FGLa/AST and Dar-1 RNAi lines

Unravelling the evolution of the Allatostatin-Type A, KISS and Galanin Peptide-Receptor gene families in Bilaterians: insights from Anopheles Mosquitoes

Allatostatin type A receptors (AST-ARs) are a group of G-protein coupled receptors activated by members of the FGL-amide (AST-A) peptide family that inhibit food intake and development in arthropods. Despite their physiological importance the evolution of the AST-A system is poorly described and relatively few receptors have been isolated and functionally characterised in insects. The present study provides a comprehensive analysis of the origin and comparative evolution of the AST-A system. To determine how evolution and feeding modified the function of AST-AR the duplicate receptors in Anopheles mosquitoes, were characterised. Phylogeny and gene synteny suggested that invertebrate AST-A receptors and peptide genes shared a common evolutionary origin with KISS/GAL receptors and ligands. AST-ARs and KISSR emerged from a common gene ancestor after the divergence of GALRs in the bilaterian genome. In arthropods, the AST-A system evolved through lineage-specific events and the maintenance of two receptors in the flies and mosquitoes (Diptera) was the result of a gene duplication event. Speciation of Anophelesmosquitoes affected receptor gene organisation and characterisation of AST-AR duplicates (GPRALS1 and 2) revealed that in common with other insects, the mosquito receptors were activated by insect AST-A peptides and the iCa(2+)-signalling pathway was stimulated. GPRALS1 and 2 were expressed mainly in mosquito midgut and ovaries and transcript abundance of both receptors was modified by feeding. A blood meal strongly up-regulated expression of both GPRALS in the midgut (p < 0.05) compared to glucose fed females. Based on the results we hypothesise that the AST-A system in insects shared a common origin with the vertebrate KISS system and may also share a common function as an integrator of metabolism and reproduction. Highlights: AST-A and KISS/GAL receptors and ligands shared common ancestry prior to the protostome-deuterostome divergence. Phylogeny and gene synteny revealed that AST-AR and KISSR emerged after GALR gene divergence. AST-AR genes were present in the hemichordates but were lost from the chordates. In protostomes, AST-ARs persisted and evolved through lineage-specific events and duplicated in the arthropod radiation. Diptera acquired and maintained functionally divergent duplicate AST-AR genes.Foundation for Science and Technology, Portugal (FCT) [PTDC/BIA-BCM/114395/2009]; European Regional Development Fund (ERDF) COMPETE - Operational Competitiveness Programme; Portuguese funds through FCT Foundation for Science and Technology [PEst-C/MAR/LA0015/2013, UID/Multi/04326/2013, PEst-OE/SAU/LA0018/2013]; FCT [SFRH/BPD/89811/2012, SFRH/BPD/80447/2011, SFRH/BPD/66742/2009]; auxiliary research contract FCT Pluriannual funds [PEst-C/MAR/LA0015/2013, UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Neuropeptide Receptor Transcriptome Reveals Unidentified Neuroendocrine Pathways

Neuropeptides are an important class of molecules involved in diverse aspects of metazoan development and homeostasis. Insects are ideal model systems to investigate neuropeptide functions, and the major focus of insect neuropeptide research in the last decade has been on the identification of their receptors. Despite these vigorous efforts, receptors for some key neuropeptides in insect development such as prothoracicotropic hormone, eclosion hormone and allatotropin (AT), remain undefined. In this paper, we report the comprehensive cloning of neuropeptide G protein-coupled receptors from the silkworm, Bombyx mori, and systematic analyses of their expression. Based on the expression patterns of orphan receptors, we identified the long-sought receptor for AT, which is thought to stimulate juvenile hormone biosynthesis in the corpora allata (CA). Surprisingly, however, the AT receptor was not highly expressed in the CA, but instead was predominantly transcribed in the corpora cardiaca (CC), an organ adjacent to the CA. Indeed, by using a reverse-physiological approach, we purified and characterized novel allatoregulatory peptides produced in AT receptor-expressing CC cells, which may indirectly mediate AT activity on the CA. All of the above findings confirm the effectiveness of a systematic analysis of the receptor transcriptome, not only in characterizing orphan receptors, but also in identifying novel players and hidden mechanisms in important biological processes. This work illustrates how using a combinatorial approach employing bioinformatic, molecular, biochemical and physiological methods can help solve recalcitrant problems in neuropeptide research

Mapping Peptidergic Cells in Drosophila: Where DIMM Fits In

The bHLH transcription factor DIMMED has been associated with the differentiation of peptidergic cells in Drosophila. However, whether all Drosophila peptidergic cells express DIMM, and the extent to which all DIMM cells are peptidergic, have not been determined. To address these issues, we have mapped DIMM expression in the central nervous system (CNS) and periphery in the late larval stage Drosophila. At 100 hr after egg-laying, DIMM immunosignals are largely congruent with a dimm-promoter reporter (c929-GAL4) and they present a stereotyped pattern of 306 CNS cells and 52 peripheral cells. We assigned positional values for all DIMM CNS cells with respect to reference gene expression patterns, or to patterns of secondary neuroblast lineages. We could assign provisional peptide identities to 68% of DIMM-expressing CNS cells (207/306) and to 73% of DIMM-expressing peripheral cells (38/52) using a panel of 24 markers for Drosophila neuropeptide genes. Furthermore, we found that DIMM co-expression was a prevalent feature within single neuropeptide marker expression patterns. Of the 24 CNS neuropeptide gene patterns we studied, six patterns are >90% DIMM-positive, while 16 of 22 patterns are >40% DIMM-positive. Thus most or all DIMM cells in Drosophila appear to be peptidergic, and many but not all peptidergic cells express DIMM. The co-incidence of DIMM-expression among peptidergic cells is best explained by a hypothesis that DIMM promotes a specific neurosecretory phenotype we term LEAP. LEAP denotes Large cells that display Episodic release of Amidated Peptides