Automated discovery of food webs from ecological data using logic-based machine learning

Networks of trophic links (food webs) are used to describe and understand mechanistic routes for translocation of energy (biomass) between species. However, a relatively low proportion of ecosystems have been studied using food web approaches due to difficulties in making observations on large numbers of species. In this paper we demonstrate that Machine Learning of food webs, using a logic-based approach called A/ILP, can generate plausible and testable food webs from field sample data. Our example data come from a national-scale Vortis suction sampling of invertebrates from arable fields in Great Britain. We found that 45 invertebrate species or taxa, representing approximately 25% of the sample and about 74% of the invertebrate individuals included in the learning, were hypothesized to be linked. As might be expected, detritivore Collembola were consistently the most important prey. Generalist and omnivorous carabid beetles were hypothesized to be the dominant predators of the system. We were, however, surprised by the importance of carabid larvae suggested by the machine learning as predators of a wide variety of prey. High probability links were hypothesized for widespread, potentially destabilizing, intra-guild predation; predictions that could be experimentally tested. Many of the high probability links in the model have already been observed or suggested for this system, supporting our contention that A/ILP learning can produce plausible food webs from sample data, independent of our preconceptions about "who eats whom." Well-characterised links in the literature correspond with links ascribed with high probability through A/ILP. We believe that this very general Machine Learning approach has great power and could be used to extend and test our current theories of agricultural ecosystem dynamics and function. In particular, we believe it could be used to support the development of a wider theory of ecosystem responses to environmental change.     

Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies

Identifying the epitope of an antibody is a key step in understanding its function and its potential as a therapeutic. Sequence-based clonal clustering can identify antibodies with similar epitope complementarity, however, antibodies from markedly different lineages but with similar structures can engage the same epitope. We describe a novel computational method for epitope profiling based on structural modelling and clustering. Using the method, we demonstrate that sequence dissimilar but functionally similar antibodies can be found across the Coronavirus Antibody Database, with high accuracy (92% of antibodies in multiple-occupancy structural clusters bind to consistent domains). Our approach functionally links antibodies with distinct genetic lineages, species origins, and coronavirus specificities. This indicates greater convergence exists in the immune responses to coronaviruses than is suggested by sequence-based approaches. Our results show that applying structural analytics to large class-specific antibody databases will enable high confidence structure-function relationships to be drawn, yielding new opportunities to identify functional convergence hitherto missed by sequence-only analysis.     

Apolipoprotein A-IV stimulates duodenal vagal afferent activity to inhibit gastric motility via a CCK1 pathway

Apolipoprotein A-IV (apo A-IV), a peptide expressed by enterocytes in the mammalian small intestine and released in response to long-chain triglyceride absorption, may be involved in the regulation of gastric acid secretion and gastric motility. The specific aim of the present study was to determine the pathway involved in mediating inhibition of gastric motility produced by apo A-IV. Gastric motility was measured manometrically in response to injections of either recombinant purified apo A-IV (200 microg) or apo A-I, the structurally similar intestinal apolipoprotein not regulated by triglyceride absorption, close to the upper gastrointestinal tract in urethane-anesthetized rats. Injection of apo A-IV significantly inhibited gastric motility compared with apo A-I or vehicle injections. The response to exogenous apo A-IV injections was significantly reduced by 77 and 55%, respectively, in rats treated with the CCK(1) receptor blocker devazepide or after functional vagal deafferentation by perineural capsaicin treatment. In electrophysiological experiments, isolated proximal duodenal vagal afferent fibers were recorded in vitro in response to close-arterial injection of vehicle, apo A-IV (200 microg), or CCK (10 pmol). Apo A-IV stimulated the discharge of duodenal vagal afferent fibers, significantly increasing the discharge in 4/7 CCK-responsive units, and the response was abolished by CCK(1) receptor blockade with devazepide. These data suggest that apo A-IV released from the intestinal mucosa during lipid absorption stimulates the release of endogenous CCK that activates CCK(1) receptors on vagal afferent nerve terminals initiating feedback inhibition of gastric motility.     

Identification of genes differentially expressed in dorsal and ventral chick midbrain during early Development

Background  

During the development of the central nervous system (CNS), patterning processes along the dorsoventral (DV) axis of the neural tube generate different neuronal subtypes. As development progresses these neurons are arranged into functional units with varying cytoarchitecture, such as laminae or nuclei for efficient relaying of information. Early in development ventral and dorsal regions are similar in size and structure. Different proliferation rates and cell migration patterns are likely to result in the formation of laminae or nuclei, eventually. However, the underlying molecular mechanisms that establish these different structural arrangements are not well understood.     

The Hydrochemical and Physical Characteristics of the Breeding Sites of the Simulium neavei Roubaud Group and their Associated Crabs in the Eastern Usambara Mountains in Tanzania

Investigations on the hydrochemical and physical parameters of the breeding sites of Simulium woodi (an onchocerciasis vector). and Simulium nyasalandicum, and on their aquatic stages and associated crabs, were carried out for 13 months in the Zigi (Sigi). River system. The conductivity, pH and concentration of the main ions and silicate were all higher in the breeding sites of S. woodi than in those of S. nyasalandicum. S. woodi was restricted to small heavily shaded streams and did not enter rivers and large streams which contained higher concentrations of ammonium and nitrite. S. nyasalandicum was most numerous in rivers and large streams, but invaded small heavily shaded streams during the rainy season when conductivity and pH values were reduced.     

Nutrient sensing in the gastrointestinal tract: Possible role for nutrient transporters

Although it is well established that the presence of nutrients in the gut lumen can bring about changes in GI function, the mechanisms and pathways by which these changes occur has not been fully elucidated. It has been known for many years that luminal nutrients stimulate the release of hormones and regulatory peptides from gut endocrine cells and that luminal nutrients activate intrinsic and extrinsic neural pathways innervating the gut. Activation of gut endocrine cells and neural pathways by nutrients in the gut lumen is key in coordination of postprandial GI function and also in the regulation of food intake. Recent evidence suggests that these pathways can be modified by long term changes in diet or by inflammatory processes in the gut wall. Thus it is important to determine the cellular and molecular mechanisms underlying these processes not only to increase our understanding of as part of basic physiology but also to understand changes in these pathways that occur in the presence of pathophysiology and disease. This review summarizes some of the latest data that we have obtained, together with information from the other laboratories, which have elucidated some of the mechanisms involved in nutrient detection in the gut wall. The focus is on monosaccharides and protein hydrolysates as there is some evidence for a role for nutrient transporters in detection of these nutrients.     

Selective ablation of spinal afferent neurons containing CGRP attenuates gastric hyperemic response to acid.

The gastric mucosa, in particular submucosal blood vessels, are innervated by afferent neurons containing neuropeptides such as calcitonin gene-related peptide. Stimulation of sensory neurons innervating the gastric mucosa increases submucosal blood flow. Since sensory neurons supplying the stomach are of dual origin from nodose and dorsal root ganglia, we examined the effect of selective ablation of either the vagal or spinal sensory innervation to the upper gastrointestinal tract on the increase in gastric mucosal blood flow in response to acid back diffusion into the gastric mucosa. Perineural application of capsaicin to the celiac/superior mesenteric ganglia, but not to the vagus nerves, significantly inhibited by 53% the hyperemic response to acid back diffusion. Tissue levels of immunoreactive calcitonin gene-related peptide in the gastric corpus were significantly reduced (by 73%) by periceliac capsaicin treatment, but unaffected by perivagal capsaicin treatment. These data suggest that spinal capsaicin-sensitive afferents containing calcitonin gene-related peptide immunoreactivity are involved in mediating increases in gastric mucosal blood flow. This increase in gastric mucosal blood flow mediated by sensory neurons may act as a protective mechanism against mucosal injury, similar to responses seen in other tissues such as skin.     

Characterising microbial protein test substances and establishing their equivalence with plant-produced proteins for use in risk assessments of transgenic crops

Most commercial transgenic crops are genetically engineered to produce new proteins. Studies to assess the risks to human and animal health, and to the environment, from the use of these crops require grams of the transgenic proteins. It is often extremely difficult to produce sufficient purified transgenic protein from the crop. Nevertheless, ample protein of acceptable purity may be produced by over-expressing the protein in microbes such as Escherichia coli. When using microbial proteins in a study for risk assessment, it is essential that their suitability as surrogates for the plant-produced transgenic proteins is established; that is, the proteins are equivalent for the purposes of the study. Equivalence does not imply that the plant and microbial proteins are identical, but that the microbial protein is sufficiently similar biochemically and functionally to the plant protein such that studies using the microbial protein provide reliable information for risk assessment of the transgenic crop. Equivalence is a judgement based on a weight of evidence from comparisons of relevant properties of the microbial and plant proteins, including activity, molecular weight, amino acid sequence, glycosylation and immuno-reactivity. We describe a typical set of methods used to compare proteins in regulatory risk assessments for transgenic crops, and discuss how risk assessors may use comparisons of proteins to judge equivalence.     

How does scientific risk assessment of GM crops fit within the wider risk analysis?

The debate concerning genetically modified crops illustrates confusion between the role of scientists and that of wider society in regulatory decision making. We identify two fundamental misunderstandings, which, if rectified, would allow progress with confidence. First, scientific risk assessment needs to test well-defined hypotheses, not simply collect data. Second, risk assessments need to be placed in the wider context of risk analysis to enable the wider 'non-scientific' questions to be considered in regulatory decision making. Such integration and understanding is urgently required because the challenges to regulation will escalate as scientific progress advances.